Treatments FOR

SKIN OF Color
Acquisitions Editor: Claire Bonnett/Russell Gabbedy
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 Treatments for

Skinof Color
Susan C Taylor MD Raechele Cochran Gathers MD

Assistant Clinical Professor of Dermatology Senior Staff Physician

College of Physicians and Surgeons Henry Ford Hospital
Columbia University Multicultural Dermatology Center
Society Hill Dermatology Detroit, MI, USA
Phildelphia, PA, USA
David A Rodriguez MD
Sonia Badreshia-Bansal MD
Voluntary Associate Professor
Clinical Instructor Dermatology and Cutaneous Surgery
Department of Dermatology University of Miami
University of California San Francisco Medical Director
Elite MD, Inc Dermatology Associates and Research
Advanced Dermatology, Laser, and Plastic Surgery Institute Coral Gables, FL, USA
Danville, CA, USA

Valerie D Callender MD

Associate Professor of Dermatology

Howard University College of Medicine
Washington DC, USA
Callender Skin and Laser Center
Glenn Dale, MD, USA

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Treatments for skin of color.
â•… 1.╇ Skin – Diseases – Treatment.â•… 2.╇ Pigmentation disorders – Treatment.â•… 3.╇ Human skin color.
â•… I. Taylor, Susan C.
â•… 616.5′0089 – dc22

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Contents

PREFACE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
LIST OF CONTRIBUTORS . . . . . . . . . . . . . . . . . . . . . . . xiii
EVIDENCE LEVELS . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . xvii

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix

Part 1. Medical Dermatology . . . . . . . . . . . . . . . . . . . . . . 1

╇ 1. Acneiform Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Sonia Badreshia-Bansal and Vivek Bansal
Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Acne vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Pomade acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Steroid acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Pediatric perspectives: Infantile acne Candrice R Heath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Pediatric perspectives: Neonatal acne (acne neonatorum) Candrice R Heath . . . . . . . . . . . . . . . . . . . . 14
Acne rosacea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Hidradenitis suppurativa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Perioral dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

╇ 2. Bullous and Pustular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Janelle Vega and David A Rodriguez
Bullosis diabeticorum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Bullous pemphigoid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Impetigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Infantile acropustulosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Pemphigus foliaceus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Pemphigus vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

v
Contents

╇ 3. Collagen Vascular Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

Sumayah J Taliaferro, Erica Chon Davis and Valerie D Callender
Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Livedoid vasculopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Lupus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Chronic cutaneous lupus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Subacute cutaneous lupus erythematosus (SCLE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Systemic lupus erythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Scleroderma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Localized scleroderma (morphea) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Systemic sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61

╇ 4. Eczematous Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

Sonia Badreshia-Bansal
Allergic contact dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Atopic dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Dyshidrotic eczema/Pomphylox . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Irritant contact dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Lichen simplex chronicus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Nummular dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

╇ 5. Granulomatous Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

Sonia Badreshia-Bansal
Granuloma annulare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Localized granuloma annulare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Generalized granuloma annulare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97

╇ 6. Hypersensitivity and Allergic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

Ninad Pendharkar, Sonia Badreshia-Bansal, Janelle Vega, and David A Rodriguez
Arthropod bites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Fixed drug eruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Erythema multiforme . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104
Erythema nodosum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Exfoliative dermatitis/Erythroderma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Polymorphous light eruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Urticaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115

╇ 7. Infectious Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

Rashmi Sarkar, Vivek Nair, Surabhi Sinha, Vijay K Garg and David A Rodriguez
Candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Oral candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Candidal intertrigo/Cutaneous candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Cellulitis and Erysipelas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Chancroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

vi
 Contents

Chlamydia trachomatis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

Donovanosis (Granuloma inguinale) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
Exanthems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Folliculitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
Furunculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Human papilloma virus (HPV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
Lymphogranuloma venereum (LGV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Pityriasis versicolor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Tinea capitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
Tinea corporis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Tinea unguium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146

╇ 8. Lichenoid Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149

Sonia Badreshia-Bansal
Lichen amyloidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Lichen nitidus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152
Lichen planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154
Cutaneous lichen planus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
Mucosal involvement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Lichen sclerosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Pediatric perspectives: Lichen sclerosus et atrophicus Candrice R Heath . . . . . . . . . . . . . . . . . . . . . . . 160
Lichen striatus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161

╇ 9. Papulosquamous Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163

Sonia Badreshia-Bansal
Parapsoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Pityriasis rosea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166
Plaque psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Pediatric perspectives: Psoriasis Candrice R Heath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174
Seborrheic dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Facial seborrheic dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Scalp seborrheic dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179

Part 2. Pigmentary Disorders . . . . . . . . . . . . . . . . . . . . . 181

10. Hyperpigmented Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183

David A Rodriguez
Acanthosis nigricans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Benign melanonychia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185
Confluent and reticulated papillomatosis of Gougerot and Carteaud (CRPGC) . . . . . . . . . . . . . . . . . . . . . . 187
Drug-induced pigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Erythema dyschromicum perstans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Exogenous ochronosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
Gingival hyperpigmentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194

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Melasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Mongolian spots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Nevus of Ota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
Pigmentary demarcation lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Post-inflammatory hyperpigmentation (PIH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Solar lentigines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Pediatric perspectives: Transient neonatal pustular melanosis Candrice R Heath . . . . . . . . . . . . . . . . . . . 209

11. Hypopigmented Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

David A Rodriguez
Hypomelanosis of Ito . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Hypopigmented cutaneous T-cell lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212
Hypopigmented sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Pityriasis alba . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Pediatric perspectives: Vitiligo Candrice R Heath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221

Part 3. Follicular Disorders and Alopecias . . . . . . . . . 225

12. Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

Raechele Cochran Gathers
Alopecia areata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Alopecia mucinosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
Central centrifugal cicatricial alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Dissecting cellulitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Discoid lupus erythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
Traction alopecia Crystal Y Pourciau . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
Traumatic alopecia: chemical, heat and mechanical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
Trichotillomania . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

13. Follicular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

Raechele Cochran Gathers
Acne keloidalis nuchae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Folliculitis decalvans Crystal Y Pourciau . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251
Pseudofolliculitis barbae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

Part 4. Tumors Benign and Malignant . . . . . . . . . . . . . 257

14. Benign Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Erica Mailler-Savage, Matthew Joseph Turner, David Robert Crowe, Erica Chon Davis and Hugh Morris Gloster Jr
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Acrochordon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260

viii
 Contents

Dermatofibroma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
Dermatosis papulosa nigra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Epidermal nevus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Congenital melanocytic nevus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
Dysplastic nevus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Epidermoid cyst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
Keloid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267

15. Malignant Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

Erica Mailler-Savage, Matthew Joseph Turner, David Robert Crowe, Erica Chon Davis and Hugh Morris Gloster Jr
Basal cell carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
Cutaneous T-cell lymphoma (CTCL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 273
Dermatofibrosarcoma protuberans (DFSP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Malignant melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Squamous cell carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279

Part 5. Cosmetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287

16. Cosmetic Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289

Valerie D Callender and Erica Chon Davis
Hair cosmetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Shampoos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Hair moisturizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
Chemical processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Hair dyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
Glossary of terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296
Camouflage techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Skin cosmetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Skin lightening agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Photoprotection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306
Camouflage techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306

17. Cosmetic Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309

Valerie D Callender, Vic A Narurkar and Erica Chon Davis
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Botulinum neurotoxin-A (BoNT-A) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Chemical peels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Fillers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
Hair transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
Lasers, light sources and other devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332

ix
Contents

Part 6. Complementary and Alternative Medicine . . 349

18. An Overview of Complementary and Alternative Medicine . . . . . . . . . . . . . . 351

Janet L Nelson and Sonia Badreshia-Bansal
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Eczema / Atopic dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375

x
Preface
There are many complexities associated with selection of
appropriate treatment for cutaneous diseases. These complexi-
ties increase when selecting treatment for patients with skin of
color due to structural and functional differences in their skin
and hair as well as differing adverse event profiles. Treatment
for Skin of Color is an important resource that will allow the
practicing clinician to quickly identify evidence-based treat-
ment options for their skin of color patients. The scope of the
book is extensive beginning with medical dermatology fol-
lowed by follicular disorders, tumors, cosmetics and conclud-
ing with alternative medicine. Each therapy covered has been
assigned an evidence level from A (the strongest scientific
evidence) to E (anecdotal case reports) reflecting the amount
of published evidence available to support its use.
The truly outstanding authors of Treatment for Skin of Color,
to whom I am indebted, were chosen for this project based
upon the strength of their clinical skills, and their ability to
educate and present information in an organized, succinct and
easily absorbable manner. The work of Drs. Rodriguez, Gathers,
Badreshia-Bansal, and Callender with diverse patient popula-
tions coupled with their clinical research experience have
allowed us to produce a unique resource.
When a question or therapeutic dilemma arises in a teach-
ing clinic or private office setting, Treatment for Skin of Color is
a quick reference for either the dermatology resident or the
more experienced clinician. Additionally, by providing exten-
sive references, it provides the first step for a seamless in-depth
look into topics of interest.
Susan C Taylor, MD
xi
This page intentionally left blank
List of Contributors

Sonia Badreshia-Bansal MD Raechele Cochran Gathers MD

Clinical Instructor Senior Staff Physician
Department of Dermatology Henry Ford Hospital
University of California San Francisco Multicultural Dermatology Center
Elite MD, Inc Detroit, MI, USA
Advanced Dermatology, Laser, and Plastic Surgery Institute
Danville, CA, USA Hugh Morris Gloster Jr MD
Vivek Bansal MD Professor of Dermatology
Director of Dermatologic Surgery and Mohs Surgery
Medical Director of Plastic Surgery
University of Cincinnati
Elite MD, Inc
Cincinnati, OH, USA
Advanced Dermatology, Laser, and Plastic Surgery Institute
Danville, CA, USA
Candrice R Heath MD
Valerie D Callender MD Physician
Associate Professor of Dermatology Children’s Healthcare of Atlanta
Howard University College of Medicine Atlanta, GA, USA
Washington DC, USA
Callender Skin and Laser Center
Erica Mailler-Savage MD
Glenn Dale, MD, USA
Clinical Instructor
David Robert Crowe MD Dermatology Department
Dermatology Resident University of Cincinnati
Department of Dermatology Cincinnati, OH, USA
University of Cincinnati
Cincinnati, OH, USA Vivek Nair MD
Erica Chon Davis MD Senior Resident
Department of Dermatology
Dermatology Research Fellow Maulana Azad Medical College
Callender Skin and Laser Center New Delhi, India
Glenn Dale, MD, USA

Vijay K Garg MD MNAMS Vic A Narurkar MD FAAD

Professor and Head of Department Chairman
Department of Dermatology Department of Dermatology
Maulana Azad Medical College California Pacific Medical Center
New Delhi, India San Fransisco, CA, USA

xiii
List of Contributors

Janet L Nelson MS Lac Surabhi Sinha MD MNAMS DNB

Practitioner of Asian Medicine Senior Resident
Elite MD, Inc Department of Dermatology
Advanced Dermatology, Laser, and Plastic Surgery Institute Maulana Azad Medical College
Danville, CA, USA New Delhi, India

Ninad Pendharkar MD Sumayah J Taliaferro MD

Dermatology Resident Dermatologist
Penn State, College of Medicine Private Practice
Department of Dermatology Metro Atlanta Dermatology
Milton S. Hershey Medical Center Atlanta, GA, USA
Hershey, PA, USA
Matthew Joseph Turner MD PhD
Crystal Y Pourciau MD MPH Dermatology Resident
Resident Physician Department of Dermatology
Department of Dermatology University of Cincinnati
Henry Ford Hospital Cincinnati, OH, USA
Detroit, MI, USA
Janelle Vega MD
David A Rodriguez MD Dermatology Resident
Clinical Assistant Professor University of Miami Miller School of Medicine
University of Miami School of Medicine Miami, FL, USA
Dermatology and Cutaneous Surgery
Miami, FL, USA

Rashmi Sarkar MD MNAMS

Associate Professor
Department of Dermatology
Maulana Azad Medical College
New Delhi, India

xiv
Evidence Levels

Each therapy covered has been assigned a letter from A (most
evidence) to E (least evidence) signifying the amount of pub-
lished evidence available to support its use. The following
table shows the criteria used in making this classification.
A DOUBLE-BLIND STUDY
C CLINICAL TRIAL < 20 SUBJECTS
Small trials with fewer than 20 subjects with significant
design limitations, very large numbers of case reports
(at least 20 cases in the literature), retrospective analyses
of data

At least one prospective randomized, double-blind, D SERIES ≥ 5 SUBJECTS

controlled trial without major design flaws (in the
author’s view) Series of patients reported to respond (at least 5 cases in
the literature)
B CLINICAL TRIAL ≥ 20 SUBJECTS
E ANECDOTAL CASE REPORTS
Prospective clinical trials with 20 or more subjects; trials
lacking adequate controls or another key facet of design, Individual case reports amounting to published experience
which would normally be considered desirable (in the of less than 5 cases
author’s opinion)

xv
This page intentionally left blank
Acknowledgements

Each of us had the invaluable opportunity to collaborate with and Beula Christopher for their assistance in completing this
extraordinary colleagues on various chapters of this book. We extensive project.
thank them for their expertise and commitment to making this
book a success. Drs. Taylor, Badreshia-Bansal,
We also thank Claire Bonnett of Elsevier Publishing who Callender, Gathers, and Rodriguez
guided this project from the very beginning and Nani Clansey

xvii
This page intentionally left blank
Introduction
Each day in dermatology practices and clinics throughout the
United States, we find ourselves increasingly challenged as we
attempt to select the most appropriate treatments for our skin
of color patients. Our challenges are two-fold. First, in the
United States, the number of individuals with skin of color
has increased significantly and continues to do so. Those who
were previously considered in the minority, by the year 2056
will become the majority of US citizens. Thus, we are increas-
ingly encountering skin of color patients including those
with more complicated and difficult to treat dermatologic
disorders. Secondly, differences in the skin and hair of indi-
viduals with skin of color have important implications regard-
ing treatment selection, success and sequelae. Treatment for
Skin of Color is designed to assist and guide clinicians in the
selection of the best therapeutic options for their skin of color
patients, assess the likelihood of success, and educate regard-
ing common and unexpected adverse events.
Who is the patient that we are primarily addressing in Treat-
ment for Skin of Color? For the purposes of this book, we are
defining skin of color patients as those who have Fitzpatrick
Skin Phototypes IV through VI (Table 1). Thus, we are concen-
trating on individuals with darker skin hues including patients
with light brown, brown and black skin tones as compared to
patients with white skin tones.
Additionally, individuals of several racial and ethnic groups
are highly represented in the group of patients with darker skin
hues including those of Southeast and South Asian, Latino or
Hispanic, African, and Native American descent. Although
there is clearly variability in skin hue amongst individuals of
these racial and ethnic groups, many have darker skin hues.
Why is it important to distinguish skin of color patients
from others when considering treatment options? Fundamen-
tal structural and functional differences exist between indi-
viduals with skin of color and those with white skin tones.
These differences may have a direct effect upon a clinician’s
selection of appropriate treatment as well as for the rate of
success of the treatment and occurrence of adverse effects. Key
differences involve melanin content and pigmentation, fibro-
sis and scarring, and tightly coiled hair and follicular disorders,
to name just a few. For example, facial seborrheic dermatitis is
a common cutaneous disorder in individuals of all skin types.
However, because of the lability of melanocytes in individuals
with darker skin tones, post-inflammatory hypopigmentation
is often the presenting complaint in skin of color seborrheic
dermatitis patients. In this patient population, treatment con-
siderations will include agents that simultaneously treat the
seborrheic dermatitis as well as the post-inflammatory hypo-
pigmentation such as lower potency corticosteroids or topical
immune modulators. Additionally, patients should be coun-
seled that the pigmentary alteration is temporary and does not
represent the more serious disorder, vitiligo. Furthermore, for
patients with concomitant scalp seborrheic dermatitis, daily
shampooing is often not the most appropriate treatment given
the tightly coiled hair with low water content and increased
fragility of this population. Rather, the addition of daily topical
treatment agents coupled with once weekly shampooing often
yields appropriate treatment results and avoids potential
adverse events.
Often, adverse event profiles are different in skin of color
patients. Consequently, the selection of treatment may vary. As
an example, a disorder in which liquid nitrogen is an accepted
treatment for white skin hues may not be the appropriate
treatment for skin of color patients due to the sequelae of
hypopigmentation or depigmentation. Additionally, cosmetic
procedures, such as laser hair removal may need to be per-
formed with a lower fluence or a particular laser may be
required given the propensity of skin of color toward laser
induced hyperpigmentation.
Some disorders may occur at increased frequency or even
exclusively in skin of color patient populations. An important
example is central centrifugal cicatricial alopecia (CCCA).
Whereas alopecia areata is covered in general treatment books,
central centrifugal cicatricial alopecia is usually not included.
CCCA appears to be responsible for more cases of scarring
alopecia in African American women as compared to all other
forms of scarring alopecia combined. For this disorder, under-
standing treatment selection, success and sequelae is critically
important. Treatment for Skin of Color will provide insight into
these types of disorders.
Likewise, there are differences in the occurrence of sys�
temic disorders in certain skin of color populations. Hyper�
tension and diabetes affect individuals of African and Latino
descent disproportionately as compared to those of Caucasian
descent. One would expect increased dermatologic disorders
related to these disorders. Examples would include dis�
orders such as drug-induced eruptions which may present
xix
Introduction
Table 1╇ Fitzpatrick Skin Phototypes and Corresponding Color Hues
Type Description
Type I Always burns, never tans (white skin tones)
Type II Always burns, minimal tan (white skin tones)
Type III Burns minimally, tans moderately and gradually (white
skin tones)
Type IV Burns minimally, tans well (light brown skin tones)
Type V Rarely burns, tans deeply (brown skin tones)
Type VI Never burns, tans deeply (dark brown/black skin tones)
differently in skin of color patients, such as photodistributed
hyperpigmentation.
Finally, the definition of treatment success may vary with
skin of color patients as compared to those of Caucasian
descent. Skin of color patients may view acne as unsuccessfully
treated if post-inflammatory hyperpigmentation (PIH) remains
after papules, pustules and comedones have resolved. There-
fore, treatment of PIH is as important as treatment of the acne
in skin of color populations. Either the selection of topical
agents that can simultaneously address acne and PIH, or the
simultaneous use of acne and PIH agents are required in this
population.
How should you use this book?
Treatment for Skin of Color is a great resource that should not
be read once and then filed away in a bookcase. Rather, it
should be kept near you in your practice or clinic to be referred
to on a daily basis. It will provide you with the most up to
date treatment recommendations and you will find that it will
be particularly helpful as you navigate treatment dilemmas.
In addition, under each disease, you will find two invaluable
sections: Commonly Encountered Pitfalls in Skin of Color and
Special Management and Counseling Considerations. These sec-
tions provide diagnostic pearls, examples of potential hin-
drances to achieving treatment goals and how to avoid them,
and effective ways to counsel your skin of color patient.
Organization of the book
Treatment for Skin of Color is organized into six easy to use
sections. Pediatric perspectives on treatment have been added
at the end of certain sections.
• Medical dermatology
• Pigmentary disorders
xx
• Follicular disorders including alopecia
• Tumors benign and malignant
• Cosmetics
• Alternative medicine.
In each section, treatment will be outlined specifically with
your skin of color patients in mind. Additionally, each treat-
ment will be evaluated and assessed based upon the current
evidence available in the literature. The evidence level scale
utilized in this book is one that you may be familiar with as
it encompasses five grades, A through E.
A Double blind, control trial
B Clinical trial involving more than 20 subjects
C Clinical trial involving fewer than 20 subjects
D Case series involving more than 5 subjects
E Anecdotal case reports involving fewer than 5 subjects.
As you will see, there is a relative paucity of data for the treat-
ment of certain diseases that occur in your skin of color
patients. In recent years, the FDA has required populations of
diverse subjects in pivotal trials for new drugs and devices.
Existing clinical trials or case series that include skin of color
patients, when available, have been cited for each treatment.
Nevertheless, there are many disorders in which there are no
clinical trials or case reports that include skin of color subjects.
In these instances, we rely on anecdotal case reports, the expe-
rience of skin of color experts or experience with non-skin of
color patients.
Unlike other books that provide a guide to treatment, we
thought it important to include a section on complementary
and alternative medicine (CAM) because of its importance to
many skin of color populations. Even if you do not suggest or
prescribe to these particular treatments, the CAM section in
this book will provide a firm foundation for you to understand
the fundamentals of these treatments. As you will learn in this
chapter, Americans spend $34 billion dollars annually on
complementary and alternative medicine. CAM’s use by adults
with dermatologic disorders in the US has been estimated at
between 50% and 62%. It has been estimated that in skin of
color patients, 50% of Native Americans, 40% of Asians, 25%
of Blacks and 25% of Hispanics utilize some form of CAM.
This section will provide insight and guide you as to treat-
ments that your patients may already be participating in.
We trust that you will find Treatment for Skin of Color a valu-
able and trusted resource. The treatment sections offer first-
line, second-line and third-line recommendations which will
provide the entire scope of available therapeutic options. We
trust that Treatment for Skin of Color will allow you to select the
most effective and safest treatments for your skin of color
patients.
Susan C Taylor, MD
 PART 1
Medical Dermatology
This page intentionally left blank
Part 1 Medical Dermatology
Acneiform Disorders
Sonia Badreshia-Bansal and Vivek Bansal
Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Acne vulgaris . . . . . . . . . . . . . . . . . . . . . . . . 3
Pomade acne . . . . . . . . . . . . . . . . . . . . . . . 12
Steroid acne . . . . . . . . . . . å°“. . . . . . . . . . . . å°“. 13
Pediatric perspectives: Infantile acne . . . . . . . . . . . 13
Pediatric perspectives: Neonatal acne
(acne neonatorum) . . . . . . . . . . . .å°“ . . . . . . . . . 14
Acne rosacea . . . . . . . . . . . . . . . . . . . . . . . . 14
Hidradenitis suppurativa . . . . . . . . . . . . . . . . . . 19
Perioral dermatitis . . . . . . . . . . . . . . . . . . . . . 21
Acne
Acne vulgaris
Acne vulgaris is a multifactorial disorder of the pilosebaceous
unit.1–4 The pathogenesis involves a complex interaction of
multiple internal and external factors. The four main factors
that cause acne include excess sebum from increased andro-
genic hormonal stimulation (especially at adrenarche), fol-
licular epidermal hyperkeratosis with subsequent plugging of
the follicle, elevated P. acnes population, and subsequent
inflammation.1–4 Medications that can precipitate acneiform
lesions include corticosteroids, lithium, some antiepileptics,
and iodides.5 Genetic factors may also play a role.6
Acne vulgaris is a common skin disease that affects over
85% of people at some time point. It is also an extremely
©2011 Elsevier Ltd, Inc, BV
1â•…
common dermatological problem among ethnic patients and
is found predominantly during adolescence.7 Acne may be
present in the first few weeks and months of life while a
newborn is still under the influence of maternal hormones
and when the androgen-producing portion of the adrenal
gland is disproportionately large.8 Neonatal acne resolves
spontaneously. Adolescent acne commonly begins prior to the
onset of puberty, when the adrenal gland begins to produce
and release higher levels of the androgen hormone. However,
acne is not limited to adolescence – 12% of women and 5%
of men at 25 years of age have acne. By 45 years of age 5% of
both men and women are still affected.7
The diagnosis of acne is primarily clinical and may be char-
acterized by comedones, papules, pustules, nodules and cysts.
Acne vulgaris affects areas of the skin more densely populated
with sebaceous follicles, including the face, upper chest, and
back. A severe inflammatory variant of acne, acne fulminans,
can be associated with fever, arthritis, and additional systemic
symptoms. Darker skin types represent a particular clinical
challenge for dermatologists treating acne due to the higher
risk of post-inflammatory hyperpigmentation (PIH), hyper-
trophic scarring, and keloids (Fig. 1.1). Additionally, acne
lesions may lead to permanent scarring. Although the overall
prognosis is good, acne can result in long-lasting psychosocial
impairment and physical scarring.
The differential diagnosis of acne is extensive. During the
neonatal period, it includes transient sebaceous hyperplasia,
miliaria, and Candida. In adolescence and adulthood, append-
ageal tumors such as trichoepithelioma, trichodiscomas, cysts,
steatocystoma multiplex, and eruptive vellus hair cysts should
be considered in the differential diagnosis. Bacterial folliculi-
tis, pseudomonas folliculitis (if on the lower trunk), rosacea,
pseudofolliculitis barbae, acne keloidalis nuchae, perioral
3
 Part 1 Medical Dermatology
Figure 1.1:╇ This African-American patient presents with active acne and PIH.
dermatitis (if previously treated with topical corticosteroids),
and steroid acne (if treated with oral corticosteroids) may also
be considered. Cultures of skin lesions to rule out Gram-
negative folliculitis are necessary when acne is unresponsive
to treatment or when improvement is not maintained with
treatment.
As with all patients, therapy should be directed toward the
known patho�genic factors. The grade and the severity of the
acne determines which of the following treatments is most
appropriate (Fig. 1.2). When using a topical or systemic anti-
biotic, a benzoyl peroxide should be utilized in conjunction
to reduce the emergence of bacterial resistance. The patient’s
skin color, skin type, and propensity for PIH can influence
choice of formulation of a topical regimen. The ideal acne
treatment for ethnic skin would specifically target the inflam-
matory process as well as the resulting hyperpigmentation.
There are several components to the treatment of mild acne
including topical retinoids, antibiotics and benzoyl peroxide.
Topical retinoids, including tretinoin, adaalene and tazaro-
tene, are comedolytic, normalize follicular hyperkeratiniza-
tion, and are anti-inflammatory.9–11 Retinoids may enhance the
penetration of other topical products and medications.12 They
are known to thin the stratum corneum, cause irritation, and
increase the risk of sunburn.13 Therefore, the use of sunscreen
is essential. Short contact method and gradual titration may
be attempted to increase tolerance and minimize contact irri-
tant dermatitis.14 Although topical retinoids may result in
improvement of PIH, the potential for irritation may provoke
further PIH. Each retinoid has unique characteristics. For
example, the synthetic retinoid, adapalene is light stable and
resistant to oxidation by benzoyl peroxide.15 Finally, retinoids
are known teratogens and contraceptive counseling must be
provided to women of childbearing age.
Benzoyl peroxide is an important bacteriostatic agent that
exerts its affect through the interaction of oxidized intermedi-
ates with elements of bacterial cells. It decreases inflammatory
damage by inhibiting the release of reactive oxygen species
from polymorphonuclear leukocytes.16 However, the risk of
irritation with subsequent PIH may occur. Benzoyl peroxide is
most effective when used in a combination as resistance to this
agent has not been reported.17–18
4
Topical antibiotics are helpful in controlling P. acnes colo-
nization and its pro-inflammatory mediators. The develop-
ment of resistance is significant when antibiotics are used as
monotherapy, and greatly lowered when used in combination
treatment with benzoyl peroxide. Clindamycin inhibits
bacterial protein synthesis by binding to the 50S ribosomal
subunits, causing inhibition of peptide-bond formation.19
Clindamycin suppresses the complement-derived chemotaxis
of polymorphonuclear leukocytes in vitro, thereby reducing
the potential for inflammation.20 Azelaic acid is a naturally
occurring dicarboxylic acid which inhibits growth of P. acnes,
alters hyperkeratinization and may help to lighten PIH.21
Sodium sulfacetamide is a generally well tolerated topical anti-
biotic that restricts P. acnes growth.22 It is available in a 10%
lotion in combination with 5% sulfur with tinted formula-
tions available. Salicylic acids are widely used over-the-counter
products for their comedolytic and mild anti-inflammatory
ability.
Moderate to severe inflammatory acne unresponsive to a
topical combination regimen will require systemic treatment.
First-line antibiotic therapy with tetracycline or its derivatives
doxycycline and minocycline, suppress growth of P. acnes and
are anti-inflammatory. At this time, minocycline is felt to have
less antibiotic resistance but increased side effects including
nausea, vomiting, esophagitis, yeast infection, and sun sensi-
tivity compared to tetracycline.23,24 In addition, minocycline
crosses the blood–brain barrier and increases susceptibility to
pseudotumor cerebri and also can cause a serum sickness-
like reaction, drug-induced lupus, or blue-black pigmenta-
tion.23,24 Erythromycin has the greatest amount of resistance.25
Other antibiotics reportedly useful include trimethoprim-
sulfamethoxazole, and azithromycin. Hormonal therapies
may be effective in the treatment of acne. When hyperandro-
genism is suspected, especially in a female patient with dys-
mennorhea or hirsutism, a hormonal evaluation including
total and free testosterone and DHEA sulfate should be
performed. Oral contraceptive agents have been shown to
be effective in decreasing circulating free testosterone while
spironolactone binds the androgen receptor and reduces
androgen production.26 Side effects with spironolactone
include breast tenderness, dysmennorhea, and abnormalities
in blood pressure.
Severe, scarring acne is best treated with the oral retinoid,
13-cis-retinoic acid. Isotretinoin normalizes follicular hyper�
keratinization and causes sebaceous gland atrophy, thus
reducing sebum production and producing an unfavorable
environment for P. acnes.9 In patients with marked inflamma-
tory acne, lower starting doses may be indicated to prevent the
induction of severe flares during the first month of treatment.28
In cases of acne fulminans or initial retinoid induced flares,
prednisone may decrease the severity of the flare and sub�
sequent exuberant granulation tissue formation. Potential
adverse events are numerous and may include generalized
xerosis, eczematous dermatitis, and elevated triglycerides,
decreased night vision, arthralgias, myalgias, headache,
depression, skeletal hyperkeratosis, elevations in liver function
tests or an abnormal blood count. Teratogenicity is among the
 1â•… Acneiform Disordersâ•… •â•… Acne

TRADITIONAL MEDICAL ACNE THERAPY

Mild Moderate Severe

BPO + R BPO + R + topical Abx +/- oral Abx BPO + R + oral Abx
(if resistant: Isotretinoin) (OR Isotretinoin)
if hyperandrogenic: add OCP +/- if hyperandrogenic: add
spironolactone OCP +/- spironolactone

8 weeks
POSTINFLAMMATORY
ACTIVE ACNE
HYPERPIGMENTATION

Mild Moderate Severe Chemical Light PDT Comedone Itralesional

peels +/- +/- extraction injections
PDT Laser
Skin Skin lightening agents
lightening +/-
agents Chemical peels
+/-
Microdermabrasion
+/-
Laser

Remission
BPO = Benzoyl peroxide
R = Retinoids ACNE SCARS
Abx = Antibiotic
PDT = Photodynamic therapy
OCP = Oral contraceptive pill
Superficial Deep Keloids

Chemical peels Lasers Intralesional injections

+/- +/- +/-
Microdermabrasion Fillers Silicone gel sheets
+/- +/- +/-
Dermabrasion Subcision or punch excision Lasers
+/- +/-
Lasers Chemical peels
+/-
Microdermabrasion
+/-
Dermabrasion

Figure 1.2:╇ Acne algorithm.20,27–31

most serious adverse events and pregnancy should not occur
during or one month post-treatment with oral isotretinoin.
Thorough contraception counseling in females of child bearing
age must be performed and two forms of contraception must
be used concomitantly.
Several other options may be used adjunctively which
include comedone extraction, intralesional injections, chemi-
cal peels, and photodynamic therapy. Comedone extraction
may improve responsiveness to prescribed comedolytic agents,
but inflamed lesions should be avoided. For deep or inflamed
cysts, intralesional corticosteroids can be effective. Chemical
peels with lipophilic comedolytics such as salicylic acid,
glycolic acid, and trichloracetic acid can decrease corneocyte
cohesion.28
The sequela of acne includes acne scarring and PIH which
may be improved after the active acne has been treated
(Fig. 1.3). Options for acne scarring may include dermabra-
sion, laser resurfacing, and soft tissue augmentation. PIH will
improve with time regardless of therapy. However, resolution
can be hastened with vigilant use of sunscreen along with
topical skin lightening agents such as hydroquinone, retinoic
acid, kojic acid, soy, niacinamide, licorice extract, azelaic acid,
glycolic acid, salicylic acid, antioxidants such as vitamin C, as
well as chemical peels and lasers.20

5
 Part 1 Medical Dermatology
Figure 1.3:╇ Asian patient with acne scarring and biopsy consistent with osteoma
cutis.
First-Line Therapies (For Mild to Moderate Acne
Vulgaris)
Topical retinoids
Topical benzoyl peroxide
Topical salicylic acid
Topical antibiotics
Topical azelaic acid
Topical sulfur
Topical dapsone
Oral antibiotics
Combination therapy
The mainstay of acne treatment includes a regimen that
targets the four pathogenic factors. There is strong evidence to
support the use of retinoids and benzoyl peroxide in every
acne regimen. In addition, in mild to moderate acne, topical
and oral anti�biotics can be considered to reduce the inflam-
matory com�ponent found in ethnic skin which is felt to lead
to PIH.
Adapalene in the treatment of African patients. Jacyk WK.
J Eur Acad Dermatol Venereol 2001; 15(Suppl 3):37–42.
To assess the efficacy and safety of topical adapalene gel
0.1% as a treatment for acne vulgaris in Black South African
patients, an open-label study was performed over a 12-week
period. In the 44 subjects completing the trial, adapalene
gel 0.1% showed clear efficacy against both inflammatory
and non-inflammatory lesions. In two-thirds of cases, patients
experienced reductions in both the number of hyperpigmented
macules and the density of hyperpigmentation. Adapalene gel
0.1% is an effective, well-tolerated topical therapy for Black
patients.
6
A comparison of adapalene gel 0.1% vs tretinoin gel
0.025% in the treatment of acne vulgaris in China. Tu P,
Li GQ, Zhu XJ, Zheng J, Wong WZ. J Eur Acad Dermatol Vene�
reol 2001; 15(Suppl 3):31–36.
In this Chinese patient population, 150 patients with grade
II-III acne vulgaris were randomized to 8 weeks of daily treat-
ment with either adapalene gel 0.1% or tretinoin gel 0.025%.
Both adapalene and tretinoin produced dramatic reductions
in total, inflammatory and non-inflammatory lesion counts,
in the range of 69–74% on average. More than 70% of
patients in both groups had complete clearance or marked
improvement. In general, irritation was mild, but was more
common and more severe in the tretinoin group vs the ada-
palene group.
Tretinoin gel microspheres 0.04% versus 0.1% in adoles-
cents and adults with mild to moderate acne vulgaris: A
12-week, multicenter, randomized, double-blind, parallel-
group, phase IV trial. Berger R, Rizer R, Barba A, Wilson D,
Stewart D, Grossman R. Clin Ther. 2007 Jun; 29(6):1086–
1097.
In this multicenter, double-blind, controlled, parallel-
group, Phase IV dose-ranging study, patients with facial
acne were randomized to apply either tretinoin gel 0.04%
or 0.1% each night for 12 weeks in 156 patients (57.1%
A white, 19% Black, 2% Asian, 18.6% Hispanic, 2% Native
A American, 1.3% Other). Both resulted in effective and similar
reductions in inflammatory and noninflammatory lesions,
A
likely from its action on the microcomedone, the precusor
A lesion of acne. However, there was greater reduction in inflam-
A matory lesions with the 0.1% concentration. The 0.4% con-
D centration resulted in fewer side effects such as dryness during
A the early phase of the treatment, but this was not found to be
A significant.
A
A multicenter, double-blind, randomized comparison study
of the efficacy and tolerability of once-daily tazarotene 0.1%
gel and adapalene 0.1% gel for the treatment of facial acne
vulgaris. Webster GF, Guenther L, Poulin YP, Solomon BA,
Loven K, Lee J. Cutis 2002; 69(2 Suppl):4–11.
The efficacy and tolerability of tazarotene 0.1% gel and
adapalene 0.1% gel over 12 weeks was compared in a multi-
center, double-blind, randomized, parallel-group study in 145
patients with mild-to-moderate facial acne vulgaris. Compared
with adapalene, treatment with tazarotene was associated with
a significantly greater incidence of treatment success and
significantly greater reductions in overall disease severity,
non-inflammatory lesion count, and inflammatory lesion
count. However, adapalene demonstrated a superior tolerabil-
ity profile, especially in the early weeks of therapy. By the end
of treatment, patients considered both treatments to be com-
parably well tolerated.
Although retinoids can improve PIH in ethnic patients, caution
must be taken to slowly titrate upward so as to avoid irritant
contact dermatitis and subsequent PIH.
Comparison of five antimicrobial regimens for treatment
of mild to moderate inflammatory facial acne vulgaris in

the community: randomised controlled trial. Ozolins M,
Eady EA, Avery AJ, Cunliffe WJ, Po AL, O’Neill C. Lancet 2004;
364(9452):2188–2195.
In this randomized, observer-masked trial, participants
with facial and/or truncal acne were allocated to one of five
antibacterial regimens. Of approximately 130 participants for
each regimen, moderate or greater improvement at 18 weeks
was reported in about 55% of participants assigned either oral
oxytetracycline or oral minocycline plus topical placebo; in an
average of 63% assigned topical benzoyl peroxide or topical
erythromycin and benzoyl peroxide in a combined formula-
tion plus oral placebo; and in an average of 63% assigned
topical erythromycin and benzoyl peroxide separately. Most
improvement occurred in the first 6 weeks. Differences in effi-
cacy were small and, generally not statistically significant. In
particular, modified-release minocycline, the most expensive
regimen, was not found to be superior. Benzoyl peroxide alone
was the most cost-effective regimen for mild to moderate facial
acne and represents the best value antimicrobial for first-line
use if irritant potential is limited.
Comparison of the efficacy and safety of a combination
topical gel formulation of benzoyl peroxide and clindamy-
cin with benzoyl peroxide, clindamycin and vehicle gel in
the treatments of acne vulgaris. Leyden JJ, Berger RS, Dunlap
FE, Ellis CN, Connolly MA, Levy SF. Am J Clin Dermatol 2001;
2(1):33–39.
Combined use of benzoyl peroxide with topical antibiotics
has been shown to decrease the emergence of antibacterial
resistant species. To determine the efficacy and safety of a
combination benzoyl peroxide plus clindamycin gel, a
10-week, multicenter, double-blind trial of 480 patients with
moderate to severe acne was performed. Patients were
randomized to receive twice-daily treatment with 5% benzoyl
peroxide plus 1% clindamycin, 5% benzoyl peroxide, 1% clin-
damycin, or vehicle. Significantly greater reductions in the
number of inflammatory and total lesions were demonstrated
in patients using combination therapy compared with those
using any of its three individual components.
A novel gel formulation of 0.25% tretinoin and 1.2% clin-
damycin phosphate: efficacy in acne vulgaris patients aged
12 to 18 years. Eichenfield LF, Wortzman M. Pediatr Dermatol.
2009 May-Jun; 26(3):257–261.
This was a subgroup analysis of a phase 3, 12-week, multi-
center, double-blind, randomized, placebo-controlled study
that compared clindamycin/retinoic acid(CLIN/RA) gel, clin-
damycin phosphate, tretinoin, and vehicle in 1710 patients
aged 12–18 years old (23% non-Caucasian). CLIN/RA is sig-
nificantly more effective in reducing mean lesion counts for
all types of lesions regardless of baseline severity than vehicle,
clindamycin, or tretinoin (p < 0.001). The difference in efficacy
was significant at or before week 2 when compared with
vehicle, week 4 when compared with tretinoin monotherapy,
and week 8 when compared with clindamycin monotherapy.
Combination therapy is ideal to offer synergy in their mecha-
nism of action. The medications should penetrate the follicle
1â•… Acneiform Disordersâ•… •â•… Acne
without causing excessive tolerability problems. The manufac-
turer of this dual product shows at least 90% of tretinoin
particles by count have sizes ≤20╯µm and at least 50% have
sizes ≤10╯µm. In addition, the gel contains a mixture of solu-
bilized and crystalline tretinoin which may impact tolerability
by slowing the delivery of tretinoin.
Adapalene-benzoyl peroxide, a fixed-dose combination for
the treatment of acne vulgaris: results of a multicenter,
randomized double-blind, controlled study. Thiboutot DM,
Weiss J, Bucko A, Eichenfield L, Jones T, Clark S; Adapalene-
BPO Study Group. J Am Acad Dermatol. 2007 Nov; 57(5):
791–799.
This was a randomized, multicenter, double-blind, parallel
group study conducted at 36 centers in the United States in
517 patients 12 years and older. Patients were 72% Caucasion,
11% Black, 13% Hispanic, 1% Asian, 3% other. They were
randomized in a 2â•›:â•›2â•›:â•›2â•›:â•›1 ratio to receive either adapalene-
BPO gel, adapalene gel, BPO gel, or gel vehicle for 12 weeks.
The combination therapy regimen consistently provided an
additional decrease of inflammatory and noninflammatory
lesions, with statistically significant differences in total lesion
counts observed as early as the first postbaseline assessment
with good tolerability. Total acne lesions were reduced by 51%,
inflammatory lesions by 63%, and noninflammatory lesions
by 51%.
Combination therapies are highly effective. Retinoids are anti-
comedogenic, antiinflammatory, and enhance penetration.
Adapalene is stable when combined with BPO in the presence
or absence of light. Adapalene and tretinoin have been shown
to induce a dose-dependent inhibition of toll-like receptor 2 in
cultured human monocytes. P acnes acts through the toll-like
receptor 2 to induce the production of proinflammatory
cytokines. There is likely a synergistic anti-inflammatory action
where BPO kills P acnes and adapalene down-regulates the
cell surface receptor that P acnes uses to induce cytokine
production.
Comparison of a salicylic acid cleanser and a benzoyl per-
oxide wash in the treatment of acne vulgaris. Shalita AR. Clin
Ther 1989; 11(2):264–267.
A 4-week crossover study to compare the efficacy of an acne
cleanser containing 2% salicylic acid with that of a 10%
benzoyl peroxide wash was conducted in 30 patients with
mild-moderate acne vulgaris. A review of four clinical studies
and a comedolytic assay attests to the efficacy and safety of
0.5% and 2% solutions of salicylic acid for the treatment of
acne vulgaris. Interestingly, patients treated with the salicylic
acid cleanser for the first 2 weeks showed a significant improve-
ment in acne, but worsened during benzoyl peroxide therapy
over the following 2 weeks. In contrast, patients initially
treated with the benzoyl peroxide wash for the first 2 weeks
continued to improve with salicylic acid cleanser over the next
2 weeks.
Utilizing combination therapy for ethnic skin. Taylor SC.
Cutis 2007; 80(1 Suppl):15–20.
7
 Part 1 Medical Dermatology
Combination therapy has become the gold standard for the
management of acne, particularly for moderate-to-severe cases.
In an attempt to treat and prevent PIH, subjects received com-
bination clindamycin 1%-benzoyl peroxide (BPO) 5% topical
gel containing glycerin and dimethicone. Subjects were rand-
omized to receive this combination therapy in addition to
either a tretinoin microsphere (RAM) gel at concentrations of
either 0.04% or 0.1% or adapalene gel 0.1%. There was a trend
toward better resolution of hyperpigmentation in the subjects
receiving the clindamycin-BPO topical gel in combination
with RAM gel 0.04%. Retinoids have anti-inflammatory activ-
ity while decreasing microcomedo formation resulting in dual
function for acne and PIH.
Early and aggressive treatment of acne and PIH while minimiz-
ing side effects is essential for successful treatment in ethnic
skin.
Versatility of azelaic acid 15% gel in treatment of inflamma-
tory acne vulgaris. Thiboutot D. J Drugs Dermatol 2008;
7(1):13–16.
Two randomized, multicenter, controlled clinical trials
compared the effects of azelaic acid (AzA) 15% gel with either
topical benzoyl peroxide 5% or topical clindamycin 1%, using
a twice-daily dosing regimen. AzA 15% gel resulted in a 70%
median reduction of facial papules and pustules compared
with a 77% reduction with benzoyl peroxide 5% gel and a
63% reduction with clindamycin. 93.9% of physicians reported
patient improvement after an average of 73.1 days. The major-
ity of patients were more satisfied with AzA than with previous
therapies.
Azelaic acid represents a mild but effective treatment option for
active acne, the maintenance phase of acne, and in reducing
PIH due to its skin lightening properties.
Two randomized studies demonstrate the efficacy and safety
of dapsone gel, 5% for the treatment of acne vulgaris.
Draelos ZD, Carter E, Maloney JM, Elewski B, Poulin Y, Lynde
C; United States/Canada Dapsone Gel Study Group. J Am Acad
Dermatol. 2007 Mar; 56(3):439.
Two 12-week, randomized, double-blind phase III studies
were conducted under identical protocols to evaluate the effi-
cacy and safety of twice daily dapsone 5% gel monotherapy
compared with a vehicle gel control in the treatment of acne
vulgaris in 3010 patients (72.9% Caucasian, 14% African
American, 9.4% Hispanic, Asian 2.2%, 1.6% other). Although
clinical improvement was observed with both inflammatory
and noninflammatory lesions, dapsone gel was particularly
effective for inflammatory acne lesions. Reductions in inflam-
matory lesions occurred earlier, within 2 weeks, and were of
greater magnitude by the end of treatment. No significant
change in hemoglobin or other laboratory values, even among
the 44 patients with G6PD deficiencies (glucose-6-phosphate
dehydrogenase) was noted.
Potential mechanisms of action of this sulfone medication in
acne include antiinflammatory and antimicrobial properties
such as direct inhibition of leukocyte trafficking, inhibition of
chemical mediators of inflammation, and altered levels and/or
8
activity of propionibacteria located in the upper third of the
follicles. Although oral dapsone has been associated with
adverse hematologic reactions especially in G6PD, topical for-
mulation has minimal systemic absorption. Although African
Americans are more likely to have G6PD deficiency, topical
dapsone is considered a safe and well tolerated option.
Topical therapy of acne vulgaris using 2% tea lotion in
comparison with 5% zinc sulphate solution. Sharquie KE,
Noaimi AA, Al-Salih MM. Saudi Med J 2008; 29(12):
1757–1761.
This is a randomized, single-blinded comparative clinical
trial in Iraq of 40 patients, ages 13–27 years. 2% tea lotion was
statistically significant in decreasing the number of inflamma-
tory lesions in acne vulgaris, while 5% zinc sulphate solution
was beneficial, but did not reach a statistical significance. 2%
tea lotion was felt to be a good alternative remedy in the treat-
ment of acne vulgaris, and was superior to topical 5% zinc
sulphate solution.
Second-Line Therapies (or First-Line Therapies For
Moderate to Severe Acne Vulgaris)
Intralesional corticosteroid B
Oral antibiotics A
Oral contraceptive pills (if clinically hyperandrogenic) A
Antiandrogens (if clinically hyperandrogenic) B
Use of more aggressive treatment options including oral
antibiotics in conjunction with retinoids and benzoyl peroxide
containing products has been observed to be effective in
first line therapies for moderate to severe acne or second line
therapy for mild to moderate acne. In addition, hormonal
flares have been treated effectively with oral contraceptive pills
and anti-androgenic agents. Treatment of individual nodulo-
cystic lesions with intralesional corticosteroids is effective.
Intralesional corticosteroids in the treatment of nodulo-
cystic acne. Levine RM, Rasmussen JE. Arch Dermatol 1983;
119(6):480–481.
Triamcinolone acetonide at a concentration of 0.63╯mg/mL
was as efficacious as the higher concentration of 2.5╯mg/mL
in the treatment of nodulocystic acne. Lower concentrations
of intralesional corticosteroids are effective, while minimizing
side effects including skin atrophy. Intralesional steroid injec-
tions are most effective as adjunctive treatment for nodulo-
cystic acne when a more rapid response is desired.
Lymecycline in the treatment of acne: an efficacious, safe
and cost-effective alternative to minocycline. Bossuyt L,
Bosschaert J, Richert B, Cromphaut P, Mitchell T, Al Abadie M.
Eur J Dermatol. 2003 Mar-Apr; 13(2):130–135.
A randomized, investigator masked UK study comparing
lymecycline and minocycline in two parallel groups of 134
patients with acne vulgaris was conducted. Lymecycline
300╯mg day is comparable to minocycline in terms of percent

decrease in lesion counts and slightly superior in terms of
efficacy compared to lowered dose of lymecycline. Treatment
with lymecycline was found to be 4 times more cost-effective
than with minocycline.
Doxycycline plus levamisole: combination treatment for
severe nodulocystic acne. Ansarin H, Savabynasab S, Behzadi
AH, Sadigh N, Hasanloo J. J Drugs Dermatol 2008; 7(8):
737–740.
A double-blind, randomized, placebo-controlled trial in
60 Iranian patients with severe and reclacitrant acne vulgaris
were randomly administered oral levamisole 2.5╯mg/kg/wk
(up to 150╯mg/wk) plus doxycycline 100╯mg daily or 100╯mg
of oral doxycycline daily and a placebo. This study is the first
clinical trial that suggests levamisole as an effective and well
tolerated new treatment for severe acne vulgaris.
Optimizing use of oral antibiotics in acne vulgaris. Del
Rosso JQ, Kim G. Dermatol Clin 2009; 27(1):33–42.
For moderate to severe facial or truncal disease, the most
common oral antibiotics for treating acne vulgaris are the
tetracycline derivatives, although macrolide agents such as
erythromycin have also been used extensively. Due to increased
resistance, efficacy of oral tetracycline and erythromycin has
markedly diminished, leading to increased use of doxycycline,
minocycline, and other agents, such as trimethoprim/
sulfamethoxazole and azithromycin. Oral azithromycin has
been reported to be effective in treating acne vulgaris in four
open and two investigator-blinded clinical trials, inclusive
of 187 subjects and 341 subjects, respectively, using various
treatment regimens. Most commonly used regimens included
intermittent dosing schedules, such as three 250╯mg doses per
week, because of a long terminal half-life of 68 hours.
Despite documentation of widespread global prevalence of
antibiotic-resistant P acnes, topical and oral antibiotics that
have been used extensively over several years, such as topical
clindamycin, oral minocycline, and oral doxycycline, continue
to show efficacy in acne vulgaris.
These oral treatments are most appropriately used in combina-
tion with a topical regimen containing benzoyl peroxide and a
topical retinoid. Trimethoprim/sulfamethoxazole may be associ-
ated with adverse reactions that are uncommon but potentially
severe, including toxic epidermal necrolysis (TEN) and Stevens-
Johnson syndrome (SJS), primarily within the first 1 to 2
months after initiation of therapy, and hematologic reactions,
including agranulocytosis, hrombocytopenia, and pancytopenia,
when used in high doses or preexisting folic acid deficiency or
megaloblastic hematopoiesis.
Low-dose adjunctive spironolactone in the treatment of
acne in women: a retrospective analysis of 85 consecutively
treated patients. Shaw JC. J Am Acad Dermatol 2000;
43(3):498–502.
Spironolactone, an established androgen receptor blocker,
is successful in treating adult women with acne, but side
effects are common at the doses reported in published studies
to date. 85 women with acne were treated with low dose
1â•… Acneiform Disordersâ•… •â•… Acne
spironolactone at 50–100╯mg/day, administered either as
single-drug therapy or as an adjunct to standard therapies for
a maximum of 24 months. Clearing or marked improvement
of acne occurred in 66% of patients treated with low doses of
spironolactone while 27% showed partial improvement, and
7% showed no improvement.
Anti-androgenic therapy using oral spironolactone for
acne vulgaris in Asians. Sato K, Matsumoto D, Iizuka F,
Aiba-Kojima E, Watanabe-Ono A, Suga H. Aesthetic Plast Surg
2006; 30(6):689–694.
Spironolactone (initial dose, 200╯mg/day) was administered
orally to 139 Japanese patients (116 females and 23 males) with
severe, recurring, or widespread acne. Most female patients
exhibited excellent improvement over 20 weeks, although some
discontinued treatment because of menstrual disturbances or
other reasons. The treatment was less efficacious for the males
than for the females, and because gynecomastia developed in
three male patients, spironolactone treatment for males was
stopped. Drug eruptions and edema in the lower extremities
were seen in three patients. Hormonal anti-androgenic treat-
ments can inhibit sebum production and acne. Obtaining this
race-specific information is important because Caucasians and
Asians respond differently to hormone therapy.
Despite its proven efficacy, other hormonal anti-androgenic
treatments have limitations. For instance, cyproterone acetate
is potentially carcinogenic, but is still widely used for severe
acne in many countries. Flutamide is also restricted due to its
hepatotoxicity.
Norgestimate and ethinyl estradiol in the treatment of acne
vulgaris: a randomized, placebo-controlled trial. Redmond
GP, Olson WH, Lippman JS, Kafrissen ME, Jones TM, Jorizzo
JL. Obstet Gynecol 1997; 89(4):615–622.
A prospective study of 250 women (84% white, 11% black,
1.7% oriental, 3.4% hispanic) were enrolled in a multicenter,
randomized, double-blind, placebo-controlled clinical trial
with moderate acne vulgaris. Subjects received either 3 con-
secutive weeks of active triphasic oral contraceptive treatment
followed by 1 week of inactive drug for 6 months or 4 weeks
of placebo tablets. Oral contraceptive group was better
than placebo for inflammatory lesions, total lesions, and
investiÂ�gator’s global assessment. Free testosterone decreased
significantly and sex hormone-binding globulin increased sig-
nificantly in the oral contraceptive group thereby reducing the
androgen stimulus in acne pathogenesis.
A combined oral contraceptive containing 3-mg
drospirenone/20-microg ethinyl estradiol in the treatment
of acne vulgaris: a randomized, double-blind, placebo-
controlled study evaluating lesion counts and participant
self-assessment. Lucky AW, Koltun W, Thiboutot D, Niknian
M, Sampson-Landers C, Korner P. Cutis 2008; 82(2):143–
150.
This study compared the efficacy of a low-dose combined
oral contraceptive containing 3-mg drospirenone and 20-
microg ethinyl estradiol administered in a 24-day active pill/
4-day inert pill (24/4) regimen and placebo in 534 women
9
 Part 1 Medical Dermatology

with moderate acne vulgaris. Greater reduction was noted

from baseline to end point in individual lesion counts
Other therapies
(papules, pustules, open and closed comedones) compared
with placebo, but did not affect nodule count.
Acne
• Chemical peels
Effectiveness of norgestimate and ethinyl estradiol in treat-
ing moderate acne vulgaris. Lucky AW, Henderson TA, Olson • Photodynamic therapy
WH, Robisch DM, Lebwohl M, Swinyer LJ. J Am Acad Derma- • Blue and red light
tol 1997; 37(5 Pt 1):746–754.
To evaluate the efficacy of a triphasic combination oral • Nonablative lasers
contraceptive compared with placebo in the treatment of • Comedone extraction
moderate acne vulgaris, 257 healthy female subjects (82%
Caucasian, 9.1% Black, 2.7% Oriental, 5.5% Hispanic, 0.9% • Microdermabrasion
Other) with moderate comedonal or inflammatory acne vul-
garis were enrolled in a multicenter, randomized, double- Acne scarring
blind, placebo-controlled clinical trial. Each month for 6 • Surgery:
months, subjects received either 3 weeks of the oral contracep- – Subcision, punch grafts, dermabrasion
tive containing 0.035╯mg of ethinyl estradiol combined with
the triphasic regimen of norgestimate followed by 7 days of • Lasers:
inactive drug. The mean decrease in inflammatory lesion count – Ablative – CO2, erbium, radiofrequency fractional resur-
was 62.0% and the mean decrease in total lesion count was facing
53.1% in the oral contraceptive group. – Nonablative – Nd:YAG, IPL, fractional photothermoly-
sis, diode, Er:YAG
• Chemical peels:
Third-Line Therapies (or First Line Therapies For Severe
– Superficial depth: glycolic, salicylic acid
Acne Vulgaris)
– Medium depth: Jessner’s, TCA 35%
– Deep peel: Focal trichloracetic acid 95–100%
Oral isotretinoin A
Keloid scarring
• Silicone gel sheeting
The most effective medication in the treatment of severe or
resistant acne is oral isotretinoin. However, the close monitor- • Intralesional corticosteroids
ing required can be a limiting factor for patients and the
• Nonablative lasers
increased regulation of the medication can be a barrier to
physicians wishing to prescribe it. • Surgical excision

Roaccutane treatment guidelines: results of an international • Radiation

survey. Cunliffe WJ, van de Kerkhof PC, Caputo R, et╯al.
Dermatology 1997; 194(4):351–357.
Twelve dermatologists from several countries reviewed the
surveys of 1000 patients. 55% of patients had severe nodular
cystic acne or severe inflammatory acne resistant to conven-
tional treatment and 45% of patients had either moderate or
mild acne which was either recalcitrant, scarring or psychologi-
cally distressing. Treatment was initiated at daily doses of
0.5╯mg/kg and increased to 1.0╯mg/kg, with the aim of achiev-
ing a cumulative dose of > 100–120╯mg/kg. Mucocutaneous
side effects occur frequently but were manageable while severe
systemic side effects were rarely problematic (2%). Significant
cost savings when treating acne patients with oral isotretinoin
as compared to other treatment modalities were further proven
in this study.
This study highlights the important role that oral isotretinoin
plays not only in patients with severe disease but also in
patients with less severe acne, especially if there is scarring and
significant psychological stress associated with their disease.
Acne patients should, when appropriate, be prescribed isotretin-
oin early in their condition to prevent further scarring.
Post-inflammatory hyperpigmentation
• Topicals:
– Lightening agents (see Chapter 10)
– Azelaic acid
– Retinoids
– Sunscreens
• Chemical peels
• Lasers
Insight into skin lightening cosmeceuticals for women of
color. Badreshia-Bansal S, Draelos ZD, J Drugs Dermatol 2007;
6(1):32–39.
This article highlights the research behind several common
skin lightening cosmeceuticals addressing their advantages
and disadvantages. Commercially available products are
discussed with mechanisms of action including phenolic and
non-phenolic compounds with tyrosinase inhibition, inhibi-
tion of melanosome transfer, antioxidants, and increased skin
turnover. Their synergistic role with sunscreens and corrective

10

cosmetic camouflage that are available over the counter are
addressed.
Commonly encountered pitfalls
Acne is the number one reason that the African-American
population consults a dermatologist.32 Acne vulgaris displays
histological and clinical differences in people with skin of color
compared with Caucasians.33 Differences may include a trend
toward greater P. acnes density and differences in sebaceous
gland size and activity.34 In skin of color acne patients, acne is
primarily inflammatory. Surprisingly comedonal lesions in
Blacks display marked inflammation and points towards a
subcategory of inflammatory comedonal acne which may pre-
dispose to PIH. This may be important when selecting appro-
priate therapy. Of the available topical treatments, benzoyl
peroxide is effective as an anti-inflammatory. Retinoids act on
both the comedonal and inflammatory components of acne
and have skin lightening properties. However, a commonly
encountered pitfall with these agents is the occurrence of an
irritant contact dermatitis. It is important that dermatologists
minimize epidermal irritation when treating skin of color
because of the risk of either PIH or postinflammatory hypop-
igmentation. In Dakar, Senegal, acne patients are commonly
treated with benzoyl peroxide and a topical retinoid for their
more advanced disease.4 It is important to note that the use of
alternative medicine occurs frequently, particularly in Asian
populations, where increasing PIH can occur.5
The family of tetracyclines are useful in the treatment of
acne in skin of color but they are not without adverse events
which can lead to common pitfalls. The tetracycline family of
antibiotics are useful in the treatment of acne in skin of color
as they are anti-inflammatory. However, they are not without
adverse events which can lead to pitfalls. Although minocy-
cline has been used safely in this population, it has been
reported to cause a drug hypersensitivity syndrome that can
resemble infectious mononucleosis, as well as fatalities in the
ethnic population.35 In addition, minocycline can induce
generalized dark brown to gray discolorations or dark blue-
black macules (localized at sites of inflammation) on the
lower legs or sun exposed areas. Doxycycline is an effective
treatment, but has photosensitizing properties.
Acne patients with ethnic skin are at an increased risk for
developing post-inflammatory hyperpigmentation and keloi-
dal scarring. Treatment approaches for acne in darker skin
patients must balance early aggressive intervention with the
selection of efficacious and non-irritating agents. For most
patients, a combination of topical retinoids, and topical or oral
antibiotics, with hydroquinone to control hyperpigmentation,
will be successful. For patients with sensitive skin, topical
agents in lower concentrations and with cream vehicles are
preferred. While PIH tends to gradually disappear over time, it
is the number one complaint among acne patients with darker
skin tones. PIH should be treated aggressively with a combina-
tion of sunblock, hydroquinone, retinoid, chemical peels, and
microdermabrasion, when appropriate. Caution must be taken
when treating ethnic skin with ablative or nonablative lasers
and superficial or deep chemical peels due to the high risk of
1â•… Acneiform Disordersâ•… •â•… Acne
further PIH, scarring, and permanent hypopigmentation.
Keloid scarring secondary to acne can be treated with pressure,
silicone gels, intralesional coritcosteroids, surgery, laser treat-
ment or radiation therapy. However, keloids treated with surgi-
cal excision can have rates of recurrence as high as 50%.
Special management & counseling considerations
Successful management of acne in ethnic patients can be
achieved with early initiation of an appropriate combination
drug regimen coupled with good patient compliance. Topical
medications, such as retinoids, may be used safely and effec-
tively to treat acne in skin of color patients. Dryness and irrita-
tion can be minimized by counseling patients to use retinoids
initially in lower concentrations with every other day applica-
tion in addition to daily use of a hydrating agent. Patients
should also be instructed to treat their skin gently, avoiding
scrubbing and picking of acne lesions. Mild, non-abrasive
cleansers, non-comedogenic moisturizers and cosmetics are
preferred. Moisturizers treat the dry skin and prevent irritant
contact dermatitis that may commonly occur. In addition, use
of cocoa butter, a comedogenic agent, is very common among
Black patients and should be avoided. For best results, clini-
cians should manage the entire grooming regimen of the skin
and hair of their ethnic patients. Patients should be advised to
avoid comedogenic hair and scalp preparations that can cause
or exacerbate acne.
Sunscreen use has been found to be scarce in ethnic
patients.32 Chemical sunscreens have a higher likelihood of
exacerbating acne and causing contact dermatitis. Physical sun-
blocks containing micronized zinc oxide or titanium dioxide
are preferred for best protection, especially with coexisting post
inflammatory hyperpigmentation. The administration of a
skin bleaching agent combined with a photo�protective agent
for application in the morning, instead of hydrating cream, is
acceptable to patients, improves com�pliance, and is effective.
Additionally, acne may be improved by controlling hor-
mones and inflammation, both of which may be influenced
by diet. Concurrent with standard anti-acne therapy, a trial of
discontinuing all dairy products and high glycemic foods
should be stopped for at least 6 months to evaluate the effect,
since it is thought to contribute to elevations in growth factors
and hormones that cause acne. Vitamin A supplementation
may help reduce plugging of pores in deficient individuals,
while foods containing ω-3 essential fatty acids (EFAs) may
help to control inflammation.36–42 Individualized care and
close monitoring is required.
References
1. Norris JF, Cunliffe WJ. A histological and immunocytochemical study
of early acne lesions. Br J Dermatol May 1988; 118(5):651–659.
2. Thiboutot D, Gilliland K, Light J, Lookingbill D. Androgen metabo-
lism in sebaceous glands from subjects with and without acne. Arch
Dermatol Sep 1999; 135(9):1041–1045.
3. Pochi PE, Strauss JS. Sebaceous gland activity in black skin. Dermatol
Clin Jul 1988; 6(3):349–351.
4. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ,
et al. Activation of toll-like receptor 2 in acne triggers inflammatory
cytokine responses. J Immunol Aug 1 2002; 169(3):1535–1541.
11
 Part 1 Medical Dermatology

5. Weiss JS. Current options for the topical treatment of acne vulgaris. 31. Quarles FN, Johnson BA, Badreshia S, Vause SE, Brauner G, Breadon
Pediatr Dermatol 1997; 14:480–488. JY, et al. Acne vulgaris in richly pigmented patients. Dermatol Ther
6. Goulden V, McGeown CH, Cunliffe WJ. The familial risk of adult acne: 2007 May–Jun; 20(3):122–127.
a comparison between first-degree relatives of affected and unaffected 32. Poli F. Acne on pigmented skin. Int J Dermatol 2007; 46(Suppl
individuals. Br J Dermatol Aug 1999; 141(2):297–300. 1):39–41.
7. Krowchuk DP, Lucky AW. Managing adolescent acne. Adolesc Med 33. Taylor SC, Cook-Bolden F, Rahman Z, Strachan D. Acne vulgaris
2001 Jun; 12(2). in skin of color. J Am Acad Dermatol 2002; 46(2 Suppl Understanding):
8. Katsambas AD, Katoulis AC, Stavropoulos P. Acne neonatorum: a study S98–S106.
of 22 cases. Int J Dermatol 1999 Feb; 38(2):128–130. 34. Paul Kelly, Susan C Taylor Dermatology for Skin of Color Chapter 12.
9. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et al. The Structure and Function of Skin of Color, Sonia Badreshia-Bansal
Global Alliance to Improve Outcomes in Acne. Management of acne: and Susan C Taylor. New York: McGraw-Hill; 2009.
a report from a Global Alliance to Improve Outcomes in Acne. J Am 35. Tsuruta D, Someda Y, Sowa J, Kobayashi H, Ishii M. Drug hypersensi-
Acad Dermatol 2003; 49(suppl 1):S1–S37. tivity syndrome caused by minocycline. J Cutan Med Surg 2006;
10. Thielitz A, Helmdach M, Röpke EM, Gollnick H. Lipid analysis of fol- 10(3):131–135.
licular casts from cyanoacrylate strips as a new method for studying 36. Koldovsky O. Hormones in milk. Vitam Horm 1995; 50:77–149.
therapeutic effects of antiacne agents. Br J Dermatol 2001; 37. Hoyt G, Hickey MS, Cordain L. Dissociation of the glycaemic and
145:19–27. insulinaemic responses to whole and skimmed milk. Br J Nutr 2005;
11. Verschoore M, Bouclier M, Czernielewski J, Hensby C. Topical retin- 93:175–177.
oids: their uses in dermatology. Dermatol Clin 1993; 11:107–115. 38. Charakida A, Charakida M, Chu AC. Double-blind, randomized,
12. Mills OH Jr, Kligman AM. Treatment of acne vulgaris with topically placebo-controlled study of a lotion containing triethyl citrate and
applied erythromycin and tretinoin. Acta Derm Venereol 1978; 58: ethyl linoleate in the treatment of acne vulgaris. Br J Dermatol 2007;
555. 157:569–574.
13. Halder RM, Brooks HL, Callender VD. Acne in ethnic skin. Dermatol 39. Treloar V, Logan AC, Danby FW, Cordain L, Mann NJ. Comment on
Clin 2003 Oct; 21(4):609–615, vii. acne and glycemic index. J Am Acad Dermatol 2008; 58:175–177.
14. Embil K, Nacht S. The Microsponge Delivery System (MDS): a topical 40. Namazi MR. Further insight into the pathomechanism of acne by
delivery system with reduced irritancy incorporating multiple trigger- considering the 5-alpha-reductase inhibitory effect of linoleic acid. Int
ing mechanisms for the release of actives. J Microencapsul 1996 Sep– J Dermatol 2004; 43:701.
Oct; 13(5):575–588. 41. Danby FW. Acne and iodine: reply. J Am Acad Dermatol 2007;
15. Martin B, Meunier C, Montels D, Watts O. Chemical stability of ada- 56:164–165.
palene and tretinoin when combined with benzoyl peroxide in pres- 42. Danby FW. Diet and acne. Clin Dermatol 2008; 26:93–96.
ence and in absence of visible light and ultraviolet radiation. Br J
Dermatol 1998; 139(suppl 52):8–11.
16. Cove H, Holland KT. The effect of benzoyl peroxide on cutaneous Pomade acne
micro-organisms in vitro. J Appl Bacteriol 1983; 54:379–382.
17. Cunliffe WJ, Holland KT. The effect of benzoyl peroxide on acne. Acta Pomades are comedogenic cosmetic and hair dressings used
Derm Venereol 1981; 61(3):267–269.
18. Bojar RA, Cunliffe WJ, Holland KT. The short-term treatment of acne
commonly to style African American hair. Pomades are oil-
vulgaris with benzoyl peroxide: effects on the surface and follicular based products used to improved hair manageability, straighten
cutaneous microflora. Br J Dermatol 1995; 132:204–208. curly hair or to mold hair into various shapes. The oils in
19. Crawford WW, Crawford IP, Stoughton RB, Cornell RC. Laboratory pomades can cause follicular plugging, setting the stage for
induction and clinical occurrence of combined clindamycin and eryth-
formation of comedones. In addition, other ingredients in
romycin resistance in Corynebacterium acnes. J Invest Dermatol 1979
Apr; 72(4):187–190. pomades may irritate skin, contributing to inflammation.
20. Badreshia-Bansal S, Draelos ZD. Insight into skin lightening African Americans are common users of pomades, oils, or
cosmeceuticals for women of color. J Drugs Dermatol 2007; ointments to style or improve the manageability of their hair,
6(1):32–39. which may lead to forehead, temple or scalp acne, called
21. Webster G. Combination azelaic acid therapy for acne vulgaris. J Am
Acad Dermatol 2000 Aug; 43(2 Pt 3):S47–S50.
pomade acne or acne cosmetica (Fig. 1.4). Pomade acne
22. Gupta AK, Nicol K. The use of sulfur in dermatology. J Drugs Dermatol
2004; 3:427–431.
23. Espersen F. Resistance to antibiotics used in dermatological practice.
Br J Dermatol 1998; 139:4–8.
24. Ochsendorf F. Minocycline in acne vulgaris: benefits and risks. Am J
Clin Dermatol 2010; 11(5):327–341.
25. Eady EA, Jones CE, Tipper JL, Cove JH, Cunliffe WJ, Layton AM.
Antibiotic resistant propionibacterium in acne: need for policies to
modify antibiotic usage. BMJ 1993; 306:555.
26. Kurokawa I, Danby FW, Ju Q, Wang X, Xiang LF, Xia L, et al. New
developments in our understanding of acne pathogenesis and treat-
ment. Exp Dermatol 2009 Oct; 18(10):821–832.
27. Zaenglein AL, Thiboutot DM. Expert Committee Recommendations
for Acne Management. Pediatrics 2006 Sep; 118(3):1188–1199.
28. Quarles FN, Brody H, Johnson BA, Badreshia S. Chemical peels
in richly pigmented patients. Dermatol Ther 2007 May–Jun;
20(3):147–148.
29. Badreshia S, Verma S. Laser and light modalities in the treatment
of acne vulgaris. The CSI Journal of Cosmetic Dermatology Feb 2006;
Vol 1:5–9.
30. Davis EC, Callender VD. A Review of acne in ethnic skin pathogenesis,
clinical manifestations, and management strategies. J Clin Aesthet
Dermatol 2010 April; 3(4):24–38. Figure 1.4:╇ Pomade acne on the forehead.

12
 1â•… Acneiform Disordersâ•… •â•… Acne

usually consists of comedones, papules, and pustules. One

study showed half of Blacks with acne used hair oil or pomade.1
Treatment of pomade acne requires discontinuing or mini-
mizing pomade use and substituting with silicone-based hair
products. If a pomade is used to decrease scalp dryness, it
should be applied 2.5╯cm (1 inch) behind the hairline. When
used to style or improve hair manageability, the pomade
should be applied only to the distal ends of the hair to avoid
contact with the scalp and hairline. Pomade acne will gradu-
ally clear if it is discontinued or if no contact is made with the
skin. However, if pomade acne persists, it should be treated as
described above for acne vulgaris.

Reference
1. Taylor SC, Cook-Bolden F, Rahman Z, Strachan D. Acne vulgaris in
skin of color. J Am Acad Dermatol 2002; 46(2 Suppl Understanding):
S98–106.
A

Steroid acne
Steroid acne presents as monomorphous papulo-pustules
located predominantly on the trunk, extremities and face.
Characteristically, it appears after the administration of topical
or systemic corticosteroids, including intravenous and inhala-
tion therapy. The eruption usually resolves after discontinua-
tion of the corticosteroid and, in addition, may respond to
the usual acne treatment regimens. In some African and Asian B
immigrant groups, use of corticosteroid-containing fade
creams is common and acne is increasingly observed in adults
using these depigmenting agents (Fig. 1.5). Discontinuation
of the corticosteroid will lead to resolution of the acne.

Pediatric perspectives: Infantile acne

Candrice R Heath

First-Line Therapies

Observation (mild cases) C

Infantile acne: a retrospective study of 16 cases. Hello M,
Prey S, Léauté-Labrèze C, et╯al. Pediatr Dermatol 2008; 25(4):
434–438.
In this retrospective review of 16 cases (11 boys and 5 girls),
the cheeks were the primary site of involvement. Cystic lesions
were reported in 25% of the patients. Information regarding
treatment was available for 15 patients; 3 of 15 resolved
without treatment, 4 were treated with benzoyl peroxide, 5
with topical antibiotics and 7 with topical retinoids. Oral
medications were used in 8 patients: 4 with zinc salts, 2 with
macrolides and 2 with isotretinoin. The disease duration was
between 9 and 42 months. Of the 8 patients who reached
C
Figure 1.5:╇ (A) Steroid acne resulting from long-term topical
clobetasol use. (B) and (C) Steroid containing fade creams.
adolescence at the time of the review, only one developed
severe adolescent acne. Of the 16 total cases reviewed, 9
reported scarring, generally atrophic.
Isotretinoin is only approved for children 12 years and older
with nodulocystic acne, though there have been reports in the
literature of use in younger age groups for recalcitrant cases.

13
 Part 1 Medical Dermatology
Second-Line Therapies
Benzoyl peroxide (inflammatory acne) C
Tretinoin (comedonal acne) C Pediatric perspectives: Neonatal acne
Topical antibiotic (erythromycin or clindamycin) C (acne neonatorum)
Adapalene gel 0.1% C
A clinical and therapeutic study of 29 patients with infantile
acne. Cunliffe WJ, Baron SE, Coulson IH. Br J Dermatol 2001;
145(3):463–466.
In this retrospective review of 29 patients (24 boys and 5
girls) with infantile acne, 24% of the cases were mild, 62%
were moderate and 14% of the cases were severe. Inflamma-
tory acne occurred in 59% of the cases, while comedonal
lesions in 17%, nodular lesions in 7% and a mixture of lesions
was seen in 17%. The patients with mild acne were treated
successfully with benzoyl peroxide, erythromycin and topical
retinoids. All of the infants with moderate acne responded
well with a combination of oral erythromycin and topical
treatment, except 2 infants. The two erythromycin resistant
cases were treated with trimethoprim. The majority of the
infants treated with oral antibiotics were treated with oral
therapy for 18 months or less. However 38% of the infants
treated with oral antibiotics required over 24 months of treat-
ment. The acne lasted between 6 and 40 months. One case
was treated successfully with a 4-month course of isotretinoin.
Five of the 29 patients were left with residual scarring.
Topical acne medications should be used very sparingly on the
skin of infants to avoid irritation.
Adapalene gel 0.1% in the treatment of infantile acne: an
open clinical study. Kose O, Koç E, Arca E. Pediatr Dermatol
2008; 25(3):383–386.
12 patients were treated with adapalene gel 0.1% once per
day for 16 weeks. Clearance of lesions was achieved in 4
patients after 3 months of treatment and the remaining 8
patients cleared in 4 months. There was no residual scarring,
however at a one-year follow-up evaluation, 3 patients had a
few mild lesions.
Third-Line Therapies
Oral antibiotics (erythromycin) C infantile acne usually does not occur until 3 to 6 months
Acne rosacea
Rosacea is a common skin disease characterized by vascular
hyper-reactivity, facial flushing, erythema, and telangiectasias.
The pathogenesis appears to be multifactorial. Demodex
mites, normal inhabitants of the human hair follicle, are
14
Oral tetracycline is not recommended in children under 8 years
old due to decreased bone growth and tooth staining.
Candrice R Heath
Although predominately a disease of adults and adolescents,
acne may occur in newborns and infants. The acne that
presents in newborns and infants is more common in males.
Hyperactivity of the sebaceous glands stimulated by androgens
has been the implicated cause of acne in both boys and girls
in this group. Open and closed comedones predominate, but
other inflammatory lesions may occur as well. Neonatal acne
appears within the first few weeks of life. While infantile acne
occurs in infants between 3 months and 6 months of age.
When infantile acne occurs, it usually persists and may be
severe.
First-Line Therapies
Observation C
Daily Cleansing with Gentle Soap
Acne neonatorum: a study of 22 cases. Katsambas AD,
Katoulis AC, Stavropoulos P. Int J Dermatol 1999;
38(2):128–130.
22 patients (18 males and 4 females) with acne neonato-
rum were evaluated. The average age of onset was 3 weeks,
with an average duration of 4 months. The cheeks were
involved in 81.8% of the cases. Papules and pustules were the
predominant lesion type in 72.7% and only 22.7% of the
patients had comedones. A family history of acne was present
in 3 cases. 18 patients were treated with a regimen of daily
cleansing with soap and water. Benzoyl peroxide 5% gel was
used in 3 patients and 1 patient was treated with benzoyl
peroxide 5% gel combined with topical clindamycin alcohol
solution. Though this is a self-limiting disorder, treatments
hastened resolution.
Neonatal acne occurs within the first few weeks of life while
of age.
found in greater numbers in rosacea patients and are thus
theorized to play a role in its pathogenesis.1–3 However, more
studies are needed to conclusively determine if Demodex
truly is pathogenic. Also, inconclusive evidence suggests that
Helicobacter pylori (H. pylori) is associated with the etiology
of rosacea, as increased levels of H. pylori antibodies have
been detected.4,5 However, many of the studies were not
controlled.
 1â•… Acneiform Disordersâ•… •â•… Acne rosacea

Figure 1.7:╇ Rhinophyma in an Indian man.

Figure 1.6:╇ Rosacea with persistent central erythema in an Asian woman.

Rosacea is most common in middle aged fair skinned indi-

viduals, but it can also be seen in individuals of any skin type.
Data on the incidence of rosacea in different racial groups is
variable and generally lacking. Rosacea appears to be more
common in light skinned and Asian populations and less
common in people who have darker skin. However, in ethnic
skin, the diagnosis can be obscured due to skin hue, causing
rosacea to appear more hyperpigmented and less erythema-
tous in darker patients with resulting misdiagnosis. Although
it is considered to be rare among Black patients, it may be
more common than believed to be in the past.6
There are four main subtypes of rosacea: vascular rosacea
characterized by flushing and persistent central erythema (Fig.
1.6); papulopustular rosacea characterized by central facial
papules or pustules; phymatous rosacea with thickened, irreg-
ular, nodular skin, (referred to as rhinophyma when the
nose is involved, Fig. 1.7); and ocular rosacea characterized by
Figure 1.8:╇ Skin eruption induced by an epidermal growth factor receptor
burning, stinging, or the sensation of a foreign body in
inhibitor (Courtesy of Emmy Graber MD, Dave Adams MD, and Diane Thiboutot MD;
the eye. Patients may present with one or a combination of Department of Dermatology, Penn State Milton S. Hershey Medical Center).
symptoms and signs such as facial burning and stinging,
edema, erythematous plaques, dryness, ocular manifestations,
or phymatous changes. Extrafacial involvement may occur Unlike with acne vulgaris, patients with rosacea generally
on the neck and the upper chest. Common rosacea triggers do not report oily skin but instead they experience dryness
include hot and/or cold temperatures, wind, hot drinks, caf- and peeling. The absence of comedones and lack of scarring
feine, exercise, spicy food, alcohol, stress, topical products is another helpful distinguishing feature from acne vulgaris.
that irritate the skin and decrease the stratum corneum Other cutaneous disorders that mimic rosacea include poly-
barrier, or medications that cause flushing. Rosacea fulminans cythemia vera, connective tissue diseases (e.g. lupus erythema-
(pyoderma faciale) is a rare complication characterized by the tous, dermatomyositis, mixed connective tissue disease),
development of nodules and abscesses with sinus tract perioral dermatitis, seborrheic dermatitis, photosensitivity,
formation accompanied by systemic signs. A rare caseating mastocytosis, neuroendocrine tumor such as pheochromocy-
granulomatous variant of rosacea, called lupus miliaris dis- toma or carcinoid, long-term application of topical steroids,
seminatus faciei, can manifest with inflammatory red-brown anticancer agents such as epidermal growth factor receptor
or flesh-colored papules distributed symmetrically across the inhibitor (Fig. 1.8), contact dermatitis, and photosensitivity.
upper part of the face, particularly around the eyes and the Clues to an endocrinopathy include tachycardia, hypertension,
nose. sweats, hot flashes, or diarrhea.

15
 Part 1 Medical Dermatology
Rosacea is a challenging disease to treat and there are very
few large well controlled studies. Additionally, vasodilation, a
key component of rosacea, is unresponsive to therapy. However,
avoiding triggers described above may help with symptoms.7-9
Sunblock may have an effect on vasodilatation since exposure
to ultraviolet radiation leads to destruction of collagen and the
surrounding supportive connecting tissue, which contributes
to vaso�dilation.10,11 Topical therapy includes the use of metro-
nidazole for inflammatory rosacea with resulting slow, gradual
response. Azelaic acid has been helpful in reducing erythema.
Sodium sulfacetamide, as an adjunct to therapy, may improve
severe disease. A combination of topical and oral therapy
usually provides the best results for initial flares. Oral therapy
consists of the tetracycline class of antibiotics administered
over several weeks with a gradual taper for initial flares. Other
options may include trimethoprim/sulfamethoxazole and cip-
rofloxacin but these may be limited by cost and resistant micro-
organisms. In the most severe cases of rosacea with resistant
inflammatory lesions and nodules or rhinophyma, isotretin-
oin therapy may be required. Persistent erythema may respond
best with vascular lasers, which are the mainstay of rosacea
therapy. Cosmetic improvement of rhinophyma may be pro-
duced by mechanical dermabrasion, surgical shave techniques,
CO2 laser or hot loop recontouring. Anecdotal evidence
indicates treatment of rosacea with medications including
beta-blockers, clonidine, naloxone, ondansetron, and
selective serotonin reuptake inhibitors may improve cutane-
ous flushing.
First-Line Therapies
Oral antibiotics A
Topical antibiotics A with SPF 15 sunscreen resulted in significant improvement in
Topical metronidazole A inflammatory lesion count, erythema and telangiectasia scores,
Topical azelaic acid A and investigator and patient global assessment scores com-
Laser surgery B pared with baseline and placebo.
There is evidence to support the use of topical metronidazole
and azelaic acid in the maintenance of rosacea. For
acute, inflammatory flares, oral antibiotics in combination
with topical agents will result in improvement. Finally,
laser therapy may help diminish the erythema associated
with rosacea, but care must be exercised when treating
ethnic patients.
American Acne & Rosacea Society rosacea medical manage-
ment guidelines. Del Rosso JQ, Baldwin H, Webster G,
American Acne & Rosacea Society. J Drugs Dermatol 2008;
7(6):531–533.
The pharmacologic agents discussed are inclusive of those
that are FDA-approved based on phase 3 pivotal trials. The
mainstay of treatment for inflammatory lesions has been oral
antibiotics, but topical metronidazole also may be effective.
Antibiotics are more effective for inflammatory lesions than
for erythema and telangiectasia. Isotretinoin may be effective
16
for inflammatory lesions, edema and rhinophyma and in
some resistant cases, but its use is limited by side effects and
teratogenecity.
Efficacy and safety of azelaic acid (15%) gel as a new treat-
ment for papulopustular rosacea: results from two vehicle-
controlled, randomized phase III studies. Thiboutot D,
Thieroff-Ekerdt R, Graupe K. J Am Acad Dermatol 2003;
48(6):836–845.
Two multicenter, double-blind, randomized, parallel-
group, vehicle-controlled studies were conducted enrolling
665 subjects (92.5% Caucasian, 0.75% African American,
5.75% Hispanic, 0.25% Asian, 0.75% Asian) with moderate
papulopustular rosacea. Azelaic acid 15% gel yielded
statistically significantly higher reductions in mean inflamma-
tory lesion count with improvement in erythema and thera-
peutic success as compared to placebo within 12 weeks of
treatment. In vitro investigations indicate that azelaic acid may
exert an anti-inflammatory effect by scavenging or reducing the
generation and/or release of proinflammatory reactive oxygen
species by neutrophils (much like the effect of tetracyclines in
rosacea).
Randomized placebo-controlled trial of metronidazole 1%
cream with sunscreen SPF 15 in treatment of rosacea.
Tan JK, Girard C, Krol A, Murray HE, Papp KA, Poulin Y,
Chin DA, Jeandupeux D. J Cutan Med Surg 2002;
6(6):529–534.
120 patients with moderate to severe rosacea were enrolled
in a randomized, placebo-controlled, double-blind study.
Study cream was applied twice daily to the entire face over
a 12-week period. Treatment with metronidazole 1% cream
Rosacea patients are prone to irritation, including from ingre-
dients found in sunscreen. It is preferable to use physical block-
ers containing zinc oxide or titanium dioxide and/or ones that
contain dimethicone or cyclomethicone to reduce possible
contact dermatitis.
Combined effect of anti-inflammatory dose doxycycline
(40-mg doxycycline, usp monohydrate controlled-release
capsules) and metronidazole topical gel 1% in the treat-
ment of rosacea. Fowler JF Jr. J Drugs Dermatol 2007;
6(6):641–645.
This 16-week, randomized, double-blind, placebo-
controlled study of an anti-inflammatory dose of doxycycline
plus topical metronidazole gel 1% for mild to moderate
rosacea is presented. At week 12, metronidazole was discon-
tinued and patients continued on either placebo or doxycy-
cline. Combination therapy significantly reduced inflammatory
lesion counts as early as week 4 and through week 12 com-
pared to topical metronidazole 1% gel monotherapy.

Long-pulsed (6-ms) pulsed dye laser treatment of rosacea-
associated telangiectasia using subpurpuric clinical thresh-
old. Jasim ZF, Woo WK, Handley JM. Dermatol Surg 2004;
30(1):37–40.
To examine the effect of long-pulsed PDL at subpurpuric
clinical threshold in the treatment of rosacea-associated tel-
angiectasia, 12 patients with rosacea-associated telangiectasia
were recruited into the study. The 595-nm PDL at a pulse
duration of 6╯ms was titrated up to a fluence between 7 and
9╯J/cm2 to produce immediate purpura lasting only a few
seconds. Pretreatment cooling was achieved by cryogen spray.
Patients were evaluated 6–8 weeks after one PDL treatment.
Two of 12 patients had more than 75% improvement, another
two had 50–75% improvement, and five had 25–50% improve-
ment. Overall, 9 (75%) of 12 patients had more than
25% improvement after a single treatment of PDL. None of
the patients reported lasting post-treatment purpura or
complications.
Caution must be taken when treating ethnic skin, especially
with lasers containing cryogen spray due to possible risk of
hyperpigmentation or hypopigmentation.
Second-Line Therapies
Topical calcineurin inhibitors A benzoyl peroxide/clindamycin by the third week of treatment
Topical sulfur C as compared to placebo. Severity scores for erythema, papules/
Topical antibiotics A pustules, and flushing/blushing decreased more with benzoyl
Oral antibiotics (ampicillin, metronidazole) A peroxide/clindamycin than with vehicle. Application site reac-
Supporting evidence of treatment with topical immuno�
modulators, benzoyl peroxide, and oral antibiotics has been
varied.
Pimecrolimus 1% cream for the treatment of steroid-induced
rosacea: an 8-week split-face clinical trial. Lee DH, Li K, Suh
DH. Br J Dermatol 2008; 158(5):1069–1076.
This investigator-blided, split-face study evaluated the effi-
cacy and safety of pimecrolimus 1% cream for the treatment
of steroid-induced rosacea. Patients applied pimecrolimus 1%
cream twice daily to a randomly allocated half face for the first
2 weeks, and then applied pimecrolimus 1% cream to both
sides of the face for 6 more weeks. After 1 week of application,
a statistically significant improvement in erythema was
observed. Asian subjects (type IV) were included in the study
but no mention was made regarding demographics. Some
patients developed hyperpigmentation as papules and pus-
tules resolved. This was most common in ethnic patients and
was considered to be PIH.
Efficacy of pimecrolimus for the treatment of steroid induced
rosacea is debated. Other case reports have concluded that
1â•… Acneiform Disordersâ•… •â•… Acne rosacea
rosaceiform eruption could be aggravated after tacrolimus or
pimecrolimus treatment.
Combination sodium sulfacetamide 10% and sulfur 5%
cream with sunscreens versus metronidazole 0.75% cream
for rosacea. Torok HM, Webster G, Dunlap FE, Egan N, Jarratt
M, Stewart D. Cutis 2005; 75(6):357–363.
In an investigator-blinded, randomized, parallel-group
study at 6 sites, after 12 weeks of treatment with sodium sul-
facetamide 10% and sulfur 5% cream with sunscreens, there
was a significantly greater percentage reduction in inflamma-
tory lesions compared with metronidazole 0.75% cream, as
well as a significantly greater percentage of subjects with
improved erythema. Seven subjects had poor tolerance to the
sodium sulfacetamide 10% and sulfur 5% cream with sun-
screens, possibly caused by a sulfa drug allergy.
Double-blind, randomized, vehicle-controlled clinical trial
of once-daily benzoyl peroxide/clindamycin topical gel in
the treatment of patients with moderate to severe rosacea.
Breneman D, Savin R, VandePol C. Int J Dermatol 2004;
43(5):381–387.
This 12-week, double-blind, vehicle-controlled, rando�
mized, prospective, parallel-group study in 53 patients with
moderate to severe rosacea showed a difference in favor of
tions were reported in 14% of patients.
Caution must be taken in skin of color with topical agents that
can cause irritant contact dermatitis, and subsequent post-
inflammatory hyperpigmentation.
Comparison of efficacy of azithromycin vs doxycycline in
the treatment of rosacea: a randomized open clinical trial.
Akhyani M, Ehsani AH, Ghiasi M, Jafari AK. Int J Dermatol
2008; 47(3):284–288.
A randomized, open clinical trial was conducted in Iran to
compare the efficacy of azithromycin with doxycycline in 77
rosacea patients who were randomized to receive either azi-
thromycin 500╯mg three times weekly (on Monday, Wednes-
day, and Saturday) in the first month, 250╯mg three times
weekly in the second month, and 250╯mg twice weekly (on
Tuesday, and Saturday) in the third month. The other group
was given doxycycline 100╯mg/day for the three months. Clini-
cal assessment was made at baseline, at the end of first, second,
third, and fifth months after treatment. Statistically significant
improvement was obtained with both drugs. In the azithromy-
cin group, 4 patients had diarrhea, while epigastric burning
was seen in 2 patients using doxycycline. This study indicates
that azithromycin is at least as effective as doxycycline in the
treatment of rosacea.
17
 Part 1 Medical Dermatology
Third-Line Therapies
Topical retinoids
Oral antibiotics: trimethoprim/sulfamethoxazole, ciprofloxacin
Oxymetazoline
Photodynamic therapy
Demodex eradication: topical permethrim, oral ivermectin
H. pylori eradication
Oral isotretinoin
Topical steroid
Ketoconazole
Bifonazole
Ondansetron
Spironolactone
Octreotide
Commonly encountered pitfalls
The various forms of rosacea are more common than once
believed in ethnic skin. The caseating granulomatous variant
may be more common in Asian or Black patients and acne
rosacea may be more common in Black patients than previ-
ously thought. However, rhinophyma has remained relatively
uncommon in Japanese and reported in only 3 cases in
African-Americans.12-15 Ocular rosacea in Black patients has
been found to range from blepharitis and conjunctival hyper-
emia to sight-threatening problems such as corneal neovascu-
larization, thinning, ulceration, and perforation.16
Treating rhinophyma is difficult due to the technical chal-
lenges of producing a good cosmesis. In Japan, almost all cases
are located to the lower half of the nose, which is treated by
full-thickness excision followed by application of either skin
grafts or direct closure.13 Laser therapy and dermabrasion,
a commonly used treatment in the US for rhinophyma, should
be used with caution in ethnic patients since risk of scarring
and pigment dyschromias are high.
Special management & counseling considerations
Combination therapy with mild skin care products, vigilant
use of sunblock, and maintenance medical therapy as well as
vascular lasers may optimize treatment results. As discussed,
care must be taken to avoid irritant contact dermatitis and
18
post-inflammatory hyperpigmentation. The daily use of broad-
spectrum sunblock is recommended for all patients, including
ethnic patients in whom sunscreen use is low. A sunscreen that
protects against both ultraviolet A and ultraviolet B rays should
be selected. Physical blockers with micronized titanium
dioxide and/or zinc oxide are well tolerated in ethnic skin but
may produce a temporary white or purple skin hue. Green
tinted sunscreens or cosmetics can provide coverage of ery-
thema if present in patients with lighter skin hues. Patients
should be encouraged to avoid astringents, toners, menthols,
camphor, waterproof cosmetics requiring solvents to be
removed, or products containing sodium lauryl sulfate which
can irritate the skin. Dietary modulation should aim at avoid-
ance of triggers.
References
1. Erbaǧci Z, Ozgöztas˛i O. The significance of Demodex folliculorum
density in rosacea. Int J Dermatol 1998; 37(6):421–425.
2. Forton F, Seys B. Density of Demodex folliculorum in rosacea: a case
control study using standardized skin-surface biopsy. Br J Dermatol
1993; 128(6):650–659.
3. Bonnar E, Eustace P, Powell FC. The Demodex mite population in
rosacea. J Am Acad Dermatol 1993; 28(3):443–448.
4. Rebora A, Drago F, Picciotto A. Helicobacter pylori in patients with
rosacea. Am J Gastroenterol 1994; 89(9):1603–1604.
5. Utas˛ S, Ozbakir O, Turasan A, Utas˛ C. Helicobacter pylori eradication
treatment reduces the severity of rosacea. J Am Acad Dermatol 1999;
40(3):433–435.
6. Rosen T, Stone MS. Acne rosacea in blacks. J Am Acad Dermatol 1987;
17(1):70–73.
7. Jansen T, Plewig G. Rosacea: classification and treatment. J R Soc Med
1997; 90:144–150.
8. Wilkin JK. Flushing reactions: consequences and mechanisms. Ann
Intern Med 1981; 95:468–476.
9. Guarrera M, Parodi A, Cipriani C, Divano C, Rebora A. Flushing in
rosacea: a possible mechanism. Arch Dermatol Res 1982; 272:311–
316.
10. Wilkin JK. Rosacea. Pathophysiology and treatment. Arch Dermatol
1994; 130:359–362.
11. Plewig G, Jansen T. Rosacea. In: Freedberg IM, Eisen AZ, Wolff K, et al,
editors. Dermatology in General Medicine. 5th ed. New York, NY:
McGraw-Hill Health Professions Division; 1999. p. 785–794.
12. Koffi-Aka V, Kouassi AA, D’Horpock FA, Boka NJ, Ehouo F.
[Rhinophyma in a black African]. Rev Laryngol Otol Rhinol (Bord)
2002; 123(2):109–110.
13. Furukawa M, Kanetou K, Hamada T. Rhinophyma in Japan. Int J
Dermatol 1994; 33(1):35–37.
14. Allah KC, Kossoko H, Yéo S, Richard Kadio M, Assi Djè Bi Djè V.
[Rhinophyma in a black African male patient]. Rev Stomatol Chir
Maxillofac 2009 Dec; 110(6):347–349.
15. Khoo CT, Saad MN. Rhinophyma in a negro: case report. Br J Plast
Surg 1980 Apr; 33(2):161–163.
16. Browning DJ, Rosenwasser G, Lugo M. Ocular rosacea in blacks. Am J
Ophthalmol 1986; 101(4):441–444.

Hidradenitis
suppurativa
Hidradenitis suppurativa (HS) results from rupture of the hair
follicle into the surrounding dermis, which leads to inflamma-
tion and subsequent abscess formation.1 A familial form with
autosomal dominance inheritance has been described. HS
occurs around puberty and women are three times more likely
to develop HS than men. It is common in Europeans and
African-Americans.
HS is a debilitating disease characterized by chronic
inflamed, swollen, painful nodules and sterile abscesses in
apocrine gland-bearing sites including the axillae, groin, and
inframmamary areas. Over time, recurrent boils lead to a hall-
mark of the disease, draining sinus tracts, fistulae, and subse-
quent hypertrophic scars (Fig. 1.9, Fig. 1.10). Often patients
are afflicted with acne, pilonidal cysts, and scalp folliculitis,
giving rise to the term follicular occlusion triad.2 Exacerbating
factors include being overweight, cigarette use, and moisture.
Several complications can occur including scarring, contrac-
ture at the sites of lesions, urethral or rectal fistulas, squamous
cell carcinomas, anemia secondary to chronic infection, and
lymphedema from chronic inflammation and scarring.3
Several treatments have been tried with varied success.
Weight reduction, limiting friction and moisture from sweat-
ing by employing maneuvers such as wearing loose undergar-
ments, using absorbent powders, antiseptic soaps, and topical
aluminum chloride, are somewhat helpful. In early lesions,
topical and intralesional corticosteroids or topical antibiotics
such as clindamycin have proven to be beneficial. In acute
cases, oral antibiotics may be necessary as a short- or long-term
treatment option. Culture of exudates often reveal staphyloco-
cci, streptococci, pseudomonas, and/or anaerobic bacteria.
Female patients presenting with HS should be screened for
Figure 1.9:╇ Severe hidradenitis supparativa (Courtesy of Dave Adams MD,
Department of Dermatology, Penn State Milton S. Hershey Medical Center).
1â•… Acneiform Disordersâ•… •â•… Hidradenitis suppurativa
underlying polycystic ovary syndrome (PCOS) and insulin
resistance. In severe cases, the best results occur with radical
excision with primary closure or grafts. Although extensive
surgery is usually considered the most effective curative
therapy, there is little experience with this approach, with most
being reports from European studies. An alternative has been
the use of ablative laser treatment with secondary intention
healing or radiation treatment. Systemic retinoids may reduce
flares but have not been a reliable cure. Acitretin may have
better results as compared to isotretinoin. Systemic cortico�
steroids often lead to dramatic improvement but results are
not sustained upon discontinuation. Topical antibacterials
containing benzoyl peroxide may be helpful to prevent or
diminish relapses. Individual lesions are slow to heal, usually
with drainage of pus. Remissions may last months to years
and recurrences are common with progressive scarring and
sinus tracts.
First-Line Therapies
Antibiotics A
Surgical excision B
Topical treatment of hidradenitis suppurativa with clin-
damycin. Clemmensen OJ. Int J Dermatol 1983; 22(5):
325–358.
This double-blind trial evaluated the efficacy of topical clin-
damycin in hidradenitis in 27 patients over 3 months. Clin-
damycin was superior to placebo. However, no difference was
found for inflammatory nodules and abscesses at the second
and third month evaluation. Topical clindamycin may be
helpful prior to radical surgery or spontaneous remission.
Combination therapy with clindamycin and rifampicin for
hidradenitis suppurativa: a series of 116 consecutive patients.
Gener G, Canoui-Poitrine F, Revuz JE, Faye O, Poli F, Gabison
Figure 1.10:╇ Hidradenitis supparativa affecting the axilla (Courtesy of Dave Adams
MD; Department of Dermatology, Penn State Milton S. Hershey Medical Center).
19
 Part 1 Medical Dermatology
G, Pouget F, Viallette C, Wolkenstein P, Bastuji-Garin S. Der-
matology. 2009; 219(2):148–154.
This retrospective study evaluated the efficacy of a com�
bination of systemic clindamycin (300╯mg twice daily) and
rifampicin (600╯mg daily) in the treatment of patients with
severe HS which was given for 10 weeks with success. The
proposed mechanism of action was the antibacterial and anti-
inflammatory effects of the two antibiotic agents. No data
regarding long-term follow-up and recurrence was reported.
This treatment regimen was aimed at being suspensive only,
therefore, a maintenance treatment with tetracyclines or zinc
gluconate was prescribed at the conclusion of the 10-week
regimen.
Topical clindamycin versus systemic tetracycline in the treat-
ment of hidradenitis suppurativa. Jemec GB, Wendelboe P.
J Am Acad Dermatol 1998; 39(6):971–974.
46 patients with hidradenitis suppurativa were treated in
a double-blind, double dummy controlled trial. Systemic
therapy with tetracyclines 1 g daily did not produce better
results than topical therapy with clindamycin twice daily after
a minimum of 3 months of treatment. Abscesses were reduced
during the first 3 months of treatment. Nodules only appeared
to be reduced in number after 3 months of treatment. The time
course suggests that nodules may be precursors to abscesses.
Surgical treatment of hidradenitis suppurativa: a retrospec-
tive study of 93 cases. Bordier-Lamy F, Palot JP, Vitry F. Ann
Dermatol Venereol 2008; 135(5):373–379.
Of 93 French patients followed for a mean of 30 months,
209 anatomical sites were operated on with curative intent,
using either limited or wide excision. The disease had been
present for an average of 7.6 years before surgical treatment,
with onset 7 years earlier in women. Surgery required hospi-
talization for an average duration of 6.6 days, caused compli-
cations in 21% of cases and was often perceived as difficult.
Relapse in the operated areas occurred in 33% of cases and
this was more frequent after limited excision. Nevertheless,
74% of patients were ultimately satisfied with their surgical
treatment and most regarded surgery as the only effective
therapy. Wide excision remains the mainstay of therapy in
extensive forms of hidradenitis suppurativa.
Surgical treatment of hidradenitis suppurativa: a 10-year
experience. Kagan RJ, Yakuboff KP, Warner P, Bemard P,
Grange F. Surgery 2005; 138(4):734–740.
This study attempted to determine which factors have the
greatest impact on outcome in order to develop an operative
treatment algorithm. An algorithm for operative treatment was
developed based on the extent of involvement, chronicity, and
comorbid conditions. 57 patients had an average duration of
symptoms of 6.7 years. 92 operative procedures were per-
formed, 50% involved the axilla, 36% involved the perineum,
and 14% involved the inguinal region. Excision and primary
closure was used for localized disease and wide excision with
or without skin grafting was used for diffuse disease. Definitive
treatment involves excision of the involved apocrine tissue and
should be individualized based on the stage and location of
the disease.
20
Total surgical excision may be required in the gluteal region to
prevent further complications including abscess, sinus tract for-
mation, fistulization, and scarring. A multidisciplinary team
approach is necessary and the patients often require an exten-
sive hospital stay with aggressive wound care management.
Surgical treatment of hidradenitis suppurativa with gen-
tamicin sulfate: a prospective randomized study. Buimer
MG, Ankersmit MF, Wobbes T, Klinkenbijl JH. Dermatol Surg
2008; 34(2):224–247.
A prospective randomized study was performed showing
gentamicin sulfate was useful in the surgical treatment of
hidradenitis suppurativa. In the 76 patients in the study,
gentamicin after primary excision of hidradenitis suppurativa
reduced the number of complications 1 week post-
operatively, including dehiscence, infection, and seroma. Fur-
thermore, in 65% of the patients treated with gentamicin, the
wound was completely healed within 2 months. No effect on
the long-term recurrence rate was noted.
Second-Line Therapies
Oral corticosteroids E
Oral isotretinoin B
Hormonal therapy B
Radical surgery B
Severe vulval apocrine acne successfully treated with pred-
nisolone and isotretinoin. Fearfield LA, Staughton RC. Clin
Exp Dermatol 1999; 24(3):189–192.
A case of a 34-year-old woman with severe vulval apocrine
acne was successfully treated initially with prednisolone and
then maintained with long-term isotretinoin. Long-term treat-
ment with isotretinoin may be more successful than a 4–6
month treatment regime.
Long-term results of isotretinoin in the treatment of 68
patients with hidradenitis suppurativa. Boer J, van Gemert
MJ. J Am Acad Dermatol 1999; 40(1):73–76.
This retrospective study assessed low-dose isotretinoin for
4–6 months in the treatment of 68 patients with mild-to-
severe HS. In 23.5% of patients, the condition completely
cleared during initial therapy and 16.2% maintained their
improvement during the follow-up period. Treatment was
more successful in the milder forms of HS. Monotherapy with
isotretinoin for patients with HS usually has a limited thera-
peutic effect.
However, another recent study found no effect or even worsen-
ing with use of oral isotretinoin. It seems unclear if isotretinoin,
which affects sebaceous glands would have an effect on apocrine
glands involved in HS. The limited therapeutic effect may be
due to absence of significant sebaceous gland involvement in
HS, as measured by sebum excretion rates and histopathologic
observation.

Hidradenitis suppurativa in 64 female patients: retrospec-
tive study comparing oral antibiotics and antiandrogen
therapy. Kraft JN, Searles GE. J Cutan Med Surg 2007;
11(4):125–131.
As HS has been linked to a hyperandrogenic state, this
retrospective study examined its association with PCOS. In
64 female HS patients, the prevalence of PCOS was 38.1%.
Antiandrogen therapy was superior to oral antibiotic therapy.
Female patients presenting with HS should be considered for
screening of underlying PCOS and insulin resistance.
A double-blind controlled cross-over trial of cyproterone
acetate in females with hidradenitis suppurativa.
Mortimer PS, Dawber RP, Gales MA. Br J Dermatol 1986;
115(3):263–268.
Ethinyloestradiol 50 micrograms/cyproterone acetate
50╯mg in a reverse sequential regimen was compared with
ethinyloestradiol 50 micrograms/norgestrel 500 micrograms
in 24 female patients. Both treatments produced substantial
improvement in disease activity. 12 patients cleared and
have remained disease free for 18 months, 5 patients improved,
four remained unchanged, while two deteriorated. Cyproter-
one acetate was not more effective than combination therapy,
and both gave a similar reduction in free androgen index.
Cyproterone has been effective in some cases but high doses may
be necessary which may raise safety issues.
Third-Line Therapies
Laser (CO2, Nd:Yag, Laser lipolysis)
Photodynamic therapy
Immunosuppressants
Infliximab
Etanercept
Cyclosporine
Adalimumab
Dapsone
Botulinum toxin
Electrosurgery
Zinc
Granulocyte colony stimulating factor
Perioral dermatitis
Perioral dermatitis is a chronic papulo-pustular and eczema-
tous facial dermatitis which occurs primarily in women. The
etiology of perioral dermatitis is unknown. However, the use
of topical steroids of any strength on the face often precedes
the manifestation of the disease. Many patients abuse topical
corticosteroid preparations, so reassurance and education
1â•… Acneiform Disordersâ•… •â•… Perioral dermatitis
Commonly encountered pitfalls
Controversy exists whether African-Americans have a differ-
ence in the size, number, and morphology of apocrine glands.4
African-Americans have been found to have a higher incidence
of HS than those of European descent. Ingrown hairs may be
a predisposing factor. Care must be taken with excision of
lesions of HS due to the high risk of hypertrophic or keloidal
scarring. Radical surgical excision may be limited in this
patient population in whom keloid scarring is frequent.
Further studies are required in ethnic populations.
Special management & counseling considerations
Unfortunately, none of the treatment modalities have a high
success rate. It is important to note that cases of squamous cell
carcimoma have been reported in longstanding HS. Despite
its low incidence, squamous cell carcinoma remains the most
serious complication and patients with darker skin are not
exempt.
References
1. Balik E, Eren T, Bulut T, Büyükuncu Y, Bugra D, Yamaner S. Surgical
approach to extensive hidradenitis suppurativa in the perineal/peri-
anal and gluteal regions. World J Surg 2009 Mar; 33(3):481–487.
2. Deschamps ME, Payet S, Tournadre A, Soubrier M, Souteyrand P,
D’Incan M. [Efficacy of infliximab in the treatment of follicular
occlusion triad]. Ann Dermatol Venereol 2010 Aug–Sep; 137(8–9):
546–550.
3. Tanaka A, Hatoko M, Tada H, Kuwahara M, Mashiba K, Yurugi S.
Experience with surgical treatment of hidradenitis suppurativa. Ann
Plast Surg 2001; 47:636–642.
4. Paul Kelly, Susan C Taylor Dermatology for Skin of Color Chapter 12.
The Structure and Function of Skin of Color, Sonia Badreshia-Bansal
and Susan C Taylor. New York: McGraw-Hill; 2009.
regarding discontinuation of steroid is essential. Cosmetics,
moisturizers, drooling, and toothpaste have also been impli-
cated in the etiology.1–5
Characteristic skin lesions are grouped perioral, perinasal,
or perioribital red follicular papules, papulovesicles, and/or
papulopustules, and is often termed periorificial dermatitis.
Skin of color patients can, in addition, present with hyper�
pigmentation or hypopigmentation. Perioral dermatitis can
resemble other conditions including rosacea and acne
vulgaris.
21
 Part 1 Medical Dermatology
Anti-inflammatory agents such as antibiotics and topical
immunomodulators may help hasten resolution. The tetracy-
cline class of antibiotics decreases the chemotactic response
of neutrophils, inhibits granuloma formation, and inhibits
protein kinase C. Photodynamic therapy has also been reported
to be helpful in small clinical studies.
First-Line Therapies
Discontinuation of corticosteroids B
Antibiotics B
Perioral dermatitis: etiology and treatment. Bendl BJ. Cutis
1976; 17(5):903–908.
95 patients with perioral dermatitis showed consistent
clearing of the eruption with oral tetracycline in combination
with a topical sodium sulfacetamide-sulfur-hydrocortisone
lotion. When compared to 50 control patients, there were
highly significant quantitative differences. Lubricating and
moisturizing products play a part in the etiology of perioral
dermatitis.
The use of topical agents containing hydrocortisone is not
recommended for treatment of perioral dermatitis.
Topical cosmetics and perioral dermatitis. Dirschka T,
Weber K, Tronnier H. J Dtsch Dermatol Ges 2004;
2(3):194–199.
75 patients with perioral dermatitis and 125 randomly
selected control patients were compared, including history of
atopic dermatitis. There were significant differences between
the patient and control group in morning skin care regimens
including the use of day creams. 25% of patients used topical
corticosteroids which were initiated after the onset of the rash.
There was a correlation also with history of atopic diseases. A
possible interaction between external factors, such as cosmet-
ics, and intrinsic factors, such as atopic dermatitis appears to
contribute to perioral dermatitis, perhaps by subclinical repeti-
tive irritation and overwhelming the reparative capacity of the
epithelial barrier function.
Critical appraisal of reports on the treatment of perioral
dermatitis. Weber K, Thurmayr R. Dermatology 2005;
210(4):300–307.
There were consistent results on a variety of therapeutic
trials regarding treatment of perioral dermatitis. The most
common and consistent treatment guidelines included use of
oral tetracycline as first line agents, topical antibiotics and
metronidazole as second line, and to a lesser extent, recom-
mending no therapy with only spontaneous resolution. The
discontinuation of topical corticosteroids and cosmetics is
thought to be important. Perioral dermatitis is thought to be
self-limited because it spontaneously clears in most patients
within approximately 3 months.
22
Second-Line Therapies
Topical corticosteroids E
Topical sulfur E
Topical metronidazole B
Topical calcineurin inhibitors B
Photodynamic therapy B
Topical azelaic acid D
Oral isotretinoin E
Topical therapy for perioral dermatitis. Bikowski JB. Cutis
1983; 31(6):678–682.
Six patients with perioral dermatitis were successfully
treated with a combination of erythromycin topical solution
twice a day and topically applied hydrocortisone valerate
cream. Hydrocortisone valerate cream, when used in a control-
led, tapered regimen, seems to prevent acute rebound flare of
perioral dermatitis from previous high-potency steroid use or
abuse.
Low-potency topical corticosteroid in cases of exacerbation (if
there is any) during the first 2 weeks after initiation of therapy
may be used.
The multifunctionality of 10% sodium sulfacetamide, 5%
sulfur emollient foam in the treatment of inflammatory
facial dermatoses. Draelos ZD. J Drugs Dermatol. 2010 Mar;
9(3):234–236.
This uncontrolled, observational, prospective, open-label,
single site, eight-week study enrolled 24 subjects (8 with
rosacea, 8 with seborrheic dermatitis, 8 with acne vulgaris) to
evaluate the safety and efficacy of this novel foam formulation.
At 8 weeks, statistically significant improvement was seen in
all conditions. Perioral dermatitis may have been overlapped
with some of these subjects. Sodium sulfacetamide possesses
anti-inflammatory and antibacterial properties while sulfur is
a nonspecific antibacterial and antifungal.
Topical metronidazole in the treatment of perioral derma-
titis. Veien NK, Munkvad JM, Nielsen AO, Niordson AM,
Stahl D, Thormann J. J Am Acad Dermatol 1991; 24(2 Pt 1):
258–260.
In a prospective, double-blind, randomized, multicenter
trial, 108 patients were treated with twice-daily 1% metroni-
dazole cream or tetracycline 250╯mg orally twice daily over 8
weeks. Oral tetracycline was significantly more effective than
topical metronidazole.
Perioral dermatitis in children – clinical presentation,
pathogenesis-related factors and response to topical metro-
nidazole. Boeck K, Abeck D, Werfel S, Ring J. Dermatology
1997;195(3):235–238.
This study investigated perioral dermatitis in children and
the possible pathogenetic mechanisms to response with
topical metronidazole 1% cream in 7 children. Pretreatment

with topical corticosteroids, skin prick test with a panel of six
common aeroallergens, and screening for gastrointestinal col-
onization with Candida albicans was performed. In all but one
child, topical corticosteroids had been used in the face prior
to the first presentation. An association with atopy or intesti-
nal Candida colonization was not found. In all children, skin
lesions resolved after 3–6 months and they remained symptom
free for 2 years.
A randomized, double-blind, vehicle-controlled study of 1%
pimecrolimus cream in adult patients with perioral derma-
titis. Schwarz T, Kreiselmaier I, Bieber T, Thaci D, Simon JC,
Meurer M. J Am Acad Dermatol 2008; 59(1):34–40.
A multicenter, randomized, double-blind, parallel-group
study was performed in 112 adult patients with perioral der-
matitis treated with pimecrolimus cream 1% twice daily or
pimecrolimus vehicle until clearance was achieved up to 4
weeks. After 8 days of treatment, 40% of the patients treated
with pimecrolimus experienced a marked improvement in
their skin symptoms compared with 10% in the vehicle group,
with no rebound over 8 weeks.
Photodynamic therapy for perioral dermatitis. Richey DF,
Hopson B. J Drugs Dermatol 2006; 5(2 Suppl):12–16.
A split-face 21-patient study was conducted in which
one side of the face was treated 4 times weekly with aminole-
vulinic acid photodynamic therapy (ALA-PDT). A protocol of
30-minute ALA incubation with blue light activation was used
while the other side was treated with topical clindamycin.
66.7% of patients completed the study. The side treated with
ALA-PDT achieved a mean clearance of 92.1% compared to
80.9% for the clindamycin-treated side. More studies are
needed to confirm these results and to elucidate the mecha-
nism of action.
Perioral dermatitis with histopathologic features of granu-
lomatous rosacea: successful treatment with isotretinoin.
Smith KW. Cutis. 1990 Nov; 46(5):413–415.
A young woman with granulomatous perioral dermatitis
failed standard therapies. Her eruption cleared after a 20 week
1â•… Acneiform Disordersâ•… •â•… Perioral dermatitis
treatment of oral isotreinoin. Isotertinoin is only indicated for
long-standing and refractory forms of perioral dermatitis.
Commonly encountered pitfalls
Ethnic patients are more likely to use topical bleaching agents
on the face which may contain high potency corticosteroids,
thus increasing their incidence of perioral dermatitis. All light-
ening creams should be assessed by the clinician, especially
from Asian or African countries where lightening creams are
more likely to be adulterated with potent corticosteroids. In
the United States, lightening creams purchased in beauty
supply stores should likewise be carefully evaluated. Discon-
tinuation of lightening agents which contain potent corti�
costeroids is the treatment of choice, though a rebound
phenomenon can occur. A taper of topical steroids may be
considered.
Special management & counseling considerations
Since many cases are associated with the use of topical corti-
costeroids, withdrawal of this medication is the most impor-
tant strategy, despite initial flares. In ethnic patients, as
previously stated, use of bleaching agents should be discon-
tinued if they are suspected of containing high potency corti-
costeroids. Patients should be advised to discard the bleaching
agent as they may be tempted to reuse if uncomfortable symp-
toms associated with a rebound flare occur.
References
1. Manders SM, Lucky AW. Perioral dermatitis in childhood. J Am Acad
Dermatol 1992; 27:688–692.
2. Cohen HJ. Perioral dermatitis. J Am Acad Dermatol 1981;
4:739–740.
3. Ferlito TA. Tartar-control toothpaste and perioral dermatitis. J Clin
Orthod 1992; 26:43–44.
4. Kalkoff KW, Buck A. Etiology of perioral dermatitis. Hautarzt 1977;
28:74–77.
5. Held E, Ottevanger V, Petersen CS, Weismann K. Perioral dermatitis in
children under steroid inhalation therapy. Ugeskr Laeger 1997;
159:7002–7003.
23
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Part 1 Medical Dermatology
Bullous and Pustular
Disorders
Janelle Vega and David A Rodriguez
Bullosis diabeticorum . . . . . . . . . . . . . . . . . . . 25
Bullous pemphigoid . . . . . . . . . . . . . . . . . . . . .26
Impetigo . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Infantile acropustulosis . . . . . . . . . . . . . . . . . . 32
Pemphigus foliaceus . . . . . . . . . . . . . . . . . . . . 33
Pemphigus vulgaris . . . . . . . . . . . . . . . . . . . . . 35
Bullosis diabeticorum
Bullosis diabeticorum (BD) is a relatively rare cutaneous com-
plication of diabetes mellitus, characterized by the spontane-
ous development of tense bullae that may range up to several
centimeters in size. BD usually arises on previously normal
skin particularly on acral areas with the feet the most common
location, (Fig. 2.1), followed by the lower legs, hands and
forearms. The blister is filled with clear, sterile fluid with a
thick consistency.1 Patients report rapid onset, with lesions
often appearing ‘overnight.’ The lesions of BD heal without
scarring in most cases.2
Diabetes mellitus is a common disease of individuals with
skin of color, particularly those of Latin and African American
decent. Although 30% of diabetic patients develop cutaneous
manifestations of their disorder, BD occurs much less com-
monly, with an incidence of 0.16% per year in one series.3,4
Patients may have more than one episode during their life-
time.5 In some cases, the development of BD heralds the onset
of diabetes or insulin resistance.6 The cause of BD is unknown,
but it has been observed in patients with diabetic microangio-
pathy, neuropathy, nephropathy, and retinopathy.7
Therapy
There are no studies regarding appropriate therapy for
BD; some articles suggest that lesions will spontaneously
©2011 Elsevier Ltd, Inc, BV
2â•…
resolve within 2–6 weeks; however, others suggest local care
including de-roofing and treatment with antibiotics when
necessary.
Incidence of bullosis diabeticorum – a controversial cause
of chronic foot ulceration. Larsen K, Jensen T, Karlsmark T,
Holstein PE. Int Wound J 2008; 5(4):591–596.
This single-center retrospective case series included 25
patients with BD; collectively, they experienced 35 episodes
with 93 total bullae. The authors recommend de-roofing
and drainage of the bullae, then the application of a non-
adherent gauze. Patients were followed, received regular
foot care and wore special shoes. Patients that had what
appeared to be an infection were treated with appropriate
antibiotics.
Commonly encountered pitfalls
Although much of the literature suggests that spontaneous
resolution is the rule, some case series have reported
subsequent chronic ulcers, osteomyelitis, and even amputa-
tion following bullosis diabeticorum.8 Careful observation
and close follow-up of these patients are required. Patients
without a history of diabetes who are present with a lesion
similar to BD should be fully evaluated for an existing
endocrinopathy.4
Special management & counseling considerations
In a study of the prevalence of diabetes in different ethnic
groups, the authors found a significantly higher prevalence of
BD in Hispanics, which was statistically significantly higher
than in Blacks, and higher than Asians and Caucasian patients
(Hispanics 334/1000; Blacks 296/1000; Asians 243/1000;
Whites 184/1000).9 Therefore, the prevalence of BD in clinical
practice may be higher depending on the population one is
treating.
25
 Part 1 Medical Dermatology
Figure 2.1:╇ Bullosis diabeticorum. A tense blister on the palm as well as
desquamation at sites of previous bullae. (From Bolognia; Dermatology 2e; Mosby,
copyright Elsevier 2008.)
Bullous pemphigoid
Bullous pemphigoid (BP) is an autoimmune blistering disor-
der equally affecting male and female patients between the
ages of 60 and 80 years. IgG autoantibodies target hemidesmo-
somal proteins (BP230 [BPAg1] and BP180 [BPAg2]) and
result in tense, fluid filled vesicles (Fig. 2.2).1 Often, the early
phase of BP is urticarial, and patients may initially present
with erythematous pruritic plaques, which evolve over time to
form bullae. Common sites of involvement include flexural
areas such as axillae, antecubital fossae, inner thighs, groin,
lower trunk, and lower legs. The one year mortality for BP is
23%; however, when BP patients were matched with controls
for age and comorbidities, there was no significant difference
in mortality. It is likely that BP does not confer increased
mortality to these patients, and mortality results from disease-
independent factors.2
First-Line Therapy
Systemic corticosteroids
Topical corticosteroids
26
References
1. Derighetti M, Hohl D, Krayenbühl BH, Panizzon RG. Bullosis diabeti-
corum in a newly discovered type 2 diabetes mellitus. Dermatology
2000; 200(4):366–367.
2. Aye M, Masson EA. Dermatological care of the diabetic foot. Am J Clin
Dermatol 2002; 3(7):463–474.
3. Bernstein JE, Medenica M, Soltani K, Griem SF. Bullous eruption of
diabetes mellitus. Arch Dermatol 1979; 115:324–325.
4. Larsen K, Jensen T, Karlsmark T, Holstein PE. Incidence of bullosis
diabeticorum – a controversial cause of chronic foot ulceration. Int
Wound J 2008; 5(4):591–596.
5. Basarab T, Munn SE, McGrath J, Russell JR. Bullosis diabeticorum.
A case report and literature review. Clin Exp Dermatol 1995;
20:218–220.
6. Lopez PR, Leicht S, Sigmon JR, Stigall L. Bullosis diabeticorum associ-
ated with a prediabetic state. South Med J 2009 May 7 [Epub ahead of
print].
7. Anand KP, Kashyap AS. Bullosis diabeticorum. Postgrad Med J 2004;
80(944):354.
8. Tunuguntla A, Patel KN, Peiris AN, Zakaria WN. Bullosis diabeticorum
associated with osteomyelitis. Tenn Med 2004; 97:503–504.
9. McBean AM, Li S, Gilbertson DT, Collins AJ. Differences in diabetes
prevalence, incidence, and mortality among the elderly of four racial/
ethnic groups: whites, blacks, hispanics, and asians. Diabetes Care
2004; 27(10):2317–2324.
Patients with mild to moderate disease can be treated ini-
tially with high potency topical corticosteroids and systemic
corticosteroids may be added if they are uncontrolled.3
The need for high dose corticosteroids has not been estab-
lished, and may confer an increased adverse event profile.
Therefore, the dosage of corticosteroids may begin at
0.5–0.75╯mg/kg/day.
Treatment of bullous pemphigoid with prednisolone only:
0.75╯mg/kg/day versus 1.25╯mg/kg/day. A multicenter rand-
omized study. Morel P, Guillaume JC. Annales de Dermatologie
et Vénéréologie 1984; 111:925–928.
In this randomized, multicenter study, patients received
either 0.75╯mg/kg/day or 1.25╯mg/kg/day of prednisolone.
There was no significant difference in clearance of lesions at
21 or 51 days with the two dosage regimens. However, there
were more deaths in the 1.25╯mg/kg/day group.
A comparison of oral and topical corticosteroids in patients
with bullous pemphigoid. Joly P, Roujeau JC, Benichou J,
Picard C, Dreno B, Delaporte E and the Bullous Diseases
French Study Group. N Engl J Med 2002; 346(5):321–327.
This multicenter, non-blinded, randomized trial of 341
participants who were randomized to receive potent topical
cortico�steroids (clobetasol propionate: 40g/d), or prednisone
A (1╯mg/kg/d) for severe disease [>10 new blisters/day]; or
A 0.5╯mg/kg/d for moderate disease [<10 new blisters/day]).
Even in patients with severe disease, survival was higher for

Figure 2.2:╇ Bullous pemphigoid. Classic presentation with multiple bullae arising
on normal and erythematous skin. Several of the bullae have ruptured leaving
circular erosions. (Courtesy Dr. Henry Lim.)
those using topical steroids (76%) versus those on oral ster-
oids (58%, OR 0.44, 95% CI 0.24–0.83). Disease control was
achieved within 3 weeks in 99% of the patients receiving
topical steroids versus 91% of those on oral steroids.
Second-Line Therapy
Topical tacrolimus
Azathioprine
Mycophenolate mofetil
Tetracycline and nicotinamide
Several case reports have demonstrated success of topical
tacrolimus in the treatment of both localized and generalized
BP. Its addition has allowed for tapering of prednisone. Topical
tacrolimus may be a good therapeutic option for patients who
cannot use topical steroids, do not improve with their use, or
for patients with facial lesions.4 One limitation to this therapy
is its high cost particularly when compared to the price of
topical corticosteroids.
Topical tacrolimus is a useful adjunctive therapy for bullous
pemphigoid. Chu J, Bradley M, Marinkovich MP. Arch
Dermatol 2003; 139:813–815.
This case series of two patients describes a 70-year-old
woman on multiple medications including doxycycline, niaci-
namide, mycophenolate mofetil and prednisone (60╯mg/d).
Physicians were unable to taper prednisone without significant
flare of the BP. Topical tacrolimus was added, and after 2
weeks, the area of application was clear of lesions. Over the
next 4 weeks, she was weaned to 20╯mg/d of prednisone
2â•… Bullous and Pustular Disordersâ•… •â•… Bullous pemphigoid
without a flare. The second patient was a 58-year-old man, on
multiple medications including prednisone (20╯mg/d),
tetracycline, and niacinamide was also able to be tapered off
of prednisone three weeks after topical tacrolimus was added
to the therapeutic regimen.
The addition of an immunosuppressive agent to a thera-
peutic regimen that includes an oral corticosteroid, allow
the dosage of the corticosteroid to be reduces or discontinued,
thus reducing possible adverse event from the corticosteroid.
A comparison of oral methylprednisolone plus azathio-
prine or mycophenolate mofetil for the treatment of bullous
pemphigoid. Beissert S, Werfel T, Frieling U, Böhm M,
Sticherling M, Stadler R, et al. Arch Dermatol 2007; 143(12):
1536–1542.
In this prospective, multicenter, randomized, non-blinded
clinical trial, patients were randomized to receive methylpred-
nisolone (0.5╯mg/kg/day) and azathioprine or mycophenolate
mofetil. Clinical remission was achieved faster in patients in
the azathioprine group (23.8 ± 18.9 days vs 42.0 ± 55.3 days),
and lower total doses of methylprednisolone were used overall
in this group (4967.0 ± 12 190.7╯mg vs 5754.0 ± 9692.8╯mg).
Higher adverse effects were seen in the azathioprine group,
with 24% of patients experiencing grade 3 or 4 adverse effects
vs 17% of patients in the mycophenolate mofetil group . There
was decreased liver toxicity in the mycophenolate mofetil
group.
Nicotinamide and tetracycline therapy of bullous pem�
phigoid. Fivenson DP, Breneman DL, Rosen GB, Hersh CS,
Cardone S, Mutasim D. Arch Dermatol 1994; 130:753–758.
In this randomized, non-blinded trial, a total of 20 patients
D were randomized to receive prednisone versus tetracycline
A (500╯mg po qid) and nicotinamide (500╯mg po tid). Only 18
A of the 20 enrolled were treated, and 6 of these were rand-
C omized to the prednisone group. There were two complete
responders in the tetracycline and nicotinamide group versus
one complete responder in the prednisone group. At 10-month
follow-up, there were only 5 participants able to be reached in
the tetracycline group, all of whom were disease free after
tapering. In the prednisone group, three patients were reached
at follow-up, all of whom had flares on a steroid taper. Severe
side effects in the prednisone group included death secondary
to sepsis and in the tetracycline group included transient renal
failure in patients with impaired renal function at the start of
the trial.
Third-Line Therapy
Methotrexate C
Intravenous immunoglobulin (IVIg) C
Rituximab E
27
 Part 1 Medical Dermatology
Low-dose methotrexate is a treatment option for BP patients
who are able to tolerate the treatment or for those who have
coexisting psoriasis. It has been demonstrated that methotrex-
ate confers no difference in mortality as compared to pred-
nisone alone.
A retrospective analysis of patients with bullous pemphig-
oid treated with methotrexate. Kjellman P, Eriksson H, Berg
P. Arch Dermatol 2008; 144(5):612–616.
This was a retrospective study of 138 patients with bullous
pemphigoid who received either methotrexate (median weekly
dosage 5╯mg/week), prednisone, methotrexate and pred-
nisone, or topical glucocorticoids alone. Mild adverse effects
occurred with methotrexate including gastrointestinal tract
irritation, transient alveolitis, anemia, and increasing liver
enzymes. There was a trend toward decreased mortality in the
patients on low dose metho�trexate, and no significant differ-
ence in survival in all groups. Two-year remission in the meth-
otrexate alone group was better than the methotrexate plus
prednisone group, and there were no clinical remissions in the
prednisone alone group.
No randomized controlled trials have been performed on
the use of IVIg in BP, but a consensus statement summarized
the available data up until 2003 which seems promising.5 It
may be helpful to add IVIg when a patient has failed 6 weeks
of prednisone at 1╯mg/kg/day, and has failed therapy even
with the addition of immunosuppressive agents for 10–12
weeks. Other indications for treatment are patients with severe
side effects on corticosteroids or immunosuppressive agents
or with contraindications to these agents. The addition of an
immunosuppressive agent and IVIg may help resolution of BP
by decreasing the burden of circulating autoantibodies, accord-
ing to one case report.
Intravenous immunoglobulin therapy for patients with
bullous pemphigoid unresponsive to conventional immu-
nosuppressive treatment. Ahmed AR. J Am Acad Dermatol
2001; 45:825–835.
In this case series of 15 patients with severe BP refractory
to high dose corticosteroids and immunosuppressive agents,
requiring multiple hospitalizations, the patients received IVIg
at 2╯g/kg per cycle. All patients achieved remission, even after
IVIg was discontinued. Time to effectiveness was a mean of 2.9
months and patients were treated for a mean of 24.4 months
with IVIg. Oral prednisone was tapered over time.
The response to rituximab therapy, a CD 20 monoclonal
antibody targeted at B cells, has been mixed, and although
effective in some patients, deaths have been associated with
its use.6
28
Rituximab in autoimmune bullous diseases: mixed responses
and adverse effects. Schmidt E, Seitz CS, Benoit S, Bröcker EB,
Goebeler M. Br J Dermatol 2007; 156(2):352–356.
In this case series, 2 of the 7 patients had BP and were
treated with intravenous rituximab weekly for one month at a
dose of 375╯mg/m2. One of the patients was a 2-year-old boy
who developed a prolonged hypogammaglobulinemia and
required parenteral feeding; the other patient died of nosoco-
mial pneumonia. These patients had partial and complete
remission of the BP.
Commonly encountered pitfalls
BP has an urticarial phase, which is commonly misdiagnosed
as urticaria. It is important to include BP in the differential
diagnosis of urticarial-like lesions. If treating an elderly patient
with urticaria, it is also helpful to warn them if the lesions
become blisters, that immediate reevaluation by their physi-
cian is required.7
Special management & counseling considerations
Patients with bullous pemphigoid tend to be older and have
more comorbidities. It may be prudent, wherever possible, to
use the least toxic therapy (i.e. topical corticosteroids) to avoid
any unwanted side effects. Mortality in this age group is high,
and it is not desirous to add therapies that further increase it.
References
1. Suárez-Fernández R, España-Alonso A, Herrero-González JE, Mascaró-
Galy JM. [Practical management of the most common autoimmune
bullous diseases]. Actas Dermosifiliogr 2008; 99(6):441–455.
2. Parker SR, Dyson S, Brisman S, Pennie M, Swerlick RA, Khan R, et al.
Mortality of bullous pemphigoid: an evaluation of 223 patients and
comparison with the mortality in the general population in the United
States. J Am Acad Dermatol 2008; 59(4):582–588.
3. Khumalo N, Kirtschig G, Middleton P, Hollis S, Wojnarowska F,
Murrell D. Interventions for bullous pemphigoid. Cochrane Database
Syst Rev 2005; (3):CD002292.
4. Ko MJ, Chu CY. Topical tacrolimus therapy for localized bullous pem-
phigoid. Br J Dermatol 2003; 149:1079–1081.
5. Czernik A, Bystryn JC. Improvement of intravenous immunoglobulin
therapy for bullous pemphigoid by adding immunosuppressive
agents: marked improvement in depletion of circulating autoantibod-
ies. Arch Dermatol 2008; 144(5):658–661.
6. Hertl M, Zillikens D, Borradori L, Bruckner-Tuderman L, Burckhard H,
Eming R, et al. Recommendations for the use of rituximab (anti-CD20
antibody) in the treatment of autoimmune bullous skin diseases.
J Dtsch Dermatol Ges 2008; 6(5):366–373.
7. Brodell LA, Beck LA. Differential diagnosis of chronic urticaria. Ann
Allergy Asthma Immunol 2008; 100(3):181–188.

Impetigo
Impetigo, a superficial infection of the skin, is the most
common cause of bacterial infections in children.1 It is
extremely contagious and can be transmitted by person-to-
person contact as well as via fomites. Children with diseases
that disrupt the epidermal barrier, such as atopic dermatitis,
are especially prone to impetigo.2,3 Atopic dermatitis is a dis-
order that occurs frequently in children with skin of color (Fig.
2.3). The bullous form of impetigo accounts for about one-
third of cases, and is sometimes referred to as pyoderma. This
form is almost always a result of Staphylococcus aureus infec-
tion, due to its ability to produce exfoliative toxins (ET-A,
ET-B), which cleave cell-to-cell adhesions, specifically, desmo-
glein 1.4 Occasionally, bullous impetigo can be caused by
β-hemolytic streptococcus pyogenes.5 Although bullae may appear
anywhere on the skin, moist intertriginous areas on the trunk
are the most common location. Lesions often resolve over
several days.
Although lesions may clear on their own, failure to treat
impetigo appropriately can result in a variety of complica�
tions including septicemia, guttate psoriasis, staphylococcal
scalded skin syndrome, and acute post-streptococcal glomeru-
lonephritis (APGN).6 APGN is a feared complication, which
can occur in as many as 5% of cases of streptococcal bullous
impetigo.7
Figure 2.3:╇ Impetigo. Widespread impetigo in a Filipino child. (From Johnson,
Moy, White: Ethnic Skin – Medical and Surgical, Mosby, copyright Elsevier 1998.)
2â•… Bullous and Pustular Disordersâ•… •â•… Impetigo
First-Line Therapy
Mupirocin A
Fusidic Acid A
Retapamulin A
Topical antibiotics are the first-line therapy for impetigo
when the patient has limited involvement, and is otherwise
well. Mupirocin, fusidic acid and retapamulin are superior to
other topical antibiotics, and have minimal side effects given
their route of administration. Additionally, the antibiotic
concentration is highest in the area intended for treatment,
and topical antibiotics are generally less expensive than oral
antibiotics.
There is a paucity of high-quality trials evaluating the
best therapy for patients with impetigo; however, there
are meta-analyses that demonstrate that topical antibiotics
are at least better than placebo, and evidence suggests that
they may be superior to oral antibiotics, in uncomplicated
cases.8,9
Mupirocin is the first line of treatment for impetigo in the
United States. The mechanism of action of mupirocin, a deriv-
ative of Pseudomonas fluorescens, is the inhibition of transfer-
RNA synthetase. A short course of 3–7 days is effective utilizing
two to three times daily dosing. However, it is important to
note that treatment for longer than 10 days should be avoided
to prevent bacterial resistance.10,11
Mupirocin resistance. Patel JB, Gorwitz RJ, Jernigan JA. Clin
Infect Dis 2009 Sep; 49(6): 935–941.
Low levels of resistance have emerged against mupirocin,
especially in strains of methicillin-resistant Staphylococcus
aureus (MRSA). This is related to its widespread use in the
general population for skin infections, as well as to the use of
mupirocin for elimination of nasal carriage of MRSA.
Topical mupirocin treatment of impetigo is equal to
oral erythromycin therapy. Mertz PM, Marshall DA, Eaglstein
WH, Piovanetti Y, Montalvo J. Arch Dermatol 1989;
125:1069–1073.
This investigator-blinded study of 75 impetigo patients
with Staphylococcus aureus, Streptococcus pyogenes, or both, used
topical mupirocin applied three times daily or oral erythromy-
cin ethylsuccinate (30–50╯mg/kg per day). Mupirocin treat-
ment produced similar clinical results to oral erythromycin
and was superior in the eradication of S. aureus, including
antibiotic-resistant S. aureus. This study proved topical mupi-
rocin to be a safe and effective alternative to oral antibiotic
therapy in the treatment of impetigo.
Fusidic acid, which is not available in the United States, is
an antibiotic derived from Fusidium coccineum that inhibits
bacterial protein synthesis by interfering with ribosome func-
tion.12 Resistance patterns to this topical antibiotic are also
emerging.
29
 Part 1 Medical Dermatology

Fusidic acid cream in the treatment of impetigo in

Second-Line Therapy
general practice: a double blind randomised placebo con-
trolled trial. Koning S, van Suijlekom-Smit LWA, Nouwen JL,
Verduin CM, Bernsen RMD, Oranje AP, et╯al. BMJ 2002; Oral antibiotics B
324:203–206.
This double-blind, randomized, placebo-controlled trial
of fusidic acid cream in combination with povidone-iodine
When bullous impetigo is extensive, treatment with oral
shampoo is compared to placebo. Patients in the fusidic acid
antibiotics may be a more practical option for patients. The
group had a 55% clinical cure rate versus only 13% in
oral route should also be considered if infection is compli-
the placebo group (OR 12.6, 95% confidence interval
cated by systemic symptoms such as fever. It is important to
[5.0–31.5]).
be familiar with resistance patterns of Staphylococci in one’s
A newly approved topical antibiotic for impetigo is retapa-
community when deciding on an oral antibiotic. If no methi-
mulin 1% cream, which has been shown to be superior to
cillin resistance is suspected or culture shows methicillin
placebo in clinical trials.13 The treatment course is similar to
sensitive Staphylococcus aureus (MSSA), β-lactamase resistant
mupirocin (BID × 5 days). This antimicrobial is derived from
penicillins, macrolides and 1st or 2nd generation cepha-
Clitopilus passeckeraianus, and functions by inhibiting the 50S
losporins (Gram-positive activity) are all viable treatment
subunit of the bacterial ribosome, which ultimately inhibits
options. Treatment duration should span 10 days; the dosing
protein synthesis. Although other antibiotics function against
varies according to the medication (see Table 2.1).
the 50S subunit, the mechanism of retapamulin is novel.10
The benefit of the drug also lies in its success against strains
of Staphylococcus aureus that are resistant to fusidic acid, methi-
cillin and mupirocin. It has been shown in trials to be as Third-Line Therapy
effective as fusidic acid and oral cephalexin in the treatment
of impetigo.14 Its recent development and unique mechanism Erythromycin B
of action makes bacterial resistance intrinsically more
unlikely.15

Efficacy and safety of retapamulin ointment as treatment of

impetigo: randomized double-blind multicentre placebo-
controlled trial. Koning S, van der Wouden JC, Chosidow O,
et╯al. Br J Dermatol 2008; 158(5):1077–1082 [Epub 2008
Mar 13].
In this randomized, double-blind, multicenter study reta-
pamulin was tested vs placebo in a total of 213 patients.
Retapamulin ointment had a success rate of 84.6% in contrast
to placebo, which had a success rate of 52.1% (p < 0.001). The
most common side effect was pruritus in the retapamulin
group (6%). Retapamulin was felt to be a safe and effective
treatment with minimal side effects in the treatment of
impetigo.
Topical retapamulin ointment (1%) twice daily for 5 days
versus oral cephalexin twice daily for 10 days in the treat-
ment of secondarily infected dermatitis: results of a rand-
omized controlled trial. Parish LC, Jorizzo JL, Breton JJ,
Hirman JW, Scangarella NE, Shawar RM, et╯al. J Am Acad
Dermatol 2006; 55:1003–1013.
This is a randomized, double-blind, double-dummy, non-
inferiority trial, evaluating the efficacy and safety of retapamu-
lin ointment 1% BID for 5 days in the treatment of secondarily
infected dermatitis vs cephalexin 500╯mg BID for 10 days. The
study yielded results demonstrating that retapamulin was just
as effective as cephalexin both clinically (85.9% vs 89.7%
respectively) and in terms of microbiologic clearance (87.2%
vs 91.8%). Of note is the fact that participants preferred topical
treatment. The study concludes that topical retapamulin is just
as effective in the treatment of secondary infected dermatitis
as oral cephalexin.
Erythromycin should be used as third-line therapy because
of gastrointestinal side effects, and studies that demonstrate
that it may be inferior to topical mupirocin.
Topical mupirocin treatment of impetigo is equal to oral
erythromycin therapy. Mertz PM, Marshall DA, Eaglstein WH,
Piovanetti Y, Montalvo J. Arch Dermatol 1989; 125:
1069–1073.
This investigator-blinded study of 75 impetigo patients
with Staphylococcus aureus, Streptococcus pyogenes, or both, used
topical mupirocin applied three times daily or oral erythromy-
cin ethylsuccinate (30–50╯mg/kg per day). Mupirocin treat-
ment produced similar clinical results to oral erythromycin
and was superior in the eradication of S. aureus, including
antibiotic-resistant S. aureus. This study proved topical mupi-
rocin to be a safe and effective alternative to oral antibiotic
therapy in the treatment of impetigo.
Commonly encountered pitfalls
As with all contagious conditions, crowded living areas,
low-income housing, impaired access to health care, lack of
appropriate sanitation and homelessness will increase a
patient’s risk of developing impetigo. Therefore, it is impera-
tive to maintain a high index of suspicion in these patients.16
The risk for acquiring community-acquired methicillin-
resistant Staphylococcus aureus (CA-MRSA) is increased in these
same conditions. Thus, in treating some patients with ethnic
skin, it is crucial to obtain cultures of bullous lesions or treat
presumptively for CA-MRSA.17

30
 2â•… Bullous and Pustular Disordersâ•… •â•… Impetigo

Table 2.1╇ Oral therapy for impetigo

Medication Adults Format (mg) Dosing Children Forms Dosing

Amoxicillin/clavulanate 250 or 500╯mg 250/125 BID 90╯mg/kg/d 125/31.25/5╯mL Divided BID

(Augmentin) 500/125 200/28.5/5╯mL
875/125 250/62.5/5╯mL
400/57/5╯mL
Cefuroxime (Ceftin) 250 or 500╯mg 250 or 500 BID 90╯mg/kg/d 125╯mg / 5╯mL Divided BID
250╯mg / 5╯mL
Cephalexin (Keflex) 250 or 500╯mg 250, 333, 500, 750 BID - QID 90╯mg/kg/d 125╯mg / 5╯mL Divided BID or QID
250╯mg / 5╯mL
Dicloxacillin (Dynapen) 250 or 500╯mg 250, 500 BID - QID 90╯mg/kg/d 250, 500╯mg BID - QID
Adapted from: George A, Rubin G. A systematic review and meta-analysis of treatments for impetigo. Br J Gen Pract 2003; 53:480–7.

Special management & counseling considerations
MRSA infection is an increasing problem in the treatment
and management of dermatologic diseases. Infection with
resistant strains should be treated according to the Infectious
Disease Society of America (IDSA) practice guidelines. For
CA-MRSA, doxycycline, minocycline, and trimethoprim-
sulfamethoxazole are viable treatment options, whereas for
more serious infection, systemic therapy with vancomycin,
linezolid, clindamycin or daptomycin can be employed.18
Tigecycline is a new glycylcycline antibiotic that has shown
efficacy comparable with that of vancomycin and can be used
in hospital settings.19
Simple practices such as handwashing and general good
hygiene have also been shown to decrease transmission of
impetigo.20
References
1. Darnstadt GL. Cutaneous bacterial infections. In: Behrman RE,
Kliegman RM, Jenson HB, editors. Nelson textbook of pediatrics.
Philadelphia: WB Saunders; 2000. p. 2028–2030.
2. Kiken DA, Silverberg NB. Atopic dermatitis in children, part 1: epide-
miology, clinical features, and complications. Cutis 2006; 78(4):
241–247.
3. Koning S, Verhagen AP, van Suijlekom-Smit LW, Morris A, Butler CC,
van der Wouden JC. Interventions for impetigo. Cochrane Database
Syst Rev 2004; CD003261.
4. Amagai M, Matsuyoshi N, Wang ZH, Andl C, Stanley JR. Toxin in
bullous impetigo and staphylococcal scalded-skin syndrome targets
desmoglein 1. Nat Med 2000; 6:1275–1277.
5. Lin JJ, Wu CT, Hsia SH, Chiu CH. Bullous impetigo: a rare presentation
in fulminant streptococcal toxic shock syndrome. Pediatr Emerg Care
2007; 23:318–320.
6. Hedrick J. Acute bacterial skin infections in pediatric medicine: current
issues in presentation and treatment. Pediatr Drugs 2003; 5(Suppl
1):35–46.
7. Oumeish I, Oumeish OY, Bataineh O. Acute bacterial skin infections
in children. Clin Dermatol 2000; 18:667–678.
8. George A, Rubin G. A systematic review and meta-analysis of treat-
ments for impetigo. Br J Gen Pract 2003; 53:480–487.
9. Mertz PM, Marshall DA, Eaglstein H, Piovanetti Y, Montalvo J. Topical
mupirocin treatment of impetigo is equal to oral erythromycin therapy.
Arch Dermatol 1989; 125:1069–1073.
10. Gelmetti C. Local antibiotics in dermatology. Dermatol Ther 2008;
21(3):187–195.
11. Patel JB, Gorwitz RJ, Jernigan JA. Mupirocin resistance. Clin Infect Dis
2009; 49(6):935–941.
12. Mason BW, Howard AJ. Fusidic acid resistance in community isolates
of methicillin susceptible Staphylococcus aureus and the use of topical
fusidic acid: a retrospective case-control study. Int J Antimicrob Agents
2004; 23:300–303.
13. Koning S, van der Wouden JC, Chosidow O, Twynholm M, Singh KP,
Scangarella N, et al. Efficacy and safety of retapamulin ointment as
treatment of impetigo: randomized double-blind multicentre placebo-
controlled trial. Br J Dermatol 2008; 158(5):1077–1082 [Epub 2008
Mar 13].
14. Parish LC, Jorizzo JL, Breton JJ, Hirman JW, Scangarella NE, Shawar
RM, et al. Topical retapamulin ointment (1%, wt/wt) twice daily for 5
days versus oral cephalexin twice daily for 10 days in the treatment of
secondarily infected dermatitis: results of a randomized controlled
trial. J Am Acad Dermatol 2006; 55:1003–1013.
15. Shawar R, Scangarella-Oman N, Dalessandro M, Breton J, Twynholm
M, Li G, et al. Topical retapamulin in the management of infected
traumatic skin lesions. Ther Clin Risk Manag 2009; 5(1):41–49 [Epub
2009 Mar 26].
16. Feldman SR, Vallejos QM, Whalley LE, Quandt SA, Brooks T,
Cabral G, et al. Blistering eruption in a Latino migrant farmworker.
J Agromedicine 2007; 12(4):81–85.
17. Cohen PR. Community-acquired methicillin-resistant Staphylococcus
aureus skin infections: implications for patients and practitioners. Am
J Clin Dermatol 2007; 8(5):259–270.
18. Stevens DL, Bisno AL, Chambers HF, Everett ED, Dellinger P,
Goldstein EJ, et al. Practice guidelines for the diagnosis and manage-
ment of skin and soft-tissue infections. Clin Infect Dis 2005; 41(10):
1373–1406 [Epub 2005 Oct 14].
19. Huang V, Cheung CM, Kaatz GW, Rybak MJ. Evaluation of dalba-
vancin, tigecycline, minocycline, tetracycline, teicoplanin and vanco-
mycin against community-associated and multidrug-resistant
hospital-associated methicillin-resistant Staphylococcus aureus. Int J
Antimicrob Agents 2010; 35:25–29 [Epub 2009 Nov 8].
20. Luby SP, Agboatwalla M, Feikin DR, Painter J, Billhimer W, Altaf A,
et al. Effect of handwashing on child health: a randomised controlled
trial. Lancet 2005; 366(9481):225–233.

31
 Part 1 Medical Dermatology
Infantile acropustulosis
Recurrent, acral pruritic, vesiculopustules during infancy char-
acterizes this rare disorder. It is most commonly seen in boys
with skin types IV–VI. The onset of lesions is within the first
6 months of age which regress within 1–2 weeks, and recur
monthly.1 The frequency of recurrence and duration of lesions
wanes until they resolve, usually around 3 years of age. Infantile
acropustulosis most commonly occurs on the palms and soles,
dorsa of hands and feet (Fig. 2.4), and between the digits.
Rarely, these lesions occur in an axial distribution. Although
this disease resolves spontaneously, extreme pruritus causes
significant discomfort, difficulty sleeping, and excoriations,
which can become secondarily infected.2
First-Line Therapies
Topical corticosteroids
Oral antihistamines
Studies have shown that medium to high potency corticos-
teroids for a brief time are safe and effective in treating pruri-
tus. If needed, the corticosteroids can be used with wet wraps
to help increase their efficacy.3 Supplementation with oral
antihistamines, usually at sedating doses, is also effective in
alleviating the symptoms.4 Although the pustules are sterile,
treatment with oral antibiotics has been reported to be helpful,
likely due to their anti-inflammatory properties. Secondarily
infected lesions should be treated with antibiotics and topical
antibiotics are usually adequate.
Infantile acropustulosis revisited: history of scabies and
response to topical corticosteroids. Mancini AJ, Frieden IJ,
Paller AS. Pediatr Dermatol 1998; 15(5):337–341 [PubMed
PMID: 9796580].
Figure 2.4:╇ Infantile acropustulosis with multiple pustules on the foot of
an African-American child. (Courtesy of Valarie Callander, MD.)
32
This is a retrospective study of 21 patients diagnosed with
infantile acropustulosis, in which the history of scabies and
prior treatment for scabies was analyzed. In 14 of 21 patients,
there was a history of scabies, but only 2 of whom had evi-
dence of scabies on microscopic analysis. All patients were
treated with topical corticosteroids ranging from class I to VI
with no adverse events.
Second-Line Therapies
Dapsone D
Dapsone, a potent inhibitor of neutrophil chemotaxis, at a
dose of 2╯mg/kg/day, is thought to be the most effective oral
medication for infantile acropustulosis, but should be reserved
for cases refractory to treatment. Potential severe side effects
including aplastic anemia, methemoglobinemia, and periph-
eral motor neuropathy precludes wide-spread use. There have
B
been no randomized controlled trials, and support for its use
E is basis of multiple case series and case reports.5,6
Atypical acropustulosis in infancy. Truong AL, Esterly NB. Int
J Dermatol 1997; 36(9):688–691.
A 20-month-old girl with lesions on the feet, extending to
the legs, chest and scalp, was treated for infantile acropustulo-
sis with dapsone therapy initially at 1╯mg/kg/day, and then
increased to 2╯mg/kg/day. Dapsone was tapered over 11
months with no recurrence of disease.
Commonly encountered pitfalls
The primary differential diagnosis for infantile acropustuloss
includes infestation with Sarcoptes scabeii, given the acral loca-
tion, pruritus, and similar clinical presentation (see Table 2.2).
Patients with scabies may have burrows interdigitally or on
the wrists, in addition to close family members with similar
symptoms.7 Microscopic confirmation of the diagnosis can be
performed with mineral oil immersion revealing eggs, scybala
and/or mites. Some authors believe that acropustulosis of
infancy represents a hypersensitivity to prior scabies infesta-
tion, which resolves over time. Other studies have demon-
strated that although many patients have been diagnosed with
and treated for scabies, few of these patients had histologic
confirmation of infection.3
Special management & counseling considerations
If dapsone is being considered for treatment of severe infantile
acropustulosis, the presence of glucose-6-phosphate dehydro-
genase (G6PD) deficiency must be considered as it has a
higher prevalence in patients of African or Mediterranean
descent. It is these very patients who are more commonly
affected by acropustulosis of infancy. Therefore, it is important
to screen for G6PD enzyme deficiency prior to instituting
therapy to avoid a hemolytic crisis.8
 2â•… Bullous and Pustular Disordersâ•… •â•… Pemphigus foliaceus
Table 2.2╇ Differential diagnosis of neonatal pustular disorders
Non-infectious causes Infectious causes
Erythema toxicum Bacterial
neonatorum • Bullous impetigo
Infantile acropustulosis • Pseudomonas aeruginosa
Transient neonatal pustular
melanosis
Neonatal acne Viral
Miliaria pustulosa • Herpes simplex
Ofuji’s disease (eosinophilic • Varicella zoster
folliculitis)
Incontinentia pigmenti Fungal
Congenital self-healing • Candidiasis (Congenital or neonatal)
Langerhans cell histiocytosis • Pityrosporum folliculitis
Parasitic
• Scabies
Adapted from: Van Praag MC, Van Rooij RW, Folkers E, Spritzer R, Menke HE, Oranje
AP. Diagnosis and treatment of pustular disorders in the neonate. Pediatr Dermatol
1997; 14:131–43.
Pemphigus foliaceus
Pemphigus foliaceus (PF) is an autoimmune blistering disor-
der similar to pemphigus vulgaris. The antigen in this disorder
is desmoglein 1, a component of desmosomes primarily
present in skin and in lesser quantity in mucosal surfaces.
Therefore, clinical disease is expressed only in the skin, with
sparing of the mucosa. This disease shares a common antigen
with staphylococcal scalded skin syndrome and bullous
impetigo, and as such, shares clinical and histologic findings
with these disorders. Subcorneal vesicles characterize the dis-
order but because of the superficial nature of the vesicle, they
are rarely seen intact. Clinically, patients have disseminated
red, scaly plaques (Fig. 2.5).
The sporadic form of PF can be seen anywhere in the world.
Its incidence in North America and Europe is 1 in 10 and it is
as common as pemphigus vulgaris.1 In contrast, the endemic
form of PF, known as fogo selvagem, is present in up to 3% of
the population in some rural areas of Brazil, Colombia, Peru
and Tunisia.2,3 Patients with endemic PF tend to be younger
than those with sporadic PF (teenage and 20s). In addition
to genetic susceptibility (HLA Class II DR4, DR 14 and DR 1
alleles), environmental factors influence the development
of fogo selvagem.4 There is a seasonal variation with higher
incidence during the rainy season. It has been associated
with crowded living conditions in underdeveloped areas,
with decreasing incidence as an area becomes urbanized.
Interestingly, there is a high prevalence of bed bugs and kissing
bugs in the homes of patients with endemic PV, and their
References
1. Mancini AJ, Frieden IJ, Paller AS. Infantile acropustulosis revisited:
history of scabies and response to topical corticosteroids. Pediatr
Dermatol 1998; 15(5):337–341.
2. Child FJ, Fuller LC, Higgins EM, Du Vivier AW. A study of the spectrum
of skin disease occurring in a black population in south-east London.
Br J Dermatol 1999; 141(3):512–517.
3. Braun-Falco M, Stachowitz S, Schnopp C, Ring J, Abeck D. Infantile
acropustulosis successfully controlled with topical corticosteroids
under damp tubular retention bandages. Acta Derm Venereol 2001;
81(2):140–141.
4. Vignon-Pennamen MD, Wallach D. Infantile acropustulosis. A clinico-
pathologic study of six cases. Arch Dermatol 1986; 122(10):
1155–1160.
5. Truong AL, Esterly NB. Atypical acropustulosis in infancy. Int J
Dermatol 1997; 36(9):688–691.
6. Kahn G, Rywlin AM. Acropustulosis of infancy. Arch Dermatol 1979;
115:831–833.
7. Kamal R, Shahab A, Loo D. Bullous scabies. J Am Acad Dermatol
2003; 49:346–350.
8. Minucci A, Giardina B, Zuppi C, Capoluongo E. Glucose-6-phosphate
dehydrogenase laboratory assay: How, when, and why? IUBMB Life
2009; 61(1):27–34.
homes are usually near rivers, which is why the black fly
(Simulium spp.) is also suspected in transmission.5,6
First-Line Therapy
Topical corticosteroids C
For severe, extensive disease, systemic treatment is the same
as for pemphigus vulgaris. In this section, we will discuss
topical therapy for PF. Topical corticosteroids are the first-line
and the most common therapy for limited cutaneous
disease. There are no large studies regarding the use of topical
steroids. One group suggests using the levels of desmoglein 1
antibodies to guide initial treatment with topical corticoster-
oids only (in the case of low levels), instead of immediately
starting systemic treatment.7 Mild pemphigus may be treated
with topical agents initially until relapse requires systemic
therapy.
The treatment of mild pemphigus vulgaris and pemphigus
foliaceus with a topical corticosteroid. Dumas V, Roujeau JC,
Wolkenstein P, Revuz J, Cosnes A. Br J Dermatol 1999;
140(6):1127–1129.
In this case series of seven patients with pemphigus vulgaris
and pemphigus foliaceus (mild), patients were treated with
clobetasol propionate cream 0.05% twice daily with no sys-
temic treatment. Within 2 weeks, all cutaneous lesions resolved
in the 7 patients, and with in one month, mucosal lesions
33
 Part 1 Medical Dermatology
Figure 2.5:╇ Pemphigus foliaceus. (Courtesy Dr. Henry Lim.)
likewise resolved. Three of the patients required systemic treat-
ment within 2–11 months, however 4 of them were main-
tained only on topical agents for at least 19 months.
Second-Line Therapy
Tacrolimus D
Tacrolimus is a topical immunomodulator, which binds
to immunophilins and decreases downstream transcription
of inflammatory pathways, specifically, IL-2 and IL-2 receptors
in T-lymphocytes. Case reports describe its use in pemphigus
foliaceus. One case report was of a split-face trial of tacrolimus
0.1% ointment compared with clobetasone butyrate in
which equivalent efficacy was demonstrated.8,9 Tacrolimus
may be beneficial in areas where one wants to avoid sec�
ondary side effects of topical corticosteroid use, such as
telangiectasias.
Equal efficacy of topical tacrolimus and clobetasone butyrate
in pemphigus foliaceus. Cohen SN, Lim RP, Paul CJ, Abdullah
A. Int J Dermatol 2006; 45(11):1379.
Case report of a 71 year old woman with pemphigus
foliaceus, on dapsone 100╯mg daily, with atrophy and tel-
angiectasias from long-term application of topical corticoster-
oids. The patient used twice daily tacrolimus ointment 0.1%
on one side, and clobetasone butyrate on the other side. After
one month, the patient had resolution of the lesions on both
sides of the face, with some post-inflammatory changes.
34
Tacrolimus caused mild irritation but otherwise both treat-
ments were tolerated well.
Third-Line Therapy
Topical epidermal growth factor A
Accelerating effects of epidermal growth factor on skin
lesions of pemphigus vulgaris: a double-blind, randomized,
controlled trial. Tabrizi MN, Chams-Davatchi C, Esmaeeli N,
Noormohammadpoor P, Safar F, Etemadzadeh H, et╯al. J Eur
Acad Dermatol Venereol 2007; 21(1):79–84.
This randomized, double-blind, controlled study in which
each patient acted as their own control, evaluated silver sul-
fadiazine cream alone versus epidermal growth factor. Patients
healed a median of 6 days earlier on EGF cream (p = 0.0003)
as compared to the comparitor, and did not have any side
effects.
Special management & counseling considerations
Patients with resolving PF may develop hyperpigmentation in
areas of resolved lesions, but in some cases, the hyperpigmen-
tation may extend to uninvolved areas. In Brazil, this change
in skin color was referred to as aurora da cura (the dawn of
healing), and was considered a sign of remission. Patients
described their skin color as changing from white to mulatto,
mulatto to black, and Blacks became gray-blue in color.10 It is
important to discuss this color change with patients, as it may
be unexpected and severe in patients with ethnic skin.
References
1. Meyer N, Misery L. Geoepidemiologic considerations of auto-immune
pemphigus. Autoimmun Rev 2010; 9:A379–A382 [Epub 2009 Nov 3].
2. Warren SJ, Lin MS, Giudice GJ, Hoffmann RG, Hans-Filho G, Aoki V,
et al. The prevalence of antibodies against desmoglein 1 in endemic
pemphigus foliaceus in Brazil. Cooperative Group on Fogo Selvagem
Research. N Engl J Med 2000 Jul 6; 343(1):23–30.
3. Uzun S, Durdu M, Akman A, Gunasti S, Uslular C, Memisoglu HR,
et al. Pemphigus in the Mediterranean region of Turkey: a study of
148 cases. Int J Dermatol 2006 May; 45(5):523–528.
4. Tron F, Gilbert D, Mouquet H, Joly P, Drouot L, Makni S, et al. Genetic
factors in pemphigus. J Autoimmun 2005 Jun; 24(4):319–328.
5. Eaton DP, Diaz LA, Hans-Filho G, Santos VD, Aoki V, Friedman H,
et al. Comparison of black fly species on an American reservation with
a high prevalence of fogo selvage to neighboring disease-free sites in
the state of Mato Grosso do Sul, Brazil. J Med Entomol 1998;
35:120–131.
6. Sagi L, Sherer Y, Trau H, Shoenfeld Y. Pemphigus and infectious agents.
Autoimmun Rev 2008 Oct; 8(1):33–35. [Epub 2008 Aug 14].
7. Aoyama Y, Tsujimura Y, Funabashi M, Sato M, Kamiya H, Kitajima Y.
An experience for ELISA for desmoglein 1, suggesting a possible diag-
nostic help to determine the initial therapy for pemphigus foliaceus.
Eur J Dermatol 2000; 10(1):18–21.
 2â•… Bullous and Pustular Disordersâ•… •â•… Pemphigus vulgaris

8. Gach JE, Ilchyshyn A. Beneficial effects of topical tacrolimus on recal-
citrant erosions of pemphigus vulgaris. Clin Exp Dermatol 2004;
29(3):271–272 [PubMed PMID: 15115509].
9. Cohen SN, Lim RP, Paul CJ, Abdullah A. Equal efficacy of topical
tacrolimus and clobetasone butyrate in pemphigus foliaceus. Int J
Dermatol 2006 Nov; 45(11):1379.
10. Hans-Filho G, Aoki V, Rivitti E, Eaton DP, Lin MS, Diaz LA.
Endemic pemphigus foliaceus (fogo selvagem) – 1998. The Cooperative
Group on Fogo Selvagem Research. Clin Dermatol 1999; 17(2):
225–235.

Pemphigus vulgaris
First-Line Therapy

Corticosteroids:
Pemphigus vulgaris is a mucocutaneous bullous disorder caused Oral B
by acquired autoantibodies targeted against desmosomes, spe- Intravenous, pulsed C
cifically, desmoglein 3 (Dsg3), and less commonly desmoglein Oral, pulsed A
1 (Dsg1). It occurs in people from all backgrounds, however, it
seems to have a higher incidence in patients of Jewish descent
and in Hispanic New Mexicans. The lesions of pemphigus vul-
garis are characterized by flaccid bullae containing clear fluid
that easily rupture with resulting erosions (Fig. 2.6 A and B). The
eroded areas may be extensive and secondary bacterial infections
may develop. Eroded areas may form crusts and granulation
tissue with resulting vegetating lesions (Fig. 2.6C).

Figure 2.6:╇ Pemphigus vulgaris. (A) Characteristic flaccid bullae of pemphigus vulgaris with rupture and secondary bacterial infection. (B) Ruptured bullae and erosions in
a patient of Indian decent. (C) Ulcerated lesions of pemphigus vulgaris. (Courtesy Dr. Sonia Badreshia-Bansal.)

35
 Part 1 Medical Dermatology
The mortality associated with pemphigus vulgaris reached
nearly 75% before the use of systemic corticosteroids com-
menced in the 1950s.1 This inexpensive therapy is considered
to be first-line treatment, although the best, most effective
schedule and route of administration has not been determined
conclusively.2 A starting dose of 1╯mg/kg/day is thought to be
safe and effective, as higher doses are coupled with an increase
in unwanted side effects.3 Induction of remission can be
expected in 21 days, although complete healing may take up
to 8 weeks under normal circumstances. Pemphigus vulgaris
patients may be the only ones who can be considered for
intravenous, pulsed corticosteroid therapy.4 Pulsed intrave-
nous corticosteroids (250–1000╯mg of methylprednisolone)
have been used for 1—5 consecutive days with intent to induce
quicker remission; however sample sizes in these trials are
small and most patients had recalcitrant disease. However, this
method requires continuous cardiac monitoring and hospi-
talization. Oral pulse therapy with 300╯mg of dexamethasone
was evaluated in a small, randomized controlled trial; however,
this did not show any benefit as compared to controls receiv-
ing standard oral therapy.5
Treatment of pemphigus vulgaris and pemphigus foliaceus:
experience with 71 patients over a 20-year period. Fernandes
NC, Perez M. Rev Inst Med Trop S Paulo 2001; 43:33–36.
This retrospective case series of 41 patients with pemphigus
vulgaris compared the use of high dose prednisone (>120╯mg/
day) versus the use of 1–2╯mg/kg/day (maximum of 120╯mg)
for 4–6 weeks with subsequent tapering, and looked at initial
response, morbidity and mortality rate. The response to
therapy and mortality in both groups was similar (no signifi-
cant difference); however, patients on the higher dose therapy
developed unwanted side effects more often (infections, dia-
betes, Cushing’s syndrome, psychosis, cataracts, aseptic necro-
sis of the femur and peptic ulcer disease).
Treatment of pemphigus vulgaris with brief, high-dose
intravenous glucocorticoids. Werth VP. Arch Dermatol 1996;
132(12):1435–1439.
This small series evaluated 15 patients with severe pemphi-
gus vulgaris, 8 of whom received intravenous methylpred-
nisolone pulse therapy for 2–5 days, 1 received two courses of
pulse therapy, and 6 controls received no intravenous therapy.
44% of the patients on intravenous therapy achieved complete
remission as compared to none in the control group, and these
patients used about half the mean maintenance doses of cor-
ticosteroid therapy after the intravenous pulsed course.
Randomized controlled trial of adjuvant oral dexametha-
sone pulse therapy in pemphigus vulgaris: PEMPULS Trial.
Mentink LF, Mackenzie MW, Tóth GG, Laseur M, Lambert FP,
Veeger NJ, et╯al. Arch Dermatol 2006; 142:570–576.
This multicenter, randomized, double-blind, placebo-
controlled clinical trial of 20 patients with new onset pemphi-
gus vulgaris or controlled disease with active flares, 11 of
whom received 300╯mg of oral dexamethasone supplementa-
tion in addition to tapered doses of 80╯mg/day of prednisolone
and azathioprine 3╯g/day. No significant difference was
36
observed between the control and the intervention group as
measured by which patients were able to discontinue systemic
therapy (8/11 of pulsed dexamethasone and 9/9 of control
group).
Second-Line Therapy
Azathioprine A
Cyclophosphamide A
Mycophenolate mofetil A
Immunosuppressive cytotoxic drugs are used in pemphigus
as steroid-sparing agents, in an effort to reduce negative side
effects of high dose corticosteroid use.
Azathioprine sodium is a purine analogue that inhibits
RNA and DNA synthesis. Its active metabolite, mercaptopu-
rine, is deactivated by thiopurine methyltransferase (TPMT),
an enzyme which shows variable activity amongst individuals.
Common toxicities include gastrointestinal discomfort
(nausea, diarrhea), as well as bone marrow toxicities, espe-
cially in people with low levels of enzyme activity.6
When used in conjunction with corticosteroids, azathio-
prine has been shown to be slightly more effective than corti-
costeroids alone in the treatment of pemphigus vulgaris, and
is superior as a steroid-sparing agent when compared to myco-
phenolate mofetil, and pulse therapy cyclophosphamide
(both in conjunction with corticosteroids).7,8
Randomized controlled open-label trial of four treatment
regimens for pemphigus vulgaris. Chams-Davatchi C, Esmaili
N, Daneshpazhooh M, Valikhani M, Balighi K, Hallaji Z, et╯al.
J Am Acad Dermatol 2007; 57(4):622–628.
This is a randomized, controlled study, with four treatment
arms, and a total of 120 patients, evaluating the use of pred-
nisolone alone, prednisolone plus azathioprine, prednisolone
plus mycophenolate mofetil, and prednisolone plus intrave-
nous cyclophosphamide pulse therapy. The study demon-
strated that prednisolone plus azathioprine was more effective
than either mycophenolate mofetil or cyclophosphamide in
reducing the total amount of corticosteroids use after a year of
treatment (only significant for prednisolone plus mycopheno-
late mofetil). However, there was no difference in its efficacy
in controlling disease activity.
Cyclophosphamide is a nitrogen mustard derivative that
suppresses the immune system by cross-linking DNA (cell
cycle independent). Its most common complication, hemor-
rhagic cystitis, is caused by the accumulation of acrolein
(a toxic metabolite). Acrolein is a carcinogen that increases
the risk of developing transitional cell carcinoma. This risk is
especially high in patients who receive low doses of cyclo�
phosphamide over long periods of time as compared to
patients who receive pulse-dose therapy of this medication.
Infertility in men and women is also a concern.9
 2â•… Bullous and Pustular Disordersâ•… •â•… Pemphigus vulgaris
Cyclophosphamide has been evaluated as an adjunctive
therapy to corticosteroids in pemphigus vulgaris, with out-
comes similar to azathioprine in efficacy (as above). Pulsed
therapy and chronic low dose cyclophosphamide in conjunc-
tion with corticosteroids have similar results in terms of effi-
cacy, but a lower risk of malignancy when used as pulse
therapy.10,11
Efficacy and safety of cyclophosphamide, azathioprine, and
cyclosporine (ciclosporin) as adjuvant drugs in pemphigus
vulgaris. Olszewska M, Kolacinska-Strasz Z, Sulej J, Labecka
H, Cwikla J, Natorska U, et╯al. Am J Clin Dermatol 2007;
8(2):85–92.
This retrospective study with long-term follow-up evaluated
101 patients with moderate to severe pemphigus vulgaris and
divided patients into four different treatment regimens: oral
prednisone at an initial dose of 100╯mg (1.1–1.5╯mg/kg) per
day as monotherapy; prednisone combined with azathioprine
at a dose of 100╯mg (1.1–1.5╯mg/kg) per day; cyclosporine
(ciclosporin) at a dose of 2.5–3╯mg/kg/day; or cyclophospha-
mide at a dose of 100╯mg (1.1–1.5╯mg/kg) per day. Time to
clinical and immunologic remission was shortest in the cyclo-
phosphamide group as compared to all other groups (4.9 ±
6.9 months; 23 ± 17 months respectively). The proportion of
patients who remained disease free after 5 years was also sig-
nificantly larger, and those patients who did relapse did so
after a longer disease-free period. The authors conclude that
cyclophosphamide at a dose of 1.1–1.5╯mg/kg/day should be
the adjuvant drug of choice in the treatment of moderate to
severe pemphigus vulgaris.
Mycophenolic acid (MPA) was isolated from Penicillium
stoloniderum as a fermentation product; its morpholinoethyl
ester form is what is known as Mucophenolate mofetil (MMF)
which has better bioavailability and tolerability than MPA.
This antimetabolite inhibits inosine monophosphate dehy-
drogenase (IMPDH), an enzyme required for the de novo syn-
thesis of purines. B and T lymphocytes, which depend on this
pathway for DNA syn�thesis, are most affected. Patients on
MMF develop gastrointestinal side effects in a dose-dependent
manner (20% at 2╯g/day), however hematologic side effects
are not as common (< 5%).9,12
MMF has been used both as adjuvant therapy and as mono-
therapy in the treatment of pemphigus vulgaris, although time
to remission seems to be longer in the latter.8,13 As a steroid-
sparing agent, it appears to be less effective than azathioprine
and cyclophosphamide; however, it does seem to be more
effective in inducing remission than azathioprine.14
A comparison of oral methylprednisolone plus azathio-
prine or mycophenolate mofetil for the treatment of
pemphigus. Beissert S, Werfel T, Frieling U, Böhm M,
Sticherling M, Stadler R, et╯al. Arch Dermatol 2006; 142(11):
1447–1454.
This is a small, randomized prospective, multicenter,
non-blinded trial of 41 patients with pemphigus vulgaris and
pemphigus foliaceus which compared azathioprine and myco-
phenolate mofetil as adjuvants to corticosteroids. MMF was
more effective than azathioprine in conjunction with methyl-
prednisolone in the induction of complete remission (95% vs
72% respectively), and was similar to azathioprine in terms of
its steroid-sparing effects. Patients in the MMF group had fewer
grade 3 toxicities and no grade 4 toxicities when compared to
azathioprine.
Efficacy and safety of long-term mycophenolate sodium
therapy in pemphigus vulgaris. Baskan EB, Yilmaz M, Tunali
S, Saricaoglu H. J Eur Acad Dermatol Venereol 2009; 23:1432–
1434 [Epub 2009 Mar 17].
A small non-blinded trial compared the safety and effective-
ness of MMF (1440╯mg/day) as monotherapy and in combina-
tion with oral prednisolone (70–100╯mg/day) in 6 patients.
Complete remission was achieved in two patients on combina-
tion therapy, partial remission in two patients with mono-
therapy, and two patients did not respond. Patients receiving
combination therapy had a faster response than those on
monotherapy.
Third-Line Therapy
Intravenous immunoglobulin A
Rituximab D
The mechanism of action of IVIg is not well understood,
but it is thought to decrease activation of complement and
cytokine expression via Fc receptors. The advantage of IVIg is
that unlike other adjuvant therapy, it does not immunosup-
press patients.15
A randomized double-blind trial of intravenous immu-
noglobulin for pemphigus. Amagai M, Ikeda S, Shimizu H,
Iizuka H, Hanada K, Aiba S, et al; Pemphigus Study Group.
J Am Acad Dermatol 2009; 60(4):595–603.
This is a randomized, double-blind, multicenter, placebo
controlled clinical trial which enrolled 61 patients with rela-
tively resistant pemphigus vulgaris and pemphigus foliaceus.
Patients were either in the placebo group, the 200╯mg/kg/day
of IVIg, or 400╯mg/kg/day group. Evaluation of efficacy was
based on time to recurrence of disease after treatment, pem-
phigus activity score, and ELISA scores of desmoglein 1 and 3.
Patients responded to IVIg in a dose-dependent manner (p <
.001), which included increased time to relapse (p < .001),
decreased disease activity at 43 and 85 days (p < .05, p < .01),
and decreased ELISA levels (p < .001).
Rituximab is a chimeric, monoclonal IgG1 antibody which
targets CD20 antigen, located on B-cells. After binding, it
induces antibody and complement dependent cell cytotoxicity
as well as apoptosis, thereby resulting in decreased circulating
levels of CD20+ B cells for 6–12 months. Its use in bullous
disorders has increased, prompting a consensus on usage from
experts in Germany, Austria and Switzerland. The panel of
experts believes that patients with failure to respond after
at least three months with standard treatments (steroids ±
immunosuppressants) or patients who cannot use standard
37
 Part 1 Medical Dermatology
therapies due to underlying conditions, are candidates for
rituximab. Patients with underlying active hepatitis, tubercu-
losis, HIV infection with CD 4+ < 250, severe heart failure or
allergy to mouse proteins should not be considered for
treatment.16,17,18
Treatment of severe pemphigus with rituximab: report of 12
cases and a review of the literature. Cianchini G, Corona R,
Frezzolini A, Ruffelli M, Didona B, Puddu P. Arch Dermatol
2007; 143(8):1033–1038.
This case series reviews the treatment of pemphigus vulgaris
in 10 patients (severe mucocutaneous disease; recalcitrant
disease; adverse side effects of steroids) and 2 patients with
pemphigus foliaceus. This was one of the largest series to date
and most patients were on a standardized dose of oral pred-
nisone (40╯mg/day); 4 patients required additional immuno-
suppressants for control. They underwent four total intravenous
treatments with 375╯mg/m2 once weekly. Patients responded
to therapy within an average of 6–10 weeks, 9 had complete
remission within 6 months of rituximab infusion, and one of
the patients required an additional dose after 6 months. Only
three of the patients required immunosuppressive treatment
in addition to corticosteroids as maintenance.
Commonly encountered pitfalls
The highest incidence of pemphigus vulgaris has been seen
in Ashkenazi Jews; Hispanic New Mexicans have a four-fold
rate of PV as compared to the general population of non-
Hispanics. Evidence suggests that the New Mexican Hispanics
are descendants of Jews who emigrated during the inquisition
in the 15th and 16th centuries. The importance of this lies in
the need to have a higher index of suspicion for pemphi�gus
vulgaris in Hispanics from the Southwest, and to be aware that
they may have an increased incidence of other diseases seen
most commonly in Ashkenazi Jews given their ancestry.19
Special management & counseling considerations
In deciding which agent to use for pemphigus vulgaris, it is
helpful to take into account the patient’s age, as the risk of
malignancy increases with increased exposure to certain medi-
cations. It is also important to consider the patient’s desire to
have children as some medications, such as azathioprine,
can cause permanent infertility. ELISA levels of Dsg1 and
Dsg3 levels parallel disease activity, and may be used to
monitor response to treatment and adjustment of medication
doses.20,21
References
1. Bystryn JC. Adjuvant therapy of pemphigus. Arch Dermatol 1984;
120(7):941–951.
2. Harman KE, Albert S, Black MM. Guidelines for the management of
pemphigus vulgaris. Br J Dermatol 2003; 149:926–937.
38
3. Fernandes NC, Perez M. Treatment of pemphigus vulgaris and pem-
phigus foliaceus: experience with 71 patients over a 20 year period. Rev
Inst Med Trop Sao Paulo 2001; 43(1):33–36.
4. Werth VP. Treatment of pemphigus vulgaris with brief, high-dose intra-
venous glucocorticoids. Arch Dermatol 1996; 132(12):1435–1439.
5. Mentink LF, Mackenzie MW, Tóth GG, Laseur M, Lambert FP, Veeger
NJ, et al. Randomized controlled trial of adjuvant oral dexamethasone
pulse therapy in pemphigus vulgaris: PEMPULS trial. Arch Dermatol
2006 May; 142(5):570–576.
6. Firooz A, Ghandi N, Hallaji Z, Chams-Davatchi C, Valikhani M,
Karbakhsh Davari M. Role of thiopurine methyltransferase activity in
the safety and efficacy of azathioprine in the treatment of pemphigus
vulgaris. Arch Dermatol 2008 Sep; 144(9):1143–1147.
7. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, Valikhani M,
Balighi K, Hallaji Z, et al. Randomized controlled open-label trial of
four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol
2007 Oct; 57(4):622–628. [Epub 2007 Jun 21].
8. Beissert S, Werfel T, Frieling U, Böhm M, Sticherling M, Stadler R,
et al. A comparison of oral methylprednisolone plus azathioprine or
mycophenolate mofetil for the treatment of pemphigus. Arch Dermatol
2006 Nov; 142(11):1447–1454.
9. Pan TD, McDonald CJ. Cytotoxic agents. In: Wolverton SE, editor.
Comprehensive dermatologic drug therapy, Philadelphia: WB
Saunders; 2001. p. 180–204.
10. Saha M, Powell AM, Bhogal B, Black MM, Groves RW. Pulsed intrave-
nous cyclophosphamide and methylprednisolone therapy in refractory
pemphigus. Br J Dermatol 2009 Nov 18 [Epub ahead of print].
11. Olszewska M, Kolacinska-Strasz Z, Sulej J, Labecka H, Cwikla J,
Natorska U, et al. Efficacy and safety of cyclophosphamide, azathio-
prine, and cyclosporine (ciclosporin) as adjuvant drugs in pemphigus
vulgaris. Am J Clin Dermatol 2007; 8(2):85–92.
12. Orvis AK, Wesson SK, Breza TS Jr, Church AA, Mitchell CL, Watkins
SW. Mycophenolate mofetil in dermatology. J Am Acad Dermatol
2009; 60(2):183–199.
13. Baskan EB, Yilmaz M, Tunali S, Saricaoglu H. Efficacy and safety of
long-term mycophenolate sodium therapy in pemphigus vulgaris.
J Eur Acad Dermatol Venereol. 2009; 23:1432–1434 [Epub 2009 Mar
17].
14. Martin LK, Werth V, Villanueva E, Segall J, Murrell DF. Interventions
for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database
Syst Rev 2009 Jan 21; (1):CD006263.
15. Amagai M, Ikeda S, Shimizu H, Iizuka H, Hanada K, Aiba S, et al.
Pemphigus Study Group. A randomized double-blind trial of intrave-
nous immunoglobulin for pemphigus. J Am Acad Dermatol 2009 Apr;
60(4):595–603.
16. Hertl M, Zillikens D, Borradori L, Bruckner-Tuderman L, Burckhard H,
Eming R, et al. Recommendations for the use of rituximab (anti-CD20
antibody) in the treatment of autoimmune bullous skin diseases. J
Dtsch Dermatol Ges 2008 May; 6(5):366–373. [Epub 2008 Jan 14].
17. Cianchini G, Corona R, Frezzolini A, Ruffelli M, Didona B, Puddu P.
Treatment of severe pemphigus with rituximab: report of 12 cases and
a review of the literature. Arch Dermatol 2007; 143(8):1033–1038.
18. Schmidt E, Goebeler M, Zillikens D. Rituximab in severe pemphigus.
Ann NY Acad Sci 2009; 1173:683–691.
19. Bordenave K, Griffith J, Hordes SM, Williams TM, Padilla RS. The
historical and geomedical immunogenetics of pemphigus among the
descendants of Sephardic Jews in New Mexico. Arch Dermatol 2001
Jun; 137(6):825–826.
20. Amagai M, Komai A, Hashimoto T, Shirakata Y, Hashimoto K, Yamada
T, et al. Usefulness of enzyme-linked immunosorbent assay using
recombinant desmogleins 1 and 3 for serodiagnosis of pemphigus.
Br J Dermatol 1999 Feb; 140(2):351–357.
21. Daneshpazhooh M, Chams-Davatchi C, Khamesipour A, Mansoori P,
Taheri A, Firooz A, et al. Desmoglein 1 and 3 enzyme-linked immu-
nosorbent assay in Iranian patients with pemphigus vulgaris: correla-
tion with phenotype, severity, and disease activity. J Eur Acad Dermatol
Venereol 2007 Nov; 21(10):1319–1324.
Part 1 Medical Dermatology
Collagen Vascular
Diseases
Sumayah J Taliaferro, Erica Chon Davis and Valerie D Callender
Dermatomyositis . . . . . . . . . . . . . . . . . . . . . . 39
Livedoid vasculopathy . . . . . . . . . . . . . . . . . . . 44
Lupus . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Chronic cutaneous lupus . . . . . . . . . . . .å°“ . . . . . . 47
Subacute cutaneous lupus erythematosus (SCLE) . . . . . 52
Systemic lupus erythematosus . . . . . . . . . . . . . . 53
Scleroderma . . . . . . . . . . . . . . . . . . . . . . . . . 58
Localized scleroderma (morphea) . . . . . . . . . . . å°“. . 58
Systemic sclerosis . . . . . . . . . . . .å°“ . . . . . . . . . 61
Dermatomyositis
Dermatomyositis is an idiopathic myopathy involving inflam-
mation of proximal muscles and characteristic cutaneous find-
ings. When the cutaneous findings occur without the typical
muscle weakness and muscle enzyme levels are normal over a
2-year period, the condition is referred to as amyopathic der-
matomyositis or dermatomyositis sine myositis. Polymyositis,
which is thought to be related to dermatomyositis, is an
inflammatory myopathy typified by muscle inflammation and
weakness in the absence of skin involvement. The relationship
between dermatomyositis and polymyositis is currently some-
what controversial as new evidence suggests different patho-
genetic mechanisms.1,2
The etiology of dermatomyositis remains unclear, but is
presumed to be of autoimmune origin. Experts speculate that
a viral infection of the muscles is a precipitating cause. Other
triggers include malignancy and medications. These stimulate
an immune-mediated inflammatory response in genetically
predisposed individuals. Ninety-five percent of patients have
positive serum antinuclear autoantibodies.
While dermatomyositis can develop at any age, it tends to
have a bimodal age distribution, most commonly occurring in
©2011 Elsevier Ltd, Inc, BV
3â•…
children between the ages of 5 and 15 and adults between the
ages of 40 and 60. Women are affected more than men with
an approximate female to male ratio of 6 to 1. The incidence
of dermatomyositis ranges from 2 to 7 cases per million.
Overall, the incidence of dermatomyositis appears to be
increasing.
The characteristic cutaneous findings of dermatomyositis
include malar erythema and poikiloderma in the V neck dis-
tribution. A hallmark feature is the presence of erythematous-
violaceous patches over the upper eyelids, known as a
‘heliotrope’ rash. Another pathognomonic sign is the presence
of Gottron’s papules, which are erythematous-violaceous
papules and plaques over the knuckles, elbows, and knees (Fig.
3.1). Both of these cutaneous signs often appear hyperpig-
mented in skin of color patients. Periungual and cuticular
changes also occur, most commonly nailfold telangiectasia.
Inflammation and weakness affect the proximal muscles. Sore-
ness and stiffness of the muscles is common. Patients may
report difficulty climbing stairs, walking, and rising from a
sitting position. Up to 40% of patients may initially present
with skin disease without muscle involvement.3 In dermato-
myositis, muscle and skin disease may occur concurrently or
one may precede the other.
While characteristic skin findings and muscle weakness are
definitive features, dermatomyositis is ultimately a multi�
system disease. Cardiac and pulmonary complications are not
uncommon.4 Specifically, interstitial lung disease and pneu�
momediastinum are potential pulmonary complications.5
The presence of Jo-1 antibody has been associated with inter-
stitial lung disease in dermatomyositis. One study showed
that Anti-Jo-1 and other myositis associated autoantibodies
were equally distributed among whites, African-Americans,
Mexican-Americans, and Japanese.6 Systemic symptoms
can be severe and include arthralgias, dysphagia, dyspnea, and
palpitations.
Juvenile dermatomyositis typically presents with slow-
onset, but progressive muscle weakness develops. Cutaneous
features may be delayed. Calcinosis and lipodystrophy are
complicating features of some patients with longstanding
childhood dermatomyo�sitis.7 A recent study identified the
39
 Part 1 Medical Dermatology
Figure 3.1:╇ Gottron’s papules over the proximal interphalangeal joints in a
dermatomyositis patient.
novel autoantibody, anti-p140 in association with calcinosis
in juvenile dermatomyositis.8 Contractures leading to long-
term disability may occur in severe disease. The association
with malignancy is not seen in juvenile dermatomyositis.
A concerning feature of dermatomyositis in adults is its
association with malignancy. Frequently it may herald the
onset of malignancy that might otherwise go unnoticed and
result in late detection. Approximately one-fourth of cases of
dermatomyositis in adults occur in the presence of an occult
malignancy. Certain malignancies occur more frequently.
These include ovarian, lung, pancreatic, colon, non-Hodgkin’s
lymphoma, and breast cancer.9 The presence of cutaneous
leukocytoclastic vasculitis may be a sign of malignancy in
dermatomyositis, and thus should prompt thorough systemic
evaluation.10
Drug-induced dermatomyositis is now well-described.
Hydroxyurea is a known precipitating cause of dermatomyosi-
tis. Other sources of possible drug-induced dermatomyositis
include D-penicillamine, non-steroidal anti-inflammatory
medications, and lipid-lowering medications.11
When dermatomyositis is suspected, serum aldolase and
creatine kinase levels should be checked. Confirmation of
muscle disease with electromyogram and muscle biopsy is also
recommended. Magnetic resonance imaging (MRI) and ultra-
sound imaging have been useful in determining extent of
muscle involvement and aiding in the identification of specific
muscles to biopsy. Some patients with amyopathic dermato-
myositis have been shown to have mild muscle inflammation
identified on MRI that is not evident clinically. Work-up for
systemic disease should include a thorough evaluation of the
cardiac, pulmonary and gastrointestinal systems. A chest X-ray,
esophageal motility test, pulmonary function test, and electro-
cardiogram are recommended. In adults, evaluation for the
presence of malignancy should also ensue, starting with
routine labwork and basic age-appropriate cancer screening
tests. Some experts recommend computed tomographic (CT)
scans of the chest, abdomen, and pelvis. Women should be
screened for ovarian cancer.12
40
First-Line Therapies
For cutaneous disease:
Sunscreens
Topical corticosteroids E
Antimalarials C
Cyclophosphamide E
For muscle disease:
Systemic corticosteroids C
Methotrexate C
Azathioprine A, E
â•… (Polymyositis) A
â•… (Dermatomyositis) E
Dermatomyositis: comparative studies of cutaneous photo-
sensitivity in lupus erythematosus and normal subjects.
Dourmishev L, Meffert H, Piazena H. Photodermatol Photo�
immunol Photomed. 2004; 20:230–234.
Ultraviolent light may play a prominent role in the patho-
physiology of dermatomyositis, in which the characteristic
skin findings occur on mostly sun-exposed areas. The authors
found that photosensitivity was a frequent sign in dermato�
myositis and sought to demonstrate this in a scientific manner
by measuring the minimal erythema dose (MED). In this
study, the MED was reduced in dermatomyositis and lupus
patients compared to healthy controls. The subjects were Cau-
casian with skin types II and III. The authors indicate that
photosensitivity should be one of the major criteria for the
diagnosis of dermatomyositis as in lupus.
Cutaneous lesions of dermatomyositis are improved by
hydroxychloroquine. Woo TY, Callen JP, Voorhees JJ, Hanno
R, Hawkins C. J Am Acad Dermatol. 1984; 10:592–600.
The cutaneous manifestations of dermatomyositis are fre-
quently more resistant to treatment with corticosteroids and
other immunosuppressives. In this open clinical trial of seven
patients, all patients with cutaneous lesions responded well
with the addition of hydroxychloroquine.
Complete resolution of dermatomyositis with refractory
cutaneous vasculitis by intravenous cyclophosphamide
pulse therapy. Tsujimura S, Saito K, Tanaka Y. Intern Med
2008; 47:1935–1940.
This case report demonstrates the effective use of cyclophos-
phamide without systemic corticosteroids in the treatment of
cutaneous ulcerations and vasculitis in a complicated case of
dermatomyositis in a 43-year-old male.
Dermatomyositis; a dermatology-based case series. Dawkins
MA, Jorizzo JL, Walker FO, Albertson D, Sinal SH, Hinds A. J
Am Acad Dermatol. 1998; 38:397–404.
In this study, a retrospective analysis of the clinical features
of sixty-five patients during a ten-year period was performed.
The authors paid special attention to the patients’ response to
systemic corticosteroids. Twenty-one of the patients were
 3â•… Collagen Vascular Diseasesâ•… •â•… Dermatomyositis

enrolled in a prospective, uncontrolled trial of prednisone Topical tacrolimus 0.1% ointment for refractory skin disease
treatment with slow tapering. Prednisone was dosed at 1╯mg/ in dermatomyositis: a pilot study. Hollar CB, Jorizzo JL.
kg/day and reduced gradually to one-half the initial dose J Dermatolog Treat. 2004; 15:35–39.
during a six-month period. Prednisone dose was slowly lowered A few case reports indicate the usefulness of topical tac-
and discontinued during a period that ranged from twenty to rolimus for cutaneous lesions of dermatomyositis. In this
sixty-three months. Findings indicate that treatment with high- report six patients with resistant cutaneous manifestations of
dose prednisone followed by slow tapering is effective. dermatomyositis showed improvement after six to eight weeks
of treatment with topical tacrolimus 0.1% ointment. Dramatic
Efficacy of early treatment of severe juvenile dermato� improvement was observed in two of the patients, a moderate
myositis with IV methylprednisolone and methotrexate. Al- response was noted in one, and three of the patients had
Mayout S, Al-Mazyed A, Bahabris S. Clin Rheumatol 2000; minimal improvement.
19:138–141.
In this small trial of 12 children with severe juvenile der- Treatment of refractory juvenile dermatomyositis with tac-
matomyositis, methotrexate and IV methylprednisolone were rolimus. Hassan J, van der Net JJ, van Royen-Kerkhof A. Clin
found to be an effective treatment combination. The study Rheumatol 2008; 27:1469–1471.
suggests that this treatment combination may prevent compli- Three patients with severe juvenile dermatomyositis, on
cations such as calcinosis. systemic corticosteroids, were treated with oral tacrolimus
(target serum level 10╯µg/l, therapeutic range 5–15╯µg/l).
Treatment of dermatomyositis with methotrexate.
There was marked improvement of the cutaneous eruptions,
Zieglschmid-Adams ME, Pandya AG, Cohen SB, Sontheimer
improvement in physical activity, and overall decrease in
RD. J Am Acad Dermatol 1995; 32:754–757.
disease that allowed for tapering of systemic corticosteroids.
This article reports five pediatric cases (ages four to twelve)
Side effects of oral tacrolimus include gastrointestinal symp-
of severe dermatomyositis in which the patients improved
toms, hypertension, nephrotoxicity and neurotoxicity, but no
with adjuvant therapy with either methotrexate alone or com-
adverse effects were noted in the patients reported here. It is
bined therapy with methotrexate and azathioprine. All patients
felt that oral tacrolimus may have beneficial effects in refrac-
were on systemic steroids. The dose of methotrexate ranged
tory cases of juvenile dermatomyositis, particularly those with
from 2–3╯mg/kg administered every two weeks. The dose of
extensive cutaneous manifestations.
azathioprine was 50╯mg daily, but was increased to 125╯mg
daily in the twelve-year old boy reported in the fifth case.
Low dose methotrexate administered weekly is an effective
Prednisone and azathioprine for polymyositis: long- corticosteroid-sparing agent for the treatment of the cutane-
term follow-up. Bunch TW. Arthritis Rheum 1981; 24:45–48. ous manifestations of dermatomyositis. Kasteler JS, Callen
The initial study of a double-blind placebo-controlled trial JP. J Am Acad Dermatol 1997; 36:67–71.
published the previous year by the same author indicated no The authors found that low-dose methotrexate adminis-
statistically significant improved effect with the addition of tered weekly was effective in treating the cutaneous disease of
azathioprine. However, it observed muscle function for a dermatomyositis. The treatment with methotrexate frequently
limited period of time. Results of this follow-up study showed allowed for a lower dose of systemic steroids or discontinua-
a long-term beneficial effect of azathioprine in combination tion of corticosteroid therapy. Thirteen patients were reviewed
with prednisone. in this retrospective analysis. The dose of methotrexate ranged
from 2.5 to 30╯mg weekly (average maximal dose of 7.5╯mg
per week). Methotrexate was tolerated well with minimal
Second-Line Therapies
toxicity.
For cutaneous disease:
Immunomodulatory treatment for dermatomyositis. Callen
Tacrolimus JP. Curr Allergy Asthma Rep 2008; 8:348–353.
â•… (topical) D Treatment of muscle disease in dermatomyositis requires
â•… (oral) E high-dose systemic steroids. The use of a steroid-sparing
Methotrexate C adjunctive agent is also recommended for early control of
Mycophenolate mofetil C disease. Recommended treatments include methotrexate,
Intravenous immunoglobulin A azathioprine, mycophenolate mofetil, and intravenous immu-
noglobulin. The author suggests use of methotrexate as a
For muscle disease: first-line agent due to its effectiveness for muscle and skin
disease with a starting dose of 5–7.5╯mg/week orally or intra-
Cyclophosphamide D
venously. Weekly increases of 2.5 or 5╯mg/week are recom-
Chlorambucil D
mended until a dose of 25–30╯mg/week is reached. The
Mycophenolate mofetil C suggested azathioprine dose is 2╯mg/kg/day. Mycophenolate
Cyclosporine B mofetil is reported to be beneficial at a dose of 2–3╯g/day.
Intravenous immunoglobulin A IVIg is effective with an infusion dose of 2╯g/kg/mo.
Clinical improvements are usually noted after 3–4 months

41
 Part 1 Medical Dermatology
with IVIg, but long-term intermittent therapy may be
required.
Intravenous cyclophosphamide pulse therapy in juvenile
dermatomyositis. A review of efficacy and safety. Riley P,
Maillard SM, Wedderburn LR, Woo P, Murray KJ, Pilkington
CA. Rheumatology (Oxford). 2004; 43:491–496.
In this review, ten out of twelve patients with severe refrac-
tory juvenile dermatomyositis showed a significant improve-
ment in muscle function and strength as well as skin disease
severity after treatment with cyclophosphamide. The mean
cumulative dose was 4.6╯g/m2. The few reported complications
included lymphopenia, herpes zoster infections, and alopecia,
which were reversible. It was noted that the dreaded possible
long-term complications (malignancy, infertility, gonadal
failure) tend to occur at doses higher than the doses required
to treat dermatomyositis.
Chlorambucil: an effective corticosteroid-sparing agent for
patients with recalcitrant dermatomyositis. Sinoway PA,
Callen JP. Arthritis Rheum. 1993; 36:319–324.
This is a report of five patients with recalcitrant dermato-
myositis who showed improved clinical response after treat-
ment with oral chlorambucil (4╯mg/day). The patients were
treated with chlorambucil after discontinuation of azathio-
prine or methotrexate. Three of the patients were treated with
prednisone and chlorambucil concomitantly. The patients
experienced improvement after four to six weeks of beginning
chlorambucil. Chlorambicil was well-tolerated. Two patients
experienced leucopenia, but no other major side effects were
noted. The muscle disease improved in these patients but the
cutaneous disease did not.
Mycophenolate mofetil as an effective corticosteroid-
sparing therapy for recalcitrant dermatomyositis. Edge JC,
Outland JD, Dempsey JR, Callen JP. Arch Dermatol. 2006;
142:65–69.
This was a small open-label retrospective chart review of
twelve patients with refractory cutaneous lesions of dermato-
myositis. Improvement was noted in ten out of twelve patients.
Doses of mycophenolate mofetil ranged from 500╯mg to 1╯g
twice a day. The majority of patients tolerated mycophenolate
mofetil well. One patient developed B-cell lymphoma of
the central nervous system and another developed abnormal
liver enzymes with resolution upon discontinuation of the
medication.
Several case studies indicate that mycophenolate mofetil is
an effective adjuvant therapy for dermatomyositis. However,
patients should be monitored carefully for side effects. High
rates of opportunistic infections have been reported in some
studies while others indicate minimal risk.
Cyclosporin A versus methotrexate in the treatment of poly-
myositis and dermatomyositis. Vencovsky J, Jarosova K,
Machaecek S, Studynkova J, Kafkova J, Bartunkova J, et al.
Scand J Rheumatol 2000; 29:95–102.
This study looked at 36 patients with either dermatomyosi-
tis (20) or polymyositis (16) who were treated with both
42
methotrexate and prednisone or cyclosporine A and pred-
nisone. The dose of cyclosporine was 3 to 3.5╯mg/kg/day. Oral
methotrexate dose ranged from 7.5╯mg to 15╯mg weekly.
Improvement in clinical features and laboratory indicators was
demonstrated in the group treated with either methotrexate or
cyclosporine without significant difference.
A controlled trial of high-dose IV immunoglobulin infu-
sions as treatment for dermatomyositis. Dalakas MC, Illa I,
Dambrosia JM, Soueidan SA, Stein DP, Otero C, et al. N Eng
J Med 1993; 329:1993–2000.
In this double-blind, placebo-controlled study, fifteen
patients who continued to receive prednisone (mean daily
dose of 25╯mg) were randomized to receive one infusion of
immune globulin (8) or placebo (7) monthly for three
months. Immune globulin was administered as 2╯g per kilo-
gram divided into two doses of 1╯g/kg each. Patients treated
with immune globulin showed significant improvement.
Maximal improvement occurred in most of the patients
between the second and third month.
Subcutaneous immunoglobulin administration: an alter�
native to intravenous infusion as adjuvant treatment for
dermatomyositis? Schleinitz N, Jean E, Benarous L, Mazodier
K, Figarella-Branger D, Bernit E, et╯al. Clin Rheumatol 2008;
27:1067–1068.
This is a case report of a patient with dermatomyositis who
displayed clinical improvement with use of subcutaneous
immunoglobulin instead of the standard intravenous form.
The patient was treated with a monthly dose of 1.7╯g/kg of
subcutaneous immunoglobulin. Offering the advantage of
at-home administration, subcutaneous immunoglobulin may
provide a more convenient adjunctive treatment for dermato-
myosits in some patients.
Safety of intravenous immunoglobulin in the treatment of
juvenile dermatomyositis: adverse reactions are associated
with immunoglobulin A content. Manlhiot C, Tyrrell PN,
Liang L, Atkinson AR, Lau W, Feldman BM. Pediatrics 2008;
121:626–630.
Intravenous immunoglobulin has been found to be effec-
tive in treating juvenile dermatomyositis, particularly cases
refractory to systemic steroid treatment. This study confirmed
that intravenous immunoglobulin is a safe treatment alterna-
tive for juvenile dermatomyositis, but children tend to have a
lower tolerance of intravenous immunoglobulin containing
high amounts of immunoglobulin A. Thus, selection of immu-
noglobulin type is important when treating children with der-
matomyositis with this agent.
Successful treatment of dermatomyositis during preg�
nancy with intravenous immunoglobulin monotherapy.
Williams L, Chang PY, Park E, Gorson KC, Bayer-Zwirello L.
Obstet Gynecol 2007; 109:561–563.
Dermatomyositis, while rare during pregnancy, is associ-
ated with poor fetal outcome without proper treatment. Cor-
ticosteroids, the mainstay of treatment, can lead to adverse
events due to the high doses required. This case report
 3â•… Collagen Vascular Diseasesâ•… •â•… Dermatomyositis
demonstrates the safe and effective use of intravenous
immunoglobulin in the treatment of dermatomyositis in a
young white primigravida at 4 weeks gestation. Intravenous
immunoglobulin was administered monthly at a dose of 1╯g/
kg/day for 2 consecutive days. Intravenous immunoglobulin
may provide a nice treatment alternative with few adverse
effects yielding good maternal and fetal outcome.
Third-Line Therapies
Dapsone E
Diltiazem E
Etanercept E Rituximab for the treatment of juvenile dermatomyositis: a
Infliximab D report of four pediatric patients. Cooper MA, Willingham
Total Body Irradiation E DL, Brown DE, French AR, Shih FF, White AJ. Arthritis Rheum
Rituximab E 2007; 56:3107–3111.
Leflunomide E This is a retrospective review of four pediatric patients with
Cutaneous involvement of dermatomyositis can respond to
dapsone therapy. Cohen JB. Int J Dermatol 2002; 41:182–
184.
Two patients with dermatomyositis who remained refrac-
tory despite treatment with prednisone and antimalarials
improved dramatically after the addition of dapsone.
Dapsone may be a good choice of adjunctive therapy for
dermatomyositis.
Regression of calcinosis during diltiazem treatment of juve-
nile dermatomyositis. Oliveri MB, Palermo R, Mautalen C,
Hubscher O. J Rheumatol 1996; 23:2152–2155.
This case report describes a child with severe dystrophic
calcifications despite treatment with methylprednisolone,
methotrexate, and later azathioprine. Pronounced regression
of calcinosis was observed during treatment with diltiazem
(2╯mg/kg/day).
Etanercept is effective in the treatment of polymyositis/der-
matomyositis which is refractory to conventional therapy
including steroids and other disease modifying agents.
Saadeh CK. Arthritis Rheum 2000; 43:S193.
Four patients responded well to etanercept after failing
corticosteroids and other immunosuppressives. No side effects
were reported. Etanercept may be useful in the treatment of
patients who remain refractory to conventional therapy.
Effectiveness of infliximab in the treatment of refractory
juvenile dermatomyositis with calcinosis. Riley P, McCann
LJ, Maillard SM, Woo P, Murray KJ, Pilkington CA. Rheumatol-
ogy (Oxford) 2008; 47:877–880.
Five patients with juvenile dermatomyositis who were
refractory to other medications showed further improvement
with infliximab, an anti-TNF-alpha monoclonal antibody.
Starting dose was 3╯mg/kg, but dose and frequency were
tailored to individual response. High levels of TNF-alpha
have been identified in patients with juvenile dermatomyositis
and calcinosis.
Response to total body irradiation in dermatomyositis. Kelly
JJ, Madoc-Jones H, Adelman LS, Andres PL, Munsat TL. Muscle
Nerve. 1988; 11:120–123.
When patients with severe resistant dermatomyositis
become too ill to tolerate immunusuppressives or have to
discontinue immunosuppressives due to complications, other
treatment options become necessary. The authors report two
cases of dermatomyositis successfully treated with irradiation.
Thrombocytopenia in one patient was the only reported side
effect.*
juvenile dermatomyositis treated with rituximab, an anti-
CD20 monoclonal antibody. Three of the four patients showed
an improved clinical response with rituximab.
Rituximab for the treatment of the skin manifestations of
dermatomyositis: a report of 3 cases. Dinh HV, McCormack
C, Hall S, Prince HM. J Am Acad Dermatol 2007; 56:
148–153.
This is a report of three patients with dermatomyositis who
were achieving good therapeutic responses for muscle disease
but inadequate control of the cutaneous manifestations. The
patients showed improvement of cutaneous disease with ritux-
imab, a monoclonal anti-CD20 antibody.
Leflunomide as adjuvant treatment of dermatomyositis.
Boswell JS, Costner MI. J Am Acad Dermatol 2008; 58:
403–406.
This is a report of three cases of recalcitrant dermatomyosi-
tis that were treated effectively with the addition of lefluno-
mide, a novel immunomodulatory medication used to
treat rheumatoid arthritis. All three patients initially failed
treatment with other immunosuppressives which included
methotrexate and hydroxychloroquine, but cleared when leflu-
nomide (20╯mg/day) was added to their therapeutic regimen.
Leflunomide may be a safe and effective adjuvant treatment in
difficult cases of dermatomyositis.
Special management & counseling considerations
Systemic oral corticosteroids are the mainstay of treatment for
dermatomyositis. The recommended initial dose is 0.5–
1.5╯mg/kg/day, followed by a slow taper to one half the start-
ing dose over 6 months with a goal of stopping therapy in 2
years. Corticosteroids should not be continued indefinitely.
Many patients need a 2–3-year duration of systemic steroids
*Other reports advise a very cautious approach due to risks and side
effects.
43
 Part 1 Medical Dermatology
but some patients respond well earlier and can discontinue
therapy as soon as 14 months.
Dermatologic manifestations of dermatomyositis can be
difficult to treat. Even after muscle disease is adequately sup-
pressed, the skin eruption may remain refractory to treatment
and require additional therapy. Aggressive sun protection with
physical barriers and sunscreen must be emphasized. Topical
corticosteroids are recommended as first-line treatment.
Hydroxychloroquine can be added as a systemic treatment in
more difficult cases. It has been noted, however, that patients
with dermatomyositis may not respond as dramatically
to antimalarial therapy or tolerate it as well as patients
with lupus erythematosus. Mycophenolate mofetil has
been shown to effectively treat the skin manifestations of
dermatomyosistis.
Calcinosis is a complicating feature frequently seen in chil-
dren with dermatomyositis. Early aggressive treatment with
high dose corticosteroids may prevent calcinosis.13 Physical
therapy should be a part of the treatment plan in children to
prevent contractures and long-term disability from muscle
weakness.
Patients of Asian ancestry may have more severe pulmonary
disease and should be screened and treated early for pulmo-
nary complications.14,15
References
1. Grundtman C, Malmstrom V, Lundberg IE. Immune mechanisms in
the pathogenesis of idiopathic inflammatory myopathies. Arthritis Res
Ther 2009; 9:208.
2. Mammen AL. Dermatomyositis and polymyositis:clinical presenta-
tion, autoantibodies, and pathogenesis. Annals of the New York
Academy of Sciences. 2009. p. 24.
Livedoid vasculopathy
Livedoid vasculopathy (LV), also known as atrophie blanche,
livedo vasculitis, livedo reticularis with summer ulceration,
and segmental hyalinizing vasculitis, is a chronic cutaneous
syndrome characterized by painful ulcerations, white stellate
scars with surrounding telangiectasia and reticulated erythema
over the distal lower extremities.1 The prevalence of LV in the
general population is estimated to be 1–5%;2 however, there
are no data on the disease prevalence among different racial/
ethnic populations. This disease predominantly affects young
to middle-aged women and can be divided into primary or
idiopathic form and secondary form, in which LV is associated
with a variety of conditions such as chronic venous insuffi-
ciency and coagulation disorders like factor V Leiden mutation
and antithrombin III deficiency.3,4 LV can also be found with
livedo reticularis.
Although the exact pathogenesis of LV remains largely
unclear, it is believed to involve fibrin thrombi formation
focally within dermal blood vessels. Histologic analysis dem-
44
3. Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A
systematic review of adult – onset clinically amyopathic dermatomy-
ositis (dermatomyositis sine myositis). A missing link within the spec-
trum of idiopathic inflammatory myopathies. J Am Acad Dermatol
2006; 54:597–613.
4. Lundberg IE. The heart in dermatomyositis and polymyositis.
Rheumatology (Oxford) 2006; 45(Suppl 4):iv18–iv21.
5. Fathi M, Lundberg IE, Tornling G. Pulmonary complications of poly-
myositis and dermatomyositis. Semin Respir Crit Care Med 2007;
28:451–458.
6. Arnett FC, Targott IN, Mimori T, Goldstein R, Warner NB, Reveille JD.
Interrelationship of major histocompatability complex class II alleles
and autoantibodies in four ethnic groups with various forms of myosi-
tis. Arthritis Rheum 1996; 39:1507–1518.
7. Ramanan AV, Feldman BM. Clinical outcomes in juvenile dermato�
myositis. Curr Opin Rheumatol 2002; 14:658–662.
8. Gunawardena H Autoantibodies to 140-kd protein in JDM are associ-
ated with calcinosis. Arthritis Rheum 2009; 60:1807–1814.
9. Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A,
et al. Frequency of specific cancer types in dermatomyositis and poly-
myositis: a population-based study. Lancet 2001; 357:96–100.
10. Hunger RE, Durr C, Brand CU. Cutaneous leukocytoclastic vasculitis
in dermatomyositis suggests malignancy. Dermatology 2001; 202:
123–126.
11. Seidler AM, Gottlieb AB. Dermatomyositis induced by drug therapy: a
review of case reports. J Am Acad Dermatol 2008; 59:872–880.
12. Callen JP. Collagen vascular diseases. J Am Acad Dermatol 2004;
51:427–439.
13. Fisler RE, Liang MG, Fuhlbrigge RC, Yalcindag A, Sundel RP. Aggressive
management of juvenile dermatomyositis results in improved outcome
and decreased incidence of calcinosis. J Am Acad Dermatol 2002;
47:505–511.
14. Morinishi Y, Oh-ishi T, Kabuki T, Joh K. Juvenile dermatomyositis:
clinical characteristics and the relatively high risk of interstitial lung
disease. Mod Rhuematol 2007; 17:413–417.
15. Kameda H, Takeuchi T. Recent advances in the treatment of interstitial
lung disease in patients with polymyositis/dermatomyositis. Endocr
Metab Immune Discord Drug Targets 2006; 6:409–415.
onstrates segmental hyalinization of superficial dermal vessel
walls as well as deposition of fibrin into the vessel lumen
(fibrin plugs) leading to epidermal necrosis.5,6 There is also
intimal proliferation and a paucity of lymphocytic infiltrates
and extravasated red blood cells surrounding these vessels.7
Although late-stage lesions demonstrate the presence of IgM,
IgG, and C3, this is believed to be a secondary immunologic
response not the primary pathologic event.8 Although it was
initially thought to be a vasculitis, the lack of neutrophilic
infiltration and nuclear fragments in LV argues in favor of LV
being a vasculopathy rather than a vasculitis.8
The most prominent and characteristic feature of livedoid
vasculopathy is atrophie blanche scarring. Lesions typically
begin as purpuric papules over the distal lower extremities that
progress to form painful superficial ulcers, which are typically
slow to heal. The ulcers eventually heal to form atrophic,
porcelain white scars in a stellate pattern surrounded by
telangiectasia and retiform purpura.1 There have been case
reports in the literature describing the presentation of LV in
African-American, Hispanic, and Asian patients.9–11 The pres-
entation and course of the disease appears to be similar
between Caucasian and non-Caucasians.
 3â•… Collagen Vascular Diseasesâ•… •â•… Livedoid vasculopathy
Management strategy
Livedoid vasculopathy remains a difficult disease entity to
treat. Since LV is believed to involve thrombus formation and
alterations in coagulation and fibrinolysis, there is increased
interest in antithrombotic, anticoagulation, and fibrinolytic
therapies. Drucker12 demonstrated platelet hyperaggregation
in nearly all patients included in the study and normalization
of platelet function and a resolution of symptoms after treat-
ment with aspirin and dipyridamole. Anticoagulation has also
been used to treat LV alone or in combination with fibrinolytic
agents like tissue plasminogen activator.
Although there is little evidence of inflammation histologi-
cally in LV, there has also been some success with the use of
steroids like danazol. Other therapies that have shown some
efficacy in treating LV include intravenous immunoglobulins,
hyperbaric oxygen therapy, pentoxifylline, psoralen-UVA, sul-
fasalazine, prostanoids, and nifedipine.1 However, large-scale
studies are needed to further prove the safety and efficacy of
these treatments.
First-Line Therapies
Local wound care
Aspirin B increased levels of plasminogen activator inhibitor, and low
Dipyridamole B levels of endogenous t-PA activity among this group of patients.
Atrophie blanche: a clinicopathological study of 27 patients.
Yang LJ, Chan HL, Chen SY, Kuan YZ, Chen MJ, Wang CN,
et╯al. Changgeng Yi Xue Za Zhi 1991; 14:237–245.
The authors studied 27 patients with LV. All patients were
initially treated with aspirin and dipyridamole and 48% of
patients responded well. Seventy percent of those patients who
did not initially improve with aspirin and dipyridamole
responded to the addition of or change to heparin. All patients
experienced relapse but 50% were disease free for up to
2 years.
Antiplatelet therapy in atrophie blanche and livedo vasculi-
tis. Drucker CR, Duncan WC. J Am Acad Dermatol 1982;
7(3):359–363.
Seven patients with LV underwent platelet function studies
before and 3 weeks after treatment with aspirin and dipyrida-
mole. Before treatment, all seven patients showed abnormali-
ties in platelet function (adhesiveness 6/7, aggregation 3/7)
but results normalized after therapy. Improvement in ulcera-
tions occurred in all patients as well as decreased pain,
increased activity, and decreased formation of new ulcers. Two
patients relapsed after therapy was stopped but improved after
the medications were restarted. The authors also noted that 5
of 7 patients developed wound infections after starting aspirin
and dipyridamole, which they felt was possibly coincidental
or due to a shift in the treatment strategy from an emphasis
on local wound care to oral medications.
Second-Line Therapies
Pentoxifylline C
Tissue plasminogen activator C
Heparin E
Warfarin E
Livedo vasculitis. Therapy with pentoxifylline. Sams WM Jr.
Arch Dermatol 1988; 124:684–687. Erratum in: Arch Derma-
tol 1989; 125:368.
Eight patients with refractory LV were treated either with
pentoxifylline alone or pentoxifylline in combination with
aspirin and dipyridamole (3 patients). Three patients experi-
enced complete healing of all lesions, four patients showed
partial improvement, and one had no response. Patients were
followed for up to 58 months and the majority of patients did
experience relapse although new ulcers were typically small.
Tissue plasminogen activator for treatment of livedoid
vasculitis. Klein KL, Pittelkow MR. Mayo Clin Proc 1992;
67(10):923–933.
Six patients with refractory LV were successfully treated
with tissue plasminogen activator (t-PA). There was a high
incidence of anticardiolipin antibodies, lupus anticoagulants,
Multiple previous treatment strategies had failed; therefore,
t-PA was started with a significant and rapid improvement in
the non-healing ulcers in 5 out of 6 patients. One patient
experienced re-thrombosis of the dermal vessels. This patient
underwent another course of t-PA with the addition of antico-
agulation with subsequent healing of the leg ulcers.
Idiopathic atrophie blanche: treatment with low-dose
heparin. Heine KG, Davis GW. Arch Dermatol 1986;
122:855–856.
The authors report the case of a 59-year-old patient with
LV for more than 20 years. Previous treatment with systemic
corticosteroids and bilateral sympathectomy failed. After 3
months of minidose heparin therapy, the patient had com-
plete healing of all ulcers and stopped treatment. No relapses
occurred within 6 months of stopping heparin. The authors
note that the risk of hemorrhage is minimal given that clotting
time increases only slightly after minidose heparin use.
A case of livedoid vasculopathy associated with factor V
Leiden mutation: successful treatment with oral warfarin.
Kavala M, Kocaturk E, Zindanci I, Turkoglu Z, Altintas S. J
Dermatol Treat 2008; 19(2):121–123.
The authors report the case of a 19-year-old man with LV
of 4 years duration. Physical exam and diagnostic work-up
revealed atrophie blanche and a factor V Leiden gene muta-
tion. The patient was started on oral warfarin with significant
clinical improvement. The authors also note that the patient
was originally diagnosed with livedo vasculitis and was treated
as such with long-term systemic corticosteroid therapy, which
45
 Part 1 Medical Dermatology
eventually led to surgery for femur necrosis. This highlights the
importance of redefining the disease entity as a vasculopathy
not a vasculitis and the impact on treatment options.
Third-Line Therapies
Danazol C
Intravenous immunoglobulin C logy 1996; 192(2):120–124.
Psoralen-UVA (PUVA) C In this study, the authors demonstrated a decreased expres-
Sulfasalazine C sion of thrombomodulin, which is upregulated by prostacyc-
Prostanoids C lin, on endothelial cells in patients with LV. Therefore, four
Nifedipine E patients with this disease were treated with beraprost sodium,
Hyperbaric oxygen C a prostacyclin analog. These patients were initially treated with
Low-dose danazol in the treatment of livedoid vasculitis.
Hsiao GH, Chiu HC. Dermatology 1997; 194(3):251–255.
The authors conducted a study of six patients with LV and
found low-dose danazol to be effective in the treatment of this
disease. All patients noted improvement in ulcer healing, pain
relief, and a halt in disease progression. There were no unac-
ceptable side effects.
Pulsed intravenous immunoglobulin therapy in livedoid
vasculitis: an open trial evaluating 9 consecutive patients.
Kreuter A, Gambichler T, Breuckmann F, Bechara FG,
Rotterdam S, Stucker M, et╯al. J Am Acad Dermatol 2004;
51(4):574–579.
Open, non-controlled clinical trial of nine patients with LV
treated with IVIg. Seven patients were refractory to previous
therapies. There was significant (p < 0.001) and rapid improve-
ment in all patients based on three clinical parameters: ery-
thema, ulceration, and pain. All but one patient had complete
healing of the ulcers. Two patients were continued on systemic
immunosuppressive drugs but these were stopped at the
second cycle of IVIg. Side effects were minimal.
Livedoid vasculitis responding to PUVA therapy. Lee JH,
Choi HJ, Kim SM, Hann SK, Park YK. Int J Dermatol 2001;
40(2):153–157.
Eight South Korean patients with LV (including 4 with
livedo reticularis also) were treated with PUVA. Half of the
patients had failed previous treatments including pred-
nisolone, aspirin, and pentoxifylline. After completion of
PUVA therapy, all patients experienced complete healing of
ulcerations within 10 weeks with minimal side effects. There
was also significant pain relief and no new ulcerations. No
data on relapses noted.
Sulfasalazine in atrophie blanche. Bisalbutra P, Kullavanijaya
P. J Am Acad Dermatol 1993; 28(2 Pt 1):275–276.
Clinical study of 8 patients with refractory LV successfully
treated with sulfasalazine. All patients experienced prior treat-
ment failures with aspirin, cyclophosphamide, prednisone,
pentoxifylline, and nifedipine. After initiating treatment with
sulfasalazine, ulcerations began healing within 1–2 weeks and
46
complete healing was noted within 8 weeks in 7 of 8 patients.
Sulfasalazine was discontinued in one patient after experienc-
ing facial edema 2 days after starting the medication. After
cessation of treatment, patients were followed for 6–10 months
and only 1 patient experienced relapse within 6 months.
Successful treatment of livedo vasculitis with beraprost
sodium: a possible mechanism of thrombomodulin upregu-
lation. Tsutsui K, Shirasaki F, Takata M, Takehara K. Dermato�
beraprost sodium alone then continued on a maintenance
regimen of low-dose aspirin with beraprost sodium at half the
original dose with good clinical responses in all four patients.
Nifedipine treatment of idiopathic atrophie blanche.
Purcell SM, Hayes TJ. J Am Acad Dermatol 1986; 14(5 Pt 1):
851–854.
This is a case report of a 13-year-old patient with idiopathic
LV. Previous treatment strategies including aspirin and dipyri-
damole failed. The patient was then started on nifedipine with
good resolution of symptoms. Relapse occurred when treat-
ment was discontinued.
Livedoid vasculopathy: long-term follow-up results follow-
ing hyperbaric oxygen therapy. Juan WH, Chan YS, Lee JC,
Yang LC, Hong HS, Yang CH. Br J Dermatol 2006; 154:
251–255.
Clinical study of 8 patients with idiopathic LV treated with
100% oxygen in a hyperbaric chamber. Patients received
between 5 and 20 treatments based on the number and sever-
ity of ulcerations. In addition, all patients received a combina-
tion of aspirin, dipyridamole, and pentoxifylline for 1 month
once all hyperbaric oxygen treatments were completed. Patients
reported decreased pain, increased ambulation, and resolution
of ulcers in 3.4 weeks. However, 6 of 8 patients experienced
relapse as early as 6 months after initiating therapy but had
improvement after undergoing additional sessions.
Commonly encountered pitfalls
Atrophie blanche must be distinguished from other similar-
looking lesions. Malignant atrophic papulosis is a systemic
thrombotic disease affecting the central nervous system, gas-
trointestinal tract, and skin. Lesions typically begin on the
trunk or extremities as a crop of small erythematous papules
and eventually form a porcelain white scar with central depres-
sion and occasionally a rim of telangiectasias.1 Skin symptoms
usually precede CNS or GI symptoms.
Special management & counseling considerations
Although the terms livedoid vasculopathy and atrophie
blanche have been used interchangeably, some believe that the

term ‘atrophie blanche’ is a morphological term describing the
atrophic, porcelain white scar in a stellate pattern.13 Atrophie
blanche is not pathognomonic for LV and various conditions
like venous stasis, cutaneous small-vessel vasculitis, and
antiphospholipid syndrome can present with atrophie
blanche-like lesions.1 Therefore, a thorough diagnostic work-up
for collagen vascular diseases among others is indicated for
patients who present with atrophie blanche.
References
1. Piette W. Cutaneous manifestations of microvascular occlusion syn-
dromes. In: Bolognia J, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd
edn. New York: Mosby Elsevier; 2008:331–345.
2. Maessen-Visch MB, Koedam MI, Hamulyak K, Neumann HA. Atrophie
blanche. Int J Dermatol 1999; 38:161–172.
3. Hegemann B, Helmbold P, Marsch WC. Livedoid vasculitis with ulcera-
tions: the role of antithrombin III deficiency and its therapeutic con-
sequences. Arch Dermatol 2002; 138(6):841–842. Erratum in: Arch
Dermatol 2002; 138(9):1212.
4. Kavala M, Kocaturk E, Zindanci I, Turkoglu Z, Altintas S. A case of
livedoid vasculopathy associated with factor V Leiden mutation: suc-
cessful treatment with oral warfarin. J Dermatol Treat 2008; 19(2):
121–123.
Lupus
Chronic cutaneous lupus
Discoid lupus erythematosus
Discoid lupus is one of the most common forms of cutaneous
lupus. Discoid lupus has a female predominance, but the ratio
(3:2 to 3:1) between men and women is not as large as that
observed with systemic lupus (8:1). All races are affected by
discoid lupus, but some data suggests a higher prevalence
among African-Americans. African-Americans with cutaneous
lupus present more commonly with discoid lupus, nephritis,
and anti-Sm and anti-RNP antibodies.1 Only 5–10% of
patients with chronic cutaneous lupus develop systemic lupus
erythematosus.
Characterized by disfiguring patches that have a predilec-
tion for the upper body, discoid lupus is divided into two
groups: localized and widespread. It is considered localized
when the skin lesions are confined to the head and neck areas
and designated as widespread when other body areas are
affected. The lesions of discoid lupus are generally easy to
identify. Classically, an eruption may begin with an erythema-
tous scaly papule or plaque that expands to form a hypopig-
mented center and hyperpigmented peripheral border (Fig.
3.2). Full central depigmentation frequently occurs in older
plaques causing significant disfigurement. The characteristic
histologic findings are interface dermatitis and dilation of fol-
licular openings with keratin plugs (follicular plugging).
Several case reports have described the development of
squamous cell skin cancer in longstanding plaques of discoid
3â•… Collagen Vascular Diseasesâ•… •â•… Lupus
5. Gray HR, Graham JH, Johnson W, Burgoon CF Jr. Atrophie blanche:
periodic painful ulcers of lower extremities. Arch Dermatol 1966;
93:187–193.
6. Barnhill RL, Nousari CH, Xu X, Barksdale SK. Vascular diseases. In:
Elder DE, Elenitsas R, Johnson BL Jr., Murphy GF, Xu X, eds. Lever’s
Histopathology of the Skin. 10th edn. Philadelphia, PA: Lippincott
Williams & Wilkins; 2009. p. 205–34.
7. Kern AB. Atrophie blanche: report of two patients treated with aspirin
and dipyridamole. J Am Acad Dermatol 1982; 6:1048–1053.
8. Browning CE, Callen JP. Warfarin therapy for livedoid vasculopathy
associated with cryofibrinogenemia and hyperhomocysteinemia. Arch
Dermatol 2006; 142:75–78.
9. Kawakami T, Kawasaki K, Mizoguchi M, Soma Y. Therapeutic effect of
lipoprostaglandin E1 on livedoid vasculitis associated with essential
cryoglobulinaemia. Br J Dermatol 2007; 157(5):1051–1053 [Epub
2007 Aug 24].
10. Gupta AK, Goldfarb MT, Voorhees JJ. The use of sulfasalazine in atro-
phie blanche. Int J Dermatol 1990; 29(9):663–665.
11. Purcell SM, Hayes TJ. Nifedipine treatment of idiopathic atrophie
blanche. J Am Acad Dermatol 1986; 14(5 Pt 1):851–854.
12. Drucker CR, Duncan WC. Antiplatelet therapy in atrophie blanche and
livedo vasculitis. J Am Acad Dermatol 1982; 7(3):359–363.
13. Leonard A, Pomeranz MK, Franks AG. A case of livedoid vasculopathy
in a 22 year-old man. J Drugs Dermatol 2004; 3(6):678–679.
lupus in African-American patients.2 Plaques on the scalp are
common and frequently lead to alopecia (Figs. 3.3, 3.4). Pho-
tosensitivity is generally present in patients with discoid lupus,
but many patients, particularly patients of color, may be
unaware of it.
Hypertrophic lupus erythematosus
The plaques of hypertrophic lupus erythematosus are charac-
terized by thick scales. This form of chronic cutaneous lupus
presents with verrucous plaques that tend to occur at sites of
trauma.
Figure 3.2:╇ Early discoid lupus lesion with a hypopigmented center and
violaceous, hyperpigmented, irregular peripheral border in a patient with Fitzpatrick
skin type IV.
47
 Part 1 Medical Dermatology

cally presents with indurated erythematous-violaceous plaques

without scale or follicular plugging. The lesions occur most
commonly on sun-exposed areas–typically the head and neck
region. Patients with lupus tumidus are highly photosensitive.
Most patients show no underlying systemic involvement.
Lupus tumidus is distinct histologically from other forms of
cutaneous lupus by the absence of alterations of the dermal–
epidermal junction and epidermis. Other histologic features
include a superficial and deep perivascular and periadnexal
lymphohistiocytic infiltrate with dense interstitial mucin dep-
osition. Direct immunoflourescence is frequently negative.

Diagnosis and work-up

The diagnosis of chronic lupus erythematosus is made based
on clinical findings followed by confirmation with a skin
biopsy. When the diagnosis of discoid lupus is made, an inves-
tigation to exclude systemic lupus should also ensue. Recom-
mended laboratory tests include a complete blood count with
differential, metabolic panel, urinalysis, erythrocyte sedimen-
tation rate, antinuclear antibodies (ANA), and anti-Ro (SSA),
Figure 3.3:╇ Depigmentation in a chronic DLE plaque with ‘burn out’ scarring
and anti-La (SSB) antibodies.
alopecia.

Management strategy
While there are numerous case reports and a few pertinent
randomized controlled trials on effective treatments for
chronic cutaneous lupus, very few randomized, double-
blind, placebo-controlled trials for medications have been
conducted.
Topical steroids are first-line therapy for chronic cutaneous
lupus. Though few randomized controlled trials have
been performed, there is a longstanding history of successful
treatment with corticosteroids by clinicians worldwide. One
randomized trial reported in the Cochrane Database did show
greater efficacy of fluocinonide cream over hydrocortisone. In
patients who are refractory to potent topical corticosteroids,
intralesional injections of corticosteroids have been found to
be effective.

Figure 3.4:╇ African-American patient with an acute DLE lesion showing peripheral
First-Line Therapies
hyperpigmentation, central depigmentation and alopecia. Note the erythematous
base.
Sunscreen C
Topical corticosteroids B
Lupus panniculitis/lupus profundus Intralesional corticosteroids B
Lupus profundus is classified as a variant of chronic cutaneous Topical immunomodulators B
lupus that primarily involves subcutaneous fat. Lupus profun-
dus is characterized by painful erythematous nodules and
indurated plaques that tend to heal with atrophy and scars. Evaluation of the capacity of sunscreens to photoprotect
lupus erythematosus patients by employing the photo-
Lupus tumidus provocation test. Stege H, Budde MA, Grether-Beck S,
First described by Gougerot and Bournier in 1930, lupus Krutmann J. Photodermatol Photoimmunol Photomed 2000;
tumidus is a rare form of chronic cutaneous lupus that classi- 16:256–259.

48

Broadband sunscreens have been shown to suppress the
induction of skin lesions in patients with cutaneous lupus
exposed to UV irradiation. In this double-blind comparative
study of 11 patients who were photoprovoked, the sunscreen
containing a combination of both UVB and UVA protector
ingredients, specifically mexoryl, showed the highest and most
beneficial protective effect. All patients with discoid lupus
should be counseled to avoid prolonged exposure to sunlight
and other artificial sources of light.
Drugs for discoid lupus erythematosus. Jessop S, Whitelaw
DA, Delamere FM. Cochrane Database of Systematic Reviews
2009(4): CD002954.
In a crossover study of 12 weeks duration, fluocinonide
0.05% cream was found to be more effective than hydrocorti-
sone 1% cream for the treatment of discoid lupus. Twenty-
seven percent of patients using fluocinonide cleared completely
or displayed excellent improvement compared to 10% of those
using hydrocortisone.
Chronic cutaneous lupus erythematosus. Callen JP. Arch
Dermatol. 1982; 118:412–416.
The clinical, laboratory, and therapeutic data of 62
patients with active discoid lupus were reviewed. Of the 40
patients treated with intralesional corticosteroids, 35 noted
improvement.
Tacrolimus vs clobetasol propionate in the treatment of
facial cutaneous lupus erythematosus: a randomized,
double-blind, bilateral comparison study. Tzung TY, Liu YS,
Chang HW. Br J Dermatol 2007; 156:191–192.
In the only randomized controlled trial on the treatment
of cutaneous lupus erythematosus with topical immunomod-
ulators, no significant difference was seen in the efficacy of
tacrolimus 0.1% ointment and clobetasol propionate 0.05%
ointment. This was a double-blind bilateral comparison study
with 20 patients. Clinical outcomes were measured on a
4-week twice-daily application of tacrolimus to one side of the
face and application of 0.05% clobetasol to the other side of
the face. Severity of lesions was assessed based on clinical signs
of erythema, desquamation, and induration. All 18 patients
who completed the study showed improvement based on the
rating scales over a 4-week period. Weekly microdermabrasion
was performed to increase penetration of tacrolimus to the
cutaneous lupus lesions. Telangiectasia was noted as a side
effect of topical clobetasol in 11 patients (61%). A major limi-
tation of the study is the small sample size. Also, it is difficult
to interpret degree of lesion improvement and clearance with
either agent for the patients in the study.
Pimecrolimus 1% cream for cutaneous lupus erythemato-
sus. Kreuter A, Gambichler T, Breuckmann F, Pawlak FM,
Stucker M, Bader A, et╯al. J Am Acad Dermatol 2004;
51:407–410.
Eleven patients with cutaneous lupus erythematosus were
treated with pimecrolimus 1% cream under semi-occlusive
conditions twice daily for 3 weeks. Significant regression of
skin lesions was observed in all patients after treatment. There
3â•… Collagen Vascular Diseasesâ•… •â•… Lupus
was a 57% improvement on clinical severity score (p < 0.001).
Pimecrolimus could be an effective and safe treatment option
for cutaneous lupus erythematosus.
Second-Line Therapies
Antimalarials A
Systemic retinoids B
Dapsone C
Patients with cutaneous lupus erythematosus who smoke
are less responsive to antimalarial treatment. Jewell ML,
McCauliffe DP. J Am Acad Dermatol 2000; 42:983–987.
Antimalarial medications, particularly hydroxychloroquine,
are considered for discoid lupus patients that topical therapy
alone is unsuccessful and when long-term management is
required. In this retrospective analysis, patients with discoid
lupus who smoked appeared to be less responsive to antima-
larial treatment than those who did not smoke.
Lupus erythematosus tumidus: response to antimalarial
treatment in 36 patients with emphasis on smoking. Kreuter
A, Gaifullina R, Tigges C, Kirschke J, Altmeyer P, Gambichler
T. Arch Dermatol 2009; 145:316–319.
In this retrospective, single-center study, the effectiveness
of antimalarial treatment of lupus tumidus was evaluated in
36 patients. Patients were treated with either hydroxychloro-
quine or chloroquine. Overall, treatment with antimalarial
medications showed a significant reduction in cutaneous
lupus disease severity score. Sixty-one percent of patients
exhibited complete or almost complete clearance of skin
lesions. There was no significant difference in efficacy between
hydroxychloroquine and chloroquine. Smokers had a lower
reduction in skin lesions. Smoking cessation should be
encouraged in patients with lupus undergoing treatment with
antimalarial medications.
Treatment of cutaneous lupus erythematosus with acitre�
tin and hydroxychloroquine. Ruzicka T, Sommerburg C,
Goerz G, Kind P, Mensing H. Br J Dermatol 1992; 127:513–
518.
This randomized double-blinded study demonstrated the
efficacy of acitretin and hydroxychloroquine in the treatment
of cutaneous lupus erythematosus. Successful improvement
and clearing of lesions occurred in approximately 50% of
patients in each treatment group. An increase in side effects
was noted in the acitretin group.
Hypertrophic lupus erythematosus treated successfully
with acitretin as monotherapy. Al-Mutairi N, Rijhwani M,
Nour-Eldin O. J Dermatol 2005; 32:482–486.
Patients with hypertrophic lupus erythematosus, a rare
subset of chronic cutaneous lupus erythematosus, have thick
verrucous lesions which are chronic and frequently refractory
to treatment. This case reports the successful treatment of
49
 Part 1 Medical Dermatology
hypertrophic cutaneous lupus on the hands, feet and legs with
acitretin in patients who previously failed topical steroids and
antimalarials.
Efficiency of acitretin in treatment of cutaneous lupus ery-
thematosus. Ruzicka T, Meurer M, Bieber T. Arch Dermatol
1988; 124:897–902.
In this study, twenty patients with cutaneous lupus ery-
thematosus (DLE and SCLE) were treated with an initial dose
of acitretin 50╯mg daily. The dose was adjusted according to
response and tolerability (range of 10–75╯mg). Fifteen patients
responded well. Half of those patients showed more improve-
ment with acitretin than with previous therapies used includ-
ing corticosteroids and antimalarials.
Isotretinoin for refractory lupus erythematosus. Shornick
JK, Formica N, Parke AL. J Am Acad Dermatol 1991;
24:49–52.
Six patients with cutaneous manifestations of lupus ery-
thematosus were treated with isotretinoin, 1╯mg/kg/day. The
cutaneous lesions were resistant to previous treatment with
systemic corticosteroids and antimalarial therapy. Treatment
with isotretinoin resulted in rapid clinical improvement in all
cases. Unfortunately, recurrences occurred rapidly when
the drug was discontinued. Side effects were minimal and
easily controlled by adjustments in dose or by the use of
lubricants.
Dapsone in the treatment of cutaneous lupus erythe�
matosus. Lindskov R, Reymann F. Dermatologica 1986; 172:
214–217.
While the authors of this article concur that hydroxychlo-
roquine remains the drug of choice for systemic treatment of
cutaneous lupus erythematosus, dapsone is felt to be a suitable
alternative treatment for those refractory to other therapies. In
this retrospective analysis, out of 33 patients with chronic
discoid lupus treated with dapsone who were observed in the
study, almost 50% had a significant improvement in skin
disease.
Third-Line Therapies
Cytotoxic agents C toin showed improvement from the fourth to the sixth week
Thalidomide B
Gold B
Clofazamine B discontinued from the study.
Phenytoin C
Sulfasalazine D Long-term thalidomide use in refractory cutaneous lesions
Interferon alpha-a E of lupus erythematosus: a series of 65 Brazilian patients.
Topical Imiquimod E Coelho A, Souto MI, Cardoso CR, Salgado DR, Schmal TR,
Efulizumab E Waddington Cruz M, et╯al. Lupus 2005; 14:434–439.
Efficacy and safety of methotrexate in recalcitrant cutaneous
lupus erythematosus: results of a retrospective study in 43
patients. Wenzel J, Brahler S, Bauer R, Bieber T, Tuting T. Br J
Dermatol 2005; 153:157–162.
50
Efficacy of low-dose methotrexate was demonstrated in 42
out of 43 (98%) patients with cutaneous lupus erythematosus
who were refractory to first-line treatments. Seven patients had
to discontinue treatment due to side effects which were not
life-threatening and resolved upon discontinuation of the
medication. Careful patient selection and close attention to
potential side effects are recommended.
Azathioprine. An effective corticosteroid-sparing therapy for
patients with recalcitrant cutaneous lupus erythematosus
or with recalcitrant cutaneous leukocytoclastic vasculitis.
Callen JP, Spencer LV, Burruss JB, Holtman J. Arch Dermatol
1991; 127:515–522.
Four of six patients with recalcitrant cutaneous lupus dem-
onstrated improvement after use of azathioprine. Five of six
patients with leukocytoclastic vasculitis improved. Due to the
significant side effects observed the authors recommended use
only in severe disease when more conventional treatments fail.
Clofazimine in the treatment of discoid lupus erythemato-
sus. Mackey JP, Barnes J. Br J Dermatol 1974; 91:93–96.
Noting similarities in the mechanisms of immunosuppres-
sion of chloroquine and clofazimine (both taken up by mac-
rophages and interrupting phagocytosis), the authors of this
study conducted an open trial to observe response of discoid
lupus to clofazimine. Seventeen of twenty-six patients went
into remission. Doses ranged from 100╯mg dosed three times
a week to 200╯mg daily. Optimal dose appeared to be 100╯mg
daily. Relapse occurred after treatment in some cases, but these
patients responded after a second course. Improvement con-
tinued months after withdrawal of the medication in 6 patients.
The lasting effect is attributed to absorption and deposition of
clofazimine in the subcutaneous fat as well as storage in the
reticuloendothelial cells.
Phenytoin in the treatment of discoid lupus erythemato�
sus. Rodriguez-Castellanos MA, Barba Rubio J, Barba Gomez
JF, Gonzalez Mendoza A. Arch Dermatol 1995; 131:620–621.
Patients with discoid lupus were observed for response to
treatment with phenytoin dosed at 100╯mg three times a day.
Ninety percent (9 patients) with disseminated disease had an
excellent response. The patients who were treated with pheny-
of treatment. Side effects were minimal and treatable. However,
6 patients developed erythema multiforme, urticarial reac-
tions, myalgia, muscle weakness and paresthesia and were
Thalidomide is very effective in the treatment of cutaneous
lupus. However, the side effects, such as teratogenicity and
neuropathy, limit its utility. This study observed the clinical
efficacy of long-term low-dose thalidomide in 65 patients with
lupus erythematosus with a special focus on the incidence
of side effects. Nearly 99% of patients showed complete or

partial improvement with thalidomide treatment. The notable
adverse effects were drowsiness and neuropathy. Drowsiness
was observed in 77% of the patients and neuropathy occurred
in 43%.
Thalidomide for the treatment of resistant cutaneous
lupus: efficacy and safety of different therapeutic regimens.
Cuadrado MJ, Karim Y, Sanna G, Smith E, Khamashta MA,
Hughes GR. Am J Med 2005; 118:246–250.
The safety and efficacy of various doses of thalidomide was
observed in patients who were unresponsive to other systemic
treatments for cutaneous lupus. The doses used were 100╯mg
daily, 50╯mg daily, or 50╯mg every other day. Eighty-one
percent of patients responded to treatment with thalidomide,
with 60% of those experiencing complete remission. Nine
patients (19%) had no response. Twenty-seven percent devel-
oped peripheral neuropathy. The other side effects observed
included drowsiness, constipation, abdominal pain, and
amenorrhea. Interestingly, there was no significant difference
in response based on dose. Also of note, side effects did not
appear to be dose-dependent.
Treatment of chronic discoid lupus erythematosus with
an oral gold compound (auranofin). Dalzial K, Going G,
Cartwright PH, Marks R, Beveridge GW, Rowell NR. Br J Der-
matol 1986; 115:211–216.
Twenty-three patients with discoid lupus were treated with
auranofin for 1 year with an average dose of 3╯mg twice daily.
Lesions completely resolved in 4 patients and 15 showed
notable improvement. Gold is rarely employed for current
therapy for discoid lupus, but if used, patients should be mon-
itored for side effects which include gastrointestinal symptoms
such as nausea and diarrhea, drug eruption, thrombocytope-
nia, and proteinuria.
Treatment of discoid lupus erythematosus with sulfasala-
zine. 11 cases. Delaporte E, Catteau B, Sabbagh N, Gosselin P,
Breuillard F, Doutre MS, et╯al. Ann Dermatol Venereol 1997;
124:151–156.
Of the 11 patients with discoid lupus treated with sulfasala-
zine in this case series, 7 were considered complete responders;
1 patient responded partially; 3 patients failed treatment.
While sulfasalazine is not a first-line agent, it can be consid-
ered in refractory cases of chronic cutaneous lupus. Sulfasala-
zine can cause photosensitivity so should be used with caution
in patients with SLE.
Response of discoid and subacute cutaneous lupus ery-
thematosus to recombinant interferon alpha 2a. Nicolas JF,
Thivolet J, Kanitakis J, Lyonnet S. J Invest Dermatol 1990;
95:142S–154S.
Some cases of discoid lupus have been successfully treated
with systemic interferon alpha 2a. In this study, patient
response was rapid and impressive, but relapse occurred in all
study patients after withdrawal of the medication.
A case of generalized discoid lupus erythematosus: success-
ful treatment with imiquimod cream 5%. Gul U, Gonul M,
3â•… Collagen Vascular Diseasesâ•… •â•… Lupus
Cakmak SK, Kilic A, Demiriz M. Adv Ther 2006; 23:
787–792.
In this case report from Turkey, a 44-year-old male with
discoid lupus on the face, scalp, ears, and limbs was treated
successfully with imiquimod 5% cream. Imiquimod was
applied to the lesions once a day three times a week. Clear�
ance and major regression of lesions occurred after 20
applications.
Efalizumab in the treatment of discoid lupus erythemato-
sus. Usmani N, Goodfield M. Arch Dermatol 2007; 143:
873–877.
Refractory cases of discoid lupus will often require cytotoxic
immunosuppressive therapy. Efulizumab, a monoclonal anti-
body against CD11a, a subunit of the leukocyte-functioning
antigen 1, is presented as a novel therapeutic alternative for
resistant cases. Good response was observed in 12 out of 13
patients after a mean of 5 weeks. One patient with poor
response had severe headaches and was withdrawn from the
study. No long-term follow-up results were reported.
Special management & counseling considerations
Alopecia is a common associated finding in patients with
discoid lupus who have scalp involvement. Management is
aimed at decreasing inflammation and treating the underlying
discoid lupus plaques as soon as possible to prevent perma-
nent scarring and follicular dropout. The incidence of alopecia
areata is also increased in patients with lupus erythematosus.3
Treatment with intralesional corticosteroids can provide hair
regrowth and in many cases provide rapid improvement of
alopecia occurring directly over discoid plaques on the scalp.
Discoid lupus is characterized by atrophy in later stages.
Thus, use of potent topical corticosteroids requires a delicate
balancing act of using the dose that is most effective for treat-
ment yet avoids exacerbation of atrophic changes.
All patients with discoid lupus, and African-Americans in
particular, should be monitored for squamous cell carcinoma
that could arise in chronic lesions of discoid lupus erythema-
tosus. Skin cancer is less common in African-Americans than
other racial groups. Discoid lupus, however, appears to be a
predisposing factor for the development of squamous cell skin
cancer in black skin. Malignant change is observed more com-
monly in men. The malignant change is in many cases associ-
ated with solar damage. Occurrence of metastases of squamous
cell skin cancer has been observed in discoid lupus, regardless
of race. Clinicians should maintain a low threshold for biopsy-
ing suspicious lesions of discoid lupus, particularly those
which are hyperkeratotic or poorly healing. In addition, those
patients with DLE who have been found to have a squamous
cell skin cancer should be monitored, as the potential for
metastasis may be greater than in squamous cell cancers
arising in normal skin.4
Some evidence suggests that smokers with discoid lupus
have more severe disease. Furthermore, patients with cutane-
ous lupus who smoke appear to be less responsive to antima-
larial treatment.5 Smoking cessation should be an integral
51
 Part 1 Medical Dermatology
part of the treatment plan for chronic cutaneous lupus in
smokers.
References
1. Cooper GS, Parks CG, Treadwell EL, St Clair EW, Gilkeson GS, Cohen
PL, et al. Differences by race, sex and age in the clinical and immuno-
logic features of recently diagnosed systemic lupus erythematosus
patients in the southeastern United States. Lupus 2002; 11:161–167.
2. Caruso WR, Stewart ML, Nanda VK, Quismorio FP. Squamous cell
carcinoma of the skin in black patients with discoid lupus erythema-
tosus. J Rheumatol 1987; 14:156–159.
3. Werth VP, White WL, Sanchez MR, Franks AG. Incidence of alopecia
areata in lupus erythematosus. Arch Dermatol 1992; 128:368–371.
4. Presser SE, Taylor R. Squamous cell carcinoma in blacks with discoid
lupus erythematosus. J Am Acad Dermatol 1981; 4:667–669.
5. Jewel ML, McCauliffe DP. Patients with cutaneous lupus erythemato-
sus who smoke are less responsive to antimalarial treatment. J Am
Acad Dermatol 2000; 42:983–987.
Subacute cutaneous lupus erythematosus (SCLE)
Subacute cutaneous lupus (SCLE) is a variant of cutaneous
lupus described in 1979 by Sontheimer, Thomas, and Gilliam.
While not uncommon among people of color, SCLE more
frequently affects Caucasian females between the ages of 15
and 40. Like other forms of cutaneous lupus, SCLE occurs in
genetically predisposed individuals. Development of SCLE has
been linked to certain HLA subtypes, such as HLA-B8, HLA-
DR3, HLAw52, and HLA-DQ1. Most patients are positive for
anti-Ro (SS-A) antibodies. The pathophysiology, while incom-
pletely understood, involves the alteration of autoantibodies,
epidermal cytokines, and adhesion molecules by ultraviolet
light which leads to keratinocyte apoptosis.
Reactions generally begin with a papular eruption with
mild pruritis. Patients present clinically with erythematous
papules that coalesce to form a psoriasiform pattern or poly-
cyclic annular arrangement with light scale in a symmetrical
distribution. The typical locations for an SCLE skin eruption
are sun-exposed areas – face, neck, upper back, and upper
anterior chest. Unlike discoid lupus, scarring is not a feature.
Patients may, however, have residual hyperpigmented and
hypopigmented changes and telangiectasia. Follicular plug-
ging is generally absent, unlike in discoid lupus; 50–71% of
patients have antibodies to Ro/SSA. It is estimated that 10–
15% of patients with subacute cutaneous lupus erythematosus
develop internal disease over time. Approximately 50% of
patients with SCLE exhibit four or more criteria for the sys-
temic lupus classification, but internal disease is generally less
severe. Approximately one-half of patients have joint involve-
ment, mostly symmetrical arthralgias affecting small joints
such as the hands and wrists. Overlapping symptoms of
Sjogren’s syndrome may occur. These patients may have dry
eyes (keratoconjunctivitis) and dry mouth (xerostomia).
Annular erythema of Sjogren’s syndrome has been classified
as a distinct entity in Japanese and Polynesian patients.
However, many experts consider this condition to be a variant
of subacute cutaneous lupus. A variant of SCLE in which
patients present with a combination of erythema multiforme-
52
like lesions, discoid lupus plaques, and chilblains has been
described as Rowell’s syndrome.
Several medications have been reported to induce the onset
of subacute cutaneous lupus erythematosus. The most
common medications include terbinafine, hydrochlorothi-
azide, griseofulvin, calcium channel blockers, and non-
steroidal anti-inflammatory drugs.
While there are no pathognomonic histologic findings,
typical features are similar to other forms of cutaneous lupus.
Superficial and deep inflammatory infiltrates are present along
with interface changes. However, epidermal atrophy is a more
common feature in SCLE than in the other forms of cutaneous
lupus.
The differential diagnosis of SCLE includes other annular
erythemas, such as erythema annulare centrifugum and granu-
loma annulare. Cutaneous SCLE can also appear clinically
similar to dermatophytosis, psoriasis, and eczema.
First-Line Therapies
Sunscreens C
Topical corticosteroids E
Antimalarials D
Systemic retinoids B
Use of sunscreens to protect against ultraviolet-induced
lupus erythematosus. Herzinger T, Plewig G, Rocken M.
Arthritis Rheum 2004; 50:3045–3046.
Sunscreens providing protection against both UVA and UVB
are very effective in protecting against UV-induced lupus
erythematosus.
The association of the two antimalarials chloroquine and
quinacrine for treatment-resistant chronic and subacute
cutaneous lupus erythematosus. Feldman R, Salomon D,
Saurat JH. Dermatology 1994; 189:425–427.
Fourteen patients who had not responded to single antima-
larial treatment with either chloroquine or hydroxychloro-
quine were treated with a combination of chloroquine 100╯mg
3×/day and quinacrine 65╯mg 3×/day. All 5 patients with SCLE
cleared completely and 5 out of 9 patients with chronic
lupus erythematosus improved significantly or completely. In
patients who are not responding as well as expected on anti-
malarial therapy, the combination of chloroquine and quina-
crine may provide a better outcome. Close monitoring of
side effects and potential eye complications should not be
overlooked.
Second-Line Therapies
Dapsone E
Antibiotics E
Systemic retinoids B
Immunosuppressive agents D

Annular subacute cutaneous lupus erythematosus respon-
sive to dapsone. McCormack LS, Elgart ML, Turner ML. J Am
Acad Dermatol 1984; 11:397–401.
This is a case report of two patients with annular subacute
cutaneous lupus erythematosus successfully treated with
dapsone. Treatment with dapsone prevented new lesions and
led to marked improvement with eventual resolution of skin
lesions. Dose of dapsone ranged from 50 to 100╯mg daily.
Patients sustained improvement over 8–12 months. A mainte-
nance dose of 25╯mg/day was required in one patient.
Low dose dapsone in the treatment of subcutaneous lupus
erythematosus. Fenton DA, Black MM. Clin Exp Dermatol
1986; 11:102–103.
This is a report of a 58-year-old male with a 3-year history
of subacute cutaneous lupus erythematosus who failed treat-
ment with potent topical corticosteroids and systemic mepa-
crine. The patient had complete clearance of lesions after 3
weeks of low-dose dapsone (25╯mg daily).
Long-term cefuroxime axetil in subacute cutaneous lupus
erythematosus. A report of three cases. Rudnicka L,
Szymanska E, Walecka I, Slowinska M. Dermatology 2000;
200:129–131.
Based on the observation of complete clearance of subacute
cutaneous lupus in three patients treated with cefuroxime
axetil, the authors suggest that this cephalosporin medication
may be a good alternative medication to consider in the treat-
ment of SCLE. The patients were treated with cefuroxime axetil
500╯mg for 30–60 days. An obvious limitation of the study is
the small number of patients reported and a condition which
may improve on its own regardless of treatment.
Efficiency of acitretin in treatment of cutaneous lupus ery-
thematosus. Ruzicka T, Meurer M, Bieber T. Arch Dermatol
1988; 124:897–902.
Azathioprine. An effective corticosteroid-sparing therapy for
patients with recalcitrant cutaneous lupus erythematosus
or with recalcitrant cutaneous leukocytoclastic vasculitis.
Callen JP, Spencer LV, Burruss JB, Holtman J. Arch Dermatol
1991; 127:515–522.
Four out of six patients with recalcitrant cutaneous lupus
demonstrated improvement after use of azathioprine. Five of
six patients with leukocytoclastic vasculitis improved. Due to
the significant side effects observed the authors recommended
use only in severe disease when more conventional treat�
ments fail.
Mycophenolate sodium for subacute cutaneous lupus ery-
thematosus resistant to standard therapy. Kreuter A, Tomi
NS, Weiner SM, Huger M, Altmeyer P, Gambichler. Br J Der-
matol 2007; 156:1321–1327.
In this prospective, non-randomized, open pilot study, 10
patients who were resistant to standard therapy were treated
with oral mycophenolate sodium 1440╯mg daily for 3 months.
Clinical improvement was achieved in all patients and no
serious side effects were seen.
3â•… Collagen Vascular Diseasesâ•… •â•… Lupus
Third-Line Therapies
Clofazimine E
Phenytoin B
IVIg C
Capacitabine E
Cytokine therapy D
Interferon C
Intravenous immunoglobulin (IVIg) for therapy-resistant
cutaneous lupus erythematosus. Goodfield M, Davison K,
Bowden K. J Dermatolog Treat 2004; 15:46–50.
IVIg is felt to be a possible alternative treatment for subcu-
taneous lupus erythematosus in patients who are refractory to
other therapies. The dose of IVIg started with 1g/kg × 2, fol-
lowed by 400╯mg/kg monthly until disease resolution or for 6
months. Approximately 75% of patients (5 patients) had com-
plete or near complete clearing of their skin disease. Two
patients had partial improvement and 3 patients had limited
response. The treatment was well-tolerated with an overall
good safety profile. Of note, 1 patient developed acute cutane-
ous vasculitis in this study.
Response of discoid and subacute cutaneous lupus ery-
thematosus to recombinant interferon alpha 2a. Nicolas JF,
Thivolet J, Kanitakis J, Lyonnet S. J Invest Dermatol 1990; 95:
142S–145S.
Eight out of ten patients with subacute cutaneous lupus
responded to treatment with interferon alpha 2a in this study.
However, all patients subsequently relapsed after withdrawal
of the medication. Further study will clarify the possible role
of interferon alpha 2a in the treatment of SCLE.
Special management & counseling considerations
SCLE may be less responsive to antimalarial treatment. Sys-
temic retinoid treatments, however, may actually yield a better
response in SCLE than other types of cutaneous lupus. In some
cases, combinations of antimalarials may need to be carefully
implemented and other alternative treatments started earlier.
References
1. Reed BR, Huff JC, Jones SK, Orton PW, Lee LA, Norris DA. Subacute
cutaneous lupus erythematosus associated with hydrochlorothiazide
therapy. Ann Intern Med 1985; 103:49–51.
2. Callen JP, Hughs AP, Kulp-Shorten C. Subacute cutaneous lupus ery-
thematosus induced or exacerbated by terbinafine. Arch Dermatol
2001; 137:1196–1198.
3. Srivastava M, Rencic A, Diglio G, Santana H, Bonitz P, Watson R, et al.
Drug-induced, Ro/SSA-positive cutaneous lupus erythematosus. Arch
Dermatol 2003; 139:45–49.
Systemic lupus erythematosus
Lupus erythematosus is the prototypic autoimmune disease
with a wide spectrum of clinical manifestations. Given its
53
 Part 1 Medical Dermatology
Table 3.1╇ American College of Rheumatology 1982 revised criteria
for classification of systemic lupus erythematosus*
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis (Non-erosive arthritis involving 2 or more peripheral joints)
Serositis (Pleurisy, pleural effusion, pericarditis, pericardial effusion)
Renal disorder (Proteinuria greater than 3+ or 0.5╯g/day, or cellular
casts)
Neurologic disorder (Seizures or psychosis not due to other underlying
factors)
Hematologic disorder (Hemolytic anemia, leukopenia, lymphopenia, or
thrombocytopenia)
Immunologic disorder (Positive anti-DNA antibody, positive anti-Smith
antibody, or false positive serologic test for syphilis)
Abnormal anti-nuclear antibody titer
*One meets the criteria for diagnosis of SLE if four or more of the 11 criteria listed are
present.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982
revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum
1982; 25:1271–1277.
multitude of cutaneous manifestations, dermatologists fre-
quently play an integral role in the management of patients
with lupus erythematosus. Systemic lupus erythematosus
(SLE) has been reported to occur in one in 10╯000 Caucasian
males, one in 1000 Caucasian females, and one in 250 African-
American females. The cause of this ethnic and gender
difference remains unclear, but there is evidence to suggest
socioeconomic status, inequities in access to healthcare, and
hormonal factors may play a major role. There are also widely
variable regional differences in the epidemiology of SLE. While
systemic lupus has the highest prevalence among African-
American women, it is interesting to note that systemic lupus
does not have a strikingly high prevalence on the African con-
tinent. The prevalence of cutaneous lupus in the United States
varies between 17 and 48 cases/100,000 persons and the trend
has been increasing over recent years.1
The etiology of lupus is complicated by the heterogeneous
nature of the disease and its variable clinical presentation. The
American College of Rheumatology developed criteria for the
classification of SLE (Table 3.1).2 Major research efforts have
shed light on the pathogenetic mechanisms of lupus, but not
culminated in complete understanding. Immunological mech-
anisms combined with genetic and environmental influences
play a role. A major paradigm of the pathogenesis involves
cross reactions to a self antigen occurring in genetically sus-
ceptible individuals. This instigates an autoimmune response
followed by a phenomenon known as epitope spreading
whereby there is expansion of the autoimmune response
leading to organ damage.3 Many of the clinical manifestations
54
Figure 3.5:╇ Malar rash of systemic lupus erythematosus.
of lupus are a result of damage from circulating immune com-
plexes on various tissues and the direct effects of
autoantibodies.
Lupus is a polygenic disorder, as no one specific gene is
responsible for the disease. In fact, over 30 susceptibility genes
have been identified for SLE. The combination of genes has
geographic, racial, and ethnic variability. Certain HLA types
are also associated with lupus, most commonly HLA-DR2,
DR3, DR4, and DR8.4 Genetic deficiency of complement
factors C1q, C2, and C4 have been demonstrated in patients
with lupus.
Studies have shown a delayed expression of inducible nitric
oxide synthase, an enzyme regulating the production of nitric
oxide, which is an important regulator of apoptosis. Aberrant
expression of nitric oxide synthase has been found in the
epidermis of patients with cutaneous lupus erythematosus.
Compared to healthy controls, skin lesions from patients with
cutaneous lupus have been found to have a significant increase
in apoptotic keratinocytes after ultraviolet irradiation.5
Lupus commonly presents in young healthy-appearing
women with complaints of fatigue and arthralgia. The most
common presenting symptom is arthralgia (62%), followed
by cutaneous manifestations (20%). Constitutional symptoms
of fever, malaise, anorexia, and weight loss are common as
well. The most frequent cutaneous manifestations of lupus
include photosensitivity, malar rash, oral ulcerations, and alo-
pecia (Figs. 3.5–3.9). Approximately 10% of patients with SLE
develop urticaria and this appears to occur more often in those
with an atopic diathesis. Other cutaneous findings include
cutaneous vasculitis, Raynaud’s phenomenon, and livido retic-
ularis. Subsets of cutaneous lupus are covered in detail in prior
sections of the chapter.
Lupus nephritis occurs in 30% of patients with SLE and is
associated with high morbidity and mortality. Musculoskeletal
manifestations include arthralgias, true inflammatory arthritis,
and myalgias as well as myositis with elevated muscle enzymes.
Patients must also be monitored for complications such as
osteopenia, osteoporosis, and even avascular necrosis of the

Figure 3.6:╇ Photosensitivity rash over the face of a SLE patient with skin
phototype V. A common presentation of this disease is a diffuse reticulated
hyperpigmentation of the skin.
Figure 3.7:╇ Photosensitivity rash in SLE.
femoral head which may develop as sequelae of long-term
corticosteroid therapy. Pulmonary features include pleurisy,
acute pneumonitis, and chronic interstitial lung disease.
Lupus patients are at increased risk for pulmonary embo�
lism and pulmonary hypertension. SLE can also involve the
3â•… Collagen Vascular Diseasesâ•… •â•… Lupus
Figure 3.8:╇ Dorsal surface of the hand with SLE photosensitivity rash.
Figure 3.9:╇ Photosensitivity rash over the neck in SLE.
cardiovascular system. Many lupus patients develop chest dis-
comfort and dyspnea due to pericardial inflammation and
effusions. Myocardial disease and endocarditis (Libman–Sacks
endo�carditis) are other potential cardiovascular complications
of lupus. The central nervous system may also be affected in
SLE. Cognitive dysfunction, CNS vasculitis, and visual changes
are potential neurologic complications.6
Race is a major predictor of clinical manifestations of SLE.
Differences in clinical and laboratory features between ethnici-
ties have been demonstrated as well. Renal manifestations
occur more commonly in African-American and Hispanic
patients compared to Caucasians with SLE. An increase in
cardiac involvement, discoid lupus, and lymphadenopathy
has also been demonstrated in African-Americans while a
decrease in photosensitivity and malar rash occurs in this
group. Anti-Sm and Anti-RNP occur more frequently in
African-Americans.7–10 A study of patients from Pakistan
showed less cutaneous, arthritic, and renal involvement, but
higher neuropsychiatric symptoms.11 Of patients living in
Malaysia, it appears that the ethnic Chinese have a higher
prevalence of SLE (with a high prevalence of renal disease)
55
 Part 1 Medical Dermatology
than the Indian and Malay patients.12 A small study of a
Vietnamese population in California in the United States dem-
onstrated a relatively high prevalence of anti-RNP antibody
and features of overlap syndrome.13 A study of patients in
Saudi Arabia showed that SLE manifests similarly to patients
in other Arab countries and Caucasians. The 5-year survival
rate (98%) was similar to that of western countries and the
10-year survival rate (97%) higher than most places. The most
common manifestations were hematologic abnormalities,
arthritis, mucocutaneous symptoms, and malar rash.14
Before making a diagnosis of systemic lupus it is important
to exclude the possibility of a drug-induced lupus-like syn-
drome. Procainamide, hydralazine, isoniazid, minocycline,
doxycycline, quinidine, and methyldopa are well-known
causes of lupus-like syndrome; 80–90% of patients with drug-
induced lupus-like syndrome have antibodies to histone.
Specific investigations
The antinuclear antibody (ANA) is the gold standard screening
test for SLE. While ANA has low specificity, it is positive in
96% of those with SLE. The pattern of immunofluorescence is
helpful. A speckled pattern is non-specific, but a homogeneous
or rimmed pattern is suggestive of lupus. When the ANA is
positive, testing for other serologies that are more specific to
lupus is recommended. Specifically, positive double-stranded
DNA (ds-DNA) antibodies are highly suggestive of SLE; 50%
of patients with SLE have autoantibodies to double stranded
DNA. Elevated levels of anti-ds-DNA may correlate with the
degree of activity of lupus and level of nephritis.
Low serum complement levels, specifically C3 and C4 are
seen in patients with SLE. This finding is associated with the
level of inflammation and correlates with disease activity.
Creatinine and blood chemistries, along with urinalysis are
appropriate to monitor for renal involvement. An electro�
cardiogram and chest X-ray may be warranted to monitor for
cardiac disease and pulmonary complications, respectively.
First-Line Therapies
NSAIDS B systemic lupus erythematosus. Bezerra EL, Vilar MJ,
Systemic corticosteroids A da Trindade Neto PB, Sato EI. Arthritis Rheum 2005; 52:
Antimalarials A 3073–3078.
Clofazimine A
Topical corticosteroids A 6 months. Twenty-seven patients completed the study. No
Celecoxib for systemic lupus erythematosus: case series and
literature review of the use of NSAIDS in SLE. Lander SA,
Wallace DJ, Weisman MH. Lupus 2002; 11:340–347.
This retrospective review of medical records from 50
patients with systemic lupus erythematosus treated with
celecoxib (200–400╯mg/day for 1–9 months) by a community-
based rheumatologist revealed a good safety profile and mod-
erate efficacy in the treatment of SLE.
56
The effect of moderate-dose corticosteroids in preventing
severe flares in patients with serologically active, but clini-
cally stable, systemic lupus erythematosus. Findings of a
prospective, randomized, double-blind, placebo-controlled
trial. Tseng CE, Buyon JP, Kim M, Belmont HM, Mackay M,
Diamond B, et╯al. Arthritis Rheum 2006; 54:3623–3632.
A total of 154 patients qualified for this trial. During a
period of clinical stability, 41 of the 154 patients developed a
serologic flare (defined as elevation of C3a level by 50% and
anti-dsDNA levels by 25%). These 41 patients were then ran-
domized to placebo or treatment with prednisone (30╯mg
daily for 2 weeks, 20╯mg daily for 1 week, and 10╯mg daily for
1 week). Four of twenty-one patients in the prednisone group
developed a mild to moderate flare. Seven of twenty patients
in the placebo group experienced at least one flare. All severe
flares occurred in the placebo group.
A randomized study of the effect of withdrawing hydroxy-
chloroquine sulfate in systemic lupus erythematosus. The
Canadian hydroxychloroquine study group. N Eng J Med
1991; 324:150–154.
In this 6-month, randomized, double-blind, placebo-
controlled study, the authors looked at the effect of discon-
tinuing hydroxychloroquine in 47 patients with clinically
stable SLE. Results showed that patients with stable SLE who
are maintained on hydroxychloroquine were less likely to
develop a flare.
Hydroxychloroquine in pregnant patients with systemic
lupus erythematosus. Parke A, West B. J Rheumatol 1996;
23:1715–1718.
The safety of hydroxychloroquine was observed in 8 preg-
nant patients on the medication. Flares of SLE can have a
detrimental effect on the fetus during pregnancy. Due to the
increased risk of a lupus flare upon discontinuation of
hydro�xychloroquine during pregnancy, the authors of this
study concede that it is safer to continue hydroxychloroquine
rather than to discontinue the drug because of pregnancy
alone.
Double-blind, randomized, controlled clinical trial of
clofazimine compared with chloroquine in patients with
Sixteen patients received clofazimine at 100╯mg/day and 17
patients received chloroquine diphosphate at 250╯mg/day for
significant difference was noted in response between the two
groups. Twelve patients in the clofazimine group and 14
patients in the chloroquine group (82%) had complete or
nearly complete clearance of lesions. The authors concluded
that clofazimine proved to be as effective as chloroquine in
the treatment of systemic lupus. However, it was noted that 5
patients in the initial clofazimine group dropped out due to a
severe lupus flare compared to only 1 patient in the chloro-
quine group. This raised the question of whether clofazimine
could possibly trigger a lupus flare.

Tacrolimus vs clobetasol propionate in the treatment of
facial cutaneous lupus erythematosus: a randomized,
double-blind, bilateral comparison study. Tzung TY, Liu YS,
Chang HW. Br J Dermatol 2007; 156:191–192.
Second-Line Therapies
Topical immunomodulators C Manger B. Br J Rheum 1996; 35:669–675.
Immunosuppressants:
Methotrexate A
Azathioprine B to side effects (an elevated creatine level and a nephritis flare).
Cyclosporin C Ten patients showed significant reduction of proteinuria. All
Topical tacrolimus and pimecrolimus in the treatment of
cutaneous lupus erythematosus: an evidence-based evalua-
tion. Tzellos TG, Kouvelas D. Eur J Clin Pharmacol 2008;
64:337–341.
This review article included 5 studies that demonstrated the
efficacy of tacrolimus and pimecrolimus in the initial cutane-
ous lesions of SLE.
Pimecrolimus 1% cream for cutaneous lupus erythemato-
sus. Kreuter A, Gambichler T, Breuckmann F, Pawlak FM,
Stucker M, Bader A, et al. J Am Acad Dermatol 2004;
51:407–410.
Double blind, randomized, placebo controlled clinical trial
of methotrexate in systemic lupus erythematosus. Carneiro
JR, Sato EI. J Rheumatol 1999; 26:1275–1279.
In this study, methotrexate was found to be effective in
controlling cutaneous and joint disease in patients with SLE.
Results were observed after 6 months of methotrexate dosed
15–20╯mg/week.
Azathioprine therapy for patients with systemic lupus
erythematosus. Abu-Shakra M, Shoenfield Y. Lupus 2001;
10:152–153.
Azathioprine has been recommended in SLE patients who
have recurrent flares or require a maintenance dose of 15╯mg
or higher of prednisone. It is used for lupus nephritis in com-
bination with systemic steroids. Azathioprine has been found
to be effective in the treatment of cutaneous lupus and in SLE
patients with pneumonitis, thrombocytopenia, and hemolytic
anemia.
Cyclophosphamide for the treatment of systemic lupus
erythematosus. Takada K, Illei GG, Boumpas DT. Lupus 2001;
10:154–161.
Due to evidence in controlled trials, cyclophosphamide has
become the standard of treatment for moderate to severe lupus
nephritis. Combining pulse cyclophosphamide with pulse
methylprednisolone further improved efficacy without an
increase in toxicity.
Patients should be monitored cautiously while on
cyclophosphamide for signs of toxicity and bone marrow
3â•… Collagen Vascular Diseasesâ•… •â•… Lupus
suppression. Intravenous pulse therapy is associated with
fewer side effects. Mesna is recommended for protection
against bladder carcinoma and cystitis. Some patients may
want to consider sperm or ovum banking in the event of
infertility.
Cyclosporin A in the treatment of systemic lupus erythema-
tosus: results of an open clinical study. Manger K, Kalden R,
Sixteen patients who had inadequate control of disease
were treated with cyclosporin A (3–5╯mg/kg) for an average of
30 months. Three patients had to discontinue treatment due
3 patients with thrombocytopenia and all 3 patients with
leukocytopenia showed improvement of platelet count and
leukocytes, respectively. The most frequent side effects were
hypertension, alteration of renal function, and hypertrichosis.
Overall, cyslosporin was well-tolerated over an extended
period of time and effective in controlling disease activity in
patients with SLE.
Cyclosporin is an effective treatment for SLE, but given the
high prevalence of renal involvement in SLE, its potential
nephrotoxic effects may limit its use.
Long-term thalidomide use in refractory cutaneous lesions
of lupus erythematosus: a series of 65 Brazilian patients.
Coelho A, Souto MI, Cardoso CR, Salgado DR, Schmal TR,
Waddington Cruz M, et al. Lupus 2005; 4:434–439.
Thalidomide for the treatment of resistant cutaneous lupus:
efficacy and safety of different therapeutic regimens.
Cuadrado MJ, Karim Y, Sanna G, Smith E, Khamashta MA,
Hughes GR. Am J Med 2005; 118:246–250.
Commonly encountered pitfalls
It is important to remember that one of the most common
causes of death in patients with SLE is infection, in many cases
due to immunosuppressives. Close monitoring for infections
and other complications is imperative. Infections can also
trigger flares in lupus patients. Thus, early and prophylactic
treatment of infection is recommended.
References
1. Tebbe B, Orfanos CE. Epidemiology and socioeconomic impact of skin
disease in lupus erythematosus. Lupus 1997; 6:96–104.
2. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al.
The 1982 revised criteria for the classification of systemic lupus ery-
thematosus. Arthritis Rheum 1982; 25:1271–1277.
3. Lee LA. Lupus erythematosus. In: Bolognia J, Jorizzo JL, Rapini RP,
eds. Dermatology. 1st edn. New York: Mosby Elsevier; 2003:601–
611.
4. Smolen JS, Klippel JH, Penner E, Reichlin M, Steinberg AD, Chused
TM, et al. HLA-DR antigens in systemic lupus erythematosus: associa-
tion with specificity of autoantibody responses to nuclear antigens.
Ann Rheum Dis 1987; 46:457–462.
57
 Part 1 Medical Dermatology
5. Kuhn A, Krammer PH, Kolb-Bachofen V. Pathophysiology of cutane-
ous lupus erythematosus – novel aspects. Rheumatology 2006; 45:
14–16.
6. Wallace DJ. Lupus: The essential clinician’s guide. Oxford American
Rheumatology Library. Oxford: Oxford University Press; 2008.
p. 21–47.
7. Petri M. The effect of race on incidence and clinical course in systemic
lupus erythematosus: the Hopkins lupus cohort. JAMWA 1998; 53:
9–12.
8. Alarcon GS, McGwin G, Petri M, Reveille JD, Ramsey-Goldman R,
Kimberly RP, et al. Baseline characteristics of a multiethnic lupus
cohort: PROFILE. Lupus 2002; 11:95–101.
9. Sestak AL, Nath SK, Kelly JA, Bruner GR, James JA, Harley JB. Patients
with familial and sporadic onset SLE have similar clinical profiles but
vary profoundly by race. Lupus 2008; 17:1004–1009.
Scleroderma
Localized scleroderma (morphea)
Localized scleroderma, also known as morphea, is a sclerosing
condition of the skin and subcutaneous tissue due to inflam-
mation. The histologic features of morphea and systemic scle-
rosis (SSc) are very similar and the two diseases probably share
a common pathogenesis. However, morphea and SSc are two
different clinical entities that are related.1 Morphea is more
common in females than males and affects children (20% of
patients) as well as adults.2 There also does not appear to be
a racial or ethnic difference in prevalence or clinical presenta-
tion of morphea.
The major categories of morphea include plaque, linear,
and generalized. Plaque morphea is the most common type
and generally begins as a slightly raised, erythematous plaque
that expands peripherally (Fig. 3.10). As the lesion evolves, the
central region becomes sclerotic. Children with morphea typi-
cally present with the linear subtype. This diagnosis is of par-
ticular importance in this patient population as untreated
Figure 3.10:╇ Slightly raised, erythematous plaque in a patient with morphea.
58
10. Jacyk WK, Steenkamp KJ. Systemic lupus erythematosus in South
African blacks: a prospective study. Int J Dermatol 1996; 35:707–710.
11. Rabbani MA, Siddiqui BK, Tahir MH, Ahmad B, Shamim A, Shah
SM, et al. Systemic lupus erythematosus in Pakistan. Lupus 2004;
13:820–825.
12. Wang F, Wang CL, Tan CT, Manivasagar M. Systemic lupus erythema-
tosus in Malaysia: a study of 539 patients and comparison of preva-
lence and disease expression in different racial and gender groups.
Lupus 1997; 6:248–253.
13. Phan JC, Bush TM, Donald F, Ward M. Clinical and laboratory features
of patients of Vietnamese descent with systemic lupus erythematosus.
Lupus 1999; 8:521–524.
14. Arfaj Al, Khalil N. Clinical and immunological manifestations in 624
SLE patients in Saudi Arabia. Lupus 2009; 18:465–473.
morphea can result in physical disability and disfigurement
from its impact on subcutaneous tissues, muscle and bone. En
coup de sabre is linear morphea of the forehead and Parry–
Romberg syndrome consists of facial hemiatrophy.1 General-
ized morphea involves rapidly expanding plaques that
eventually coalesce to cover the entire trunk and can include
the extremities as well. Other variants include guttate morphea,
atrophoderma of Pasini and Pierini, deep morphea, nodular
or keloid morphea, and bullous morphea.2
The prognosis for morphea is generally very good as the
survival rate of morphea patients is comparable to that of the
general population.2 Although most lesions undergo sponta-
neous resolution within 3–5 years of disease onset, some cases
can persist for up to 10 years or recur (Figs. 3.11, 3.12).
Management strategy
There are a variety of treatment modalities currently available
for the treatment of morphea. Phototherapy appears to be
particularly promising. Psoralen can be given orally, applied
as a cream, or applied in a bath followed by UVA irradiation
with good responses. Low doses (20╯J/cm2) of UVA, UVA1 in
Figure 3.11:╇ Morphea over the face and neck in a patient with skin phototype VI.
Note the areas of hyper- and hypopigmented, sclerotic skin.

Figure 3.12:╇ Morphea. Note the hyperpigmented, indurated skin of the upper back
and subscapular region.
particular, have also been shown to significantly reduce dermal
thickness.3 Extracorporeal photochemotherapy has been used
successfully in severe, generalized morphea. Further investiga-
tions are needed to determine the efficacy of photodynamic
therapy.
Both topical and oral immunosuppressants have
been used with some success. Methotrexate (MTX) has
been used alone or in combination with corticosteroids.
Studies have shown that the combination of MTX plus corti-
costeroids may be particularly effective in the treatment of
pediatric patients.4,5 Oral corticosteroids alone may help
decrease inflammation associated with morphea; however,
once the tissue becomes sclerotic, corticosteroids are not
likely to be helpful.1 There is also only anecdotal evidence
for the use of topical or intralesional corticosteroids.
Morphea lesions have also responded well to topical tac-
rolimus but further large-scale controlled trials are needed.
Cyclosporin has not been shown to be effective in the treat-
ment of morphea.
Topical and oral vitamin A and D derivatives are also
under investigation. A small study by Elst6 showed the
benefit of using oral calcitriol in the treatment of linear
morphea in children. However, a double-blind, placebo-
controlled trial of 20 adult morphea patients showed no dif-
ference in efficacy between oral calcitriol and placebo.7 Further
studies are needed to determine efficacy in different patient
populations.
Physical therapy is particularly important for patients with
morphea to maintain mobility and strength. Surgical proce-
dures are typically reserved for severe disfigurement.
3â•… Collagen Vascular Diseasesâ•… •â•… Scleroderma
First-Line Therapies
UVA1 B
PUVA bath photochemotherapy C
PUVA photochemotherapy C
PUVA-cream photochemotherapy D
Broad band UVA C
Low-dose UVA1 phototherapy for the treatment of localized
scleroderma. Kerscher M, Volkenandt M, Gruss C, Reuther T,
von Kobyletzki G, Freitag M, et╯al. J Am Acad Dermatol 1998;
38:21–26.
Twenty patients with severe morphea were treated with 30
sessions of UVA1 phototherapy at 20╯J/cm2 per body half. In
18 of 20 patients, more than 80% of the sclerotic lesions disap-
peared or greatly improved within 3 months. The two non-
responders had subcutaneous morphea. Dermal thickness
decreased significantly after treatment (p < 0.001).
PUVA bath photochemotherapy for localized scleroderma.
Kerscher M, Meurer M, Sander C, Volkenandt M, Lehmann P,
Plewig G, et╯al. Arch Dermatol 1996; 132:1280–1282.
Seventeen patients with either disseminated or linear
morphea underwent 25–35 treatments of PUVA bath
photochemotherapy. The mean cumulative UVA dose was
41.5╯J/cm2. Clinical and ultrasound analysis revealed that scle-
rotic lesions either completely disappeared or were greatly
improved in 13 of the 17 patients. This reduction in skin thick-
ness was significant (p < 0.001).
Photochemotherapy for localized morphoea: effect on clini-
cal and molecular markers. Usmani N, Murphy A, Veale D,
Goulden V, Goodfield M. Clin Exp Dermatol 2008; 33:
698–704.
Open prospective study of 13 patients evaluating the effi-
cacy of PUVA for the treatment of morphea. Two patients
underwent PUVA bath and the remaining 11 patients were
treated with oral 8-MOP. The median number of PUVA
sessions was 26 and the median cumulative exposure was
135╯J/cm2. The skin score was significantly improved in 11 of
13 patients (p = 0.003).
PUVA-cream photochemotherapy for the treatment of local-
ized scleroderma. Grundmann-Kollmann M, Ochsendorf F,
Zollner TM, Spieth K, Sachsenberg-Studer E, Kaufmann R,
et╯al. J Am Acad Dermatol 2000; 43:675–678.
Four patients with localized scleroderma were treated with
psoralen cream directly followed by UVA irradiation. All
patients underwent 30 sessions with a mean cumulative UVA
dose of 89.5╯J/cm2. Clinical, ultrasonographic, and histologic
analysis confirmed that dermal thickness had either greatly
improved or returned to normal range after therapy in all
patients. However, further large-scale studies are needed to
confirm the results.
59
 Part 1 Medical Dermatology

Low-dose broad-band UVA in morphea using a new method calcineurin inhibitor, in the treatment of morphea. All patients
for evaluation. El-Mofty M, Zaher H, Bosselia M, Yousef R, were treated with tacrolimus on one morphea plaque and
Saad B. Photodermatol Photoimmunol Photomed 2000; petrolatum on another plaque twice daily for 12 weeks. There
16:43–49. was a significant difference between tacrolimus and petrola-
Twelve patients with morphea underwent 20 treatments of tum with regard to durometer score (p < 0.005) and the clini-
broad-band UVA at a dose of 20╯J/cm2 per session. Clinically cal feature score (p = 0.019). Larger controlled studies are
all patients experienced a softening of the lesions and there needed to confirm efficacy.
was a significant decrease in the mean concentration of col-
lagen per surface area in plaques exposed to UVA. Topical calcipotriene for morphea/linear scleroderma.
Cunningham BB, Landells ID, Langman C, Sailer DE, Paller
AS. J Am Acad Dermatol 1998; 39:211–215.
Second-Line Therapies
Open-label study of 12 patients evaluating the efficacy of
topical calcipotriene 0.005% ointment, a topical vitamin D
Methotrexate B preparation, in the treatment of localized scleroderma. All 12
Methotrexate + corticosteroids C patients experienced a significant reduction in erythema (p <
Topical tacrolimus B 0.01), telangiectasia (p < 0.01), dyspigmentation (p < 0.01),
Topical calcipotriene C and induration (p < 0.005). All patients tolerated the treat-
Topical tocoretinate C ment well and there were no adverse effects.
Topical imiquimod D
Topical tocoretinate improved hypertrophic scar, skin scle-
rosis in systemic sclerosis and morphea. Mizutani H, Yoshida
Effectiveness, side effects and period of remission after the T, Nouchi N, Hamanaka H, Shimizu M. J Dermatol 1999;
treatment with methotrexate in localized scleroderma and 26:11–17.
related sclerotic skin diseases: an inception cohort study. Twelve patients (4 patients each with morphea, SSc, and
Kroft EB, Creemers MC, van den Hoogen FH, Boezeman JB, hypertrophic scars) were treated with topical tocoretinate, an
de Jong EM. Br J Dermatol 2009; 160:1075–1082. alpha-tocopherol esterified to retinoic acid for 6 months to 3
The authors conducted an inception cohort study of 49 years. All patients improved with therapy by clinical and his-
patients with morphea treated with either MTX alone (43 tologic exam.
patients) or MTX plus prednisolone (6 patients). The median
dose for MTX was 15╯mg weekly and the median period of First case series on the use of imiquimod for morphea.
treatment was 46 weeks for MTX and 77 weeks for MTX plus Dytoc M, Ting PT, Man J, Sawyer D, Fiorillo L. Br J Dermatol
prednisolone. The majority of patients in the MTX only arm 2005; 153:815–820.
and all of the patients in the MTX plus prednisolone arm Review of 12 patients with morphea treated successfully
experienced clinical improvement. The majority of patients with topical 5% imiquimod, an inducer of interferon-gamma.
reached remission status after one treatment and those who All patients experienced a significant improvement in indura-
relapsed had received a lower cumulative dose of MTX. tion (p < 0.03). There was also some improvement in dyspig-
However, large prospective trials are needed to confirm the mentation and erythema.
results of this study.

Third-Line Therapies
Pulsed high-dose corticosteroids combined with low-dose
methotrexate in severe localized scleroderma. Kreuter A,
Gambichler T, Breuckmann F, Rotterdam S, Freitag M, Stuecker Penicillin E
M, et╯al. Arch Dermatol 2005; 141:847–852. D-Penicillamine D
Fifteen patients with severe localized scleroderma were Oral calcitriol B (Adults), D (Pediatrics)
treated with oral MTX 15╯mg weekly combined with pulsed Systemic retinoid B
intravenous methylprednisolone (1000╯mg for 3 days every Extracorporeal photochemotherapy E
month). The mean duration of treatment was 9.8 months. The
majority of patients experienced significant clinical improve-
ment and reduction in skin score (p < 0.001). Ultrasound and Effect of penicillin G on corium thickness in linear morphea
histologic exam confirmed these results. of childhood: An analysis using ultrasound technique.
Mohrenschlager M, Jung C, Ring J, Abeck D. Pediatr Dermatol
Efficacy of topical tacrolimus 0.1% in active plaque morphea: 1999; 16:314–316.
randomized, double-blind, emollient-controlled pilot Case report of a child with a 6-year history of linear morphea
study. Kroft EB, Groeneveld TJ, Seyger MM, de Jong EM. Am successfully treated with intravenous penicillin G (5╯MU)
J Clin Dermatol 2009; 10:181–187. three times per day for 10 days. Ultrasound confirmed the
Randomized, double-blind, controlled pilot study of 10 reduction in dermal thickness. Large, controlled studies are
patients evaluating the efficacy of topical 0.1% tacrolimus, a needed to confirm its efficacy.

60

D-Penicillamine in the treatment of localized scleroderma.
Falanga V, Medsger TA. Arch Dermatol 1990; 126:609–
612.
The authors reviewed the cases of 11 patients with severe
localized scleroderma treated with D-penicillamine. Seven of
the eleven patients (64%) had a favorable response to treat-
ment. The mean daily dose was 2.1–14╯mg/kg and the mean
duration of treatment was 21 months. However, the authors
suggest that doses between 2 and 5╯mg/kg should be adequate
for response. One patient developed nephrotic syndrome after
20 months of treatment, which resolved after discontinuing
the drug. Mild proteinuria occurred in 3 patients, which
resolved after discontinuing the drug and then restarting at a
lower dose.
Treatment of linear scleroderma with oral 1,25-
dihydroxyvitamin D3 (calcitriol) in seven children. Elst EF,
van Suijlekom-Smit LW, Oranje AP. Pediatr Dermatol 1999;
16:53–58.
Seven pediatric patients were treated with 1,25-
dihydroxyvitamin D3, calcitriol, for linear scleroderma. Five of
the seven patients obtained a good to excellent clinical
response. The authors suggest that calcitriol may be effective
for pediatric patients with linear scleroderma; however, a study
in adults (next paragraph) found calcitriol to be ineffective
for morphea.
Double-blind, placebo-controlled study of oral calcitriol
for the treatment of localized and systemic scleroderma.
Hulshof MM, Bouwes Bavinck JN, Bergman W, Masclee AA,
Heickendorff L, Breedveld FC, et╯al. J Am Acad Dermatol 2000;
43:1017–1023.
Double-blind, placebo-controlled trial of 20 morphea
patients treated with either oral calcitriol or placebo. There was
no significant difference in skin score between the two treat-
ment groups. The authors suggest that calcitriol is ineffective
for morphea.
Tigazon in the therapy of patients with circumscribed scle-
roderma. Samsonov VA, Gareginian SA. Vestn Dermatol
Venerol 1990; 11:17–20 [Russian].
This study examined the efficacy of tigazon, an oral retin-
oid, in 50 patients with morphea. The authors found tigazon
to be effective in all active stages in the course of the disease.
Extracorporeal photochemotherapy for generalized deep
morphea. Neustadter JH, Samarin F, Carlson KR, Girardi M.
Arch Dermatol 2009; 145:127–130.
Case report of a patient with severe, generalized, deep
morphea successfully treated with extracorporeal photoche-
motherapy (ECP). The patient’s disease progressed despite
multiple prior therapeutic interventions but noted improve-
ment within 1–2 months of starting ECP.
Special management & counseling considerations
Although morphea and systemic sclerosis (SSc) likely
share a similar pathogenesis, clinically the two can be clearly
3â•… Collagen Vascular Diseasesâ•… •â•… Scleroderma
differentiated from one another. Sclerosis in morphea is typi-
cally patchy or linear whereas in SSc it is usually symmetric.
There is an absence of Raynaud’s phenomenon and sclerodac-
tyly, and visceral organ involvement is very rare in morphea.
The differential diagnosis of a sclerodermoid lesion can
include scleredema, scleromyxedema, drug-induced sclerosis,
and chronic graft-versus-host disease. However, it is important
to perform a thorough assessment of the patient to rule out
other diagnoses and begin the appropriate treatment for
morphea early, particularly in children, to prevent disability
and disfigurement.
References
1. Rocken M, Ghoreschi K. Morphea and lichen sclerosus. In: Bolognia
JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd edn. New York: Mosby
Elsevier; 2009:1469–1483.
2. Chung L, Lin J, Furst DE, Fiorentino D. Systemic and localized sclero-
derma. Clin Dermatol 2006; 24:374–392.
3. Kerscher M, Volkenandt M, Gruss C. Low-dose UVA1 phototherapy for
the treatment of localized scleroderma. J Am Acad Dermatol 1998;
38:21–26.
4. Uziel Y, Feldman BM, Krafchik BR, Yeung RS, Laxer RM. Methotrexate
and cortico�steroid therapy for pediatric localized scleroderma. J Pediatr
2000; 136:91–95.
5. Weibel L, Sampaio MC, Visentin MT, Howell KJ, Woo P, Harper JI.
Evaluation of methotrexate and corticosteroids for the treatment of
localized scleroderma (morphoea) in children. Pediatr Dermatol
2006; 155:1013–1020.
6. Elst EF, van Suijlekom-Smit LW, Oranje AP. Treatment of linear sclero-
derma with oral 1,25-dihydroxyvitamin D3 (calcitriol) in seven chil-
dren. Pediatr Dermatol 1999; 16:53–58.
7. Hulshof MM, Bouwes Bavinck JN, Bergman W, Masclee AA,
Heickendorff L, Breedveld FC, et al. Double-blind, placebo-controlled
study of oral calcitriol for the treatment of localized and systemic
scleroderma. J Am Acad Dermatol 2000; 43:1017–1023.
Systemic sclerosis
Scleroderma, also known as systemic sclerosis (SSc), is an
autoimmune connective tissue disease of unknown etiology
characterized by thickened, sclerotic skin, vascular changes,
and internal organ damage. As with most other autoimmune
diseases, there is a 3:1 to 4:1 female-to-male predominance
and typical age of onset is between 30 and 50 years.1 Although
the exact pathogenesis of SSc is unknown, there are a few
important pathologic events that lead to the development of
SSc. These include dysfunction and injury to the microvascu-
lature, immune activation, and systemic tissue fibrosis.2 The
American College of Rheumatology has developed criteria for
the diagnosis of scleroderma (Table 3.2).3
Scleroderma can be separated into two distinct but related
entities, localized (morphea) and systemic (systemic sclerosis).
There are two major clinical subtypes of SSc, limited and
diffuse (Table 3.3). In limited disease, sclerosis occurs in the
distal upper extremities and face and patients can also develop
CREST syndrome (calcinosis, Raynaud’s phenomenon, esopha-
geal dysmotility, sclerodactyly, and telangiectasia), gastrointes-
tinal abnormalities, and pulmonary hypertension.2 Diffuse
disease starts distally then generalizes to the entire upper
61
 Part 1 Medical Dermatology

Table 3.2╇ American College of Rheumatology criteria for the

classification of systemic sclerosis (scleroderma)*

Major criterion Proximal symmetric cutaneous sclerosis

Minor criteria Sclerodactyly
Digital pitting scars or loss of substance from the
distal finger pad
Bilateral bibasilar pulmonary fibrosis

*The presence of the major criterion or two or more of the minor criteria is sufficient
for the diagnosis of SSc.
Masi AT. Preliminary criteria for the classification of systemic sclerosis (scleroderma).
Subcommittee for scleroderma criteria of the American Rheumatism Association
Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum 1980; 23:581–590.
Figure 3.13:╇ Scleroderma in a patient with Fitzpatrick skin type VI. Note the tight,
shiny appearance of the sclerotic facial skin particularly surrounding the oral cavity
and telangiectasias on the nose.
Table 3.3╇ Clinical features more commonly found in limited systemic
sclerosis versus diffuse systemic sclerosis*

Organ system Limited SSc Diffuse SSc

Pulmonary Pulmonary hypertension Interstitial lung disease

Cardiovascular Cardiomyopathy
Gastrointestinal Esophageal dysmotility
Small bowel disease
Renal Renal crisis
Cutaneous Sclerosis (Distal Sclerosis (Distal &
extremities, face) proximal extremities,
Raynaud’s phenomenon trunk, face)
Calcinosis cutis Arthralgia
Mat telangiectasia Proximal weakness
Immunologic Anti-nuclear antibody Anti-nuclear antibody Figure 3.14:╇ Telangiectasias over the nose and periorbital region in a scleroderma
Anti-centromere Anti-Scl 70 patient with Fitzpatrick skin type IV.
antibody (topoisomerase 1)
antibody
include diffuse hyperpigmentation, leukoderma (localized
*Although these clinical features occur more commonly in one clinical subtype over the
other, overlap can and does occur. areas of depigmentation with sparing of the perifollicular skin,
Adapted from Connolly, MK. Systemic sclerosis (scleroderma) and related disorders. ‘salt and pepper’ sign), matted telangiectasias (Fig. 3.14), and
In: Bolognia J, Jorizzo JL, Rapini RP, eds. Dermatology, 2nd edn. New York: Mosby capillary abnormalities in the proximal nailfold.2 SSc patients
Elsevier, 2009. can also develop calcinosis cutis and cutaneous ulcers, particu-
larly on fingertips or over interphalangeal joints.5
There are specific racial and ethnic differences in the clinical
extremities, trunk, face and lower extremities, and has an presentation and serologic profiles of SSc patients. African-
earlier onset of interstitial lung disease, cardiomyopathy, Americans are more likely to present at a younger age
renal crisis, and worse prognosis than limited SSc.4 All SSc and have anti-topoisomerase I (Scl-70) autoantibodies as
patients are usually positive for antinuclear antibody but compared to anti-centromere autoantibodies in Caucasian
anti-centromere autoantibodies are typically associated with patients.4,6 Therefore, diffuse disease is more common among
limited disease and anti-topoisomerase I (scl-70) with diffuse Black patients (70%) than Caucasian patients (30–40%).1,2,4,7
disease.2 There is also a higher frequency of anti-U1-RNP autoanti�
Patients typically present with arthralgia, stiffness, and bodies, which are associated with overlap syndromes with
upper extremity edema then as the skin becomes sclerotic, it other autoimmune diseases, among African-Americans.8
develops a tight, shiny appearance. Patients develop character- Blacks also have more severe disease than Caucasians with
istic expressionless faces, beak-like nose, and tightened perio- greater skin, lung, and renal involvement and higher mortality
ral skin with radial folds (Fig. 3.13). Cutaneous findings can rates.4 One study also showed that Blacks as well as Hispanics

62

were more likely to have diffuse skin involvement and dyspig-
mentation, digital ulcers, and early-onset pulmonary hyper-
tension (Blacks).8 Another study found that although Chinese
patients were more commonly positive for anti-topoisomerase
I autoantibodies, they also had less frequent digital ulcers,
renal crisis, and joint and gastrointestinal involvement but did
have increased prevalence of myositis.9 Choctaw Native Ameri-
cans in southeastern Oklahoma had the highest overall preva-
lence of SSc (66/100╯000) in any population, which the
authors attribute to a unique HLA haplotype.10 The majority
of these patients were positive for anti-topoisomerase I autoan-
tibodies, diffuse disease, and pulmonary fibrosis.
Management strategy
SSc remains a difficult disease entity to treat and requires a
multidisciplinary approach. Patients should be referred to the
appropriate specialist for treatment of lung, renal, gastrointes-
tinal tract, and heart involvement. SSc renal crisis and related
deaths are much less common due to the use of ACE inhibi-
tors.2 Gastrointestinal involvement is usually treated with
proton pump inhibitors and prokinetic agents. Therapy for
interstitial lung disease typically includes immunosuppressive
agents like cyclophosphamide and prostanoids for pulmonary
artery hypertension.2
Cutaneous manifestations of SSc are also a challenge
to treat but there are some effective therapies available. Patient
education and behavior modification are first-line therapies
for Raynaud’s phenomenon (RP). It is important to educate
patients on avoiding RP triggers and the use of tobacco prod-
ucts. SSc patients who smoke are three to four times more
likely than patients who never smoked to require treatment
for digital vascular complications.5 Studies have also shown
calcium channel blockers (e.g. nifedipine) and prostacyclin
analogues (e.g. iloprost) to be effective treatments for RP.
However, it is important to monitor patients for side effects as
calcium channel blockers can aggravate gastroesophageal
reflux disease by lowering systemic blood pressure, and
decreasing peripheral blood flow which can exacerbate the
problem.2 Other therapies for RP include sildenafil, losartan,
prozosin, and alprostadil. Initial studies with fluoxetine and
low-molecular-weight heparin show promising results but
further studies are needed. Invasive interventions such as nerve
blocks and sympathectomies are reserved for extremely refrac-
tory cases. Most topical agents have been ineffective.
Cutaneous ulcers are also difficult to treat successfully and
are a source of great morbidity for SSc patients. The initial
management approach to ulcers is similar to the treatments
for RP. Patient education and behavior modification are also
important in the prevention and treatment of digital ulcers.
Identify risk factors and sources of injury by taking detailed
occupational and recreational histories. Local wound care with
occlusive, hydrocolloid dressings is protective and provides a
better wound healing environment.5 Studies have shown that
bosentan (an oral endothelin receptor antagonist) prevented
occurrence of new digital ulcers but did not speed recovery of
existing lesions.11 Other agents like iloprost (prostacyclin
3â•… Collagen Vascular Diseasesâ•… •â•… Scleroderma
analogue) and sildenafil may also have some efficacy in the
treatment and prevention of digital ulcers. As with RP,
surgical intervention is a last resort for refractory cases;
however, skin grafts can often stimulate wound healing and
decrease pain.2
Currently, there is no completely effective medical therapy
for cutaneous sclerosis. Treatment modalities are typically
immunomodulatory or antifibrotic agents. Methotrexate and
cyclophosphamide have been used with mixed success.
However, further large randomized controlled trials are
needed. Methotrexate, in particular, can be helpful in SSc
patients with overlap syndromes.2 A study of 109 patients with
SSc suggests that there may be some benefit with myco�
phenolate mofetil.12 Other therapies include azathioprine,
cyclosporin, corticosteroids, and UVA. There is questionable
efficacy with minocycline and photopheresis as there are some
studies which provide contradictory results. In addition, a
study of low-dose versus high-dose D-penicillamine showed
no difference between the two treatments;13 however, a recent
retrospective analysis showed a significant improvement
in skin scores and suggested that these results warrant
further investigation of the drug.14 Emerging therapies include
hematopoietic stem cell transplantation, tolerance to human
type I collagen, antitumor necrosis factor, and targeted thera-
pies against transforming growth factor beta and connective
tissue growth factor.
Raynaud’s phenomenon and cutaneous ulcers
First-Line Therapies
Patient education/behavior modification
Nifedipine A
Iloprost B
Bosentan (cutaneous ulcers) A
Local Wound Care (cutaneous ulcers) C
Calcium-channel blockers for Raynaud’s phenomenon in
systemic sclerosis. Thompson AE, Shea B, Welch V, Fenlon D,
Pope JE. Arthritis Rheum 2001; 44:1841–1847.
Meta-analysis of 6 randomized controlled trials (109
patients) to determine the efficacy of calcium-channel blockers
(CCB) in the treatment of RP secondary to SSc. Five of the six
trials compared nifedipine to placebo, which found a signifi-
cant reduction in the frequency and severity of RP attacks in
patients treated with CCB compared to placebo.
Comparison of intravenous infusions of iloprost and oral
nifedipine in treatment of Raynaud’s phenomenon in
patients with systemic sclerosis: A double blind randomized
study. Rademaker M, Cooke ED, Almond NE, Beacham JA,
Smith RE, Mant TG, et╯al. BMJ 1989; 298:561–564.
Randomized, double-blind, placebo-controlled trial of 23
patients with RP secondary to SSc comparing the efficacies of
63
 Part 1 Medical Dermatology
IV iloprost, a prostacyclin analogue, versus oral nifedipine.
Both treatments showed a decrease in the frequency, duration,
and severity of RP attacks. In addition, the mean number
of digital ulcers was decreased from baseline to 16 weeks
for both iloprost and nifedipine. The authors concluded that
both drugs were effective in the treatment of RP secondary
to SSc.
Iloprost and cisaprost for Raynaud’s phenomenon in pro-
gressive systemic sclerosis. Pope J, Fenlon D, Thompson A,
Shea B, Furst D, Wells G, et╯al. Cochrane Database of System-
atic Reviews 2000(2): CD000953.
Meta-analysis of seven randomized, controlled trials (332
patients) to assess the efficacy and safety of prostaglandin
analogues in the treatment of Raynaud’s phenomenon (RP)
secondary to scleroderma. Intravenous iloprost was found to
be effective in both decreasing frequency and severity of RP
attacks and in the prevention or healing of digital ulcers. Oral
iloprost was less effective than intravenous and oral cisaprost
had minimal or no efficacy.
Digital ulcers in systemic sclerosis: prevention by treatment
with bosentan, an oral endothelin receptor antagonist. Korn
JH, Mayes M, Matucci-Cerinic M, Rainisio M, Pope J, Hachulla
E, et╯al. Arthritis Rheum 2004; 50:3985–3993.
Prospective, randomized, double-blind, placebo-controlled
trial (RAPIDS-1) of 122 patients with digital ulcers secondary
to SSc evaluating the efficacy of bosentan, an endothelin recep-
tor antagonist, in the prevention of new digital ulcers. Second-
ary measures involved healing of existing digital ulcers and
improvement in hand function. There was a 48% reduction in
the mean number of new ulcers in patients receiving bosentan
compared to placebo (p = 0.008). Patients in the bosentan
treatment group also showed significant improvement in the
overall score for hand function (p < 0.005). However, there
was no difference between treatment groups in the healing of
ulcers.
Treatment of scleroderma skin ulcers with a hydrocolloid
membrane. Milburn PB, Singer JZ, Milburn MA. J Am Acad
Dermatol 1989; 21(2 Pt1):200–204.
This is a paired-comparison trial of 7 patients with digital
ulcers secondary to SSc. The ulcers treated with hydrocolloid
membranes healed more rapidly and pain reduction was faster
than in control ulcers. One patient developed an infection
with Pseudomonas aeruginosa but responded rapidly to appro-
priate therapy and resumed treatment with hydrocolloid
membrane dressings after the infection resolved.
Second-Line Therapies
Sildenafil B
Losartan B Prazosin
Atorvastatin A Alprostadil
64
Sildenafil in the treatment of Raynaud’s phenomenon resist-
ant to vasodilatory therapy. Fries R, Shariat K, von Wilmowsky
H, Bohm M. Circulation 2005; 112:2980–2985.
Randomized, double-blind, controlled, crossover study of
18 patients assessing the efficacy of sildenafil, a phosphodi-
esterase V inhibitor, in the treatment of primary and secondary
RP. There was a statistically significant decrease in the fre-
quency and duration of attacks in the 16 patients with second-
ary RP. Laser Doppler anemometer also showed a significant
increase in mean capillary blood flow velocity after treatment
with sildenafil.
Oral sildenafil for the treatment of Raynaud’s phenomenon
and digital ulcers secondary to systemic sclerosis. Gore J,
Silver R. Ann Rheum Dis 2005; 64:1387.
Retrospective chart review of 10 patients with RP secondary
to SSc. Eight patients had digital ulcers refractory to initial
management. Of these, 6 patients experienced complete ulcer
healing after treatment with sildenafil.
Losartan therapy for Raynaud’s phenomenon and sclero-
derma: Chemical and biochemical findings in a 15-week,
randomized, parallel-group, controlled trial. Dziadzio M,
Denton CP, Smith R, Howell K, Blann A, Bowers E, et╯al.
Arthritis Rheum 1999; 42:2646–2655.
Randomized, parallel-group, controlled trial of 52 patients
with primary and secondary (SSc) RP evaluating the efficacy
of losartan, an angiotensin II receptor antagonist, versus nifed-
ipine. Overall, patients in the losartan treatment group had
significantly greater improvement than those treated with
nifedipine. However, when subgroup analysis was performed,
patients with RP secondary to SSc who were treated with losa-
rtan had clinically apparent improvement in frequency and
severity of attacks (45% and 36%, respectively) but these
results just failed to reach statistical significance (p = 0.09 and
p = 0.06, respectively).
Statins: Potentially useful therapy in systemic sclerosis-
related Raynaud’s phenomenon and digital ulcers. Abou-
Raya A, Abou-Raya S, Helmii M. J Rheumatol 2008; 35:
1801–1808.
Randomized, double-blind, placebo-controlled trial of 84
patients evaluating the efficacy of atorvastatin in the treatment
of RP and digital ulcers. Patients were randomized to two
groups and received either 40╯mg/day of atorvastatin or
placebo daily for 4 months. There was a significant decrease
in the total number of digital ulcers (p = 0.001) and the
number of new ulcers (p = 0.003) in the treatment group
compared to placebo group. Functional status was also
improved in the atorvastatin treatment arm.
Third-Line Therapies
A
C

Prazosin for Raynaud’s phenomenon in progressive sys-
temic sclerosis. Pope J, Fenlon D, Thompson A, Shea B, Furst
D, Wells G, et╯al. Cochrane Database of Systematic Reviews
1998(2): CD000956.
Meta-analysis of two randomized, controlled trials (40
patients) assessing the safety and efficacy of prazosin versus
placebo in the treatment of RP secondary to SSc. Prazosin was
found to be more effective than placebo; however, positive
responses to treatment were modest.
Comparison between iloprost and alprostadil in the treat-
ment of Raynaud’s phenomenon. Marasini B, Massarotti M,
Bottasso B, Coppola R, Papa ND, Maglione W, et╯al. Scand J
Rheumatol 2004; 33:253–256.
Eighteen patients with SSc were randomly assigned to treat-
ment with either intravenous iloprost or alprostadil. Symp-
toms from RP improved significantly with alprostadil from
baseline to the endpoint (p = 0.01); however, skin score and
digital ulcers improved more with iloprost.
Cutaneous sclerosis
First-Line Therapies
Methotrexate A Black CM, et╯al. Rheumatology 2007; 46:442–445.
Cyclophosphamide and Prednisone B Retrospective analysis of 109 patients treated with myco-
Comparison of methotrexate with placebo in the treatment
of systemic sclerosis: a 24-week randomized double-blind
trial, followed by a 24-week observational trial. Van den
Hoogen FH, Boerbooms AM, Swaak AJ, Rasker JJ, van Lier HJ,
van de Putte LB. Br J Rheumatol 1996; 35:364–372.
Randomized, double-blind, placebo-controlled trial of 29
patients evaluating the efficacy of methotrexate (MTX) in SSc.
Patients received 15–25╯mg MTX or placebo weekly for 24
weeks followed by an observational trial for 24 weeks. Those
treated with MTX had a significant improvement in total skin
score (p = 0.04), grip strength (p = 0.02), and visual analogue
scale (p = 0.02). However, the following study suggests that
MTX may not be as effective in SSc.
A randomized, controlled trial of methotrexate versus
placebo in early diffuse scleroderma. Pope JE, Bellamy N,
Seibold JR, Baron M, Ellman M, Carette S, et╯al. Arthritis
Rheum 2001; 44:1351–1358.
Randomized, double-blind, placebo-controlled trial of 71
patients with early diffuse SSc to determine the efficacy of
MTX. Thirty-five patients received 7.5–50╯mg of MTX weekly
versus 36 patients receiving placebo. When analyzing skin
score and other outcomes, there was a trend in favor of
MTX over placebo; however, results were not statistically
significant.
The efficacy of oral cyclophosphamide plus prednisone
in early diffuse systemic sclerosis. Calguneri M, Apras S,
3â•… Collagen Vascular Diseasesâ•… •â•… Scleroderma
Ozbalkan Z, Ertenli I, Kiraz S, Ozturk MA, et╯al. Clin Rheuma-
tol 2003; 22:289–294.
Twenty-seven patients with early diffuse SSc were treated
with oral cyclophosphamide (1–2╯mg/kg/day) plus oral pred-
nisolone (40╯mg/every other day) between 1995 and 1998
and followed prospectively for 2 years. The efficacy and safety
of cyclophosphamide were compared with results obtained
from 22 patients with early SSc treated with oral D-penicillamine
between 1992 and 1995. The cyclophosphamide treatment
group showed a significant improvement in skin (p < 0.05),
maximal oral opening (p = 0.001), flexion index (p = 0.007),
predicted forced vital capacity (p = 0.002), and carbon mon-
oxide diffusing capacity (p = 0.001).
Second-Line Therapies
Mycophenolate mofetil C
Azathioprine C
Prednisolone B
UVA C
Mycophenolate mofetil in diffuse cutaneous systemic scle-
rosis: a retrospective analysis. Nihtyanova SI, Brough GM,
phenolate mofetil (MMF) and 63 control subjects treated with
other immunosuppressive drugs to evaluate the efficacy of
MMF. There was a significantly lower frequency of sympto-
matic pulmonary fibrosis and better 5-year survival in the
MMF-treated cohort. Although there was a significant reduc-
tion in skin score from baseline to 1 year (p < 0.01), there was
no significant difference in skin score between the two treat-
ment groups. Further prospective trials are needed.
Twelve-month azathioprine as maintenance therapy in early
diffuse systemic sclerosis patients treated for one year
with low-dose cyclophosphamide pulse therapy. Paone C,
Chiarolanza I, Cuomo G, Ruocco L, Vettori S, Menegozzo M,
et╯al. Clin Exp Rheumatol 2007; 25:613–616.
Prospective study of 13 patients with early diffuse SSc who
completed a year of treatment with low-dose intravenous pulse
cyclophosphamide (CYC) then began treatment with azathio-
prine for an additional year. Outcome measures were skin
score, disability index, spirometry results, which improved
after CYC treatment. These improvements were maintained by
azathioprine treatment and no outcome measure decreased.
The authors recognize the need for further studies evaluating
the efficacy of azathioprine.
Treatment of early diffuse cutaneous systemic sclerosis
patients in Japan by low-dose corticosteroids for skin
involvement. Takehara K. Clin Exp Rheumatol 2004; 22(3
Suppl 33):S87–S89.
Twenty-three patients with diffuse cutaneous SSc were
treated with low-dose oral prednisolone with the following
65
 Part 1 Medical Dermatology
conditions: early onset, edematous changes, and rapid pro-
gression. At the 3-year endpoint, there was a significant reduc-
tion in skin score from baseline (p < 0.001). Two patients did
not respond to treatment. Further large-scale, prospective
studies are needed.
Different doses of broad-band UVA in the treatment of
morphea and systemic sclerosis: a clinic-pathologic study.
El-Mofty M, Mostafa W, El-Darouty M, Bosseila M, Nada H,
Yousef R, et╯al. Photodermatol Photoimmunol Photomed
2004; 20:148–156.
Fifteen patients with SSc received 20 sessions of UVA (320–
400╯nm) each with total UVA doses ranging from 100 to
400╯J/cm2. There was a satisfactory clinical response in these
patients and the authors noted no significant difference in
outcomes between low and high UVA doses.
Third-Line Therapies
Photopheresis A 750╯mg/day. The authors recognize the limitations of this
Cyclosporin C study but emphasize the need for re-evaluating the utility of
D-penicillamine A
Minocycline C
A randomized, double-blind, placebo-controlled trial of
photopheresis in systemic sclerosis. Knobler RM, French LE,
Kim Y, Bisaccia E, Graninger W, Nahavandi H, et╯al. J Am Acad
Dermatol 2006; 54:793–799.
Randomized, double-blind, placebo-controlled trial of 64
patients to evaluate the efficacy of photopheresis in the treat-
ment of SSc. There was a significant improvement in skin
scores from baseline to 12 months (p = 0.008) in the active
photopheresis treatment group but not in those receiving the
sham photopheresis. However, there was no significant differ-
ence between the two treatment groups, which the authors
attribute to the small sample size of the study arms. Joint
involvement was also improved in the active treatment group.
The Food and Drug Administration has not approved photo-
pheresis for the treatment of scleroderma. The following study
suggests that photopheresis may not be effective in the treat-
ment of SSc.
Treatment of patients with systemic sclerosis with extracor-
poreal photochemotherapy (photopheresis). Enomoto DN,
Mekkes JR, Bossuyt PM, Yong SL, Out TA, Hoekzema R, et╯al.
J Am Acad Dermatol 1999; 41:915–922.
Clinical study of 19 patients randomized into two groups
and receiving either photopheresis or no treatment for one
year. Although the average skin score in the treatment group
improved by 5.4% and the skin score in the control group
decreased by 4.5%, these results were not statistically
significant.
Cyclosporin in systemic sclerosis: results of a forty-
eight-week open safety study in ten patients. Clements PJ,
66
Lachenbruch PA, Sterz M, Danovitch G, Hawkins R, Ippoliti
A, et╯al. Arthritis Rheum 1993; 36:75–83.
Open study of 10 patients with SSc evaluating the safety
and efficacy of cyclosporin A. There was a significant improve-
ment in skin score (p < 0.001); however, cyclosporin A was
ineffective in pulmonary and cardiac disease. The authors also
note that side effects were frequent but transient. However, the
most serious side effect was nephrotoxicity, which is concern-
ing given that SSc patients are already prone to renal dysfunc-
tion pretreatment.
A retrospective randomly selected cohort study of D-
penicillamine treatment in rapidly progressive diffuse cuta-
neous systemic sclerosis of recent onset. Derk CT, Huaman
G, Jimenez SA. Br J Dermatol 2008; 158:1063–1068.
Retrospective analysis of a cohort of 84 patients with diffuse
SSc treated with D-penicillamine to determine its efficacy in
skin and internal organ disease. There was a significant reduc-
tion in the skin score (p < 0.01) as well as improvement in
cardiac, pulmonary, and renal function at a median dose of
this drug and need for further studies.
High-dose versus low-dose D-penicillamine in early diffuse
systemic sclerosis: analysis of a two-year, double-blind,
randomized, controlled clinical trial. Clements PJ, Furst DE,
Wong WK, Mayes M, White B, Wigley F, et╯al. Arthritis Rheum
1999; 42:1194–1203.
Sixty-eight patients were randomized into two groups and
treated with either high dose D-penicillamine (D-Pen) (750–
1000╯mg daily) or low-dose D-Pen (125╯mg every other day).
Both the low-dose and high-dose treatment groups had signifi-
cant improvements in skin scores from baseline to the end
point (p < 0.001 and p < 0.012, respectively); however, there
was no difference between the two treatment groups. The
majority of adverse events (proteinuria, rash, myasthenia
gravis, thrombocytopenia, flu-like illness and stomatitis)
occurred in the high-dose treatment group. The authors
acknowledge that the study does not prove that low-dose
D-Pen is ineffective but suggest that there is no advantage in
using doses higher than 125╯mg every other day.
Minocycline in early diffuse scleroderma. Le CH, Morales A,
Trentham DE. Lancet 1998; 352:1655–1656.
Open trial of 11 patients with early diffuse SSc to evaluate
the efficacy of minocycline. Patients were given 100╯mg for 1
month then increased to 200╯mg for the remaining 11 months.
Four patients had complete resolution of skin disease at the
end of the treatment period. However, the following study
suggests that minocycline may not be effective in the treatment
of SSc.
Minocycline is not effective in systemic sclerosis: results of
an open-label multicenter trial. Mayes MD, O’Donnell D,
Rothfield NF, Csuka ME. Arthritis Rheum 2004; 50:553–557.
Open-label trial of 31 patients found no significant
difference in skin score or treatment effect between the

Table 3.4╇ Specific autoantibodies and the associated overlap
syndromes seen in SSc
Autoantibody Overlap syndrome
Anti-U1-RNP Mixed connective tissue disease
Anti-PM-Scl Polymyositis-SSc overlap
Denton CP, Black CM. Scleroderma (systemic sclerosis). In: Wolff K, Goldsmith LA,
Katz SI, Gilchrest BA, Paller AS, Leffell DJ, eds. Fitzpatrick’s Dermatology in General
Medicine. 7th edn. New York: McGraw Hill Medical; 2008:1553–1562.
minocycline-treated patients and those previously treated in a
D-penicillamine trial.
Special management & counseling considerations
Up to 20% of cases of SSc may present with clinical symptoms
that overlap with other autoimmune diseases (Table 3.4).15
These overlap syndromes have been associated with anti-U1-
RNP autoantibodies for SSc with systemic lupus erythemato-
sus or arthritis and anti-PM-Scl for SSc with polymyositis.15
Studies have shown a higher frequency of anti-U1-RNP and
antifibrillarin antibodies in African-Americans.8 Therefore, it is
important to keep this in mind during the initial diagnostic
work-up of the patient. A complete serologic panel of all
autoantibodies should be ordered and a detailed medical
history, particularly with screening questions regarding multi-
ple autoimmune disorders, should be obtained.
References
1. Mayes MD. Classification and epidemiology of scleroderma. Semin
Cutan Med Surg 1998; 17:22–26.
2. Connolly MK. Systemic sclerosis (scleroderma) and related disorders.
In: Bolognia J, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd edn. New
York: Mosby Elsevier; 2009:585–596.
3â•… Collagen Vascular Diseasesâ•… •â•… Scleroderma
3. Masi AT. Preliminary criteria for the classification of systemic sclerosis
(scleroderma). Subcommittee for scleroderma criteria of the American
Rheumatism Association Diagnostic and Therapeutic Criteria
Committee. Arthritis Rheum 1980; 23:581–590.
4. McKinley-Grant L, Warnick M, Singh S. Cutaneous manifestations of
systemic diseases. In: Taylor SC, Kelly AP, eds. Dermatology for skin of
color. New York: McGraw Hill Medical; 2009:481–510.
5. Ramien M, Brassard A. The challenge of scleroderma ulcers. J Cutan
Med Surg 2009; 13(Supp 1):S42–S48.
6. Pudifin DJ, Dinnematin H, Duursma J. Antinuclear antibodies in sys-
temic sclerosis: clinical and ethnic associations. S Afr Med J 1991;
80:438–440.
7. Reveille JD. Ethnicity and race and systemic sclerosis: how it affects
suspectibility, severity, antibody genetics, and clinical manifestations.
Curr Rheum Rep 2003; 5:160–167.
8. Reveille JD, Fischbach M, McNearney T, Friedman AW, Aguilar MB,
Lisse J, et al. Systemic sclerosis in 3 US ethnic groups: a comparison
of clinical, sociodemographic, serologic, and immunogenetic determi-
nants. Semin Arthritis Rheum 2001; 30:332–346.
9. Low AH, Johnson SR, Lee P. Ethnic influence on disease manifestations
and autoantibodies in Chinese-descent patients with systemic sclero-
sis. J Rheumatol 2009; 36:787–793.
10. Arnett FC, Howard RF, Tan F, Moulds JM, Bias WB, Durban E, et al.
Increased prevalence of systemic sclerosis in a native american tribe in
Oklahoma: association with an Amerindian HLA haplotype. Arthritis
Rheum 1996; 39:1362–1370.
11. Korn JH, Mayes M, Matucci-Cerinic M, Rainisio M, Pope J, Hachulla
E, et al. Digital ulcers in systemic sclerosis: prevention by treatment
with bosentan, an oral endothelin receptor antagonist. Arthritis
Rheum 2004; 50:3985–3993.
12. Nihtyanova SI, Brough GM, Black CM, Denton CP, Mycophenolate
mofetil in diffuse cutaneous systemic sclerosis: a retrospective analysis.
Rheumatology 2007; 46:442–445.
13. Clements PJ, Furst DE, Wong WK, Mayes M, White B, Wigley F, et al.
High-dose versus low-dose D-penicillamine in early diffuse systemic
sclerosis: analysis of a two-year, double-blind, randomized, controlled
clinical trial. Arthritis Rheum 1999; 42:1194–1203.
14. Derk CT, Huaman G, Jimenez SA. A retrospective randomly selected
cohort study of D-penicillamine treatment in rapidly progressive
diffuse cutaneous systemic sclerosis of recent onset. Br J Dermatol
2008; 158:1063–1068.
15. Denton CP, Black CM. Scleroderma (systemic sclerosis). In: Wolff K,
Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, eds.
Fitzpatrick’s Dermatology in General Medicine. 7th edn. New York:
McGraw Hill Medical; 2008:1553–1562.
67
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Part 1 Medical Dermatology
Eczematous Disorders
Sonia Badreshia-Bansal
Allergic contact dermatitis . . . . . . . . . . . . . . . . .
Atopic dermatitis . . . . . . . . . . . . . . . . . . . . . .
Dyshidrotic eczema/Pomphylox . . . . . . . . . . . . . .
Irritant contact dermatitis . . . . . . . . . . . . . . . . .
Lichen simplex chronicus . . . . . . . . . . . . . . . . .
Nummular dermatitis . . . . . . . . . . . . . . . . . . . .
Allergic contact
dermatitis
Specific diagnosis
Allergic contact dermatitis (ACD) is a type IV, delayed or cell-
mediated reaction that occurs when the skin contacts an exter-
nal allergen. Several agents commonly produce allergic contact
dermatitis including nickel (the leading cause of ACD in the
world), dyes, preservatives, rubber, topical medications, for-
maldehyde, fragrances, and permanent press chemicals (Fig.
4.1). Photoallergy occurs when a substance becomes an aller-
gen following exposure to ultraviolet radiation (UVR), which
occur with sunscreens, pesticides, and certain fragrances such
as musk amberette.
ACD is characterized by pruritic papules and vesicles that
are well demarcated and localized to the site of contact with
the external allergen. Poison ivy, the classic example of acute
ACD in North America, is characterized by papules or vesicles
in a linear array that develop at the site where the plant has
been in direct contact with the skin. In ethnic patients, ery-
thematous reactions are noted less often than in Caucasians.
The most common presentation is dry, scaly skin with hyper-
pigmentation, hyperkeratosis, fissuring, or lichenification.
Overall, the clinical presentation of ACD is varied and can
include hyperpigmentation, hypopigmentation, acneiform,
eczematous or urticarial eruptions. Hands are the most
common location, particularly when related to occupation
(Fig. 4.2). Airborne allergic contact dermatitis can occur when
©2011 Elsevier Ltd, Inc, BV
4â•…
69 chemicals in the air produce a dermatitis typically on the
eyelids, head and neck.
74
Patients with ACD require a much more detailed history
81 compared to those with most other dermatologic disorders.
84 Questions regarding occupation, hobbies, outdoor exposure,
and atopic background should be considered. Potassium
87
hydroxide (KOH) preparation and/or fungal culture to exclude
90 tinea are often indicated for dermatitis involving the hands
and feet.
Allergen identification with allergen avoidance and the use
of barrier agents are the mainstay of therapy. Cool compresses
with saline or aluminum acetate solution are helpful for acute
vesicular dermatitis (e.g. poison ivy). Some individuals with
widespread vesicular dermatitis may obtain relief from luke-
warm oatmeal baths. Sedating oral antihistamines may dimin-
ish pruritus and corticosteroids reduce inflammation, but have
also been reported to cause ACD. Calcineurin inhibitors are
steroid-sparing agents that can be used safely on sensitive areas
such as the eyelids and face. Emollients and moisturizing
creams are used to break the itch-scratch cycle and to repair
and maintain skin barrier integrity.
Patch testing remains the gold standard for diagnosis of
ACD (Table 4.1). Differences in patch test results between
different racial groups have been identified, possibly due
to genetic differences or variations in allergen exposure.
For instance, nickel sulfate and thimerosal were more
common sensitizers in white subjects while nickel sulfate and
p-phenylenediamine (PPD) were more common among
blacks.1 A study found that PPD and imidazolidinyl urea were
more common allergens in black men versus white men.2
In India, when comparing people of different skin photo-
types living within the same community, there was a lower
incidence of positive patch test results among patients with
racial origins from the Indian subcontinent compared with
white Europeans, likely due to differing exposure to contact
allergens rather than variability in susceptibility.3 In India,
footwear dermatitis is the most common suspected diagnosis,
followed by ACD to medications, cosmetics and plants.4
Footwear dermatitis is most often caused by leather processing
chemicals, metal buckles, black dyes, adhesives, plastic, rubber,
and polishing agents. In Indian men, potassium dichromate,
followed by sesquiterpene lactones (SQL) mix and PPD are
69
 Part 1 Medical Dermatology

Figure 4.1:╇ A child with allergic contact dermatitis due to nickel found in metal
Figure 4.2:╇ Allergic contact dermatitis secondary to latex glove allergy. (Courtesy
button on blue jeans. (Courtesy of Katie Headley MD; Department of Dermatology,
of Jim Marks MD; Department of Dermatology, Penn State Milton S. Hershey
Penn State Milton S. Hershey Medical Center.)
Medical Center.)

Table 4.1╇ Differences in patch test results by race1–16

Race Patch test Allergens

Caucasian NACD Nickel,* thimerosal,* formaldehyde, glutaraldehyde, formaldehyde-releasing preservatives, lanolin, epoxy resin,
thioureas, balsam of Peru
African-American NACD Nickel,* PPD,* cobalt chloride, thioureas, PTBP formaldehyde resin, imidazolidinyl urea
Asian
â•… India ESS Potassium dichromate,* nickel,* SQL,* PPD,*
Cobalt, fragrance, formaldehyde, colophony, neomycin sulfate, mercapto mix
â•… India ISS Nickel,* potassium dichromate, neomycin, mercaptobenzothiazole, nitrofurazone, colophony, fragrance mix,
cobalt chloride, parthenium, fragrance mix, preservatives, PPD, cetrimide, tertiary butyl hydroquinone
â•… India ESS Potassium dichromate,* nickel sulfate,* SQL mix, PPD, cobalt , fragrance mix, formaldehyde, colophony,
neomycin sulfate, mercapto mix
â•… India ISS Parthenium,* potassium dichromate, xanthium, nickel sulphate, chrysanthemum, mercaptobenzothiazole, garlic
â•… India ISS Vegetables,* nickel,* potassium dichromate
â•… Thailand ESS Potassium dichromate,* nickel,* fragrance mix, cobalt chloride
â•… Singapore ESS Nickel,*clioquinol-mix, balsam of Peru, fragrance mix, PPD
â•… Hong Kong ESS Nickel,* fragrance mix, cobalt chloride, PPD, balsam of Peru
â•… China ESS Nickel, fragrance mix, PPD, carba mix, thimerosal
Hispanic unknown Carba mix, nickel sulphate, thiuram mix, PTBP formaldehyde resin, PPD, neomycin
Israeli ESS Nickel,* fragrance mix,* potassium dichromate,* balsam of Peru, MCI/MI, cobalt
Turkish ESS Nickel,* potassium dichromate,* palladium chloride, cobalt chloride, thiuram mix
Key:
NACD = North American Contact Dermatitis Group
ESS = European Standard Series
ISS = Indian Standard Series
PPD = para-phenylenediamine
MCI/MI = Methylchloroisothiazolinone/methylthiazolinone
PTBP = para-tertiary butylphenol
SQL = sesqueterpine lactone mix
* = most common allergens

70
 4â•… Eczematous Disordersâ•… •â•… Allergic contact dermatitis
the most common sensitizers as compared to nickel and SQL
in women.4,5 However, SQL mix is not an adequate screen for
parthenium sensitivity and patch testing with extracts of the
plant should be done.5 Occupational profiles most commonly
included household workers, masons, students, and factory
workers.
In Thailand, the most frequent allergen was potassium
dichromate, followed by nickel sulfate, fragrance mix, and
cobalt chloride.6 There are likely geographic cultural differ-
ences in the prevalence of the allergens in Asian-Pacific
populations.
In Singapore, nickel allergy was significantly more common
in the younger age group while medication allergy (clioquinol-
mix), balsam of Peru, fragrance-mix, and PPD were slightly
more prevalent in older Singaporean patients.6 Overall, there
was a higher prevalence of ACD in older patients, especially
with involvement of the extremities. In another Singaporean
study, SQL allergy was observed more commonly in younger
females compared to classical compositae dermatitis.7 The sen-
sitization rate was comparable to other studies, although
clinical relevance was only 11%. The most common clinical
presentations were dermatitis of the hands, face, and general-
ized involvement. The most common concomitant allergens
were nickel, balsam of Peru, and fragrance mix.
A study from Hong Kong, predominately of patients of
Chinese origin, found that nickel was the most common sen-
sitizer in females while dichromate sensitivity was more
common in males. Significant risk factors for nickel sensitivity
include the female gender, age <40 years, truncal and upper
limb involvement, absence of lower limb involvement, and a
positive atopy history.8 In China, the most common ACD was
from metals, fragrance, cosmetics, and rubber materials.9
In a Hispanic population, a correlation was observed
between paratertiary butylphenol and involvement of the feet;
PPD and generalized dermatitis; and potassium dichromate
and occupational exposure.10 The most common allergens
identified were carba mix, nickel sulphate, thiuram mix,
paratertiary butylphenol formaldehyde resin, paraphenylene-
diamine, and neomycin sulphate.
In Israel, age and sex differences were noted in ACD.11 Posi-
tive reactions to nickel sulfate were more common among
women, especially those in the younger age group (<40 years).
Positive reactions to balsam of Peru were more common
among men, especially those in the older age group
(>40 years).
In a Turkish study, occupational contact dermatitis was
diagnosed primarily among construction workers and house
painters who showed relevant sensitizations to potassium
dichromate, cobalt chloride, thiuram mix and carba mix.12
First-Line Therapies
Emollients B
Topical or systemic corticosteroids B after the introduction of topical corticosteroids. In addition, oral
Topical calcineurin inhibitors B corticosteroids, when used for severe ACD, for prolonged periods
Chelators D is often associated with severe and sometimes irreversible sys-
ACD is best treated with elimination of the offending agent
along with topical emollients or immunomodulating thera-
pies such as corticosteroids or calcineurin inhibitors. There is
anecdotal evidence that chelators which act by chelating nickel
may improve ACD.
Role of topical emollients and moisturizers in the treatment
of dry skin barrier disorders. Lodén M. Am J Clin Dermatol
2003; 4(11):771–788.
A ceramide-dominant lipid mixture improved atopic der-
matitis and decreased transepidermal water loss (TEWL) in an
open-label study in children. In double-blind studies, moistur-
izers with urea have been shown to reduce TEWL in atopic and
ichthyotic patients. Urea also makes normal and atopic skin
less susceptible to irritation by sodium lauryl sulfate. Treat-
ments improving the barrier function may reduce the likeli-
hood of further aggravation of the disease. In order to have
optimum effect, it is conceivable that moisturizers should be
tailored with respect to the epidermal abnormality.
Prevention of sodium lauryl sulfate irritant contact derma-
titis by Pro-Q aerosol foam skin protectant. Patterson SE,
Williams JV, Marks JG Jr. J Am Acad Dermatol 1999;
40(5 Pt 1):783–785.
Twenty volunteers with a history of sensitivity to poison ivy
completed a randomized, controlled, double-blind study to
investigate the efficacy of Pro-Q to prevent irritant contact
dermatitis from sodium lauryl sulfate (SLS) and allergic
contact dermatitis from urushiol, the resinous sap of poison
ivy and poison oak. Pro-Q is a skin protectant product com-
posed of dimethicone and glycerin with various inactive ingre-
dients to comprise an aerosolized foam vehicle. Pro-Q was
significantly effective in reducing the irritation from sodium
lauryl sulfate but did not prevent the allergic reaction to urush-
iol. The mechanism of action of the product is unknown, but
is thought to be formation of a “membrane” that physically
blocks or partially blocks skin penetration by the contactant.
Efficacy of topical corticosteroids in nickel-induced contact
allergy. Hachem JP, De Paepe K, Vanpée E, Bogaerts M,
Kaufman L, Rogiers V, et╯al. Clin Exp Dermatol 2002;
27(1):47–50.
A topical corticosteroid and its vehicle were applied twice
daily on two different sites with ACD, beginning on day 4 of
the ACD. TEWL was significantly decreased on the topical-
corticosteroid-treated sites in the early phase of ACD (day 4)
while clinical efficacy showed significant improvement on days
7 and 8. The vehicle was found to improve skin hydration only
on day 8.
It is important to keep in mind that corticosteroids have side
effects. Topical corticosteroids may cause skin atrophy, striae,
and even worsening of ACD. A high index of suspicion is
needed when chronic dermatitis fails to clear or is exacerbated
temic side effects such as osteoporosis, growth retardation,
71
 Part 1 Medical Dermatology

myopathy, posterior subcapsular cataracts, open angle glau-
coma, neuropsychiatric symptoms, epidural lipomatosis, hyper-
glycemia, weight gain, Cushingoid facies, hypocalcemia,
hypokalemic alkalosis, hypertension and atherosclerosis, predis-
position to infections and reactivation of tuberculosis, and
hypothalamo-pituitary-axis suppression.
A prospective randomized clinical trial of 0.1% tacrolimus
ointment in a model of chronic allergic contact dermatitis.
Belsito D, Wilson DC, Warshaw E, Fowler J, Ehrlich A,
Anderson B. J Am Acad Dermatol. 2006 Jul; 55(1):40–46.
A randomized, double-blind, vehicle-controlled, right/left
arm comparative study was conducted on 98 patients (White
66%, Black 28%, Asian 2%, Hispanic 2%). Tacrolimus 0.1%
ointment proved to be significantly more effective than vehicle
control in ameliorating symptoms of ACD in patients
who were exposed to nickel daily. A rapid onset of action
was observed with statistically significant improvements as
early as day 8 with sustained improvement despite allergen
exposure. This treatment may allow patients who cannot
avoid exposure to allergens to control their ACD and remain
on the job.
The inhibitory effects of topical chelating agents and anti-
oxidants on nickel-induced hypersensitivity reactions.
Memon AA, Molokhia MM, Friedmann PS. J Am Acad Derma-
tol 1994; 30(4):560–565.
This study investigated the effects of “barrier” ointments
containing either chelating agents (clioquinol or
ethylenediaminetetra-acetic acid [EDTA]) or antioxidants
(ascorbic acid or alpha-tocopherol) and 1% hydrocortisone on
nickel-induced hypersensitivity reactions. Clioquinol (3%)
completely abolished the allergic reaction in all 29 subjects
tested. EDTA (15%), ascorbic acid (20%), and alpha-tocopherol
(10%) were less effective, and 1% hydrocortisone had no
significant effect.
Second-Line Therapies
completing at least a 6 month follow up, 3 patients required
oral corticosteroid in the initial 2–4 weeks.
Parthenium hysterophorus is the most common cause of air-
borne contact dermatitis in India. Several studies are conducted
using this model.
Azathioprine versus betamethasone for the treatment
of parthenium dermatitis: A randomized controlled
study. Verma KK, Mahesh R, Srivastava P, Ramam M,
Mukhopadhyaya AK. Indian J Dermatol Venereol Leprol. 2008
Sep–Oct; 74(5):453–457.
This Indian study was a double blind, randomized, con�
trolled study in 55 patients with parthenium dermatitis
allocated to treatment with the steroid sparing agent, azathio-
prine 100╯mg daily or betamethasone 2╯mg daily for 6
months. Initial use of oral antihistamines once daily and
clobetasol propionate cream were allowed. 95% of patients in
the azathioprine group and 100% of patients in the betame-
thasone group had an excellent clinical response. However,
betamethasone-induced side effects like acne, striae, Cushin-
goid features, and weight gain were statistically significant.
Azathioprine in weekly pulse doses has been found to be effec-
tive without any serious adverse effects in the treatment of
parthenium dermatitis. The cost of therapy with this regimen
is reduced by 60%.
Narrowband ultraviolet B radiation suppresses contact
hypersensitivity. Shintani Y, Yasuda Y, Kobayashi K, Kernebeck
K, Gross N, Aragane Y, et╯al. Photodermatol Photoimmunol
Photomed 2008; 24(1):32–37.
Narrowband UVB therapy generally induces a relatively
long remission period for ACD. The shaved abdomens of
C3H/HeN mice were irradiated with broadband or narrow
band UVB. Narrowband UVB exposure dose dependently
suppressed contact hypersensitivity. Significant suppression
was observed at doses between 1000 and 3000╯mJ/cm2
(p < 0.05). The suppressive effect achieved with 1000╯mJ/cm2
narrowband UVB was very similar to the effect achieved with
100 mJ/cm2 broadband UVB.

Immunosuppressives Disulfiram and low nickel diet in the management of hand

â•… methotrexate
â•… azathioprine
Phototherapy
Diet
Widespread ACD may be treated with systemic medications
such as immunosuppressives, phototherapy, or dietary modi-
fication and chelation therapy.
Treatment of parthenium dermatitis with methotrexate.
Sharma VK, Bhat R, Sethuraman G, Manchanda Y. Contact
Derm 2007; 57(2):118–119.
16 Indian patients unresponsive to topical treatment were
treated with oral methotrexate (15╯mg/week). Of 7 patients
D eczema: a clinical study. Sharma AD. Indian J Dermatol
D Venereol Leprol 2006; 72(2):113–118.
D According to this single – blinded, placebo controlled study,
D unless the dietary intake of nickel is minimized and the exist-
ing amount of nickel in the body of the sensitized individual
is depleted, long-term remission of ACD is unlikely. This
Indian study evaluated the efficacy of oral disulfiram, a nickel-
chelating agent and low nickel diet in reducing the clinical
symptoms and preventing frequent relapse of chronic, vesicu-
lar hand eczema in 21 nickel-sensitive individuals. The study
group was given disulfuram for 4 weeks along with a low
nickel diet initiated 2 weeks prior to disulfuram. Hand eczema
healed completely in 90.9% treated with disulfiram and low
nickel diet. Mild relapse was noted in 5 patients between
2 and 12 weeks of follow-up. 3 patients had mild elevations
in liver function tests.

72
 4â•… Eczematous Disordersâ•… •â•… Allergic contact dermatitis
Figure 4.3:╇ The modern self adhesive bindi adorned on the forehead in South
Asian women.
The Indian diet is rich in plant foods, which is a major source
of nickel in comparison to the western diet, which is rich in
animal food. Based on the food habits of the Indian commu-
nitiy, low nickel foods included milk, rice, paneer, fish, meat,
and eggs. Partial restriction was given for green gram (mung
daal), potato, and green leafy vegetables. Subjects were allowed
mustard oil, butter (and ghee), sugar, salt, chillies, and garam
masala spice.
After oral intake, disulfuram is slowly and incompletely
absorbed from the gut and metabolized slowly in the liver into
diethyldithiocarbamate. The metabolite causes chelation of
nickel from the body tissue and gets excreted from the body
mostly through urine and in small amount in bile and sweat.
Although low nickel diet and short course of oral disulfiram
therapy can be considered an alternative option for the control
of chronic hand eczema in nickel-sensitive individuals, care
must be taken with disulfiram as it can cause hepatic toxicity
with long term use.
Commonly encountered pitfalls
Exposure to several allergens is common in various ethnic
communities and knowledge of these allergens is important
for diagnosis of ACD. Examples include dermatitis from herbal
medications used by some ethnic populations,17 sodium meta-
bisulfite in bleaching creams,18 henna paints (pseudotattoo-
ing),19 bindi (adorned on the forehead of Indian women for
religious and social purposes) (Fig. 4.3),20 and kumkum (also
called sindhoor which are colored cos�metics applied to the
center of the forehead for religious purposes in India.21 Pig-
mented allergic contact dermatitis to “kumkum” has been
reported that was associated with Brilliant Lake Red R and
Sudan I allergy.21 Bindi dermatitis can occur from sandal-
wood20 or a nickel-containing bindi.22
Figure 4.4:╇ Persistent contact dermatitis secondary to paraphenylendiamine (PPD)
in black henna tattoo. (Courtesy of Andrea L. Zaenglein MD; Department of
Dermatology, Penn State Milton S. Hershey Medical Center.)
Today, temporary henna tattoos drawn on the skin are fash-
ionable and have become increasingly popular. Pure henna
has a very low allergic potential. However, allergic reactions
following henna tattoos has increased worldwide (Fig. 4.4). In
most cases, allergic reactions are caused by the mixtures which
contain not only natural henna but also many chemical color-
ing agents such as diaminotoluenes and diaminobenzenes.20
Henna dermatitis occurs from henna contaminated with PPD
or p-toluenediamine, common sensitizers found in hair dye
preparations. The long duration of skin contact, the high con-
centrations of sensitizing materials, and the lack of a neutral-
izing agent dramatically increase the risk of skin sensitization.
Because of the worldwide popularity of skin painting, future
cases of sensitization to p-phenylenediamine and diaminoben-
zenes or diaminotoluenes are expected.
Special management & counseling considerations
Allergic contact dermatitis is a condition that may be affected
by differences in genetics or environmental exposures which
ultimately may account for variations in the manner that white
and black patients respond to specific allergens. It has been
suggested that differences in sensitization rates, especially for
PPD, may reflect variations in allergen exposure among racial
groups or interindividual variations in the N-acetylation (N-
acetyltransferase 1 [NAT1] and 2 [NAT2]) capacities of human
skin for PPD. Black patients readily acquire ACD from
contactants such as PPD, nickel, chromates, and mercaptoben-
zothiazole. This dermatitis is often complicated by hyper�
pigmentation and lichenification unless treated early and
vigorously with systemic corticosteroids.
73
 Part 1 Medical Dermatology
Use of complementary medicine to treat ACD is high.23 A
UK study showed that many users were of Indo-Asian descent.
Its use was higher in the Indo-Asian group where 62% had
tried some form of complementary medicine. Most patients
who used complementary medicine were happy to recom-
mend it to other patients, even though only 30% reported an
improvement in their skin condition. The most frequently
used treatments were herbal medicine, traditional Indian
medicine, and aromatherapy.
References
1. Deleo VA, Taylor SC, Belsito DV, Fowler JF Jr, Fransway AF, Maibach
HI, et al. The effect of race and ethnicity on patch test results. J Am
Acad Dermatol 2002; 46(2 Suppl Understanding):S107–S112.
2. Dickel H, Taylor JS, Evey P, Merk HF. Comparison of patch test results
with a standard series among white and black racial groups. Am J
Contact Dermat 2001; 12(2):77–82.
3. Fairhurst DA, Shah M. Comparison of patch test results among white
Europeans and patients from the Indian subcontinent living within
the same community. J Eur Acad Dermatol Venereol 2008; 22(10):
1227–1231.
4. Bajaj AK, Saraswat A, Mukhija G. Patch testing experience with 1000
patients. Indian J Dermatol Venereol Leprol 2007; 73(5):313–318.
5. Sharma VK, Chakrabarti A. Common contact sensitizers in Chandigarh,
India. A study of 200 patients with the European standard series.
Contact Derm 1998; 38(3):127–131.
6. Boonchai W, Iamtharachai P, Sunthonpalin P. Prevalence of allergic
contact dermatitis in Thailand. Dermatitis 2008; 19(3):142–145.
7. Tan E, Leow YH, Ng SK, Goh CL. A study of the sensitization rate
to sesquiterpene lactone mix in Singapore. Contact Derm 1999;
41(2):80–83.
8. Lam WS, Chan LY, Ho SC, Chong LY, So WH, Wong TW. A retrospective
study of 2585 patients patch tested with the European standard series
in Hong Kong (1995–99). Int J Dermatol 2008; 47(2):128–133.
9. Li LF, Guo J, Wang J. Environmental contact factors in eczema and the
results of patch testing Chinese patients with a modified European
standard series of allergens. Contact Derm 2004; 51(1):22–25.
Atopic dermatitis
Atopic dermatitis (AD) is a chronic, pruritic skin disease of
unknown etiology that is often associated with allergic rhinitis,
bronchial asthma, and food allergies. It is a disease with
diverse manifestations presenting as an acute, subacute or
chronic disorder that ranges in severity from a mild localized
skin irritation to widespread, severe dermatitis. The clinical
presentation of AD may vary from the typical appearance
of red, scaly plaques to thickened, lichenified, brown or
gray plaques frequently seen in patients of darker skin
tones. Additionally, xerosis, papular lesions, vesicles, fissures,
infraorbital folds, and palmar hyperlinearity may be present
(Figs. 4.5 & 4.6).
A strong familial inheritance pattern is frequently observed
in AD. In addition to the adult form, an infantile form is well
recognized with 60% of patients experiencing their first out-
break by 1 year of age and 90% by 5 years of age. Asthma typi-
cally affects about a third of children with AD.1 African-American
children have a high risk for aerosensitization particularly to
74
10. Collazo MH, Figueroa LD, Sánchez JL. Prevalence of contact allergens
in a Hispanic population. P R Health Sci J 2008; 27(4):333–336.
11. Freireich-Astman M, David M, Trattner A. Standard patch test results
in patients with contact dermatitis in Israel: age and sex differences.
Contact Derm 2007; 56(2):103–107.
12. Akasya-Hillenbrand E, Ozkaya-Bayazit E. Patch test results in 542
patients with suspected contact dermatitis in Turkey. Contact Derm
2002; 46(1):17–23.
13. Tomar J, Jain VK, Aggarwal K, Dayal S, Gupta S. Contact allergies to
cosmetics: testing with 52 cosmetic ingredients and personal products.
J Dermatol 2005; 32(12):951–955.
14. Singhal V, Reddy BS. Common contact sensitizers in Delhi. J Dermatol
2000; 27(7):440–445.
15. Suman M, Reddy BS. Pattern of contact sensitivity in Indian patients
with hand eczema. J Dermatol 2003; 30(9):649–654.
16. Lazarov A. European Standard Series patch test results from a contact
dermatitis clinic in Israel during the 7-year period from 1998 to 2004.
Contact Derm 2006; 55(2):73–76.
17. Li LF, Wang J. Patch testing in allergic contact dermatitis caused
by topical Chinese herbal medicine. Contact Derm 2002; 47(3):
166–168.
18. Huang PY, Chu CY. Allergic contact dermatitis due to sodium metabi-
sulfite in a bleaching cream. Contact Derm 2007; 56(2):123–124.
19. Le Coz CJ, Lefebvre C, Keller F, Grosshans E. Allergic contact dermatitis
caused by skin painting (pseudotattooing) with black henna, a mixture
of henna and p-phenylenediamine and its derivatives. Arch Dermatol
2000; 136(12):1515–1517.
20. Kozuka I, Goh CL, Doi T, Yioshikawa K. Sudan I as a cause of pig-
mented contact dermatitis in “kumkum” (an Indian cosmetic). Ann
Acad Med Singapore 1988; 17(4):492–494.
21. Tewary M, Ahmed I. Bindi dermatitis to ‘chandan’ bindi. Contact Derm
2006; 55(6):372–374.
22. Baxter KF, Wilkinson SM. Contact dermatitis from a nickel-containing
bindi. Contact Derm 2002 Jul; 47(1 by topical Chinese herbal
medicine):55.
23. Nicolaou N, Johnston GA. The use of complementary medicine by
patients referred to a contact dermatitis clinic. Contact Derm 2004;
51(1):30–33.
outdoor allergens.2 Several other triggers have been identified
including excessive bathing, swimming, hand-washing, lip
licking, and extreme temperature changes (dry, cold winter
weather and/or hot, humid weather). In adults, other exacer-
bating factors may include stress, contact with irritant chemi-
cals, cosmetics, or even cigarette smoke, which can impair the
skin barrier (Table 4.2).
Black and/or Asian children in England and the United
States, may have an increased prevalence of atopic dermatitis.3
The numbers of per capita visits for atopic dermatitis among
blacks and Asian/Pacific Islanders were 2-fold and 6-fold
higher, respectively, than for whites.4 Thus, blacks and Asian/
Pacific Islanders are much more likely to visit physicians for
atopic dermatitis than are whites and they may benefit from
education and early intervention efforts concerning the
disease.
The pattern of atopic dermatitis in Singapore is similar to
that reported in the Western literature, except for a lower preva-
lence (2%) and a significant proportion of adult-onset atopic
dermatitis.5 In a Singaporean study, AD was accompanied
by ichthyosis vulgaris which was present in 8% of patients
and pityriasis alba in 3% of patients (Fig. 4.7).6 Common

Figure 4.5:╇ Papular atopic dermatitis. (Courtesy of Jeff Miller MD; Department of
Dermatology, Penn State Milton S. Hershey Medical Center.)
Figure 4.6:╇ Fissures in a patient with classic location of atopic dermatitis.
(Courtesy of Jeff Miller MD; Department of Dermatology, Penn State Milton S.
Hershey Medical Center.)
aggravating factors included exercise, heat and sweating, grass
intolerance, thick clothing and stress. In Singaporean school
children, atopic dermatitis was more common among Chinese
(21.6%) and Malays (19.8%) compared with Indians (16%)
and other races (14%). The relatively high prevalence of atopic
4â•… Eczematous Disordersâ•… •â•… Atopic dermatitis
Table 4.2╇ Pathogenesis of atopic dermatitis
Stressors
(pH, stress, humidity, dry skin) TEWL
Scratching/Excoriation Stratum Corneum bacterial/viral entry
Barrier Disruption
cytokine cascade
Inflammation (T cell and mast cell activation)
Epidermal Hyperplasia
dermatitis in Singapore is similar to that observed in devel-
oped countries, suggesting that environmental factors may be
important in determining the expression of the disease.6 In a
randomized survey of the Indian population, the incidence of
atopy was estimated to be 28.96%.7
Major and minor criteria exist as guidelines for arriving at
a diagnosis of AD, and surveys from Western countries have
shown that these features, in particular the minor features,
may vary with ethnicity and genetic background. In a Nigerian
study, many conventional minor features were found, but
some occurred less frequently than in other countries, which
may be attributed to ethnic variations.8 The most commonly
observed minor features in descending order included xerosis,
papular lichenoid lesions, infraorbital folds, palmar hyperlin-
earity, and elevated peripheral blood eosinophils, particularly
in those with severe AD (Fig. 4.8).
Treatment is dependent upon several factors including the
patient’s age, severity of the condition, and subjective symp-
toms. During asymptomatic periods, the most important treat-
ment is active moisturization of the skin with emollients to
preserve the integrity and continuity of the stratum corneum,
thus inhibiting entry of allergens and irritants and preventing
flares. Basic skin care, includes the use of mild or soap free
cleansers, bathing for short periods of time with lukewarm
water, application of petrolatum-based or other lipid or cera-
mide containing moisturizers while still damp and frequent
and consistent moisturization. Antihistamines can control
itching and subsequent scratching, especially during sleep. In
mild atopic dermatitis, low potency corticosteroids, especially
for children and in sensitive body areas (face, axilla, and geni-
tals), are used. Steroids should be applied within minutes of
bathing for increased penetration and emollients should be
used as well to seal in moisture. Calcineurin inhibitors also
have a role as steroid sparing agents which are approved for
use in patients older than 2 years of age. The mechanism of
action includes down-regulation of antigen-specific T-cell
activities and associated proinflammatory cytokine produc-
tion. Theoretical long-term side effects may include increased
risk for malignancy which has not been fully elucidated. In
moderate AD, treatment with high potency topical corticoster-
oids should be considered. In addition, phototherapy may
75
 Part 1 Medical Dermatology
A B
C D
Figure 4.7:╇ (A–D) African american teenager with classic atopic dermatitis in flexural folds and hypopigmented patches characteristic of pityriasis alba. Note improvement
after a series of NB-UVB treatments in Figure D.
prove useful. Coexisting bacterial infection is treated with sys-
temic macrolides, quinolones, or cephalosporins. For severe
AD, treatment with systemic immunosuppressive therapy such
as short-course corticosteroids, cyclosporine, azathioprine,
mycophenolate mofetil, or methotrexate may be used.
First-Line Therapies for Mild to Moderate
Atopic Dermatitis
Emollients
Topical corticosteroids
Topical immunomodulators
76
For asymptomatic or mild AD, placebo controlled trials
have demonstrated that moisturizing creams and emollients
used adjunctively alongside topical corticosteroids or steroid-
sparing agents enhance stratum corneum hydration and
improve skin inflammation.
Ceramide-dominant barrier repair lipids alleviate child-
hood atopic dermatitis: changes in barrier function provide
a sensitive indicator of disease activity. Chamlin SL, Kao J,
Frieden IJ, Sheu MY, Fowler AJ, Fluhr JW, et╯al. J Am Acad
B Dermatol 2002; 47(2):198–208.
A The efficacy of a ceramide-dominant, physiologic lipid-
B based emollient was assessed when substituted for currently
used moisturizers, in 24 children (3 white subjects, 16 Asian

Figure 4.8:╇ African american infant with atopic dermatitis of the face. Note the
Dennie-Morgan lines and central facial pallor. (Courtesy of Dermatology, Elsevier,
2nd ed., 2008.)
Americans, 4 African Americans, and 1 Hispanic American)
with recalcitrant AD while topical steroids, oral antihistamines
and/or antibiotics were permitted. Improvement was noted
between weeks 6 and 20 in TEWL, SC integrity and hydration.
This uncontrolled trial suggests that use of ceramide rich mois-
turizers benefits both dry skin and the inflammatory compo-
nent in this predominantly stratum corneum lipids and
ceramide deficient condition.
Of note, petrolatum-based moisturizers have an immediate
barrier-repairing effect in delipidized stratum corneum. In
double-blind studies, moisturizers with urea have been shown
to reduce TEWL in atopic and ichthyotic patients. Urea also
makes normal and atopic skin less susceptible to irritation from
sodium lauryl sulfate. Treatments improving the barrier func-
tion may reduce the likelihood of further aggravation of the
disease. In order to have optimum effect it is conceivable that
moisturizers should be tailored with respect to the epidermal
abnormality.
Topical corticosteroids for atopic eczema: clinical and cost
effectiveness of once-daily vs more frequent use. Green C,
Colquitt JL, Kirby J, Davidson P. Br J Dermatol 2005;
152(1):130–141.
This systematic review assessed the clinical and cost effec-
tiveness of once-daily vs more frequent use of same-potency
topical corticosteroids in atopic eczema. Clinical effectiveness
of once-daily versus more frequent use of topical corticoster-
oids was found to be similar with respect to outcomes. Adverse
events were comparable in most cases, and less frequent
4â•… Eczematous Disordersâ•… •â•… Atopic dermatitis
dosing proved to be more cost effective. Clinicians may con-
sider once-daily use of topical corticosteroids in patients with
atopic eczema.
In addition, topical corticosteroids with occlusion or wet wrap
dressings, which employ the use of a moist physical barrier
incorporating a topical corticosteroid, can prove to be very useful
during severe acute flares.
Use of pimecrolimus cream 1% in the treatment of atopic
dermatitis in infants and children: the effects of ethnic
origin and baseline disease severity on treatment outcome.
Eichenfield LF, Lucky AW, Langley RG, Lynde C, Kaufmann R,
Todd G, et╯al. Int J Dermatol 2005; 44(1):70–75.
589 patients with AD, ages 3 months to 17 years, were
studied on a 6-week, retrospective, randomized, multicenter
study. 321 Caucasians and 268 non-Caucasian patients (41.8%
Black, 11.6% Oriental Asian, 46.6% Other, mainly Hispanic)
with mild, moderate, or severe disease were treated with pime-
crolimus cream 1% or vehicle twice daily. Significantly higher
efficacy was achieved in the pimecrolimus treated group irre-
spective of ethnic origin.
This study suggests there are no differences in ethnic skin
biology, including differences in drug response or tolerability in
patients of different ethnic origins.
A multicenter trial of the efficacy and safety of 0.03% tac-
rolimus ointment for atopic dermatitis in Korea. Won CH,
Seo PG, Park YM, Yang JM, Lee KH, Sung KJ, et╯al. J Derma-
tolog Treat 2004; 15(1):30–34.
An open, non-comparative, multicenter study of 180
patients, ages 2–57 years, were treated with 0.03% tacrolimus
ointment twice daily with 4-week follow-up. Moderate
improvement was observed by 4 weeks with a marked decrease
of pruritus, and mild or moderate improvement observed after
the treatment period. The most common adverse events associ-
ated with tacrolimus treatment were transient skin burning
sensation and application site pruritus. Tacrolimus ointment
was found to be effective and safe in both Korean children and
adults with moderate to severe atopic dermatitis.
Comparison of the efficacy and safety of 0.1% tacrolimus
ointment with topical corticosteroids in adult patients with
atopic dermatitis: review of randomised, double-blind clini-
cal studies conducted in Japan. Nakagawa H. Clin Drug
Investig 2006; 26(5):235–246.
Two phase III randomized, controlled clinical trials were
conducted in Japanese adult patients with atopic dermatitis to
compare the efficacy and safety of topical 0.1% tacrolimus
versus topical corticosteroid ointments. In the first study in
moderate to severe atopic dermatitis, similar improvement was
observed after 3 weeks in patients treated with either topical
0.1% tacrolimus or the mid-potency topical corticosteroid
0.12% betamethasone valerate for lesions on the trunk and
extremities. The same was true when topical 0.1% tacrolimus
was compared with the corticosteroid, 0.1% alclometasone
dipropionate for lesions on the head and neck. In a long-term
open-label study involving 568 patients, at least a moderate
global improvement in symptoms was observed in 85%
77
 Part 1 Medical Dermatology

of patients at 6 weeks, increasing to 91% at both 26 weeks Langerhans cells and mast cells in the dermis, while NB-UVB
and 52 weeks, maintained throughout the 2-year duration of causes apoptosis, reduction of skin surface bacteria, suppres-
the study. sion of superantigen production from Staphylococcus aureus,
and modulation of antimicrobial peptide profiles.
Second-Line Therapies for Moderate–Severe NB-UVB is the treatment of choice due to its advantages
Atopic Dermatitis including less heat load (which may be an important factor in
patient comfort, especially for ethnic skin) and shorter duration
Phototherapy of phototherapy. As NB-UVB and UVA1 are relatively new
PUVA A phototherapeutic modalities, no definite data on long-term risks
UVB or UVA A such as photocarcinogenesis are available. However, it has been
UVA1 A shown that BB-UVB is more carcinogenic than BB-UVA in
NB-UVB B experimental induction of squamous cell carcinoma. The impact
of UVB radiation can be inferred from point mutations in p53
Systemic corticosteroids B
found in human nonmelanoma skin cancer. In contrast, much
Systemic antibiotics A of the carcinogenic action of UVA appears to be mediated
Topical antibiotics A through reactive oxygen species and increased risk of malignant
Systemic antihistamines A melanoma.
Systemic antifungal E
Treatment of persistent severe atopic dermatitis in 113
Japanese patients with oral psoralen photo-chemotherapy.
Moderate to severe AD usually involves more widespread
Uetsu N, Horio T. J Dermatol 2003; 30(6):450–457.
disease. There are several well controlled clinical trials that
This is the first report of oral PUVA therapy in a large series
demonstrate the efficacy of phototherapy and systemic corti-
of Japanese patients with AD. 113 hospitalized Japanese
costeroids. Adjunctive use of antibiotics and antihistamines,
patients with persistent severe AD were treated three times a
when clinically indicated, may be very useful. Various bio�
week with PUVA in addition to their current regimen. 8 weeks
logic agents are currently under clinical investigation for the
after PUVA therapy, AD severity score decreased by 80%, and
treatment of atopic dermatitis.
the cumulative dose of UVA was 115.3╯J/cm2. After discharge,
maintenance therapy with UVB phototherapy and/or conven-
Phototherapy in the management of atopic dermatitis: a
tional treatment of AD kept the patients in remission.
systematic review. Meduri NB, Vandergriff T, Rasmussen H,
Jacobe H. Photodermatol Photoimmunol Photomed 2007; Rebound phenomenon to systemic corticosteroid in atopic
23(4):106–112. dermatitis. Forte WC, Sumita JM, Rodrigues AG, Liuson D,
Ultraviolet (UV) phototherapy is an efficacious treatment Tanaka E. Allergol Immunopathol (Madrid) 2005; 33(6):
for AD, but its use is limited by a lack of guidelines for optimal 307–311.
choice of modality and dosing. This systematic review of two Three Spanish children with atopic dermatitis took oral
trials in adult patients revealed superiority of combined UVA corticosteroids for a period of approximately 15 days during
and UVB in the management of chronic AD. Two additional emergency care. All 3 pediatric patients experienced a rebound
studies demonstrated that narrow-band UVB (NB-UVB) is or worsening of disease after or during the removal of oral
more effective than either broad-band UVA (BB-UVA) or UVA1 corticosteroid. The corticosteroids reduced the inflammatory
for managing chronic AD. Phototherapy with medium-dose process, but may have exacerbated IgE mediated hypersensitiv-
(50 J/cm2) UVA1, if available, should be used to control acute ity, especially during drug tapering or discontinuation, accen-
flares of AD while UVB modalities, specifically narrow-band tuating the Th2 pattern typical in the acute phase of atopic
UVB, should be used for the management of chronic AD. dermatitis.
Future studies should focus on standardized dosing regimens,
cumulative exposures, UV wavelengths, and patient evaluation Clinical features associated with nasal Staphylococcus aureus
methods, in order to establish comprehensive therapeutic guide- colonization in Chinese children with moderate-to-severe
lines and cross comparisons. atopic dermatitis. Hon KL, Lam MC, Leung TF, Kam WY,
Li MC, Ip M, et╯al. Ann Acad Med Singapore 2005; 34(10):
Medium-dose ultraviolet (UV) A1 vs. narrowband UVB 602–605.
phototherapy in atopic eczema: a randomized crossover Nasal and body swabs were obtained in 55 Chinese chil-
study. Gambichler T, Othlinghaus N, Tomi NS, Holland-Letz dren with moderate-to-severe AD. Moderate-to-heavy growth
T, Boms S, Skrygan M. Br J Dermatol. 2009 Mar; 160(3):652– of S. aureus was present in 22% of the nasal swabs, and 58%
658. in one or more flexural swabs. Only a third of the most severe
This randomized, double-blind, controlled, crossover study lesions grew S. aureus, suggesting acute exacerbations with
of 84 adult atopic dermatitis patients comparing UVA1 and oozing are due to inflammation alone, without infection. All
NB-UVB mono-phototherapy showed comparably significant specimens of methicillin-sensitive S. aureus were sensitive to
improvement over 6 weeks. It is hypothesized that UVA may cloxacillin while methicillin-resistant S. aureus was isolated in
induce T-lymphocyte apoptosis and reduce the number of 1 patient. The anterior nares are an important harbor for S.

78

aureus and significant nasal S. aureus colonization was clini-
cally associated with more extensive lesions and the presence
of oozing or crusting.
Cultures should be considered in children with chronically
extensive atopic dermatitis, but also during acute flares with
worsening of either the lesions or the extent of involvement.
The nares should also be treated to prevent future outbreaks if
cultures are positive.
Skin colonization by Staphylococcus aureus in patients with
eczema and atopic dermatitis and relevant combined topical
therapy: a double-blind multicentre randomized controlled
trial. Gong JQ, Lin L, Lin T, Hao F, Zeng FQ, Bi ZG. Br J Der-
matol 2006; 155(4):680–687.
In this Chinese study, the therapeutic effect of mupirocin
plus hydrocortisone butyrate was compared to hydrocortisone
butyrate and the vehicle ointment of mupirocin. An antibiotic-
corticosteroid combination and corticosteroid alone both
produced a good therapeutic effect in eczema and in AD, and
both reduced colonization by S. aureus. Administration of the
antibiotic–corticosteroid combination was most beneficial in
patients with moderate to severe AD during the early stages of
disease. It was unnecessary to use antibiotics at later stages of
disease or in patients with mild eczema or AD.
Long-term treatment with cetirizine of infants with atopic
dermatitis: a multi-country, double-blind, randomized,
placebo-controlled trial (the ETAC trial) over 18 months.
Diepgen TL; Early Treatment of the Atopic Child Study Group.
Pediatr Allergy Immunol 2002; 13(4):278–286.
Long-term use of cetirizine in this prospective, multicoun-
try, double-blind, randomized, placebo-controlled trial, Early
Treatment of the Atopic Child (ETAC) was studied in 817
infants under 12 months old. Patients who had AD and history
of atopic disease in a parent or sibling were treated for 18
months with either cetirizine (0.25 mg/kg) or placebo twice
daily. All concomitant medications for the treatment of AD
were allowed and were made aware to the investigator, except
the concomitant use of H1-antihistamines was discouraged.
The use of cetirizine might help to reduce the duration
and the amount of moderate-to-potent topical corticosteroids
used in the treatment of infants and children with AD.
However, further studies designed with the primary end-point
of AD are clearly indicated to confirm the benefits of the use
of H1-antihistamines in the management of AD.
Minimum effective dosage in the treatment of chronic
atopic dermatitis with itraconazole. Takechi M. J Int Med Res
2005; 33(3):273–283.
Fungi including Malassezia furfur and Candida albicans may
be involved in the development of atopic dermatitis. Three
oral administration regimens with itraconazole were studied:
single-phase treatment including regimen 1: 100╯mg/day for 1
week with a 3-week rest, repeating over 12 weeks, and regimen
2: 200╯mg/week for 4 weeks, repeating over 12 weeks; and
dual-phase treatment regimen 3: 100╯mg/day for 1 week
(introduction phase) then 200╯mg/week (maintenance phase)
4â•… Eczematous Disordersâ•… •â•… Atopic dermatitis
for 11 weeks. All three regimens reduced AD symptoms, with
regimen 3 being the most effective and efficient therapy as
evaluated by overall efficacy and low drop-out rate.
Some preliminary data suggested that oral itraconazole treat-
ment in AD patients reduced the need for topical corticoster-
oids, provided clinical improvement particularly in head and
neck AD, reduced the cutaneous and intestinal fungal coloniza-
tion that may trigger AD, reduced the percentage of positive
Malassezia cultures and demonstrated a decrease in C. albicans
and Malassezia RAST values. Furthermore, beside its antifun-
gal action, itraconazole in part relieves pruritus and inflamma-
tion. Oral itraconazole or fluconazole treatment can alleviate
AD severity in selected patients. Further research is warranted
to identify whether the load in skin surface fungal agents,
the fungal RAST values and specific prick testing should be
assessed in order to optimize the antifungal management in
AD patients.
Third-Line Therapies
Immunosuppressives
methotrexate
azathioprine
mycophenolate mofetil
cyclosporine
Interferon gamma
IVIG
Lasers
Elimination diets
Dust mite reduction and immunotherapy
Probiotics
Leukotriene antagonists
Hydroxychloroquine
Leflunomide
Complementary and Alternative Medicine (see Chapter 18)
Commonly encountered pitfalls
Black children with atopic dermatitis have six times the risk of
having severe atopic dermatitis than white children.9,10 General
practitioners and dermatologists should note that erythema
can be an inadequate and misleading indicator of AD severity
in black children. Difficulties of assessment of erythema
due to underlying skin pigmentation may result in misdi�
agnosis or underdiagnosis of severe cases of infantile atopic
dermatitis (Fig. 4.9). Misdiagnosis can also occur when atopic
dermatitis presents as erythroderma.
Kaposi’s varicelliform eruption (eczema herpeticum) is a
distinct cutaneous eruption caused by herpes simplex virus
and certain other viruses that infect patients with pre-existing
79
 Part 1 Medical Dermatology
Figure 4.9:╇ Atopic dermatitis on the face of an infant. Involvement of the cheeks
is characteristic of the infantile pattern of atopic dermatitis. (Courtesy of
Dermatology, Elsevier, 2nd ed., 2008.)
dermatosis, such as AD (Fig. 4.10). Kaposi’s varicelliform erup-
tion often presents with distinct punched-out ulcerations and
crusting. This potentially serious condition should be rapidly
diagnosed and treated early to prevent complications.
In HIV prone regions, HIV-infected adults commonly
develop a condition that closely resembles atopic dermatitis.
AD and other atopic-like disorders have also been described
as common manifestations of pediatric HIV infection.
Special management & counseling considerations
There have been some advancements in genetic linkage studies
and AD. In the first genome-wide linkage study of AD in an
Asian population, a novel locus on chromosomes 15q21 and
1q24 has been found to be linked to AD.11 However, its exact
role remains uncertain.
Dietary manipulation by parents of children with atopic
dermatitis occurs commonly. In one study, 75% of patients
(59% white, 35% Indo-Asian, 3% Afro-Caribbean and 3%
mixed race) tried some form of dietary elimination; the most
common foods were dairy products, eggs, and cow’s milk.12
Additionally, 41% tried some form of dietary supplementa-
tion, the most common being evening primrose oil, of whom
13% felt the primrose oil was useful. The proportion of
patients who reported that unsupervised dietary manipulation
was beneficial was 39%. Studies from Europe also revealed a
similar trend with frequent use of complementary and alterna-
tive medicine for AD.13 Common motivating factors were dis-
satisfaction with conventional treatment and frustration with
the chronic nature of the condition. Vitamin supplementation
and herbal creams were the most common alternative treat-
ments used (see Chapter 18). Therapy utilizing medicinal
Chinese herbs is an empirical modality of treatment which
may provide good immediate results. However, long-term
studies have shown reversible or irreversible hepatotoxicity.
In a study of the knowledge, attitudes and practices of
Southeast Asian dermatologists in the management of atopic
dermatitis, familiarity with diagnostic criteria varied consider-
ably.14 Use of moisturizers by the respondents from Vietnam
80
Figure 4.10:╇ Eczema herpeticum in a child with atopic dermatitis. (Courtesy of
Dermatology, Elsevier, 2nd ed., 2008.)
and Indonesia was significantly less frequent than respondents
from other countries. Topical corticosteroids were used only
for severe disease. A minority in the Philippines and Vietnam
prescribed systemic antibiotics only for severe infection. With
the exception of those in Singapore, the majority of respond-
ents did not use phototherapy. Familiarity with diagnostic
criteria, the early and judicious use of moisturizers and topical
corticosteroids, as well as the treatment of Staphylococcus aureus
superinfection with penicillinase-stable antibiotics should be
emphasized in these regions. In addition, proactive treatment
approaches in disease-free intervals may reduce exacerbations
and total medication use.
References
1. Williams HC, Grindlay DJ. What’s new in atopic eczema? An analysis
of the clinical significance of systematic reviews on atopic eczema
published in 2006 and 2007. Clin Exp Dermatol 2008; 33(6):685–688
[Epub 2008 Aug 7].
2. Stevenson MD, Sellins S, Grube E, Schroer K, Gupta J, Wang N, et al.
Aeroallergen sensitization in healthy children: racial and socioeco-
nomic correlates. J Pediatr 2007; 151(2):187–191.
3. Zar HJ, Ehrlich RI, Workman L, Weinberg EG. The changing preva�
lence of asthma, allergic rhinitis and atopic eczema in African adoles-
cents from 1995 to 2002. Pediatr Allergy Immunol 2007; 18(7):
560–565.
4. Janumpally SR, Feldman SR, Gupta AK, Fleischer AB Jr. In the United
States, blacks and Asian/Pacific Islanders are more likely than whites to
seek medical care for atopic dermatitis. Arch Dermatol 2002; 138(5):
634–637.
5. Tay YK, Khoo BP, Goh CL. The profile of atopic dermatitis in a tertiary
dermatology outpatient clinic in Singapore. Int J Dermatol 1999;
38(9):689–692.
 4â•… Eczematous Disordersâ•… •â•… Dyshidrotic eczema/Pomphylox

6. Tay YK, Kong KH, Khoo L, Goh CL, Giam YC. The prevalence and
descriptive epidemiology of atopic dermatitis in Singapore school chil-
dren. Br J Dermatol 2002; 146(1):101–106.
7. Shaikh WA, Shaikh SW. Allergies in India: an analysis of 3389 patients
attending an allergy clinic in Mumbai, India. J Indian Med Assoc 2008;
106(4):220, 222, 224 passim.
8. Nnoruka EN. Current epidemiology of atopic dermatitis in south-
eastern Nigeria. Int J Dermatol 2004; 43(10):739–744.
9. Ben-Gashir MA, Hay RJ. Reliance on erythema scores may mask severe
atopic dermatitis in black children compared with their white coun-
terparts. Br J Dermatol 2002; 147(5):920–925.
10. Paul Kelly, Susan C Taylor Dermatology for Skin of Color Chapter 12.
The Structure and Function of Skin of Color, Sonia Badreshia-Bansal
and Susan C Taylor. New York: McGraw-Hill; 2009.
11. Enomoto H, Noguchi E, Iijima S, Takahashi T, Hayakawa K, Ito M,
et al. Single nucleotide polymorphism-based genome-wide linkage
analysis in Japanese atopic dermatitis families. BMC Dermatol 2007;
7:5.
12. Johnston GA, Bilbao RM, Graham-Brown RA. The use of dietary
manipulation by parents of children with atopic dermatitis. Br J
Dermatol 2004; 150(6):1186–1189.
13. Simpson EL, Basco M, Hanifin J. A cross-sectional survey of comple-
mentary and alternative medicine use in patients with atopic derma-
titis. Am J Contact Dermatol 2003; 14(3):144–147.
14. Chan YC, Tay YK, Sugito TL, Boediardja SA, Chau DD, Nguyen KV,
et al. A study on the knowledge, attitudes and practices of Southeast
Asian dermatologists in the management of atopic dermatitis. Ann
Acad Med Singapore 2006; 35(11):794–803.

skin such as the palms and soles. Calcineurin inhibitors may

Dyshidrotic eczema/ have a small role as steroid-sparing agents. In addition, allergy
avoidance, antihistamines, and treatment of secondary infec-

Pomphylox tions will allow complete healing. If the condition is recalci-

trant, use of oral corticosteroids, immunosuppressants, or

Pomphylox is a chronic, relapsing, inflammatory vesiculobul-

lous disease of the hands and feet within the spectrum of
eczema. Hand eczema is a common skin disorder affecting
more than 1% of the adult population with 10% showing a 1
year prevalence in several studies.1 The cause of dyshidrotic
eczema is unknown, but likely multifactorial. The condition
often appears associated with other skin conditions including
atopic and allergic contact dermatitis, allergy to ingested
metals, dermatophyte and bacterial infections, environmental
and genetic factors, or emotional stress.1–4 Additionally, an
association with increased perspiration rate has been sug-
gested, but a primary versus secondary role is debated.5 There
is considerably higher prevalences among certain occupational
groups engaged in wet work such as hairdressers, cooks,
domestic housewives, nurses, and print workers. However, a
change of job does not necessarily lead to healing.6 Regardless,
most cases are classified as idiopathic.
Symmetrical crops of deep seated, tapioca-like vesicles and/
or bullae on the palms and lateral aspects of fingers character- Figure 4.11:╇ Infected dyshidrotic eczema.
ize dyshidrotic eczema. Feet, soles, and the lateral aspects
of toes may also be affected (Fig. 4.11). They typically
resolve without rupture, followed by desquamation. In ethnic
patients, hyperkeratosis and hyperpigmentation may be noted
(Fig. 4.12).
Other conditions that should be considered in the differ-
ential diagnosis of dyshidrotic eczema include fungal infec-
tion, allergic contact dermatitis, and atopic dermatitis.
Therefore, a patch test, potassium hydroxide preparation, and
bacterial culture should be performed (to rule out bacterial
superinfection). If bullae are present, a skin biopsy will rule
out pemphigus vulgaris or bullous pemphigoid.
Patients with dyshidrotic eczema must be advised to follow
a daily hand care regimen consisting of mild cleansers and fre-
quent use of emollients. In addition, when localized, potent
topical corticosteroids, preferably in an ointment vehicle, may Figure 4.12:╇ Symmetric distribution of dyshidrotic eczema with post-inflammatory
be of benefit, with less risk of skin atrophy when used on thick hyperpigmentation.

81
 Part 1 Medical Dermatology
phototherapy with local bath PUVA or NBUVB may prove
useful. Use of botulinum toxin may have a role as an anticholin-
ergic agent to decrease perspiration, which is thought to be a
contributor to dyshidrotic eczema. Oral retinoids, such as
isotretinoin, are useful in hyperkeratotic cases. If bullae are
present, use of Burrow’s solution (10% aluminum acetate) may
be helpful. Low nickel or low cobalt diets are rarely successful.
Patients should be counseled to avoid known contact irritants
or allergens, including nickel. Stress reduction may be helpful.
Few trials are available investigating the general category of
eczema including dyshidrotic eczema. Therefore, treatment
of this entity is similar to that of all of the eczematous
dermatitides.
First-Line Therapies
Topical/oral corticosteroids A/D
Calcineurin inhibitors C cases of dyshidrotic eczema, it should be considered with high
Allergy avoidance E levels of ingestion of nickel and/or cobalt, regardless of patch
Antibiotics (when secondarily infected) E
Oral antihistamines E
There is very limited data on the specific treatment of dys-
hidrotic eczema as its treatment is included in that for eczema
in general (see ‘atopic dermatitis’, and ‘irritant’ or ‘allergic
contact dermatitis,’ and ‘nummular dermatitis’ sections).
Overview of studies of treatments for hand eczema-the
EDEN hand eczema survey. Van Coevorden AM, Coenraads
PJ, Svensson A, Bavinck JN, Diepgen TL, Naldi L. European
Dermato-Epidemiology Network (Eden). Br J Dermatol. 2004
Aug; 151(2):446–451.
Nine treatments have been studied by randomized control
trials in the past 25 years (in less than 1200 patients), with
double blinding in 11 studies. None of the studies analyzed
ethnicity, age-, and sex-specific therapeutic responses. The
majority of the trials reviewed ultraviolet irradiation followed
by topical or oral corticosteroids. 86% of the studies stated a
positive or promising effect, which may point towards publica-
tion bias. Only a few papers addressed the issue of blinding
and the importance of long term follow up to document
disease duration and frequency of relapse.
The use of halcinonide solution, 0.1%, in the treatment of
eczematous diseases. Lynfield YL. Cutis 1983; 31(2):
203–204.
Twice daily application of halcinonide solution 0.1% was
used to treat 66 patients with eczematous dermatoses. The
majority of the responses were excellent, with the condition
clearing completely in 8 patients within the first week.
Hyperkeratotic disease may require occlusion or penetration
enhancers in order to increase penetration of topical
therapies.
82
Topical tacrolimus (FK506) and mometasone furoate in treat-
ment of dyshidrotic palmar eczema: a randomized, observer-
blinded trial. Schnopp C, Remling R, Möhrenschlager M, Weigl
L, Ring J, Abeck D. J Am Acad Dermatol 2002; 46(1):73–77.
This randomized, controlled, observer-blinded, 4-week trial
of 16 patients with twice-daily topical application of topical
tacrolimus versus mometasone furoate showed a simliar 50%
reduction in severity after 2 weeks of treatment for chronic
palmar involvement, but not for plantar dyshidrotic eczema. 14
patients relapsed, requiring retreatment within 3 weeks with
topical tacrolimus. Tacrolimus may be be considered an alter-
native immunosuppressive treatment when conventional treat-
ment has failed. Alternatively, it may allow for for rotational
therapy, thus reducing steroid toxicity in patients with long-
standing disease.
Low-cobalt diet for dyshidrotic eczema patients. Stuckert J,
Nedorost S. Contact Derm 2008; 59(6):361–365.
Although metal hypersensitivity does not play a role in all
test results. Oral challenge may be a valuable adjunctive diag-
nostic procedure in patients with pompholyx who have negative
routine patch tests. This article offers an updated and simplified
approach to published guidelines for low-cobalt diets.
Metals allergens such as nickel, chromate, and cobalt represent
high rates of contact sensitization worldwide. The most common
sources of nickel allergy are costume jewelry, belt buckles, wrist
watches and eyeglass frames. The most common sources of
chromate allergy were cement, leather and metal objects.
Second-Line Therapies
Phototherapy A
Botulinum toxin D
Comparison of localized high-dose UVA1 irradiation versus
topical cream psoralen-UVA for treatment of chronic vesicu-
lar dyshidrotic eczema. Petering H, Breuer C, Herbst R, Kapp
A, Werfel T. J Am Acad Dermatol 2004; 50(1):68–72.
This study compared the effects of localized high-dose
UVA1 irradiation versus topical PUVA for treatment of chronic
vesicular dyshidrotic eczema (>6 months). Of 27 patients
(Fitzpatrick skin type I-II), 24 showed a good response to
localized UVA1 irradiation or topical PUVA (5/week for 3
weeks titrating to a max dose of 130╯J/cm2), 48% had history
of atopic dermatitis, 5% had nickel sulfate hypersensitivity,
and 70% with nicotine abuse. Dyshidrotic Area and Severity
Index (DASI) scores significantly decreased on both sides and
were reduced to half of the pretreatment values. No statistically
significant differences between localized UVA1 irradiation or
topical PUVA could be detected.
The longer wavelength of the UVA1 spectrum (340–400╯nm),
which peaks at approximately 365╯nm, compared with the UVA
proportion of the UVA/UVB emission spectrum (320–400╯nm),
 4â•… Eczematous Disordersâ•… •â•… Dyshidrotic eczema/Pomphylox
leads to deeper dermal penetration and may stimulate photo�
immunologic effects up to 210-µm in depth. The mechanism is
theorized to be a reduced survival of transformed T and B
lymphocytes by mediating singlet-oxygen damage thus trigger-
ing immediate preprogrammed cell death.
Adjuvant botulinum toxin A in dyshidrotic hand eczema: a
controlled prospective pilot study with left–right compari-
son. Wollina U, Karamfilov T. J Eur Acad Dermatol Venereol
2002; 16(1):40–42.
8 adult patients with dyshidrotic hand eczema (atopic type)
were included in a prospective, side-by-side, controlled, pilot
study using topical corticosteroids on both hands in combina-
tion with intracutaneous injections of 100 units of BTXA
(Botox) on the more severely affected hand on day 1. The
mean DASI score changed from 28 to17 with topical therapy
alone and from 36 to 3 with adjuvant BTXA. Itching and
vesiculation were inhibited earlier when using the combina-
tion of corticosteroids and BTXA. There was one relapse in the
corticosteroid group and none in the BTXA group. Interruption
of sweating by BTXA improves the outcome and reduces
relapses in patients with dyshidrotic hand eczema.
Botulinum toxin A is a potent inhibitor of acetylcholine release
that induces eccrine sweat production and release. Inhibition
of sweating by other measures, such as tap water iontophoresis,
has been shown to be beneficial in dyshidrotic hand eczema.
BTXA is antipruritic as well, suggesting that it not only interacts
with acetylcholine release but also with substance P release. The
major disadvantages are the need for injections, the discomfort
and the cost.
Third-Line Therapies
Immunosuppressants
mycophenolate mofetil
azathioprine
methotrexate
cyclosporine
Etanercept
Oral retinoids
Topical khellin
Chelating agents
Low-dose external beam radiation
Iontophoresis
Diaminodiphenylsulphone (DDS)
Ranitidine
Pentoxifylline
Iontophoresis
Complementary and Alternative Medicine (biofeedback, vitamins)
– (See Chapter 18)
Commonly encountered pitfalls
In ethnic patients, chronic, vesicular dyshidrotic eczema may
resolve with hyperpigmentation. Additionally, itching can
increase the risk of hyperpigmentation just as in other inflam-
matory skin diseases. Many exogenous factors may trigger a
flare including dermatophyte infections, contact deramatitis,
and metal hypersensitivity with resulting bacterial or fungal
superinfection. Patch testing and cultures should be performed
when clinically indicated.
Special management & counseling considerations
Patients with dyshidrotic eczema must be advised to follow a
daily hand care regimen including frequent prophylactic use
of emollients and daily use of mild cleansers. Use of corticos-
teroids with occlusion will significantly increase penetration.
Allergy to topical corticosteroids may occur and present
as worsening of disease with corticosteroid use. In this case,
discontinuation of treatment and patch testing should be
implemented. Caution should be exercised if topically applied
psoralen derivatives are used as this treatment may provoke
phototoxic reactions with blistering, which may produce long-
lasting hyperpigmentation.7,8
References
1. Barth JH, Venning VA, Wojnarowska F. Palmo-plantar involvement in
auto-immune blistering disorders – pemphigoid, linear IgA disease
and herpes gestationis. Clin Exp Dermatol 1988; 13:85–86.
2. Veien NK. Systemic contact dermatitis. In: Zhai H, Wilhelm K-P,
Maibach HI, editors. Marzulli and Maibach’s dermatotoxicology. 7th
ed. Boca Raton (FL): CRC Press; 2008. p. 135–153.
3. Kaaman T, Torssander J. Dermatophytid—a misdiagnosed entity? Acta
Derm Venereol (Stockh) 1983; 63:404–408.
4. Veien NK, Hattel T, Laurberg G. Plantar Trichophyton rubrum infec-
tions may cause dermatophytids on the hands. Acta Derm Venereol
(Stockh) 1994; 74:403–404.
5. Kutzner H, Wurzel RM, Wolff HH. Are acrosyringia involved in the
pathogenesis of “dyshidrosis”? Am J Dermatopathol 1986; 8(2):
109–116.
6. Meding B, Jarvholm B. Hand eczema in Swedish adults—changes in
prevalence between 1983 and 1996. J Invest Dermatol 2002; 118:
719–723.
7. Grundmann-Kollmann M, Behrens S, Peter RU, Kerscher M. Treatment
of severe recalcitrant dermatoses of the palms and soles with PUVA-
bath versus PUVA-cream therapy. Photodermatol Photoimmunol
Photomed 1999; 15:87–89.
8. Petrozzi JW, Kaidbey KM, Kligman AM. Topical methoxsalen and
blacklight in the treatment of psoriasis. Arch Dermatol 1977; 113:
292–296.
83
 Part 1 Medical Dermatology

Irritant contact
dermatitis
Irritant contact dermatitis (ICD) is a multifactorial inflamma-
tory condition caused by the direct cytotoxic effect of a chemi-
cal or physical agent on the skin. ICD is characterized by
polymorphous lesions including sharply demarcated ery-
thematous or skin colored patches or plaques, edema, vesicu-
lation, or erosions. In ethnic skin, the condition may present
with hyperkeratosis, hyperpigmentation, hypopigmentation,
or fissuring. Constant rubbing can lead to lichenification and
lichen simplex chronicus. The hands are the most common
sites for ICD, especially from repeated workplace exposure. A
Healthcare workers are commonly affected due to frequent
hand washing.1,2 The annual prevalence of hand eczema is
estimated to be 7–12% in the general population in Northern
Europe and possibly higher in the U.S.3–5
Almost any material may cause ICD given sufficient expo-
sure in time and/or concentration. Offending agents include
harsh substances, alcohol, alkali (Fig. 4.13), detergents
(sodium lauryl sulfate), water, and solvents.6 Solvents are a
major cause of ICD because they remove essential fats and oils
from the skin which increases transepidermal water loss
(TEWL), thus increasing susceptibility for ICD. Physical irri-
tants such as friction and exfoliants can also produce reactions.
In children, ICD manifests as diaper dermatitis due to direct
skin irritation by urine and feces.
Although all ages and ethnic groups can develop ICD, the
elderly population is most susceptible. With aging, there are
alterations in the properties of the skin causing it to become B
dehydrated, thin, and intolerant to soaps and solvents. In
addition, individuals with pre-existing skin conditions, such Figure 4.13:╇ Self inflicted irritant contact dermatitis due to a suspected bleaching
as atopic dermatitis or psoriasis, are more prone to developing solution on the hands.
ICD. Furthermore, the condition can worsen in winter months
and with low ambient humidity due to increased TEWL from prescribed in an ointment vehicle. In extensive and treatment-
disruption of the stratum corneum as well as pH alterations resistant cases, oral corticosteroids or phototherapy should
from irritant substances. ICD can also be exacerbated by occlu- be considered. However, these therapies do not address the
sion, excessive humidity, and maceration which increases the underlying problem of irritant exposure. Evaluation for super-
water content of the stratum corneum and enhances penetra- imposed infections should be performed and if present,
tion of water-soluble substances.7 treated with appropriate topical or oral antibiotic or antifungal
The diagnosis of ICD rests on exclusion of other conditions. agents. Recurrences are likely if individuals continue the same
Patch testing should be done to rule out an allergic compo- skin care routine.
nent. An important component of management of ICD
includes the use of non-irritating or hypoallergenic cleansers,
cosmetics, moisturizers, and protectants. Frequent use of First-Line Therapies
bland emollients containing ceramides, avoidance of irritants
and allergens, and use of barrier creams containing dime- Barrier creams B
thicone or petrolatum are the mainstays of treatment for ICD, Emollients B
all of which help to restore the epidermal barrier. The genera- Physical skin protectants B
tion of cleansers that are soap-free, called synthetic detergents Topical or intralesional corticosteroids B
or syndets, are good alternatives. Certain agents found com- Topical calcineurin inhibitors B
monly in cosmetics that should be avoided include propylene
glycol, acids, urea, and sodium lauryl sulfate. Topical corticos-
teroids and topical calcineurin inhibitors may control symp- ICD has been poorly studied compared to allergic contact
toms and decrease inflammation, and preferably should be dermatitis. There are currently no evidence-based guidelines

84
 4â•… Eczematous Disordersâ•… •â•… Irritant contact dermatitis
specifically for the management of chronic hand eczema, and
evidence for established treatments for hand eczema is not of
sufficient quality to guide clinical practice.
Evaluation of efficacy of a skin lipid mixture in patients
with irritant contact dermatitis, allergic contact dermatitis
or atopic dermatitis: a multicenter study. Berardesca E,
Barbareschi M, Veraldi S, Pimpinelli N. Contact Derm 2001;
45(5):280–285.
The aim of this study was to evaluate the efficacy of a topical
skin lipid mixture in the treatment of ICD, ACD and AD. 580
patients with ICD, ACD or AD were treated with a skin lipid
mixture containing ceramide-3 and patented nanoparticles.
There was improvement in all conditions with decreased ery-
thema, pruritus, fissuring, and overall disease severity.
Emollients are the first line of treatment used to decrease itching
and reduce dryness and scaling. Regular and liberal use of
hydrating emollients facilitates the hydration state of stratum
corneum and improves the barrier function of skin. The addi-
tion of lotions containing alpha-hydroxy acids, such as glycolic
or lactic acid, is suggested for thick scaly plaques if fissuring is
not present.
Efficacy of a skin-protective foam in the treatment of chronic
hand dermatitis. Fowler JF Jr. Am J Contact Derm 2000;
11(3):165–169.
To determine if hand dermatitis, primarily of an occupa-
tional nature, could be improved by the use of a protective
foam containing dimethicone and glycerin, 28 adult subjects
were enrolled. Each of the subjects had chronic uncontrolled
hand dermatitis for at least 12 months, which was felt to be
either allergic, irritant, or a combination of both. A skin-
protective foam was applied without disruption of their
current occupation. At 2 and 6 weeks, the skin was evaluated.
Topical corticosteroid usage was reduced in 53.6% of subjects
and 70.0% had improved by the end of the study.
Long-term, intermittent treatment of chronic hand eczema
with mometasone furoate. Veien NK, Olholm Larsen P,
Thestrup-Pedersen K, Schou G. Br J Dermatol 1999; 140(5):
882–886.
In a prospective, open, randomized trial, 120 patients with
chronic hand eczema were treated daily with mometasone
furoate cream until the dermatitis cleared or for a maximum
of 9 weeks. It is interesting to note that 3 patients had mild or
moderate atrophy at the onset of the study which disappeared
during the study. Those who cleared were randomized to treat-
ment for up to 36 weeks with intermittent mometasone or no
further treatment. Long-term intermittent treatment of chronic
hand eczema with mometasone furoate was necessary and the
use of emollients alone was insufficient to control, in particu-
lar, dorsal hand eczema. The described treatment rarely pro-
duced atrophy which was mild when present.
Topical steroids should be used sparingly and in the lowest
concentration that is effective therapeutically. Low to medium
potency topical steroids such as hydrocortisone valerate and
desonide are useful for prolonged use. For palmar involvement,
longer-term intermittent use of a potent corticosteroid prepara-
tion is more beneficial and well tolerated. Refractory cases may
also respond to daily application of a potent steroid under occlu-
sion for short periods. Intradermal injection of triamcinolone
acetonide (10╯mg/ml) or oral corticosteroid for recalcitrant
localized patches of hand eczema has been recommended.
Pimecrolimus cream 1%: a potential new treatment for
chronic hand dermatitis. Belsito DV, Fowler JF Jr, Marks JG Jr,
Pariser DM, Hanifin J, Duarte IA, et╯al. Multicenter Investigator
Group. Cutis 2004; 73(1):31–38.
A multicenter, randomized, vehicle-controlled, 3-week
study was conducted in patients with chronic hand dermatitis
of various etiologies to identify subgroups particularly respon-
sive to pimecrolimus cream 1% twice a day with overnight
occlusion. A total of 294 patients were randomized to the
study. By the final visit on day 22, there was a trend toward
greater clearance in patients who received pimecrolimus than
in those treated with vehicle cream.
Pimecrolimus cream is a safe alternative to steroids for the
treatment of ICD, especially in sensitive areas involving the
face, axilla, and groin region. It is most appropriate for early
intervention at the first signs and/or symptoms of a relapse
during the remission phase which may prevent the occurrence
of more severe flares and therefore reduce corticosteroid expo-
sure in the long term.
Tacrolimus ointment in the treatment of occupationally
induced chronic hand dermatitis. Schliemann S, Kelterer D,
Bauer A, John SM, Skudlik C, Schindera I, Wehrmann W,
Elsner P, et╯al. Contact Derm 2008; 58(5):299–306.
In this pilot study, a prospective, open, multicentre trial of
29 patients with mild-to-moderate chronic hand dermatitis
were treated with tacrolimus ointment twice a day for 4 weeks
followed by a 2-month optional treatment period. 44% of
patients cleared from chronic hand dermatitis. However,
worsening of the dermatitis occurred in 7%, possibly due to
irritation from the medication.
Second-Line Therapies
NBUVB C
PUVA C
Cyclosporine C
Oral alitretinoin A
Local narrowband UVB phototherapy vs local PUVA in the
treatment of chronic hand eczema. Sezer E, Etikan I. Photo-
dermatol Photoimmunol Photomed 2007; 23(1):10–14.
This randomized, controlled, prospective study in 15
patients with biopsy proven resistant chronic hand eczema
compares NBUVB with PUVA. The initial dose of 150mJ/cm2
was increased until a total dose of 2000╯mJ/cm2 was reached.
At the end of the treatment period, both NBUVB and PUVA
irradiation provided a statistically significant reduction of
total clinical scores over 9 weeks. In the PUVA group, palmar
85
 Part 1 Medical Dermatology
hyperpigmentation was observed in three cases (25%) which
showed slow resolution over time.
One major concern with the use of NB-UVB phototherapy is
the potential carcinogenic risks. In animal studies it has been
estimated that the cancer risk of NB-UVB treatment should not
be greater than BB-UVB, and likely, less than PUVA.
Comparison of the influence of cyclosporine and topical
betamethasone-17,21-dipropionate treatment on quality of
life in chronic hand eczema. Granlund H, Erkko P, Reitamo
S. Acta Derm Venereol 1997; 77(1):54–58.
In a randomized, controlled, cross over study, the authors
demonstrated that cyclosporine at 3╯mg/kg/day is as effective
as topical betamethasone-17,21-dipropionate in the treatment
of chronic hand eczema. 41 patients were treated with either
treatment for 6 weeks. Treatment failures crossed over to the
other treatment for another 6 weeks. Improvement was noted
in all clinical assessments, i.e. disease activity, extent of the
disease, itch, sleep disturbances and use of emollients.
Efficacy and safety of oral alitretinoin (9-cis retinoic acid)
in patients with severe chronic hand eczema refractory to
topical corticosteroids: results of a randomized, double-
blind, placebo-controlled, multicentre trial. Ruzicka T, Lynde
CW, Jemec GB, Diepgen T, Berth-Jones J, Coenraads PJ. Br J
Dermatol. 2008 Apr; 158(4):808–817.
This is a randomized, double-blind, placebo-controlled,
prospective, multi-center trial in 1032 patients (ethnic patients
8%) with severe refractory chronic hand eczema randomized
to placebo, 10╯mg or 30╯mg of oral alitretinoin once daily for
up to 24 weeks with emollient therapy. Both alitretinoin
treatment regimens induced durable remission, with a
median of 5–6 months. Patients relapsed with 75% of their
initial signs and symptoms. Adverse events included headache,
mucocutaneous events, hyperlipidemia, and decreased free
thyroxine and TSH. The biological effects of alitretinoin are
mediated by retinoic acid receptor A and/or retinoic acid
receptor X (RXR).
This is the largest study ever conducted for chronic hand
eczema. Regular monitoring of symptoms and laboratory evalu-
ations should be undertaken. Headache was the most frequent
adverse event leading to 4% of patient withdrawals in the
30╯mg group, 1% in the 10╯mg group, and 1% in the placebo
group. Increases in serum cholesterol and triglyceride levels
were the most commonly reported abnormalities. Reduced
thyroid-stimulating hormone was also reported with apparent
dose-dependent frequency, but did not always lead to corre-
sponding reductions in thyroxine levels.
Third-Line Therapies
Superficial radiotherapy
Bexarotene gel
86
Commonly encountered pitfalls
Racial differences in skin reactivity have not been thoroughly
investigated utilizing objective methods; existing data are
often contradictory. There is a widespread, but largely unsub-
stantiated view that certain skin types may be more suscepti�
ble to the effect of skin irritants than others. Some have stated
blacks are less reactive and Asians are more reactive than Cau-
casians,8 though the data supporting this hypothesis rarely
reaches statistical significance.9 In a matched panel of Cauca-
sian and Japanese women volunteers, both acute and cumula-
tive topical irritant reactions to a range of materials was
studied.10 Acute irritant responses were greater in the Japanese
panel and this reached statistical significance with the stronger
irritants. Cumulative irritation was observed only with the
weaker irritants, especially in Japanese subjects, but it rarely
reached significance. Evaluation of racial differences in barrier
function and permeability after removal of stratum corneum
through tape strippings showed that TEWL was highest in
Asians.11 Another study suggests a superior barrier function
and greater resistance to irritants in African-American skin.
Stratum corneum disruption, parakeratosis, spongiosis,
perivascular inflammatory infiltrate, and TEWL were more
severe in Caucasian participants when ICD was induced by a
common dishwashing liquid or 4% sodium lauryl sulfate,12,13
suggesting a superior barrier function of African-American
skin. However, there were no differences in the hyperprolifera-
tive response after irritant exposure and this indicated similar
kinetics for the two groups. However, other evidence indicates
that, within any particular group, inter-individual variation is
likely to be much larger than variations between racial or
ethnic groups.14 A given individual’s response to one chemical
or exposure condition may not always predict their response
to another.
Although it is unclear, there may be ethnic differences in
skin barrier permeability to irritants. Most research shows that
TEWL is greater in black skin compared to white skin.15,16
Studies of TEWL in Asian skin are inconclusive. Black skin
may tend to have more xerosis clinically, owing to a 2.5-fold
increase in spontaneous desquamation rate compared with
Caucasians and Asians. In addition, mast cells found in black
skin have different structural properties, larger granules and
differences in enzymes compared with white skin, potentially
accounting for differences in pruritus. Black skin has variable
reactivity rate and decreased skin surface pH. Although some
deductions have been made about Asian and Hispanic
skin, further evaluation needs to be performed. Differences in
water content, corneocyte desquamation, elastic recovery/
extensibility, lipid content, and skin microflora, although sta-
tistically significant, are inconclusive.
Special management & counseling considerations
ICD is the most common occupational skin disorder. If clini-
cally suspected, evaluation of infection should be performed
and if present, treated with appropriate topical or oral
antibiotic or antifungal agents. Presence of ICD facilitates the
 4â•… Eczematous Disordersâ•… •â•… Lichen simplex chronicus
Figure 4.14:╇ Indian female presented with an incidental rash that was self treated
with garlic which caused this exuberant vesicular irritant contact dermatitis.
development of allergic contact dermatitis (many cutaneous
allergens are also irritants). Self treatment and use of comple-
mentary medicine is high among the ethnic population
(Fig. 4.14).
References
1. Lodi A, Mancini LL, Ambonati M, Coassini A, Ravanelli G, Crosti C.
Epidemiology of occupational contact dermatitis in a North Italian
population. European Journal of Dermatology 2000; 10:128–132.
2. Mahmoud G, Lachapelle JM, Van Neste D. Histological assessment of
skin damage by irritants: Its possible use in the evaluation of a ‘barrier
cream’. Contact Dermatitis 1984; 11:179–185.
Lichen simplex
chronicus
Lichen simplex chronicus (LSC), a response to chronic rubbing
or scratching, is characterized by thickening of the skin and
accentuation of the skin markings. LSC can be primary or
secondary to an existing skin disorder such as atopic dermati-
tis, psoriasis, or allergic contact dermatitis.1 Neurodermatitis
is often used interchangeably with LSC, suggesting a role of
anxiety, depression, and obsessive–compulsive disorder as part
of the pathological process of developing lesions.2 In general,
psychosomatic factors have been estimated to be present in at
least one-third of dermatologic patients.3
LSC may present as one or more well circumscribed ery-
thematous, scaly, hyperkeratotic, or leathery plaques with
exaggerated skin lines. Plaques may have a predilection for the
neck, extensor surfaces of the forearms and lower legs, and the
3. Burnett CA, Lushniak BD, McCarthy W, Kaufman J. Occupational
dermatitis causing days away from work in U.S. private industry, 1993.
American Journal of Industrial Medicine 1998; 34:568–573.
4. Cherry N, Meyer JD, Adisesh A, Brooke R, Owen-Smith V, Swales C,
et al. Surveillance of occupational skin disease: EPIDERM and OPRA.
The British Journal of Dermatology 2000; 142:1128–1134.
5. Coenraads PJ, Diepgren TL. Risk for hand eczema for employees with
past or present atopic dermatitis. International Archives of Occupational
and Environmental Health 1998; 71:7–13.
6. Diepgen TL, Coenraads PJ. The epidemiology of occupational contact
dermatitis. International Archives of Occupational and Environmental
Health 1999; 72:496–506.
7. Jungersted JM, Høgh JK, Hellgren LI, Jemec GB, Agner T. Skin barrier
response to occlusion of healthy and irritated skin: Differences in
trans-epidermal water loss, erythema and stratum corneum lipids.
Contact Dermatitis 2010 Aug 20.
8. Robinson MK. Population differences in acute skin irritation responses.
Race, sex, age, sensitive skin and repeat subject comparisons. Contact
Derm 2002; 46(2):86–93.
9. Modjtahedi SP, Maibach HI. Ethnicity as a possible endogenous factor
in irritant contact dermatitis: comparing the irritant response among
Caucasians, blacks, and Asians. Contact Derm 2002; 47(5):272–278.
10. Foy V, Weinkauf R, Whittle E, Basketter DA. Ethnic variation in the skin
irritation response. Contact Derm 2001; 45(6):346–349.
11. Kompaore F, Marty JP, Dupont C. In vivo evaluation of the stratum
corneum barrier function in blacks, Caucasians and Asians with two
non-invasive methods. Skin Pharmacol 1993; 6(3):200–207.
12. Astner S, Burnett N, Rius-Díaz F, Doukas AG, González S, Gonzalez E.
Irritant contact dermatitis induced by a common household irritant:
a non-invasive evaluation of ethnic variability in skin response. J Am
Acad Dermatol 2006; 54(3):458–465.
13. Hicks SP, Swindells KJ, Middelkamp-Hup MA, Sifakis MA, González
E, González S. Confocal histopathology of irritant contact dermatitis
in vivo and the impact of skin color (black vs white). J Am Acad
Dermatol 2003; 48(5):727–734.
14. Robinson MK. Intra-individual variations in acute and cumulative skin
irritation responses. Contact Derm 2001; 45(2):75–83.
15. Wesley NO, Maibach HI. Racial (ethnic) differences in skin properties:
the objective data. Am J Clin Dermatol 2003; 4(12):843–860.
16. Paul Kelly, Susan C Taylor Dermatology for Skin of Color Chapter 12.
The Structure and Function of Skin of Color, Sonia Badreshia-Bansal
and Susan C Taylor. New York: McGraw-Hill; 2009.
genital areas. Rubbing plays an important role and is reflected
in white scratch marks, erosions, and ulcerations. Exacerbating
factors may include atopy and xerosis. LSC must be differenti-
ated from psoriasis, mycosis fungoides, dermatophyte infec-
tions, lichen planus, and lichen amyloidosis. In ethnic skin,
LSC can present with ashy brown or gray plaques (Fig. 4.15).
Therapy is aimed at reducing symptoms and improving
existing lesions. The most important element in treatment is
breaking the itch–scratch cycle. A multimodality approach is
important for effective treatment. Potent topical cortico�
steroids along with emollients are the current treatment of
choice as they decrease inflammation and pruritus, soften
hyperkeratosis, and reduce lesion size. Occlusion provides a
physical barrier from scratching while increasing penetration
of corticosteroids. However, prolonged use of potent cor�
ticosteroids should be discouraged due to the potential for
permanent skin related changes. Management also involves
consideration of underlying emotional factors. Hence, oral
anxiolytics and antihistamines should be considered. For
infected lesions, an antibiotic will assist with healing. For
87
 Part 1 Medical Dermatology
Figure 4.15:╇ Lichen simplex chronicus in a young child with atopic dermatitis.
Exaggerated skin markings are seen on the extensor surfaces of the arm. (Courtesy
of Dermatology, Elsevier, 2nd ed., 2008.)
resistant or facial lesions, safer alternatives include the topical
immunomodulators, tacrolimus and pimecrolimus, which
have been demonstrated to be effective. Other anecdotal and
investigational therapies include botulinum toxin A. Coun-
seling patients to avoid temperature extremes, stress, exposure
to potential irritants and allergens and scratching may be
helpful. Regular and frequent use of moisturizers may serve to
prevent relapses.
First-Line Therapies
Topical corticosteroids/with occlusion
Intralesional steroid
Behavioral modification
The mainstay of treatment involves corticosteroids in
conjunction with vigilant use of daily moisturizers. However,
due to the psychological aspect of the condition, anecdotal
evidence exists regarding behavior modification or use of
anxiolytic medications.
Flurandrenolone tape in the treatment of lichen simplex
chronicus. Bard JW. J Ky Med Assoc 1969; 67(9):668–670.
10 patients used flurandrenolone tape and 8 used a topical
corticosteroid preparation without occlusion. Lasting remis-
sions were seen in 70% of those using the tape vs 25% of those
using topical corticosteroid without occlusion.
Topical corticosteroid with occlusion is the gold standard for
treatment. Hypopigmentation has been reported following use
of the tape.
88
A double-blind, multicenter trial of 0.05% halobetasol
propionate ointment and 0.05% clobetasol 17-propionate
ointment in the treatment of patients with chronic,
localized atopic dermatitis or lichen simplex chronicus.
Datz B, Yawalkar S. J Am Acad Dermatol 1991; 25(6 Pt 2):
1157–1160.
In a double-blind, parallel-group, multicenter comparative
trial of 127 patients with chronic, localized atopic dermatitis
or lichen simplex chronicus, healing was reported in a higher
percentage of patients treated with halobetasol propionate
ointment than in those in the clobetasol propionate treatment
group. Marked improvement or clearance was observed within
3 days, and tolerability was similar in the two treatment
groups.
Topical corticosteroids are often used to treat LSC but after
withdrawal, relapse can occur.
Neurodermatitis and intralesional steroids. Vasistha LK,
Singh G. Dermatologica 1978; 157(2):126–128.
30 cases of neurodermatitis were treated with intralesional
injections. 15 were treated with triamcinolone acetonide
(0.25╯mg/cm2 of the skin) and the remainder with water every
week for 8 weeks, and then followed for another 4 weeks. The
results of treatment were excellent in 66% of triamcinolone-
treated cases. However, 46% of water-treated cases were also
excellent, although not statistically significant. The authors
concluded that the water might have acted as a placebo in
emotionally labile individuals.
The behavioral treatment of neurodermatitis through habit-
reversal. Rosenbaum MS, Ayllon T. Behav Res Ther 1981;
19(4):313–318.
4 patients with neurodermatitis underwent behavioral
modification in which they learned to substitute a competing
response for their urge to scratch. At 6 months, scratching was
markedly reduced in 3 patients and completely eliminated in
one patient who had the mildest disease.
A/C
B
D Second-Line Therapies
Calcineurin inhibitors C
Capsaicin cream E
Doxepin cream A
Cryotherapy E
Alternatives for treatment of LSC, but with limited
evidence, include calcineurin inhibitors and topical antipru-
ritic agents. Cryotherapy may be considered for thicker, resist-
ant lesions.
Pimecrolimus 1% cream for pruritus in postmenopausal
diabetic women with vulvar lichen simplex chronicus: a
prospective non-controlled case series. Kelekci HK, Uncu
HG, Yilmaz B. J Dermatolog Treat 2008; 11:1–5.
 4â•… Eczematous Disordersâ•… •â•… Lichen simplex chronicus
12 postmenopausal diabetic women with vulvar lichen
simplex chronicus were treated with pimecrolimus 1% cream
applied twice daily in a thin layer to the vulvae for 3 months.
A substantial decrease in pruritus was reported by the patients
at week 4. Follow-up after 3 months of treatment showed that
complete cure occurred in 83.3% and improved pruritus in
16.7% patients.
Topical tacrolimus for the treatment of lichen simplex
chronicus. Aschoff R, Wozel G. J Dermatolog Treat 2007;
18(2):115–117.
A 13-year-old boy with LSC on the temple healed com-
pletely with tacrolimus 0.1% ointment in approximately 9
months. No adverse drug reaction was observed. The patient
was completely free of symptoms 3 years after cessation of
treatment.
Topical tacrolimus is an especially useful treatment for sensitive
areas such as the face, axilla, and genital area.
Treatment of prurigo nodularis with topical capsaicin.
Ständer S, Luger T, Metze D. J Am Acad Dermatol. 2001 Mar;
44(3):471–478.
33 patients with severe resistant prurigo nodularis applied
capsaicin cream under occlusion 4 to 6 times daily for 2 weeks
up to 10 months. All patients experienced resolution of pruri-
tius within 12 days and led to gradual healing. Confocal laser
scanning microscopy confirmed decrease in substance P.
However, in almost half of patients, pruritus recurred within
2 months following cessation of treatment. Complete regres-
sion of skin lesions with postinflammatory hyperpigmenta-
tion or residual flat scars was achieved in 9 patients.
Capsaicin is extractable from chili pepper, and may interfere
with the perception of pruritus and pain by depletion of neu-
ropeptides, specifically substance P, in small sensory cutaneous
nerves. The transient symptoms are neurogenic inflammation
(burning sensation and erythema). In this study, it is difficult
to differentiate improvement related to topical capsaicin or
physical occlusion of prurigo.
The antipruritic effect of 5% doxepin cream in patients with
eczematous dermatitis. Doxepin Study Group. Drake LA,
Millikan LE. Arch Dermatol 1995; 131(12):1403–1408.
This multicenter, double-blind trial, evaluated the safety
and antipruritic efficacy of 5% doxepin hydrochloride cream
4 times a day for 7 days in 136 patients with LSC, 87 patients
with nummular eczema, and 86 patients with contact derma-
titis. Sixty percent of doxepin-treated patients experienced pru-
ritus relief within 24 hours. The response rate increased to
84% by the end of the study.
Cryosurgical treatment of nodular neurodermatitis with
Refrigerant 12. McDow RA, Wester MM. J Dermatol Surg
Oncol 1989; 15(6):621–623.
Neurodermatitis is a relatively common skin condition
characterized by patches of scaly, pruritic skin in one or more
of several classic locations. It can be treated with cryosurgery
using Refrigerant 12 with successful clinical and aesthetic
results.
Third-Line Therapies
Ketotifen
Photochemotherapy
Etretinate
Thalidomide
Cyclosporine
Surgical excision
Botulinum toxin
Alternative and complementary therapies (see Chapter 18)
Commonly encountered pitfalls
Although the literature previously claimed that LSC was more
common in Asians and African-Americans, there are no
reported racial differences in frequency. Although controver-
sial, this may be due to ethnic differences and skin barrier
permeability to irritants, especially total epidermal water loss
(TEWL).4 In addition, black skin contains larger mast cell gran-
ules and differences in structural properties and enzymes of
mast cells compared with white skin, potentially accounting
for differences in pruritus. The appearance of lesions on darker
skin may demonstrate follicular prominence. Secondary pig-
mentary alterations are also more severe in individuals with
darker skin. Care must be taken with treating darkly pigmented
individuals with cryotherapy due to the high risk of permanent
hypopigmentation.
Special management & counseling considerations
If LSC is resistant to treatment, the lesion should be biopsied
and cultured to evaluate other dermatoses, and to rule out
underlying malignancy. Additionally, it is important to
evaluate for the presence of infections such as lice or scabies,
especially in lower socioeconomic communities where
its prevalence may be high. Patch testing is useful, especially
in patients who are suspected of having allergic contact
dermatitis.
References
1. Wu Y, Lin Y, Liu HJ, Huang CZ, Feng AP, Li JW. Childhood psoriasis:
a study of 137 cases from central China. World J Pediatr 2010 Aug;
6(3):260–264.
2. Martín-Brufau R, Corbalán-Berná J, Ramirez-Andreo A, Brufau-
Redondo C, Limiñana-Gras R. Personality differences between patients
with lichen simplex chronicus and normal population: A study of
pruritus. Eur J Dermatol 2010 May–Jun; 20(3):359–363.
3. Lotti T, Buggiani G, Prignano F. Prurigo nodularis and lichen simplex
chronicus. Dermatol Ther 2008; 21(1):42–46.
4. Paul Kelly, Susan C Taylor Dermatology for Skin of Color Chapter 12.
The Structure and Function of Skin of Color, Sonia Badreshia-Bansal
and Susan C Taylor. New York: McGraw-Hill; 2009.
89
 Part 1 Medical Dermatology
Nummular dermatitis
The etiology of nummular dermatitis, also known as discoid
eczema, is unknown and probably multifactorial. It is fre-
quently associated with atopic dermatitis, contact sensitiza-
tion, and/or stasis dermatitis. Nummular dermatitis is
common, with prevalence ranging from 0.1% to 9.1%.1 Men
are affected slightly more and at a later stage than women.
Certain medications can also increase the tendency to develop
this condition such as cholesterol lowering agents, isotretin-
oin, metyhyldopa, and gold.2–3
The literature supports an association, in rare cases, with
nummular dermatitis and giardiasis as well as Helicobacter
pylori (H. pylori) infection. One study in Japanese patients
showed antibacterial treatment for H. pylori was effective in
54% of patients with nummular dermatitis.4 In patients with
chronic skin disease, persistent infection with H. pylori may be
a trigger of disease activity and may cause deterioration of
existing disease into an intractable and chronic form.
Nummular (meaning coin-shaped) dermatitis is a form of
eczema that presents clinically with well demarcated, coin-
shaped, pruritic plaques. They are commonly found on the
extremities, particularly the legs, but may occur anywhere on
the trunk, hands, or feet. Lesions are often symmetrically dis-
tributed. The sequela of nummular eczema in ethnic skin is
post-inflammatory hyperpigmentation and permanent brown
macules, especially on the lower extremities. Hyperkeratosis
and lichen simplex chronicus involving the foot were
found to be the most common presentation in Indians
(Fig. 4.16).5
Nummular dermatitis may resemble tinea corporis which
should be excluded with a potassium hydroxide preparation.
Figure 4.16:╇ Nummular dermatitis on leg. (Courtesy of Jeff Miller MD; Department
of Dermatology, Penn State Milton S. Hershey Medical Center.)
90
For lesions with yellow crust suggestive of impetiginization, a
bacterial culture is useful, particularly to rule out community-
acquired MRSA infection, which is increasing in incidence.
Some studies have recommended patch testing because of the
high incidence of allergic contact dermatitis in patients with
nummular dermatitis. Atopic dermatitis, contact dermatitis,
stasis dermatitis, psoriasis, Bowen’s disease, and mycosis fun-
goides are also in the differential diagnosis of nummular
eczema.
Treatment goals include hydration of the skin, treatment of
infection, and reduction of inflammation. Lukewarm or cool
baths or showers reduce itching and help to hydrate the skin.
Patients should moisturize frequently with emollients. The
“soak and smear” method involves “soaking” in water for
15–20 minutes, followed by “smearing” of a corticosteroid
ointment first, followed by application of an emollient, to
damp or wet skin which dramatically aids in penetration. This
method is enhanced by occlusion. Use of mild, non-drying,
non-irritating cleansers, frequent moisturization, a room
humidifier and use of cotton clothing will help prevent recur-
rence. When lesions are localized, topical steroids, preferably
in an ointment formulation, in addition to emollients can
help calm inflammation and erythema. Oral antihistamines
may help reduce pruritus. If lesions are generalized or severe,
oral corticosteroids, steroid-sparing agents, phototherapy, and
psychotherapy have been used with varied success. If there is
any sign of secondary infection, oral antibiotics should be
used. Once the eruption has resolved, ongoing aggressive skin
hydration is essential to prevent recurrence. Few trials investi-
gate nummular dermatitis, and most involve treatment of
general eczema which is appropriate for nummular eczema.
First-Line Therapies
Emollients C
Topical/Intralesional corticosteroids C
Oral antibiotics (if superinfected) E
Oral antihistamines E
Topical doxepin B
For further support from the literature, refer to the atopic
dermatitis, irritant or allergic contact dermatitis sections as
there is considerable treatment overlap for most types of
eczema.
Successful treatment of chronic skin diseases with clobeta-
sol propionate and a hydrocolloid occlusive dressing.
Volden G. Acta Derm Venereol 1992; 72(1):69–71.
The lesions of 141 patients with a variety of chronic skin
diseases unresponsive to therapy, were treated once a week
with clobetasol propionate lotion under an occlusive Duoderm
patch. In 131 patients, the lesions resolved completely, while
partial remission was observed in the remaining 10. The mean
time needed to obtain complete remission for nummular
eczema was 8 days.

The antipruritic effect of 5% doxepin cream in patients with
eczematous dermatitis. Doxepin Study Group. Drake LA,
Millikan LE. Arch Dermatol 1995; 131(12):1403–1408.
This multicenter double-blind trial was conducted to evalu-
ate the safety and antipruritic efficacy of 5% doxepin hydro-
chloride cream in 136 patients with lichen simplex chronicus,
87 patients with nummular eczema, or 86 patients with
contact dermatitis. A total of 309 patients with moderate to
severe pruritus were randomly assigned to apply either doxepin
cream or vehicle cream to eczematous areas 4 times per day
for 7 days. 60% of doxepin-treated patients experienced pru-
ritus relief within 24 hours and response rate increased to 84%
by conclusion of the study. The two most common adverse
effects were stinging and drowsiness, which were transient and
mild to moderate in severity.
Second-Line Therapies
PUVA/NBUVB
Topical immunomodulators
Immuosuppressants
â•… Cyclosporine
â•… Azathioprine
â•… Mycophenolate mofetil
Hypnosis
Alternative and complementary therapies (see Chapter 18)
Azathioprine in dermatological practice. An overview with
special emphasis on its use in non-bullous inflammatory
dermatoses. Scerri L. Adv Exp Med Biol 1999; 455:343–348.
This was a retrospective study of 10 patients with atopic
eczema, 6 patients with pompholyx, 6 patients with plaque
psoriasis, and 2 patients with chronic actinic dermatitis. All
patients had severe refractory disease warranting systemic
second line therapy. The starting dose of azathioprine, which
was used as monotherapy, was 100–150╯mg/day, and the
maintenance dose 50–100╯mg/day with a mean duration of
treatment of 33.5 months. 75% showed a good to excellent
sustained clinical response to azathioprine evenly represented
among all four dermatoses. The adverse reactions encountered
were raised mean corpuscular volume (MCV), leukopenia,
elevated hepatic enzymes, and dyspepsia. Azathioprine was
discontinued due to adverse reactions in 2 patients (dyspepsia,
raised hepatic enzymes) which were reversible.
The main disadvantages of azathioprine therapy are a delayed
onset of action (6–8 weeks) and rare profound bone marrow
toxicity. Susceptibility to bone marrow toxicity is due to a geneti-
cally determined metabolic defect (1 in 300). Patients at risk
of such toxicity may be identified by screening of a thiopurine
methyltransferase enzyme. Azathioprine is a low cost and gener-
ally well tolerated drug.
Hypnosis in dermatology. Shenefelt PD. Arch Dermatol 2000;
136(3):393–399.
Hypnosis is an alternative or complementary therapy that
has been used to treat medical and dermatologic problems.
4â•… Eczematous Disordersâ•… •â•… Nummular dermatitis
Reduction of pruritus and resolution of lesions have been
reported, with use of hypnotic suggestion as a complementary
therapy for nummular dermatitis.
Commonly encountered pitfalls
Patients with nummular dermatitis are at significant risk of
developing secondary allergic contact dermatitis. Those with
chronic recalcitrant nummular dermatitis must be patch
tested. One study in Indian patients found the most frequent
sensitizers were colophony, nitrofurazone, neomycin, and
nickel.6 Reactions to antigens in topical medications, cosmet-
ics and toiletries were also common.7–18
Special management & counseling considerations
Patients must be counseled that nummular eczema is often
recurrent. Avoidance of exacerbating factors and increased fre-
C quency of moisturization are essential for control. Patients
should be counseled to avoid scratching as excoriations may
C
leave permanent brown macules or scarring as well as increas-
ing the risk of infection. Treatment should be aimed at control-
E ling pruritus and increasing skin hydration.
E
E References
E
1. Marks R, ed. Eczema. London: Martin Dunitz, 1992.
2. Rowe JA, Hattenhauer MG, Herman DC. Adverse side effects associated
with latanoprost. Am J Ophthalmol 1997; 124:683–685.
3. Church R. Eczema provoked by methyl dopa. Br J Dermatol 1974;
91:373–378.
4. Sakurane M, Shiotani A, Furukawa F. Therapeutic effects of antibacte-
rial treatment for intractable skin diseases in Helicobacter pylori-positive
Japanese patients. J Dermatol 2002; 29(1):23–27.
5. Chougule A, Thappa DM. Patterns of lower leg and foot eczema in
south India. Indian J Dermatol Venereol Leprol 2008; 74(5):458–461.
6. Krupa Shankar DS, Shrestha S. Relevance of patch testing in patients
with nummular dermatitis. Indian J Dermatol Venereol Leprol 2005;
71(6):406–408.
7. Veien NK, Hattel T, Justesen O, Norholm A. Oral challenge with metal
salts. (II). Various types of eczema. Cont Dermat 1983; 9:407–410.
8. Belsito DV. Contact Dermatitis to ethyl-cyanoacrylate containing glue.
Cont Dermat 1987; 17:234–236.
9. Caraffini S, Lisi P. Nummular dermatitis-like eruption from ethylenedi-
amine hydrochloride in 2 children. Cont Dermat 1987; 17:313–314.
10. Patrizi A, Rizzoli L, Vincenzi C, Trevisi P, Tosti A. Sensitization to
thiomerosal in atopic children. Cont Dermat 1999; 40:94–97.
11. Pigatto PD, Guzzi G, Persichini P. Nummular lichenoid dermatitis
from mercury dental amalgam. Cont Dermat 2002; 46:355–356.
12. Adachi A, Horikawa T, Takashima T, Ichihashi M. Mercury-induced
nummular dermatitis. J Am Acad Dermatol 2000; 43:383–385.
13. Le Coz CJ. Contact nummular (discoid) eczema from depilating
cream. Cont Dermat 2002; 46:111–112.
14. Morrow DM, Rapaport MJ, Strick RA. Hypersensitivity to aloe. Arch
Dermatol 1980; 116:1064–1065.
15. Aoyama H, Tanaka M, Hara M, Tabata N, Tagami H. Nummular
eczema: An addition of senile xerosis and unique cutaneous reactivities
to environmental aeroallergens. Dermatology 1999; 199:135–139.
16. Shenoi DS, Srinivas CR, Balachandran C. Results of patch testing with
a standard series of allergens at Manipal. Indian J Dermatol Venereol
Leprol 1994; 60:133–135.
17. Fleming C, Parry E, Forsyth A, Kemmett D. Patch testing in discoid
eczema. Cont Dermat 1997; 36:261–264.
18. Khurana S, Jain VK, Aggarwal K, Gupta S. Patch testing in discoid
eczema. J Dermatol 2002; 29:763–767.
91
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Part 1 Medical Dermatology
Granulomatous Disorders
Sonia Badreshia-Bansal
Granuloma annulare . . . . . . . . . . . . . . . . . . . . 93
Localized granuloma annulare . . . . . . . . . . . .å°“ . . . 93
Generalized granuloma annulare . . . . . . . . . . . .å°“ . . 95
Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . 97
Granuloma annulare
Granuloma annulare (GA) is a benign inflammatory, self-
limited dermatosis of unknown etiology. There are numerous
disease associations including tuberculosis, diabetes, lipid
abnormalities, paraneoplastic reaction to solid tumors, trauma,
sun exposure, thyroiditis, and viral infections, including HIV,
Epstein–Barr virus, and herpes zoster virus.1–6 More common
in females, GA is seen two-thirds of the time in children and
young adults.
The clinical variants of GA are localized, generalized,
nodular, perforating, and subcutaneous. GA often presents
with papules, the centers of which may be slightly hyperpig-
mented and depressed relative to their borders. Generalized
GA is characterized by numerous papules and annular plaques
symmetrically distributed on the trunk and extremities. An
atypical or more generalized appearance may be a marker of
an associated disease. In ethnic patients, GA may not appear
erythematous but may be brown or gray in color. Additionally,
there may be a higher likelihood of resulting post-inflammatory
hyperpigmentation in these patients (Fig. 5.1). The histology
of GA is one of a histiocytic infiltrate or palisading granulo-
matous dermatitis with focal degeneration of collagen and
elastin and mucin deposition.7
Other conditions that can mimic classic GA include annular
lichen planus, tinea corporis, lupus erythematosus, and
mycosis fungoides. If clinically indicated, evaluation including
blood tests (complete blood count, chemistry, antinuclear
antibody, rheumatoid factor, HIV) and a skin biopsy may be
performed.
For localized, asymptomatic disease, the treatment of choice
may be reassurance and observation. First line and local thera-
©2011 Elsevier Ltd, Inc, BV
5â•…
pies may include potent topical corticosteroids with or without
occlusion for 4–6 weeks or intralesional corticosteroids. Other
therapies which have been shown to be effective include cryo-
therapy and steroid-sparing agents such as tacrolimus and
pimecrolimus. Generalized GA tends to be more persistent
and severe, requiring systemic therapies. First-line therapies for
generalized GA include isotretinoin or phototherapy with
PUVA. Other anecdotal reports include the use of niacina�
mide, antimalarials, dapsone, chlorambucil, cyclosporine, and
pentoxifylline, some of which require regular laboratory
testing. Larger scale, double-blind, placebo-controlled studies
are needed to evaluate efficacy and safety of these therapies.
However, spontaneous resolution often occurs within 2 years
in 50% of cases, although there is a high recurrence rate.
Localized granuloma annulare
First-Line Therapies
Topical corticosteroids D
Intralesional corticosteroids B
Cryotherapy B
Localized granuloma annulare and autoimmune thyroiditis:
a new case report. Vázquez-López F, González-López MA,
Raya-Aguado C, Pérez-Oliva N. J Am Acad Dermatol. 2000
Nov; 43(5 Pt 2):943–945.
A 29-year-old Spanish woman with history of autoimmune
thyroiditis associated with GA cleared with topical clobetasol
proprionate 0.05%.
The association of GA and thyroid disease remains to be clari-
fied, but may be as high as 6-13%. Therefore, when treating
patients with GA, consideration must be given to consider
checking TSH and/or antimicrosomal or antithyroglobulin anti-
bodies prior to administering medications, such as potassium
iodide or interferon, which could affect thyroid function.
93
 Part 1 Medical Dermatology
Figure 5.1:╇ Coalescing annular plaques distinctive of granuloma annulare.
(Courtesy of Jim Marks MD; Department of Dermatology, Penn State Milton S.
Hershey Medical Center.)
Granuloma annulare and necrobiosis lipoidica treated by jet
injector. Sparrow G, Abell E. Br J Dermatol 1975; 93(1):
85–89.
45 cases of granuloma annulare were treated with 0.1╯mL
triamcinolone acetonide (5╯mg/mL) or sterile normal saline.
Complete clearance was achieved in nearly 70% of those
receiving triamcinolone following 2.9 treatments every 6–8
weeks, versus 44% with saline placebo. The recurrence after
treatment occurred in about half of patients, but re-treatment
was usually successful.
Successful outcome of cryosurgery in patients with granu-
loma annulare. Blume-Peytavi U, Zouboulis CC, Jacobi H,
Scholz A, Bisson S, Orfanos CE. Br J Dermatol 1994; 130(4):
494–497.
This prospective, uncontrolled clinical trial evaluated 31
patients with localized GA treated by cryosurgery. Cryotherapy
using liquid nitrogen or nitrous oxide as refrigerants was
found to be effective for localized GA. A better cosmetic result
was obtained with smaller lesions.
Secondary dyschromia may be a complication of cryotherapy,
especially in ethnic skin.
Second-Line Therapies
Imiquimod
PUVA or UVA1
Photodynamic therapy
Laser surgery
Intralesional interferon
Surgery
94
Successful treatment of granuloma annulare with imiqui-
mod cream 5%: a report of four cases. Badavanis G,
Monastirli A, Pasmatzi E, Tsambaos D. Acta Derm Venereol
2005; 85(6):547–548.
This pilot study evaluated the efficacy and safety of imiqui-
mod 5% in biopsy proven GA resistant to standard therapies.
Four subjects had either single or multiple lesions, primarily
on the extremities. Imiquimod 5% cream was applied for
10–12 hours without occlusion, and then removed by washing.
Subjects used the medication three times weekly for 6–12
weeks. 75% noted complete clearance and many lesions had
no recurrence up to 18 months.
Cream psoralen plus ultraviolet A therapy for granuloma
annulare. Grundmann-Kollmann M, Ochsendorf FR, Zollner
TM, Tegeder I, Kaufmann R, Podda M. Br J Dermatol 2001;
144(5):996–999.
5 patients with biopsy proven GA were treated with topical
PUVA cream four times a week. After a mean of 26 treatments
and mean cumulative UVA dose of 55.9╯J/cm2, four patients
showed complete remission and one patient had a significant
improvement of GA lesions. Like bath PUVA, cream PUVA
therapy may induce either direct effects on inflammatory cells
or through PUVA-induced release of mediators from epider-
mal cells that inhibit the recruitment and activation of inflam-
matory cells. Cream PUVA has the advantage of targeting
localized body areas.
Transient hyperpigmentation after PUVA therapy occurred in
one patient with skin type III and, therefore, should be used
cautiously in darker skin types.
Photodynamic therapy for granuloma annulare: more than
a shot in the dark. Weisenseel P, Kuznetsov AV, Molin S,
Berking C, Prinz JC. Dermatology 2008; 217(4):329–332.
Photodynamic therapy (PDT) was performed in 7 patients
(skin types I-III) with chronic biopsy proven disseminated GA
located on the extremities. The control side consisted of red
light only while the treated side consisted of 20% aminole-
vulinic acid (ALA) gel applied under an occlusive dressing for
5╯h, followed by illumination with 100╯J/cm2 by a standard
red-light source. In total, 2–3 PDT sessions were performed at
an interval of 2–4 weeks between each session. The overall
response rate was 57%. In 28.5% of patients, GA cleared com-
pletely (with slight transitional hyperpigmentation of the
target lesions), in 28.5% of patients the skin lesions improved
markedly, and in 43% of patients no clinical response was
observed. There was no significant correlation between the
outcome of PDT treatment and the patients’ sex, skin type,
previous treatment modalities or the duration of the disease.
PDT may not reach deeper or subcutaneous forms of GA to
D exert an effect, which may explain the lack of response in 3 of
the 7 patients reported.
D
D
Treatment of granuloma annulare with the 585╯nm pulsed
E dye laser. Sniezek PJ, DeBloom JR 2nd, Arpey CJ. Dermatol
D Surg 2005; 31(10):1370–1373.
E Case report of a patient with a single plaque of GA present
on the left wrist for 3 years was treated three times with a

585╯nm flashlamp-pumped pulsed dye laser. Significant flat-
tening and reduction of erythema were evident. After a second
treatment at month 5 and a third treatment at month 13,
further improvement was noted, and long-term remission was
achieved.
Prospective studies are needed to verify these results as variabil-
ity in individual response is more likely. In addition, extra
caution must be taken in treating ethnic skin due to the high
risk of post-inflammatory hyperpigmentation.
Treatment of granuloma annulare by local injections with
low-dose recombinant human interferon gamma. Weiss JM,
Muchenberger S, Schöpf E, Simon JC. J Am Acad Dermatol
1998; 39(1):117–119.
A small trial was performed involving 3 patients with local-
ized granuloma annulare treated with intralesional injections
of recombinant human interferon gamma (2.5 × 10−5╯IU/
lesion) vs normal saline. Lesions were treated on 7 consecutive
days and thereafter 3/week for 2 weeks. All lesions cleared
after the treatment period leaving only residual hyperpigmen-
tation and remained disease free at 12 months follow up.
Interferon gamma may inhibit the delayed hypersensitivity
reaction of GA.
Surgical pearl: surgical treatment of tumor-sized granuloma
annulare of the fingers. Shelley WB, Shelley ED. J Am Acad
Dermatol 1997; 37(3 Pt 1):473–474.
This case reports successful treatment of multiple lesions
of nodular granuloma annulare on the mid-interphalangeal
joints by shave excision with healing by secondary intention.
There was no recurrence after 1 year, no interference of func-
tion, and minimal scarring.
Generalized granuloma annulare
First-Line Therapies
Photochemotherapy
Isotretinoin
Topical calcineurin inhibitors
Oral dapsone
UVA1 phototherapy for disseminated granuloma annulare.
Schnopp C, Tzaneva S, Mempel M, Schulmeister K, Abeck D,
Tanew A, et╯al. Photodermatol Photoimmunol Photomed
2005; 21(2):68–71.
20 patients with long-standing, stable disease underwent
UVA1 phototherapy. 16 patients were treated with a high-dose
regimen (median single dose 110╯J/cm2) and 4 patients with
a medium-dose regimen (median single dose 50╯J/cm2). 5
patients each had substantial improvement or near complete
clearance. Another 5 patients had a moderate response, 3
patients were considered as poor responders, and 2 patients
were treatment failures. Of the patients with good or excellent
5â•… Granulomatous Disordersâ•… •â•… Granuloma annulare
responses, recurrence was noted after discontinuation of
treatment.
Isotretinoin in the treatment of granuloma annulare. Looney
M, Smith KM. Ann Pharmacother 2004; 38(3):494–497.
This review highlights 10 case reports of the successful use
of isotretinoin 0.5–1╯mg/kg/day in disseminated GA. However,
some patients required dosage decreases in response to drug-
related liver function test elevations, and two instances of drug
failure were identified. Isotretinoin is thought to have pro�
liferative and inhibitory effects on collagen synthesis that
improve GA symptoms.
The treatment success of isotretinoin is difficult to measure since
failure rates may be underreported and the disease has a high
spontaneous resolution rate. Due to the potential of serious
adverse effects and teratogenicity associated with isotretinoin,
the agent should be reserved for disseminated and refractory
cases of GA.
Successful treatment of disseminated granuloma annulare
with topical tacrolimus. Jain S, Stephens CJ. Br J Dermatol
2004; 150(5):1042–1043.
4 patients with resistant disseminated GA were treated with
topical tacrolimus for 6 weeks; 2 patients had complete clear-
ance maintained over the 6 week period, while 2 had marked
improvement noted after 10–21 days of application. Tac-
rolimus is thought to inhibit the activation of various cytokines,
including IL-2 and TNF-α, which may account for its ability to
reduce inflammation and to treat GA effectively.
Efficacy of dapsone in disseminated granuloma annulare:
a case report and review of the literature. Martín-Sáez E,
Fernández-Guarino M, Carrillo-Gijón R, Muñoz-Zato E, Jaén-
Olasolo P. Actas Dermosifiliogr. 2008 Jan–Feb; 99(1):64–68.
This case report reviews an elderly Spanish female patient
with resistant biopsy proven disseminated GA. She responded
favorably with dapsone 100╯mg daily with improvement in
symptoms and skin lesions within 2 months of treatment and
remained disease free at 15 months. The patient had only
C residual hyperpigmented macules remaining after 12 months
C of treatment which resolved.
E The primary side effects of dapsone include hemolytic anemia
C and methemoglobinemia blood dyscrasias, heart, liver, and
kidney abnormalities. Pregnancy as well as glucose-6-phosphate
dehydrogenase or folic acid deficit should be ruled out with
laboratory testing prior to treatment. During treatment, blood
and urine tests should also be performed every week for the first
month and every month thereafter.
Second-Line Therapies
Cyclosporine E
Pentoxifylline E
Fumaric acid esters D
Oral corticosteroid E
95
 Part 1 Medical Dermatology

administration. Side effects include gastrointestinal complaints

Antimalarials D
such as nausea, diarrhea, and stomach cramps and flushing.
Chlorambucil D In addition, kidney function and blood count require close
Hydroxyurea E monitoring during therapy. There are no reports of long-term
Infliximab E severe or irreversible side effects.
Efaluzimab E
Low-dose chlorambucil in the treatment of generalized
Doxycycline E
granuloma annulare. Kossard S, Winkelmann RK. Dermato-
Defibrotide E
logica 1979; 158(6):443–450.
Adalimumab E 5 of 6 adults with generalized GA responded favorably to
KI E therapy with low-dose chlorambucil; 5 of the patients had
Oral/topical vitamin E E recurrent, long-standing, and resistant GA to conventional
Lasers E treatments. Low-dose chlorambucil, 2╯mg three times daily,
may be effective in a short-term therapy program but should
be used only in patients with persistent, widespread, or
Disseminated granuloma annulare: efficacy of cyclosporine unusual forms of generalized GA.
therapy. Spadino S, Altomare A, Cainelli C, Franchi C, Frigerio Caution must be taken with treatment and it requires careful
E, Garutti C, et╯al. Int J Immunopathol Pharmacol 2006; hematologic monitoring which can be the major and dose limit-
19(2):433–438. ing effect. Patients should be informed of the risk of the major
This Italian study highlights 4 patients with disseminated toxicities associated with chlorambucil, including hypersensitiv-
GA who were treated with cyclosporine for 6 weeks at a dose ity, drug fever, myelosuppression, hepatic toxicity, infertility,
of 4╯mg/kg/day for 4 weeks, and subsequently reduced by seizures, GI toxicity, and secondary malignancies.
0.5╯mg/kg/day every 2 weeks. Complete resolution was noted
within 3 weeks, and there were no relapses during the dose- Rapid improvement of recalcitrant disseminated granuloma
tapering period or the following 12 months. annulare upon treatment with the tumour necrosis factor-
alpha inhibitor, infliximab. Hertl MS, Haendle I, Schuler G.
Patients on cyclosporine should receive baseline and periodic
Br J Dermatol 2005; 152(3):552–555.
blood and platelet count, serum chemistries, including blood
A 59-year-old white female patient with history of breast
urea nitrogen, creatinine, potassium, magnesium, uric acid,
cancer and insulin-dependent diabetes had long-standing,
liver function tests, and lipids as well as blood pressure
resistant, and generalized GA lesions. Infliximab was admin-
assessments.
istered intravenously at weeks 0, 2 and 6 and thereafter at a
Generalised granuloma annulare successfully treated with monthly interval for an additional 4 months. Most of the GA
pentoxifylline. Rubel DM, Wood G, Rosen R, Jopp-McKay A. plaques resolved within 4–6 weeks, leaving post-inflammatory
Australas J Dermatol 1993; 34(3):103–108. brownish macules. She remained disease free at 16 months.
Pentoxifylline is thought to reduce blood viscosity via GA is characterized by a predominant mononuclear infiltrate
effects on all major blood components. A patient with a around necrobiotic areas which presumably represents a
10-year history of generalized GA showed dramatic clearing of population of target cells susceptible to infliximab-induced
the majority of papules after 4 weeks of treatment with pen- antibody-dependent cellular cytotoxicity.
toxifylline. The clinical effectiveness in generalized GA lends The major potential side effects of treatment with infliximab
support to a model of immune-mediated vasculitis in the are the increased incidence of tuberculosis and the rare inci-
pathogenesis of this disorder. dence of autoimmune disorders. Thus, prior to infliximab treat-
ment, tuberculosis must be ruled out by thorough history as well
Disseminated granuloma annulare – treatment with fumaric as a thoracic X-ray and/or Mantoux reaction test. Combination
acid esters. Eberlein-König B, Mempel M, Stahlecker J, Forer therapy of infliximab with immunosuppressive drugs constitutes
I, Ring J, Abeck D. Dermatology 2005; 210(3):223–226. an additional risk.
8 patients with disseminated granuloma annulare were
treated with oral fumaric acid esters according to the standard Successful treatment of disseminated granuloma annulare
therapy regimen used in psoriasis. Treatment induced a signifi- with adalimumab. Rosmarin D, LaRaia A, Schlauder S,
cant clinical improvement in skin lesions, especially at high Gottlieb AB. J Drugs Dermatol 2009; 8(2):169–171.
doses. Complete remission in 3 patients and partial remission A 61-year-old female with a 4-year history of resistant dis-
in 4 patients were observed. Fumaric acid esters may shift a seminated granuloma annulare was successfully treated with
T-helper cell 1 immune response to a T-helper cell 2 immune the anti-tumor necrosis factor (TNF)-alpha antibody, adalimu-
response. One patient remained unchanged. Side effects asso- mab. The patient had failed high potency topical glucocorti-
ciated with the therapy were seen in 6 patients including coids, hydroxychloroquine, and narrow-band ultraviolet light
diarrhea, dizziness, nausea, flushing and stomach pains. (UV)-B phototherapy.
Although fumaric acid esters can be effective in patients with Interestingly, a link between TNF inhibition and the develop-
disseminated forms of granuloma annulare, side effects of ment of generalized GA has been reported in some patients
fumaric acid ester may be limiting and prevent higher dose treated for rheumatoid arthritis with infliximab, adalimumab,

96
 5â•… Granulomatous Disordersâ•… •â•… Sarcoidosis

and etanercept. When dealing with patients on these agents, it

is important to be aware of possible adverse events and the
References
potential development of such complications.
Commonly encountered pitfalls
It is important to investigate for the presence of systemic dis-
eases that are associated with GA and that occur commonly in
ethnic patients including diabetes, sarcoidosis and HIV. For
example, multiple lesions of GA in children may be associated
with significantly lower serum insulin values and mildly
impaired glucose tolerance.8 A Spanish study showed an asso-
ciation with localized GA and autoimmune thyroiditis.9 Recent
reports have clearly demonstrated GA occurring in association
with sarcoidosis, and thus GA may act as a precursor lesion to
the more mature sarcoidal granuloma. There was also a case
of GA masquerading as molluscum contagiosum in an HIV
positive African-American woman.10 Laboratory evaluation
may include hematologic and chemistry analysis, antinuclear
antibodies, rheumatoid factor, and thyroid function tests.
Special management & counseling considerations
Certain treatments must be used with caution in ethnic
10. McGregor JM, McGibbon DH. Disseminated granuloma annulare as a
patients. For instance, care must be taken if liquid nitrogen or
nitrous oxide refrigerants or lasers are to be used since these
treatments can lead to secondary hypopigmentation or hyper-
pigmentation as a complication.
1. Smith MD, Downie JB, DiCostanzo D. Granuloma annulare. Int J
Dermatol 1997; 36:326–333.
2. Studer EM, Calza AM, Saurat JH. Precipitating factors and associated
diseases in 84 patients with granuloma annulare: a retrospective study.
Dermatology 1996; 193:364–368.
3. Nebesio CL, Lewis C, Chuang TY. Lack of an association between
granuloma annulare and type 2 diabetes mellitus. Br J Dermatol 2002;
146:122–124.
4. Li A, Hogan DJ, Sanusi ID, Smoller BR. Granuloma annulare and
malignant neoplasms. Am J Dermatopathol 2003; 25:113–116.
5. Akyol M, Killcarsian H, Goze F, Emre S. Granuloma annulare associ-
ated with prostate carcinoma. J Eur Acad Dermatol Venereol 2003;
17:464–465.
6. Toro JR, Chu P, Yen TS, LeBoit PE. Granuloma annulare and human
immunodeficiency virus infection. Arch Dermatol 1999; 135:
1341–1346.
7. Mallory SB. Infiltrative diseases. In: Schachner LA, Hansen RC, editors.
Pediatric Dermatology. 2nd ed. New York, N.Y.: Churchill Livingstone;
1995. p. 834–836.
8. Kakourou T, Psychou F, Voutetakis A, Xaidara A, Stefanaki K, Dacou-
Voutetakis C. Low serum insulin values in children with multiple
lesions of granuloma annulare: a prospective study. J Eur Acad
Dermatol Venereol 2005; 19(1):30–34.
9. Vázquez-López F, Pereiro M Jr, Manjón Haces JA, González López MA,
Soler Sánchez T, Fernández Coto T, et al. Localized granuloma annu-
lare and autoimmune thyroiditis in adult women: a case-control study.
J Am Acad Dermatol 2003; 48(4):517–520.
presentation of acquired immunodeficiency syndrome (AIDS). Clin
Exp Dermatol 1992; 17(1):60–62.

marily pulmonary sarcoidosis. Sacoidosis has been described

Sarcoidosis in HIV positive patients.
Sarcoidosis is called the “great imitator” because it
can display almost any morphology. Other rare lesions of
Specific diagnosis cutaneous sarcoidosis are ichthyosiform, lichenoid, vasculitic,

Sarcoidosis is a multisystem disease of unknown etiology. A

hyperactive T-cell mediated immune system, specifically CD4+
T-helper cells of the Th1 subtype following antigen presenta-
tion by monocytes, causes epithelioid granulomas. Patients
with sarcoidosis have impaired delayed-type immune reac-
tions.1 The causative antigen remains unidentified. Some
propose an autoimmune etiology, while others propose an
infectious etiology.
Sarcoidosis occurs in all races and both sexes, with a
bimodal age distribution which peaks at mean 30 years and
again at about 50 years.2 The incidence is highest in African-
American women followed in order by African-American men,
Caucasian women, and Caucasian men. The most common
internal organ involved is the lung.2 Cutaneous involvement
is seen in 25% of patients, which may be the first clinical sign
of the disease. Macular or papular sarcoidal lesions are the
most common, particularly in African-American women. Red-
brown to violaceous papules and plaques appear most often
on the face, lips, neck, upper back, and extremities (Figs. 5.2,
5.3). Variants of sarcoidosis include subcutaneous, lupus
pernio, and ulcerative. Lupus pernio is usually more common
in African-American women with long-standing systemic, pri- Figure 5.2:╇ Violaceous papules of sarcoid. (Courtesy of Susan Taylor, MD.)

97
 Part 1 Medical Dermatology
Figure 5.3:╇ Waxy papules of sarcoid. (Courtesy of Dave Adams MD; Department
of Dermatology, Penn State Milton S. Hershey Medical Center.)
psoriasiform, erythrodermic, verrucous, papillomatous, and
ulcerative lesions. Granulomatous acne rosacea may mimic
sarcoidosis clinically and histopathologically. Erythema
nodosum may be a non-specific marker of sarcoid.
A combination of clinical, radiologic, and histologic criteria
are used to diagnose sarcoidosis. Laboratory evaluations
include complete blood count, serum calcium, 24-hour urine
calcium, serum angiotensin-converting enzyme (ACE) level,
blood urea nitrogen (BUN), creatinine, hepatic tests, chest X
ray (CXR), pulmonary function test (PFT), ANA, and dsDNA.
Histologic diagnosis includes the presence of superficial and
deep dermal epithelioid granulomas with non-caseating
centers.
Medical therapy is based upon symptoms, extent of
disease, and progression. The course of the disease is variable
from spontaneous remission to chronic progressive disease.
Morbidity and mortality is most commonly due to systemic
involvement or from complications of therapy. Virtually every
treatment is based on minimal evidence-based data and relies
almost exclusively on anecdotal information. Topical or
intralesional corticosteroids at monthly intervals are first-line
treatments for limited, non-disfiguring skin involvement.
Worldwide accepted standard therapies for sarcoidosis include
the administration of corticosteroids, antimalarials, and
methotrexate. Chronic forms recalcitrant to treatment which
can lead to greater scarring should be treated aggressively with
these agents.
Though experience is limited and anecdotal, other therapies
with promise may include cyclosporine, oral isotretinoin,
allopurinol, minocycline, doxycycline, PUVA, thalidomide,
and biologics such as infliximab, etanercept, and adalimumab.
Both cyclosporine and chlorambucil have been largely aban-
doned given their associated toxicity and disappointingly
unreliable efficacy. Radiation has been used to treat resistant
cutaneous lesions. Surgical excision of small lesions may be
attempted but risk of recurrence and keloidal scarring is high
amongst ethnic patients. Laser therapy is a quick, non-invasive
newer treatment option for cutaneous sarcoidosis. Laser
98
surgery has also been attempted in treating disfiguring skin
plaques and lupus pernio.
First-Line Therapies
Topical corticosteroid C
Intralesional corticosteroid C
Oral corticosteroid C
Antimalarials B
Evidence-based therapy for cutaneous sarcoidosis. Doherty
CB, Rosen T. Drugs 2008; 68(10):1361–1383.
A stepwise approach in treating cutaneous sarcoidosis is
reviewed. In mild skin disease, potent topical corticosteroids
or repeated intralesional injections of triamcinolone (3–
10╯mg/mL) may result in improvement. Recalcitrant, wide-
spread, or deforming skin lesions may respond to oral
corticosteroids (e.g. prednisone 40–80╯mg/day) used alone or
in combination with second-line steroid sparing agents such
as antimalarials or methotrexate. The worldwide accepted
standard therapy for sarcoidosis is corticosteroids and it is
theorized that the usefulness of corticosteroids lies in their
ability to suppress inflammation and to thus halt ensuing
granuloma formation. Other promising treatments include the
tumor necrosis factor-alpha inhibitors, infliximab and adali-
mumab. Infliximab is administered via intravenous infusion
at doses of 3–10╯mg/kg at 0, 2 and 6 weeks and as indicated
thereafter, whereas adalimumab is injected subcutaneously at
doses of 40╯mg either weekly or every 2 weeks. Isotretinoin,
0.5–2.0╯mg/kg/day, has been used successfully in a handful of
reported cases. Thalidomide at dosages of 50 to > 400╯mg/day
also has limited, albeit promising, supporting data. However,
access is restricted in many countries. Melatonin (20╯mg/day)
and allopurinol (100–300╯mg/day) are not well studied. There
are reports of therapeutic benefit with both doxycycline and
minocycline. Pentoxifylline (400╯mg, three times daily) has
been of use in a small number of reported cases of pulmonary
sarcoidosis, but there are no reports on its use in patients with
primarily cutaneous disease. Improvement of otherwise refrac-
tory cutaneous and respiratory sarcoidosis has been docu-
mented with leflunomide 20╯mg/day therapy.
The maximum dosages of antimalarials should not exceed 3.5
and 6.5╯mg/kg/day for chloroquine or hydroxychloroquine,
respectively, due to potential ocular toxicity. Weekly low dose
methotrexate 10–30╯mg may be used with close monitoring of
hematological, gastrointestinal, pulmonary and hepatic enzymes.
The high teratogenic potential of isotretinoin and thalidomide
limits its use considering the primary demographic group likely
to develop sarcoidosis is women of childbearing potential.
Intralesional triamcinolone for cutaneous palpebral sar-
coidosis. Bersani TA, Nichols CW. Am J Ophthalmol 1985;
99(5):561–562.
Cosmetically disfiguring bilateral palpebral sarcoidal der-
matitis in a 32-year-old woman was treated with intradermal

triamcinolone. There was rapid and complete resolution of
lesions and there was no evidence of recurrence or hypopig-
mentation at a one-year follow-up.
Intralesional triamcinolone at concentrations of 3–20╯mg/mL
are another localized treatment option for cutaneous sarcoido-
sis, with injections being most advantageous for small sarcoid
plaques and papules. Potential adverse effects include hypopig-
mentation and atrophy.
Treatment of cutaneous sarcoidosis with chloroquine.
Review of the literature. Zic JA, Horowitz DH, Arzubiaga C,
King LE Jr. Arch Dermatol 1991; 127(7):1034–1040.
Antimalarial agents have a relatively long history of use
in the treatment of sarcoidosis and are considered standard
therapy, typically in conjunction with corticosteroids as steroid
sparing agents or for patients in whom corticosteroids are
neither desirable nor necessary for long-term treatment. With
a judiciously determined daily dosage and regular 6-month
ophthalmologic follow-up examinations, the risk of develop-
ing retinopathy can be avoided, because the daily dosage rate
rather than total dose accumulation determines the develop-
ment of chloroquine-induced retinopathy.
As is true of corticosteroids, there are no placebo controlled or
paired comparison studies investigating the usefulness of anti-
malarials in cutaneous sarcoidosis. Agranulocytosis is a rare but
serious complication of therapy in skin of color patients, espe-
cially since G6PD deficiency is common in this population.
Potential ocular effects are the most serious adverse events
associated with antimalarial treatment and include the devel-
opment of corneal deposits, central retinopathy, or permanent
vision impairment when receiving long term chloroquine
therapy. Dose should not exceed 3.5╯mg/kg/d for chloroquine
and 6.5╯mg/kg/d for hydroxychloroquine to avoid corneal drug
deposits.
Second-Line Therapies
Methotrexate C
Topical tacrolimus E were at the greatest risk of developing sarcoidosis, which was
Prolonged use of methotrexate for sarcoidosis. Lower EE,
Baughman RP. Arch Intern Med 1995; 155(8):846–851.
A non-randomized interventional study of 50 patients with
chronic sarcoidosis were treated with methotrexate for at least
2 years. Most patients had systemic involvement and received
oral methotrexate 10╯mg weekly in conjunction with pred-
nisone. In those with cutaneous involvement, a good response
was observed. At low doses, methotrexate is an antiinflamma-
tory agent and is thus thought to suppress granuloma forma-
tion. Methotrexate can be offered as a steroid sparing agent at
reduced doses or during the time of transition.
Cutaneous sarcoidosis successfully treated with topical tac-
rolimus. Katoh N, Mihara H, Yasuno H. Br J Dermatol 2002;
147(1):154–156.
5â•… Granulomatous Disordersâ•… •â•… Sarcoidosis
A case report of a 62-year-old Japanese woman with a
10-year history of orange-yellow plaques of sarcoidosis on
her face is presented. Cutaneous lesions responded to topical
tacrolimus ointment after unsuccessful treatment with topical
and systemic corticosteroids. Marked improvement was noted
within 2 weeks of therapy and complete resolution within 4
weeks. Relapse was noted following cessation of therapy. One
possible mechanism of topical tacrolimus is inhibiting the
activation of Th1 cells accumulating in the granulomas.
Third-Line Therapies
Allopurinol
Mycophenolate mofetil
Azathioprine
Infliximab
Etanercept
Adalimumab
Thalidomide
ACE inhibitor
Colchicine
Doxycycline, minocycline
Isotretinoin
Mepacrine (quinacrine)
Chlorambucil
Clofazamine
Surgery
Laser
Pentoxifylline
Cyclosporine
Melatonin
Commonly encountered pitfalls
In a Detroit study, African-American females aged 30–39 years
a three-fold higher risk compared to Caucasians.3 In addition,
African-American patients tended to be younger when they
presented with uveitis and/or adnexal granulomas.4 Sarcoido-
sis is quite common in American and West Indian Blacks, with
incidences up to 10 times higher than in Whites.5 Sarcoidosis
is generally believed to be rarer in African Blacks, especially
along the West African coast, from which American Blacks
trace their ancestry. The most common presentation of sar-
coidosis in West Africa was in longstanding tribal marks, where
tribal scarification is common. In a study of South-East Asians
with diverse ethnic groups, cutaneous sarcoidosis was found
to be rare, especially in Singapore, but extracutaneous involve-
ment was common.6 Once thought to be rare in Chinese, it is
being encountered with increasing frequency in Taiwan.7 In
Arabs, the clinical profile was similar to the Western pattern of
the disease, but there were several differences including an
older age group, more frequent constitutional symptoms, the
99
 Part 1 Medical Dermatology
rarity of ocular and central nervous system involvement, and
initial presentation as a chest infection.8
Cutaneous sarcoidosis in Blacks tends to be more severe
and recalcitrant to therapy. Management of these patients
poses a challenge. In one study of African-Americans with
recalcitrant cutaneous sarcoid, treatment with a stepwise
approach showed that all patients required second-line treat-
ment agents.9 Cutaneous lesions of sarcoidosis may indicate
internal involvement. However, an Indian study demon-
strated that symptomatology and abnormal laboratory results
do not necessarily correlate with the severity of cutaneous
involvement.10
It has also been noted that sarcoidosis in African-Americans
is characterized by more severe extrapulmonary involvement
and more exuberant skin lesions. In a study in Black South
Africans, with systemic sarcoidosis, lung, eye, and acral bone
involvement were the most common areas of involvement.11
Atypical cutaneous lesions (hypopigmented, ichthyosiform,
lymphedematous, mutilating, ulcerative, verrucous) were also
common. In systemic sarcoidosis, African-American patients
had a two-fold greater median granuloma density than Cau-
casians in bronchiolar lung tissue, which may explain racial
differences in diagnostic yield by lung biopsy and disease
severity at diagnosis.12
Extracutaneous involvement is not rare and tends to affect
women older than 40 years, often manifesting with angio-
lupoid lesions on the face.13 In an Indian study, constitutional
symptoms such as fever, weight loss and pulmonary infiltrates
were more frequently encountered as compared to Western
studies.14 In a study of over 200 cases of sarcoidosis in East
India, clinical course and prognosis differed considerably from
that seen in Caucasians, African-Americans, South-African
Bantus and Japanese.15 Sarcoidosis was more common in
wealthy males over 40 years, who had a history of atopy, and
presented with constitutional symptoms such as low-grade
fever with malaise, arthralgias, anorexia, and respiratory symp-
toms. These patients also had hypercalciuria and raised serum
angiotensin converting enzyme levels. Course and prognosis
also differed from Western patients. A different treatment
schedule, avoiding oral prednisolone, was found to be effective
in this particular study.15 Confidently excluding other causes
of granuloma formation, particularly tuberculosis, is required,
particularly in developing nations.
Special management & counseling considerations
In a study of long-term prognosis of sarcoidosis in Arabs and
Asians, the presence of arthralgias and early stage of disease
were the most important predictors of a good prognosis. Sex,
age, ethnicity, and presence of erythema nodosum did not
influence the prognosis.16 Although EN is the most common
non-specific lesion associated with sarcoid, it is a less frequent
finding in Black or Asian patients.17
Because G6PD deficiency is common in skin of color, it is
essential to screen these patients prior to initiating therapy.
African, Mediterranean, and Southeastern Asians should be
100
especially identified to screen for G6PD deficiency to prevent
a hemolytic episode during treatment with antimalarial
agents.18
Spontaneous remissions may occur. Adverse prognostic
factors include the African-American race, chronic cutaneous
lesions, chronic uveitis, age at onset older than 40 years, cystic
bone lesions, neurosarcoidosis, myocardial involvement, and
stage III or IV pulmonary disease. The course of sarcoidosis is
variable, ranging from self-limited acute disease to a chronic
debilitating disease that may result in death. Additionally,
socioeconomic factors play a role in prognosis. Lower socio-
economic status leads to decreased access to medical care,
more frequent relapses, and a worse prognosis.
References
1. Prasse A, Georges CG, Biller H, Hamm H, Matthys H, Luttmann W,
et al. Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveo-
lar CD4+ and CD8+ T cells. Clin Exp Immunol. 2000 November;
122(2):241–248.
2. Labow TA, Atwood WG, Nelson CT. Sarcoidosis in the American Negro.
Arch Dermatol 1964 May; 89:682–689.
3. Rybicki BA, Major M, Popovich J Jr, Maliarik MJ, Iannuzzi MC.
Racial differences in sarcoidosis incidence: a 5-year study in a
health maintenance organization. Am J Epidemiol 1997; 145(3):
234–241.
4. Evans M, Sharma O, LaBree L, Smith RE, Rao NA. Differences in clini-
cal findings between Caucasians and African-Americans with biopsy-
proven sarcoidosis. Ophthalmology 2007; 114(2):325–333.
5. Alabi GO, George AO. Cutaneous sarcoidosis and tribal scarifications
in West Africa. Int J Dermatol 1989; 28(1):29–31.
6. Chong WS, Tan HH, Tan SH. Cutaneous sarcoidosis in Asians: a report
of 25 patients from Singapore. Clin Exp Dermatol 2005; 30(2):
120–124.
7. Chao SC, Yan JJ, Lee JY. Cutaneous sarcoidosis among Taiwanese.
J Formos Med Assoc 2000; 99(4):317–323.
8. Diab SM, Karnik AM, Ouda BA, Denath FM, Fettich J, Francis IM.
Sarcoidosis in Arabs: the clinical profile of 20 patients and review of
the literature. Sarcoidosis 1991; 8(1):56–62.
9. Mosam A, Morar N. Recalcitrant cutaneous sarcoidosis: an evidence-
based sequential approach. J Dermatolog Treat 2004; 15(6):353–359.
10. Mahajan VK, Sharma NL, Sharma RC, Sharma VC. Cutaneous sar-
coidosis: clinical profile of 23 Indian patients. Indian J Dermatol
Venereol Leprol 2007; 73(1):16–21.
11. Jacyk WK. Cutaneous sarcoidosis in black South Africans. Int J
Dermatol 1999; 38(11):841–845.
12. Burke RR, Stone CH, Havstad S, Rybicki BA. Racial differences in sar-
coidosis granuloma density. Lung 2009; 187:1–7 [Epub 2008 Aug 21].
13. Lee JY, Chao SC, Yang MH, Yan JJ. Sarcoidosis in Taiwan: clinical
characteristics and atypical mycobacteria. J Formos Med Assoc 2002;
101(11):749–755.
14. Sharma SK, Mohan A, Guleria JS. Clinical characteristics, pulmonary
function abnormalities and outcome of prednisolone treatment in 106
patients with sarcoidosis. J Assoc Physicians India 2001; 49:697–704.
15. Gupta SK. Sarcoidosis: a journey through 50 years. Indian J Chest Dis
Allied Sci 2002; 44(4):247–253.
16. Behbehani N, Jayakrishnan B, Khadadah M, Al-Sawi M. Long-term
prognosis of sarcoidosis in Arabs and Asians: predictors of good
outcome. Sarcoidosis Vasc Diffuse Lung Dis 2006; 23(3):209–214.
17. Minus HR, Grimes PE. Cutaneous manifestations of sarcoidosis in
blacks. Cutis 1983 Oct; 32(4):361–363, 372.
18. Beutler E, Duparc S; G6PD Deficiency Working Group. Glucose-6-
phosphate dehydrogenase deficiency and antimalarial drug develop-
ment. Am J Trop Med Hyg 2007 Oct; 77(4):779–789.
Part 1 Medical Dermatology

Hypersensitivity and
Allergic Disorders
Ninad Pendharkar, Sonia Badreshia-Bansal, Janelle Vega, and David A Rodriguez
6â•…
Arthropod bites . . . . . . . . . . . . . . . . . . . . . . 101 randomized clinical trials, however, to determine the best
therapy for bug bites. Treatment is mainly symptomatic and
Fixed drug eruption . . . . . . . . . . . . . . . . . . . . 102
includes short-term use of medium to high potency corticos-
Erythema multiforme . . . . . . . . . . . . . . . . . . . 104 teroids as well as oral antihistamines. Oral corticosteroids have
Erythema nodosum . . . . . . . . . . . . . . . . . . . . 108 been used in severe reactions, but in some cases have shown
no benefit. If the bites become superinfected, both topical and
Exfoliative dermatitis/Erythroderma . . . . . . . . . . . 111
oral antimicrobials are indicated.
Polymorphous light eruption . . . . . . . . . . . . . . . 113 Most of the literature regarding arthropod bites discusses
Urticaria . . . . . . . . . . . . . . . . . . . . . . . . . . 115 treatment of Cimex lenticularis, although it is sparse and no
randomized trials have been conducted. Data consists prima-
rily of case reports.

Arthropod bites Bedbug bites masquerading as urticaria. Scarupa MD,

Janelle Vega and David A Rodriguez Economides A. J Allergy Clin Immunol 2006; 117(6):
1508–1509.
Papular and urticarial reactions to arthropod bites are fre- 17 patients with bedbug bites were seen in a clinic. No data
quent, and can occur as a reaction to different species includ- is presented; however, the author describes that antihistamines
ing Sarcoptes scabiei (scabies),1 Cimex lectularius (bedbugs),2 decreased pruritus in most patients, although the clinical
mosquitoes, and less commonly Tunga penetrans (tungiasis). appearance of the lesions did not change. Patients did not
Bullae are a rare occurrence in response to arthropod bites respond well to high dose oral corticosteroids.
and their development is mediated by a Type I hypersen�
sitivity reaction to antigens derived from saliva and fluid trans-
ferred during the bite.3 Patients often report the sudden Disseminated bullous eruption with systemic reaction
onset of a pruritic eruption, but not all patients will recall an caused by Cimex lectularius. Liebold K, Schliemann-Willers S,
exposure to arthropods prior to the onset of the itching. The Wollina U. J Eur Acad Dermatol Venereol 2003; 17(4):
lesions may begin as erythematous papules and progress to 461–463.
vesicles and bullae; on occasion they may be associated with Case report of a patient who improved within 2 days with
purpura.4 oral antihistamines and topical corticosteroids.

First-Line Treatment
Second-Line Treatment

Oral antihistamines D
Oral corticosteroids E
Topical corticosteroids D

Targeted systemic therapy may be required for reactions There are scattered reports of improvement with oral corti-
caused by specific arthropods (i.e. bedbugs, scabies or tungia- costeroids, however most cases report no improvement with
sis) to eliminate the causative agent. There have not been any this oral therapy.

©2011 Elsevier Ltd, Inc, BV 101

 Part 1 Medical Dermatology
A case of imported bedbug (Cimex lectularius) infestation in
Israel. Mumcuoglu KY. Isr Med Assoc J 2008; 10(5):388–389.
A 22-year-old patient with pruritus was treated ‘repeatedly
with scabicides and systemic corticosteroids’ which did not
improve the itching. He finally improved after fumigation with
methyl bromide.
Special management & counseling considerations
Often, bullous insect bite reactions represent a diagnostic
dilemma as they can mimic other bullous dermatoses clini-
cally and histologically, especially bullous pemphigoid. They
may be distinguished by direct immunofluorescence.5 Bullous
arthropod reactions also occur more frequently in patients
with underlying systemic diseases such as malignant hemato-
logic disorders and systemic lupus erythematosus.6,7 It
is important to consider arthropod bites in the differential
of bullous dermatoses, especially in patients that are
immunocompromised.
Commonly encountered pitfalls
Patients with skin types III to VI often have post-inflammatory
hyperpigmentation after resolution of an insect bite reaction.
It is important to address this complication with the patient
in order to provide complete care. In treating PIH, the clinician
Fixed drug eruption
Ninad Pendharkar and Sonia Badreshia-Bansal
A fixed drug eruption (Fig. 6.1) is a common side effect of
certain medications. It is characterized by the sudden onset of
round or oval, red patches which may become edematous and
form vesicles, bullae, or erosions. In skin of color patients,
lesions may have a dusky or gray appearance. They may be
symptomatic with burning and/or pruritus. An important
characteristic of a fixed drug eruption is that it recurs at the
same site on the skin or mucous membranes with each expo-
sure to the medication. Although most patients, particularly
those of color, experience prolonged or permanent post-
inflammatory hyperpigmentation at the affected site, a non-
pigmenting variant does exist.
The incidence of fixed drug eruptions has been reported
between 2.5% and 22%. The variability in incidence is associ-
ated with geographic area, socioeconomic factors, literacy,
availability of medications and their use. Although fixed drug
eruptions have been reported in all age groups, they most
commonly occur in patients of ages 20–40 years (Table 6.1).
Both sexes are affected.
Histologically, an interface dermatitis is observed with
intraepidermal and subepidermal vesicle formation, necrotic
102
should consider medical therapies such as bleaching creams
(hydroquinones, azelaic acid), retinoids, corticosteroids, as
well as physical modalities to reduce pigmentation such as
dermabrasion, chemical peels, or laser treatments (Q-switched
ruby laser, fractional photothermolysis). These methods must
be used with caution to avoid further hyperpigmentation or
depigmentation, irritant dermatitis or hypertrophic scarring.8
References
1. Shahab RKA, Loo DS. Bullous scabies. J Am Acad Dermatol 2003;
49:346–350.
2. Goddard J, deShazo R. Bedbugs (Cimex lectularius) and clinical conse-
quences of their bites. JAMA 2009; 301(13):1358–1366.
3. Leverkus M, Jochim RC, Schäd S, Bröcker EB, Andersen JF, Valenzuela
JG, et al. Bullous allergic hypersensitivity to bedbug bites mediated by
IgE against salivary nitrophorin. J Invest Dermatol 2006; 126:91–96.
4. Bircher A. Systemic immediate allergic reactions to arthropod stings
and bites. Dermatology 2005; 210:119–127.
5. Shahab RKA, Loo DS. Bullous scabies. J Am Acad Dermatol 2003;
49:346–350.
6. Dodiuk-Gad RP, Dann EJ, Bergman R. Insect bite-like reaction associ-
ated with mantle cell lymphoma: a report of two cases and review of
the literature. Int J Dermatol 2004; 43:754–758.
7. Blum RR, Phelps RG, Wei H. Arthropod bites manifesting as recurrent
bullae in a patient with chronic lymphocytic leukemia. J Cutan Med
Surg 2001; 5:312–314.
8. Katz TM, Goldberg LH, Firoz BF, Friedman PM. Fractional thermolysis
for the treatment for post-inflammatory hyperpigmentation. Dermatol
Surg 2009; 35:1844–1848.
keratinocytes and a mixed superficial and deep infiltrate.1,2 The
stratum corneum is usually normal, with papillary dermal
fibrosis and deep perivascular pigment incontinence.
The diagnosis of a fixed drug eruption is based primarily
on a precise clinical history or drug exposure. The recurrence
of the skin lesion at the site of a previous lesion upon
re-exposure to the medication supports the diagnosis. The
primary treatment for fixed drug eruptions is discontinuing
and avoiding the offending medication. However, spontane-
ous resolution of fixed drug eruptions has been reported.
First-Line Therapies
Identify and discontinue use of medication E
Avoid use of implicated medication and chemically E
related medications
Topical corticosteroids D
Fixed drug eruption (FDE): changing scenario of incrimi-
nating drugs. Sehgal V, Srivastava G. Int J Dermatol 2006;
45:897–908.
Review article emphasizing the most common medications
implicated in fixed drug eruptions and the respective sites of
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Fixed drug eruption
A
B whether environmental factors are responsible for a higher
Figure 6.1:╇ (A) Fixed drup eruption secondary to trimethoprim-sulfamethoxazole.
(B) Fixed drug eruption secondary to ciprofloxacin. As lesions heal circular areas of
hyperpigmentation are commonly seen. (Courtesy of Dermatology, Elsevier, 2nd
ed., 2008.)
lesions. Also discusses the non-pigmenting and bullous variant
of fixed drug eruption. Recommended treatment is avoiding
the offending medication.
Fixed drug eruption. A brief review. Korkij W, Soltani K. Arch
Dermatol 1984; 120:520–524.
Review article highlighting the epidemiology, clinical fea-
tures, etiology, pathogenesis, and treatment of fixed drug
eruptions. Recommended treatment is avoiding the offending
medication.
Table 6.1╇ Causes of fixed drug eruption1,2
Antibacterial agents: trimethoprim-sulfamethoxazole (most common),
tetracycline, penicillins, erythromycin, rifampicin, clarithromycin,
fluoroquinolones, and metronidazole
Antifungal agents: griseofulvin, fluconazole, ketoconazole, terbinafine
Anticonvulsants: barbiturates (common), carbamazepine, lamotrigine,
chlordiazepoxide, oxazepam
Non-narcotic analgesics: especially pyrazolone derivatives,
phenylbutazone and oxyphenbutazone, aspirin, ibuprofen,
acetaminophen, naproxen, piroxicam, chlormesanone, celecoxib
Phenolphthalein in laxatives
Anesthetic agents
Antihistamines: cetirizine, hydroxyzine, loratidine, diphenhydramine
Antiplatelet agents: ticlopidine
Decongestants: amlexanon, citiolone, pseudoephedrine, and codeine
Botulinum toxin
Ondansetron
Quinine, quinacrine
Chinese and Japanese herbs
Commonly encountered pitfalls
In deeply pigmented races, fixed drug eruptions may present
as a diffuse hypomelanosis. Involvement can be widespread
involving the face, trunk, and extremities, and is usually
symmetric. This unique clinical picture presents diagnostic
difficulty.1
Fixed drug reactions were reported more commonly in the
Indian literature. This raises the question of whether this
patient population has a genetic predisposition to developing
fixed drug eruptions, increased exposure to causative agents or
prevalence.3,4 Further studies would be necessary to further
elucidate this association.
Special management & counseling considerations
Some reports suggest patients with HLA-B22 are more likely
to develop fixed drug eruptions. Medications that cause fixed
drug eruption usually are taken intermittently. NSAIDs are the
most commonly implicated class of medications causing lip
involvement. Sulfonamides are the most common cause of
genital fixed drug eruptions.4
Although systemic symptoms are unusual with fixed
drug eruptions, anorexia, malaise, fever, nausea, diarrhea,
abdominal pain and dysuria may occur.1 Rarely, a generalized
bullous variant of fixed drug eruption may occur which can
be so severe that it mimicks Stevens–Johnson syndrome
or toxic epidermal necrolysis.1 Rifampicin, metronidazole,
103
 Part 1 Medical Dermatology

paracetamol, paclitaxel, vinburnine, erythromycin, and ibu-

profen have all been implicated in causing generalized bullous
fixed drug reaction. The non-pigmenting variant of fixed drug
eruption is commonly caused by pseudoephedrine.2
The prognosis for fixed drug eruptions is good, with most
patients noting resolution within weeks of discontinuation of
the offending medication. However, some patients may experi-
ence the same eruption when a related compound is taken.
For example, sulfonamides can induce an exacerbation in a
dapsone sensitive patient.5 Patch testing may be beneficial in
identifying offending agents. However, a reaction will only be
noted in a previously affected area of skin.2
References
1. Sehgal V, Srivastava G. Fixed drug eruption (FDE): changing scenario
of incriminating drugs. Int J Dermatol 2006; 45:897–908.
2. James WH, Berger TG, Elston DM. Andrews’ Diseases of the skin: clini-
cal dermatology. 10th ed. Philadelphia, PA: Saunders Elsevier; 2006.
p. 127–128.
3. Gupta R. Drugs causing fixed drug eruptions: confirmed by provoca-
tion tests. Indian J Dermatol Venereol Leprol 2003; 69(2):120–121.
4. Pudukadan D, Thappa, D. Pattern of drug eruption in south India.
Indian J Dermatol Venereol Leprol 2004; 70(1):20–24.
5. Korki, W, Soltani K. Fixed drug eruption. A brief review. Arch Dermatol
1984; 120:520–524.

Erythema multiforme
Ninad Pendharkar and Sonia Badreshia-Bansal

Erythema multiforme (EM) is considered a self-limited disease

characterized by well circumscribed erythematous macules
that progress to raised edematous papules or plaques with a
ring of erythema at the periphery and a flat, dusky, purpuric-
appearing central area (Figs. 6.2–6.5). Lesions are often
described as targetoid. EM commonly occurs in young adults,
with multiple episodes, each lasting 1–4 weeks.
Etiologies of EM are varied and are listed in Table 6.2. In
general, the most commonly implicated medications include
sulfonamides and other antibiotics, NSAIDs, allopurinol, and
anticonvulsants. An Indian study reported anticonvulsants, Figure 6.2:╇ Targetoid lesions of erythema multiforme on the plantar surface.
(Courtesy of Stacy Klepeiss, MD; Department of Dermatology, Penn State Milton S.
antibiotics, and NSAIDs being the classes of medications most
Hershey Medical Center.)
frequently implicated in the development of Stevens–Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN) in their
population.1 In most skin of color patients, medications are
a very common cause of EM. A Malaysian study reported
cases of SJS/TEN associated with first line anti-tuberculosis
medications listed in Table 6.3. A Kenyan study reported a
case of bullous EM in a patient treated with combination
antimalarials.4 Some reports suggest strong associations of
HLA-B 1502 and HLA-B 5801 with carbamazepine- and
allopurinol-induced EM in the Han Chinese population.5
Another association was found between HLA-B 5801 and
allopurinol induced SJS/TEN in Japanese patients.6 Many anti-
retroviral agents have been associated with SJS/TEN. With the
high prevalence of HIV in Africa and Asia, it is of particular
importance to have a high index of suspicion for EM/SJS/TEN
in patients from these areas.7
Basal vacuolar change with interface dermatitis is seen his-
topathologically in erythema multiforme.2 Additionally, spon-
giosis and edema of the papillary dermis may also be observed
with formation of intraepidermal and subepidermal vesicles
and bullae. The dermal infiltrates consist predominantly of Figure 6.3:╇ Penile lesions of erythema multiforme. (Courtesy of Stacy Klepeiss,
monocytes, with some lymphocytes and eosinophils. MD; Department of Dermatology, Penn State Milton S. Hershey Medical Center.)

104
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Erythema multiforme
Figure 6.4:╇ Oral lesions of erythema multiforme. (Courtesy of Stacy Klepeiss, MD;
Department of Dermatology, Penn State Milton S. Hershey Medical Center.)
Figure 6.5:╇ Stevens–Johnson syndrome. (Courtesy of Sonia Badreshia-Bansal,
MD.)
Table 6.2╇ Causes of erythema multiforme2
Herpes simplex-associated EM (most common)
Mycoplasma-induced EM / SJS
Medications
Radiation
Idiopathic
Historically SJS/TEN were considered part of a continuum
of EM. However, recent literature suggests that EM is a distinct
entity from SJS and TEN. EM is strongly linked to an anteced-
ent herpetic infection, while SJS and TEN are linked to medica-
tion. However, some overlap does exits. Hence, SJS and TEN
will be discussed in this section.
Table 6.3╇ Medications commonly implicated in EM, SJS and TEN1,2
Trimethoprim-sulfamethoxazole
Sulfadoxine-pyrimethamine
Nevirapine
Lamotrigine
Carbamezapine
Pencillins
NSAIDs
Allopurinol
Quinolones
Anti-tuberculosis medications (rifampin, isoniazid, ethambutol,
pyrazinamide)
Anti-retroviral medications (amprenavir, fosamprenavir, atazanavir,
darunavir, efavirenz, etravirine, abacavir)
Anti-malarial agents
SJS and TEN are bullous skin diseases that represent an
adverse reaction to medication (Table 6.3). SJS is characterized
by cutaneous targetoid lesions with vesicles and erosions
coupled with mucous membrane involvement (oral, conjunc-
tival, and genital mucosa) (Fig. 6.5). In SJS, there is usually
<10% body surface area involvement. SJS/TEN overlap is
defined by 10–30% body surface area involvement, while TEN
is considered epidermal detachment involving >30% body
surface area. The incidence of TEN and SJS is rare, 0.4–1.2 per
million person-years and 1.2–6.0 per million person-years
respectively. The pathogenesis of these entities is still contro-
versial with many mechanisms proposed.
Histopathologically, a lymphocytic infiltrate at the der-
moepidermal junction with necrosis of keratinocytes and epi-
dermal detachment is characteristic of SJS/TEN.2
Management of EM can be difficult since the exact etiology
is difficult to identify in many cases. Since herpes simplex virus
(HSV) infection is the most common cause of EM, antiviral
treatment may be of benefit. For patients with recurrent or
chronic EM other treatment options including immunosup-
pressants may be warranted.
First-Line Therapies for EM
Acyclovir B
A double-blind, placebo-controlled trial of continuous acy-
clovir therapy in recurrent erythema multiforme. Tatnall F,
Schofield JK, Leigh IM. Br J Dermatol 1995; 132(2):267–270.
Six of 11 patients treated with acyclovir 400╯mg twice daily
for 6 months had no episodes of EM, while all patients in the
placebo group continued to have episodes. Two patients dem-
onstrated complete remission of disease. One patient with
105
 Part 1 Medical Dermatology
non-herpes associated EM also demonstrated suppression of
disease with acyclovir.
Continuous treatment with acyclovir 400╯mg twice daily is
useful in suppressing EM, and can be used in non-herpes associ-
ated EM as well. Acyclovir can be used for more than six
months given its favorable long-term safety profile.
Second-Line Therapies for EM
Dapsone D multiforme; report of two cases. Conejo-Mir J, del Canto S,
Azathioprine D Muñoz MA, Rodríguez-Freire L, Serrano A, Hernandez C,
Thalidomide E Pulpillo A. J Drugs Dermatol 2003; 2(1):40–44.
Potassium iodide D
Mycophenolate mofetil D major adverse event with thalidomide, in addition to tera-
Systemic corticosteroids D togenicity, is neuropathy, which can be monitored with nerve
Recurrent erythema multiforme: Clinical characteristics,
etiologic associations, and treatment in a series of 48
patients at Mayo Clinic, 2000 to 2007. Wetter D, Davis M.
J Am Acad Dermatol 2010; 62:45–53.
This was a retrospective review of 48 patients with recurrent
EM. 37 patients received systemic corticosteroids, which led to
disease control. However, upon tapering or discontinuing the
medication a significant flare in their disease was noted. 16 of
33 patients receiving continuous antiviral treatment demon-
strated partial or complete disease suppression. 6 of 8 patients
receiving mycophenolate mofetil (≤2╯g daily) noticed partial
or complete response. Dapsone (≤200╯mg daily) was used to
treat 10 patients, 5 of whom showed partial or complete
response. Azathioprine (≤200╯mg daily) elicited partial or
complete response in 2 of 5 patients. One of 3 patients treated
with IVIG showed a complete response. Thalidomide, flucona-
zole, itraconazole, and azithromycin were used in one patient
each and demonstrated a complete response. One of 6 patients
with hydroxychloroquine had partial response, while the
one patient treated with pentoxyfylline had partial response.
Methotrexate, colchicine, cyclosporine, minocycline, erythro-
mycin, potassium iodide, and sulfasalazine did not elicit any
responses.
Azathioprine therapy in the management of persistent
erythema multiforme. Jones R. Br J Dermatol 1981;
105(4):465–467.
2 patients treated with azathioprine 100–150╯mg daily
noticed improvement in disease allowing a decrease in their
dose of corticosteroids.
Dapsone in the treatment of persistent erythema multi-
forme. Hoffman L, Hoffman M. J Drugs Dermatol 2006;
5(4):375–376.
Case report of one patient with persistent EM successfully
treated with dapsone.
106
Potassium iodide in erythema nodosum and other ery-
thematous dermatoses. Horio T, Danno K, Okamoto H,
Miyachi Y, Imamura S. J Am Acad Dermatol 1983;
9(1):77–81.
14 of 16 patients with EM treated with potassium iodide
300╯mg three times daily noticed complete resolution after 1
week of treatment. The medication was discontinued after 2
weeks of treatment with only one patient demonstrating a
recurrence.
Thalidomide as elective treatment in persistent erythema
Report of two cases of severe persistent EM treated with
thalidomide resulting in complete disease suppression. The
conduction studies.
Management of SJS/TEN is similar to that of a patient with
extensive burns. Therefore, patients should be managed in a
specialized burn unit where appropriate nutritional support,
skin care, eye care, and pain control can be provided. The use
of corticosteroids and IVIg is controversial. Some studies
suggest that intravenous corticosteroids in the initial stages of
TEN may help reduce mortality. However, other studies
point to an increased mortality with the use of corticosteroid
therapy. There are studies that suggest IVIg may reduce the
mortality rate from TEN, whereas others demonstrated no
significant benefit. Seemingly, there is no consensus regarding
treatment.
First-Line Therapies for SJS/TEN
Systemic corticosteroids C
IVIG B
Plasmapheresis D
Cyclosporine D
Supportive care (ocular care, pain control, wound care, E
nutrition support)
Topical corticosteroids E
Antihistamines E
Intravenous immunoglobulin treatment for Stevens–
Johnson syndrome and toxic epidermal necrolysis. Bachot
N, Bachot N, Revuz J, Roujeau JC. Arch Dermatol 2003;
139:33–36.
This is a prospective open trial of 34 consecutive patients
with SJS, TEN or overlap treated with 2╯g/kg of IVIg within 2
days of onset of symptoms. The proportion of epidermal
detachment was measured before and after treatment and the
death rate was estimated on admission based on a SCORTEN
(a calculated prognosis score).The confidence interval of the
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Erythema multiforme
observed death rate showed no decrease in the mortality with
treatment, and there was no effect on the progression of
detachment.
Status of plasmapheresis for the treatment of toxic epider-
mal necrolysis in Japan. Yamada H, Takamori K. Therapeutic
Apheresis Dialysis 2008; 12(5):355–359.
This study reviewed 47 TEN patients treated with plas-
mapheresis, 36 of whom had been unresponsive to treatment
with corticosteroids. The number of plasmapheresis sessions
ranged from 1 to 6 with a mean of 3.1. Both simple plasma
exchange filtration and double filtration plasmapheresis were
utilized and the rate of effectiveness was 80.9%. There were
11 deaths.
Toxic epidermal necrolysis/Stevens–Johnson syndrome:
current trends in management. Dalli R, Kumar R, Kennedy
P, Maitz P, Lee S, Johnson R. Aust NZ J Surg 2007; 77:
671–676.
Retrospective chart review of 16 patients with SJS/TEN iden-
tifying trends in outcomes based on the selection of dressing.
Cases earlier in the study utilized Vaseline-impregnated gauze,
while cases after 2003 used nanocrystalline silver dressings.
Fewer dressing changes were required with this dressing type
allowing rapid re-epithelialization, decreased need for skin
grafting, and no adverse effects.
There is very limited data and more studies are necessary.
Corticosteroid therapy in an additional 13 cases of Stevens–
Johnson syndrome: a total series of 67 cases. Tripathi D,
Ditto AM, Grammer LC, Greenberger PA, McGrath KG, Zeiss
CR, Patterson R. Allergy Asthma Proc 2000; 21(2):101–105.
13 consecutive patients with SJS were treated with intrave-
nous methylprednisolone 160–240 mg daily upon admission
resulting in no mortality or permanent sequelae due to SJS.
One death was unrelated to SJS.
Dexamethasone pulse therapy for Stevens–Johnson
syndrome/toxic epidermal necrolysis. Kardaun A, Jonkman
M. Acta Derm Venereol 2007; 87:144–148.
Retrospective study of 12 patients with SJS/TEN treated with
short-term dexamethasone pulse therapy. The first 4 patients
received dexamethasone 100╯mg intravenously daily for 3 con-
secutive days with one dose of cyclophosphamide 500╯mg
on the first day. The remaining patients received dexametha-
sone 1.5╯mg/kg body-weight intravenously for 3 consecutive
days. Disease stabilization occurred after 2.3 days on average,
and total re-epithelialization after 13.9 days. One patient
died.
Toxic epidermal necrolysis and systemic corticosteroids.
Stables G, Lever RS. Br J Dermatol 1993; 128:357.
Case report of a patient with TEN successfully treated with
prednisolone 60╯mg daily.
Toxic epidermal necrolysis treated with cyclosporine. Hewitt
J, Ormerod A. Clin Exp Dermatol 1992; 17:264–265.
Two cases of TEN treated successfully with cyclosporine.
One patient received 3.6╯mg/kg/day while the other received
3╯mg/kg/day.
Treatment of toxic epidermal necrolysis with cyclosporine
A. Arévalo J, Lorente JA, González-Herrada C, Jiménez-Reyes
J. J Trauma. 2000; 48:473–478.
11 consecutive patients with TEN treated with cyclosporine
3╯mg/kg daily were compared to six historic controls treated
with cyclophosphamide and corticosteroids. Patients treated
with cyclosporine demonstrated improved outcomes meas-
ured as rapid re-epithelialization, less multi-organ failure, and
reduced mortality.
Commonly encountered pitfalls
A study from Taiwan reviewed the cases of 30 pediatric patients
with EM, SJS, TEN or SJS/TEN overlap. The most common
etiology of EM was infection (particularly Mycoplasma pneumo-
nia), while medications (most commonly carbamazepine)
accounted for almost all cases of SJS/TEN. Patients were ini-
tially treated with 1–2╯mg/kg/day of prednisolone. Those who
showed a poor response were then treated with IVIG. No
mortality was noted in this group.8 Another study from Japan
demonstrated a decrease in mortality from both SJS and TEN
from over the past 17 years.9 Patients in this group were treated
with a combination of corticosteroids, IVIG, and/or plas-
mapheresis. The liver was the most commonly involved inter-
nal organ. Conversely, a study from Singapore revealed no
improvement in outcomes in pediatric patients with SJS and
TEN treated with IVIg or systemic steroids.10 This further high-
lights the controversy over the treatment of these conditions.
Also, most studies suggest that early institution of therapy
leads to better outcomes. However, diagnosing SJS/TEN in its
early stages can be difficult.
Special management & counseling considerations
Ocular complications are common in patients with SJS/TEN
and early ophthalmologic care is warranted. A prospective case
series of 5 patients with SJS/TEN demonstrated that the appli-
cation of topical betamethasone 5 times daily to the eyes for
2 weeks prevented corneal epithelial stem cell loss and cicatri-
cial changes.11
Mucosal involvement is also common in SJS/TEN resulting
in odynophagia, poor oral intake, and increased aspiration
risk. A retrospective study of patients with SJS/TEN with
mucosal involvement discussed the role of a speech patholo-
gist in minimizing odynophagia and promoting safe oral
intake thereby facilitating nutritional input necessary for
recovery.12
It is important to closely monitor skin of color patients
on anti-retroviral agents from Africa and Asia for signs of
EM/SJS/TEM.7
107
 Part 1 Medical Dermatology

7. Borrás-Blasco J, Navarro-Ruiz A, Borrás C, Casterá E. Adverse cutaneous

References
1. Sharma V, Sethuraman G. Adverse cutaneous reactions to drugs: an
overview. J Postgrad Med 1996; 42(1):15–22.
2. James WH, Berger TG Elston DM. Andrews’ Diseases of the skin: clini-
cal dermatology. 10th ed. Philadelphia, PA: Saunders Elsevier; 2006.
p. 129–130 and 140–142.
3. Tan W. Two years of review of cutaneous adverse drug reaction from
first line anti-tuberculous drugs. Med J Malaysia 2007; 62(2):
143–146.
4. Remich A, Otieno W, Polhemus ME, Ogutu B, Walsh DS. Bullous
erythema multiforme after treatment with malarone, a combination
antimalarial composed of atovaquone and proguanil hydrochloride.
Trop Doct 2008; 38(3):190–191.
5. Man C, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, et al. Association
between HLA-B 1502 allele and antiepileptic drug-induced cutaneous
reactions in Han Chinese. Epilepsia 2007; 48(5):1015–1018.
6. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, JSAR
research group, et al. HLA-B locus in Japanese patients with anti-
epileptics and allopurinol-related Stevens–Johnson syndrome and
toxic epidermal necrolysis. Pharmacogenomics 2008; 9(11):1617–
1622.
reactions associated with the newest antiretroviral drugs in patients
with human immunodeficiency virus infection. J Antimicrob
Chemother 2008; 62:879–888.
8. Lam NS, Yang YH, Wang LC, Lin YT, Chiang BL. Clinical characteristics
of childhood erythema multiforme, Stevens–Johnson syndrome, and
toxic epidermal necrolysis in Taiwanese children. J Microbiol Immunol
Infect 2004; 37:366–370.
9. Yamane Y, Aihara M, Ikezawa Z. Analysis of Stevens–Johnson syn-
drome and toxic epidermal necrolysis in Japan from 2000–2006.
Allergol Int 2007; 56:419–425.
10. Koh M, Tay Y. Stevens–Johnson syndrome and toxic epidermal necrol-
ysis in Asian children. J Am Acad Dermatol 2010; 62:54–60.
11. Araki Y, Sotozono C, Inatomi T, Ueta M, Yokoi N, Ueda E, et al.
Successful treatment of Stevens–Johnson syndrome with steroid pulse
therapy at disease onset. Am J Ophthalmol 2009; 147(6):
1004–1011.
12. Clayton N, Kennedy P. Management of dysphagia in toxic epidermal
necrolysis (TEN) and Stevens–Johnson syndrome (SJS). Dysphagia
2007; 22:187–192.

Histopathologically, EN is a septal panniculitis.1 The inflam-

Erythema nodosum matory infiltrate involves the connective tissue septa between
the fat lobules. Early lesions are characterized by a neutrophilic
infiltrate with some edema and hemorrhage. Later lesions
Ninad Pendharkar and Sonia Badreshia-Bansal reveal a mixed infiltrate of lymphocytes, histiocytes, and multi-
nucleated giant cells. Miescher’s radial granuloma is a charac-
Erythema nodosum (EN), the most commonly encountered teristic feature of EN which is an aggregation of histiocytes
panniculitis, is characterized by an acute eruption of erythema- around stellate and banana-shaped clefts. Leukocytoclastic
tous, tender nodules and plaques (Fig. 6.6). usually on the vasculitis is not seen.
extensor surfaces of the lower extremities. Often bilateral and
symmetrical, the lesions may also occur on the upper legs,
extensor arms, neck and face. Initially, the skin overlying the
nodules is bright red, smooth, elevated, and shiny. Within a
few days they may become flat with a purplish color resem-
bling a deep bruise. EN can be associated with malaise,
leg edema, arthritis, arthralgias, fever, headache, episcleritis,
conjunctivitis and gastrointestinal complaints. The lesions
spontaneously resolve over days to weeks without residual
scarring, ulceration or atrophy. However, in some patients with
skin of color, these lesions may heal with post inflammatory
hyperpigmentation (Fig. 6.6).1
Acute EN is a reactive process and may occur at any age with
the peak incidence between 20 and 30 years of age. It is more
frequent in young women with a female to male ratio of 3–6:1.
Variation in incidence is seen based upon race and geographic
differences. This is due to differences observed in the preva-
lence of diseases which are the etiologic factors of EN. The
causes of acute EN are listed in Table 6.4.
A chronic variant of EN has been reported which occurs
more often in older women, is unilateral or asymmetric, and
is not associated with systemic symptoms. With a prolonged Figure 6.6:╇ Patient with erythema nodosum and healing post inflammatory
course of months to years, the lesions are painless or less hyperpigmentation. (Courtesy of Renee Straub, MD; Department of Dermatology,
tender, and are not associated with underlying diseases. Penn State Milton S. Hershey Medical Center.)

108
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Erythema nodosum

Review article that discusses the report by Schulz & Whiting

Table 6.4╇ Causes of erythema nodosum1 in 1976 that 24 of 28 patients with erythema nodosum and
16 of 17 patients with erythema induratum achieved sym�
Infections Streptococcal infections (most common) ptomatic relief in 2 days with resolution in 2 weeks after treat-
Tuberculosis ment with potassium iodide with doses of 360–900╯mg daily.
Atypical mycobacterial infections Other articles outlining uses of potassium iodide are also
Yersinia discussed.
Salmonella
Shigella Potassium iodide in erythema nodosum and other ery-
Coccidiomycosis thematous dermatoses. Horio T, Danno K, Okamoto H,
Histoplasmosis Miyachi Y, Imamura S. J Am Acad Dermatol 1983; 9(1):
Sporotrichosis 77–81.
Blastomycosis 12 of 16 patients observed relief of symptoms with resolu-
Toxoplasmosis tion in 10–14 days after treatment with potassium iodide
Brucellosis 300╯mg three times daily. 6 patients noted recurrent attacks
Psittacosis over the next 1–12 months which resolved with similar treat-
Cat-scratch disease ment with potassium iodide.
HIV
Drugs Oral contraceptives and hormone replacement Chronic erythema nodosum treated with indomethacin.
therapy (most common) Barr W. Ann Intern Med 1981; 95(5):659.
Sulfonamides Case report of a 32-year-old female with EN successfully
Bromides treated with indomethacin 25╯mg three times daily for 1
Selective serotonin reuptake inhibitors month.
Anti-TNF alpha agents
Interferon alpha Suppression of erythema nodosum by indomethacin.
Echinacea Ubogy Z, Persellin R. Acta Derm Venereol 1982; 62(3):
Systemic diseases Sarcoidosis 265–266.
Inflammatory bowel disease 3 patients with severe EN secondary to streptococcal phar-
Behcet’s disease yngitis unresponsive to treatment with aspirin and oral anti-
Hematologic malignancies biotics were treated with indomethacin 100–150╯mg daily for
2 weeks. All noted resolution of cutaneous as well as systemic
Sweet’s syndrome
symptoms.

Control of chronic erythema nodosum with naproxen.

Lehman C. Cutis 1980; 26(1):66–67.
First-Line Therapies Case report of patient with EN for 2 years unresponsive
to aspirin and phenylbutazone who was treated with naproxen
Discontinue offending medication E 250╯mg twice daily for 1 month with resolution of symptoms.
Treat underlying or associated cause E Upon discontinuing naproxen she noted recurrence of symp-
Aspirin and NSAIDs D toms, which responded to treatment with naproxen.
Curtailing vigorous physical activities E
Potassium iodide D Second-Line Therapies

Colchicine E
Erythema nodosum. Requena L, Sanchez Yus E. Dermatol Hydroxychloroquine E
Clin 2008; 26:425–438. Corticosteroids (systemic and intralesional) E
Review article highlighting etiologies of erythema nodosum,
clinical features, workup, and treatment options. Aspirin and
NSAIDs such as oxyphenbutazone, 400╯mg daily, indometh- Hydroxychloroquine and chronic erythema nodosum. Jarrett
acin 100–150╯mg daily or naproxen 500╯mg daily provided P, Goodfield M. Br J Dermatol 1996; 134(2):373.
analgesia and resolution of symptoms. Colchicine 0.6–1.2╯mg Report of patients with chronic erythema nodosum
bid is reported to be a useful second line treatment. responding to hydroxychloroquine 200╯mg twice daily.

Potassium iodide in dermatology: a 19th century drug for Erythema nodosum treated with colchicine. Wallace S. JAMA
the 21st century – uses, pharmacology, adverse effects, and 1967; 202:144.
contraindications. Sterling J, Heymann W. J Am Acad Derma- Case report of one patient with EN successfully treated with
tol 2000; 43:691–697. colchicines.

109
 Part 1 Medical Dermatology
Third-Line Therapies
Anti-TNF agents E In areas with endemic tuberculosis, it is important to rule out
Mycophenolate mofetil E
Etanercept treatment of erythema nodosum. Boyd A.
Skinmed 2007; 6(4):197–199.
Case report of one patient with chronic erythema nodosum
refractory to treatment with oral corticosteroids, NSAIDs,
dapsone, saturated solution of potassium iodide (SSKI) and
methotrexate with no underlying systemic illness treated suc-
cessfully with etanercept. She received 25╯mg subcutaneously
twice weekly for 6 months, followed by a maintenance dose
of 25╯mg weekly, resulting in sustained clearance of her lesions.
Refractory chronic erythema nodosum successfully treated
with adalimumab. Ortega-Cnento N, Callejas-Rubio JL,
Sanchez-Cano D, Caballero-Morales T. JEADV 2007; 21:
408–410.
Letter to the editor discussing the case of a patient with
chronic erythema nodosum without any underlying etiology
refractory to multiple systemic treatments who noted resolu-
tion with adalimumab treatment 40╯mg subcutaneously every
14 days. Seven months after starting therapy, the patient dem-
onstrated sustained response to adalimumab.
Treatment of chronic erythema nodosum with infliximab.
Clayton T, et╯al. Clin Exp Dermatol 2006; 31:823–824.
Case report describing a patient with inflammatory bowel
disease and erythema nodosum refractory to multiple systemic
agents treated successfully with infliximab. After receiving
5╯mg/kg of infliximab at 0, 2, and 6 weeks, she demon�
strated a dramatic response in her gastrointestinal as well as
cutaneous disease. She maintained good disease control with
infliximab infusions every 3 months.
It is unclear whether the improvement in the patient’s erythema
nodosum was due to the effect of infliximab on her cutaneous
lesions or due to the improvement of her underlying inflamma-
tory bowel disease.
Use of mycophenolate mofetil in erythema nodosum. Boyd
A. J Am Acad Dermatol 2002; 47(6):968–969.
Letter to the editor describing an EN patient unresponsive
to treatment with NSAIDs, methotrexate, colchicine, and aza-
thioprine successfully treated with mycophenolate mofetil.
Initially she received 500╯mg twice daily for 3 weeks with
stabilization of her disease. Her dose was then increased to
1500╯mg daily. After 3 months of treatment she noticed reso-
lution of her disease with a sustained response upon being
weaned off mycophenolate mofetil.
110
Commonly encountered pitfalls
this diagnosis as the underlying cause of EN before attributing
the eruption to other causes such as medications.1 Intradermal
tuberculin test should be performed in these patients as well
as those whose history raises concerns for tuberculosis expo-
sure. Additionally, a detailed clinical history including travel
history to areas known for endemic tuberculosis infections is
important for all patients. A study from Thailand identified
the most common cause of EN in 154 patients over a 10-year
period was tuberculosis.2 In contrast, a retrospective study
from Singapore showed that the etiologies of EN are similar
to those in Western industrialized nations.3 An Israeli study
demonstrated that in Israeli children most cases of erythema
nodosum were related to streptococcal and Epstein–Barr virus
infections or chronic inflammatory conditions like inflamma-
tory bowel disease.4
Special management & counseling considerations
EN seen in Lofgren’s syndrome (sarcoidosis, fever, cough, joint
pain, bilateral hilar adenopathy, and erythema nodosum) is
seen more commonly in Scandinavian, Irish and Puerto Rican
women.5 A chest X-ray to rule out pulmonary disease as the
underlying etiology is important.5
A throat culture and antistreptolysin O titer are indicated
for most patients with EN since streptococcal infection is a
common trigger.1 Also, there are reports of patients with HIV
who present with EN.6 As a result, HIV should be considered
as a possible etiology, especially in high risk patients. In
patients with EN related to tuberculosis, thalidomide is a com-
monly used treatment.
References
1. Requena L, Yus E. Erythema nodosum. Dermatol Clin 2008;
26:425–438.
2. Tantisirin O, Puavilai S. Long-term follow-up of erythema nodosum.
J Med Assoc Thai 2003; 86(12):1095–1100.
3. Tay Y. Erythema nodosum in Singapore. Clin Exp Dermatol 2000;
25(5):377–380.
4. Garty B, Pozananski O. Erythema nodosum in Israeli children. IMAJ
2000; 2:145–151.
5. James WH, Berger TG, Elston DM. Andrews’ Diseases of the skin: clini-
cal dermatology, 10th edn. Philadelphia, PA: Saunders Elsevier; 2006:
487–489.
6. Loutherenoo W, Lertprasertsuke N, Kasitanon N, Sukitawut W.
Erythema nodosum as a manifestation of HIV infection. Asian Pac J
Allergy Immunol 2002; 20(3):175–178.
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Exfoliative dermatitis/Erythroderma

Exfoliative dermatitis/ Table 6.5╇ Causes of exfoliative dermatitis1,2

Erythroderma
Systemic diseases Lymphoma – primarily cutaneous T-cell
(10–40%) lymphoma (CTCL)
Leukemia
Ninad Pendharkar and Sonia Badreshia-Bansal Multiple myeloma
Carcinoma of the lung, prostate, colon, and
Exfoliative dermatitis, or erythroderma, is a general erythema-
thyroid
tous, scaly dermatitis associated with high morbidity and vari-
able mortality rates. Usually due to the generalization of a Graft-versus-host disease
pre-existing dermatosis; medications, internal malignancies, Immunodeficiency, including HIV
mycosis fungoides, and immune disorders may also cause Hodgkin disease
erythroderma. Exfoliative dermatitis may be idiopathic. The
Cutaneous diseases Psoriasis
causes of exfoliative dermatitis are listed in Table 6.5. The
(10–40%) Seborrheic dermatitis
etiology of erythroderma is frequently difficult to establish,
Atopic dermatitis
and is usually delayed, due to the poor specificity of clinical
Stasis dermatitis
and histopathologic signs. In skin of color, the patient’s body
Contact dermatitis
surface is a dull scarlet color with small laminated scales that
Pityriasis rubra pilaris
show severe exfoliation. Involvement of the scalp with exten-
Pemphigus foliaceus
sive telogen effluvium may also be seen. Itching is severe and
Mycosis fungoides
is often accompanied by systemic symptoms including fever
Dermatophytosis
and chills. Patients may develop secondary infections. Severe
Lichen planus
complications associated with exfoliative dermatitis include
sepsis, high output cardiac failure, acute respiratory distress Drugs (3–10%) Dimercaprol (British anti-lewisite [BAL])
syndrome, and capillary leak syndrome. Exfoliative dermatitis Codeine
retains the histologic features of the original disease process.1 Captopril
However, non-specific findings such as hyperkeratosis, acan- Diphenylhydantoin
thosis and focal parakeratosis can be seen. Treatment of exfo- Gold
liative dermatitis is variable and targets the underlying disease Iodine
state. Supportive treatment is aimed at the skin, cardiovascular Antimicrobials – sulfas, penicillin (PCN),
and respiratory systems, and treating infection. cephalosporins, minocycline, isoniazid
Granulocyte colony-stimulating factor (GCSF)
Phenytoin
First-Line Therapies Allopurinol
Mercury
Treat underlying cause E Arsenic
Bedrest E Quinidine
Supportive treatment: protect from hypothermia, cool E Barbiturates
oatmeal baths, moisturization Trimethadione
Aspirin
Carbamazepine
(Acitretin reported)
Second-line Therapies
Idiopathic (15–45%)
Topical corticosteroids C
Systemic steroids D
PUVA C
Re-PUVA E
Extracorporeal photochemotherapy C Treatment of papuloerythroderma of Ofuji with Re-PUVA: a
Cyclosporine D case report and review of the therapy. Mutluer S, Yerebakan
O, Alpsoy E, Ciftcioglu MA, Yilmaz E. J Eur Acad Dermatol
Oral retinoid E
Venereol 2004; 18(4):480–483.
Infliximab E
Papuloerythroderma of Ofuji is characterized by intensely
Cytotoxic/antimetabolites E pruritic and widespread, red, flat-topped papules with sparing
UVA phototherapy E of the body folds and creases found commonly in elderly men.
Interferon alpha 2b E A case of a 60-year-old man who responded to retinoid plus
PUVA (Re-PUVA) treatment is reported.

111
 Part 1 Medical Dermatology
Long-term follow-up of patients with cutaneous T-cell lym-
phoma treated with extracorporeal photochemotherapy. Zic
JA, Stricklin GP, Greer JP, Kinney MC, Shyr Y, Wilson DC,
King LE Jr. J Am Acad Dermatol 1996; 35(6):935–945.
This study followed the long-term outcome of 20 patients
with cutaneous T-cell lymphoma (CTCL) treated with at least
6 months of extracorporeal photochemotherapy (ECP). A
complete response was obtained in 25% of patients, a partial
response (disappearance of at least 50% of lesions) in 25% of
patients, and 50% were weaned from ECP without relapse.
ECP is a safe, effective alternative therapy for refractory CTCL
that may induce a long-term, disease-free remission in a
minority of patients.
Oral bexarotene in a therapy-resistant Sézary syndrome
patient: observations on Sézary cell compartmentalization.
El-Azhary RA, Bouwhuis SA. Int J Dermatol 2005; 44(1):
25–28.
A 63-year-old man with therapy-resistant Sézary syndrome
was treated with oral bexarotene showing gradual improve-
ment in erythema, pruritus, and scale after 16 weeks. From
weeks 20 to 40, continued improvement of the erythroderma
was noted with a decrease in the lymph node burden. However,
the absolute Sézary cell count inversely increased. By week 40,
a recurrence of the pruritus and erythroderma was noted and
treatment was discontinued.
Bexarotene appears to be well tolerated but more studies are
needed.
Photoaccentuated erythroderma associated with CD4+
T lymphocytopenia: successful treatment with 5-
methoxypsoralen and UVA, interferon alfa-2b, and extracor-
poreal photopheresis. Wolf P, Müllegger R, Cerroni L,
Aigner R, Fueger G, Höfler G, et╯al. J Am Acad Dermatol 1996;
35(2 Pt 2):291–294.
This is a case of a 53-year-old man with chronic CD4+
T lymphocytopenia and photoaccentuated erythroderma
with lymphoma-like histologic changes whose erythroderma
responded completely to 5-methoxypsoralen and UVA (PUVA),
interferon alfa-2b, and extracorporeal photopheresis. However,
his course was complicated by opportunistic skin infections,
including tinea corporis, warts, and disseminated molluscum
contagiosum.
Psoriatic erythroderma and bullous pemphigoid treated
successfully with acitretin and azathioprine. Roeder C,
Driesch PV. Eur J Dermatol 1999; 9(7):537–539.
A 59-year-old male patient developed bullous pemphigoid
during chronic, severe psoriasis, which had been treated with
different topical treatments, PUVA, and UV-B radiations. The
patient was successfully treated with a combination of acitretin
and azathioprine (follow-up 28 months), thus avoiding the
need for systemic corticosteroid treatment.
Commonly encountered pitfalls
In the young, Black, male population, exfoliative dermatitis
may be a marker for HIV infection. Ofuji papuloerythroderma
112
has been documented in a patient with AIDS.3 A Singaporean
study shows exfoliative dermatitis was most common among
the elderly and Malay population, in comparison to Indians
and Chinese.4 A Pakistani study demonstrated the most fre-
quent causes of erythroderma were pre-existing dermatoses,
including psoriasis, dermatitis, ichthyosis, and pemphigus
foliaceus, followed by idiopathic cases, malignancy, and drugs.
Hair and nails were more frequently involved. Mucosal
involvement was common along with reports of the ‘deck
chair sign’ and islands of normal skin.5 In Thai patients, the
most common causative factors include drugs followed by
pre-existing dermatoses. Hepatomegaly, jaundice and abnor-
mal liver function tests were found more commonly in the
drug allergy group, while in cases with pre-existing dermatoses
nail involvement was a common finding.6 In Nairobi, derma-
toses and HIV/AIDS were the most frequent causes of erythro-
derma.7 An Iranian study showed the most common causative
factors were pre-existing dermatoses, followed by drug reaction
(most commonly from carbamazepine), malignancies, and
idiopathic cases. Apart from scaling and erythema, pruritus
was the most common finding, followed by fever, lymphaden-
opathy, edema, and hyperkeratosis. The onset was insidious
except in cases of drug-induced erythroderma, where it
was acute.2
In children, immunodeficiency should be suspected in
cases of severe erythroderma with alopecia, failure to thrive,
infectious complications, or evocative histologic findings. The
prognosis is poor with a high mortality rate in immunodefi-
ciency disorders and severe chronic diseases such as Nether-
ton’s syndrome.8 When Sézary cell syndrome is associated
with exfoliative dermatitis, rarely palmoplantar keratoderma
is associated.9
Underlying etiologic factors of erythroderma may show
geographic variations. However, clinical features are identical.
Special management & counseling considerations
It is important to perform laboratory studies based on clinical
suspicion or history that may help to establish the primary
cause of exfoliative dermatitis. These studies include evalua-
tion of vital signs and temperature, cardiac failure and renal
and intestinal dysfunction, CBC with differential, liver
enzymes, creatinine level, urinalysis, serum albumin, ESR,
HIV, T-cell receptor analysis and lymph node biopsy, connec-
tive tissue disease screen, and immunodeficiency screen in
neonates. The most common laboratory abnormalities are
anemia, hypoalbuminemia, eosinophilia, and an elevated
ESR. Imaging studies should be obtained based on suspicion
of underlying systemic disease or when other causes are
excluded.
In general, long-term prognosis is good for patients with
drug-induced disease after the offending agent is withdrawn
and proper supportive measures are undertaken. For patients
with idiopathic exfoliative dermatitis, the prognosis is poor.
Frequent recurrences or chronic symptoms require long-term
steroid therapy and its attendant sequelae. For patients with
underlying disease or malignancy, prognosis rests on the
outcome and course of the disease process.
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Polymorphous light eruption
Clinicopathologic correlation often shows chronic non-
specific dermatitis or psoriasiform dermatitis, without any clue
as to its origin. The best clinicopathologic correlation occurs
in cases associated with CTCL and PRP related erythroderma.
The most important discriminating histologic feature in
patients with Sézary syndrome is the presence of a monoto-
nous band-like or perivascular infiltrate in the papillary dermis,
mainly composed of large cerebriform-mononuclear cells.
References
1. James WD, Berger TG, Elston, DM. Andrews’ Diseases of the skin:
clinical dermatology. 10th ed. Philadelphia, PA: Saunders Elsevier;
2006. p. 215–216.
2. Lonnee ER, Toonstra J, van der Putte SC, van Weelden H, van Vloten
WA. Papuloerythroderma of Ofuji in a HIV-infected patient. Br J
Dermatol 1996 Sep; 135(3):500–501.
Polymorphous light
eruption
David A Rodriguez
Polymorphous light eruptions (PMLE), the most common
eruption of all the photodermatoses, is an idiopathic and
immunologically mediated photodermatosis characterized by
recurrent and delayed reactions to ultraviolet light. Although
most authorities now consider UVA light as the causative factor
in PMLE eruption, UVB, or even visible light, may be respon-
sible in some individuals.
The incidence of PMLE is likely to be underestimated
because many patients do not seek medical attention. PMLE
affects all races, but it is more common in fair-skinned indi-
viduals. In a retrospective analysis over 7 years of 135 patients
with photodermatosis, 48% were African-Americans, 40%
were Caucasian, and 12% were patients of other races.1 In
African-Americans and Caucasians, the frequency of diagnoses
in descending order included PMLE, systemic phototoxicity,
chronic actinic dermatitis, porphyrias, and solar urticaria.1 The
study noted a statistically significantly higher proportion of
African-Americans with PMLE compared with Caucasians. In
an Asian population in Singapore, PMLE was observed to be
the most common photodermatosis.2 In the study, Indians
appeared to be more predisposed to PMLE, while actinic
prurigo was more common in Chinese. The spectrum of
photodermatosis in the Asian population approximates that
seen in Caucasian cohorts. A study in a Chinese village showed
the prevalence of PMLE at 0.65% and it was 3.8 times higher
in women compared with men.3
PMLE is a clinical diagnosis with many different morpholo-
gies on sun-exposed areas, but usually only one morphology
dominates in a given individual. PMLE may be characterized
by recurrent, symmetric papules, papulovesicles, plaques or
erythema multiforme–like lesions (Fig. 6.7). Sun-exposed
3. Chua-Ty G, Goh CL, Koh SL. Pattern of skin diseases at the National
Skin Centre (Singapore) from 1989–1990. Int J Dermatol 1992 Aug;
31(8):555–559.
4. Pal S, Haroon T. Erythroderma: a clinico-etiologic study of 90 cases.
Int J Dermatol 1998; 37(2):104–107.
5. Leenutaphong V, Kulthanan K, Pohboon C, Suthipinittharn P,
Sivayathorn A, Sunthonpalin P. Erythroderma in Thai patients. J Med
Assoc Thai 1999 Aug; 82(8):743–748.
6. Munyao TM, Abinya NA, Ndele JK, Kitili PN, Maimba JM, Kamuri EN,
et al. Exfoliative erythroderma at Kenyatta National Hospital, Nairobi.
East Afr Med J 2007 Dec; 84(12):566–570.
7. Akhyani M, Ghodsi ZS, Toosi S, Dabbaghian H. Erythroderma: a clini-
cal study of 97 cases. BMC Dermatol 2005 May 9; 5:5.
8. Pruszkowski A, Bodemer C, Fraitag S, Teillac-Hamel D, Amoric JC, de
Prost Y. Neonatal and infantile erythrodermas: a retrospective study of
51 patients. Arch Dermatol 2000 Jul; 136(7):875–880.
9. Duangurai K, Piamphongsant T, Himmungnan T. Sézary cell count in
exfoliative dermatitis. Int J Dermatol 1988 May; 27(4):248–252.
skin, especially that normally covered in winter (e.g. upper
chest, arms), is affected, but autosensitization may lead to
generalized involvement. Outbreaks are most common in
spring and early summer after minutes or hours of sun expo-
sure. The eruption lasts for one to several days or occasionally
weeks, particularly with continuing exposure. Phototesting
with UVA, UVB, and visible light should be performed, often
with positive results. Photopatch testing to rule out a photoal-
lergic contact dermatitis should also be performed. In African-
Americans, a variant of PMLE with pinpoint papules can be
observed on sun-exposed areas, with sparing of the face and
flexural surfaces. This variant is more common in middle aged
African-American women with skin types IV–VI.4
The mainstay of treatment includes preventive therapies
with restriction of ultraviolet radiation exposure, wearing pro-
tective clothing, and daily use of broad-spectrum sunscreen.
Combining a potent antioxidant with a broad-spectrum
sunscreen has been noted to be more effective in preventing
PMLE than sunscreen alone.5 Oral vitamin E supplementation
Figure 6.7:╇ Grouped papules and plaques of polymorphous light eruption.
(Courtesy of Jeffrey Miller, MD; Department of Dermatology, Penn State Milton S.
Hershey Medical Center.)
113
 Part 1 Medical Dermatology

(400╯IU) with sunblock was shown to decrease the markers of There is evidence that the ‘hardening’ phenomenon of the
oxidative stress and lipid peroxidation.6 Prophylactic photo- skin can be achieved by gradually increasing exposure to
therapy or photochemotherapy using low dose broad spec- various forms of UV light.
trum or narrow-band UVB phototherapy may improve PMLE
over a 4–6-week period. Antimalarial therapy has been shown UVB phototherapy and photochemotherapy (PUVA) in the
to have modest protection. Antimalarials at low doses may be treatment of polymorphic light eruption and solar urticaria.
helpful in patients with a large papular variety of PMLE. Oral Addo HA, Sharma SC. Br J Dermatol 1987; 116(4):539–547.
beta carotene may be an alternative to chloroquine. Potent 40 subjects including 36 with PMLE and 4 with solar urti-
topical corticosteroids may reduce symptoms of inflammation caria were treated during the spring and early summer with
and pruritus, although tachyphylaxis and skin atrophy may either UVB phototherapy or photochemotherapy with PUVA
limit their use. For generalized eruptions, a short course of oral consisting of 18 treatment courses. Both forms of prophylactic
corticosteroids administered early can hasten resolution, while therapy were found to be effective in 90% of patients with
steroid-sparing agents such as the immunosuppressants, aza- polymorphic light eruption. PUVA was effective in 100% of
thioprine or cyclosporine, may be appropriate for more severe patients with solar urticaria. The optimum duration of treat-
and disabling disease. Thalidomide has been found to be effec- ment was 5 weeks. Adverse reactions, although common, were
tive in Native American patients with PMLE, but it is limited usually mild and rarely required alteration of the treatment
by side effects including peripheral neuropathy, sedation, con- regimen.
stipation, and weight gain as well as difficulty obtaining the
medication. Mechanisms of phototherapy and photochemotherapy for
photodermatoses. Hönigsmann H. Dermatol Ther 2003;
First-Line Therapies 16(1):23–27.
The possible mechanisms of photoprevention are discussed
for polymorphic light eruption (PMLE), actinic prurigo,
Broad-spectrum sunscreen B
chronic actinic dermatitis, and solar urticaria. The ‘hardening’
Restriction of sun exposure E phenomenon, which consists of slowly increasing a subject’s
Protective clothing E tolerance to sunlight, has proven to be an important part of
Topical corticosteroid E treatment. The pathogenesis may involve immunosuppression
Antihistamines E by UV exposure with down-regulation of cell adhesion mole-
cule expression and the depletion of endogenous antigens
which cause a delayed-type hypersensitivity reaction.
The most important treatments include sun avoidance, use
of broad-spectrum sunblock and protective clothing, although
most of the literature documents small series or anecdotal Third-Line Therapies
evidence. For mild forms of PMLE, efficacy of treatment is
anecdotal. Prednisolone E
Antimalarials E
Broad-spectrum sunscreens provide better protection from
solar ultraviolet-simulated radiation and natural sunlight- Nicotinamide E
induced immunosuppression in human beings. Moyal DD, Oral Vitamin E E
Fourtanier AM. J Am Acad Dermatol 2008; 58(5 Suppl Oral carotenoid E
2):S149–S154. Thalidomide E
Recent studies have shown that UVA (320–400╯nm) and
UVB (290–320╯nm) radiation are immunosuppressive. A
broad-spectrum sunscreen providing a significant protection
in the UVA range reduced local UV-induced immunosup� Commonly encountered pitfalls
pression and prevented subsequent effects. Sunscreen prod�
ucts providing efficient photoprotection throughout the PMLE should be differentiated from other photodermatoses,
entire UV spectrum are appropriate for certain skin conditions including actinic prurigo. In one study, 28% of Caucasian
such as PMLE, in which immunosuppression may have an patients and 53% of African-American patients were found
effect. to have actinic prurigo.7 Hence, ethnic patients who are
suspected of PMLE and are non-Native Indians should
be screened for actinic prurigo, specifically asking about
Second-Line Therapies
American Indian heritage and the occurrence of photosensitiv-
ity in relatives.
PUVA C Idiopathic photodermatoses, such as PMLE, are common
NBUVB C disorders in populations that live in the northern latitudes,
Broadband UVB C presumably because of an increased population of lighter
skinned individuals. In a study investigating idiopathic

114
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Urticaria

photodermatoses in a Mediterranean country, its prevalence

appears to have a similar trend to that of countries in the
northern latitude.8 Distinct features in the series include its
higher incidence in patients with a fair-skinned complexion
(skin types II–III) and the frequent appearance of photo-
induced eruptions during sunny vacations and during
the winter. However, in ethnic skin, this condition is often
missed due to the common assumption that darker skinned
individuals are more resistant to the development of sun
sensitivity.
Special management & counseling considerations
It has been established that preventive therapy avoiding sun-
light, protective clothing, and broad-spectrum sunscreen is
essential for treatment of PMLE and ethnic patients must be
educated about this therapy. Because sunscreen use is low in
ethnic patients, counseling is particularly important. Also, due
to the high prevalence of outdoor work in ethnic patients,
counseling should also include avoiding sunlight during the
hours of most intense UV radiation (10am to 4pm), wearing
protective clothing (hats, gloves, & long sleeves), and reap-
plication of sunscreen throughout the day.
References
1. Kerr HA, Lim HW. Photodermatoses in African-Americans: a retrospec-
tive analysis of 135 patients over a 7-year period. J Am Acad Dermatol
2007; 57(4):638–643.
2. Wong SN, Khoo LS. Analysis of photodermatoses seen in a predomi-
nantly Asian population at a photodermatology clinic in Singapore.
Photodermatol Photoimmunol Photomed 2005; 21(1):40–44.
3. Deng D, Hang Y, Chen H, Li H. Prevalence of photodermatosis in four
regions at different altitudes in Yunnan province, China. J Dermatol
2006; 33(8):537–540.
4. Kontos AP, Cusack CA, Chaffins M, et al. Polymorphous light eruption
in African-Americans: pinpoint papular variant. Photodermatol
Photoimmunol Photomed 2002; 18(6):303–306.
5. Hadshiew IM, Treder-Conrad C, v Bülow R, Klette E, Mann T, Stäb F,
et al. Polymorphous light eruption (PLE) and a new potent antioxi-
dant and UVA-protective formulation as prophylaxis. Photodermatol
Photoimmunol Photomed 2004 Aug; 20(4):200–204.
6. Ahmed RS, Suke SG, Seth V, Jain A, Bhattacharya SN, Banerjee BD.
Impact of oral vitamin E supplementation on oxidative stress & lipid
peroxidation in patients with polymorphous light eruption. Indian J
Med Res 2006 Jun; 123(6):781–787.
7. Fusaro RM, Johnson JA. Hereditary polymorphic light eruption of
American Indians: occurrence in non-Indians with polymorphic light
eruption. J Am Acad Dermatol 1996; 34(4):612–617.
8. Stratigos AJ, Antoniou C, Papathanakou E, Daboudi M, Tranaka K,
Tsara K, et al. Spectrum of idiopathic photodermatoses in a
Mediterranean country. Int J Dermatol 2003 Jun; 42(6):449–454.

Urticaria
Ninad Pendharkar and Sonia Badreshia-Bansal

Urticaria is a common skin disorder characterized by circum-

scribed erythematous, edematous, pruritic wheals (Figs. 6.8-
6.9) which resolve within 24 hours before recurring. It is
classified as acute if it lasts for less than 6 weeks, and chronic,
if more than 6 weeks. The incidence of urticaria is 15–25%
during a person’s life with only 30% of cases progressing to
chronic urticaria. The peak age of onset is 20–40 years, with
some studies suggesting that females are affected more often
than males. Urticaria may be difficult to diagnose in patients
with ethnic skin, since erythema associated with the wheal can
be less prominent. Additionally, Black patients are more likely
to have angioedema associated with urticaria than Caucasian
patients.
Urticaria is caused by vasoactive mediators, primarily hista-
mine, released by mast cells (Table 6.6). It may be associated
with angioedema of the respiratory or gastrointestinal tracts
causing respiratory compromise and abdominal pain, respec-
tively. Angioedema is usually due to bradykinin production
and generally is not pruritic. The etiology of urticaria is often
difficult to identify and many cases are deemed idiopathic. Figure 6.8:╇ Wheals characteristic of chronic idiopathic urticaria. (Courtesy of
Histopathologically, there is mild dermal edema with mar- Gregory Fulchiero, MD; Department of Dermatology, Penn State Milton S. Hershey
gination of neutrophils within post-capillary venules in acute Medical Center.)

115
 Part 1 Medical Dermatology

Table 6.6╇ Causes of urticaria1,2

Drugs Antibiotics – penicillins (most common),

sulfonamides, cephalosporins, aminoglycosides,
tetracyclines
NSAIDs, salicylates – most common cause of
non-IgE mediated urticaria
Angiotensin converting enzyme inhibitors – most
common cause of angioedema in Black
population
Anticonvulsants
Narcotics (codeine)
Anesthetic agents
Radio-contrast media
Muscle relaxants
Mannitol
Hydralazine
Quinidine
Infections Streptococcal infection
Helicobacter pylori
Hepatitis B and C
Acute infectious mononucleosis
Urinary tract infections
Viral respiratory infections (more common in
pediatric population)
Parasites/helminths
Systemic Systemic lupus erythematosus
Figure 6.9:╇ Chronic idiopathic urticaria. (Courtesy of Jeffrey Miller, MD; diseases Sjogren’s syndrome
Department of Dermatology, Penn State Milton S. Hershey Medical Center.) Cryoglobulinemia
Urticarial vasculitis
Autoimmune thyroiditis
urticaria.1 In later stages, a mixed inflammatory infiltrate of Lymphoproliferative disorders
neutrophils, lymphocytes, and eosinophils is seen.
Mast cells are the primary effector cells in urticaria which Physical urticaria Dermographism
upon activation rapidly release histamine, leukotrienes, and Pressure induced
prostaglandins causing vasodilation and leakage of plasma Cold contact urticaria
from post-capillary venules. This is followed by a secretion of Heat contact urticaria
inflammatory cytokines which contribute to the inflammatory Idiopathic
infiltrate. Some patients with chronic idiopathic urticaria have
circulating histamine releasing IgG autoantibodies that bind
to the high affinity IgE receptor causing mast cell degranula-
tion. In contrast, there are some agents that cause urticaria by
IgE independent mechanisms. First-Line Therapies
The key to the treatment of urticaria is to identify the causa-
tive agent. Drug-induced urticaria usually resolves once the
Avoidance or elimination of obvious triggering factors E
offending agent is discontinued. Counseling regarding avoid-
Second generation H-1 antihistamine A
ance of triggering stimuli is also important. In order to deter-
mine non-medication related etiologies, a detailed history is Treat any underlying causes E
one of the most important elements in evaluating a patient
with urticaria. Laboratory investigations should be based on
history and may include: CBC with differential, ESR, CRP,
metabolic panel, thyroid function tests, thyroid autoantiÂ� Urticaria. Zuberbier T. Allergy 2003; 58:1224–1234.
bodies, ANA, C3, C4, cryoglobulins, immunoglobulins and Review article which highlights different etiologies of urti-
protein electrophoresis, serology for infections, stool for ova caria and provides algorithm for diagnosis. Also provides
and parasites, and urine analysis. Skin prick testing may be of tables enumerating studies of different treatments for urticaria
benefit in certain cases.2 In general, there is a good response and level of evidence. Recommends second generation H-1
to H-1 antihistamine treatment. antihistamines as first-line treatment option.

116
 6â•… Hypersensitivity and Allergic Disordersâ•… •â•… Urticaria

Levocetirizine in the treatment of chronic idiopathic urti- 10╯mg daily with cetirizine as needed for 6 weeks. After a
caria: a randomized, double-blind, placebo-controlled 2-week washout period, they received placebo with cetirizine
study. Nettis E, Colanardi MC, Barra L, Ferrannini A, Vacca A, as needed for 6 weeks. Group B received the exact opposite.
Tursi A. Br J Dermatol 2006; 154:533–538. More significant decreases in the urticaria severity scores were
Randomized double-blind placebo controlled study of noted with montelukast therapy when compared to placebo.
106 patients treated with levocetirizine 5╯mg daily compared Also, cetirizine was used less frequently when patients were
to placebo for 6 weeks showed that the treatment group receiving montelukast therapy.
experienced reduction in number of daily episodes, total
number of wheals, and overall severity of symptoms. Patients Treatment of chronic urticaria with narrowband ultraviolet
reported better quality of life. However, the benefits lasted only B phototherapy: a randomized controlled trial. Ozdemir E,
during the treatment period. Upon evaluation 1 week after Engin B, Ozdemir M, Balevi A, Mevlitoğlu I. Acta Derm Vener-
discontinuing treatment, patients noted worsening of their eol 2008; 88(3):247–251.
disease. 48 of 81 patients with chronic idiopathic urticaria received
narrowband ultraviolet B (NBUVB) phototherapy and an oral
Desloratadine for chronic idiopathic urticaria: a review of antihistamine, while the remainder received only an oral anti-
clinical efficacy. DuBuske L. Am J Clin Dermatol 2007; histamine. Both groups were evaluated after the NBUVB group
8(5):271–283. received 10 treatments, 20 treatments and at 3 months post-
Review article discussing results of randomized, double- treatment. The NBUVB group showed statistically significantly
blind, placebo-controlled studies using desloratadine for the lower mean urticaria activity score at all three evaluations.
treatment of moderate to severe chronic idiopathic urticaria in
both adults and children. In general, desloratadine minimized Narrowband ultraviolet B phototherapy is beneficial in
pruritus severity, decreased number and size of wheals, and antihistamine-resistant symptomatic dermographism: a
improved quality of life. The adverse effect profile was similar pilot study. Borzova E, Rutherford A, Konstantinou GN, Leslie
to placebo. KS, Grattan CE. J Am Acad 2008; 59:752–757.
8 patients with dermographism resistant to treatment with
oral antihistamines were treated with fexofenadine (180╯mg
Second-Line Therapies per day) and narrowband ultraviolet B (NBUVB) phototherapy
3 times per week for 6 weeks. Patients were followed for 3
Other H-1 antihistamines A months post-therapy at 6 week intervals. All noted improve-
H-2 antihistamine B ment in itching and 6 of 8 patients noticed an improvement
Leukotriene receptor antagonists A in wheals at the end of phototherapy. However, most patients
Oral corticosteroids B noticed a relapse in symptoms 12–18 weeks after completing
Narrow band UVB B phototherapy.
PUVA C

Third-Line Therapies

Efficacy of leukotriene receptor antagonist in chronic urti- Cyclosporine A B

caria. A double-blind, placebo-controlled comparison of
Plasmapheresis D
treatment with montelukast and cetirizine in patients with
chronic urticaria with intolerance to food additive and/or Interferon E
acetylsalicylic acid. Pacor M, Pacor ML, Di Lorenzo G, IVIG D
Corrocher R. Clin Exp Allergy 2001; 31(10):1607–1614. Danazol D
This randomized double-blind, placebo-controlled trial of Dapsone B
51 patients compared the clinical efficacy and safety of mon- Anakinra E
telukast 10╯mg daily and cetirizine 10╯mg daily with placebo, Acupuncture B
in the treatment of patients with chronic urticaria. A statisti-
cally significant increase in the number of symptom-free days
from hives and itching was demonstrated in patients treated
with montelukast when compared to placebo, which was Prospective randomized non-blinded clinical trial on the
similar to cetirizine. use of dapsone plus antihistamine vs antihistamine in
patients with chronic idiopathic urticaria. Engin B, Özdemir
The leukotriene receptor antagonist montelukast in the M. JEADV 2008; 22:481–486.
treatment of chronic idiopathic urticaria: a single-blind, 65 patients with refractory chronic idiopathic urticaria
placebo-controlled, crossover clinical study. Erbagci Z. J were randomized to two groups, with one group receiving
Allergy Clin Immunol 2002; 110:484–488. dapsone (50╯mg daily) with desloratadine 10╯mg daily for 3
30 patients with refractory chronic idiopathic urticaria were months, and the other group receiving desloratadine 10╯mg
randomly assigned to 2 groups. Group A received montelukast daily for 3 months. At the end of the study, in the dapsone

117
 Part 1 Medical Dermatology
and desloratadine group, 9 patients had a complete response,
27 had a partial response, and 2 had no response. None of the
control subjects had a complete response.
Randomized double-blind study of cyclosporine in chronic
‘idiopathic’ urticaria. Grattan CE, O’Donnell BF, Francis DM,
Nimi N, Barlow RJ, Seed PT, Kobza Black A, Greaves MWE. Br
J Dermatol 2000; 143:365–372.
30 patients with severe chronic idiopathic urticaria were
treated with cyclosporine 4╯mg/kg daily or placebo for 4
weeks. Patients in the placebo group and non-responders were
then offered open label cyclosporine for 4 weeks. 19 of 30
patients showed some response during the trial. Five of the
responders were clear or almost clear at 6 months. The remain-
ing noted a relapse of their disease.
Complete remission of severe idiopathic cold urticaria on
interleukin-I receptor antagonist (anakinra). Bodar EJ,
Simon A, de Visser M, van der Meer JW. Neth J Med 2009;
67(9):302–305.
Case report of a patient with severely debilitating cold
induced urticaria and oropharyngeal angioedema successfully
treated with anakinra 100╯mg subcutaneously daily for 2 years.
Acupuncture in dermatology: an historical perspective.
Tan EK, Millington GW, Levell NJ. Int J Dermatol 2009;
48:448–452.
Review article that discusses three trials, two of which
compared acupuncture for chronic idiopathic urticaria to
antihistamines, and one trial to placebo. All three trials
revealed a higher response rate in the acupuncture group.
An approach to the patient with urticaria. Deacock S. Clin
Exp Immunol 2008; 153:151–161.
Review article outlining a classification system of urticaria,
diagnostic studies, and treatment algorithms.
Commonly encountered pitfalls
The medications, minocycline and phenytoin, which can cause
urticaria, are more likely to cause a severe drug hypersensitivity
syndrome in black populations.3 Studies also suggest racial
differences exist in the kallikrein-kinin system making
African-American patients more susceptible to angioedema.4
A retrospective study evaluating photodermatoses in African-
Americans revealed a lower incidence of solar urticaria when
compared to Caucasian patients.5
118
In India, malaria may commonly present as urticaria.6 As a
result, evaluation of patients from endemic regions for under-
lying infections as the cause of urticaria is warranted.
Special management & counseling considerations
Patients who present with angioedema in addition to their
urticaria, usually experience a prolonged disease course.2 A
recent study suggested African-American patients have a higher
rate of hospitalization for angioedema.7 Patients with physical
urticaria tend to have a poorer response and prolonged clinical
course.2
As listed in the treatment section, acupuncture is an accepted
treatment for both acute and chronic urticaria in traditional
Chinese medicine. It is important when counseling patients
to be aware of the side effects of this modality which
include vasovagal events, local infections, damage to internal
organs, pneumothorax, spinal cord injury, and hepatitis B
infections.8
A Chinese study reported association of chronic urticaria
with HLA-DRB1, DQB1 alleles.9 Further studies identifying
genetic susceptibility markers for chronic urticaria could assist
with management of this condition in the future.
References
1. James WD, Berger TG, Elston DM. Andrews’ Diseases of the skin: clini-
cal dermatology. 10th ed. Philadelphia, PA: Saunders Elsevier; 2006.
p. 149–156.
2. Deacock S. An approach to the patient with urticaria. Clin Exp
Immunol 2008; 153:151–161.
3. Muller P. Drug hypersensitivity syndrome in a West-Indian population.
Eur J Dermatol 2003; 13:478–481.
4. Gainer JV, Nadeau JH, Ryder D, Brown NJ. Increased sensitivity to
bradykinin among African Americans. J Allergy Clin Immunol 1996
Aug; 98(2):283–287.
5. Kerr H, Lim H. Photodermatoses in African-Americans: a retrospective
analysis of 135 patients over a 7-year period. J Am Acad Dermatol
2007; 57(4):638–643.
6. Mitra A. Malaria presenting with urticaria as the initial feature. Indian
Pediatr 1989; 26(7):728.
7. Lin R, Shah S. Increasing hospitalizations due to angioedema in the
United States. Ann Allergy Asthma Immunol 2008; 101(2):185–192.
8. Tan EK, Millington GW, Levell NJ. Acupuncture in dermatology: an
historical perspective. Int J Dermatol 2009; 48:448–452.
9. Chen J, Tan Z, Li J, Xiong P. Association of HLA-DRB1, DQB1 alleles
with chronic urticaria. J Huazhong Univ Sci Technolog Med Sci 2005;
25(3):354–356.
Part 1 Medical Dermatology
Infectious Diseases
Rashmi Sarkar, Vivek Nair, Surabhi Sinha, Vijay K Garg and David A Rodriguez
Candidiasis . . . . . . . . . . . . . . . . . . . . . . . . 119
Oral candidiasis . . . . . . . . . . . å°“. . . . . . . . . . 119
Candidal intertrigo/Cutaneous candidiasis . . . . . . . . 120
Cellulitis and Erysipelas . . . . . . . . . . . . . . . . . . 121
Chancroid . . . . . . . . . . . . . . . . . . . . . . . . . 123
Chlamydia trachomatis . . . . . . . . . . . . . . . . . . 125
Donovanosis (Granuloma inguinale) . . . . . . . . . . . 126
Exanthems . . . . . . . . . . . . . . . . . . . . . . . . . 128
Folliculitis . . . . . . . . . . . . . . . . . . . . . . . . . 130
Furunculosis . . . . . . . . . . . . . . . . . . . . . . . . 131
Human papilloma virus (HPV) . . . . . . . . . . . . . . . 133
Lymphogranuloma venereum (LGV) . . . . . . . . . . . 135
Pityriasis versicolor . . . . . . . . . . . . . . . . . . . . 137
Syphilis . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Tinea capitis . . . . . . . . . . . . . . . . . . . . . . . . 142
Tinea corporis . . . . . . . . . . . . . . . . . . . . . . . 145
Tinea unguium . . . . . . . . . . . . . . . . . . . . . . . 146
Candidiasis
Yeast infections can cause a range of cutaneous diseases as
many species of yeast can be pathogenic. Candida albicans is
the most commonly implicated agent, but other species of
yeast, such as C. glabrata, C. parapsilosis, C. guilliermondii,
C. rugosa, C. krusei, and C. tropicalis, can likewise cause disease.
Candidiasis is commonly seen in neonates and elderly
patients, individuals with local tissue damage or maceration,
diabetes mellitus, HIV infection, hypothyroidism, Cushing’s
syndrome and local or systemic immunosuppression.
©2011 Elsevier Ltd, Inc, BV
7â•…
The following clinical types of cutaneous candidiasis may
be observed:
1. Oral candidiasis or perleche (Fig. 7.1).
2. Candidial intertrigo or flexural candidiasis: moist ery-
thematous plaques with well defined margins and pus�
tules and erosions at the periphery. Satellite pustules are
characteristic (Fig. 7.2).
3. Candidal paronychia and candidal onychomycosis: proxi-
mal nail fold erythema and swelling with marked tender-
ness. Deep palpation over the proximal nailfold may yield
scant creamy exudate. Discoloration and onycholysis of the
nail plate may accompany the paronychia.
4. Napkin candidiasis: clinically appears similar to candidal
intertrigo but occurs in neonates and infants in the diaper
distribution.
Diagnosis is achieved via direct microscopic examination
which reveals budding yeast cell pseudohyphae and yeast cells.
Culture on Sabouraud’s dextrose agar produces creamy white,
smooth colonies that appear within 2–4 days. C. albicans pro-
duces chlamydospores on cornmeal agar medium.
Oral candidiasis
First-Line Therapies
Nystatin oral rinse A
Clotrimazole troches A
Comparative trial of oral clotrimazole and nystatin for
oropharyngeal candidiasis prophylaxis in orthotopic liver
transplant patients. Ruskin JD, Wood RP, Bailey MR, et al.
Oral Surg Oral Med Oral Pathol 1992; 74(5):567–571.
This study assessed the effectiveness of clotrimazole troches
and nystatin suspension to prevent oral candidiasis in immu-
nosuppressed orthotopic liver transplant patients. 34 patients
received either clotrimazole troches, 10╯mg, five times daily, or
nystatin suspension, 500,000 units, four times daily. Each of
119
 Part 1 Medical Dermatology
Figure 7.1:╇ Oral candidiasis involving the palate with Candida albicans. Severe
candidiasis of the mouth and gastrointestinal tract is commonly seen in AIDS
patients. (From Peters and Pasvol, Atlas of Tropical Medicine and Parasitology, 6e,
copyright Elsevier 2007.)
Figure 7.2:╇ Intertrigo or flexural candidiasis.
the treatment groups experienced a 5.9% infection rate and
were deemed effective at preventing oral candidiasis.
Clotrimazole treatment for prevention of oral candidiasis
in patients with acute leukemia undergoing chemotherapy.
Results of a double-blind study. Cuttner J, Troy KM, Funaro
L, et al. Am J Med 1986; 81:771–774.
Double-blind controlled study in 30 patients with acute
leukemia in which the effectiveness of clotrimazole troches in
preventing oropharyngeal candidiasis was assessed. Patients
were randomly assigned to receive 10╯mg troches of clotrima-
zole or a placebo three times per day. Of 12 patients with oral
candida infection, 11 were taking placebo and 1 was taking
clotrimazole.
Second-Line Therapies
Oral fluconazole
120
This agent is typically reserved for refractory oral candidiasis
or esophageal involvement.
Single-dose fluconazole versus standard 2-week therapy for
oropharyngeal candidiasis in HIV-infected patients: a rand-
omized, double-blind, double-dummy trial. Hamza OJ,
Matee MI, Brüggemann RJ, et al. Clin Infect Dis 2008;
47(10):1270–1276.
220 HIV-infected patients with clinical and mycological
evidence of oropharyngeal candidiasis were randomly assigned
in a 1╛:╛1 ratio to receive either a 750╯mg single dose of orally
administered fluconazole (110 patients) or 150╯mg of orally
administered fluconazole once per day for 2 weeks (110
patients). Single-dose fluconazole was equivalent to a 14-day
course of fluconazole in achieving clinical and mycological
cure, with clinical cure rates of 94.5% and 95.5%, respectively.
Candidal intertrigo/Cutaneous candidiasis
First-Line Therapies
Topical miconazole A
Topical clotrimazole A
Cutaneous candidiasis: treatment with miconazole nitrate.
Cullin SI. Cutis 1977; 19(1):126–129.
Double-blind, randomized study of 30 patients with cuta-
neous candidiasis treated with a 2% miconazole nitrate lotion
or its placebo control. By the 14th day, 13 of the 15 patients
(87%) treated with miconazole nitrate achieved clinical and
mycologic cures.
A double-blind randomized comparative trial: eberconazole
1% cream versus clotrimazole 1% cream twice daily in
Candida and dermatophyte skin infections. del Palacio A,
Ortiz FJ, Pérez A, et al. Mycoses 2001; 44:173–180.
Double-blind, phase III study of the efficacy and tolerability
of eberconazole 1% cream compared with clotrimazole 1%
cream, applied twice daily for four consecutive weeks in 157
patients. At the end of the trial, the proportion of patients with
effective treat�ment was 73% and 50% for clotrimazole and
eberconazole, respectively.
Second-Line Therapies
Castellani’s paint E
Catsellani’s paint, also known as carbolfuschin, is known
to have antifungal properties, and is a mixture of phenol and
fuschin.
Candidal intertrigo: treatment with filter paper soaked in
Castellani’s paint. Shanmuga V, Sundaram CR, Srinivas M,
et al. Indian J Dermatol, Venereol, Leprol 2006; 72:386–387.
A Castellani’s paint was used in 4 patients with conformed
Candidal intertrigo, all of whom improved with treatment.

Cellulitis and Erysipelas
Cellulitis is an acute, subacute or chronic infection of the deep
subcutaneous tissue (Fig. 7.3). Erysipelas is a streptococcal
infection of the upper subcutaneous tissue and lymphatic
vessels. Cellulitis and erysipelas are most commonly caused by
Strep. pyogenes, and occasionally by Staph. aureus or Gram-
negative bacilli. The two conditions may be distinguished
from one another by the more superficial involvement and the
sharp margin in erysipelas as compared to cellulitis. These
conditions are more frequently seen in patients with diabetes
mellitus or immunocompromised states. Malnutrition and
alcoholism are other predisposing factors. Cellulitis appears as
an erythematous edematous plaque with less distinct borders
as compared to erysipelas.
Erysipelas presents as a tense, erythematous, edematous
plaque which may develop a peau d’orange appearance due to
lymphatic occlusion. The margins of the lesion are sharply
demarcated. In acute stages, vesicles or erosions at the margins
may be present. Erysipelas most commonly occurs on the
abdominal wall in infants, face or limbs in children, and the
ear, face or the legs in adults. Associated systemic features are
usually present with both cellulitis and erysipelas.
First-Line Therapies
Coverage for S. aureus and Streptococcal species
Penicillin G A cellulitis.
Flucloxacillin/floxacillin A
Figure 7.3:╇ Cellulitis.
7â•… Infectious Diseasesâ•… •â•… Cellulitis and Erysipelas
Amoxicillin with clavulanic acid
Intravenous ceftriaxone with probenecid
B
A
Intravenous Cefazolin with probenecid
Roxithromycin (not approved in the USA) A
Vancomycin A
Intramuscular bipenicillin vs intravenous penicillin in the
treatment of erysipelas in adults: randomized controlled
study. Zeglaoui F, Dziri C, Mokhtar I. J Eur Acad Dermatol
Venereol 2004; 18(4):426–428.
Prospective randomized trial in 112 patients, 57 in the
intramuscular group and 55 in the intravenous group. The
failure rate was 14% for intramuscular group and 20% for
the intravenous group.
Flucloxacillin alone or combined with benzylpenicillin to
treat lower limb cellulitis: a randomised controlled trial.
Leman P, Mukherjee D. Emerg Med J 2005; 22(5):342–346.
A randomized controlled trial in 81 patients with lower
limb cellulitis requiring intravenous antibiotics. The main
outcome measure was the mean number of doses of
antibiotic required until clinical response. The mean number
of doses required was 8.47 in the benzylpenicillin and flu-
cloxacillin combined group. In the flucloxacillin only group,
8.71 doses were required. The study provided no evidence
to support the addition of intravenous benzylpenicillin to
intravenous flucloxacillin in the treatment of lower limb
Experience with parenteral and sequential parenteral–
oral amoxicillin/clavulanate (augmentin) in hospitalized
patients. Büchi W, Casey PA. Infection 1988; 16(5):306–
312.
Efficacy and safety of sequential parenteral-oral augmentin
(amoxicillin plus clavulanic acid) therapy was evaluated in an
open study with 249 adult patients. The patients had a variety
of infections including the respiratory tract, skin and/or soft
tissues, urinary tract, or female pelvic organs, and bacteremia
in 36. The overall bacteriological success rate was 94.1%.
Augmentin achieved a satisfactory clinical response (cure or
improvement) in 96.7% of the infections treated, with a
response of 95.7% in skin and soft tissue infections.
Ceftriaxone versus cefazolin with probenecid for severe
skin and soft tissue infections. Brown G, Chamberlain R,
Goulding J, et al. J Emerg Med 1996; 14(5):547–551.
Randomized, double-blind study conducted to evaluate the
hypothesis that a single daily administration of cefazolin and
probenecid and a single daily administration of ceftriaxone
and probenecid would be equally effective, in combination
with oral antibiotics, for the outpatient treatment of skin and
soft tissue infections. Patients presenting to the Emergency
Department with the primary diagnosis of cellulitis or soft
121
 Part 1 Medical Dermatology
tissue infection, excluding patients requiring immediate hos-
pital admission, received either 2╯g of ceftriaxone or 2╯g of
cefazolin, each with 1╯g of probenecid, on a daily basis as
outpatients. The patients were given a prescription for oral
penicillin and cloxacillin for independent procurement. A
total of 194 patients were randomized to receive ceftriaxone
(96) or cefazolin (98). The single daily administration of 2╯g
of either cefazolin, in combination with probenecid, or ceftri-
axone are equivalent in efficacy in the outpatient treatment of
skin and soft tissue infections and is a more cost-effective
approach.
Roxithromycin versus penicillin in the treatment of erysip-
elas in adults: a comparative study. Bernard P, Plantin P,
Roger H, et al. Br J Dermatol 1992; 127(2):155–159.
A prospective, randomized, multicenter trial was conducted
in 72 patients with erysipelas in order to evaluate the efficacy
and safety of roxithromycin (150╯mg bid orally) and penicillin
(2.5╯MU × 8 daily intravenously, then 6╯MU daily orally). 31
patients in the roxithromycin group and 38 patients in the
penicillin group completed the trial. The overall efficacy rates
(cure without additional antibiotics) were 84% (26/31) in
the roxithromycin group and 76% (29/38) in the penicillin
group.
The efficacy and safety of daptomycin vs vancomycin for the
treatment of cellulitis and erysipelas. Pertel PE, Eisenstein BI,
Link AS, et al. Int J Clin Pract 2009; 63(3):368–375.
Prospective, evaluator-blinded, multicenter trial for adults
with erysipelas and cellulitis. Patients were randomized to
receive daptomycin 4╯mg/kg once daily or vancomycin, accord-
ing to standard of care, for 7–14 days. The clinical success rates
were 94.0% for daptomycin and 90.2% for vancomycin.
There was no difference in the rate of resolution of cellulitis
or erysipelas among patients treated with daptomycin or
vancomycin.
Second-Line Therapies
Ciprofloxacillin A
Daptomycin A Hematopoietic growth factors in treatment of necrotizing
Imipenem cilastatin A cellulitis patients with drug-induced neutropenia. Souidia F,
Agents like imipenem-cilastatin and meropenem are
reserved for refractory unresponsive cases involving soft tissue
infection.
122
Oral ciprofloxacin vs parenteral cefotaxime in the treatment
of difficult skin and skin structure infections. A multicenter
trial. Gentry LO, Ramirez-Ronda CH, Rodriguez-Noriega E,
et al. Arch Intern Med 1989; 149(11):2579–2583.
Prospective, randomized, double-blind, multicenter study
of hospitalized patients to compare the efficacy and safety of
oral ciprofloxacin (dosage, 750╯mg every 12 hours) with intra-
venous cefotaxime (dosage, 2.0╯g every 8 hours) as mono-
therapy for difficult skin and skin structure infections requiring
hospitalization. 570 patients were assessed for an analysis of
safety and 461 patients were assessed for an analysis of efficacy.
The most common infections were infected ulcers and
abscesses. At the end of therapy, there was a higher incidence
of recurrent or persistent organisms in the cefotaxime. Oral
ciprofloxacin therapy is as safe and effective as parenteral cefo-
taxime in the treatment of difficult infections of the skin and
skin structures.
A post hoc subgroup analysis of meropenem versus
imipenem/cilastatin in a multicenter, double-blind, rand-
omized study of complicated skin and skin-structure infec-
tions in patients with diabetes mellitus. Embil JM, Soto NE,
Melnick DA. Clin Ther 2006; 28(8):1164–1174.
Multicenter, international, double-blind, randomized clini-
cal trial involving hospitalized patients with complicated skin
and skin-structure infections using meropenem and imipenem/
cilastatin (both administered 500╯mg intravenously every 8
hours). Of the 1076 patients enrolled in the original study, in
the clinically evaluable population, the satisfactory clinical
response rate was 85.6% for patients with diabetes mellitus
receiving meropenem and 72.4% for those receiving imipenem/
cilastatin; for patients without diabetes mellitus, those rates
were 86.6% and 89.0%, respectively. Both agents were deemed
to be efficacious
Third-Line Therapies
Granulocyte colony stimulating factor (G CSF) E
Chosidowa O, Cordonnierb C, et al. Dermatology 1993; 187:
71–72.
Three cases of necrotizing cellulitis associated with drug-
induced neutropenia are reported. The outcome was favorable
in all cases with a combination of granulocyte colony-
stimulating factor and conventional treatment.

Chancroid
Often described as a ‘soft chancre’, chancroid has a global
incidence of 7 million cases annually.1 It is caused by Haemo-
philus ducreyi, a Gram-negative bacillus. Primarily a disease of
developing nations it is most prevalent in Asia, Africa, South
America and the Caribbean islands. It is the most common
cause of genital ulceration in all countries where the adult HIV
prevalence rate exceeds 8%. A high turnover of sex partners is
needed to sustain the disease and thus infected commercial
sex workers are the major source of infection. HIV transmis-
sion rates are increased 4–10 times in the presence of chan-
croidal ulcers. The disease is much more common in men than
women.
After an incubation period of 3–7 days, an erythematous
papule, often with a surrounding halo, appears at the site of
inoculation. This develops into a painful ulcer over the next
24–48 hours, at which stage the patient usually presents to the
healthcare provider (Fig. 7.4). Lesions may start out as multi-
ple or become multiple through auto-inoculation. The classic
chancroidal ulcer is extremely tender, bleeds on palpation and
has ragged undermined margins. The base is non-indurated
and the floor covered by a necrotic slough. Ulcer size varies
from a few millimeters to 2╯cm (Fig. 7.5). Tender inguinal
lymphadenopathy (unilateral > bilateral) which appears
around 1 week after the ulcer occurs in 50% of patients. The
enlarged lymph nodes may subside spontaneously or suppu-
rate to form unilocular bubos. These in turn may suppurate,
Figure 7.4:╇ Chancroid. Differential diagnosis of penile ulcers includes syphilis,
chancroid and granuloma inguinale. (From Johnson, Moy, White: Ethnic Skin –
Medical and Surgical, Mosby, copyright Elsevier 1998.)
7â•… Infectious Diseasesâ•… •â•… Chancroid
discharging thick, creamy pus. Patients usually feel better
when this occurs as the pain in the bubos subsides, however,
the ulcer which forms in the inguinal region may heal with
scarring and lead to complications later.
Without treatment the course of the illness is protracted
with slow and often incomplete resolution. There are no sys-
temic symptoms barring malaise and low grade fever in some
patients, as H. ducreyi does not cause systemic infection. Like
syphilis, infection does not confer immunity and re-infection
is possible. Unlike syphilis, congenital infection does not
occur.
The diagnosis of chancroid is most commonly made with
via a smear, culture of skin biopsy.
• Smear. A specimen is collected from the base of the ulcer
with a cotton swab and stained with either Gram or Giemsa
stain (Fig. 7.6). The causative bacteria are seen as Gram-
negative cocco-bacilli arranged in chains or clusters often
described as a ‘school of fish’ or a ‘rail-road-track appear-
ance’. Smears are negative in 50% of the cases so definitive
diagnosis often requires other methods.
• Culture. No satisfactory transport medium exists to trans-
port H. ducreyi, so samples taken from the ulcer base must
immediately be plated onto enriched media such as blood
or chocolate agar. Colonies appear in 2–4 days, are
yellowish-gray, non-mucoid and can typically be pushed
across the agar surface. The sensitivity of the test is 75%, an
added advantage being that antimicrobial sensitivity to
antibiotics can be tested.
Figure 7.5:╇ Chancroid. (A) A painful, solitary, foul smelling ulcer. (B) Multiple
ulcers of chancroid. (Courtesy of Michael O. Murphy MD; from White, Diseases of
the Skin, 2e, copyright Elsevier 2005.)
123
 Part 1 Medical Dermatology
Figure 7.6:╇ Chlamydia trachomatis. Giemsa-staining demonstrates the typical
granular appearance of groups of elementary bodies in this cell monolayer.
(From Peters and Pasvol, Atlas of Tropical Medicine and Parisitology, 6e,
copyright Elsevier 2007.)
• Biopsy. Done mostly to rule out malignancy in non-healing
ulcers, H & E shows three typical zones arranged vertically.
The first zone contains neutrophils, RBCs, necrosis and
fibrin. The second zone shows angiogenesis with occlusion
of the blood vessel lumens leading to thrombosis. The deep
zone contains a dense infiltrate of plasma cells and lym-
phoid cells.
• Others. These are newer tests designed to detect genetic
material or other antigens of H. ducreyi. However, being
expensive, they remain out of reach of most healthcare
providers in developing countries where the infection is
most rampant and where diagnosis is still most often made
clinically.
First-Line Therapies
Azithromycin 1╯g orally single dose
Ceftriaxone 250╯mg IM single dose
Ciprofloxacin 500╯mg orally 2 times a day for 3 days
Erythromycin base 500╯mg orally 3 times a day for
7 days
Treatment recommendations of the CDC and World Health
Organization (WHO) are similar. According to the WHO, the
use of doxycycline and penicillin are not indicated in the treat-
ment of chancroid.2,3
Single dose azithromycin for the treatment of chancroid: a
randomized comparison with erythromycin. Tyndall MW,
Agoki E, Plummer FA, et al. Sex Transm Dis 1994; 21(4):
231–234.
124
A randomized, single-blinded study of 127 men presenting
to a referral STD clinic with culture proven chancroid, com-
pared the efficacy of azithromycin, administered as a single 1╯g
dose, with erythromycin 500╯mg given 4 times daily for 7 days.
Cure rates were 89% (73 of 82) in the azithromycin group and
91% (41 of 45) in the erythromycin group. Single dose azi-
thromycin is an effective treatment for chancroid in men, and
offers major prescribing advantages over QID erythromycin.
Single-dose ceftriaxone for chancroid. Bowmer MI, Nsanze
H, D’Costa LJ, et al. Antimicrob Agents Chemother 1987;
31(1):67–69.
Men with genital ulcers that were culture positive for Hae-
mophilus ducreyi were treated with intramuscular ceftriaxone
and randomized to three different dosage regimens. All but 1
of 50 men treated with 1╯g of intramuscular ceftriaxone were
cured. Similarly, 0.5 and 0.25╯g cured 43 of 44 men and 37 of
38 men, respectively. A single dose of 250╯mg of intramuscular
ceftriaxone is an effective treatment for chancroid.
Treatment of chancroid with ciprofloxacin. A prospective,
randomized clinical trial. Naamara W, Plummer FA,
Greenblatt RM, et al. Am J Med 1987: 82(4A):317–320.
A double-blind, randomized clinical trial was conducted
comparing a single-dose ciprofloxacin regimen (500╯mg) and
a 3-day ciprofloxacin regimen (500╯mg twice daily) with a
3-day regimen of trimethoprim-sulfamethoxazole (160 and
800╯mg, respectively, twice daily) for the treatment of chan-
croid. The 3-day ciprofloxacin regimen successfully eradicated
H. ducreyi, and resulted in rapid clinical improvement in all
40 patients followed, with no failures.
Randomized, double-blind, placebo-controlled trial of
erythromycin versus ciprofloxacin for the treatment of chan-
croid. Moses S, Malonza IM, Tyndall M, et al. Int Conf AIDS
1998; 12:300.
Double-blind, placebo controlled trial in which 245 men
and women with clinically suspected chancroid were rand-
A omized to receive either oral erythromycin, 500╯mg tid for 7
A days (E group) or single-dose oral ciprofloxacin, 500╯mg (C
A group). In 91 patients with confirmed HD infection, the cure
A rates were 91.2% (44/48) in the C group and 90.7% (39/43)
in the E group. Both the ciprofloxacin and erythromycin regi-
mens appear to be effective for the treatment of chancroid in
both HIV infected and uninfected individuals.
References
1. Habif TP, Campbel JL, Chapman S, Dinulos JGH, Zug A. Skin diseases:
diagnosis and treatment. 2nd ed. St. Louis: Elsevier/Mosby; 2004.
2. Centers for Disease Control and Prevention. Workowski KA, Berman
SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR
Recomm Rep 2006; 55:1–94.
3. World Health Organization. Guidelines for the management of sexu-
ally transmitted infections. Geneva: WHO; 2003.

Chlamydia trachomatis
Chlamydia trachomatis, an obligate intracellular bacterium, is
commonly implicated in cases of urogenital infection. Chlamy-
dial infections of this sort are caused by immunotypes D–K
which represent a separate clinical entity from immunotypes
L1–L3 that cause lymphogranuloma venereum (see p. 135).1
According to CDC, C. trachomatis is the most commonly
reported sexually transmitted disease in the US and has a high
prevalence in the young adult population (18–26 years old).2
Alarmingly, 2.8 million new cases are estimated to occur
every year.3
In women, the infection ascends through the reproductive
tract and can cause cervicitis and salpingitis. In the asympto-
matic female carrier, the disease can work insidiously and
eventually lead to pelvic inflammatory disease (PID). It is
estimated that 10–40% of women with an untreated ChlaÂ�
mydial infection develop PID; of these 20% can become
infertile.4
As is the case with women, men are typically asymptomatic.
When present, symptoms are usually secondary to urethritis,
while epididymitis and prostatitis can occur. In men who
engage in sex with men, proctitis and proctocolitis have been
reported.5
A battery of tests are available to diagnose Chlamydial
infection. Since C. trachomatis and N. gonorrhea are often coin-
fectors, a Gram stain of urethral discharge can usually rule in
Chlamydia with the absence of Gram-negative diplococcic
(GNDC); though this technique is by no means diagnostic.
Culture of the organism is possible, but it is resource intensive
and results are delayed, leading to scant usage of this modality.
In clinical practice, commonly used tests are nucleic acid
amplification tests (NAATs), a common example being a
urine-based test.5 Evidence based recommendations include
screening pregnant women who are under 25, at risk-non
pregnant women, as well as women who are older. Routine
screening of men is not recommended.6
As aforementioned, N. gonorrhea and C. trachomatis often
coinfect the same individual, thus treating for both organisms
remains the standard of care. The following section outlines
treatment for C. trachomatis.
First-Line Therapies
Azithromycin 1╯g orally in a single dose A patients were asymptomatic. Bacteriological eradication was
Doxycycline 100╯mg orally twice a day for 7 days A confirmed in 99% of doxycycline-treated patients.
A controlled trial of a single dose of azithromycin for the
treatment of chlamydial urethritis and cervicitis. The Azi-
thromycin for Chlamydial Infections Study Group. Martin
DH, Mroczkowski TF, Dalu ZA, et al. N Engl J Med 1992;
327(13):921–925.
299 female patients and 158 male patients with uncompli-
cated genital infection and a positive C. trachomatis antigen test
7â•… Infectious Diseasesâ•… •â•… Chlamydia trachomatis
were randomly assigned to receive either azithromycin (1╯g
once orally) or doxycycline (100╯mg orally twice daily for 7
days). 5 of the 141 patients treated with azithromycin did not
respond to treatment when compared with 3 of the 125
patients treated with doxycycline. Of the patients evaluated
21–35 days after treatment, none of 112 treated with azithro-
mycin and 1 of 102 treated with doxycycline had a positive
culture. A single dose of azithromycin was found to be as effec-
tive as a 7-day course of doxycycline.
A randomized trial of azithromycin versus amoxicillin for
the treatment of Chlamydia trachomatis in pregnancy. Kacmar
J, Cheh E, Montagno A, et al. Infect Dis Obstet Gynecol 2001;
9(4):197–202.
Randomized single-blind trial of 39 women diagnosed with
C. trachomatis before 33 weeks gestation. Women were ran-
domly assigned to either 500╯mg amoxicillin orally three times
per day for 7 days or a single dose of 1╯g azithromycin orally.
19 received amoxicillin and 20 received azithromycin. Of
patients who returned for follow-up evaluation for cure, 3 of
15 (20%) in the amoxicillin group were positive compared
with 1 of 19 (5%) in the azithromycin group. Those taking
azithromycin did experience more gastrointestinal side effects.
Randomized trial of erythromycin and azithromycin for
treatment of chlamydial infection in pregnancy. Rosenn MF,
Macones GA, Silverman NS. Infect Dis Obstet Gynecol 1995;
3(6):241–244.
48 pregnant women with cervical chlamydial infections
diagnosed by routine screening tests were randomly assigned
to receive either erythromycin, 500╯mg qid for 7 days (N = 24),
or azithromycin, 1╯g as a one-time dose (N = 24). There was
no significant difference in cure rates noted between the eryth-
romycin group and the azithromycin group, 77% vs 91%
respectively. Gastrointestinal side effects were reported more
frequently among patients treated with erythromycin com-
pared with patients treated with azithromycin.
Chlamydial cervicitis and urethritis: single dose treatment
compared with doxycycline for seven days in community
based practises. Thorpe EM Jr, Stamm WE, Hook EW 3rd.
Genitourinary Med 1996; 72(2):93–97.
Randomized, unblinded, comparative trial, involving 597
patients demonstrating clinical evidence of genital chlamydia
and a positive non-culture assay for Chlamydia trachomatis. A
7-day regimen of doxycycline was used. Two weeks after the
first dose, 86% of azithromycin and 83% of doxycycline
A double blind study of single dose azithromycin and doxy-
cycline in the treatment of chlamydial urethritis in males.
Nilsen A, Halsos A, Johansen A, et al. Genitourinary Med
1992; 68(5):325–327.
Double-blind, randomized treatment study using 130
males with clinical signs and symptoms of urethritis. Patients
were randomly allocated to 1000╯mg azithromycin as single
dose or doxycycline 100╯mg twice daily for 7 days. Clinical,
125
 Part 1 Medical Dermatology
bacteriological and safety assessments were made at entry and
after 1 and 2 weeks. Safety data were also repeated after 4
weeks. Demographic data were similar in both groups. At the
week 1 assessment bacteriological eradication was achieved in
44 of 44 evaluable azithromycin treated patients and in 42 of
42 in the doxycycline group.
Second-Line Therapies
Erythromycin base 500╯mg orally four times a day for 7 A
days
Levofloxacin 500╯mg orally once daily for 7 days
Ofloxacin 300╯mg orally twice a day for 7 days B
Chlamydia in pregnancy: a randomized trial of azithromy-
cin and erythromycin. Adair CD, Gunter M, Stovall TG, et al.
Obstet Gynecol 1998; 91(2):165–168.
85 pregnant women with positive DNA antigen assays for
Chlamydia trachomatis completed a study in which they were
randomized to either azithromycin, 1╯g single dose orally, or
erythromycin, 500╯mg every 6 hours for 7 days. While similar
treatment efficacy was noted between azithromycin and eryth-
romycin, a better gastrointestinal side effect profile and easier
dosing regimen make azithromycin the preferred agent.
Randomized clinical trial of azithromycin vs erythromycin
for the treatment of chlamydia cervicitis in pregnancy.
Edwards MS, Newman RB, Carter SG, et al. Infect Dis Obstet
Gynecol 1996; 4(6):333–337.
140 women who tested positive for Chlamydia cervicitis
were prospectively randomized to receive either azithromycin
1╯g orally at enrollment, or erythromycin 500╯mg orally 4
times a day for 7 days. There were 4 (6.2%) treatment failures
in the azithromycin group and 18 (27.7%) in the erythromy-
cin group. Gastrointestinal side effects and resultant non-
compliance were significantly related to treatment failure with
erythromycin.
Donovanosis
(Granuloma inguinale)
Also known as granuloma inguinale, Donovanosis is chronic,
slowly progressive cause of genital ulceration.1 A disease
almost limited to developing nations, Donovanosis is endemic
in Africa, South East Asia, portions of India, South America
and Australia. It has still not been proven to be exclusively a
sexually transmitted disease, although it is clear that sexual
intercourse is the predominant mode of transmission. To this
end, some authors have proposed a fecal auto-inoculation
126
Ofloxacin versus doxycycline for treatment of cervical infec-
tion with Chlamydia trachomatis. Hooton TM, Batteiger BE,
Judson FN, et al. Antimicrob Agents Chemother 1992;
36(5):1144–1146.
56 women with culture-proven Chlamydia trachomatis cervi-
cal infection were randomized to receive either ofloxacin
(300╯mg) or doxycycline (100╯mg), orally twice daily for 7
days. All 56 had negative cultures 5–9 days after treatment.
Four weeks after treatment, 26 (93%) of 28 ofloxacin-treated
patients and all 22 doxycycline-treated patients were cured.
Adequate levofloxacin treatment schedules for uterine cervi-
citis caused by Chlamydia trachomatis. Mikamo H, Sato Y,
Hayasaki Y, et al. Chemotherapy 2000; 46(2):150–152.
Levofloxacin at a dosage of 300╯mg tid for 5, 7 and 14 days
was orally administered to 18, 33 and 35 Japanese patients,
respectively. The eradication rate and the recurrence rate in the
different treatment schedules of C. trachomatis were evaluated.
The eradication rate in 5-, 7- or 14-day courses was 44.4, 87.9
or 88.6%, respectively. Levaquin was found to be an acceptable
agent in the treatment of chlamydial infection.
References
1. Centers for Disease Control and Prevention. Workowski KA, Berman
SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR
Recomm Rep 2006; 55:1–94.
2. Sexually Transmitted Diseases Surveillance, 2008. Centers for Disease
Control. 2008. [Accessed February 8, 2010 from http://www.cdc.gov/
STD/stats08/chlamydia.htm]
3. Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases
among American youth: incidence and prevalence estimates, 2000.
Perspect Sex Reprod Health 2004; 36:6–10.
4. Report To Congress. Infertility and Prevention of Sexually
Transmitted Diseases 2000–2003. Centers for Disease Control 2004
[Accessed February 8, 2010 from http://www.cdc.gov/std/infertility/
ReportCongressInfertility.pdf]
5. Screening tests to detect Chlamydia trachomatis and Neisseria gonor-
rhoeae infections – 2002. MMRW/CDC. [Accessed February 8, 2010
from http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5115a1.htm]
6. Meyers DS et al. Screening for chlamydial infection: an evidence
update for the U.S. Preventive Services Task Force. Ann Intern Med
2007; 147(2):135–142.
theory as the causative organism, Klebsiella granulomatis, has
been isolated from the feces. Another feature that sets it apart
from other genito-ulcerative diseases is the occasional occur-
rence of metastatic lesions in the liver, lungs, bones and intes-
tines. Very rarely these may occur without ano-genital lesions
creating diagnostic difficulties. Lastly, 0.25–0.5% of patients
may develop squamous cell carcinoma in longstanding ulcers.
The incubation period varies from 1 week to 6 months,
although this determination can be difficult to ascertain since
the index case may not be remembered correctly. A painless,
reddish papule appears at the site of inoculation, gradually
enlarges and breaks down to form a painless ulcer. The ulcer
is typically ‘beefy red’ with well defined margins, bleeds
on touch and varies in size (Figs. 7.7–7.9). It is slightly
 7â•… Infectious Diseasesâ•… •â•… Donovanosis (Granuloma inguinale)
Figure 7.7:╇ Donovanosis. (From James et al, Andrew’s Diseases of the Skin
Clinical Dermatology, 10e, copyright Elsevier 2006.)
Figure 7.8:╇ Donovanosis. (From James et al, Andrew’s Diseases of the Skin
Clinical Dermatology, 10e, copyright Elsevier 2006.)
Figure 7.9:╇ Donovanosis of penis and adjacent skin of leg. (From James et al,
Andrew’s Diseases of the Skin Clinical Dermatology, 10e, copyright Elsevier 2006.)
elevated above the surrounding skin and resembles exuberant
granulation tissue. Atypical lesions include the hypertrophic,
necrotic and cicatricial variants. The latter two may lead to
significant destruction of tissue and complications like ampu-
tation of the penis and esthiomene in women. Lymphatic
involvement is not a feature of Donovanosis and there is no
regional lymphadenopathy. The course of the disease is chronic
with little or no tendency for spontaneous healing. Diagnostic
tests for Dovovanosis are reviewed in Table 7.1.
The Centers for Disease Control and Prevention in the
United States has recommended a twice daily regimen of
Doxycyline 100 mg for 3 weeks and until all lesions are com-
pletely healed as first-line therapy.2
First-Line Therapies
Doxycycline 100╯mg orally twice a day for at least 3 weeks and
until all lesions have completely healed.
Second-Line Therapies
Azithromycin 1╯g orally once weekly for 3 weeks and B
until all lesions have completely healed.
Ciprofloxacin 750╯mg orally twice daily for 3 weeks and E
until all lesions have completely healed
Erythromycin base 500╯mg orally four times a day for E
3 weeks and until all lesions have completely healed
Trimethoprim-sulfamethoxazole one double-strength D
(160╯mg/800╯mg) tablet orally twice daily for 3 weeks
and until all lesions have completely healed
127
 Part 1 Medical Dermatology
Table 7.1╇ Diagnostic tests for Donovanosis (granuloma inguinale)
Test Features
Direct visualization of Klebsiella granulomatis
Tissue smear Tissue smears are made either by the crush or
impression technique, and after air drying are
stained with Giemsa or Wright’s stain for 10
minutes or in case of suspected false-negative
result, the stain can be left overnight for
improved sensitivity. Under 100× power the
bacilli appear as bright pink ovoid bodies
(Donovan bodies) with a dark nucleus and
peripheral condensation of chromatin (bipolar).
These may be seen lying singly or more
often in clusters both within and outside
macrophages. This is the single most useful
test to diagnose Donovanosis and must be
repeated on at least three consecutive days
before being declared negative.
Biopsy Primarily performed to rule out malignant
transformation, DB can be demonstrated with
special stains such as Giemsa and Delafield’s
haematoxylin and eosin.
Other tests
PCR Recently developed, this is a promising tool as it
can differentiate C. granulomatis from closely
related species of Klebsiella.
Culture Culture is possible in peripheral blood
lymphocytes but the test has little clinical use.
Serological tests Complement fixation test available for population
surveys. Not useful in individual cases due to
poor sensitivity.
Exanthems
See Table 7.2.
128
Pilot study of azithromycin in the treatment of genital
donovanosis. Bowden FJ, Mein J, Plunkett C, et al. Genitourin
Med 1996; 72:17–19.
Patients with histologically confirmed Donovanosis were
randomized to receive one of two open-label azithromycin
dosage regimens – regimen A, 1.0╯g once weekly for 4 weeks;
or regimen B, 500╯mg daily for 7 days. 7 patients received
regimen A and 4 received regimen B. Six weeks after commenc-
ing treatment, the genital ulcers of 4 patients receiving regimen
A and 1 patient receiving regimen B had healed; the lesions of
the other 6 patients (3 in each regimen) were ‘improved’. No
patient failed to respond and no significant adverse reaction
was recognized. The 11 patients were reviewed after complet-
ing the 6-week trial; all lesions had re-epithelialized without
further antibiotic treatment, no relapses had occurred.
A further 17 patients with Donovanosis who were unable
to meet the entry criteria were also treated successfully with
azithromycin during the study period.
Successful treatment of donovanosis with ciprofloxacin.
Ahmed BA, Tang A. Genitourinary Med 1996; 72(1):73–74.
A 38-year-old male from Zambia presented with confirmed
Donovanosis responded to treatment with ciprofloxacin
500╯mg BID. Complete re-epithelialization occurred within
2 weeks.
The treatment of Donovanosis (granuloma inguinale). Latif
AS, Mason PR, Paraiwa E. Sex Transm Dis 1988; 15:27–29.
37 patients with genital ulcer disease attending a clinic for
sexually transmitted diseases were found to have Donovanosis.
All patients responded well to either a combination of
intramuscular streptomycin plus oral tetracycline given over
14 days, or a 14-day course of oral trimethoprim-
sulfamethoxazole.
References
1. Valia RG, Valia AR, editors. IADVL Textbook of Dermatology. 3rd ed.
Mumbai: Bhalani Publishing House; 2008.
2. Centers for Disease Control and Prevention. Workowski KA, Berman
SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR
Recomm Rep 2006; 55:1–94.
First-Line Therapies
Measles-mumps-rubella varicella (MMRV) Vaccine A
Measles (rubeola)
German measles (rubella)
Chicken pox (varicella)
Scarlet fever (Streptococcus pyogenes)
Penicillin (Bicillin L A, Beepen VK, Pen Vee K) A
(see Table 7.2)
Table 7.2╇ Exanthems

Disease Incubation period Clinical features

Viral exanthems
Measles (rubeola) 8–12 days Flu like prodrome with the development of Koplick’s spots which appear on the oral mucosa just before
the exanthem and last 2 to 4 days. Exanthem begins on 4th or 5th day of fever in the posterior
auricular area. Erythematous macules and papules that blanch on pressure are typically seen.
Exanthem fades after 5 to 10 days. Complications include bronchopneumonia, diarrhea, otitis media
and acute encephalitis. Vitamin A deficiency may be precipitated.
German measles 14–23 days 25 to 50% infections are subclinical. Mild prodrome followed by exanthem that begins on the face
(rubella) and spreads downwards. Tender retroauricular and/or suboccipital lymphadenopathy are a hallmark.
They may appear up to a week before the rash and be maximal in intensity at its onset.
Chickenpox Fever, malaise, anorexia for 2 days followed by erythematous macules that evolve into vesicles
(varicella) containing serous fluid (which may later become turbid) on an erythematous base (described as a
‘dew drop on rose petal’); Polymorphic lesions may be seen, as well as different stages of the lesions
seen simultaneously. Central umbilication can be observed.
Roseola Infantum 5–15 days Classically the rash begins suddenly on the day the fever subsides, usually the 6th day giving rise to the
(Exanthema term ‘sixth disease’. Pale, pink almond shaped macules are the characteristic lesions. Fever may be
subitum) high grade during the prodrome; febrile seizures are possible; however little else is abnormal during
(HHV6 > this period. Rash fades within 2 days without sequelae. Since children are generally not ill, no
HHV7) vaccine has been developed for this condition. With the exception of Aspirin, antipyretic or anti-
inflammatory medications as well as hydration is usually adequate therapy.
Erythema 13–18 days Mild or absent prodrome. Exanthem has three distinct, overlapping and classically distinct stages: Facial
Infectiosum erythema (slapped cheek appearance), reticulate erythema and the recurrent phase where lesions
(Fifth disease) may fade only to reappear in 2 to 3 weeks. The exanthem may last up to 2 weeks, much longer than
(Parvovirus seen in other viral exanthematous conditions. Complications include papular-purpuric “gloves and
B19) stocking” syndrome and polyarthropathy and pruritic syndrome. Patients are deemed no longer
infectious when rash is manifested.5,6 Up to 1╯gm% fall in hemoglobin in immunocompetent
individuals. Red cell aplasia and a chronic anemia can occur in immunosuppressed patients. No
lymphadenopathy. There is no specific vaccine against or treatment for Erythema Infectiosum.
Hand, foot and 4–6 days Mild prodrome. Exanthema of apthae-like erosions in the oral cavity is the presenting feature in the
mouth disease majority of cases. Followed within one day by the exanthem of small macules that develop a vesicular
(HFMD) center with a red areola. The typical picture is that of a variable number of pale, greyish, oval vesicles
(Coxsackie present over the acral areas, fading within 7 days. Rare complications include aseptic meningitis,
virus A16 and encephalomyelitis and pulmonary edema. No specific treatment exists for this condition. Symptoms
enterovirus may be addressed with analgesics, or antipyretics. However, since the disease is self limiting, there
71) is no compelling need to treat.
Non-specific viral Variable The most common viral exanthem caused by a multitude of viruses, including the above named types.
exanthema Manifesting as generalized erythematous maculo-papules associated with a typical ‘viral fever’, it
(the ‘viral often cannot be distinguished from drug eruptions. The rash is usually asymptomatic. Urticarial,
rash’) petechial and vesicular lesions are possible. Palms and soles may be involved. Encephalitis, as in
most viral infections, is a possible, albeit very rare complication. In most cases the rash fades without
sequelae.
Bacterial exanthems
Scarlet fever 2–4 days Sudden onset fever and pharyngitis. Oral cavity shows a “white strawberry tongue” caused by the
(Streptococcus hypertrophy of lingual papillae protruding through the coated white tongue. The yellowish-white coat
pyogenes) is shed later to produce the classical “red strawberry tongue”. The exanthem begins 2 days after the
fever. Starting from the head and neck area, it spreads in another 2 days to involve the rest of the
body, sparing the soles and palms. The rash has a pinpoint sandpaper like quality and in fair skin
confluence of the rash leads to a vivid scarlet hue. Circumoral pallor and pastia’s sign are other
features. The rash fades in 5–7 days followed by pronounced desquamation of skin over the palms
and soles.
1. Richardson M, Elliman D, Maguire H, Simpson J, Nicoll A. Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable
diseases in schools and preschools. Pediatr Infect Dis J 2001; 20(4):380–91.
2. Edlich RF, Winters KL, Long WB, Gubler KD. Rubella and congenital rubella (German measles). J Long Term Eff Med Implants 15(3):319–28.
3. Weir E et al. A refresher on rubella. CMAJ 2005; 172(13):1680–1.
4. Habif TP. Clinical dermatology: a color guide to diagnosis and therapy. New York: Mosby, 2003:467.
5. Sabella C, Goldfarb J. Parvovirus B19 infections. Am Fam Phys 1999;60(5):1455–60.
6. Servey JT, Reamy BV, Hodge J. Clinical presentations of parvovirus B19 infection. Am Fam Physician 2007; 75(3):373–6.

129
 Part 1 Medical Dermatology

Scarlet fever Adult References

• Penicillin VK: 250–500╯mg PO qid for 10╯d
• Penicillin G benzathine: 1.5 million U IM once 1. Richardson M, Elliman D, Maguire H, Simpson J, Nicoll A. Evidence
base of incubation periods, periods of infectiousness and exclusion
policies for the control of communicable diseases in schools and
Scarlet fever Pediatric preschools. Pediatr Infect Dis J 2001; 20(4):380–391.
• Penicillin VK: 2. Edlich RF, Winters KL, Long WB, Gubler KD. Rubella and congenital
rubella (German measles). J Long Term Eff Med Implants 2005;
– < 12 years: 25–50╯mg/kg/d PO divided qid; not to exceed
15(3):319–328.
3╯g/d 3. Weir E, et al. A refresher on rubella. CMAJ 2005; 172(13):
– > 12 years: administer as in adults 1680–1681.
• Penicillin G benzathine: 4. Habif TP. Clinical dermatology: a color guide to diagnosis and therapy.
– < 12 years: 25,000–50,000╯U/kg IM once; not to exceed New York: Mosby; 2003. p. 467.
5. Sabella C, Goldfarb J. Parvovirus B19 infections. Am Fam Phys 1999;
1.2 million U/dose 60(5):1455–1460.
– > 12 years: administer as in adults 6. Servey JT, Reamy BV, Hodge J. Clinical presentations of parvovirus B19
infection. Am Fam Phys 2007; 75(3):373–376.

Second-Line Therapies

Scarlet fever (Streptococcus pyogenes) for penicillin allergic patients

Erythromycin (E.E.S.) A
Adult: 250╯mg PO qid for 10╯d
Pediatric: 30–50╯mg/kg/d PO divided qid for 10╯d

Virtually any anti-staphylococcal penicillin or cepha-

Folliculitis losporin will be an effective agent in the treatment of
un�complicated folliculitis, typically caused by Gram-negative
organisms or methicillin-sensitive S. aureus (MSSA).
Folliculitis may be classified as either superficial or deep with
Efficacy and safety of 2% mupirocin ointment in the treat-
superficial folliculitis referring to inflammation of the terminal
ment of primary and secondary skin infections – an open
portion of the hair follicle and deep folliculitis to inflamma-
multicentre trial. Bork K, Brauers J, Kresken M. Br J Clin Pract
tion of the entire hair follicle. Both types of folliculitis are
1989; 43(8):284–288.
caused by Staphylococcus aureus. The use of occlusive dressings,
Study examining the efficacy and safety of mupirocin in
mineral oil, adhesive tapes, and coal tar preparations are some
1391 general practice patients with superficial skin infections.
of the predisposing factors for superficial folliculitis. Chronic
The most common skin infections treated were pyoderma (e.g.
folliculitis is seen more often in individuals who are carriers
impetigo, folliculitis) and secondarily infected skin lesions. At
of S. aureus.
the end of the treatment 961 (73.7%) patients were cured and
Superficial folliculitis is characterized by dome shaped pus-
tules with a hair or follicular orifice in the center as well as
perifollicular erythema (Fig. 7.10). Deep folliculitis preferen-
tially affects the beard area (sycosis barbae) or the nape of the
neck (sycosis nuchae).These lesions are erythematous papulo-
pustules with a central follicular orifice and crusting, which
typically heals with scarring. The diagnosis is made clinically
by observing the characteristic lesions. However, a Gram’s stain
will reveal polymorphonuclear leucocytes and Gram-positive
cocci.

First-Line Therapies

Topical therapy
2% Mupirocin ointment A

Oral therapy Figure 7.10:╇ Bacterial folliculitis. Hyperpigmented papules with slight erythema are
Cephalexin B seen. (From Johnson, Moy, White: Ethnic Skin – Medical and Surgical, Mosby,
copyright Elsevier 1998.)

130

in 293 (22.5%) patients the symptoms of the infection had
markedly improved. In total, 525 bacterial strains were iso-
lated from the wounds of 445 patients, which were predomi-
nantly staphylococci (n = 344) and streptococci (n = 93).
Mupirocin was deemed an effective agent without systemic
absorption.
Comparative double-blinded study between mupirocin and
tetracycline ointments for treating skin infections. Wong KS,
Lim KB, Tham SN, et al. Singapore Med J 1989; 30(4):
380–383.
A double-blinded study compared the efficacy of mupirocin
and tetracycline ointments in the treatment of skin infections.
Of 111 patients, 53 were treated with mupirocin and 58 treated
with tetracycline. Clinically, both groups were improved, and
there was no significant difference between the groups. Bacte-
riological assessment, however, revealed a better response to
mupirocin. Staphylococcus aureus and Streptococcus pyogenes
were the most common organisms isolated. 99% of Staphylo-
cocci were sensitive to mupirocin compared with 61% to
tetracycline and 29% to penicillin G. 57% of Group A
beta haemolytic Streptococci were resistant to tetracycline
compared to 14% to mupirocin. Gram-negative organisms
were mostly resistant to both preparations.
Topical antibiotics in the treatment of superficial skin infec-
tions in general practice – a comparison of mupirocin with
sodium fusidate. White DG, Collins PO, Rowsell RB. J Infect
1989; 18(3):221–229.
Randomized clinical trial comparing the clinical and bacte-
riological efficacy of mupirocin (Bactroban) ointment with
sodium fusidate (Fucidin) ointment for treating superficial
skin infections in 413 patients. Mupirocin was applied twice
daily and sodium fusidate three times daily for 7 days. Both
treatments were similarly effective with 97% patients treated
with mupirocin and 93% patients treated with sodium fusi-
date responding. Mupirocin was significantly more effective in
the treatment of acute primary skin infections and in the treat-
ment of a subgroup of patients with impetigo. Of the organ-
isms detected before treatment began, 93% were not found
after treatment with mupirocin compared with 89% after
treatment with sodium fusidate. Staphylococcus aureus and/or
beta-haemolytic streptococci appeared to be eliminated in
significantly more patients treated with mupirocin (96%)
compared with those treated with sodium fusidate (88%).
Cefdinir vs cephalexin for mild to moderate uncomplicated
skin and skin structure infections in adolescents and adults.
Furunculosis
A furuncle, also referred to as a boil, is a painful, erythematous
papule or nodule centered around a hair follicle. It then
progresses to become a walled off collection of purulent mate-
rial which can develop an opening to the skin surface. These
7â•… Infectious Diseasesâ•… •â•… Furunculosis
Giordano PA, Elston D, Akinlade BK, et al. Curr Med Res Opin
2006; 22(12):2419–2428.
Investigator-blinded, multicenter study in which 391
patients at least 13 years of age with uncomplicated skin and
soft tissue infections were randomized to receive 10 days of
cefdinir 300╯mg twice daily (BID) or cephalexin 250╯mg four
times daily. Abscess(es) (26%), wound infection (24%), and
cellulitis (21%) were the most common infections. The clinical
cure rate for both treatment groups was 89% (151/170 for
cefdinir and 154/174 for cephalexin). This study demonstrated
that empiric coverage of uncomplicated skin infections
with cephalosporin therapy remains an appropriate clinical
strategy.
Second-Line Therapies
Trimethoprim-sulfamethoxazole B
Doxycycline B
In the era of methicillin-resistant S. aureus (MRSA), the
clinician must be alert to infection caused by this organism.
Two oral agents with activity against MRSA have emerged as
effective options for folliculitis and soft tissue infections.
Prospective randomized trial of empiric therapy with
trimethoprim-sulfamethoxazole or doxycycline for outpa-
tient skin and soft tissue infections in an area of high preva-
lence of methicillin-resistant Staphylococcus aureus. Cenizal
MJ, Skiest D, Luber S, et al. Antimicrob Agents Chemother
2007; 51:2628–2630.
Thirty-four subjects were included in this study, of whom
14 received trimethoprim-sulfamethoxazole (8 with MRSA)
and 20 received doxycycline (15 with MRSA). 3 of the 33
subjects (9%) in whom data was obtained at 10–14 days were
classified as clinical failures. All 3 clinical failures occurred in
the trimethoprim-sulfamethoxazole group (3 failures out of
14 [21%] subjects on trimethoprim-sulfamethoxazole therapy),
with no clinical failures in the doxycycline group. By culture,
two of the clinical failures with trimethoprim-sulfamethoxazole
had MRSA, and one had Streptococcus milleri. All other subjects
were reported to have had a good response at 10–14 days after
initial presentation.
are sometimes referred to as abscesses, however, unlike a
furuncle, an abscess can occur on non-hair-bearing skin. The
suppuration found in furuncles is deeper than in folliculitis,
and can progress to carbuncles, where there are multiple
walled off furuncles connected by draining sinus tracts. Furun-
cles are most commonly seen in hair-bearing areas of the body,
especially where there is friction such as the face, neck, axillae,
buttocks, thighs and perineum.
131
 Part 1 Medical Dermatology
Some patients may develop recurrent furunculosis. Those
at risk for developing recurrent lesions include prisoners, ath-
letes, men who have sex with men, those with poor personal
hygiene, a history of sleeping in overcrowded areas, a history
of hospitalizations, and prior antibiotic therapy. A positive
family history of furunculosis is the most correlated independ-
ent risk factor in logistic regressions. Other characteristics of
patients who develop recurrent lesions include obesity, immu-
nologic dysfunction, immunosuppressive therapy, anemia and
diabetes.1,2,3
Furuncle-like lesions can be caused by a variety of infectious
agents; the most common agent by far is Staphylococcus aureus.4
Clinically, a clue to infection with this agent is a rim of scale
surrounding the central punctum.5 As with other soft tissue
infections, methicillin resistant S. aureus (MRSA) is becoming
an increasing concern, affecting both patients in the commu-
nity as well as patients with recent hospitalizations.6
Worldwide, as well as in travelers to foreign countries, the
physician should be aware that furunculosis or furuncle-like
lesions can be caused by a variety of organisms, and include
Dermatobia hominis, Cordylobia anthropophaga, Cuterebra spp,
Tunga penetrans, Wohlfahrtia vigil, W. opaca, Cordylobia anthro-
pophaga and atypical mycobacteria.7,8 In human myiasis, fly
larvae invade the skin, an inflammatory reaction ensues, the
central punctum is left after larvae penetrate, and through this,
the larvae breathe. The larvae that commonly cause human
furuncular myiasis are Dermatobia hominis (North, Central,
and South America), Cordylobia anthropophaga (tropical Africa),
Cuterebra spp (United States), Wohlfahrtia vigil, and W. opaca
(young children). Patients may have sensation of movement
in the lesion and have severe, nocturnal, ‘lightning-like’ pain.9
Tunga penetrans, a sand flea, is the cause of tungiasis in Latin
America, Africa and India, and it develops after the female flea
buries itself in the skin it comes in contact with (usually the
feet and toes).10 There have been several reports of women
developing furunculosis secondary to mycobacteria from stag-
nant water in the footbath after pedicures (Mycobacteria fortui-
tum, M. mageritense and M. chenlonae have all been reported
in immunocompetent hosts).11
First-Line Therapy
Staphylococcus aureus furunculosis
Incision and drainage B Intervention
Oral antibiotics B
Incision and drainage
Evidence suggests that antibiotics may not even be necessary
in the treatment of furunculosis, and that incision and drain-
age may be sufficient for therapy.
Treatment of abscesses in the era of methicillin resistant
Staphylococcus aureus: are antibiotics necessary [abstract]?
Rejandran PM, Young D, Maurer T, et al. J Am Coll Surg 2006;
203(suppl):S62.
This randomized, placebo-controlled trial included 166
patients, including patients with comorbid conditions (HIV,
132
diabetes mellitus, hepatitis). After incision and drainage,
patients either received placebo, or a course of cephalexin.
Cure rates were similar for both groups (not statistically sig-
nificant; cephalexin 86% vs placebo 89%). When analyzed
for patients who had MRSA, there remained no statistical
difference between the antibiotic (88%) and the placebo
group (89%) in terms of cure rates.
Oral antibiotics
Patients who may become systemically ill from furuncles,
developing, fever, chills and leukocytosis, will require oral
antibiotic therapy. There are reports of bacterial endocarditis
in patients with chronic furunculosis.12 Two clinical situations
which necessitate the use of oral antibiotics are in furuncles
within and around the nares and external auditory ear canal.
Patients with chronic furunculosis or furuncles resistant to
treatment should also receive oral antibiotics. Lastly, when a
surrounding cellulitis ensues, antibiotics are required.13 As in
impetigo, treatment should be culture directed; when MRSA is
of high suspicion, the appropriate antibiotics must be selected.
Special management considerations
In otherwise healthy patients with recurrent furunculosis,
decolonization is important because some strains of S. aureus
are extremely virulent, and have the potential to cause necro-
tizing pneumonias in even healthy people.14 Strains with the
Panton-Valentine leukocidin gene, which encode for lukS-lukF,
are the main cause for recurrent furunculosis. Decolonization
entails a 5-day course which includes mupirocin nasal oint-
ment twice to three times daily, chlorhexidine 0.1% gargle
three times daily, and daily skin and hair washing with an
octenidin-based wash. This combination decolonization
therapy has been shown to be successful in a village with an
epidemic of staphylococcal furunculosis.15 A 10-day course of
rifampin as well as low dose azithromycin have also been
successful in the elimination of nasal carriage of S. aureus16,17
(see Table 7.3).
Table 7.3╇ Methods for decolonization of staphylococcal nasal carriage
Dose/route Frequency Duration
Topical
Mupirocin Topically BID – TID 5 days
Fusidic acid Topically BID – TID 5 days
Chlorhexidine 0.1% Orally TID 5 days
gargle
Antibacterial soap and Topically Daily
shampoo
Systemic
Rifampin 450–600╯mg Daily 10 days
Azithromycin 500╯mg Weekly 12 weeks
 7â•… Infectious Diseasesâ•… •â•… Human papilloma virus (HPV)
References
1. El-Gilany AH, Fathy H. Risk factors of recurrent furunculosis. Dermatol
Online J 2009; 15(1):16.
2. Kang SS, Kauls LS, Gaspari AA. Toll-like receptors: applications to
dermatologic disease. J Am Acad Dermatol 2006; 54(6):951–983.
3. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin physiol-
ogy and skin manifestations of obesity. J Am Acad Dermatol 2007;
56(6):901–916.
4. Bernard P. Management of common bacterial infections of the skin.
Curr Opin Infect Dis 2008; 21(2):122–128.
5. Levy AL, Simpson G, Skinner RB Jr. Medical pearl: circle of desquama-
tion – a clue to the diagnosis of folliculitis and furunculosis caused by
Staphylococcus aureus. J Am Acad Dermatol 2006; 55(6):1079–1080.
6. Elston DM. Community-acquired methicillin-resistant Staphylococcus
aureus. J Am Acad Dermatol 2007; 56(1):1–16.
7. Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engl
J Med 2002; 347(7):505–516.
8. McGraw TA, Turiansky GW. Cutaneous myiasis. J Am Acad Dermatol
2008; 58(6):907–926.
9. Maier H, Hönigsmann H. Furuncular myiasis caused by Dermatobia
hominis, the human botfly. J Am Acad Dermatol 2004; 50(2 Suppl):
S26–S30.
10. Nordlund JJ. Cutaneous ectoparasites. Dermatol Ther 2009; 22(6):
503–517.
Human papilloma
virus (HPV)
Human papillomaviruses, or HVP, are a class of DNA viruses
commonly implicated in sexually transmitted infections. They
invade squamous epithelium and trigger cell proliferation; this
abnormal growth in turn leads to cutaneous lesions. There are
more than 100 different types of viruses, many of them simply
causing benign self-limiting growths (verrucae or simple warts;
Fig 7.11). However, about 30 types can infect the genital epi-
thelium and are of concern, as they can be oncogenic. High-
risk types are associated with anogenital (Table 7.4) and
cervical cancers, particularly types 16, 18, 31 and 35. The onco-
genic HPV viruses are responsible for 99.7% of all cervical
cancers; however most infections do not lead to cervical cancer.
HPV occurs commonly. A recent study found the prevalence
of HPV among women aged 14–59 in the US to be 26.8%. A
review of the literature found that the prevalence of HPV
among men ranged from 1.3% to 72.9%.
Clinical features
The classic anogenital wart, also known as condyloma acumi-
nata, is a soft, pink, pedunculated papilliferous mass. The
surface is pointed, irregular and fissured. They are highly vas-
cular and show a punctuated pattern on mucosal surface on
magnification. They may coalesce to form large plaques or
cauliflower like lesions particularly in pregnant or immuno-
11. Redbord KP, Shearer DA, Gloster H, et al. Atypical Mycobacterium
furunculosis occurring after pedicures. J Am Acad Dermatol 2006;
54(3):520–524.
12. Bahrain M, Vasiliades M, Wolff M, Younus F. Five cases of bacterial
endocarditis after furunculosis and the ongoing saga of community-
acquired methicillin-resistant Staphylococcus aureus infections. Scand
J Infect Dis 2006; 38:702–707.
13. Daum RS. Skin and soft-tissue infections caused by methicillin-
resistant Staphylococcus aureus. N Engl J Med 2007; 357:380–390.
14. Gillet Y, Issartel B, Vanhems P, et al. Association between Staphylococcus
aureus strains carrying gene for Panton-Valentine leukocidin and highly
lethal necrotising pneumonia in young immunocompetent patients.
Lancet 2002; 359:753–759.
15. Wiese-Posselt M, Heuck D, Draeger A, et al. Successful termination
of a furunculosis outbreak due to lukS-lukF-positive, methicillin-
susceptible Staphylococcus aureus in a German village by stringent
decolonization, 2002–2005. Clin Infect Dis 2007; 44(11):e88–e95.
16. Mashhood AA, Shaikh ZI, Qureshi SM, Malik SM. Efficacy of rifampicin
in eradication of carrier state of Staphylococcus aureus in anterior nares
with recurrent furunculosis. J Coll Physicians Surg Pak 2006; 16:
396–399.
17. Aminzadeh A, Demircay Z, Ocak K, et al. Prevention of chronic furun-
culosis with low-dose azithromycin. J Dermatol Treat 2007; 18:
105–108.
suppressed patients. Papular warts are discrete, dome shaped,
raised lesions 1–10╯mm in diameter. When pigmented they
should be biopsied to rule out intraepithelial neoplasia. The
third most common morphology is macular or flat condy-
loma. These are usually found on mucosal surfaces and are
best seen after aceto-whitening and magnification (colpos-
copy). Again biopsy is needed to rule out vulvar or penile
intraepithelial neoplasia. Giant condyloma (Buschke–
Lowenstein tumor), caused by HPV 6 and 11, is characterized
by aggressive downward as well as upward growth and presents
as a single, large, foul smelling, tumor-like mass. Dysplastic
Figure 7.11:╇ Human papilloma Virus (HPV). Verrucae vulgares, or common warts.
(From Bolognia; Dermatology 2e; fig 78.6 pp 1187; 2008, with permission from
Elsevier Ltd.)
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 Part 1 Medical Dermatology

regions may be seen on histopathology, however the lesion Diagnosis

does not metastasize. Local destruction, however, can be exten-
sive. Verrucous carcinomas are well differentiated squamous Clinical examination is usually sufficient to diagnose most
cell carcinomas whose appearance may clinically mimic giant external genital warts. The aceto-whitening test is sometimes
condylomas. These lesions follow an indolent course, although useful to identify suspect lesions despite low sensitivity and
metastases may occur. Uncommon presentations of anogenital specificity: 3–5% acetic acid is applied with a swab or cotton
warts include verruca vulgaris type keratotic warts, verruca ball to the area under investigation. Whitening is a positive
plana like sessile warts and the often overlooked, macular or end point and appears after 20–60 seconds on mucosa (cervix,
flat warts. anal canal) and 3–5╯min in keratinized epithelium (vulva,
penis, peri-anal skin). This whitish appearance is caused by
denaturation of the proteins in the relatively undifferentiated
Table 7.4╇ HPV types commonly associated with anogenital lesions virus infected keratinocytes.
Biopsy, when necessary, shows acanthosis and papilloma-
HPV type Associated clinical conditions tosis of the epidermis, variable parakeratosis and the presence
of koilocytes, which are rounded squamous cells having a peri-
6 Anogenital warts/laryngeal papillomas nuclear halo due to peripheral condensation of the cytoplasm.
The nucleus is hyperchromatic and may show mitotic activity.
11 Anogenital warts/laryngeal papillomas Though considered the diagnostic hallmark of HPV infection,
16 Anogenital warts/CIN/VIN/PIN/cervical carcinoma koilocytic changes are often subtle and other cellular changes
18 Genital warts/CIN/cervical carcinoma may mimic koilocytosis. HPV typing of anogenital warts does
31 Anogenital warts/CIN/cervical carcinoma not add information of clinical use.
35 Anogenital warts/CIN/Cervical cancer
CIN = cervical intraepithelial neoplasia, PIN = penile intraepithelial neoplasia, Treatment
VIN = vulval intraepithelial neoplasia.
See Table 7.5.

Table 7.5╇ Treatments for human papilloma virus1,2,3

Modality Mode of application Clearance Recurrence Side effect

Patient-applied treatment
Podophyllotoxin (0.5% Twice a day for 3 consecutive days in a week 60–90% 10–40% Irritation, erosion, ulceration
soln, 0.15% cream) for 4–6 weeks
Imiquimod 5% cream Three times a week; applied alternate day at 40–60% 10–20% Irritation, erosion, ulceration
bed time for up to 16 weeks
5-FU cream (5%) Two to three times per week for 6–10 weeks 40–70% 30% Irritation, erosion, ulceration
Physician-applied treatment
Podophyllin resin (15–25% Weekly for 4–6 weeks, must be washed off 60–80% 20–30% Irritation, erosion, ulceration. Systemic
in tincture of benzoin after 4–8 hours. Rx must not exceed toxicity possible
compound) 0.1╯ml/cm2
Trichloroacetic acid Weekly till maximum response, usually 4–6 70–80% 30–60% Chemical burn of surrounding skin
(80–90% soln) weeks possible, irritation, erosion,
ulceration
Cryotherapy 15–20 second freeze times, repeated every 70% 30–60% Pain, discharge, blistering, irritation,
1–3 weeks for 3 months erosion, ulceration
CO2 laser ablation Single session usually sufficient. Continuous 100% Not available Irritation, erosion, ulceration
wave ablation to papillary dermis
Surgical excision Removal of all grossly infected tissue. – Operative risk, infection
Curettage Wart curetted until level plane with – 10–25% Mild pain after procedure
surrounding skin
Interferon Intra-lesional injection once a week for 6 15% 0–45% Systemic toxicity possible, flu like
weeks reaction

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 7â•… Infectious Diseasesâ•… •â•… Lymphogranuloma venereum (LGV)

A double-blind, randomized phase 3 trial was conducted

Prevention
HPV vaccine
The introduction of the HPV vaccine presents a major step
towards the eradication of cervical cancer.
Quadrivalent vaccine against human papillomavirus to
prevent anogenital diseases. Garland SM, Hernandez-Avila
M, Wheeler CM, et al. N Engl J Med 2007; 356(19):
1928–1943.
A double-blind, randomized phase 3 trial conducted to
evaluate the efficacy of a prophylactic quadrivalent vaccine in
preventing anogenital diseases associated with human papil-
lomavirus (HPV) types 6, 11, 16, and 18. Trial involved 5455
women between the ages of 16 and 24 years; authors assigned
2723 women to receive vaccine and 2732 to receive placebo
at day 1, month 2, and month 6. The end points were the
incidence of genital warts, vulvar or vaginal intraepithelial
neoplasia, or cancer and the incidence of cervical intraepithe-
lial neoplasia, adenocarcinoma in situ, or cancer associated
with HPV type 6, 11, 16, or 18. The women were followed for
an average of 3 years after administration of the first dose.
Vaccine efficacy was 100% for each of the end points and the
quadrivalent vaccine significantly reduced the incidence of
HPV-associated anogenital diseases in young women.
to evaluate a quadrivalent vaccine against HPV types 6, 11, 16,
and 18 (HPV-6/11/16/18) for the prevention of high-grade
cervical lesions associated with HPV-16 and HPV-18. 12,167
women between the ages of 15 and 26 years received three
doses of either HPV-6/11/16/18 vaccine or placebo, adminis-
tered at day 1, month 2, and month 6. The end point was
cervical intraepithelial neoplasia grade 2 or 3, adenocarci-
noma in situ, or cervical cancer related to HPV-16 or HPV-18.
Vaccine efficacy for the prevention of the primary composite
end point was 98% (95.89% confidence interval [CI], 86 to
100) in the per-protocol susceptible population and 44%
(95% CI, 26 to 58) in an intention-to-treat population of all
women who had undergone randomization.
References
1. Habif TP. Clinical dermatology: a colour guide to diagnosis and
therapy, 4th edn. New York: Mosby; 2003.
2. World Health Organization. Guidelines for the Management
of Sexually Transmitted Diseases. http://www.who.int/hiv/topics/
vct/sw_toolkit/guidelines_management_sti_treatment_specific_
infections.pdf, 2009 [accessed 15.12.09].
3. Centers for Disease Control and Prevention, Workowski KA, Berman
SM: Sexually transmitted diseases treatment guidelines, 2006. MMWR
Recomm Rep 2006; 55:1–94.

Quadrivalent vaccine against human papillomavirus to

prevent high-grade cervical lesions. FUTURE II Study Group.
N Engl J Med 2007; 356(19):1915–1927.

Lymphogranuloma
venereum (LGV)
Lymphogranuloma venereum (LGV), caused by Chlamydia tra-
chomatis types L1, L2 and L3, requires microtrauma to colum-
nar epithelium for inoculation of the causative organism to
occur. Much more prevalent in tropical and sub-tropical coun-
tries, LGV has shown a declining incidence in recent years in
some endemic regions. Annual incidence in India is below 5%
of all STD cases seen.1

Clinical features
See Table 7.6.

Investigations Figure 7.12:╇ LGV. A large inguinal node resulting from lymphogranuloma
venereum. (From Johnson, Moy, White: Ethnic Skin – Medical and Surgical,
See Table 7.7. Mosby Inc., copyright Elsevier 1998.)

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 Part 1 Medical Dermatology

Table 7.6╇ Lymphogranuloma venereum

Stage Clinical features

Primary stage Incubation period varies from 7 to 12 days. The most common primary lesion is herpetiform and because it is
painless, often goes unnoticed. Atypical presentations are possible such as papulonodules, ulcers, urethritis and
balanitis.
Inguinal syndrome Localization to the inguinal region is more common in men who present with enlarged inguinal lymph nodes (bubo) 10
days to 6 months after contact with an infected partner. The enlargement is unilateral in two-thirds of cases, with
the femoral nodes being involved in 20% of cases. When this occurs it creates the classic ‘sign of groove’, wherein
the enlarged inguinal and femoral lymph nodes are separated by the Poupart’s ligament (Fig. 7.12). The buboes are
multilocular, in contrast to chancroid, and on rupture produce multiple draining sinuses which heal with scarring.
Spontaneous resolution without significant sequelae is also possible.
Anorectal syndrome Occurring primarily in women and homosexual men, the anorectal syndrome is caused by either direct inoculation of
chlamydia during anal intercourse or via lymphatic spread from the posterior urethra in men and cervix and
posterior vaginal wall in women. A subacute proctocolitis occurs which leads to fibrosis over 6–12 months
producing the characteristic symptom of tenesmus, leucorrhea and ‘ribbon stools’. The peri-rectal lymph nodes may
suppurate and rupture producing perianal sinuses. Other complications of this syndrome include recto-vaginal
fistulae, pelvic inflammatory disease and infertility, peritonitis, intestinal obstruction and rectal cancer (< 5% cases).
Genito-anorectal syndrome This syndrome refers to the occurrence of the aforementioned symptoms of the anorectal syndrome occurring with
hyperplastic ulcerative changes of the genitalia. The hyperplasia is a result of chronic lymphedema due to lymphatic
obstruction caused by scarring.
Other symptoms Follicular conjunctivitis may occur due to auto-inoculation of Chlamydia. Various types of transient skin eruptions
varying from a morbilliform rash to erythema multiforme and erythema nodosum have been described in the
disease.

Table 7.7╇ Features of lymphogranuloma venereum

Test Features

Serological tests Complement fixation and micro-immunofluorescence tests are used to detect anti-chlamydial antibodies. These antibodies
are not serovar specific and do not differentiate the different chlamydial infections. A titre of less than 1â•›:â•›32 essentially
rules out LGV whereas, higher titres (> 1â•›:â•›256) are more supportive of the diagnosis (as other chlamydial infections lead
to lower levels of antibody response).
PCR and RFLP These tests are very sensitive and detect even minute levels of chlamydial antigen (DNA/RNA). These can be designed for
serovar typing.
Histology Giemsa staining may identify the typical inclusion body in tissue or secretions. However, secondary infection makes the
sensitivity of this test poor. Electron microscopy can be used to visualize the elementary, intermediate and reticulate
bodies. HPE of infected tissue shows a chronic granulomatous response with areas of necrosis surrounded by epithelioid
cells and giant cells.
Isolation of Chlamydia This is done by inoculating infected material into mouse brain, yolk-sac, or tissue culture (HeLa, McCoy cell lines). A
positive result is confirmatory but sensitivity of culture methods remain below 50%.
PCR – Polymerase chain reaction, RFLP – Restriction fragment length polymorphism, HPE – Histopathological examination. Frei test: Intradermal delayed hypersensitivity reaction to
chlamydial antigen; now of historical interest only.

Treatment
WHO2 and CDC3 treatment guidelines for LGV are essentially First-Line Therapies
similar; the WHO recommends a shorter duration of treat-
ment (14 days). There are reports of this disease responding Doxycycline 100╯mg BID for 21 days
to a single dose of azithromycin.

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 7â•… Infectious Diseasesâ•… •â•… Pityriasis versicolor

Second-Line Therapies References

Erythromycin base 500╯mg orally QID for 21 days
Azithromycin 1╯gm (one dose)
Treatment of chancroid with azithromycin. Ballard RC, Ye H,
Matta A, et al. Int J STD AIDS 1996; 7(Suppl 1):9–12.
A randomized, comparative study in which 1gm single dose
of azithromycin resulted in cure of both chancroid and lym-
phogranuloma venereum.
1. Habif TP. Clinical dermatology: a colour guide to diagnosis and
therapy, 4th edn. New York: Mosby; 2003.
2. World Health Organization. Guidelines for the Management of
Sexually Transmitted Diseases. 2009. [Accessed December 15, 2009.
http://www.who.int/hiv/topics/vct/sw_toolkit/guidelines_
management_sti_treatment_specific_infections.pdf]
3. Centers for Disease Control and Prevention. Workowski KA, Berman
SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR
Recomm Rep 2006; 55:1–94.

Pityriasis versicolor First-Line Therapies

Topical ketoconazole A
Pityriasis versicolor (tinea versicolor) is a superficial mycosis Topical clotrimazole A
characterized by patchy discoloration of the skin associated Topical terbinafine A
with scaling (Fig. 7.13). The causative organisms are Malassezia Selenium sulfide A
species, most commonly M. furfur, M. globosa and M. sympodia-
Topical tioconazole B
lis. A hot and humid environment predisposes to development
of P. versicolor and it is more common in tropical than temper- Sulfur salicylic acid shampoo B
ate areas.1 Zinc pyrithione shampoo B
The characteristic lesions of P. versicolor are either hyperpig- Topical bifonazole C
mented or hypopigmented macules (Fig. 7.14) covered with
fine scales. The macules usually become confluent to form
large figurate areas on the upper back, neck, shoulders and
upper chest with a few scattered discrete macules at the periph-
ery.2 P. versicolor inversus primarily involves the extremities
with relative sparing of the trunk.
A KOH preparation from the advancing edge reveals char-
acteristic yeast and mycelia which are described as ‘bananas
and grapes’ or ‘spaghetti and meatball’.

B
Figure 7.13:╇ Pityriasis veriscolor. A fine scale when scraped is characteristic of
pityriasis versicolor. (From White & Cox, Diseases of the Skin, A Color Atlas and Figure 7.14:╇ (A and B) Tinea versicolor. (Courtesy of Dr. Sonia
Text, 2E, Mosby Inc, copyright Elsevier 2006.) Badreshia-Bansal.)

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 Part 1 Medical Dermatology
Double-blind comparison of 2% ketoconazole cream and
placebo in the treatment of tinea versicolor. Savin RC,
Horwitz SN. J Am Acad Dermatol 1986; 15:500–503.
Double-blind comparative study in 101 patients with recur-
ring lesions of tinea versicolor, who were randomly assigned
to once-daily ketoconazole 2% or placebo cream. At the end
of treatment, 98% of the patients using ketoconazole and 28%
of those using placebo responded clinically. Ketoconazole-
treated patients who were cured at the end of treatment
remained cured 8 weeks later. By contrast 75% of those
responding to placebo had relapsed by the 8-week follow-up
visit.
Double-blind trial of 1% clotrimazole cream and Whit�
field ointment in the treatment of pityriasis versicolor.
Clayton R, Du Vivier A, Savage M. Arch Dermatol 1977;
113:849–850.
Double-blind trial of clotrimazole compared with benzoic
and salicylic acid (Whitfield) ointment in the treatment of
pityriasis versicolor. Clotrimazole cream was demonstrated to
be as effective as Whitfield ointment and was more acceptable
to the patient. Culture of Malassezia furfur showed a constant
and persistent sensitivity to clotrimazole, suggesting its suita-
bility for treatment of relapse.
Pityriasis versicolor: clinical experience with Lamisil cream
and Lamisil DermGel. Faergemann J, Hersle K, Nordin P.
Dermatology 1997; 194(Suppl 1):19–21.
Prospective, double-blind, placebo-controlled, randomized,
parallel-group, comparative, multicentre study, in which 61
patients were included, 31 in the Lamisil DermGel group and
30 in the placebo gel group. The gel was applied once daily
for 7 days and the patients were followed up for 8 weeks. 21/28
(75%) were cured in the Lamisil-DermGel-treated group com-
pared to 4/29 (14%) in the placebo group.
A double-blind comparative study of sodium sulfacetamide
lotion 10% versus selenium sulfide lotion 2.5% in the treat-
ment of pityriasis (tinea) versicolor. Hull CA, Johnson SM.
Cutis 2004; 73:425–429.
A double-blind comparative study between once-
daily sodium sulfacetamide lotion and selenium sulfide
lotion. Both treatments were safe and efficacious. Selenium
sulfide was statistically more efficacious (76.2% vs 47.8%,
P = .013).
Comparative study of tioconazole and clotrimazole in the
treatment of tinea versicolor. Alchorne MM, Paschoalick RC,
Forjaz MH. Clin Ther 1987; 9:360–367.
A comparative study of tioconazole and clotrimazole in
32 patients with tinea versicolor. 16 patients were treated
with 1% tioconazole lotion and 16 with 1% clotrimazole
solution. At the end of the study, all patients were clinically
138
and mycologically cured. Tioconazole was found to be as
efficacious as clotrimazole.
Treatment of tinea versicolor with sulfur-salicylic shampoo.
Bamford JT. J Am Acad Dermatol 1983; 8:211–213.
One half of the randomly allocated patients used the active
preparation of sulfur-salicylic shampoo and the other half
used a bland oil-in-water lotion as a placebo. Three months
after completing treatment, 19 of 22 using sulfur-salicylic acid
shampoo were still negative on KOH examination, whereas
only 1 of 16 controls was negative.
Double-blind comparison of a zinc pyrithione shampoo
and its shampoo base in the treatment of tinea versicolor.
Fredriksson T, Faergemann J. Cutis 1983; 31:436–437.
40 patients with tinea versicolor were treated with either
zinc pyrithione shampoo or shampoo base (placebo). The 20
patients treated with zinc pyrithione shampoo cleared and
none of the 20 placebo patients cleared.
Ultra-short topical treatment of pityriasis versicolor with
2.5% bifonazole cream. Galimberti RL, Bonino M, Flores V,
et al. Clin Exp Dermatol 1993; 18:25–29.
In this study, group A used bifonazole only on days 1, 2
and 3, and the Group C on days 1, 3 and 5. Of the patients in
Group A, 56% had a negative mycological examination at the
end of the study. 92% of patients in group B had a negative
mycological examination at the end of the study.
Second-Line Therapies
Oral itraconazole A
Oral ketoconazole A
Oral fluconazole A
A double-blind, randomized, placebo-controlled evaluation
of short-term treatment with oral itraconazole in patients
with tinea versicolor. Hickman JG. J Am Acad Dermatol 1996;
51:785–787.
Efficacy and safety of oral itraconazole compared with that
of placebo in 36 patients with mycologically proven tinea
versicolor. Patients were randomly assigned to 7 days of treat-
ment with either itraconazole, 200╯mg once daily, or placebo.
94% of itraconazole-treated patients were considered to be
healed or markedly improved at the study’s end point com-
pared with 6% of placebo-treated patients.
Fluconazole versus ketoconazole in the treatment of tinea
versicolor. Farschian M, Yaghoobi R, Samadi K. J Dermatolog
Treat 2002; 13:73–76.

128 patients with tinea versicolor, ages 15–55 years, were
entered into a randomized, double-blind, clinical trial com-
paring the efficacy and tolerability of two regimens of oral
treatment. The patients were randomly divided in two groups:
group 1 received two 150╯mg capsules of fluconazole in a
single dose repeated weekly for 2 weeks; and group 2 received
two 200╯mg tablets of ketoconazole in a single dose repeated
weekly for 2 weeks. Fluconazole and ketoconazole demon-
strated similar efficacy in the treatment of TV.
Third-Line Therapies
Ciclopirox B
Whitfield’s ointment B
Propylene glycol C References
Topical application of a 0.1% ciclopiroxolamine solution
for the treatment of pityriasis versicolor. Corte M, Jung K,
Linker U, et al. Mycoses 1989; 32(4):200–203.
Syphilis
Syphilis is caused by Treponema pallidum, an organism so thin
that it cannot be visualized by conventional microscopy, but
requires dark ground illumination or silver impregnation for
visualization. Present since antiquity, syphilis remains to this
day widely prevalent. Syphilis may present atypically, hence
the term, ‘the great imitator’. In India, the prevalence of syphi-
lis ranges from 2.7% to 26.6% in serological surveys. Due to
the HIV epidemic, a rise in the number of syphilis cases world-
wide has been seen.
Clinical features
See Table 7.8.
Investigations1
See Table 7.9.
7â•… Infectious Diseasesâ•… •â•… Syphilis
90 patients with pityriasis versicolor used a 0.1% solution
of ciclopiroxolamine for a topical 4-week treatment. 74% of
the patients were cured clinically and mycologically after a
4-week therapy. Following additional 4 weeks the responder
rate rose to 86%.
Propylene glycol in the treatment of tinea versicolor.
Faergemann J, Fredriksson T. Acta Derm Venereol 1980;
60(1):92–93.
20 patients with tinea versicolor were treated with propyl-
ene glycol 50% in water twice daily for 2 weeks. All were cured
when evaluated 2 weeks after the last day of treatment.
1. Rippon JW. Dermatophytosis and dermatophytomycosis. In: Medical
mycology. The pathologic fungi and the pathogenic actinomycetes.
2nd edn. Philadelphia: WB Saunders; 1982. p. 154–9.
2. Mycology. Hay RJ, Roberts SOB, Mackenzie DWR. In: Champion RH,
Burton JL, Ebling FJG, editors. Textbook of dermatology. Oxford:
Blackwell Scientific Publications; 1992. p. 1128.
First-Line Therapies
Penicillin A
Primary and secondary syphilis
Benzathine penicillin G 2.4 million units IM in a single dose (Note:
the CDC reports that no comparative trials have been adequately
conducted to guide the selection of an optimal penicillin regimen.
Additionally, less data is available for non-penicillin regimens.)
Early latent syphilis
Benzathine penicillin G 2.4 million units IM in a single dose
Late latent syphilis or latent syphilis of unknown duration
Benzathine penicillin G 7.2 million units total, administered as 3
doses of 2.4 million units IM each at 1-week intervals
Tertiary syphilis
Benzathine penicillin G 7.2 million units total, administered as 3
doses of 2.4 million units IM each at 1-week intervals
Neurosyphilis
Aqueous crystalline penicillin G 18–24 million units per day,
administered as 3–4 million units IV every 4 hours or continu-
ous infusion, for 10–14 days
Procaine penicillin 2.4 million units IM once daily PLUS Probenecid
500╯mg orally four times a day, both for 10–14 days
139
 Part 1 Medical Dermatology

Table 7.8╇ Clinical features of syphilis

Stage Clinical features

Primary syphilis The incubation period varies from 9 to 90 days, depending on the size of the inoculum, followed by the appearance of a
(3–6 weeks) syphilitic chancre (a painless ulcer with well defined margins and an indurated base) at the site of inoculation. The floor is
covered with a gray slough and a clear serous fluid may discharge either spontaneously or on pressure. Atypical
presentations, both genital and extra-genital are now more common. Regional lymphadenopathy develops within a week of
the chancre.
Secondary Systemic features of the disease appear 3–6 weeks after the appearance of the chancre caused by dissemination of T.
syphilis pallidum. Non-specific flu like symptoms are accompanied by a rash, generalized lymphadenopathy and mucosal lesions. The
classical lesion, the roseolar syphilide, is a 1╯cm or smaller area of faint macular erythema presenting as rose pink, rounded
macules (Fig. 7.15). Lesions gradually become dull red and papular as well as generalized. Characteristically, the palms and
soles are involved (Fig. 7.16). The eruption may appear coppery in dark skinned patients. Condyloma lata, moist, broad
based, flat papules, which are very infectious, may develop in intertriginous areas (Fig. 7.17). Other organ systems are
involved in less than 10% of patients. Neurological involvement is common in HIV patients which may rapidly progress to
neurosyphilis.
Latent syphilis In this stage, which is asymptomatic, serologic evidence of syphilis, without clinical features, occurs. Early latent syphilis occurs
within one year of infection and late latent syphilis occurs after 1 year. Some authorities consider the cut-off between the
early and latent phase to be 2 years. When there is no reliable history regarding the primary stage, the term latent syphilis of
unknown duration is used. These cases are treated as late latent syphilis.
Tertiary syphilis Includes late benign syphilis, neurosyphilis and cardiovascular syphilis. Late benign syphilis involves proliferative or gummatous
changes in non-vital systems, such as the skin (Fig. 7.18), musculoskeletal system, eyes, etc. Rarely seen since early
syphilis can be effectively treated. Neurosyphilis may be asymptomatic, meningeal, meningovascular, parenchymatous or
gummatous. Notable conditions are tabes dorsalis and general paresis of the insane. Cardiovascular syphilis is due to
endarteritis of the vasa vasora leading to ischemic changes in larger vessels. Healing occurs with fibrosis leading to
weakening of the vessel wall. Aneurysms may develop.

Figure 7.16:╇ Syphilis. Involvement of the palms in secondary syphilis is classic.

Figure 7.15:╇ Syphilis. Annular forms of secondary syphilis on the face. (Courtesy (Courtesy of Steven Goldberg, MD; from Johnson, Ethnic Skin, copyright Elsevier
of Michael O. Murphy MD; from Johnson, Ethnic Skin, copyright Elsevier 1998.) 1998.)

140

Figure 7.17:╇ Secondary syphilis. Perianal condymal lata: these lesions are teeming
with Treponema pallidum. (Courtesy of Michael O. Murphy MD; from White,
Diseases of the Skin, 2e, copyright Elsevier 2005.)
Second-Line Therapies
Typically reserved for penicillin allergic patients
Doxycycline
Tetracycline
Ceftriaxone
Primary/secondary syphilis
doxycycline 100╯mg orally twice daily for 14 days
tetracycline 500╯mg four times daily for 14 days
Early latent syphilis / late latent syphilis or latent syphilis of unknown
duration
doxycycline 100╯mg orally twice daily for 28 days
tetracycline 500╯mg orally four times daily for 28 days
Neurosyphilis
ceftriaxone 2 g daily either IM or IV for 10–14 days
A pilot study evaluating ceftriaxone and penicillin G as
treatment agents for neurosyphilis in human immunodefi-
ciency virus-infected individuals. Marra CM, Boutin P,
McArthur JC, et al. Clin Infect Dis 2000; 30:540–544.
This study compared IV ceftriaxone versus IV penicillin G
as therapy for neurosyphilis. Blood and CSF were collected
before and 14–26 weeks after therapy on the 30 subjects (14
on ceftriaxone, 16 on penicillin G) infected with human
7â•… Infectious Diseasesâ•… •â•… Syphilis
Figure 7.18:╇ Syphilis. Tertiary syphilis. An annular lesion in a darker skinned
patient. (Courtesy of the Department of Dermatology, University of San Diego,
California; from White, Diseases of the Skin, 2e, copyright Elsevier 2005.)
immunodeficiency virus and who had serologic evidence of
syphilis. Significantly more ceftriaxone recipients had a decline
in serum RPR titers (8 [80%] of 10 vs 2 [13%] of 15; P =
.003). IV ceftriaxone may be an alternative to penicillin
for treatment of HIV-infected patients with neurosyphilis and
concomitant early syphilis.
Third-Line Therapies
B
Azithromycin A
B
B
Single-dose azithromycin versus penicillin G benzathine for
the treatment of early syphilis. Riedner G, Rusizoka M, Todd
J, et al. N Engl J Med 2005; 353:1236–1234.
A total of 328 Tanzanian subjects, 25 with primary and 303
with high-titer RPR ≥ 1â•›:â•›8 were randomly assigned to receive
2 g of azithromycin orally (163 subjects) or 2.4 million units
of penicillin G benzathine intramuscularly (165 subjects).
Cure was defined was a decline in the RPR titer of at least two
dilutions by 9 months after treatment and, in primary syphilis,
by epithelialization of ulcers within 1 or 2 weeks. Cure rates
were 97.% (95% confidence interval, 94.0–99.4) in the azi-
thromycin group and 95.0% (95% confidence interval, 90.6–
97.8) in the penicillin G benzathine group. Authors found that
single-dose oral azithromycin is effective in treating syphilis,
though resistance might be of concern.
Treatment during pregnancy
• Treatment during pregnancy should be the penicillin
regimen appropriate for the stage of syphilis
141
 Part 1 Medical Dermatology

Table 7.9╇ Testing for syphilis

Test Features

Direct visualization of Treponema pallidum

Dark ground illumination T. pallidum is seen as a motile curvilinear rod identified by its movements which consist of angulation (most
commonly seen), buckling, compression, looping and undulation. Unlike saprophytic spirochetes, T. pallidum
does not exhibit locomotion.
DFA – TP Fluorescent antibodies are used to visualize the spirochete under a fluorescent microscope.
Serological tests for syphilis
Non-treponemal tests (Cardiolipin antigen, Reagin antibody – IgG & IgM)
VDRL Widely used and most useful test for monitoring response to therapy and relapse or reinfection. Becomes positive
3–4 weeks after infection. After successful treatment, falls 4-fold within 6 months, becoming negative within 12
months of treatment of primary syphilis and 24 months of treatment of secondary syphilis.
RPR Another slide flocculation test, RPR can be read without a microscope (unlike the VDRL test) and can also be
automated (ART). Available as a card test, so especially useful in field conditions.
Treponemal tests (T. pallidum antigens, T. pallidum specific IgGa & IgM)
FTA-ABS This indirect immunofluorescent test is the most sensitive serological test for syphilis, especially in the early
stages. It becomes positive in the third week of infection. False positive reactions may occur due to the
presence of auto-antibodies like rheumatoid factor.
TPHA Hemagglutination assay. Becomes positive slightly after FTA-ABS. It is less sensitive as compared to FTA-ABS in
primary syphilis, becoming comparable in later stages. However, being a cheaper and less cumbersome test to
do, it is of particular use in developing countries. Variations of the test include microhemagglutination assays
(MHA-TP & AMHA-TP)
ELISA Can be designed to detect IgG or IgM antibodies. Standard ELISA technique is used with microwells coated with a
treponemal antigen. IgM Captia ELISA is the first test to become positive after infection (end of second week of
infection). EIA is more specific than FTA-ABS and recent studies suggest that EIA used as a single test is a
suitable alternative to the combination of VDRL/RPR and FTA-ABS/TPHA tests.
Others TPI is now of historic significance as it is expensive & time consuming, and does not have any advantage over the
newer treponemal tests. Western blot is a research tool.
DFA – TP: Direct fluorescent antibody staining of T. pallidum, VDRL: Venereal disease research laboratory, RPR: rapid plasma reagin, ART: automated reagin test, FTA – ABS:
Fluorescent treponemal antibody absorption test, TPHA: treponemal pallidum hemagglutination assay, ELISA: Enzyme linked immunosorbent assay.

Reference
1. Centers for Disease Control and Prevention. Workowski KA, Berman
SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR
Recomm Rep 2006; 55:1–94.

Tinea capitis Infection occurs predominantly in prepubertal children

Tinea capitis, a dermatophyte infection of the scalp is the most
common mycosis in children. Dermatophytes causing tinea
capitis can be grouped into following types:
• Anthropophilic – Trichophyton tonsurans, Microsporum
audouinii, M. ferrugineum, T. violaceum
• Geophilic – M. gypseum, M. fulvum
• Zoophilic – M. canis, T. verrucosum, T. mentagrophytes
over 6 months of age. Boys are more commonly infected than
girls, probably due to short hair and, therefore, easy transport
of the spores to the scalp surface. Studies in India have shown
that approximately 68% of patients come from overcrowded
areas with poor hygiene and low socioeconomic status.1,2
Protein deficiency along with vitamin A deficiency also predis-
poses to tinea capitis.3 Transmission can occur through close
personal contact, shared items such as hats, combs and helmet
as well as linen.

142

A favus). Fluorescence is not seen with endothrix organisms.
B
Figure 7.19:╇ Tinea capitis. A fungal infection of the scalp may present as a boggy
mass of tissue or kerion (A) or as a scale alone, resembling seborrheic dermatitis
(B). Note the swollen lymph node in (A). (From Johnson, Moy, White: Ethnic Skin
– Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)
The cardinal feature of tinea capitis is partial hair loss with
inflammation of variable intensity. The clinical presentation
may be inflammatory, non-inflammatory or favus (Fig. 7.19):
• Non-inflammatory:
– Gray patch: patches of partial hair loss with numerous
broken hairs that are lusterless and dull gray due to
coating by arthrospores. It is most commonly caused by
M. audouinii (ectothrix).
– Black dot: multiple polygonal areas of partial hair loss
with ‘black dots’ signifying infected hair broken off at
the level of the scalp. Some hair is spared within the area
of involvement. It is commonly caused by T. tonsurans or
T. violaceum (endothrix).
7â•… Infectious Diseasesâ•… •â•… Tinea capitis
• Inflammatory:
– Kerion: a boggy indurated swelling studded with broken
hairs and pustules or an agminate folliculitis presenta-
tion. This inflammatory form of tinea capitis is most
commonly caused by T. verrucosum or T. mentagrophytes.
Matting of hairs is common and occasionally an id erup-
tion may be present.
• Favus: is characterized by yellow cup shaped crusts (’scutula’)
which are composed of densely packed hyphae and epithe-
lial debris. A typical musty odor may also be present. The
most common etiologic agent is T. schoenleinii.
For accurate diagnosis, the hair shaft may be examined
under low power microscopy for visualization of ectothrix or
endothrix spores. Additionally, hair may be examined under
Wood’s light for detection of fluorescence which may be bright
green (caused by ectothrix organisms) or dull green (seen in
Hair may also be cultured for fungus.
First-Line Therapies
Griseofulvin A
Terbinafine A
Itraconazole A
Meta-analysis: griseofulvin efficacy in the treatment of tinea
capitis. Gupta AK, Cooper EA, Bowen JE. J Drugs Dermatol
2008; 7(4):369–372.
A review of the literature examined seven studies that used
griseofulvin for tinea capitis. The overall mean effective cure
(negative KOH and culture) of griseofulvin at 4–6 weeks post-
treatment was 73.4% ± 7% (n = 438 patients). Higher efficacy
rates appeared to be reported with the use of higher dosages
of griseofulvin (> 18╯mg/kg/d). Griseofulvin remains an effec-
tive therapy for tinea capitis.
Terbinafine hydrochloride oral granules versus oral griseof-
ulvin suspension in children with tinea capitis: results of
two randomized, investigator-blinded, multicenter, interna-
tional, controlled trials. Elewski BE, Cáceres HW, DeLeon
et al. J Am Acad Dermatol 2008; 59:41–54.
The authors compared the efficacy and safety of a new
pediatric formulation of terbinafine hydrochloride oral gran-
ules with griseofulvin oral suspension in the treatment of tinea
capitis. Children (4–12 years of age) with clinically diagnosed
and potassium hydroxide microscopy-confirmed tinea capitis
were randomized in two identical studies (trial 1, trial 2) to
once-daily treatment with terbinafine or griseofulvin adminis-
tered for 6 weeks followed by 4 weeks of follow-up. Rates of
complete cure and mycologic cure were significantly higher for
terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5%
vs 55.5%, respectively; P < .05 limitations). This data suggests
that terbinafine is efficacious and well tolerated in the treat-
ment of tinea capitis.
Itraconazole versus griseofulvin in the treatment of tinea
capitis: a double-blind randomized study in children.
143
 Part 1 Medical Dermatology
López-Gómez S, Del Palacio A, Van Cutsem J, et al. Int J Der-
matol 1994; 33:743–747.
34 children and 1 adult with clinical signs and symptoms
of tinea capitis and with positive culture and microscopy for
dermatophytes were included in this double-blind compari-
son between itraconazole, 100╯mg daily, and ultramicronized
griseofulvin, 500╯mg daily. Both drugs were given for 6 con-
secutive weeks. 15 of 17 patients were cured with itraconazole
(88%) and 15 of 17 patients with griseofulvin (88%). Itraco-
nazole is the first azole derivate that matches griseofulvin for
the treatment of tinea capitis in children and the drug also
appears to be better tolerated than griseofulvin.
Second-Line Therapies
Fluconazole B
A randomized controlled trial assessing the efficacy of flu-
conazole in the treatment of pediatric tinea capitis. Foster
KW, Friedlander SF, Panzer H, et al. J Am Acad Dermatol 2005;
53:798–809.
A randomized, multicenter, third-party-blind, three-arm
trial which assessed the efficacy, safety, and optimal dose and
duration of fluconazole therapy compared with standard-dose
griseofulvin in the treatment of pediatric tinea capitis. Authors
compared fluconazole 6╯mg/kg per day for 3 weeks followed
by 3 weeks of placebo, vs fluconazole 6╯mg/kg per day for 6
weeks, vs griseofulvin 11╯mg/kg per day for 6 weeks. At the end
of treatment, mycological cures were present in 44.5%, 49.6%,
and 52.2% of the fluconazole 3-week, fluconazole 6-week, and
griseofulvin 6-week groups, respectively. No superior agent
was found. Authors deemed that fluconazole may be useful in
select patients with a contraindication or intolerance to high-
dose griseofulvin.
Third-Line Therapies
Ketoconazole shampoo C pared to griseofulvin alone in cases with kerions.
Selenium sulfide shampoo C
Corticosteroids E
The role of corticosteroids in the management of tinea
capitis or the more aggressive kerion celsi is controversial. One
study found no benefit to the use of prednisolone in kerion
cells while a smaller study did find a benefit.
Successful treatment of tinea capitis with 2% ketoconazole
shampoo. Greer DL. Int J Dermatol 2000; 39:302–304.
16 Black children, ages 3–6 years, all with proven tinea
capitis caused by Trichophyton tonsurans, were treated daily for
8 weeks with 2% ketoconazole shampoo for a total of 56 treat-
ments. Clinical and mycologic examinations were performed
every 2 weeks and again at 4 weeks following treatment.
Patients with positive cultures after 8 weeks were placed on
144
oral griseofulvin; those with negative cultures were followed
monthly by culture for an additional 12 months. Marked clini-
cal improvement occurred in all patients within 2 weeks and
absence of pruritus was noted by the patients as early as 2–6
days. At 8 weeks of treatment the number of colonies remained
at 20 or fewer. Six of the 15 children (40%) had negative
cultures after 2, 4, and 6 weeks. Complete cures were obtained
in 5/15 (33%) of the children. The children remained clini-
cally and mycologically clear for as long as 1 year after
treatment.
Selenium sulfide: adjunctive therapy for tinea capitis. Allen
HB, Honig PJ, Leyden JJ et al. Pediatrics 1982; 69:81–83.
Of 16 children with Trichophyton tonsurans tinea capitis, 15
had negative fungal cultures at 2 weeks following a regimen
of daily oral griseofulvin and selenium sulfide shampooing
twice weekly. All patients treated with griseofulvin alone or in
combination with either a bland shampoo or topical clotrima-
zole had positive cultures not only at the 2-week interval but
also as long as 8 weeks later. In vitro analysis shows selenium
sulfide to be sporicidal, correlating well with in vivo observa-
tions. Selenium sulfide can also help decrease transmission of
tinea capitis.
A randomized, comparative trial of treatment of kerion celsi
with griseofulvin plus oral prednisolone vs griseofulvin
alone. Hussain I, Muzaffar F, Rashid T, et al. Med Mycol 1999;
37:97–99.
In this randomized study, the efficacy of combination
therapy with oral griseofulvin and oral prednisolone (n = 17)
was compared to oral griseofulvin alone (n = 13) in the treat-
ment of kerions. Both groups were treated with oral griseoful-
vin for 8 weeks whereas oral prednisolone was given in
tapering doses for 3–4 weeks only to the first group. Final
evaluation at week 12 showed a cure rate of 100% in both
groups without any significant difference in terms of clinical
or mycological cure (P > 0.05). The authors found that the
combination of oral prednisolone with griseofulvin does not
result in additional objective or subjective improvement com-
Beneficial effect of corticosteroid therapy in Microsporum
canis kerion. Keipert JA. Australas J Dermatol 1984; 25:
127–130.
Three children diagnosed with kerion due to Microsporum
canis were treated with oral corticosteroid therapy. The inflam-
matory changes responded dramatically with rapid healing of
the kerions.
References
1. Kumari S, Bagga GR, Singh R, et al. A clinicomycological study of
dermatophytoses in Delhi. J Commun Dis 1985; 17:68–71.
2. Sehgal VN, Saxena AK, Kumari S. Tinea capitis: a clinic–etiological
correlation. Int J Dermatol 1985; 24:116–119.
3. Vanbreuseghem R. Tinea capitis in Belgian Conga and Ruanda Urundi.
Trop Geogr Med 1958; 10:103–112.

Tinea corporis
Tinea corporis is dermatophytosis of the glabrous skin exclud-
ing the palms, soles and groin. All three genera of dermato-
phytes i.e. Trichophyton, Epidermophyton and Microsporum
may cause tinea corporis. In the United States, Trichophyton
rubrum is the most common dermatophyte implicated in tinea
corporis.1
Predisposing factors for tinea corporis include poor hygiene
and nutrition, diabetes mellitus and living in tropical areas.
Typical lesions are annular, erythematous plaques with papu-
lovesicles, and scale at the margins with central clearing. Tinea
imbricata is a variant caused by T. concentricum which presents
as concentric lamellar plaques with overlapping scales.2
A KOH preparation from the margin of the lesion is used
for diagnosis (Figs. 7.20, 7.21).
First-Line Therapies
Topical terbinafine
Topical clotrimazole
Comparative study between terbinafine 1% emulsion-gel
versus ketoconazole 2% cream in tinea cruris and tinea cor-
poris. Bonifaz A, Saúl A. Eur J Dermatol 2000; 10(2):107–109.
An open, prospective, comparative, randomized and
parallel-group study of 65 patients was conducted to evaluate
the efficacy and safety of topical 1% emulsion-gel of terbin-
Figure 7.20:╇ Tinea corporis in a hair bearing area. (From Johnson, Moy, White:
Ethnic Skin – Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)
7â•… Infectious Diseasesâ•… •â•… Tinea corporis
afine versus 2% ketoconazole cream in the treatment of tinea
corporis and tinea cruris. 33 patients in the terbinafine group
and 32 in the ketoconazole group were evaluated for efficacy
and safety. At the end of the study, rates of mycological cure
were 94% for terbinafine emulsion-gel and 69% for ketocona-
zole cream (p = 0.027). A clinical and mycological overall
evaluation was obtained for 72% of patients receiving terbin-
afine emulsion gel and 31% of patients receiving ketoconazole
cream (p = 0.002).
Comparative efficacy of topical 1% butenafine and 1%
clotrimazole in tinea cruris and tinea corporis: a rand-
omized, double-blind trial. Singal A, Pandhi D, Agrawal S,
et al. J Dermatol Treat 2005; 16(5–6):331–335.
80 patients, diagnosed clinically to have tinea cruris or
localized tinea corporis and confirmed on KOH examination,
were randomly assigned to one of the two treatment groups
in a double-blind manner; butenafine once daily for 2 weeks
or clotrimazole twice daily for 4 weeks. Follow-up was done
at 1, 2, 4 and 8 weeks. Butenafine recipients exhibited higher
clinical cure as compared with clotrimazole recipients at the
end of 1 week (26.5% vs 2.9%) as well as higher mycological
B cure (61.7% vs 17.6%) but the difference was not statistically
A significant at 4 and 8 weeks of treatment.
Second-Line Therapies
Oral terbinafine A
Oral itraconazole A
Oral fluconazole A
Oral griseofulvin A
Oral treatment of tinea corporis and tinea cruris with
terbinafine and griseofulvin: a randomized double blind
comparative study. Voravutinon V. J Med Assoc Thai 1993;
76(7):388–393.
Figure 7.21:╇ Tinea corporis with partial central clearing in a patient with dark skin.
(From White & Cox, Diseases of the Skin, A Color Atlas and Text, 2E, Mosby Inc,
copyright Elsevier 2006.)
145
 Part 1 Medical Dermatology
64 patients with clinically and mycologically diagnosed
tinea corporis and tinea cruris were randomly allocated to
receive either 250╯mg of oral terbinafine once daily or 500╯mg
of griseofulvin once daily for 2 weeks. The clinical response in
both groups was the same. At 6 weeks follow-up, the mycologi-
cal cure in terbinafine and griseofulvin group was 87.1% and
54.8%, respectively (P < 0.05). The clinical response of the
terbinafine group was also significantly higher than in the
griseofulvin group. A higher relapse rate was observed in
the griseofulvin group than in the terbinafine group. The result
showed that oral terbinafine was more effective than oral gri-
seofulvin in the treatment of tinea corporis or tinea cruris.
A comparison of itraconazole and griseofulvin in the treat-
ment of tinea corporis and tinea cruris: a double-blind
study. Panagiotidou D, Kousidou T, Chaidemenos G, et al. J
Int Med Res 1992; 20(5):392–400.
40 patients with clinically and mycologically documented
tinea corporis or tinea cruris were treated with 100╯mg/day
itraconazole (n = 19) or 500╯mg/day griseofulvin (n = 21) for
15 days. At the end of treatment, 88.2% of itraconazole and
80.9% of griseofulvin treated patients were classed as respond-
ers. Both treatments were equally effective at the end of 15
days’ treatment with 66.7% of patients cured, but itraconazole
Tinea unguium
Tinea unguium is defined as a dermatophyte infection of the
nail plate. It is most commonly caused by T. rubrum and T.
mentagrophytes, though multiple pathogens can invade the
same nail.1 Some of the factors known to predispose to tinea
unuium are occlusive shoes, immunocompromised state, male
sex, palmoplantar hyperhidrosis and associated tinea pedis.
Tinea unguium is divided into four clinical types (Fig. 7.22):2
1. Distal and Lateral Subungual Onychomycosis (DLSO): this
is the most common type, often caused by T. rubrum, and
characterized by subungual hyperkeratosis and nail plate
discoloration at the distal and lateral edges of the nails.
Toenails are more often involved as compared to
fingernails.
2. White Superficial Onychomycosis: appears as circum-
scribed powdery white patches on the distal dorsum of the
nail. The surface of the nail plate is usually rough and
friable. Invasion of the dorsal surface of the nail plate is
usually caused by T. mentagrophytes.
3. Proximal Subungual Onychomycosis: a rare variant of
tinea unguium, commonly caused by T. rubrum, occurs
when invasion of the ventral aspect of the nail from the
proximal nailfold occurs.
4. Total Dystrophic Onychomycosis: the end stage of all types
of tinea unguium.
146
was superior to griseofulvin at the 15-day follow-up visit
(77.8% of itraconazole-treated patients compared with 66.7%
of griseofulvin-treated patients were cured).
A multicentre (double-blind) comparative study to assess
the safety and efficacy of fluconazole and griseofulvin in the
treatment of tinea corporis and tinea cruris. Faergemann J,
Mörk NJ, Haglund A, et al. Br J Dermatol 1997; 136(4):
575–577.
A double-blind, parallel group study compared fluconazole
150╯mg once weekly with griseofulvin 500╯mg once daily for
4–6 weeks in the treatment of tinea corporis or tinea cruris. 84
of 114 patients (74%) (39% after 3 weeks) were clinically
cured in the fluconazole group compared with 72 of 116
(62%) (39% after 3 weeks) in the griseofulvin group (P =
0.06). Fluconazole was deemed effective.
References
1. Foster KW, Ghannoum MA, Elewski BE. Epidemiologic surveillance of
cutaneous fungal infection in the United States from 1999 to 2002.
J Am Acad Dermatol 2004; 50(5):748–752.
2. James WD, Berger TG, et al. Andrews’ Diseases of the Skin: Clinical
Dermatology. New York: Elsevier; 2006.
For proper diagnosis, a KOH examination should be
performed where the nail plate is clipped as proximally as
possible, the debris underlying the plate scraped, 10–20%
potassium hydroxide added and the slide examined under low
power microscopy.
First Line Therapies
Terbinafine A
Itraconazole A
Evaluation of 6 weeks treatment of terbinafine in tinea
unguium in a double-blind trial comparing 6 and 12 weeks
therapy. The Lagos V Study Group. Tausch I, Bräutigam M,
Weidinger G, et al. Br J Dermatol 1997; 136(5):737–742.
148 patients received 250╯mg terbinafine daily for either 6
or 12 weeks. Cure of the nail infection was defined as negative
mycological tests (mycological cure) and progressive growth
of normal nail (clinical cure). The overall clinical and myco-
logical cure rates for the two groups were 28 of 61 (45.9%)
and 33 of 56 (58.9%), respectively. The authors suggested that
toenail infections respond better to 12 weeks of therapy
whereas 6 weeks of therapy should be sufficient for fingernail
disease.

A conazole. Korting HC, Schäfer-Korting M, Zienicke H, et al.
B
C in the terbinafine group and to 39% in the griseofulvin group.
Figure 7.22:╇ Tinea unguium. (A) Total dystrophic onychomycosis; (B) Distal/lateral
subungual variant; (C) White superficial onychomycosis. (Courtesy Jean Bolognia
MD; from Bolognia, Dermatology, 2e, copyright Elsevier 2008.)
Randomised double blind comparison of terbinafine and
itraconazole for treatment of toenail tinea infection. Seventh
Lamisil German Onychomycosis Study Group. Bräutigam M,
Nolting S, Schopf RE, et al. Br Med J 1995; 311(7010):919–
922.
7â•… Infectious Diseasesâ•… •â•… Tinea unguium
Study comparing the efficacy and tolerability of terbinafine
and itraconazole in the treatment of toenail tinea unguium.
195 patients with tinea unguium, 86 patients in the terbin-
afine group and 84 patients in the itraconazole group. Patients
received a daily dose of 250╯mg terbinafine or 200╯mg itraco-
nazole for 12 weeks, with follow-up for an additional 40
weeks. At the end of the study mycological cure rates were 81%
(70 out of 86) for terbinafine and 63% (53 out of 84) for
itraconazole (2P < 0.01). Terbinafine was found to be more
efficacious than itraconazole.
Treatment of tinea unguium with medium and high doses
of ultramicrosize griseofulvin compared with that with itra-
Antimicrob Agents Chemother 1993; 37(10): 2064–2068.
Griseofulvin was once considered the medication of choice
for this condition but has since fallen out of favor. This study
compared ultramicrosize griseofulvin (UMSG) with itracona-
zole in 109 patients. Cure or partial cure was found in 6%
UMSG at 660╯mg, 14% UMSG at 990╯mg, and 19% itracona-
zole at 100╯mg (P = 0.2097); marked improvement was found
in 36, 44, and 39% of patients in the three treatment groups,
respectively. Most patients required treatment for 18 months.
Stable cure was not obtained with UMSG at 660╯mg as the
higher dose of UMSG and itraconazole provided stable cures.
Second-Line Therapies
Griseofulvin A
Fluconazole C
Treatment of toenail onychomycosis. A randomized, double-
blind study with terbinafine and griseofulvin. LAGOS II
Study Group. Hofmann H, Bräutigam M, Weidinger G, et al.
Arch Dermatol 1995; 131:919–922.
Randomized, double-blind study of 195 patients with
severe dermatophyte infections of the toenails was performed
comparing a 24-week treatment with terbinafine (250╯mg/d)
with 48-week treatment with micronized griseofulvin
(1000╯mg/d). After 48 weeks, effective treatment was achieved
in 67% of the patients treated with terbinafine and in 56% of
those treated with griseofulvin (two-tailed P = .120). At a
follow-up visit 24 weeks later, cure rates had decreased to 60%
An evaluation of the safety and efficacy of fluconazole
in the treatment of onychomycosis. Smith SW, Sealy DP,
Schneider E, et al. South Med J 1995; 88:1217–1220.
16 subjects were enrolled in this open-label non-comparative
study to evaluate the safety and efficacy of fluconazole as a
single daily dose for a period of 6 months. Fluconazole proved
to be safe and efficacious in the treatment of onychomycosis.
Fluconazole in the treatment of onychomycosis caused by
dermatophytes. Kuokkanen K, Alava S. J Dermatol Treat 1992;
3:115–117.
147
 Part 1 Medical Dermatology
Study investigated response of Trichophyton rubrum ony-
chomycosis to fluconazole in 46 of the most severely affected
nails of 20 patients. All fingernails and 92% of toenails were
clinically and mycologically free of infection at the end of
treatment. After 6 months follow-up, the cure rate in toenails
was 83% and in fingernails 100%.
Third-Line Therapies
Topical amorolfine B group: 119, vehicle group: 118). Results showed that ciclopirox
Topical ciclopirox A
Topical tioconazole D Trichophyton rubrum, and for mild to moderate toenail ony-
A randomized trial of amorolfine 5% solution nail lacquer
in association with itraconazole pulse therapy compared
with itraconazole alone in the treatment of Candida finger-
nail onychomycosis. Rigopoulos D, Katoulis AC, Ioannides D,
et al. Br J Dermatol 2003; 149(1):151–156.
Study compared itraconazole pulse therapy combined with
amorolfine vs itraconazole alone in the treatment of Candida
fingernail onychomycosis. 90 patients with moderate to severe
Candida fingernail onychomycosis were randomized into two
treatment groups of 45 subjects each. Group 1 received itraco-
nazole pulse therapy for 2 months and applied amorolfine 5%
solution nail lacquer for 6 months, while group 2 received
monotherapy with three pulses of itraconazole. At the 3-month
visit, mycological cure was seen in 32 (74%) of 43 patients in
group 1 and in 25 (60%) of 42 patients in group 2. At the
9-month visit, a global cure was seen in 40 patients (93%)
in group 1 and in 34 patients (81%) in group 2. Statistical
analysis showed no statistically significant difference (P >
0.1) between the two treatment groups. While differences in
cure rates were not found to be statistically significant, the
addition of amorolfine to oral itraconazole pulse therapy is
efficacious and more cost effective than using three pulses of
itraconazole alone.
148
Ciclopirox nail lacquer topical solution 8% in the treatment
of toenail onychomycosis. Gupta AK, Fleckman P, Baran R.
J Am Acad Dermatol 2000; 43:(4 Suppl).
Two identically designed, double-blind, vehicle controlled,
parallel group multicenter studies were performed in the
United States to evaluate the use of ciclopirox nail lacquer to
treat mild to moderate toenail onychomycosis caused by der-
matophytes. In the first study, 223 patients were randomized
to treatment (ciclopirox group: 112, vehicle group: 111), and
in the second study, 237 subjects were randomized (ciclopirox
nail lacquer 8% topical solution is significantly more effective
than placebo in the treatment of onychomycosis caused by
chomycosis without lunula involvement. At the end of the
48-week treatment period, the mycologic cure rate (negative
culture and negative light microscopy) in study I was 29% vs
11% in the ciclopirox and vehicle groups, respectively. Simi-
larly, the mycologic cure rate for study II was 36% vs 9%,
respectively. In the non-US studies, the mycologic cure rates
ranged from 46.7% to 85.7%.
Tioconazole nail solution – an open study of its efficacy in
onychomycosis. Hay RJ, Mackie RM, Clayton YM. Clin Exp
Dermatol 1985; 10(2):111–115.
27 patients with onychomycosis received treatment with
tioconazole (28%) for up to 12 months. Six patients (22%)
achieved complete clinical remission and were free of infection
at follow-up, 3 months after therapy. They included infections
caused by Trichophyton rubruni, Hendersonula toruloidea and
Acremonium. The results indicate that cures of onychomycosis
are possible after topical therapy, however, only fingernails
responded to tioconazole; toenails did not respond to this
topical therapy.
References
1. Haneke E. Fungal infections of the nail. Semin Dermatol 1991; 10:41.
2. Zaias N. Onychomycosis. Arch Dermatol 1972; 105:273.
Part 1 Medical Dermatology

Lichenoid Disorders
Sonia Badreshia-Bansal
Lichen amyloidosis . . . . . . . . . . . . . . . . . . . .
Lichen nitidus . . . . . . . . . . . . . . . . . . . . . . .
Lichen planus . . . . . . . . . . . . . . . . . . . . . . .
Cutaneous lichen planus . . . . . . . . . . . .å°“ . . . . .
Mucosal involvement . . . . . . . . . . . . . . . . . . .
Lichen sclerosus . . . . . . . . . . . . . . . . . . . . . .
Pediatric perspectives: Lichen sclerosus
et atrophicus . . . . . . . . . . . . . . . . . . . . . . . .
Lichen striatus . . . . . . . . . . . . . . . . . . . . . . .
8â•…
149 for lichen amyloid includes lichen simplex chronicus and
hypertrophic lichen planus, both of which are characterized
152
by pruritic plaques often on the shins. Lichen amyloidosis can
154 be associated with multiple endocrine neoplasia type 2A
155 (MEN 2A), also known as Sipple syndrome. The cardinal triad
of this autosomal dominant syndrome is medullary thyroid
156
carcinoma, pheochromocytoma, and hyperparathyroidism.
158 Many cases of familial LA were reported in families with MEN
2A. LA in this syndrome is usually localized to the interscapu-
160 lar region consisting of lichenoid papules, with hyperpigmen-
tation and fine scaling. In addition, LA has been reported in
161 association with atopic dermatitis, lichen planus, and mycosis
fungoides.3
Histochemical stains can yield the diagnosis of amyloido-
sis. Amyloid deposits are found within the upper papillary

Lichen amyloidosis dermis. The deposits may expand the papillae and displace the
elongated rete ridges laterally. The overlying epidermis is acan-
thotic and hyperkeratotic.4,5 Crystal violet stain is a very simple
Amyloidosis is a term used to refer to several diseases that and sensitive method to detect the existence of amyloid. In
share the common feature of abnormal extracellular deposi-
tion of amyloid. Dermatologists are likely to encounter the
more common cutaneous forms of amyloid that are primary
or secondary to skin tumors, and less frequently the systemic
forms. Lichen amyloidosis (LA) is a variant of primary local-
ized cutaneous amyloidosis (PLCA) characterized by deposi-
tion of amyloid in normal skin without systemic involvement.
Other types of PLCA include macular (Fig. 8.1) and nodular
forms. Severe and therapy-resistant pruritus is the most promi-
nent feature of lichen amyloidosis that leads to further amyloid
deposition by recurrent frictional trauma to the epidermis.
LA is the most common form of PLCA and usually presents
as persistent, intensely pruritic, hyperkeratotic plaques on the
extensor surfaces of the extremities, especially the pretibial
surfaces. Lesions are usually unilateral, but bilateral distribu-
tion can develop. There have been cases of hypopigmentation
as a predominant feature with or without reticular hyperpig-
mentation.1 LA is rare in Western countries, but is relatively
common in Asia, affecting Chinese, Taiwanese, Malaysians, Figure 8.1:╇ Hyperpigmentation with macular and biphasic amyloidosis with the
and Indonesians.2 LA is believed to be more common in characteristic rippled pattern (superiorly) as well as papules of lichenoid amyloidosis
persons of Chinese ancestry. The primary differential diagnosis (inferiorly). (Courtesy of Dermatology, Elsevier, 2nd ed., 2008.)

©2011 Elsevier Ltd, Inc, BV 149

 Part 1 Medical Dermatology
addition, Congo-red stain produces an apple-green birefrin-
gence under polarizing light in the presence of amyloid. Other
stains that identify amyloid deposits include crystal violet
stain, Periodic acid-Schiff stain (PAS), various cotton dyes
(pagoda red, Sirius red), and the fluorescent dyes.
Current therapies for LA are unsatisfactory, with high
relapse rates and treatment failures. Additionally, no treatment
is curative or completely effective but may provide sympto-
matic relief. Since pruritus is a possible primary stimulus for
the deposition of amyloid, treatment is directed at relieving
pruritus. Potent topical corticosteroids, under occlusion or
with a keratolytic such as salicylic acid, may have some
benefit. Intralesional steroids, topical tacrolimus, and topical
dimethyl sulfoxide (DMSO) have been reported to be some-
what beneficial. It is thought that DMSO has an antipruritic
effect and dissolves amyloid deposits, though results may be
transient. Phototherapy, sedating antihistamines, and anecdo-
tal evidence of oral retinoids have been reported. However,
there have also been failures reported with DMSO and etreti-
nate. Low dose cyclophosphamide has been shown to be ben-
eficial, although side effects may outweigh the benefits.
Antihistamines and menthol have been used successfully to
relieve pruritus.6
First-Line Therapies
Topical corticosteroids D
Intralesional corticosteroids D
Topical calcineurin inhibitors E
Topical calcipotriol D Successful treatment of lichen amyloidosus associated with
Dimethyl sulfoxide (DMSO) D atopic dermatitis using a combination of narrowband ultra-
Although treatments have not been found to be uniformly
effective and do not lead to removal of amyloid deposits, the
goal is to alleviate symptoms and perhaps prevent worsening
of the condition.
Calcipotriol ointment vs betamethasone 17-valerate oint-
ment in the treatment of lichen amyloidosis. Khoo BP, Tay
YK, Goh CL. Int J Dermatol 1999; 38(7):539–541.
16 Asian patients presenting clinically with symmetrically
distributed lichen amyloidosis (LA) on the extremities, were
enrolled in this double-blind, right–left comparison pilot
study to evaluate the efficacy of calcipotriol ointment vs beta-
methasone 17-valerate ointment over 12 weeks. Calcipotriol
was used successfully to alleviate symptoms including pruri-
tus, roughness, and hyperpigmentation.
Lichen amyloidosis: clinical study of 40 cases. Choi JY, Sippe
J, Lee S. Tay C, Dacosta J. Br J Dermatol 1970; 82:129–136.
40 patients with lichen amyloidosis in a Singapore general
medical hospital, most of whom were middle-age Chinese
females with > 20 years history of the disease, were evaluated.
150
Pruritus was absent in 37.5%. The common cutaneous lesions
were papules and plaques found mostly on the shins and
thighs. Treatment with intralesional and topical steroids are
discussed.
Intermittent use of topical dimethyl sulfoxide in macular
and papular amyloidosis. Ozkaya-Bayazit E, Kavak A, Güngör
H, Ozarmagan G. Int J Dermatol 1998; 37(12):949–954.
In this controlled study, 13 patients with biopsy proven
cutaneous amyloidosis (5 macular amyloidosis [MA], 5 lichen
amyloidosis [LA] and 6 biphasic) were treated with a 50 or
100% DMSO solution until pruritus disappeared. The mean
time for disappearance of pruritus was 4.1 weeks with signifi-
cant flattening of the papules after an average of 9 weeks.
After a total of 6.5 months, nearly 50% remission in pigmenta-
tion and > 70% flattening of papules were achieved. The
longest effective DMSO application interval was 8.6 days.
Interval therapy was better tolerated than daily therapy,
maintained effectiveness, and enabled patients to tolerate side
effects , including burning, desquamation, and urticaria more
easily.
Second-Line Therapies
NBUBV E
PUVA E
Systemic retinoids E
violet B phototherapy, topical corticosteroids and an anti-
histamine. Oiso N, Yudate T, Kawara S, Kawada A. Clin Exp
Dermatol 2009 Dec; 34(8):e833–e836.
A Japanese man with atopic dermatitis-associated LA was
successfully treated with narrowband ultraviolet B photother-
apy, topical corticosteroids, and an oral antihistamine.
Successful treatment of lichen amyloidosis with combined
bath PUVA photochemotherapy and oral acitretin. Grimmer
J, Weiss T, Weber L, Meixner D, Scharffetter-Kochanek K. Clin
Exp Dermatol 2007; 32(1):39–42.
2 patients with resistant lichen amyloidosis received a com-
bined regimen with bath psoralen and ultraviolet A (PUVA)
and oral acitretin, resulting in nearly complete resolution of
the papules and significant relief of severe pruritus which had
persisted for 8 months.
Oral retinoids require close monitoring of blood tests and con-
traception to prevent pregnancy in fertile women. In addition,
baseline and regular monitoring of liver function and lipids
should be performed.
Acitretin for lichen amyloidosis. Choi JY, Sippe J, Lee S.
Australas J Dermatol 2008; 49(2):109–113.
Two case reports of lichen amyloidosis were successfully
treated with oral retinoids. A 57-year-old Vietnamese woman

with extensive, recalcitrant lichen amyloidosis for 23 years was
treated with oral etretinate (25 mg/day) for 3 years, and later
oral acitretin (10 mg/day) for 10 years. Improved pruritus and
flattening of hyperkeratotic papules was noted. However,
lesions recurred within weeks of discontinuing acitretin but
improved with reintroduction. The second case is a 51-year-old
Australian Aboriginal woman with a 2-year history of lichen
amyloidosis affecting her lower legs. A 2-month course of oral
acitretin (25 mg twice daily) produced a marked improvement
in both the pruritus and hyperkeratotic papules. Symptoms
recurred 2 years later.
Third-Line Therapies
Dexamethasone
Cyclosporine
Cyclophosphamide
Lasers (Q Switched Nd:YAG, CO2, pulse dye laser)
Dermabrasion
Dermatologic surgery
Commonly encountered pitfalls
In a study of 794 Chinese patients, lichen amyloid was the
most common type of PLCA.7 Anosacral amyloidosis is a dis-
order also seen in Asian patients. This disorder could easily be
misdiagnosed as lichen simplex chronicus, post-inflammatory
hyperpigmentation or tinea cruris if the practitioner is not
familiar with this entity. A Chinese study of 10 patients with
anosacral amyloidosis suggested a racial predispostion as it
was found to be relatively common in Taiwanese.8 In previous
reports, anosacral cutaneous amyloidosis was thought to be a
senile disorder, but half of the patients in this study developed
the disease before the age of 60. Apoptosis may be the initial
event causing amyloid deposition, although the mechanism is
unclear. Three patients were found to have diabetes mellitus,
but its association is unclear. A thorough history, a careful
physical examination and a skin biopsy are needed to establish
the diagnosis of anosacral amyloidosis.
A Brazilian study investigating characteristics of familial
PLCA in two families, suggested that although most cases are
sporadic, approximately 10% of cases may have been familial.9
Familial PLCA displays autosomal dominant inheritance, with
clinical and genetic heterogeneity and variable clinical pene-
trance. Spontaneous improvement, after age 25, occurred in
three subjects from both families studied. All affected indi-
viduals in family 1 had a heterozygous missense mutation in
an OSMR gene, but no pathogenic mutation in OSMR was
found in family 2. Mutations in the OSMR gene provide new
insight into mechanisms of itching and apoptosis in human
8â•… Lichenoid Disordersâ•… •â•… Lichen amyloidosis
skin. A familial predisposition should be considered when
evaluating cases of PLCA.
Special management & counseling consideration
Although DMSO has been reported to have some benefit in
alleviating the symptoms of LA, decreasing hyperpigmenta-
tion, and dissolving amyloid deposits, there are some reports
in which it does not improve the condition.10 An open label,
prospective trial of 25 patients treated with topical DMSO for
biopsy proven macular and papular lichen amyloidosis,
revealed only transient improvement of pruritus with minimal
improvement in papules, and little difference in the lightening
of pigmentation. Post-treatment skin biopsies did not reveal a
reduction or disappearance of the amyloid deposits indicating
that DMSO does not reduce amyloid deposition. During the
follow-up period, all patients relapsed. Likewise, a case study
of a Japanese woman with chronic extensive truncal lichen
amyloidosis revealed that the application of DMSO ointment
had no clinical effect.11 Histologically, amyloid deposits per-
sisted despite the treatment. The administration of a topical
corticosteroid led to gradual clinical improvement.
References
1. Ho MS, Ho J, Tan SH. Hypopigmented macular amyloidosis with or
without hyperpigmentation. Clin Exp Dermatol 2009; 34:e547–
e551.
2. Tan T. Epidemiology of primary cutaneous amyloidoses in southeast
Asia. Clin Dermatol 1990; 8(2):20–24.
3. Kang MJ, Kim HS, Kim HO, Park YM. A case of atopic dermatitis-
associated lichen amyloidosis successfully treated with oral cyclosporine
and narrow band UVB therapy in succession. J Dermatolog Treat.
2009; 20(6):368–370.
4. Kumakiri M, Hashimoto K. Histogenesis of primary localized cutane-
ous amyloidosis: sequential change of epidermal keratinocytes to
amyloid via filamentous degeneration. J Invest Dermatol 1979;
73:150–162.
5. Habermann MC, Montenegro MR. Primary cutaneous amyloidosis;
clinical, laboratorial and histopathological study of 25 cases: identifi-
cation of gammaglobulins and C3 in the lesions by immunofluores-
cence. Dermatologica 1980; 160:240–248.
6. Frolich M, Enk A, Diepgen TL, Weisshaar E. Successful treatment of
therapy-resistant pruritus in lichen amyloidosis with menthol. Acta
Derm Venereol. 2009; 89(5):524–526.
7. Wang WJ, Chang YT, Huang CY, Lee DD. Clinical and histopathologi-
cal characteristics of primary cutaneous amyloidosis in 794 Chinese
patients. Zhonghua Yi Xue Za Zhi (Taipei) 2001; 64(2):101–107.
8. Wang WJ, Huang CY, Chang YT, Wong CK. Anosacral cutaneous amy-
loidosis: a study of 10 Chinese cases. Br J Dermatol 2000; 143(6):
1266–1269.
9. Sakuma TH, Hans-Filho G, Arita K, Odashiro M, Odashiro DN, Hans
NR, Hans-Neto G, McGrath JA. Familial primary localized cutaneous
amyloidosis in Brazil. Arch Dermatol 2009; 145(6):695–699.
10. Pandhi R, Kaur I, Kumar B. Lack of effect of dimethylsulphoxide in
cutaneous amyloidosis. J Dermatolog Treat 2002; 13(1):11–14.
11. Kobayashi T, Yamasaki Y, Watanabe T, Onoda N. Extensive lichen
amyloidosis refractory to DMSO. J Dermatol 1995; 22(10):755–
758.
151
 Part 1 Medical Dermatology
Lichen nitidus
Lichen nitidus is a relatively common, chronic inflammatory
skin condition of uncertain etiology which is characterized by
clusters of pinpoint, flat topped, skin colored, shiny papules
on the flexor surfaces of the upper extremities, dorsal hands,
genitalia, and the anterior trunk (Fig. 8.1). The papules occur
in a linear array as a result of koebnerization. Whereas lichen
planus appears to be more prevalent in children and young
adults, lichen nitidus was not found to be restricted to a spe-
cific population group based on race, sex, or age.1 Lichen
nitidus shares clinical similarities with lichen planus.2,3
In a study of skin diseases in Blacks over a 25-year period,
the incidence of lichen nitidus was 0.034%. In ethnic patients,
the papules of lichen nitidus may be hypopigmented or hyper-
pigmented. In fact, hypopigmentation is a characteristic that
is recognized more easily in skin of color (Fig. 8.2).4
A
B
Figure 8.2:╇ (A) Hypopigmented papules of lichen nitidus on an African American
patient. (Courtesy of Dave Adams MD; Department of Dermatology, Penn State
Milton S. Hershey Medical Center.) (B) Close up view shows the shiny surface of
lichen nitidus. (Courtesy of Dermatology, Elsevier, 2nd ed., 2008.)
152
Histology shows a very distinct pattern. The papules are
composed of well circumscribed infiltrates of lymphocytes,
epithelioid cells, and occasional Langhans giant cells typically
clutched by hyperplastic rete ridges that create the distinctive
“ball and claw” pattern.5
Due to the rarity of the condition, few symptoms, and rela-
tively mild nature with resolution within 1 year, no treatment
has been rigorously tested in controlled trials. Anecdotal
evidence has shown that corticosteroids, oral retinoids,
topical tacrolimus, phototherapy, and antihistamines may
show some benefit. One study showed that in 69% of patients,
the duration was 1 year or less, with the longest duration being
8 years.1
First-Line Therapies
Topical corticosteroids E
Topical tacrolimus E
Localized cases of lichen nitidus are best treated with
topical medications. Anecdotal evidence suggests topical cor-
ticosteroids and tacrolimus may prove beneficial.
Lichenoid eruptions in children. Tilly JJ, Drolet BA, Esterly
NB. J Am Acad Dermatol. 2004 Oct; 51(4):606–624.
This article reviews lichenoid reactions, including lichen
nitidus in children. Topical treatment with mid- to high-
potency corticosteroids has hastened resolution of lesions in
some children as discussed in systemic therapies below.
Lichen nitidus treated with topical tacrolimus. Dobbs CR,
Murphy SJ. J Drugs Dermatol 2004; 3(6):683–684.
A 32-year-old Philippino male with a penile rash of 2
months’ duration had biopsy proven lichen nitidus and was
successfully treated with the non-indicated therapy of Protopic
0.1% twice daily for 4 weeks. The patient had no recurrence
during his 4 week follow up.
Tacrolimus inhibits several proinflammatory cytokines including
interleukin 2 and tumor necrosis factor alpha. This treatment is a
good alternative as a steroid sparing agent, especially in areas such
as the groin, axilla, and facial involvement.
Second-Line Therapies
NBUVB E
PUVA E
Oral corticosteroids E
Antihistamines D
Oral retinoids E
Generalized cases of lichen nitidus are best treated with
phototherapy and systemic agents such as corticosteroids
and retinoids. Symptomatic relief can be achieved with

antihistamines. Because of the anecdotal nature of reports of
response to treatments, and the propensity for the disease to
resolve spontaneously, these cases can be difficult to objec-
tively evaluate the true effectiveness of various therapies.
Two cases of generalized lichen nitidus treated successfully
with narrow-band UV-B phototherapy. Kim YC, Shim SD. Int
J Dermatol 2006; 45(5):615–617.
Two cases of lichen nitidus persisting for 3 and 6 months
in duration in two Korean children were presented. Narrow-
band UVB phototherapy resulted in almost complete clearance
during the 30th and 17th treatments respectively.
Treatment of generalized lichen nitidus with PUVA. Randle
HW, Sander HM. Int J Dermatol 1986; 25(5):330–331.
Generalized lichen nitidus refractory to topical and
systemic corticosteroids responded completely to PUVA. The
similarity of lichen nitidus to lichen planus and the presumed
lymphocytotoxic effect of PUVA were the basis for use of oral
photochemotherapy.
Generalized lichen nitidus. Report of two cases treated with
astemizol. Ocampo J, Torné R. Int J Dermatol. 1989 Jan–Feb;
28(1):49–51.
This Spanish study reviewed 2 adult cases of generalized
lichen nitidus. Both patients dramatically improved with the
H1 blocking antihistamine, astemizole 10╯mg daily over 6–12
days. Astemizole offers a worthwhile improvement in side
effect profile over ‘traditional’ H1-histamine receptor antago-
nists, especially in patients bothered by the sedative effects of
these drugs.
Treatment of palmoplantar lichen nitidus with acitretin.
Lucker GP, Koopman RJ, Steijlen PM, van der Valk PG. Br J
Dermatol. 1994 Jun; 130(6):791–793.
This Dutch report presents a young male with an unusual
variant, palmoplantar hyperkeratosis with lichen nitidus. The
features are usually tiny yellow papules, but sometimes a non-
specific keratoderma resembling chronic eczema. Acitretin
75╯mg PO QD showed significant improvement.
Third-Line Therapies
Itraconazole E onstrates the characteristic lesions of lichen nitidus but in a
Dinitrochlorobenzene (DNCB) E
Isoniazid E
Cyclosporine E
Treatment of lichen planus and lichen nitidus with itraco-
nazole: reports of six cases. Libow LF, Coots NV. Cutis 1998;
62(5):247–248.
6 patients with either lichen planus or lichen nitidus were
treated with itraconazole. All showed at least a partial response.
Itraconazole may be worth considering in patients who have
failed other therapies.
8â•… Lichenoid Disordersâ•… •â•… Lichen nitidus
Improvement of lichen nitidus after topical dinitrochlo-
robenzene application. Kano Y, Otake Y, Shiohara T. J Am
Acad Dermatol 1998; 39(2 Pt 2):305–308.
A lichen nitidus (LN) patient with peripheral CD4+ T lym-
phocytopenia was treated with topical dinitrochlorobenzene
(DNCB) application. Complete clearance occurred after
4 months.
Local alterations of the pattern of cells and cytokines by topical
DNCB application could have contributed to the resolution.
First, the infiltrate responsible for the development of LN might
be nonspecifically affected by repeated application of DNCB.
Alternatively, induction of allergic contact dermatitis by topical
DNCB might locally alter the pattern of cells and cytokines
resulting in resolution of LN lesions.
Generalized lichen nitidus successfully treated with an
antituberculous agent. Kubota Y, Kiryu H, Nakayama J. Br J
Dermatol 2002; 146(6):1081–1083.
A Japanese girl with generalized and resistant lichen nitidus
with concomitant M. tuberculosis showed almost complete
clearance of lichen niditus after receiving oral isoniazid for
6 months.
The authors speculated that Th1 cells, continuously activated
by contact dermatitis and possibly M. tuberculosis infection,
produced immunological activation promoting or inducing LN.
Alternatively, isoniazid, in addition to its antituberculous
action, may have beneficial anti-inflammatory properties.
Generalized purpuric lichen nitidus. Report of a case
and review of the literature. Rallis E, Verros C, Moussatou V,
Sambaziotis D, Papadakis P. Dermatol Online J. 2007 May 1;
13(2):5.
This report reviews generalized purpuric lichen nitidus, a
rare and unusual variant of lichen nitidus. In all reported cases,
the purpuric lesions initially developed on the lower legs of
the patients (dorsa of feet, ankles, distal thirds of legs) simulat-
ing pigmented purpuric dermatosis. Biopsies were consistent
with lichen nitidus with subepidermal hemmorhage. This case
highlights treatments including topical and oral steroids,
acitretin, and cyclosporine.
Commonly encountered pitfalls
Lichen nitidus actinicus, a rare variant of lichen nitidus, dem-
photodistributed pattern. This entity is also referred to as sum-
mertime actinic lichenoid eruption (SALE). Often blended
within the spectrum of lichen planus, the condition was first
described in 25 Indian patients.6 Lichen niditus actinicus is a
pruritic disorder occurring in dark skinned young adults with
skin type IV or V following prolonged summer sun exposure.
The characteristic lesions are lichenoid pinhead sized papules.
There have been cases where there was prominent facial
involvement.7 Histopathologic features include early basal cell
degeneration, spongiotic vesiculation with or without focal
parakeratosis and an intense lymphocytic infiltrate in the
dermis. A broadened clinical spectrum of SALE includes
various types of lichenoid eruptions such as annular
153
 Part 1 Medical Dermatology
hyperpigmented plaques, melasma-like patches, grayish-white
pinhead papules, and typical LP-like papules and plaques.8
One proposal suggests separating these distinct clinical entities
and aborting the use of SALE. Instead, papules exclusively
dispersed on sun-exposed areas with lichen nitidus-like histo-
logic features would be coined lichen nitidus actinicus, while
the term lichen planus actinicus would be used for annular
lesions with histologic features of lichen planus.9
Special management & counseling considerations
Actinic lichenoid eruption, as described above, responds favo-
rably to sun avoidance, sun protection, and corticosteroid
cream but recurrences are common during the subsequent
summers when the lesions tend to become more persistent,
pruritic and lichenified. Despite strong clinical evidence of its
relation to sunlight, the lesions are not easily reproducible by
artificial light.
The controversy regarding the etiology of lichen nitidus, and
relationship of lichen nitidus to lichen planus is still unre-
solved. Some believe lichen nitidus to be a variant of lichen
planus. Although most reports show complete clearance
without hyerpigmentation or residual hypopigmentation, there
are reports of residual and prominent hyperpigmentation
following resolution of lichen nitidus.10,11,12,13 Progression
from lichen nitidus to lichen planus has also been observed.14
Administration of the treatments described above in very
young patients has to be weighed against the potential benefits
for this usually self-limiting condition. Etretinate, acitretin,
PUVA, and dinitrochlorobenzene application seem to be obvi-
ously contraindicated in very young patients. Although initial
Lichen planus
Lichen planus (LP) is an idiopathic, pruritic, inflammatory
disease of the skin, hair, and mucous membranes character-
ized by flat topped, polygonal, violaceous papules and plaques
with fine scale (Fig. 8.3). There is a predisposition for the
wrists, flexor surfaces of the upper extremities, genitalia, and
mucous membranes. Oral lichen planus is a chronic disease
that causes bilateral white striations, papules, or plaques on
the buccal mucosa, tongue, and gingiva. Variants include
annular, bullous, hypertrophic, linear, ulcerative, and lichen
planopilaris.
Cutaneous LP has been reported in 0.22–1% of the popula-
tion depending on the region,1 while oral lesions have been
described in 1–4% of the population.2 There is no relationship
to racial or ethnic background. The onset of lichen planus
occurs most commonly during the fifth or sixth decade, with
two-thirds of patients developing the disease between ages 30
and 60. Mucosal involvement may be observed in up to 75%
of patients with cutaneous lichen planus.
LP is caused by an autoimmune response that causes
cytotoxic T-cell mediated apoptosis of basal keratinocytes.3,4
154
reports suggest a good response to astemizole, others have not
indicated encouraging response to this medication.13
References
1. Lapins NA, Willoughby C, Helwig EB. Lichen nitidus. A study of forty-
three cases. Cutis 1978; 21(5):634–637.
2. Ellis FA, Hill WF. Is lichen nitidus a variety of lichen planus? Arch
Dermatol Syphilol 1938; 38:569–573.
3. Ellis FA. Histopathology of lichen planus based on analysis of one
hundred biopsy specimens. J Invest Dermatol 1967; 48:143–148.
4. Sordet M, Chavaz P. [Three cases of lichen nitidus in black people
(author’s transl)]. Dermatologica 1981; 162(6):455–461.
5. Savin JA. Lichen nitidus. Br J Derm 1970; 82:423–424.
6. Bedi TR. Summertime actinic lichenoid eruption. Dermatologica
1978; 157(2):115–125.
7. Modi S, Harting M, Metry D. Lichen nitidus actinicus: a distinct facial
presentation in 3 pre-pubertal African-American girls. Dermatol
Online J 2008; 14(4):10.
8. Isaacson D, Turner ML, Elgart ML. Summertime actinic lichenoid erup-
tion (lichen planus actinicus). J Am Acad Dermatol 1981; 4(4):
404–411.
9. Hussain K. Summertime actinic lichenoid eruption, a distinct entity,
should be termed actinic lichen nitidus. Arch Dermatol 1998;
134(10):1302–1303.
10. Arizaga AT, Gaughan MD, Bang RH. Generalized lichen nitidus. Clin
Exp Dermatol 2002; 27(2):115–117.
11. Bettoli V, De Padova MP, Corazza M, Virgili A. Generalized lichen
nitidus with oral and nail involvement in a child. Dermatology 1997;
194: 367–369.
12. Bercedo A, Cabero MJ, Garcia-Consuegra J, Hernado M, Yaez S,
Fernández-Llaca H. Generalized lichen nitidus and juvenile chronic
arthritis: an undescribed association. Pediatr Dermatol 1999; 16:406–
407.
13. Al-Mutairi N, Hassanein A, Nour-Eldin O, Arun J. Generalized lichen
nitidus. Pediatr Dermatol 2005 Mar-Apr; 22(2):158–160.
14. Stankler L. The identity of lichen planus and lichen nitidus. Br J
Dermatol 1967; 83:74–77.
Possible exogenous agents include viruses, medications, and
contact allergens. Attention has recently focused on the asso-
ciation with hepatitis C virus, where it appears to be the
strongest in Japanese and Mediterranean populations, perhaps
due to high prevalence. A variety of medications can induce
Figure 8.3:╇ Hypertrophic lichen planus. (Courtesy of Jeff Miller MD; Department of
Dermatology, Penn State Milton S. Hershey Medical Center.)

an LP-like reaction. Oral LP is likely mutifactorial and precipi-
tating factors may include dental materials, stress, drugs, and
infectious agents.3,4,5
A study in Nigeria, Singapore, and India showed classic
lichen planus was the most common type, followed by hyper-
trophic, linear, eruptive, generalized, atrophicus, actinicus, fol-
licularis, and pemphigoides.6,7,8 In Asians, a Singaporean study
showed a striking predominance in Indians, as compared to
the low incidence in Chinese and Malays. Mucosal involve-
ment was common, including in adults and children. Nail
involvement was rare. There was an association with diabetes
mellitus and a more protracted course.4
The histopathologic features of LP uniformly show hyper-
keratosis, focal increase in the granular layer, acanthosis
with a ‘saw toothing’ of the epidermis and a lichenoid infil-
trate.9 Apoptotic cells can be seen, known as colloid bodies,
when dyskeratotic keratinocytes remain in the lower levels of
the epidermis and superficial dermis, and Civatte bodies,
which remain in the lower levels of the epidermis. In Asian
patients (Indians, Chinese, Malays), immunofluorescence of
lichen planus lesions conformed to that observed in other
races with intense staining for IgM combined with a shaggy
deposition of fibrinogen along the basement membrane, and
presence of colloid bodies around the basement membrane
zone.10
Treatment of LP should be individualized as patients vary
greatly in severity of symptoms, extent of lesion involvement
and response to treatment. Unfortunately, many treatments
are based on anecdotal evidence and more randomized control
trials are needed. For widespread cutaneous LP, systemic ster-
oids, phototherapy, or oral retinoids are appropriate. However,
one must recognize that spontaneous remissions occur in 85%
of patients within 18 months.11 Oral LP has been reported to
have a mean duration of 5 years, and the erosive form rarely
resolves spontaneously. For oral LP, topical steroids, topical
and systemic cyclosporine, topical calcineurin inhibitors, or
topical retinoids may improve symptoms. It is unknown if
improved control of the inflammatory disease lessens the risk
of malignancy, notably squamous cell carcinoma. Even with
treatment, LP commonly relapses.
Cutaneous lichen planus
First-Line Therapies for Localized Lichen Planus
Topical corticosteroids C rowband UVB therapy. 85% were still in remission after a
Intralesional corticosteroid D median of 34 months. The response rate and need for higher
Antihistamines C cumulative exposure doses were not influenced by sex, age,
First line therapies for localized cutaneous LP include cor-
ticosteroids. In addition, antihistamines can also help with
symptomatic relief.
Treatment of lichen planus. An evidence-based medicine
analysis of efficacy. Cribier B, Frances C, Chosidow O. Arch
Dermatol 1998; 134:1521–1530.
8â•… Lichenoid Disordersâ•… •â•… Lichen planus
This is a critical appraisal review of the literature highlight-
ing various treatments for lichen planus with recommenda-
tions from experts. There are no large randomized trials with
definitive results in the medical literature examining the effi-
cacy of the various drugs or physical treatments for LP. The
recommendations are based on 83 clinical trials. To summa-
rize, clinical trials show potent topical corticosteroids are effec-
tive in treating early or localized cutaneous lichen planus over
2–3 weeks. Occlusion enhances the effect of topical corticos-
teroids. For resistant or hyperkeratotic plaques, intralesional
corticosteroid injections or potent corticosteroids under occlu-
sion may be a good choice for this localized cutaneous disease.
In mild cases, symptomatic therapy includes topical corticos-
teroids and oral antihistamines to reduce pruritus, especially
for children.
Oral corticosteroids are effective for patients with general-
ized cutaneous lichen planus, although recommendations
concerning dosage and duration of therapy vary. Other studies
suggest treating patients at lower doses of prednisone or with
other forms of corticosteroids, including short courses of oral
prednisolone or intravenous methylprednisolone. While sys-
temic corticosteroids alleviate symptoms in most patients, it is
unclear whether this therapy affects the total duration of the
disease.
Second-Line Therapies (or First-Line Therapies for
Widespread Lichen Planus)
Narrowband UVB C
PUVA C
Griseofulvin C
Systemic corticosteroids C
Systemic retinoids (acitretin, isotretinoin) A
Sulfasalazine C
Metronidazole C
Widespread LP requires systematic treatments including
corticosteroids, retinoids, phototherapy, and sulfasalazine.
Ultraviolet-B treatment for cutaneous lichen planus: our
experience with 50 patients. Pavlotsky F, Nathansohn N,
Kriger G, Shpiro D, Trau H. Photodermatol Photoimmunol
Photomed 2008; 24(2):83–86.
This retrospective, non-randomized Israeli study showed a
70% complete response in patients treated with primarily nar-
skin type, presence of additional diseases, failure of previous
treatment or disease duration.
Psoralen plus UVA vs UVB-311 nm for the treatment
of lichen planus. Wackernagel A, Legat FJ, Hofer A, Quehen-
berger F, Kerl H, Wolf P. Photodermatol Photoimmunol Pho-
tomed 2007; 23(1):15–19.
This retrospective analysis showed all 15 patients treated
with oral PUVA achieved a complete or partial clinical response
155
 Part 1 Medical Dermatology

in comparison to 10 patients treated with UVB-311 nm. There 60% of patients, over a follow-up period of 5–36 months.
was no statistically significant difference between the PUVA Worsening of lesions was observed in 1 patient.
and UVB-311 nm-treated patient groups or mean number of Metronidazole is hypothesized to have immunomodulatory
treatment exposures. Recurrence was noted in 47% of PUVA activity in addition to its antimicrobial activity which is a pos-
treated patients after mean follow-up of 20 months versus sible mechanism for treatment of lichen planus.
a recurrence of 30% in UVB-311 nm after mean follow up of
35 months.
Third-Line Therapies
Treatment of lichen planus with a short course of oral pred-
nisolone [Letter]. Kellett JK, Ead RD. Br J Dermatol 1990; Efaluzimab
123:550–551. Trimethoprim-Sulfamethoxazole
While systemic corticosteroids alleviate symptoms in most Itraconazole
patients, it is unclear whether this therapy affects the total Cyclosporine
duration of the disease. The recommended prednisone dose is
Interferon
30–60 mg once daily tapering over 4–6 weeks. Oral corticos-
teroids are the most common treatment for patients with gen-
eralized cutaneous lichen planus. Other studies suggest treating
patients at lower doses of prednisone or with other forms of Mucosal involvement
corticosteroids, including short courses of oral prednisolone
or intravenous methylprednisolone.
First-Line Therapies
The minimal effective dose of prednisone to treat lichen planus
is 15–20 mg for 2–6 weeks, and gradually tapering over several Topical corticosteroids A
weeks. Although rebound and relapses will occur, long-term
Topical immunomodulators A
maintenance should be avoided.
Topical retinoid C
Treatment of lichen planus with acitretin. A double-blind, Intralesional steroid B
placebo-controlled study in 65 patients. Laurberg G, Geiger
JM, Hjorth N, Holm P, Hou-Jensen K, Jacobsen KU, et al. J Am
Acad Dermatol 1991; 24(3):434–437. Second-Line Therapies
An 8-week multicenter, double-blind, placebo controlled
trial of 65 patients with lichen planus reported 64% of patients Topical cyclosporine B
treated with 30 mg/day of acitretin experienced remission or Systemic corticosteroid C
marked improvement. Also, during the subsequent 8-week
PUVA C
open phase, 83% of previously placebo-treated patients
Antimalarials C
responded favorably to acitretin therapy. This study shows that
acitretin is an effective and acceptable therapy for severe cases Systemic retinoids C
of lichen planus.
Typical retinoid clinical and laboratory adverse events must be
monitored. Third-Line Therapies

Successful treatment of lichen planus with sulfasalazine in Low dose methotrexate

20 patients. Bauzá A, España A, Gil P, Lloret P, Vázquez Doval Low dose cyclosporine
FJ. Int J Dermatol 2005; 44(2):158–162. Griseofulvin
This Spanish study included 20 patients with biopsy proven
Biologic agents
cutaneous and/or mucosal lichen planus resistant to corticos-
Infliximab
teroid and retinoid therapy who were treated with sulfasala-
zine titrating doses up to 3 g/day for 4–16 weeks. Some Etanercept
patients also received tapering doses for 2–12 months. All 20 Efaluzimab
patients responded, 13 with complete response and 7 with Alefacept
partial response. All patients reported early resolution of the Basiliximab
pruritus. However, no changes were detected in mucosal LP. Photodynamic therapy
Laser (CO2, excimer)
Oral metronidazole treatment of lichen planus. Büyük
Interferon
AY, Kavala M. J Am Acad Dermatol 2000; 43(2 Pt 1):260–
262. Sulodexide
19 patients with generalized lichen planus were treated Extracorporeal photopheresis
with oral metronidazole, 500 mg twice daily, for 20–60 days. Thalidomide
79% of patients improved with complete responses in over

156

A B
Figure 8.4:╇ Lichen planus with extensive post-inflammatory hyperpigmentation. (Courtesy of Ninad Pendharkar MD; Department of Dermatology, Penn State Milton S.
Hershey Medical Center.)
Commonly encountered pitfalls
Hyperpigmentation of the skin is often a very dramatic
component of LP and is a common complaint among
ethnic patients consulting with dermatologists for LP treat-
ment. Post-inflammatory hyperpigmentation is challenging
and prolonged, often lasting 6–12 months or longer given
the presence of dermal melanin. Treatment of LP-induced
hyperpigmentation is often difficult requiring a great deal
of patience and knowledge of a variety of therapeutic
modalities to achieve success (Fig. 8.4). Directly addressing the
challenges of treating PIH with your patient is extremely
important.
Lichen planus pigmentosus, a distinct clinical entity com-
monly documented in the Indian and Korean population,
should be considered as a variant of lichen planus.12 Lichen
planus pigmentosus exhibits dark brown macules and/or
papules and a longer clinical course without pruritus or
scalp, nail, or mucosal involvement. Histologically, the disease
shows orthokeratosis, basal hydropic degeneration, and scarce
lymphohistiocytic infiltrate and numerous melanophages. The
diagnosis of lichen planus pigmentosus should not be over-
looked in skin of color populations.
Special management & counseling considerations
LP has been associated with hepatitis C, chronic active hepa-
titis, and primary biliary cirrhosis. Chinese patients with oral
lichen planus were found to have a significantly higher fre-
quency of serum autoantibodies than healthy control sub-
jects.13 However, a recent study found no causal relationship.14
A Nigerian study found a higher prevalence of HBsAg in
patients with LP when compared with patients with other
cutaneous dermatosis and normal individuals.15 Although a
causal relationship between LP and hepatitis B has not been
8â•… Lichenoid Disordersâ•… •â•… Lichen planus
established from this study, this report reiterates the impor-
tance of screening patients for the presence of both hepatitis
B, in addition to hepatitis C virus. Hepatitis should be particu-
larly considered in patients with widespread or unusual pres-
entations of lichen planus.
LP has been associated with other diseases of altered immu-
nity including ulcerative colitis, alopecia areata, vitiligo, der-
matomyositis, morphea, lichen sclerosis, and myasthenia
gravis. In addition, lichenoid drug reactions may occur with
several medications including antimicrobials, antihyperten-
sives, antimalarials, metals, NSAIDS, and diuretics. Therefore,
it is important to query patients about their current medica-
tions as well use of herbal remedies which can produce LP-like
cutaneous reactions.
References
1. Boyd AS, Neldner KH. Lichen planus. J Am Acad Dermatol 1991;
25(4):593–619.
2. Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M, et al.
Update on oral lichen planus: etiopathogenesis and management. Crit
Rev Oral Biol Med 1998; 9(1):86–122.
3. Arndt KA. Lichen planus. In: Fitzpatrick TB, Eisen AZ, Wolff K,
Freedberg IM, Austen KF, editors. Dermatology in general medicine.
4th ed. New York: McGraw-Hill; 1993. p. 1134–1144.
4. al-Fouzan AS, Habib MA, Sallam TH, el-Samahy MH, Rostom AI.
Detection of T lymphocytes and T lymphocyte subsets in lichen planus
in situ and in peripheral blood. Int J Dermatol 1996; 35:426–429.
5. Boyd AS, Neldner KH. Lichen planus. J Am Acad Dermatol 1991;
25:593–619.
6. Nnoruka EN. Lichen planus in African children: a study of 13 patients.
Pediatr Dermatol 2007; 24(5):495–498.
7. Vijayasingam SM, Lim KB, Yeoh KH, Cheong WL, Chong YY, Daniel
M, et al. Lichen planus: a study of 72 cases in Singapore. Ann Acad
Med Singapore 1988; 17(4):541–544.
8. Singh OP, Kanwar AJ. Lichen planus in India: an appraisal of 441 cases.
Int J Dermatol 1976;15:752–756.
9. Vincent SD, Fotos PG, Baker KA, Williams TP. Oral lichen planus: the
clinical, historical and therapeutic features of 100 cases. Oral Surg Oral
Med Oral Pathol 1990; 70:165–171.
157
 Part 1 Medical Dermatology
10. Lim KB. An immunofluorescence study of lichen planus among
Asians in Singapore. Ann Acad Med Singapore 1988; 17(4):545–
547.
11. Samman PD. A note on the natural history of lichen planus. Br J
Dermatol 1956; 68:175–181. Irvine C, Irvine F, Champion RH. Long-
term follow-up of lichen planus. Acta Derm Venereol 1991;
71:242–244.
12. Kanwar AJ, Dogra S, Handa S, Parsad D, Radotra BD. A study of 124
Indian patients with lichen planus pigmentosus. Clin Exp Dermatol
2003; 28(5):481–485.
Lichen sclerosus
Lichen sclerosus (LS) is a chronic autoimmune inflamma�
tory condition of unknown etiology. It is most common in
perimenopausal women, but the condition can also occur
in men and children.1 LS presents with white atrophic
plaques most commonly in the anogenital region. Purpura,
telangiectasias, and hemorrhagic blisters may be present. The
condition may be asymptomatic or cause intense pruritus.
In women, the characteristic clinical findings are vulvar hypo-
pigmentation and thin, wrinkled atrophic skin in a figure-
of-eight distribution encircling the vulvar and perianal
region. Scarring can lead to narrowing of the introitus in
women and inability to retract the foreskin in men with
resultant urinary obstruction. In addition, there is a higher
risk of malignancy, especially squamous cell carcinoma.2,3,4
Extragenital LS may also occur and favors the submammary
region, shoulders, neck, and wrists and presents with asymp-
tomatic hypopigmented atrophic patches with follicular
plugging.
Although the etiology is unclear, one theory is that Borrelia
or another spirochete is the causative agent. LS may be asso�
ciated with HLA-DQ77. Although most studies involve Cauca-
sian patients, LS can be found in African-American and Asian
patients. In a military study, the incidence of LS in Black and
Hispanic patients was double that in White patients.5 These
results may have been influenced by the greater access to
medical care in the military.
The goal of treatment of genital LS is to control the disease
and prevent progression. Previously, topical testosterone was
the treatment of choice; however, its use was not proven to be
more effective than placebo. Treatment with potent topical
class I corticosteroids is now the well established therapy of
choice. Although regimens vary, twice daily steroid application
for 3–6 months, followed by occasional use for maintenance,
has demonstrated efficacy. Relief of symptoms is often noted
within weeks of treatment but scarring is irreversible. Other
treatments include topical calcineurin inhibitors, which may
have a slower onset of action or alternatively may be used
for maintenance therapy. However, supporting evidence is
variable. In addition, there are a wide variety of destructive
procedures such as ablative and non-ablative lasers, cryother-
apy, photodynamic therapy, and surgical excision which have
been reported to be beneficial, but their use is often contro-
158
13. Chang JY, Chiang CP, Hsiao CK, Sun A. Significantly higher frequencies
of presence of serum autoantibodies in Chinese patients with oral
lichen planus. J Oral Pathol Med 2009; 38:48–54 [Epub 2008 Aug 31].
14. Zhou Y, Jiang L, Liu J, Zeng X, Chen QM. The prevalence of hepatitis
C virus infection in oral lichen planus in an ethnic Chinese cohort of
232 patients. Int J Oral Sci 2010 Jun; 2(2):90–97.
15. Daramola OO, George AO, Ogunbiyi AO, Otegbayo JA. Hepatitis B
virus in Nigerians with lichen planus. West Afr J Med 2004;
23(2):104–106.
versial. Other systemic therapies such as anti-Borrelia antibiot-
ics, potassium benzoate, and penicillamine have limited
supporting studies or have not been proven to be very effective.
Since extragenital LS is often asymptomatic, treatment is
not required. Prognosis is good for acute genital cases, but is
poor for extragenital cases and for chronic atrophic genital
disease.
First-Line Therapies
Topical corticosteroids A
Topical vitamin A analogs B
Topical vitamin D analogs E
Topical calcineurin inhibitors B
Topical corticosteroids are the mainstay of therapy. Non-
steroidal based topical therapies such as topical retinoids or
topical immunomodulators may prove effective.
Does treatment of vulvar lichen sclerosus influence its prog-
nosis? Cooper SM, Gao XH, Powell JJ, Wojnarowska F. Arch
Dermatol 2004; 140(6):702–706.
In this descriptive cohort study, 327 girls and women with
vulvar lichen sclerosus were followed over 66 months. The
mean age at onset of symptoms in children and adults com-
bined was 43.9 years. Girls were more likely to have urinary
or bowel symptoms and purpura at first presentation than
women for reasons that are unclear. In 96% of patients, symp-
toms improved with treatment, with 66% becoming symptom
free and 30% with a partial response. In those with a response
to treatment, 23% showed total response, with return to
normal skin texture and color and 68% showing partial
response. Moderate or severe scarring occurred less often in
girls. Squamous cell carcinoma developed in 2.4% of women
over a mean follow up of 69 months. Topical ultrapotent
steroid relieved symptoms in most patients and completely
reversed the skin changes in approximately one-fifth of
patients.
Vulvar lichen sclerosus in postmenopausal women: a com-
parative study for treating advanced disease with clobetasol
propionate 0.05%. Diakomanolis ES, Haidopoulos D, Syndos
M, Rodolakis A, Stefanidis K, Chatzipapas J, et al. Eur J Gynae-
col Oncol 2002; 23(6):519–522.

This study evaluated the efficacy and safety of treating
severe lesions in 137 postmenopausal women for several
months on a regular basis. The first group applied clobetasol
propionate 0.05% for 3 months and afterwards on an ‘as
required’ basis; the second group used the ointment for 6
months on a regular basis. At the 6-month and 12 month
follow-up, the second group had a 25% higher improvement
rate. The clinical appearance of the disease demonstrated com-
plete response after 6 months in 30% of the first group, and
55.5% of the second group, and 26% and 41% respectively
after 12 months. There were no side effects from the long-term
use of clobetasol propionate 0.05%.
Topical corticosteroids may have an effect on cell cycle proteins
in genital skin and, in particular, genital skin with lichen
sclerosus changes. The usual length of treatment with corticos-
teroids is 2–12 weeks. Long-term maintenance therapy of
vulvar lichen sclerosus with a moisturizing cream can maintain
the symptom relief induced by topical corticosteroids in women
with vulvar lichen sclerosus and be associated with a reduction
in topical corticosteroid use.
Open study of topical 0.025% tretinoin in the treatment of
vulvar lichen sclerosus. One year of therapy. Virgili A,
Corazza M, Bianchi A, Mollica G, Califano A. J Reprod Med
1995; 40(9):614–618.
An open, uncontrolled clinical study in which 22 patients
affected by histologically confirmed vulvar lichen sclerosus
were treated with topical 0.025% tretinoin applied once a day,
5 days a week, for 1 year. Symptoms, gross appearance and
histopathologic features improved and were maintained over
the 4–13 month follow up period. Cutaneous side effects were
observed but rapidly disappeared with no withdrawals from
the study.
Extragenital lichen sclerosus successfully treated with
topical calcipotriol: evaluation by in vivo confocal laser
scanning microscopy. Kreuter A, Gambichler T, Sauermann K,
Jansen T, Altmeyer P, Hoffmann K. Br J Dermatol. 2002 Feb;
146(2):332–333.
A 69-year-old caucasian woman was presented with a
9-month history of sclerotic skin lesions and hyperkeartotic
plaques with biopsy proven extragenital lichen sclerosus. In
vivo confocal laser scanning microscopy revealed compact
hyperkeratosis and an increased epidermal thickness. Mono-
therapy with calcipotriol ointment applied under occlusion
twice daily over 12 weeks showed improvement after 3 weeks.
The effectiveness of calcipotriol may be due to alteration of
collagen and fibronectin synthesis and inhibition of fibroblast
proliferation, which have an increased sensitivity to binding of
vitamin D3 receptors.
Pimecrolimus 1% cream in the treatment of vulvar lichen
sclerosus in postmenopausal women. Oskay T, Sezer HK,
Genç C, Kutluay L. Int J Dermatol 2007; 46(5):527–532.
A total of 16 patients applied pimecrolimus cream 1% twice
a day over the first 3 months and then as required, with
follow-up over 12 months. Using pimecrolimus, most of the
8â•… Lichenoid Disordersâ•… •â•… Lichen sclerosus
patients exhibited a significant improvement in symptoms and
the clinical appearance of the disease. After 3 months of treat-
ment, complete remission was seen in 11 patients and partial
remission in 4 patients. Over the subsequent 12 months of
follow-up, 10 patients exhibited complete remission, while 5
had partial remission. 4 cases with complete remission expe-
rienced a few relapses during the follow-up period. Older
patients and those with an advanced stage of the disease
responded poorly.
Care must be taken as pimecrolimus is an immunosuppressant
and further risk of progression to squamous cell carcinoma is
unknown.
Multicentre, phase II trial on the safety and efficacy of
topical tacrolimus ointment for the treatment of lichen scle-
rosus. Hengge UR, Krause W, Hofmann H, Stadler R, Gross G,
Meurer M, et al. Br J Dermatol 2006; 155(5):1021–1028.
A multicenter, phase II trial of 84 patients with chronic
active LS treated with tacrolimus ointment 0.1% twice daily
for 16 weeks were followed for a period of 18 months. Clear-
ance of active lichen sclerosus occurred in 43% of patients at
24 weeks of treatment with partial resolution in 34%. Maximal
effects occurred between weeks 10 and 24 of therapy. Treat-
ment led to improvement in itching, erythema, erosions and
induration. There were three (9%) recurrences during the
follow-up period. No malignancies were identified. Systemic
absorption was low.
Second-Line Therapies
Circumcision B
Intralesional corticosteroids C
Secondary treatments include more invasive therapy with
intralesional injections of corticosteroids or circumcision in
male patients.
Lichen sclerosus et atrophicus causing phimosis in boys: a
prospective study with 5-year follow-up after complete cir-
cumcision. Meuli M, Briner J, Hanimann B, Sacher P. J Urol
1994; 152(3):987–989.
A prospective investigation of 100 pediatric patients suffer-
ing from phimosis found a 10% incidence of lichen sclerosus
et atrophicus. This is the first evidence that the development
of secondary phimosis with no apparent reason in school-age
boys is highly suggestive for lichen sclerosus et atrophicus.
Complete circumcision is the therapy of choice because it
completely removes all affected tissue and promotes spontane-
ous regression of disease. There was no recurrence after 5 years
of follow-up.
Intralesional injection of triamcinolone in the treatment of
lichen sclerosus. Mazdisnian F, Degregorio F, Mazdisnian F,
Palmieri A. J Reprod Med 1999; 44(4):332–334.
159
 Part 1 Medical Dermatology

As an alternative to topical corticosteroids, intralesional cyte supernatant which plays a role in proliferation and migra-
triamcinolone was used for 8 patients with symptomatic tion of melanocytes. This impact on keratinocytes or fibroblasts
lichen sclerosus. There was a decrease in severity scores of by tacrolimus may cause increased stem cell factor which may,
symptoms, physical findings, and histopathologic findings. in turn, be responsible for the mechanism of pigmentation in
this patient.
Third-Line Therapies
Special management & counseling considerations
Low dose UVA1 phototherapy
Care must be taken to recognize the potential relationship
CO2 laser
between LS and squamous cell carcinoma. The presence or
Photodynamic therapy (PDT) duration of symptoms is not a useful indicator of potential
Topical testosterone cancer risk. Biopsies may be required to exclude malignant
Surgery transformation, especially since these malignancies tends to
Hydroxychloroquine be very aggressive. In men, other penile carcinomas to exclude
Methotrexate include erythroplasia of Querat and verrucal carcinoma.
PUVA Women presenting with vulvar carcinomas tend to be older.
NBUVB Careful monitoring and close follow up is required in chronic
cases of lichen sclerosus.
Anti-Borrelia antibiotics
Cryotherapy
Ultrasound References
Oral calcitriol 1. Powell J, Wojnarowska F. Lichen Sclerosus. Lancet 1999; 353:
Etretinate 1777–1783.
2. Wallace HJ. Lichen sclerosus et atrophicus. Trans St Johns Hosp
Dermatol Soc 1971; 57:9–30.
3. Carli P, Cattaneo A, De Magnis A, Biggeri A, Taddei G, Giannotti B.
Commonly encountered pitfalls Squamous cell carcinoma arising in vulval lichen sclerosus: a longitu-
dinal cohort study. Eur J Cancer Prev 1995; 4:491–495.
4. Walkden V, Chia Y, Wojnarowska F. The association of squamous cell
Hyperpigmentation is a commonly occurring problem in skin carcinoma of the vulva and lichen sclerosus: implications for follow
of color patients. Hyperpigmentation has been reported as an up. J Obstet Gynaecol 1997; 17:551–553.
adverse event in a Korean woman using topical tacrolimus 5. Kizer WS, Prarie T, Morey AF. Balanitis xerotica obliterans: epidemio-
0.1% applied twice daily for LS. In this case report, a brownish logic distribution in an equal access health care system. South Med J
2003; 96(1):9–11.
pigmentation localized at the site of tacrolimus application 6. Kim YJ, Kang HY. Pigmentation after using topical tacrolimus to treat
was noted after 3 months of therapy.6 Additionally, it has been lichen sclerosus: possible role of stem cell factor. J Am Acad Dermatol
reported that tacrolimus increases stem cell factor in keratino- 2007; 57(5 Suppl):S125–S127.

Ultrapotent topical steroids (clobetasol 0.05%, diflorasone

Pediatric perspectives: diacetate 0.05%, betamethasone dipropionate 0.05% or beta-

methasone dipropionate 0.05% without propylene glycol)

Lichen sclerosus were applied sparingly twice a day for 6 weeks in this case
series. All subjects’ lesions improved at the time of follow-up.

et atrophicus
4 of the 10 were improved, but were not clear at the 6-week
follow-up. 4 subjects complained of burning from the initial
corticosteroid prescribed, but were changed to another potent
corticosteroid and continued to improve. One of the subjects
Candrice R Heath
was prescribed a third potent topical steroid (without propyl-
ene glycol) before improvement occurred. The 10 subjects
First-Line Therapies were followed for 4–36 months. Although recurrence(s)
occurred in 6 subjects, they were brief and responded to
Topical corticosteroids C ultrapotent topical corticosteroid. None of the subjects experi-
enced steroid-induced atrophy or telangiectasias on follow-up
Topical tacrolimus C
examinations.
Topical pimecrolimus D
Unlike adult lichen sclerosus et atrophicus, childhood cases
usually do not progress to squamous cell carcinoma. However,
Ultrapotent topical corticosteroid treatment of childhood patients with lichen sclerosus et atrophicus continuing or
genital lichen sclerosus. Garzon MC, Paller AS. Arch Derma- presenting after puberty need to be monitored for signs of
tol 1999; 135(5):525–528. carcinoma.

160

Successful treatment of anogenital lichen sclerosus with
topical tacrolimus. Böhm M, Frieling U, Luger TA, Bonsmann
G. Arch Dermatol 2003; 139(7):922–924.
This case series of 6 patients included 3 pre-pubertal girls
aged 5 years, 9 years and 9 years. Topical tacrolimus 0.1%
ointment was applied once daily. Improvement and decreased
pruritus was noted after 1–2 weeks of treatment. The 5-year-
old patient was in remission by 1.5 months of use and one of
the 9-year-olds was in remission after 4.5 months of using
topical tacrolimus. The other 9-year-old reported resolution of
pain upon defecation after 2 months of use and complete
resolution at 7 months. Application of topical tacrolimus
0.1% ointment is well-tolerated and does not produce atrophy
in the genital area.
Pediatric patients with lichen sclerosus et atrophicus may
present with a variety of symptoms including itching and/or
constipation. Some patients may even be misdiagnosed as
victims of sexual abuse or child abuse.
Safety and tolerability of adjuvant topical tacrolimus treat-
ment in boys with lichen sclerosus: a prospective phase 2
study. Ebert AK, Rosch WH, Vogt T. Eur Urol. 2008 Oct;
54(4):932–937. Epub 2008 Mar 19.
222 boys had foreskin excision for varying reasons includ-
ing phimosis (68%), fibrosing phimosis (5%), acute balanitis
with urinary retention (1.4%), meatal stenosis (1.8%), hypo-
spadias repair (23.4%) and concealed penis (0.5%). Histopa-
thology examination revealed boys with acute balanitis,
non-specific chronic balanitis, fibrosing phimosis, lichenoid
tissue reaction suggestive of early lichen sclerosus and full scale
lichen sclerosus. 20 of the 25 boys with full scale lichen scle-
rosus participated in this prospective trial. Pre-operatively,
75% of these participants had clinical signs suggesting full
scale lichen sclerosus. The participants ranged in age from
5.2–16.1 years old. Three weeks after surgery, the 20 boys were
instructed to apply tacrolmus 0.1% ointment twice daily for 3
weeks to the glans and meatus. Mild-moderate itching was
noted in 20% of the boys after tacrolimus application. This
itching resolved spontaneously. There were no episodes of
erythema, burning or severe itching reported. Topical tac-
Lichen striatus
Lichen striatus is an uncommon, benign, asymptomatic, and
self-limited eruption of unknown etiology. Environmental
agents, such as viruses, have been implicated given the sea-
sonal variation, occurrence in the spring and summer months,
and the predominance in children.1,2 A somatic mutation
during fetal development along the lines of Blaschko has also
been proposed.2,3 Precipitating factors such as a viral infection,
injury, trauma, or hypersensitivity reaction may lead to a cyto-
toxic T-cell mediated reaction that attacks the mutated kerati-
nocyte clone.1-3
Characteristic lesions of lichen striatus are multiple pink,
tan, or flesh-colored flat topped papules that follow the lines
8â•… Lichenoid Disordersâ•… •â•… Lichen striatus
rolimus is considered a safe and tolerable adjunvant treatment
in boys who undergo foreskin excision for lichen sclerosus.
Despite the lack of double-blind, randomized controlled clinical
trials demonstrating the efficacy of tacrolimus in the treatment
of pediatric lichen sclerosus, it is often used as first-line treat-
ment based largely on anecdotal support and case series.
Multicentre, phase II trial on the safety and efficacy of
topical tacrolimus ointment for the treatment of lichen scle-
rosus. Hengge DR, Krause W, Hofmann H, Stadler R, Gross G,
Meurer M, et al. Br J Dermatol 2006; 155(5):1021–1028.
This trial included 84 participants between the ages of 5
years and 85 years. Eight people withdrew from the study and
their ages were not specified. Tacrolimus ointment 0.1% was
applied twice a day to anogenital and extra-genital lichen scle-
rosus areas for 16 weeks. If deemed clinically beneficial, the
tacrolimus 0.1% ointment was continued through week 24.
The patients were then followed at 1 month, 3 months and 18
months post-treatment. At week 16, 16% of the participants
had a complete response. At weeks 20 and 24, 21% and 43%
respectively had a complete response, except for atrophy and
induration. A complete resolution of erythema, erosion, crust-
ing, edema, burning, itching, pain and soreness defined a
complete response. While a partial response was at least 50%
improved and progressive disease was classified as 25% wors-
ening of symptoms. During the 3 month follow-up phase, 3
participants developed recurrence. Although the results are
encouraging, only 3 girls were included in the study. The age
of the girls was not defined. The authors reported that there
was no significant difference in response to treatment when
the patients’ ages and sexes were analyzed. However, the age
groups were analyzed as under the age of 50 years or over the
age of 50 years.
Second-Line Therapies
Circumcision (males) B
of Blaschko (Fig. 8.5). It occurs most commonly on the proxi-
mal extremities. Digital involvement can lead to nail dystro-
phy. In darkly pigmented individuals, eruptions may appear
as a band-like area of hypopigmentation that may resolve with
post-inflammatory hyper- or hypopigmentation.
The differential diagnosis includes linear forms of
dermatosis such as linear lichen planus, linear psoriasis,
and inflammatory linear verrucous epidermal nevus. Linear
lichen planus and lichen striatus can be indistinguishable
histologically. However, a frequent sequela of lichen
striatus is hypopigmentation while in lichen planus, it is
hyperpigmentation.
Treatment is usually unnecessary due to its asymptomatic
and transient nature. Symptomatic disease responds to class I
topical corticosteroids. Treatment under occlusion may hasten
resolution.
161
 Part 1 Medical Dermatology

A rare case of chronic, biopsy proven bilateral lichen stria-

tus on the lower extremities is described with resolution with
topical corticosteroid.

Lichen striatus in adults and pimecrolimus: open, off-label

clinical study. Campanati A, Brandozzi G, Giangiacomi M,
Simonetti O, Marconi B, Offidani AM. Int J Dermatol 2008;
47(7):732–736.
This pilot study included 3 adult patients with generalized,
recurrent, and symptomatic lichen striatus. All patients were
treated with pimecrolimus 1% twice daily for 6 weeks or until
complete resolution. All patients were noted to experience
improvement without recurrence for 14 months with minimal
to no side effects.

Facial lichen striatus: successful treatment with tacrolimus

Figure 8.5:╇ Linear array of pink flat topped papules on the hand in association
with nail dystrophy. (Courtesy of Dermatology, Elsevier, 2nd ed., 2008.)
First-Line Therapies
Topical corticosteroids
Topical corticosteroids under occlusion
Second-Line Therapies
Topical pimecrolimus
Topical tacrolimus
Anecdotal evidence suggests that local topical treatment
with corticosteroids or calcineurin inhibitors are all that may
be required for symptomatic disease. If asymptomatic, no
treatment is required.
Bilateral lichen striatus. Kurokawa M, Kikuchi H, Ogata K,
Setoyama M. J Dermatol. 2004 Feb; 31(2):129–132.
ointment. Fujimoto N, Tajima S, Ishibashi A. Br J Dermatol
2003; 148(3):587–590.
A 22-year-old Japanese woman with biopsy proven facial
lichen striatus was treated with tacrolimus ointment once or
twice daily, resulting in dramatic improvement in a short
period of time. Since lichen striatus is a T-cell mediated disease,
tacrolimus ointment may be an effective treatment, especially
when alternatives are needed for facial lesions.
Early treatment of multiple and spreading lichen striatus
with topical tacrolimus. Jo JH, Jang HS, Park HJ, Kim MB,
Oh CK, Kwon KS. J Am Acad Dermatol 2007; 57(5):
904–905.
This small case series highlights two pediatric cases with
histologically proven lichen striatus treated with tacrolimus
0.03% twice daily. The first case is a split study showing com-
E plete resolution of lichen striatus within 1 month of treatment
E without subsequent hypopigmentation. The second case
shows resolution of lichen striatus within 2 months of treat-
ment, leaving post-inflammatory hyperpigmentation with
gradual spontaneous improvement. Early treatment might be
beneficial in the treatment of multiple and spreading lichen
striatus in patients with dark skin to reduce hypochromic
E sequelae.
E
References
1. Hafner C, Landthaler M, Vogt T. Lichen striatus (blaschkitis) following
varicella infection. J Eur Acad Dermatol Venereol 2006; 20:
1345–1347.
2. Racette AJ, Adams AD, Kessler SE. Simultaneous lichen striatus in
siblings along the same Blaschko line. Pediatr Dermatol 2009; 26:
50–54.
3. Müller CS, Schmaltz R, Vogt T, Pföhler C. Lichen Striatus and blasÂ�
chkitis: reappraisal of the concept of blaschkolinear dermatoses.
Br J Dermatol 2010 Sep 17.

162
Part 1 Medical Dermatology
Papulosquamous
Disorders
Sonia Badreshia-Bansal
Parapsoriasis . . . . . . . . . . . . . . . . . . . . . . .
Pityriasis rosea . . . . . . . . . . . . . . . . . . . . . .
Plaque psoriasis . . . . . . . . . . . . . . . . . . . . . .
Pediatric perspectives: Psoriasis . . . . . . . . . . . . .
Seborrheic dermatitis . . . . . . . . . . . . . . . . . . .
Facial seborrheic dermatitis . . . . . . . . . . . å°“. . . .
Scalp seborrheic dermatitis . . . . . . . . . . . å°“. . . .
Parapsoriasis
Small plaque parapsoriasis (SPP) and large plaque parapso-
riasis (LPP) are chronic, asymptomatic, papulosquamous
disorders classified under the umbrella of parapsoriasis. They
are idiopathic conditions characterized histologically by abun-
dant superficial lymphoid infiltrates composed of clonal
T-cells that have an increased risk of progression to lym-
phomas.1 It is unclear if these variants are precursors of
cutaneous T cell lymphoma (CTCL). Although parapsoriasis
may occur in all ages, it is more common in the middle-
aged and elderly population, peaking at ages 40–50 years
old. The condition occurs in all racial groups and across all
geographic regions.
Small plaque parapsoriasis consists of well circumscribed,
slightly scaly, light salmon colored patches measuring less
than 5╯ cm located on the trunk and extremities. Large
plaque parapsoriasis manifests as faint erythematous scaly
patches with lesions greater than 5╯ cm and may display
an atrophic ‘cigarette paper’ wrinkling quality. Other forms
of parapsoriasis include the acute variant, called pityriasis
lichenoides et varicelliformis acuta (PLEVA) and the chronic
variants, pityriasis lichenoides chronica (PLC) and lympho-
©2011 Elsevier Ltd, Inc, BV
9â•…
163 matoid papulosis. Ethnic skin may display less erythema,
and greater brown, black or gray hues. Also, as the lesions
166
resolve, the underlying inflammation leads to a greater pro-
168 pensity for post-inflammatory hyperpigmentation (PIH) or
174 rarely hypopigmentation.
SPP can resemble mycosis fungoides (MF), psoriasis,
177
drug eruptions, pityriasis rosea, nummular dermatitis, and
177 secondary syphilis. The differential for LPP includes der�
179 matomyositis, lupus, poikilodermatous genodermatosis, and
chronic radiodermatitis.
Treatment of SPP is based on treatment of symptoms as
well as progression of disease. SPP generally tends to be a
benign, self-limiting disease. Emollients may be sufficient
along with a trial of mid-potency topical steroids to enhance
clinical improvement. Spontaneous remission can occur or
remission can be induced with phototherapy. Repeat biopsy
to rule out progression to MF should be performed under the
following circumstances: increasing numbers of lesions,
increasing lesion size, changes in induration or epidermal
atrophy. Close follow-up on at least a yearly basis is
important.
LPP tends to be indolent, but can progress over several
years. Treatment is recommended because it may prevent
transformation to CTCL. It is speculated that the pathophysio�
logy is long-term antigen stimulation associated with a domi-
nant T-cell clone, one that may represent up to 50% of the
T-cell infiltrate. LPP will not enter remission without
therapy. Topical treatments include high potency steroids and
alkylating agents such as nitrogen mustard and carmustine
(BCNU). Phototherapy can be helpful in inducing remission.
Follow-up every 6 months for repeat biopsies to detect early
progression is important. If the histologic appearance is
benign, without atypical lymphocytes, classification of large
plaque parapsoriasis is made. If atypical lymphocytes are
present, many would classify such patients as having patch
stage CTCL.
163
 Part 1 Medical Dermatology
First-Line Therapies for Small- and Large-Plaque
Parapsoriasis
Emollients E
Topical corticosteroids E Treatment of parapsoriasis and mycosis fungoides: the
Topical tacrolimus E role of psoralen and long-wave ultraviolet light A (PUVA).
NBUVB C Powell FC, Spiegel GT, Muller SA. Mayo Clin Proc 1984;
PUVA C 59(8):538–546.
UVB/UVA E 12 patients with parapsoriasis and 19 patients with mycosis
For limited disease, SPP and LPP can be treated with emol-
lients and mid- and high-potency topical corticosteroids. For
more extensive disease, various forms of phototherapy have
been shown to be helpful. Given the propensity for LPP to
develop into patch stage of CTCL and the limited studies in
parapsoriasis, we have included supporting literature of patch
stage CTCL in this section.
Topical corticosteroids for mycosis fungoides. Experience in
79 patients. Zackheim HS, Kashani-Sabet M, Amin S. Arch
Dermatol 1998; 134(8):949–954.
This prospective study demonstrated significant effective-
ness in clinical clearing in mostly patch stage MF patients with
potent topical corticosteroids over 9 months. Plaque stage MF
may have a more limited role in penetration of topical prod-
ucts to the reticular dermis. Approximately 13% of the patients
experienced temporary depression of serum cortisol levels
which were asymptomatic and were readily reversible.
Successful treatment of patch type mycosis fungoides with
tacrolimus ointment 0.1%. Rallis E, Economidi A, Verros C,
Papadakis P. J Drugs Dermatol 2006; 5(9):906–907.
This is a case report of a 29-year-old man with biopsy
proven patch stage MF, treated with tacrolimus ointment 0.1%
twice daily for 1 month. Complete remission was achieved but
relapse occurred 3 months later. The relapse was successfully
treated with the same therapeutic regimen.
Of interest is the fact that tacrolimus, an immunomodulating
agent that reduces T-cell stimulation, has been implicated in
the occurrence of secondary malignancies including CTCL.
Narrowband UVB (311╯nm, TL01) phototherapy for pityria-
sis lichenoides. Aydogan K, Saricaoglu H, Turan H. Photoder-
matol Photoimmunol Photomed. 2008 Jun; 24(3):128–133.
This Turkish study demonstrated a 65.2% complete
response in PLEVA patients with a mean cumulative dose of
23╯J/cm(2) after a mean number of 43.4 exposures. NB-
UVB treatment led to CR in seven out of eight PLC patients
(87.5%) with a mean cumulative dose of 18.4╯J/cm(2) after
a mean number of 45.8 exposures. 4 patients relapsed within
6 months.
NB-UVB has several advantages over treatment with broad-
band UVB and PUVA offering a safer treatment option. Further
larger studies with longer follow-up periods are necessary to
164
determine the proper clinical response and long-term complica-
tions of NB-UVB therapy in this disease. Postinflammatory
hyperpigmentation is a risk in darker skin types, but has also
been documented in type II and III skin.
fungoides were treated with PUVA. Excellent results were
obtained in the 12 parapsoriasis patients with either consider-
able improvement or complete clearing. The response to PUVA
in patients with mycosis fungoides varied according to the
stage of the disease, with patients with early stage I or II disease
having at least 80% improvement. Therefore, PUVA is highly
effective in the treatment of parapsoriasis as well as in early
stage mycosis fungoides.
PUVA has the disadvantages of increasing risk of skin cancers,
including malignant melanoma, which has been reported
during MF therapy.2 In addition, PUVA requires the wearing
of goggles during the treatment and monitoring for possible
development of cataracts.
Medium-dose ultraviolet A1 therapy for pityriasis lichenoides
et varioliformis acuta and pityriasis lichenoides chronica.
Pinton PC, Capezzera R, Zane C, De Panfilis G. J Am Acad
Dermatol. 2002 Sep; 47(3):410–414.
This controlled study reports the clinical results obtained
with UVA1 (340–400╯nm) therapy in the treatment of 3
patients with PLEVA and 5 patients with PLC. 6 patients had
clinical and histological clearance. Further controlled clinical
trials to compare medium-dose UVA1 phototherapy with well-
established treatment options such as UVB phototherapy and
PUVA. In addition, prospective studies with a long-term
follow-up are needed for the assessment of the carcinogenic
potential.
Evidence suggest approximately 10% to 40% of UVA1 applied
to the skin can penetrate the epidermis and deep dermis, target-
ing CD4+ and CD8+ mononuclear cells, ultimately leading to
apoptosis.3,4,5 Unlike UVA1, both UVB (280–320╯nm) and
UVA2 (320–340╯nm) wavelengths, which are the most active
for psoralen sensitization, have a poor penetration into the
dermis.6,7
Second-Line Therapies for Large Plaque Parapsoriasis
Topical nitrogen mustard (mechlorethamine) B
C
Topical carmustine (BCNU)
LPP must be treated aggressively. There are clinical trials
supporting the benefit of alkylating agents and retinoids in
treating LPP and preventing progression to CTCL.
Treatment of early-stage mycosis fungoides with twice-
weekly applications of mechlorethamine and topical

corticosteroids: a prospective study. de Quatrebarbes J,
Estève E, Bagot M, et al. Arch Dermatol 2005; 141(9):1117–
1120.
This was a prospective, non-randomized study in 64 patients
with newly diagnosed early-stage mycosis fungoides treated
during a 6-month period with twice-weekly applications of a
0.02% aqueous solution of mechlorethamine followed by an
application of betamethasone cream. 58% had complete
response after a mean duration of 3.6 months. 28% developed
severe cutaneous reactions causing discontinuation of therapy
which are lower than other similar studies. Relapse was seen
in 46% of patients which was more common for those with
more advanced disease. Decreased frequency of application
provides an advantage to patients in regard to ease of use and
limited adverse effects.
Topical nitrogen mustard is an effective primary or salvage
therapy in early stage mycosis fungoides. A high proportion
of patients treated with mechlorethamine develop allergic
contact dermatitis and possible increased risk of skin cancer.
When used as an ointment preparation instead of an aqueous
solution, fewer side effects with contact hypersensitization are
experienced.
Topical carmustine (BCNU) for patch/plaque mycosis fun-
goides. Zackheim HS. Semin Dermatol. 1994 Sep; 13(3):
202–206.
This article represents the UCSF clinical experience treating
172 patients with early patch or plaque stage mycosis fun-
goides. 92% of stage-T1 (less than 10% skin involvement) and
64% of stage-T2 (10% or more skin involvement) patients
were either in complete or partial remission when followed
over 26 weeks. Minimal side effects were not a major deterrent
to continuation of therapy.
Carmustine does not increase the risk of skin cancer but com-
monly causes erythematous reactions that may be followed by
telangiectasia and can cause bone marrow depression.
Third-Line Therapies
Photodynamic therapy
Excimer laser
Balneotherapy
Oral retinoids
Electron beam therapy
Commonly encountered pitfalls
The highly variable presentation of this condition in ethnic
skin often poses a diagnostic challenge. One study demon-
strated that 51% of patients with lighter skin types (skin type
I–III), developed post-inflammatory hyperpigmentation.8
9â•… Papulosquamous Disordersâ•… •â•… Parapsoriasis
It is known that ethnic patients with parapsoriasis have an
increased propensity to develop PIH. However, PLC has also
been reported with extensive hypopigmentation with promi-
nent facial, limbs, or axillary fold involvement.9,10 Therefore
an ethnic skin patient who presents with a widespread hypo-
pigmented rash should be considered for a form of parapso-
riasis. It is important for clinicians to recognize that treatments
such as phototherapy, especially in high doses, or use of irritat-
ing topical therapies such as topical nitrogen mustard can
induce further PIH.
Special management & counseling considerations
In general, parapsoriasis can be managed conservatively based
on symptoms. Clinical response does not always equate to
histologic clearance, and recurrence may occur. Small plaque
disease lasts several months to years and can spontaneously
resolve. Large plaque parapsoriasis must be treated in order to
induce remission and prevent progression to CTCL. There is a
thin line between the diagnosis of parapsoriasis and cutaneous
T-cell lymphoma. If atypical lymphocytes are present in the
patches, patients would be classified as having patch stage
CTCL. Therefore follow-up every 6 months with possible
biopsy is recommended. Increasing number of lesions,
increased size of lesions, or poikilodermatous changes are
signals for a repeat biopsy.
References
1. Khachemoune A, Blyumin ML. Pityriasis lichenoides: pathophysio�
logy, classification, and treatment. Am J Clin Dermatol 2007;
8(1):29–36.
2. Reseghetti A, Tribbia G, Locati F, Naldi F, Marchesi L. Cutaneous malig-
nant melanoma appearing during photochemotherapy of mycosis
fungoides. Dermatology 1994; 189:75–77.
3. Krutmann J, Diepgen L, Luger TA, Grabbe S, Meffert H, Sönnichsen N,
et al. High dose UVA1 therapy for atopic dermatitis: results of a
multicenter trial. J Am Acad Dermatol 1998; 38:589–593.
4. Plettemberg H, Stege H, Megahed M, Ruzicka T, Hosokawa Y, Tsuji T,
et al. Ultraviolet A1 (340–400╯nm) phototherapy for cutaneous T-cell
lymphoma. J Am Acad Dermatol 1999; 41:47–50.
5. Godar DE. UVA1 radiation mediates singlet-oxygen and superoxide-
anion production which trigger two different final apoptotic pathways:
the S and P site of mitochondria. J Invest Dermatol 1999; 112:3–12.
6. Bruls WAG, Slaper H, van der Leun JC, Berrens C. Transmission of
human epidermis and stratum corneum as a function of thickness in
the ultraviolet and visible wavelengths. Photochem Photobiol 1984;
40:485–494.
7. Calzavara-Pinton PG. Efficacy and safety of stand-up irradiation cubi-
cles with UVA metal-halide lamps (and a new filter) of UVA fluorescent
lamps for photochemotherapy of psoriasis. Dermatology 1997;
195:243–247.
8. Aydogan K, Karadogan SK, Tunali S, Adim SB, Ozcelik T. Narrowband
UVB phototherapy for small plaque parapsoriasis. J Eur Acad Dermatol
Venereol 2006; 20(5):573–577.
9. Lane TN, Parker SS. Pityriasis lichenoides chronica in black patients.
Cutis 2010 Mar; 85(3):125–129.
10. Clayton R, Warin A. Pityriasis lichenoides chronica presenting as hypo-
pigmentation. Br J Dermatol 1979 Mar; 100(3):297–302.
165
 Part 1 Medical Dermatology

Pityriasis rosea
Pityriasis rosea (PR) most commonly occurs in healthy ado-
lescents or young adults between ages 10 and 35. There is no
racial predilection and the condition appears worldwide with
a slight female predominance. There may be a seasonal varia-
tion with the spring and fall months being most favored. A
Singapore study showed a pattern similar to that reported in
other countries, except for a male predominance and absence
of seasonal variation. A lower incidence and an older group of
patients were also seen as compared to African patients.1
Although the cause of PR is unknown, a viral or bacterial etiol-
ogy has been hypothesized but remains unproven. The most
common etiology has been linked to human herpesvirus 7 A
(HHV-7) and less so to HHV-6.
Pityriasis rosea is a common acute exanthem that presents
with an initial ‘herald patch’ followed by the development of
a papulosquamous eruption consisting of pink or salmon
colored, thin, oval, round, or annular plaques with a central
collarette of scale. PR in ethnic skin may appear as small, dark,
slightly raised pinkish-brown bumps with some scale. PR is
most commonly seen on the trunk and proximal extremities
and follows Langer’s lines of cleavage (Fig. 9.1). Less common
variants include inverse, vesicular, purpuric, and pustular
forms.
Racial differences in the clinical presentation of PR have
been reported. In African-American children greater facial
involvement (30%) and scalp involvement (8%) as compared
to White children have been demonstrated. Approximately
one-third of African-American children will present with
papular lesions as opposed to plaques, and 48% will have B
residual hyperpigmentation.2
PR can be difficult to distinguish from other conditions. Figure 9.1:╇ Extensive thin scaly plaques in an Asian patient with pityriasis rosea.
Several medications and herbs have been linked to PR-like (Courtesy of Ninad Pendharkar MD; Department of Dermatology, Penn State Milton
lesions including gold, ACE inhibitors, beta blockers, cloni- S. Hershey Medical Center.)
dine, antibiotics, isotretinoin, and even mustard oil. As hyper-
tension occurs more frequently in Hispanics and Blacks, use than 80% of patients, although it can persist for 5 months
of beta blockers and clonidine may occur more frequently or more.
resulting in PR-like drug reactions. This eruption may take a
longer period of time to resolve and medication discontinua-
tion is recommended.
The initial herald patch of PR can resemble tinea corporis, First-Line Therapies
nummular dermatitis, or guttate psoriasis. For resistant
plaques, pityriasis lichenoides should be considered. Finally, Topical corticosteroids E
several diseases, the most serious of which is secondary syphi- Emollients E
lis, can mimic PR. Secondary syphilis, which may affect the Oral antihistamines E
palms and soles in addition to the typical PR-like rash, can
be easily ruled out with serological testing.
Supportive treatment with antihistamines, topical anti-
pruritic agents, and excellent skin care with mild cleansers, There are small trials that report some improvement with
oatmeal baths, and moisturization is helpful. There is topical agents including corticosteroids and bland emollients.
some anecdotal evidence that erythromycin and ultraviolet Supportive therapy with oral antihistamines adjunctively is
radiation may hasten resolution, but may resolve with hyper- helpful.
pigmentation at the site of PR lesions. In ethnic skin, if the
disease is severe or widespread, topical or oral steroids may Pityriasis rosea update: 1986. Parsons JM. J Am Acad Derma-
prove helpful. The rash typically lasts about 5–8 weeks in more tol 1986; 15:159–167.

166

A comprehensive review article citing the author’s experi-
ence of using topical corticosteroids, emollients, and oral anti-
histamines in the treatment of pityriasis rosea. He claims all
three treatments to have some benefit.
Second-Line Therapies
UVB B Dapsone
UVA1 D
Ultraviolet radiation therapy has been found to be effective
in some controlled trials.
UVB phototherapy for pityriasis rosea: a bilateral compari-
son study. Leenutaphong V, Jiamton S. J Am Acad Dermatol
1995; 33(6):996–999.
A bilateral comparison study was performed with unilateral
UVB phototherapy and 1╯J/cm2 of UVA as placebo on the
untreated side given 5/week for 10 weeks in 17 patients (15
patients with type IV, 2 patients with type V skin) with severe
PR. The overall reduction of severity score showed a significant
difference after the third treatment and superior results with
UVB irradiation, independent of duration of disease.
Although UVB phototherapy resulted in decreased severity
of disease, the itching and the course of the disease were
unchanged.
UVB phototherapy for pityriasis rosea. Valkova S, Trashlieva
M, Christova P. J Eur Acad Dermatol Venereol 2004; 18:
111–112.
This study involved 101 patients of various ages and pho-
totypes in whom PR had lasted a mean of 16 days. One
group was treated with an initial 80% minimal erythema
dose that was progressively increased. The right half of the
body was irradiated with UVB, and UVA (1╯ J/cm2) was given
as a placebo to the left half of the body. A second group
was given UVB irradiation on the whole body with an initial
dose determined by the patient’s phototype. The procedures
were performed four times weekly. UVA irradiation had no
effect on the course of the disease, but total clearing of the
rash was observed after UVB phototherapy. Patients having
more severe disease and longer duration of the disease
required more treatments.
Low-dose Ultraviolet A1 Phototherapy for Treating Pityriasis
Rosea. Lim SH, Kim SM, Oh BH, Ko JH, Lee YW, Choe YB,
Ahn KJ. Ann Dermatol. 2009 Aug; 21(3):230–236.
This Korean study evaluated the use of low-dose (10–30╯J/
cm2) UVA1 therapy 2–3/week as a possible treatment for PR
in 15 patients (skin types II-IV). The mean duration of treat-
ment was 11 days and no recurrence was noted over 3 months.
It was hypothesized that UVA1 may be most beneficial in the
early stages of the disease due to more inflammatory infiltrate
that acts as a target for T-cell mediated apoptosis and regula-
tion of pro-inflammatory cytokines.
9â•… Papulosquamous Disordersâ•… •â•… Pityriasis rosea
Third-Line Therapies
Antibiotics
Oral erythromycin
Oral azithromycin
Corticosteroid
Acyclovir
Commonly encountered pitfalls
The knowledge of features found more frequently in dark-
skinned population may be helpful to physicians for diagnos-
ing the atypical features of PR. Facial and scalp involvement,
post-inflammatory disorders of pigmentation and papular
lesions are characteristics typically associated to black patients
with PR. In addition, presence of intense pruritus may be
observed in black children and it must not rule out the
diagnosis of PR.3-6 Hypopigmentary or hyperpigmentary skin
changes may follow the inflammatory stage. A potassium
hydroxide test to rule out fungal infection and RPR to rule out
syphilis should be strongly considered, especially where there
is a high incidence in developing countries.
Special management & counseling considerations
Resolution of pityriasis rosea may be hastened by ultraviolet
light therapy but not without the risk of hyperpigmentation.
Caution must be taken with high dose ultraviolet B radiation
therapy as this can also increase risk for post-inflammatory
hyperpigmentation in ethnic patients.
Because the rash is generally asymptomatic and self-limited,
reassurance and patient education is adequate. Education
regarding the expected subsequent pigmentary alteration and
its persistence is also important. Since complementary use is
high among ethnic skin, a thorough drug history including
herbal medications should be taken to rule out a PR-like reac-
tion. Pityriasis rosea generally requires only supportive treat-
ment. Treatment is recommended in extensive disease for the
purpose of achieving more rapid improvement.
References
1. Tay YK, Goh CL. One-year review of pityriasis rosea at the National
Skin Centre, Singapore. Ann Acad Med Singapore 1999; 28(6):
829–831.
2. Amer A, Fischer H, Li X. The natural history of pityriasis rosea in Black
American children: how correct is the “classic” description? Arch
Pediatr Adolesc Med 2007; 161(5):503–506.
3. Chuh A, Zawar V, Lee A. Atypical presentations of pityriasis rosea: case
presentations. J Eur Acad Dermatol Venereol 2005; 19:120–126.
4. Jacyk WK. Pityriasis rosea in Nigerians. Int J Dermatol 1980; 19:
397–399.
5. Vollum DI. Pityriasis rosea in the African. Trans St Johns Hosp
Dermatol So 1973; 59:269–271.
6. Cheong WK, Wong KS. An epidemiological study of pityriasis rosea in
Middle Road Hospital. Singapore Med J 1989; 30:60–62.
167
 Part 1 Medical Dermatology
Plaque psoriasis
Psoriasis is a chronic inflammatory autoimmune disorder
that affects 2% of the world’s population.1 Although psoriasis
is more common in Caucasians, it is not rare in Africans,
African-Americans, and Asians. In one study, psoriasis was
more common in persons of East Indian descent compared
to those of African origin.2 The cause of this cutaneous
disorder is multifactorial with various external and/or internal
factors serving as triggers in genetically predisposed individu-
als. Research has elucidated the role of T helper and sup-
pressor cells in the etiology of psoriasis, which leads to a
cascade of cytokine production, crucial in the control of
epidermal proliferation, differentiation, and inflammation.
Triggers may include infection, medications or trauma.
Chronic plaque psoriasis is the most common type of pso-
riasis with guttate, pustular, inverse and erythrodermic pso-
riasis occurring less commonly. Plaque psoriasis is diagnosed
clinically by the characteristic well demarcated pink plaques
with silvery white scale, often involving extensor surfaces of
the knees and elbows, but also can affect the scalp and
trunk (Fig. 9.2). Scalp involvement is common, affecting
one half of patients and may present specific treatment issues
for skin of color patients. Psoriatic arthritis and nail changes
may be present.
There are several important differences in the clinical
features of psoriasis in ethnic skin as compared to Caucasian
skin. These include the color or hue of the psoriatic plaques
which often do not assume the characteristic pink color
but are usually darker in color exhibiting a brown, black
or gray color. Additionally, there is often less lesional ery-
thema or if present it is less frequently recognized by the
clinician (Fig. 9.3). There is a greater propensity for post-
inflammatory hyperpigmentation after lesion resolution,
similar to other acute inflammatory reactions in this popu-
lation. Another important difference in ethnic skin is the
Figure 9.2:╇ A Hispanic female with generalized plaque psoriasis.
168
greater likelihood of hyperkeratotic plaques, especially on
the palms and soles.
An epidemiological study of childhood psoriasis in north-
ern India showed delayed onset, less frequent facial involve-
ment, uncommon guttate lesions, more frequent involvement
of the soles, and less frequent history of familial occurrence.3
A Korean study revealed that early onset psoriasis patients as
compared to late onset, showed significantly increased tenden-
cies to worsen at times of psychological stress and in winter,
with improvement in summer. Thus, Korean patients with
psoriasis exhibited onset of disease prior to 40 years of age,
had greater susceptibility to seasonal changes, more psycho-
logical stress and increased inheritability compared with
patients with later onset.4
Long-term psoriasis therapy must be individualized in each
patient taking into consideration the actual severity of disease,
the patient’s perception of severity, lifestyle issues and the
potential for side effects as the drivers of therapeutic selection.
The goals of treatment are to initiate and achieve rapid control
of the disease process, decrease the percentage of body surface
area involved, decrease or eliminate lesions, achieve and
maintain long-term remission, minimize adverse events, and
improve patient quality of life.
Topical treatment for mild psoriasis includes cortico�
steroids, calcipotriene, tazarotene, tar, anthralin and immuno�
modulators (pimecrolimus, tacrolimus) with emollients and
keratolytics used as adjunctive therapy. The treatment of
moderate-to-severe psoriasis includes the addition of ultra-
violet radiation or systemic therapies. Systemic therapy with
agents such as methotrexate, acitretin, cyclosporine, hydroxyu-
rea and the array of biologics are most appropriate for severe
disease. In selecting the appropriate systemic agents, the age
of the patient, previous therapies, and reproductive and
general health status are key considerations. Topical treat-
ment can be effective using combination, rotational or
sequential regimens for patients with more severe disease.
Combination treatments with biologics can be more effica-
cious while minimizing side effects. When starting specific
Figure 9.3:╇ Psoriatic plaques in an ethnic patient which demonstrate decreased
erythema. (Courtesy of Jeff Miller MD; Department of Dermatology, Penn State
Milton S. Hershey Medical Center.)
 9â•… Papulosquamous Disordersâ•… •â•… Plaque psoriasis

systemic therapies, baseline laboratory evaluation is required formulations should be avoided on the face, axilla, and groin
which may include a complete blood count and chemistry region.
profile, triglyceride levels, liver profile, renal functions, and
TB screening (for biologics). A two-compound product containing calcipotriol and beta-
methasone dipropionate provides rapid, effective treatment
of psoriasis vulgaris regardless of baseline disease severity.
First-Line Therapies for Mild Psoriasis
van de Kerkhof PC, Wasel N, Kragballe K, Cambazard F, Murray
S. Dermatology 2005; 210(4):294–299.
Topical corticosteroids A A meta-analysis of the data from four randomized, double
Vitamin D analogues A blind studies including 1534 patients demonstrates that the
Topical tazarotene A two-compound product once daily provided highly effective
Coal tar A treatment of psoriasis, regardless of the category of base�
Emollients B line disease severity. Although there was greater improve�
Sun exposure (also see Chapter 18) B ment with more severe disease, it was not statistically
significant.
Anthralin (Dithranol) A
Keratolytics B Calcipotriol therapy is most effective in combination with
topical corticosteroids in the initial weeks of therapy since cor-
Topical tacrolimus B
ticosteroids offer improvement in the first 2 weeks, as compared
Topical pimecrolimus A to 6–8 weeks with calcipotriol.

A comparison of twice-daily calcipotriol ointment with

Primary treatment of mild psoriasis involves the use of
topical corticosteroids, vitamin D analogues, tazarotene and
coal tar with adjunctives such as emollients and sun exposure.
The efficacy of topical therapy in the treatment of plaque pso-
riasis is well established with documentation in the general
population and in some cases, in skin of color. Data support-
ing the efficacy of treatment in the skin of color population,
when available, may involve open-label trials or those with
smaller numbers of subjects. In this section our final evidence
scale reflects the data obtained for the greater population
unless otherwise noted.
once-daily short-contact dithranol cream therapy: quality-
of-life outcomes of a randomized controlled trial of super-
vised treatment of psoriasis in a day-care setting. de Korte J,
van der Valk PG, Sprangers MA, Damstra RJ, Kunkeler AC,
Lijnen RL, et al. Br J Dermatol 2008; 158(2):375–381.
In a multicenter, randomized, controlled trial of Dutch
patients with chronic plaque psoriasis, 54 patients received
calcipotriol ointment twice daily and 52 patients received
dithranol cream once daily in a 12-week intensive treatment
program. No statistically significant differences in improve-
ment of quality of life could be found.

Clobetasol-17-propionate lotion under hydrocolloid
dressing once weekly versus unoccluded clobetasol-17-
propionate ointment twice daily in psoriases: an immuno-
histochemical study on remission and relapse. Van Der
Vleuten CJ, Van Vlijmen-Willems IM, De Jong EM, van de
Kerkhof PC. Arch Dermatol Res 1999; 291(7–8):390–395.
Clobetasol-17-propionate lotion under a hydrocolloid
dressing (HCD) once weekly to enhance penetration versus
clobetasol-17-propionate ointment twice daily without occlu-
sion was assessed clinically and histologically. Combination
of HCD and corticosteroids is able to induce relatively fast
remission compared to corticosteroid monotherapy. Relapse
and safety characteristics are comparable to the unoccluded
corticosteroid therapy. Clinically, there were no signs of skin
atrophy but histologically, epidermal thinning occurred to the
same extent with both therapies but proved to be reversible
within 6 weeks of discontinuation of treatment.
Once daily application of corticosteroids has been shown to
be as effective as twice-daily application, and long-term remis-
sions may be maintained by alternate days or weekend-only
application. Recalcitrant or severe plaques often require occlu-
sion, but have little difference with respect to relapse. Side
effects of topical corticosteroids include striae, telengectasia,
atrophy, tachyphylaxis, folliculitis, and steroid acne. Potent
Given the ease of use, calcipotriol, being more practical and
patient friendly, can be considered as a first-line approach in
clinical practice. Short-contact dithranol, leaving on 5 minutes
and increasing 5 minutes every other day as tolerated, is proven
effective but some may consider using it as a second-line treat-
ment due to its irritation and staining potential.
Comparative study of calcipotriol (0.005%) ointment and
tazarotene (0.05% and 0.1%) gel in the treatment of stable
plaque psoriasis. Kaur I, Dogra S, Jain R, Kumar B. Indian J
Dermatol Venereol Leprol 2008; 74(5):471–474.
This prospective comparative split-side study in India was
performed on 20 patients with plaque psoriasis. Topical cal-
cipotriol 0.005% ointment is more effective than tazarotene
0.05% gel; however, its efficacy is comparable to tazarotene
0.1% gel in the treatment of stable plaque psoriasis. Irritation
of tazarotene may be the most important local cutaneous
reaction.
Calcipotriol acts in psoriasis by inhibiting keratinocyte prolif-
eration, inducing cellular differentiation and exerts an anti-
inflammatory action while tazarotene modulates keratinocyte
hyperproliferation, abnormal keratinocyte differentiation, and
dermal and epidermal inflammatory infiltration by binding
retinoic acid receptors. Dose of UVB light may need to be

169
 Part 1 Medical Dermatology

reduced when used in combination with tazarotene to avoid

burns. It is a category X drug. Table 9.1╇ Common Combination Treatment Approaches

A comparative study of tar and betamethasone valerate Acitretin plus

in chronic plaque psoriasis: a study in Thailand. Thaworn- • Phototherapy
chaisit P, Harncharoen K. J Med Assoc Thai 2007; 90(10): • Cyclosporine
1997–2002. • Biologics
Thai patients with stable mild to moderate plaque psoriasis Cyclosporine and methotrexate
were randomized to treatment with coal tar cream or betam- Cytotoxic agents (i.e methotrexate) plus
ethasone valerate cream 0.1%. The betamethasone valerate • Phototherapy
group was significantly superior to the coal tar group. Adverse • Biologics
effects from both drugs were limited to mild local irritation. Mycophenolate mofetil and cyclosporine
The coal tar cream was described as messy, malodorous, and Topical agents plus
had a tendency to stain clothes. • Acitretin
Cancer epidemiology studies fail to show a link between coal • Phototherapy
tar therapy and increased risk of cancer. Although the Cosmetic
Ingredient Review (CIR) Expert Panel believes that coal tar use
as an antidandruff ingredient in over-the-counter (OTC) drug Topical immunomodulators are effective steroid-sparing
preparations is adequately addressed by the FDA regulations, alternatives on the face and in intertriginous psoriatic
the appropriate and maximum concentration that does not lesions, thereby limiting the adverse effects associated with
induce a biological effect is unclear. corticosteroids.
Moisturizing cream ameliorates dryness and desquamation
A clinician’s paradigm in the treatment of psoriasis. Lebwohl
in participants not receiving topical psoriasis treatment.
M. JAAD 2005; 53(1 Suppl 1):S59–S69.
Draelos ZD. Cutis 2008; 82(3):211–216.
This article details topical treatments for mild psoriasis and
30 participants with mild to moderate plaque psoriasis
systemic treatments for severe psoriasis. Treatment algorithms
(5–10% body surface area) were treated as monotherapy with
developed by a 2002 consensus conference are described.
only a moisturizing cream. Subjects were objectively moni-
Treatments utilizing a combination, rotational, or sequential
tored over 4 weeks for skin barrier function, hydration, and
regimen approach is highlighted to reduce side effects and
desquamation. Skin hydration and desquamation measure-
achieve quicker reponse (See Table 9.1).
ments showed significant improvement. One of the basic goals
of therapy is to relieve dryness, since dry skin will potentiate
the itch-scratch cycle. Second-Line Therapies (or First-Line Therapies for
Moderate-to-Severe Psoriasis)
The role of salicylic acid in the treatment of psoriasis.
Lebwohl M. Int J Dermatol 1999; 38:16–24. Phototherapy A
Salicylic acid 2–10% is an effective keratolytic agent that Acitretin A
allows for penetration of active medications including topical
Cyclosporine A
corticosteroids, tar, or anthralin. Salicylic acid should not be
Biologics
used with calcipotriol as it can lead to product inactivation or
with phototherapy as it blocks UVB from entering the cutane- â•… Adalumimab A
ous surface. â•… Etanercept A
Salicylic acid has a substantial keratolytic effect and is best used â•… Alefacept A
in conjunction with corticosteroids. Application to localized â•… Infliximab A
areas can be done daily, but with more widespread disease, â•… Ustekinumab A
2–3 applications per week is sufficient to prevent systemic Methotrexate A
intoxication.

Efficacy and tolerability of topical tacrolimus ointment for
the treatment of male genital psoriasis. Bissonnette R, Nigen
S, Bolduc C. J Cutan Med Surg 2008; 12(5):230–234.
An open-label study in 12 male patients with genital pso-
riasis showed improvement in PASI with topical tacrolimus
0.1% ointment twice daily for 8 weeks. Mild pruritus or
burning sensation of limited duration was reported. When
treatment options are limited in the genital area, topical tac-
rolimus ointment appears efficacious, safe, and well tolerated
in genital psoriasis.
First-line treatment for moderate-to-severe plaque psoriasis
or second-line treatment for mild psoriasis with inadequate
response to initial therapy includes phototherapy, oral retin-
oids, and the immunosuppressive agents cyclosporine, metho�
trexate, and biologic agents. Again, there is significant data
supporting the efficacy of these therapies, often allowing an ‘A’
rating for psoriasis patients in the general population. Data
supporting the efficacy of treatment in the skin of color popu-
lation, when available, may involve open-label trials or those
with smaller numbers of subjects. In this section our evidence

170

scale reflects the data obtained for the greater population
unless otherwise noted.
Comparison of phototherapy two times and four times
a week with low doses of narrow-band ultraviolet B in
Asian patients with psoriasis. Leenutaphong V, Nimkulrat P,
Sudtim S. Photodermatol Photoimmunol Photomed 2000;
16(5):202–206.
The optimum phototherapy regimen was investigated in
69 Asian patients, phototypes III–IV, with moderate-to-severe
psoriasis. In comparing 2/week and 4/week therapy with low
dose narrow-band therapy, clearance was achieved in the
twice weekly therapy in half the time while minimizing acute
and long-term risk.
Modern modified ‘ultra’ Goeckerman therapy: a PASI assess-
ment of a very effective therapy for psoriasis resistant to
both prebiologic and biologic therapies. Lee E, Koo J. J Der-
matolog Treat. 2005 Apr; 16(2):102–107.
25 psoriasis patients underwent Goeckerman therapy until
near clearance or for a maximum of 3 months. All patients
reached PASI 75 within 12 weeks of treatment with rapid onset
of treatment.
Goeckerman therapy may be prescribed to treat severe or resist-
ant psoriasis. Few hospitals and psoriasis treatment centers in
the United States offer this treatment which involves a series
of oupatient visits using ultraviolet light treatment and applying
a prescription coal tar mixture to the psoriasiatic lesions. The
coal tar mixture usually remains on the skin for several hours.
Goeckerman therapy tends to offer the longest remission time
for moderate to severe psoriasis. The average remission time
for treatment with Goeckerman therapy is 6 to 12 months.
(Fig. 9.4)
Randomized double-blind trial of the treatment of chronic
plaque psoriasis: efficacy of psoralen-UV-A therapy vs nar-
rowband UV-B therapy. Yones SS, Palmer RA, Garibaldinos
TT, Hawk JL. Arch Dermatol 2006; 142(7):836–842.
This was the first double-blinded randomized study in 93
patients of all skin phototypes (49% skin types I-II, 32% skin
types II-IV, 19% skin types V-VI) treated with twice weekly
PUVA or NBUVB at 70% erythema dose showed that patients
with skin types V and VI had a lower rate of clearance (24%
versus 75%) than those with skin types I–IV. PUVA was more
effective in achieving clearance with fewer treatments and
sustained remission, but also had greater side effects, espe-
cially with erythema.
In this study, dosage was adjusted according to visual erythema,
which may have been difficlut to assess in darker skin types,
causing underdosing, and a lowered rate of clearance. PUVA
may cause nausea, requires the use of eye protection, cannot be
used during pregnancy, is contraindicated in patients with
significant hepatic impairment or those on warfarin or pheny-
toin, requires the previous administration of psoralen, and
has the greatest potential to cause skin cancer after 160 to
200 lifetime treatments, which exceeds the risk to NB-UVB
sessions.5,6 (Fig. 9.5)
9â•… Papulosquamous Disordersâ•… •â•… Plaque psoriasis
Figure 9.4:╇ Tar application in a patient receiving Goeckerman regimen. (Courtesy
of John Koo, MD and Tina Bhutani, MD; UCSF Psoriasis Center, Department of
Dermatology, UCSF Medical Center.)
A randomized comparison of acitretin-narrow-band TL-01
phototherapy and acitretin-psoralen plus ultraviolet A for
psoriasis. Ozdemir M, Engin B, Baysal I, Mevlitoǧlu I. Acta
Derm Venereol 2008; 88(6):589–593.
This randomized, prospective, and blinded study in 60
patients with skin types II-IV with moderate to severe pso-
riasis was investigated. Acitretin combined with narrowband
TL-01 was as effective as acitretin-PUVA with all patients
achieving remission following treatment at 3 months.
Acitretin may cause thinning of the stratum corneum, allow-
ing enhanced penetration. Mucocutaneous side effects, such
as dry lips and mouth, were the most common complaints
in both groups.
Acitretin, like other retinoids, probably work by binding RAR
receptors and altering the transcription of genes coding for
proteins causing psoriasis. For fertile females, isotretinoin
phototherapy may be an alternative to acitretin, but also
requires close monitoring of blood tests and contraception to
prevent pregnancy. In addition, baseline and regular monitor-
ing of liver function and lipids should be performed.
Adalimumab for severe psoriasis and psoriatic arthritis: an
open-label study in 30 patients previously treated with
other biologics. Papoutsaki M, Chimenti MS, Costanzo A,
Talamonti M, Zangrilli A, Giunta A. J Am Acad Dermatol 2007;
57(2):269–275.
30 patients with resistant plaque psoriasis PASI 10 or higher
received monotherapy with adalimumab 40 mg subcutane-
ously once weekly. At week 12, 87% achieved a PASI score of
75. The mean PASI score at week 24 corresponded to an 88.5%
improvement from baseline. Adalimumab had a rapid onset of
action in patients with refractory psoriasis.
Adalimumab is a fully human recombinant antibody targeted
against TNF-α. Routine screening for tuberculosis for patients
treated with adalimumab, infliximab, and etanercept is advised,
especially given the high prevalence of tuberculosis in several
countries.
171
 Part 1 Medical Dermatology

A B

C D

Figure 9.5:╇ (A, B) Filipino male with generalized psoriatic plaques before PUVA therapy. (C, D) Dramatic improvement after PUVA therapy. (Courtesy of John Koo, MD and
Tina Bhutani, MD, UCSF Psoriasis Center, Department of Dermatology, UCSF Medical Center.)

Efficacy and safety of cyclosporine versus methotrexate in
severe psoriasis: a study from north India. Sandhu K, Kaur
I, Kumar B, Saraswat A. J Dermatol 2003; 30(6):458–463.
In comparing the efficacy and safety of daily cyclosporine
3–4╯mg/kg/day with weekly methotrexate 0.5╯mg/kg in 30
Indian patients with severe psoriasis, median time to achieve
PASI 75 was 5.3 weeks with cyclosporine compared to 6.8
weeks with methotrexate. Patients on methotrexate were found
to have more rapid and complete clearance than those on
cyclosporine. Side effects in both the treatment groups were
minor, transient, and manageable. At doses with comparable
safety profiles, methotrexate resulted in more rapid and
cost effective clearance of patients with severe psoriasis.
Cyclosporine can provide an effective and safe alternative.
Methotrexate blocks DNA synthesis in rapidly proliferating
epidermal cells, inhibits T and B lymphocytes, and disrupts
cytokine secretion. Patients on methotrexate should have base-
line blood, platelet counts, liver function tests, and potentially
Hepatitis B and C testing. Baseline liver biopsies are not recom-
mended in those without liver disease. Periodic liver biopsies
should be performed to monitor for hepatic fibrosis. Patients
with risk factors of liver disease including fatty liver, obesity,
and diabetes should not receive methotrexate.
Cyclosporine is an immunosuppressive drug that acts to
prevent T-cell activation and the transcription of interleukin 1
and other cytokines that are important in the pathogenesis of
psoriasis. Ideally, cyclosporine should be used for short courses
of 3–4 months for rapid and excellent disease control. Patients
on cyclosporine should receive baseline and periodic blood and
platelet count, serum chemistries, including blood urea nitro-
gen, creatinine, potassium, magnesium, uric acid, liver func-
tion tests, and lipids as well as blood pressure assessments.
Low-dose etanercept therapy in moderate to severe psoriasis
in Korean patients. Na JI, Kim JH, Park KC, Youn SW. J Der-
matol 2008; 35(8):484–490.
A retrospective analysis of 26 Korean patients with
moderate-to-severe psoriasis received low dose etanercept. The
regimen included twice-weekly injections of 25╯mg etanercept
s.c. for at least 4 weeks, followed by once-weekly injection
when they reached PASI 50. PASI 75 was achieved in 54% of
patients. Patients with initial PASI < 10% showed earlier

172

responses and higher PASI 75 rates. This is the first report on
the effectiveness of low-dose etanercept on Asian patients with
moderate-to-severe psoriasis. It may be a valuable option for
even moderate psoriasis patients not responsive to conven-
tional treatment.
Tuberculosis screening is advised prior to initiation of therapy.
An open-label study of alefacept plus ultraviolet B light as
combination therapy for chronic plaque psoriasis. Ortonne
JP, Khemis A, Koo JY. J Eur Acad Dermatol Venereol 2005;
19(5):556–563.
In this open-label, parallel-group study conducted in
France and the United States, patients received 12-weekly
injections of alefacept 15╯ mg intramuscularly and were fol-
lowed over 12 weeks in 60 subjects. In addition, patients
were randomized to receive narrowband, broadband, or no
combination therapy. Combination therapy resulted in more
rapid and higher overall response. 75–100% of patients in
the combination group sustained a PASI 50 (in those that
achieved this endpoint) 2 weeks following completion of
therapy.
Alefacept, a selective biological recombinant protein, binds
CD2 on T cells to block T-cell activation and proliferation and
interacts with FcgammaRIII receptors on accessory cells to
produce selective T-cell apoptosis. Baseline and total CD4
counts must be followed at least weekly. Monotherapy tends to
be slow, usually requiring 2 courses of treatment, with maximal
effect, several weeks following the course. Long-term remission
is the primary advantage in those patients who are able to
achieve PASI 75, which is usually a minority.
Infliximab for severe, treatment-resistant psoriasis: a pro-
spective, open-label study. Smith CH, Jackson K, Bashir SJ,
Perez A, Chew AL, Powell AM. Br J Dermatol 2006; 155(1):
160–169.
In this open-label study of 23 patients who had failed at
least two systemic therapies, 77% achieved a PASI 75 at week
10, suggesting that infliximab is a rapidly effective treatment
for patients with severe, treatment-resistant disease. However,
25% of patients had to discontinue therapy due to the devel-
opment of serious adverse effects including infection, infusion
reaction, thrombcytopenia, and malignancy.
Infliximab, is a mouse-human chimeric monoclonal antibody
directed against tumour necrosis factor-α. Infliximab infusion
requires administration over 2 hours and frequent monitoring.
Long-term follow-up, and further controlled comparative studies
will be required to fully evaluate the risks associated with
infliximab.
Ustekinumab: an evidence-based review of its effectiveness
in the treatment of psoriasis. Krulig E, Gordon KB. Core Evid
2010 Jul 27;5:11–22.
This was an evidence based review to assess the emerging
evidence for ustekinumab in the management of recalcitrant
moderate to severe psoriasis. Phase III trials (PHOENIX 1 and
2) demonstrated a statistically significant difference between
PASI 75 responses achieved by patients receiving ustekinumab,
given as a 45 mg or 90 mg subcutaneous injection every 12
9â•… Papulosquamous Disordersâ•… •â•… Plaque psoriasis
weeks, than their placebo counterparts. Phase III trials dem-
onstrated ustekinumab’s sustained long-term clinical responses
up to 76 weeks of treatment.
Ustekinumab is a fully human monoclonal antibody binding
IL-12 and IL-23, thus targeting both the Th1 and Th17 arms
of immunity. Ustekinumab was approved by the FDA for its use
in the United States in September 2009 and has been approved
in Canada and Europe. It is administered as a subcutaneous
injection, has rapid onset of action, and easier dosing profiles
which makes this agent a potentially valuable alternative for
psoriatic patients.
Third-Line Therapies
Combination therapy
Immunosuppressives
Hydroxyurea
5-Fluorouracil (topical or intralesional)
Mycophenolate mofetil
Thioguanine
Azathioprine
Lasers (excimer laser, pulse dye laser)
Photodynamic therapy
Other
Dead Sea
Balneotherapy
Colchicine
Fumaric acid ester
Alternative and Complementary Therapies (see Chapter 18)
Commonly encountered pitfalls
Ethnic variations in response to psoriasis treatment have been
reported and should be carefully considered when selecting a
treatment. A Turkish and Japanese study detected vitamin D
receptor gene polymorphism in these populations. This poly-
morphism may play a role in partial resistance to calcipotriol
therapy in some individuals of Turkish or Japanese decent.7,8
Obesity is a special consideration for African-American and
Hispanic populations and it may have a negative effect on
treatment outcome. Body mass index (BMI) and weight loss
have been found to affect the early clinical response to
systemic treatment. One study found obese patients with
moderate-to-severe psoriasis increased their response to low-
dose cyclosporine if a calorie-controlled diet was included
in the treatment regimen.9 Consequently, patients with a
lowered BMI may respond better to treatments that are
weight dependent.
Ethnic patients are at higher risk of developing post-
inflammatory hyperpigmentation and will show less ery-
thematous plaques. Patients may become more distraught
with hyperpigmentation with their perception that this is a
marker of scarring or worsening of their condition. Ethnic
patients should be advised to use sunscreen on areas of PIH
173
 Part 1 Medical Dermatology
to hasten resolution and should be counseled that the pigmen-
tation is temporary and will resolve with time.
Special management & counseling considerations
Variations in effective dosage of medication or energy
levels have been reported in certain ethnic groups. One study
evaluated a split study on 100% minimal erythema dose
(MED) versus 70% MED (suberythemogenic dose) and noted
no difference in PASI between both sides. Therefore, they rec-
ommended a reduction in the dose regimen of NBUVB and
consequently the cumulative UVB dose by using a subery-
themogenic dosing schedule in both fair-skinned and dark-
skinned population10. One advantage of treating ethnic skin
with ultraviolet radiation is their much lower risk of develop-
ing carcinomas when compared to fair skinned individuals.
In another study as noted above, low dose etanercept was
found to be effective in Asian patients, thus lowering medical
cost compared to the standard regimen in White patients.
Patients received twice-weekly injections of 25╯mg etanercept
s.c. for at least 4 weeks, followed by once-weekly injection
when they achieved a 50% reduction of the psoriasis area
severity index (PASI 50).11 This improvement with low doses
may be attributed to a generally lowered BMI in Asians com-
pared to other ethnic groups.
A study from Singapore reported that eye complications
were commonly found in Asian patients with psoriasis.12
These complications, which included glaucomatous optic
neuropathy and cataracts, were unrelated to treatment.
Although no control population was used in the study, the
data suggest that eye symptoms should be elicited during
history-taking.
A Japanese survey showed that the most common systemic
treatments used by this population were herbal medicines.
Retinoids were the second most common treatment. This
study highlights the importance of eliciting all drugs used by
patients when taking a thorough history. Additionally, knowl-
edge of herbal ingredients or access to an appropriate reference
is likewise important (see Chapter 18).13
Pediatric perspectives:
Psoriasis
Candrice R Heath
Quite often, medications are utilized for pediatric psoriasis
patients that are scientifically proven in adults but have not
been evaluated in children. You will find that some treatments
that have an ‘A’ evidence level in adults will have a ‘B’ or ‘C’
level in children because randomized, double-blind trials were
not performed. In this section, we report only evidence based
on trials that involved pediatric populations.
174
References
1. Gelfand JM, Stern RS, Nijsten T, Feldman SR, Thomas J, Kist J, et al.
The prevalence of psoriasis in African-Americans: results from a
population-based study. JAAD 2005; 52(1):23–26.
2. Suite M. The epidemiology of psoriasis in a dermatology clinic in a
general hospital in Port-of-Spain, Trinidad and Tobago, West Indies.
West Indian Med J 2006; 55(6):399–402.
3. Kumar B, Jain R, Sandhu K, Kaur I, Handa S. Epidemiology of child-
hood psoriasis: a study of 419 patients from northern India. Int J
Dermatol 2004; 43(9):654–658.
4. Youn JI, Park BS, Park SB, Kim SD, Suh DH. Characterization of early
and late onset psoriasis in the Korean population. J Dermatol 1999;
26(10):647–652.
5. British Photodermatology Group. British Photodermatology Group
guidelines for PUVA. Br J Dermatol. 1994; 130:246–255.
6. Jayaprakasam A, Darvay A, Osborne G, McGibbon D. Comparison of
assessments of severity and quality of life in cutaneous disease. Clin
Exp Dermatol 2002; 27:306–308.
7. Saeki H, Asano N, Tsunemi Y, Takekoshi T, Kishimoto M, Mitsui H,
et al. Polymorphisms of vitamin D receptor gene in Japanese patients
with psoriasis vulgaris. J Dermatol Sci 2002; 30(2):167–171.
8. Dayangac-Erden D, Karaduman A, Erdem-Yurter H. Polymorphisms of
vitamin D receptor gene in Turkish familial psoriasis patients. Arch
Dermatol Res 2007; 299(10):487–491.
9. Gisondi P, Del Giglio M, Di Francesco V. Weight loss improves the
response of obese patients with moderate-to-severe chronic plaque
psoriasis to low-dose cyclosporine therapy: a randomized, controlled,
investigator-blinded clinical trial. Am J Clin Nutr 2008; 88(5):
1242–1247.
10. Youssef RM, Mahgoub D, Mashaly HM, Zamboni M, Girolomoni G.
Different narrowband UVB dosage regimens in dark skinned psoriat-
ics: a preliminary study. Photodermatol Photoimmunol Photomed
2008; 24(5):256–259.
11. Na JI, Kim JH, Park KC, Youn SW. Low-dose etanercept therapy in
moderate to severe psoriasis in Korean. J Dermatol 2008; 35(8):
484–490.
12. Chandran NS, Greaves M, Gao F, Lim L, Cheng BC. Psoriasis and the
eye: prevalence of eye disease in Singaporean Asian patients with
psoriasis. J Dermatol 2007; 34(12):805–810.
13. Kawada A, Tezuka T, Nakamizo Y, Kimura H, Nakagawa H,
Ohkido M, et al; Japanese Society for Psoriasis Research. A survey of
psoriasis patie patients in Japan from 1982 to 2001. J Dermatol Sci
2003; 31(1):59–64.
First-Line Therapies
Topical corticosteroids C
Vitamin D analogs A
Anthralin (dithranol) B
Tar preparations C
Efficacy and safety of treatments for childhood psoriasis: a
systematic literature review. de Jager ME, de Jong EM, van de
Kerkhof PC, Seyger MM. J Am Acad Dermatol 2010; 62:1013–
1030 [Epub 2009 Nov 8].
A systematic review of 64 studies on pediatric psoriasis
treatment, safety and efficacy was performed. Though most
 9â•… Papulosquamous Disordersâ•… •â•… Pediatric perspectives: Psoriasis
conclusions are not based on the results of randomized,
double-blind, placebo-controlled studies, many topical and
systemic psoriasis treatments given in pediatric psoriasis are
efficacious with only mild short-term effects. First-line
treatments include calcipotriene with or without corticoster-
oids then dithranol. The systemic treatment of choice is
methotrexate.
A comprehensive systematic review of all pediatric psoriasis
treatments.
Halobetasol propionate cream by day and halobetasol pro-
pionate ointment at night for the treatment of pediatric
patients with chronic, localized plaque psoriasis and atopic
dermatitis. Herz G, Blum G, Yawalkar S. J Am Acad Dermatol
1991; 25:1166–1169.
In this multicenter, open-label prospective clinical trial of
11 subjects (aged 5–15 years), 72.7% of psoriasis patients’
lesions healed and 18.2% had moderate improvement after 2
weeks of applying halobetasol propionate cream by day and
halobetasol propionate ointment at night.
Clobetasol propionate emulsion formulation foam 0.05%:
review of phase II open label and phase III randomized
controlled trials in steroid responsive dermatoses in adults
and adolescents. Kimball AB, Gold MH, Zib B, Davis MW. J
Am Acad Dermatol 2008; 59:448–454.
In this review of phase II and phase III trials for clobetasol
propionate emulsion, adults and adolescents with atopic der-
matitis and psoriasis were examined. During the second phase
III multicenter randomized double-blind study conducted to
assess safety and efficacy of clobetasol EF foam 0.05% versus
vehicle foam versus study clobetasol ointment, subjects 12
years of age and older with mild to moderate plaque psoriasis
were examined. The treatments were applied twice daily for
2 weeks. A subgroup of subjects 12 years old to under 18
years old, using either clobetasol EF foam or vehicle foam,
were shown to have good response in the treatment group.
This clobetasol EF foam group contained 25% (2 of 8)
who obtained treatment success (minimal to clear erythema,
induration and lesion thickness) by week 2 compared to 0%
(0 of 1) for the vehicle foam group.
Topical calcipotriol in childhood psoriasis. Oranje AP,
Marcoux D, Svensson A, et al. J Am Acad Dermatol 1997; 36(2
Pt 1):203–208.
This prospective 8-week randomized placebo-controlled
trial of 77 children between the ages of 2 and 14 with less
than 30% psoriasis body surface area of involvement demon-
strated a 52% reduction in PASI score in the vitamin D group
and a 37.1% reduction in PASI score in the placebo group,
but these findings were not statistically significant. The only
statistically significant findings in the treatment group were
reduced redness, scaliness and improved physician overall
assessment.
Topical calcipotriol in childhood psoriasis. Patrizi A, Neri I,
Rizzoli L, Varotti C. Acta Derm Venereol 1999; 79:477.
20 pediatric subjects aged 2–13 years were included in this
prospective, double-blind parallel group study. After 8 weeks
of treatment 30% demonstrated > 75% improvement whereas
45% experienced 50–70% improvement.
Topical application of 1,25-dihydroxyvitamin D3 (calci-
triol) is an effective and reliable therapy to cure skin lesions
in psoriatic children. Saggese G, Federico G, Battini R. Eur J
Pediatr 1993; 152:389–392.
10 subjects (5–17 years) in a randomized, double-blind
clinical trial applied petrolatum to a control lesion and calci-
triol to another, both under occlusion once per day for 4
weeks. The calcitriol-treated site cleared in all subjects after
4-week treatment with only residual mild erythema.
Pilot study of topical calcitriol (1,25-dihydroxyvitamin D3)
for treating psoriasis in children. Perez A, Chen TC, Turner
A, Holick MF. Arch Dermatol 1995; 131:961–962.
Four patients were treated with petrolatum jelly or calcitriol
in petrolatum for 8 weeks during this double-blind intra�
patient trial. The placebo-treated lesions had no statistically
significant improvement. The calcitriol-treated areas had a
decrease in the mean global severity score as well as decreased
scaling (62.5% ± 23.9%), erythema (54.1% ± 4.1%) and
plaque thickness (62.5% ± 12.5%).
Efficacy of short-contact therapy with dithranol in child-
hood psoriasis. Zvulunov A, Anisfeld A, Metzker A. Int J Der-
matol 1994; 33:808–810.
A retrospectively reviewed open-label trial of 58 children,
ages 2–15 years who applied dithranol daily for 30 minutes
to psoriatic plaques. 81% of the subjects achieved remission
(no scale or erythema) with a mean of 2 months and remis-
sion lasted a median of 4 months; 20% of subjects experienced
mild adverse effects. Short-contact dithranol is efficacious and
well tolerated.
Genotoxic hazard and cellular stress in pediatric patients
treated for psoriasis with the Goeckerman regimen. Borska
L, Andrys C, Krejsek J, et al. Pediatr Dermatol 2009; 26(1):
23–27.
The Goeckerman regimen (crude coal tar and UV irradia-
tion) was highly effective in pediatric psoriasis patients achiev-
ing significant decreases in PASI scores. An increased genotoxic
effect of the Goeckerman regimen was also demonstrated by
chromosomal aberrations in peripheral blood lymphocytes
and release of heat shock protein.
Tar has been used for years as an adjunctive therapy in pediatric
psoriasis as 1–10% crude coal tar or 5–10% liquor carbonis
detergens. It is often found in over-the-counter products for
psoriasis and may be compounded with topical steroids or sali-
cylic acid for overnight treatments. However, combining tar and
UV is considered controversial by some physicians.
Second-Line Therapies
Phototherapy (UVB) C
Tazarotene gel (nail psoriasis) E
Tacrolimus C
175
 Part 1 Medical Dermatology
Narrow-band UV-B phototherapy in childhood psoriasis.
Jain VK, Aggarwal K, Jain K, Bansal A. Int J Dermatol 2007;
46:320–322.
An open-label trial of 20 patients, aged 6–14 years using
narrow-band UVB for 12 weeks. PASI 90 was obtained in 60%
of the patients and 10% had less than 50% improvement. All
of the patients in the study had Fitzpatrick skin type IV.
Narrowband UVB has good results in the treatment of pediatric
guttate and plaque psoriasis with generally only mild side
effects.
Experience with UVB phototherapy in children. Tay YK,
Morelli JG, Weston WL. Pediatr Dermatol 1996; 13:406–409.
10 patients, ages 14 months to 12 years, all achieved clear-
ance after a mean treatment period of 11.9 weeks.
Tacrolimus ointment is effective for psoriasis on the face
and intertriginous areas in pediatric patients. Brune A, Miller
DW, Lin P, Cotrim-Russi D, Paller AS. Pediatr Dermatol 2007;
24(1):76–80.
11 patients aged 6–15 years were followed for 180 days in
this open label clinical trial evaluating safety and efficacy.
Within the first 30 days of treatment, each patient either
cleared or had significant improvement. One patient experi-
enced pruritus.
This product is not FDA approved for children under the age
of 2 years.
Third-Line Therapies
Systemic treatments (recalcitrant severe psoriasis only)
â•… Methotrexate C treatment for children and adolescents with plaque psoria-
â•… Cyclosporine D sis. Paller AS, Siegfried EC, Langley RG, Gottlieb AB, Pariser
â•… Acitretin/etretinate C D, Landells I, et al. N Engl J Med 2008; 358:241–251.
Biologicals
â•… Etanercept A psoriasis patients (4–17 years old) with weekly subcutaneous
Methotrexate treatment in 13 children with severe plaque
psoriasis. Collin B, Vani A, Ogboli M, Moss C. Clin Exp Der-
matol 2009; 34:295–298.
This series of 13 patients treated with low dose methotrex-
ate included 11 patients with clearance of their psoriasis; 3
patients required two courses and 1 patient required three
courses of treatment. When carefully monitored, methotrexate
can be a safe and effective treatment in pediatric patients with
psoriasis.
Live vaccines should not be given to children taking weekly
methotrexate.
Systemic methotrexate treatment in childhood psoriasis:
further experience in 24 children from India. Kaur I, Dogra
S, De D, Kanwar AJ. Pediatr Dermatol. 2008; 25:184–188.
In this retrospective chart review, 22 of 24 patients had a
greater than 75% decline in PASI score and the remaining 2
patients exhibited a 50–75% reduction in PASI score. PASI 75
was achieved in 91.7% of the patients and PASI 50–75 was
achieved in 8.3%. An average of 5.1 weeks was required for
176
50% reduction in PASI. The treatment courses ranged between
2 and 16 months.
Cyclosporine in childhood psoriasis. Perrett CM, Ilchyshyn
A, Berth-Jones J. J Dermatolog Treat 2003; 14(2):113–118.
Three children (7 and 11 years of age) with severe psoriasis
were treated with cyclosporine for 6 weeks to 4 months.
Cyclosporine was deemed effective and well tolerated in 2 of
the 3 children; 1 developed nausea and diarrhea. Impaired
renal function or hypertension were not observed.
Live vaccines should not be given to children taking cyclosporine.
There is also a concern for development of leukemia, lymphoma
and skin cancers.
Etretinate in severe psoriasis of children. Rosinska D, Wolska
H, Jablonska S, Konca I. Pediatr Dermatol 1988; 5:266–272.
A retrospective review of 5 patients with generalized pustu-
lar psoriasis and 5 patients with erythrodermic psoriasis
treated with etretinate. The treatment course varied from 3
weeks to greater than 12 months. Complete clearance was
achieved in the pustular psoriasis group and 2 of the 5 eryth-
rodermic patients. In the remaining 3 erythrodermic psoriasis
patients, improvement but not complete clearance was noted.
Etretinate therapy for generalized pustular psoriasis in
children. Shelnitz LS, Esterly NB. Arch Dermatol 1987; 123:
230–233.
Two 19-month-olds with recalcitrant pustular psoriasis
were treated with etretinate intermittently for 3.5 years; both
patients improved dramatically without altered growth or
development.
Etanercept Pediatric Psoriasis Study Group. Etanercept
48-week randomized double-blind trial of 211 pediatric
etanercept injections for 12 weeks followed by open-label use
for 24 weeks. At week 12, 57% of patients receiving etanercept
achieved PASI 75, as compared with 11% of those receiving
placebo. At 12 weeks, PASI 90 was achieved by 27% on etaner-
cept and 7% on placebo. After 24 weeks of open-label etaner-
cept (at week 36), rates of PASI 75 were 68% and 65% for
patients initially assigned to etanercept and placebo, respec-
tively. From weeks 36 to 48, 29 of the 69 patients randomized
to a withdrawal period lost their initial response. Children and
adolescents with moderate-to-severe plaque psoriasis signifi-
cantly reduced the severity of their psoriasis while using
etanercept.
Successful treatment of pediatric psoriasis with infliximab.
Menter MA, Cush JM. Pediatr Dermatol 2004; 21(1):87–88.
Case report detailing treatment of a 13-year-old patient
with infliximab, who failed topical treatments, phototherapy
and methotrexate. Treatments began at 200 mg (3.3 mg/kg) at
weeks 0, 2, and 6, and then every 8 weeks thereafter. The
patient’s trunk and limb plaques cleared after six infusions.
The patient also experienced significant improvement in pal-
moplantar psoriatic disease.
 9â•… Papulosquamous Disordersâ•… •â•… Seborrheic dermatitis

Seborrheic dermatitis
Seborrheic dermatitis is a chronic dermatitis that occurs in
sebum-rich areas of the scalp, forehead, eyebrows, nasolabial
folds, beard area, central chest, or flexural areas. This disorder
is linked to an abnormal immunologic response to the
lipophilic fungus Malassezia furfur, which can behave like an
opportunistic pathogen. The condition occurs in all races and
all ages, though it is more common in males and the elderly.
Its prevalence is estimated at about 5%. The infantile form
occurs during the first 3 months of life and the adult form
appears in the fourth to sixth decade.
Commonly aggravated during periods of stress, humidity,
seasonal changes, and trauma, skin lesions of seborrheic der-
matitis manifest as greasy scale overlying red, inflamed patches A
of skin. Scalp appearance varies from mild, patchy scaling to
widespread, thick, adherent crusts. Disseminated lesions can
be seen on the face, retroauricaular folds, neck, trunk, and
proximal extremities.
Unique features of seborrheic dermatitis may occur in
darker skin tones. These include hypopigmentation without
the classic erythema and scaling seen in seborrheic dermatitis.
Annular seborrheic dermatitis, also called petaloid seborrheic
dermatitis (or seborrhea petaloides), which presents with
semi-circular lesions may be frequently observed in patients
with darker skin tones (Fig. 9.6).1
Infantile seborrheic dermatitis begins one week after birth
and may persist for several months as mild greasy scales adher-
ent to the vertex and anterior fontanelle, also know as cradle
cap. Infantile seborrheic dermatitis can have an appearance
similar to atopic dermatitis, irritant diaper dermatitis, candi-
diasis, psoriasis, and less common genodermatoses such as B
Langerhans cell histiocytosis, Wiscott–Aldrich syndrome, and
Leiner’s disease. Adult seborrheic dermatitis can mimic several Figure 9.6:╇ (A) Note hypopigmented scaley patches along the nasolabial folds and
entities including psoriasis, atopic dermatitis, rosacea, lupus, the hair line in an African American male. (Courtesy of Susan Taylor, MD).
and pityriasis rosea. and (B) and in an Indian female. (Courtesy of Dave Adams MD; Department of
Seborrheic dermatitis severity varies from mild dandruff to Dermatology, Penn State Milton S. Hershey Medical Center).
exfoliative erythroderma. Erythroderma occurs more often in
association with AIDS, congestive heart failure, Parkinson’s
disease, and immunosuppression in premature infants. Topical
antifungal agents and steroids are the mainstay of therapy.
However, chronic use of corticosteroids may result in skin ketoconazole or fluconazole improves severe or unresponsive
atrophy, increased intraocular pressure, or further hypopig- seborrheic dermatitis. Finally, it is important to note that this
mentation. Care should be taken with long-term use of corti- condition can be a cutaneous marker for HIV infection,
costeroids and non-steroid based therapies should be selected especially if severe, explosive, and treatment resistant disease
for chronic use. These include calcineurin inhibitors (which exists.
can have immunomodulating effects), sulfur (which has anti-
fungal, antibacterial, and keratolytic effects), or sulfonamides.
Seborrheic dermatitis of the scalp responds well to frequent
Facial seborrheic dermatitis
shampooing with salicylic acid, tar, selenium, sulfur, or zinc
based shampoos used in an alternating schedule. Selenium
sulfide, ketoconazole, and ciclopirox shampoos may help in First-Line Therapies
reducing Malassezia yeast scalp reservoirs. However, in skin of
color patients who have tightly coiled hair which tends to be Topical ketoconazole A
inherently fragile, daily or even every other day shampooing Topical corticosteroid A
is not an appropriate therapeutic recommendation. Systemic

177
 Part 1 Medical Dermatology

There are several controlled trials that demonstrate facial
involvement responds well to antifungal and corticosteroid
therapies.
A novel foam formulation of ketoconazole 2% for the treat-
ment of seborrheic dermatitis on multiple body regions.
Elewski BE, Abramovits W, Kempers S, Schlessinger J, Rosen T,
Gupta AK, et al. J Drugs Dermatol 2007; 6(10):1001–1008.
This study is the largest randomized and double blind trial
investigating ketoconazole. A topical foam formulation of
ketoconazole 2% was studied for use on the scalp, body, and
face. 1162 subjects with mild to severe seborrheic dermatitis
were randomized to receive ketoconazole foam, vehicle foam,
ketoconazole cream, or vehicle cream twice daily for 4 weeks.
Ketoconazole foam was shown to be equivalent to ketocona-
zole cream.
The foam formulation allows for a better cosmetic acceptance
and penetration into hair bearing areas.
Comparative study of 2% ketoconazole cream and 1%
hydrocortisone cream in the treatment of infantile sebor-
rheic dermatitis. Wannanukul S, Chiabunkana J. J Med Assoc
Thai 2004; 87(Suppl 2):S68–S71.
This Thai study demonstrated response to 2% ketoconazole
cream compared with 1% hydrocortisone cream in 48 patients
with infantile seborrheic dermatitis. There were no statistically
significant differences at 2-3 days of treatment; by 1 week both
creams had similar improvement; by 2 weeks, all lesions had
cleared. Ketoconazole was found to be a safer option, avoiding
the side effects of topical corticosteroid, in long-term use and
on large surface areas of infantile seborrheic dermatitis.
Double-blind studies in adults with seborrheic dermatitis dem-
onstrate similar clinical results with excellent responses to both
ketoconazole or hydrocortisone.
lithium gluconate ointment 8% or placebo b.i.d. for 8 weeks
with complete remission of erythema and scaling. Lithium
gluconate ointment induced clinical remission in 29.1% of
patients at 8 weeks. It is hypothesized that lithium salts may
act as an anti-inflammatory agent.
Randomized, open-labeled, non-inferiority study between
ciclopiroxolamine 1% cream and ketoconazole 2% foaming
gel in mild to moderate facial seborrheic dermatitis.
Chosidow O, Maurette C, Dupuy P. Dermatology 2003;
206(3):233–240.
This randomized clinical study compared ciclopirox-
olamine 1% cream and ketoconazole 2% foaming gel in 282
patients with mild to moderate facial seborrheic dermatitis.
Ciclopiroxolamine is antiinflammatory with antifungal activ-
ity against M furfur. Patients were randomly allocated to apply
the medication during an initial phase followed by a mainte-
nance protocol. Treatment response to ciclopiroxolamine
cream b.i.d., followed by a daily maintenance regimen was
greater than ketoconazole foaming gel twice a week followed
by once-weekly maintenance. However, these results are diffi-
cult to interpret because of the much lower frequency of appli-
cation for ketoconazole than for ciclopiroxolamine.
An open pilot study using tacrolimus ointment in the
treatment of seborrheic dermatitis. Meshkinpour A, Sun J,
Weinstein G. J Am Acad Dermatol 2003; 49(1):145–147.
In a single-center, open-label study, 18 consecutive patients
with seborrheic dermatitis were treated with 0.1% tacrolimus
ointment for a total of 28 days or until complete clearance
occurred. All patients showed 70–100% clearance. This pilot
study suggests that topical tacrolimus is efficacious in the
short-term treatment of seborrheic dermatitis. Calcineurin
inhibitors prevent T-cell activation by down-regulating the
activity of type 1 and type 2 T-helper cells.

Pilot trial of 1% pimecrolimus cream in the treatment of

Second-Line Therapies
Lithium succinate/lithium gluconate
Topical ciclopiroxolamine
Calcineurin inhibitors
â•… Topical tacrolimus
â•… Topical pimecrolimus
Topical sulfur
Several well controlled studies have shown the utility of
alternative non-steroid based treatments including lithium,
ciclopirox, calcineurin inhibitors, and sulfur.
Lithium gluconate in the treatment of seborrheic dermatitis:
a multicenter, randomized, double-blind study versus
placebo. Dreno B, Moyse D. Eur J Dermatol 2002; 12(6):
549–552.
129 patients with moderate to severe facial seborrheic der-
matitis for at least two months were randomized to either
seborrheic dermatitis in African-American adults with asso-
ciated hypopigmentation. High WA, Pandya AG. J Am Acad
A Dermatol 2006; 54(6): 1083–1088.
A This pilot trial is the only study to examine the improve-
C ment of hypopigmentation associated with seborrheic der-
matitis in African-American adults. Five African-American
C
adults with seborrheic dermatitis used pimecrolimus b.i.d.
A for 16 weeks. All participants noted a marked decrease in
D the severity of their condition in addition to improvement
in hypopigmentation which was objectively measured
by a mexameter within the initial 2 weeks of therapy.
Topical pimecrolimus may be an excellent alternative
therapeutic modality for treating seborrheic dermatitis in
African-Americans, particularly in those with associated
hypopigmentation.
Pimecrolimus, like tacrolimus, can be useful for long-term
therapy as a steroid sparing agent. However, one concern with
the topical immuno�modulators includes the possible suppression
of skin cancer surveillance.2 This may be of particular concern
in area of high incidental sun exposure, such as the face, ears,
and neck–areas often involved with seborrheic dermatitis.

178
 9â•… Papulosquamous Disordersâ•… •â•… Seborrheic dermatitis
Results of a randomized, double-blind, vehicle-controlled
efficacy trial of pimecrolimus cream 1% for the treatment
of moderate to severe facial seborrheic dermatitis. Warshaw
EM, Wohlhuter RJ, Liu A, Zeller SA, Wenner RA, Bowers S,
et al. J Am Acad Dermatol 2007; 57(2):257–264.
This double-blind, vehicle-controlled, 4-week trial rand-
omized 96 mostly elderly men (96% Caucasian) with
moderate-to-severe sebor�rheic dermatitis (with mostly glabel-
lar involvement) to pimecrolimus b.i.d. or vehicle. The mean
change from baseline to 4 weeks in the total target-area score
with twice daily 1% pimecrolimus was significantly greater
than with placebo in a per-protocol analysis but not in an
intention-to-treat analysis.
High response rates have been reported in many trials with the
use of a placebo alone. However, it remains uncertain whether
these rates are due to a placebo response or due to an emollient
effect of the placebo.
The use of sulfur in dermatology. Gupta AK, Nicol K. J Drugs
Dermatol 2004; 3(4):427–431.
Sulfur was used in a variety of dermatological disorders
such as acne vulgaris, rosacea, seborrheic dermatitis, dandruff,
pityriasis versicolor, scabies, and warts. Sulfur with sodium
sulfacetamide lotion is able to effectively ameliorate seborrhea
and acne lesions without excessive erythema or peeling. Sulfur
is thought to possess keratolytic activity, mild antifungal
(against M. furfur), and antibacterial activity (against P. acnes).
When applied to skin, sulfur is thought to interact with
cysteine, present in the stratum corneum, to form hydrogen
sulfide. Hydrogen sulfide can break down keratin, thus dem-
onstrating sulfur’s keratolytic activity, especially in the pres-
ence of salicylic acid.
Third-Line Therapies
Oral itraconazole
Oral ketoconazole
Oral terbenafine
Phototherapy
Scalp seborrheic dermatitis
First-Line Therapies
Ketoconazole shampoo A to be a better topical formulation compared with previous
Ciclopirox shampoo A therapies used by the patients. Its clinical effect is also main-
Zinc pyrithione shampoo B tained after a 2-month wash-out period.
Topical corticosteroid B
Several well controlled studies have shown the effectiveness
of antifungal, corticosteroid, and keratolytic based therapies
in the treatment of scalp seborrheic dermatitis.
A multicenter randomized trial of ketoconazole 2% and
zinc pyrithione 1% shampoos in severe dandruff and sebor-
rheic dermatitis. Piérard-Franchimont C, Goffin V, Decroix J,
Piérard GE. Skin Pharmacol Appl Skin Physiol 2002;
15(6):434–441.
This open, randomized, parallel-group 4-week trial of 331
subjects with severe dandruff or seborrheic dermatitis of the
scalp showed beneficial effects for both medicated shampoos.
However, zinc pyrithione was less effective than 2% ketocona-
zole when used as a twice-weekly shampoo in reducing the
severity of dandruff at 4 weeks (67% improvement in the
severity score vs. 73% improvement, P<0.02).
Clinical efficacies of shampoos containing ciclopiroxo�
lamine (1.5%) and ketoconazole (2.0%) in the treatment of
seborrheic dermatitis. Ratnavel RC, Squire RA, Boorman GC.
J Dermatolog Treat 2007; 18(2):88–96.
A randomized, double-blind, placebo controlled trial of
350 patients with scalp seborrheic dermatitis showed both
shampoos applied over 4 weeks were superior to placebo.
Ciclopirox shampoo was superior to placebo clinically and as
perceived by patients and was at least as effective as ketocona-
zole shampoo.
A randomized, single-blind, single-centre clinical trial to
evaluate comparative clinical efficacy of shampoos contain-
ing ciclopiroxolamine (1.5%) and salicylic acid (3%), or
ketoconazole (2%) for the treatment of dandruff/seborrheic
dermatitis. Squire RA, Goode K. J Dermatolog Treat 2002;
13(2):51–60.
Since salicylic acid has keratolytic properties and aids in
removing scales, a shampoo containing 1.5% ciclopiroxo�
lamine and 3% salicylic acid (CPO/SA) was compared with
ketoconazole shampoo used 3 times weekly for 4 weeks in a
study involving 70 subjects with seborrheic dermatitis of the
scalp. In the two groups, seborrheic dermatitis improved sig-
nificantly throughout treatment. However, only the subjects
treated with CPO/SA shampoo showed a significant reduction
in itching.
Efficacy of betamethasone valerate 0.1% thermophobic
foam in seborrheic dermatitis of the scalp: an open-label,
multicentre, prospective trial on 180 patients. Milani M,
Antonio Di Molfetta S, Gramazio R, Fiorella C, Frisario C,
Fuzio E, et al. Curr Med Res Opin 2003; 19(4):342–345.
An open-label, prospective, multicenter trial of 180 patients
with moderate to severe scalp seborrheic dermatitis were
treated over 4 weeks with betamethasone valerate 0.1% ther-
mophobic foam. 85% of patients considered the foam vehicle
Second-Line Therapies
Selenium sulfide shampoo A
A randomized, double-blind, placebo-controlled trial of
ketoconazole 2% shampoo versus selenium sulfide 2.5%
179
 Part 1 Medical Dermatology
shampoo in the treatment of moderate to severe dandruff.
Danby FW, Maddin WS, Margesson LJ, Rosenthal D. J Am Acad
Dermatol 1993; 29(6):1008–1012.
This randomized, double-blind, placebo-controlled trial of
246 patients with moderate-to-severe dandruff, 2.5% selenium
sulfide shampoo, 2% ketoconazole shampoo, and placebo
were compared. All shampoos were used twice weekly. Reduc-
tions in the score for dandruff at week 4 were 67% with sele-
nium sulfide, 73% with ketoconazole, and 44% with placebo;
the reductions were significantly larger with both medicated
shampoos than with placebo. Itching and burning sensations
were more common with selenium sulfide shampoo than with
ketoconazole.
Commonly encountered pitfalls
The variant annular seborrheic dermatitis requires differentia-
tion of other similar conditions including sarcoid, secondary
syphilis, tinea capitis, atopic dermatitis with pityriasis alba,
and discoid lupus which can leave areas of hypopigmenta�
tion. Additionally, symptoms in ethnic skin can include
scalp itching and dryness, and in some cases, hair breakage
and loss.
Special management & counseling considerations
Hypopigmented seborrheic dermatitis is commonly observed
in skin of color subjects. In fact, hypopigmentation may be the
presenting complaint for these patients as compared to ery-
thema and scaling for patients with light skin tones. A study
cited above evaluated treatment of this presentation of sebor-
rheic dermatitis and determined improvement with topical
pimecrolimus within the first 2 weeks of 16 weeks of therapy.3
However, a study in Korean patients demonstrated relapse was
180
most commonly observed between 3 and 8 weeks after discon-
tinuation of pimecrolimus for facial seborrheic dermatitis.4
In African-American patients with scalp dermatitis, careful
consideration is needed regarding shampoo recommenda-
tions and hair care. Although shampoos for seborrheic derma-
titis are most effective when used frequently and daily
shampooing is recommended for many patients, these shamp-
pos are very harsh on chemically treated hair or the tightly
coiled hair of women of color. It is more appropriate to recom-
mend use of a medicated shampoo once weekly to parallel
normal grooming patterns in this population. This recom-
mendation may necessitate the use of additional topical
agents. Finally, as hair may be fragile and intrinsically dry, a
recommendation may be made to apply the shampoo directly
to the scalp for 10–15 minutes and rinse out. Next, a condi-
tioning shampoo may be used to shampoo the actual hair.
Thus, increased compliance and improvement in the condi-
tion will be achieved.
References
1. McLaurin CI. Annular facial dermatoses in blacks. Cutis 1983;
32(4):369–370, 384.
2. Ormerod AD. Topical tacrolimus and pimecrolimus and the risk of
cancer: how much cause for concern? Br J Dermatol 2005;
153:701–705.
3. High WA, Pandya AG. Pilot trial of 1% pimecrolimus cream in the
treatment of seborrheic dermatitis in African-American adults with
associated hypopigmentation. J Am Acad Dermatol 2006; 54(6):
1083–1088.
4. Kim BS, Kim SH, Kim MB, Oh CK, Jang HS, Kwon KS. Treatment of
facial seborrheic dermatitis with pimecrolimus cream 1%: an open-
label clinical study in Korean patients. J Korean Med Sci 2007;
22(5):868–872.
 PART 2
Pigmentary Disorders
This page intentionally left blank
Part 2 Pigmentary Disorders

Hyperpigmented
Disorders
David A Rodriguez
10â•…
Acanthosis nigricans . . . . . . . . . . . . . . . . . . . 183 The etiology of AN is unknown. However, if the onset of
lesions is rapid and the lesions are generalized, then malig-
Benign melanonychia . . . . . . . . . . . . . . . . . . . 185
nancy must be suspected and an evaluation undertaken.4
Confluent and reticulated papillomatosis of AN can be seen in a wide range of individuals, from those
Gougerot and Carteaud (CRPGC) . . . . . . . . . . . . . 187 completely healthy as a normal variant to those with underly-
Drug-induced pigmentation . . . . . . . . . . . . . . . . 189 ing medical conditions, although it is most often observed in
darker pigmented individuals. One source reports the inci-
Erythema dyschromicum perstans . . . . . . . . . . . . 191 dence of AN as 13%, 6% and 1% in African-Americans, Latinos
Exogenous ochronosis . . . . . . . . . . . . . . . . . . 192 and Caucasians respectively.5
Gingival hyperpigmentation . . . . . . . . . . . . . . . . 194 AN is also believed to be a marker of endocrine distur-
bances, namely increased insulin secretion and insulin resist-
Melasma . . . . . . . . . . . . . . . . . . . . . . . . . . 195 ance.6 Therefore the most common type of AN is associated
Mongolian spots . . . . . . . . . . . . . . . . . . . . . . 199 with conditions with an elevated insulin blood level, such as
Nevus of Ota . . . . . . . . . . . . . . . . . . . . . . . . 201 in diabetes and obesity. There are many other possible causes
of AN, including:
Pigmentary demarcation lines . . . . . . . . . . . . . . 203
• Hypothyroidism
Post-inflammatory hyperpigmentation (PIH) . . . . . . . 204
• Addison’s Disease
Solar lentigines . . . . . . . . . . . . . . . . . . . . . . 207 • Pituitary disorders.
Pediatric perspectives: Transient neonatal pustular Medications associated with AN,
melanosis . . . . . . . . . . . . . . . . . . . . . . . . . 209
• Insulin6
• Glucocorticoids
• Growth Hormone
• Diethylstilbestrol
• Vitamin B3 (Niacin)
• Methyltestosterone

Acanthosis nigricans
Classical acanthosis nigricans (AN) is characterized by sym-
metrical areas of verrucous, brown to black, velvety plaques,
typically located on the posterior and lateral neck and axillae.1,2
Flexor surfaces, of the extremities, inframammary folds and
perianal area may also be affected.3 Interestingly, patients often
refer to the appearance of the lesions as a ‘dirty area’, which
they are known to vigorously scrub (Fig. 10.1).
• Oral contraceptives.7
The mainstay of AN treatment is management of the under-
lying disease. If AN occurs as a result of obesity, weight loss is
required.4,6 If malignancy is the underlying cause, successful
surgery or chemotherapy will ameliorate AN.
Topical treatments such as salicylic acid or tretinoin may be
helpful in some individuals. Lasers or dermabrasion have also
been used successfully, especially with veruccous protrusions.
If AN is attributed to an offending agent, discontinuation of
the drug should lead to resolution.

©2011 Elsevier Ltd, Inc, BV 183

 Part 2 Pigmentary Disorders
A Malakar S. Indian J Dermatol Venerol Leprol 1996; 62:
B 2006; 5(9):884–889.
Figure 10.1:╇ (A) Acanthosis nigricans on the lateral neck. (B) Acanthosis
nigricans in the axilla.
First-Line Therapies
Tretinoin 0.05%
Metformin
Topical calcipotriol
Treatment of acanthosis nigricans with tretinoin. Darmstadt
GL, Yokel BK, Horn TD. Arch Dermatol 1991; 127(8):
1139–1140.
This case report details the treatment of a 55-year-old
Indian man with AN involving the axillae, popliteal fossae, the
dorsal surface of his toes and the posterior aspect of his neck,
as well as a general darkening of his complexion, that began
after taking nicotinic acid 500╯mg TID for hypercholestero-
lemia. After 16 weeks of treatment, the patient’s cholesterol
value dropped significantly; however, the skin changes were
cosmetically unacceptable. The left axilla was treated with
184
topical 0.1% tretinoin gel (retinoic acid) 2 times daily for a
2-week trial period. The right axilla served as the control. After
the initial trial period, there was nearly complete resolution of
clinical lesions in the left axilla.
Topical therapy with tretinoin and ammonium lactate for
acanthosis nigricans associated with obesity. Blobstein SH.
Cutis 2003; 71(1):33–34.
This study reports the successful use of a combination of
12% ammonium lactate cream and 0.05% tretinoin cream to
treat AN associated with obesity.
Topical tretinoin in acanthosis nigricans. Lahiri K,
159–161.
Efficacy of topical tretinoin was assessed in 30 cases of
idiopathic acanthosis nigricans which were recalcitrant to
conventional modalities of treatment. Topical tretinoin
0.05% qhs was found to be very effective both clinically
and histologically.
Treatment of acanthosis nigricans with oral isotretinoin.
Katz RA. Arch Dermatol 1980; 116(1):110–111.
This article describes a patient with extensive acanthosis
nigricans who was treated successfully with oral isotretinoin
to test its effectiveness in disorders of keratinization. Selection
of this disease for treatment with a oral retinoid agent was
based on the success of using topical tretinoin in patients with
acanthosis nigricans.
Comparison of metformin versus rosiglitazone in patients
with acanthosis nigricans: a pilot study. Bellot-Rojas P,
Posadas-Sanchez R, Caracas-Portilla N, et╯al. J Drugs Dermatol
The aim of this 12-week randomized, open-label pilot
study was to compare the efficacy of metformin versus rosigli-
tazone on AN lesions of the neck as well as their effects on
metabolic and anthropometric variables. Overweight or obese
subjects with AN were randomized to either metformin (n =
4) or rosiglitazone (n = 3). Only the rosiglitazone group
showed a significant reduction in insulin levels. No effect on
E the severity of AN was observed, but modest improvements
D of skin texture occurred in both treatment groups. Results
E showed that metformin and rosiglitazone were well tolerated.
Although efficacy on skin lesions was very modest, their
use in acanthotic subjects might be useful during longer treat-
ment periods.
Hyperkeratosis of the nipple associated with acanthosis nig-
ricans: treatment with topical calcipotriol. Lee HW, Chang
SE, Lee MW, Choi JH, Moon KC, Koh JK. J Am Acad Dermatol
2005; 52(3 Pt 1):529–530.
A 26-year-old obese woman presented with a 7-year history
of asymptomatic, hyperpigmented, hyperkeratotic lesions on
both nipples; velvety, hyperpigmented patches on both axillae
and groin; and hyperpigmented papillary papules on the tip
of the tongue, that began after a 10╯kg weight gain over a
3-month period. She was diagnosed with hyperkeratosis of the
 10â•… Hyperpigmented Disordersâ•… •â•… Benign melanonychia

nipple associated with AN and treated with topical calcipotriol
ointment twice daily. After 3 months, the lesions on both
nipples were significantly improved.
Commonly encountered pitfalls
Although acanthosis nigricans commonly occurs on the neck,
it is important not to overlook other locations such as the
axillae, lateral cheek and chest.
The finding of acanthosis nigricans, especially in an over-
weight patient, is likely a marker of insulin resistance, diabetes
mellitus or another endocrine abnormality. As such, referral
to an endocrinologist should be initiated.
However, while clinicians reflexively focus on endocrinopa-
thies, acanthosis may also indicate an underlying malignancy,
especially in adults. Gastric carcinoma is one such associated
malignancy. Hence, a thorough evaluation for malignancy is
indicated.
Special management & counseling considerations
If evidence of insulin resistance or diabetes mellitus is not
found in overweight patients, it is likely that the condition will
resolve with weight loss. Therefore, these patients should be
counseled regarding weight reduction and diet modification.
When a concomitant pathologic process has been ruled out,
one can safely assume AN is benign. Benign hereditary forms
of acanthosis also exist. In the aforementioned cohort, cos-
metic treatment should be offered.
References
1. Schwartz RA, Archer JA, Gorden P, Martin MM. Acanthosis nigricans.
J Am Acad Dermatol 1994; 31:1–19.
2. Schwartz RA. Acanthosis nigricans. In: Demis DJ, ed. Clinical
dermatology (unit 12–26). 18th edn. Philadelphia: JB Lippincott;
1999:1–11.
3. Pollitzer S. Acanthosis nigricans: a symptom of a disorder of the
abdominal sympathetic. J Am Med Assoc 1909; 53:1369–1373.
4. Kahn CR, Flier JS, Bar RS, et al. The syndromes of insulin resistance
and acanthosis nigricans: insulin-receptor disorders in man. N Eng J
Med 1976; 294:739–745.
5. Kim NY, Pandya AG. Pigmentary Diseases. Med Clin North Am 1998;
82(5):1185–1207.
6. Curth HO. Acanthosis nigricans. Birth Defects 1971; 7:31–39.
7. Stals H, Vercammen C, Peeters C, Morren M-A. Acanthosis nigricans
caused by nicotinic acid: case report and review of the literature.
Dermatology 1994; 189:203–206.

into the nail matrix.7 Dominguez and Martin biopsied 68

Benign melanonychia patients with longitudinal melanonychia and determined that
68% had racial melanonychia, 5.7% benign melanocytic
hyperplasia and 5.7% a nail malignancy.9
Melanonychia is a longitudinal or transverse brown streak
The following common etiologies of melanonychia involve
involving the nail plate or alternatively, complete discolora-
melanocyte activation:4
tion of the plate. Longitudinal melanonychia also termed,
melanonychia striata, is the most common presentation.1 It • Drug-induced:
can present as a single band on one or more digit although – Antimalarials
the entire nail plate may also be involved Figure 10.2 illustrates – Antiretrovirals
such a case. Transverse melanonychia is an uncommon condi- – Chemotherapeutic agents (doxorubicin, cyclophospha-
tion caused by radiation therapy and chemotherapy. A quite mide, and hydroxyurea)
interesting study outlines 3 cases caused by the use electron – Metals.
beam therapy.2 • Post-inflammatory:
More prevalent in individuals of color, benign melanony- – Chronic paronychia
chia may be associated with the normal aging process.1,3 Up – Onychotillomania (nail biting)
to 100% of African Americans older than 50 years of age – Friction/trauma.
exhibit melanonychia, termed racial melanonychia.4 A study • Infectious:
of 800 Japanese individuals found the prevalence of melaÂ� – Onychomycosis.
nonychia at 20% and 23% for males and females respectively.5 • Systemic causes
It is a much rarer phenomenon among Caucasians.6 – Endocrinopathies.
There are many causes of melanonychia both benign • Benign tumors:
and malignant.7,8 The physiologic processes responsible for – Myxoid cysts
melanonychia are melanocyte activation and melanocyte – Verrucae.
hyperplasia. The majority of cases of melanonychia occur as a • Non-melanocytic malignant causes:
result of melanocyte activation, during which hypermelanotic – Bowen’s disease
melanocytes are taken up from the nail bed and incorporated – Squamous cell carcinoma.

185
 Part 2 Pigmentary Disorders
A B
Figure 10.2:╇ (A and B) Benign longitudinal melanonychis.
The following conditions are caused by melanocytic hyper-
plasia and can also lead to ML:4
• Lentigo/benign melanocytic hyperplasia
• Nail matrix nevi
• Melanoma
Melanonychia induced by chemotherapy is reversible and
most commonly occurs when the patient is treated with drugs
like doxorubicin, cyclophosphamide, and hydroxyurea.
Evaluation of melanonychia includes a thorough inspec-
tion of the nail and associated structures, such as the proximal
and lateral nail folds and hyponychium, as well as the exact
location of the pigmentation.9 In order to assist the clinician
distinguish benign from malignant longitudinal melanony-
chia, Levit et╯al. proposed the following guidelines for malig-
nant melanonychia.4
• A – Age (peak incidence in the fifth to seventh decade)
• B – Brownish-black band with breadth greater than 3╯mm
• C – Change in morphology
• D – Digit that is involved (The thumb is more likely than
the great toe; the great toe more likely than the index
finger.)
• E – Extension of the brownish-black pigment of the
nail bed, nail matrix, and nail plate onto the adjacent
cuticle and proximal and/or lateral nail folds (Hutchinson’s
sign)
• F – Family history.
If melanoma or another serious condition is suspected, nail
matrix biopsy is recommended for diagnosis. Traditional
biopsy techniques should be considered, provided they yield
an adequate tissue sample.2,11 Treatment should be directed
towards the underlying cause of the melanonychia. If the
melanonychia is suspected to be drug-induced, removal of the
offending drug may be necessary, if medically feasible.
186
Commonly encountered pitfalls
While longitudinal melanonychia is a common and often
normal finding in individuals with dark skin, the clinician
should not lower his or her index of suspicion for subungual
melanoma. Additionally, melanoma should be suspected in
patients with lighter skin tones who have melanonychia. It is
imperative that a biopsy specimen be obtained from the nail
matrix to ensue the diagnosis of melanoma, as a nail plate
biopsy will not be sufficient.
Special management & counseling considerations
Skin of color patients are often unaware that melanoma may
present as longitudinal melanonychia. Therefore, education
regarding this possibility and self-examination is important.
They should also be counseled to have yearly cutaneous
examinations by a dermatologist including fingernails and toe-
nails. Finally, patients undergoing nail matrix biopsy, should
be warned regarding possible permanent post-biopsy nail
distrophy.
References
1. Leung AK, Kao CP. An atlas of nail disorders. Consultant 2001;
41:58–64.
2. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail
pigmentations. J Am Acad Dermatol 2007; 56(5):835–847.
3. Duhard E, Calvet C, Mariotte N, Tichet J, Vaillant L. [Prevalence of
longitudinal melanonychia in the white population]. Ann Dermatol
Venereol 1999; 122(9):586–590.
4. Tosti A, Piraccini BM, de Farias DC. Dealing with melanonychia. Semin
Cutan Med Surg 2009; 28(1):49–54.
5. Tasaki K. On band or linear pigmentation of the nail. Jpn J Dermatol
1933; 33:568.
 10â•… Hyperpigmented Disordersâ•… •â•… Confluent and reticulated papillomatosis of Gougerot and Carteaud
6. Kopf A, Waldo E. Melanonychia striata. Aust J Dermatol 1980;
21:59–70.
7. André J, Lateur N. Pigmented nail disorders. Dermatol Clin 2006;
24(3):329–339.
8. Levit EK, Kagen MH, Scher RK, Grossman M, Altman E. The ABC rule
for clinical detection of subungual melanoma. J Am Acad Dermatol
2000; 42(2 Pt 1):269–274.
9. Baran R, Kechijian P. Longitudinal melanonychia (melanonychia
striata): diagnosis and management. J Am Acad Dermatol Dec 1989;
21(6):1165–1175.
Confluent and
reticulated
papillomatosis of
Gougerot and
Carteaud (CRPGC)
Gougerot and Carteaud described this dermatologic condition
in the early part of the twentieth century. It was first labeled
‘papillomatose pigmenteé innominée’ and then ‘confluent
and reticular papillomatosis’ became the widely accepted
term.1 Lesions are characterized by hypochromic or blue-gray
papules which coalesce and become confluent in the center
A B
Figure 10.3:╇ (A and B) Confluent and reticulated papillomatosis.
10. Quinlan KE, Janiga JJ, Baran R, Lim HW. Transverse melanonychia
secondary to total skin electron beam therapy: a report of 3 cases.
J Am Acad Dermatol 2005; 53(2 Suppl 1):S112–S114.
11. Bormann G, Marsch WC, Haerting J, Helmbold P. Concomitant
traumas influence prognosis in melanomas of the nail apparatus. Br J
Dermatol 2006; 155(1):76–80.
with a reticular pattern in the periphery. Lesions are typically
located in the epigastrium and inframammary areas (Fig.
10.3). However, they may involve the neck, shoulders and
pubic area in advanced cases.2,3 The disease has shown no
gender or racial predilection.4 Electron microscopy imaging
has shown a defect of keratinization, a granular layer decrease
and associated hypermelanosis.5
The etiology of CRPGC etiology is unknown, but theories
abound. Since response to antifungal agents has been docu-
mented, heavy colonization with Pityrosporum orbiculare has
been theorized as the causative agent.6,7 Several antibiotics
have also been effective, and their anti-inflammatory proper-
ties have been thought to be the responsible mechanism of
action.8 Others have posited abnormal keratinization as a
factor, and this is supported by the histopathologic findings
mentioned above.9 A propensity towards obesity and an endo-
crinopathy have been observed anomalies.10 Finally, genetics
may play a role.11
187
 Part 2 Pigmentary Disorders
First-Line Therapies
Minocycline D Confluent and reticulated papillomatosis: response to tazar-
Azithromycin D otene. Bowman P, Davis LS. J Am Acad Dermatol 2003;
Fusidic acid E 48(5):S80–S81.
Ketoconazole E Case report of an 11-year-old Black girl with confluent and
Selenium sulfide (typically found in shampoos) E reticulated papillomatosis who was treated with tazarotene
Retinoids E gel. The treatment was well tolerated and the patient cleared
Confluent and reticulated papillomatosis: response to
minocycline. Montemarano AD, Hengge M, Sau P, Welch M.
J Am Acad Dermatol 1996; 34:253–256.
The objective of this study was to evaluate the effectiveness
of oral minocycline in 9 patients with CRP. These subjects were
treated with oral minocycline 50╯mg twice a day, for 6 weeks.
The average follow-up period was 11 months. Recurrence rate,
side effects, and effectiveness of therapy were assessed. All
patients except two had a 90–100% response to therapy. Recur-
rences were noted in 3 patients, all of whom responded to
re-treatment with minocycline. None of the 9 patients had an
adverse reaction. Minocycline 50╯mg twice a day is safe and
effective for treatment of CRP.
Confluent and reticulated papillomatosis was improved by
treatment with minocycline hydrochloride: report of two
cases. Koizumi N, Hatamochi A, Shinkai A. Rinsho Derma
2002; 44:63–67.
An 18-year-old male and a 12-year-old female with CRPGC,
both obese, responded to treatment with minocycline.
Treatment of confluent and reticulated papillomatosis with
azithromycin. Atasoy M, Ozdemir S, Aktaş A, Aliaǧaoǧlu C,
Karakuzu A, Erdem T. J Dermatol 2004; 31:682–686.
This is the case of a 21-year-old male patient with confluent
and reticulated papillomatosis initially treated with ketocona-
zole cream for 2 weeks without improvement. The patient
demonstrated a significant response to treatment with
azithromycin.
A case of confluent and reticulated papillomatosis respon-
sive to ketoconazole cream. Hamaguchi T, Nagase M, Higuchi
R, Takiuchi I. Nippon Ishinkin Gakkai Zasshi 2002; 43:
95–98.
A case report of a patient responding to ketoconazole
cream, as fungal spores were found in the skin.
Confluent and reticulated papillomatosis responsive to sele-
nium sulfide. Nordby CA, Mitchell AJ. Int J Dermatol 1986;
25:194–199.
Case report of CRP that showed a significant therapeutic
response to topical selenium sulfide. In previously described
188
cases, response to this agent and to other medications, both
antifungal and keratolytic, were variable.
completely.
Six cases of confluent and reticulated papillomatosis allevi-
ated by various antibiotics. Jang HS, Oh CK, Cha JH, Cho
SH, Kwon KS. J Am Acad Dermatol 2001; 44(4):652–655.
This study reports 6 cases of CRP alleviated by various
antibiotics. The patient described in case 1 is a 16-year-old girl
whose disease was alleviated by oral minocycline, 100╯mg
daily for 8 weeks. Cases 2 and 3 describe an 18-year-old
woman and a 17-year-old male adolescent whose disease was
reduced by oral fusidic acid, 1000╯mg daily for 4 weeks. Case
4 describes a 14-year-old girl who received oral clarithromycin,
500╯mg daily for 5 weeks. Case 5 describes a 22-year-old
woman whose disease was reduced by oral erythromycin,
1000╯mg daily for 6 weeks. Case 5 reports a 24-year-old man
who received oral azithromycin, 500╯mg daily 3 times per
week for 3 weeks. Complete clearing after treatment with the
above mentioned antibiotics was reported.
References
1. Inalöz HS, Patel G, Knight AG. Familial confluent and reticulated
papillomatosis. Arch Dermatol 2002; 138:276–277.
2. Schwartz RA. Confluent and reticulated papillomatosis. Emedicine.
http://emedicine.medscape.com/article/1106748-overview [accessed
December 18, 2009].
3. Ferreira LM, Diniz LM, Ferreira CJ. Confluent and reticulated papil-
lomatosis of Gougerot and Carteaud: report of three cases. An Bras
Dermatol 2009; 84(1):78–81.
4. Scheinfeld N. Confluent and reticulated papillomatosis: a review of
the literature. Am J Clin Dermatol 2006; 7:305–313.
5. Lee SH, Choi EH, Lee WS, et al. Confluent and reticulated papilloma-
tosis: a clinical, histopathological, and electron microscopic study.
J Dermatol 1991; 18:725–730.
6. Hamaguchi T, Nagase M, Higuchi R, Takiuchi I. A case of confluent
and reticulated papillomatosis responsive to ketoconazole cream.
Nippon Ishinkin Gakkai Zasshi 2002; 43:95–98.
7. Roberts SO, Lachapelle JM. Confluent and reticulate papillomatosis
(Gougerot–Carteaud) and pityrosporum orbiculare. Br J Dermatol
1969; 81:841–845.
8. Chang SN, Kim SC, Lee SH, Lee WS. Minocycline treatment for conflu-
ent and reticulated papillomatosis. Cutis 1996; 57:454–457.
9. Carrozzo AM, Gatti S, Ferranti G, et al. Calcipotriol treatment of con-
fluent and reticulated papillomatosis (Gougerot–Carteaud syndrome).
J Eur Acad Dermatol Venereol 2000; 14:131–133.
10. Koizumi N, Hatamochi A, Shinkai A. Confluent and reticulated papil-
lomatosis was improved by treatment with minocycline hydrochlo-
ride: report of two cases. Rinsho Derma 2002; 44:63–637.
11. Inalöz HS, Patel G, Knight AG. Familial confluent and reticulated
papillomatosis. Arch Dermatol 2002; 138:276–277.
 10â•… Hyperpigmented Disordersâ•… •â•… Drug-induced pigmentation

The pathophysiology of medications may vary. However,

Drug-induced several broad mechanisms of action exist:2

• drug or drug metabolite deposition in the dermis and
pigmentation epidermis
• enhanced melanin production
• cutaneous drug-induced post-inflammatory changes
Exposure to a wide range of pharmacologic agents can induce • reduced number of skin melanocytes
clinically significant pigmentary changes. Though these • enzymatic blockade of melanogenesis
changes are typically benign, the cosmetic effects can have a • inhibition of melanosome transfer.
severe psychological impact on affected individuals, especially
on those with darker skin (Fig. 10.4).1 Table 10.1 describes the particular cutaneous manifesta-
Three classes of drug-induced pigmentary changes have tions of common medications. Cutaneous manifestations are
been described:2 specific to each drug.4
The effect of the antimalarial chloroquine on the pigmen-
• hyperpigmentation/melanosis tary system has been well described. This medication
• hypopigmentation/leukoderma appears to bind to melanin and becomes concentrated
• dyspigmentation. in melanin-containing structures.
Pharmacologically related cutaneous changes are fairly The popular antibiotic, minocycline, can lead to diffused
common as 10–20% of all cases of hyperpigmentation are pigmentary changes which have been categorized into three
attributed to drug reactions.3 Drug reactions have been strongly types:
associated with specific drugs and/or classes of drugs: • Type I – blue-black/gray pigment on the face in areas of
• chloroquine scarring or inflammation associated with acne
• minocycline • Type II – blue-gray pigment on normal skin on the shins
• amiodarone and forearms
• chlorpromazine • Type III – diffuse muddy-brown discoloration in areas of
• NSAIDs sun exposure.
• trimethoprim-sulfamethoxazole According to Geria et╯al, Types I and II will resolve over time
• phenolphthalein (found in laxatives) while type III seems to be permanent.5 Treatment is outlined
• heavy metals below. A complete history and physical examination will
• chemotherapeutic agents. typically elucidate the diagnosis with a biopsy reserved for
equivocal cases.
Discontinuation of the offending agent is the sine qua non
of this condition. Reassurance of the (usually) temporal nature
of the event is also important. Use of sunscreen to prevent
progression is recommended as the combination of sunlight
and certain drugs may exacerbate the condition. Finally, laser
therapy is useful in selected cases.

First-Line Therapies

Q-switched alexandrite laser D

Q-switched ruby laser E

Minocycline-induced hyperpigmentation treated with a

Figure 10.4:╇ Drug-induced pigmentation resulting from chloroquine (Courtesy of
Neil Fenske, MD, Tampa, FL; From Callen, Color Atlas of Dermatology, 2e,
copyright Elsevier 1999.)
755-nm Q-switched alexandrite laser. Alster TS, Gupta SN.
Dermatol Surg 2004: 30(9):1201–1204.
6 patients with minocycline-induced hyperpigmentation
on the face or legs were treated with a Q-switched alexandrite
laser on a bimonthly basis until pigmentation was eradicated.
Cutaneous pigmentation resolved completely in all patients in
an average of four laser sessions. Side effects were limited to
transient purpura and mild desquamation without scarring or
dyspigmentation.

189
 Part 2 Pigmentary Disorders
Table 10.1╇ Cutaneous manifestations of common offending agents
Drug/drug group Clinical features
Antipsychotics • Bluish-gray pigmentation, especially in
(chlorpromazine sun-exposed areas
and related • Pigmentation is cumulative and some areas
phenothiazines) may develop a purplish tint
• Pigmentation of the conjunctiva in the eye
may also occur, along with cataracts and
corneal opacities
Phenytoin • 10% of patients develop pigmentation of the
face and neck resembling chloasma (clearly
defined, roughly symmetrical dark brown
patches)
• Fades after a few months when drug has
been stopped
Antimalarials • About 25% of patients receiving chloroquine
or hydroxychloroquine for several years
develop bluish-gray pigmentation on face,
neck and sometimes lower legs and
forearms
• Continuous long-term use may lead to
blue-black patches, especially in sun-
exposed areas
• Nail bed and corneal and retinal changes
may also develop
Cytotoxic drugs • Busulfan, cyclophosphamide, bleomycin and
adriamycin have all produced
hyperpigmentation to some degree
• Banded or diffuse pigmentation of nails often
occurs
Amiodarone • Blue-gray pigmentation in sun-exposed
areas (face and hands)
• Photosensitivity occurs in 30–57% of
patients whilst 1–10% show skin
pigmentation
• Skin pigmentation is reversible but may take
up to 1 year for complete resolution after the
drug has been stopped
NSAIDs • Often associated with fixed drug eruptions
(drugs that cause a single or few sharply
demarcated erythematous lesions which
resolve promptly but leave a local brown
pigmentation)
• May occur on the face, extremities and
genitalia
190
Laser treatment of imipramine-induced hyperpigmentation.
Atkin DH, Fitzpatrick RE. J Am Acad Dermatol 2000; 43(1 Pt
1):77–80.
One patient with significant imipramine- (a tricyclic
antidepressant) induced pigmentation underwent treatment
with carbon dioxide, erbium, alexandrite, and ruby lasers on
hyperpigmented areas. Biopsies were performed before treat-
ment, immediately after treatment, and at clearing with the
alexandrite laser. The Q-switched alexandrite and ruby lasers
resulted in clinical improvement in the patient’s hyperÂ�
pigmentation and a decrease in pigment granules on light
microscopy.
Amiodarone-induced skin pigmentation: Q-switched laser
therapy, an effective treatment option. Wiper A, Roberts DH,
Schmitt M. Heart 2007; 93(1):15.
Case report of successful treatment of amiodarone-induced
hyperpigmentation using a Q-switched ruby laser on a 48-year-
old man.
Commonly encountered pitfalls
Drug induced hyperpigmentation can be confused with a
variety of dermatoses. This may lead to a delay in both diag-
nosis and discontinuation of the offending medication. The
consequences of mis�diagnosis can be particularly deleterious
as drug-induced pigmentation may be permanent.
Special management & counseling considerations
If possible, the causative agent should be immediately
discontinued.
Patients should be informed that drug induced hyperpig-
mentation may be permanent. Pigmentation caused by amio-
darone, for example, may require one year to resolve.
The use of sunscreen, sun avoidance and protective clothing
can help ameliorate the condition.
References
1. Halder RM, Nandedkar MA, Neal KW. Pigmentary disorders in ethnic
skin. Dermatol Clin 2003; 21(4):617–628.
2. Butler DF, Henderson DZ. Drug-induced pigmentation. Emedicine.
2008. http://emedicine.medscape.com/article/1069686-overview [Acc�
essed August 23, 2009].
3. Dereure O. Drug-induced skin pigmentation: epidemiology, diagnosis
and treatment. Am J Clin Dermatol 2001; 2(4):253–262.
4. Dermnet NZ. Photosensitivity. http://www.dermnetnz.info/reactions/
photosensitivity.html [accessed August 25, 2009].
5. Geria AN, Tajirian AL, Kihiczak G. Minocycline-induced skin pigmen-
tation: an update. Acta Dermatovenerol Croat 2009; 17(2):123–126.
 10â•… Hyperpigmented Disordersâ•… •â•… Erythema dyschromicum perstans
Erythema
dyschromicum
perstans
Erythema dyschromicum perstans (EDP) was first described in
1957. C. Oswaldo Ramirez of San Salvador, El Salvador,
referred to patients with this disease as Los cenicientos, which
is Spanish for “the ashen ones”.1 EDP was later named derma-
tosis ceniciento which directly translates to ashy dermatosis.
This name refers to the blue-gray hyperpigmented macules
that characterize the disease.1 These hyperpigmented macules
usually erupt on the face, neck (Fig. 10.5), trunk and arms as
oval, polycyclic, or irregularly shaped. At onset the macules
appear gray in color with an occasional erythematous or ele-
vated border. There are no known systemic symptoms or
associations.
The etiology of EDP is unknown but several theories
abound. Some authors consider it to be a variation of lichen
planus actinicus.2 Other authors have considered the geo-
graphic distribution of EDP and suggested environmental
factors as the etiology. However, all attempts to identify
pollutants within the geographic distribution have been
unsuccessful.
EPD is prevalent in darker-skinned adults, particularly
those of Hispanic decent.3 In contrast, most children with EDP
have fair-skin.4
In 2007, a study was published in which histocompatibility
complexes in Mexican Mestizo patients were analyzed.5
Researchers found that HLA-DR4 was the most commonly
associated complex in individuals with EDP, 65% versus
23% for a control group, which lends credence to a genetic
etiology.5
Figure 10.5:╇ Erythema dyschromicum perstans. Numerous oval to polygonal,
gray-brown macules on the lower extremities. (Courtesy of Wake Forest University;
from Bolognia, Dermatology, 2e, copyright Elsevier 2008.)
First-Line Therapies
Clofazimine C
Dapsone C
Many therapeutic options are available for EDP, but few
have been effective, with the exception of clofazimine. Clofaz-
imine, a lipophilic rhimophenazine dye with both anti�
microbial and anti-inflammatory properties, was originally
developed to treat tuberculosis. Although its mechanism of
action is unclear, it seems to influence cell mediated immunity
and effect neutrophils and monocytes in a variety of ways, such
as stimulating phagocytosis and release of lysosomal enzymes.6
Clinical trial with clofazimine for treating erythema dys-
chromicum perstans. Evaluation of cell-mediated immunity.
Piquero-Martín J, Pérez-Alfonzo R, Abrusci V, et╯al. Int J Der-
matol 1989; 28(3):198–200.
Eight patients with erythema dyschromicum perstans
(EDP), treated with clofazimine, had T-helper/T-suppressor
cytotoxic ratio (CD-4/CD-8) and in vitro lymphoproliferative
response on stimulation with phytohemaglutin (PHA) and
concanavalin A (Con A) analyzed pre- and post-treatment.
Seven of the 8 patients had excellent to good responses. A
significant change in the CD-4/CD-8 ratio was observed in the
immunologic evaluation after treatment. A decreased response
to PHA, and no change in the response to Con A was noted.
Clofazimine produced a favorable cosmetic result and induces
changes in cell-mediated response.
Involvement of cell adhesion and activation molecules in
the pathogenesis of erythema dyschromicum perstans (ashy
dermatitis). Baranda L, Torres-Alvarez B, Cortes-Franco R,
et╯al. Arch Dermatol 1997; 133(3):325–329.
Using a immunohistochemical technique, the expression of
cell adhesion and activation molecules was assessed in skin
biopsy samples obtained from 6 patients with erythema dys-
chromicum perstans. The skin biopsies were obtained before
and after 3 months of clofazimine therapy (100╯mg daily). Our
results suggest that some cell adhesion and activation mole-
cules are involved in the pathogenesis of erythema dyschromi-
cum perstans. Clofazimine appears to have an important effect
on the inflammatory phenomenon of erythema dyschromi-
cum perstans.
Erythema dyschromicum perstans: response to dapsone
therapy. Bahadir S, Cobanoglu U, Cimsit G, Yayli S, Alpay K.
Int J Dermatol 2004: 43(3);220–222.
Various treatments have been used for EDP but without
benefit, including sun protection, chemical peels, antibiotics,
corticosteroids, vitamins, isoniazid, griseofulvin, and chloro-
quine. The authors support the efficacy of clofazimine and
dapsone. The authors report a case of EDP that responded
remarkably well to treatment with dapsone.
191
 Part 2 Pigmentary Disorders

Erythema dyschromicum perstans: response to dapsone
therapy. Kontochristopoulos G, Stavropoulos P, Pantelos D.
Int J Dermatol 1998; 37:790–799.
This study reports two cases of EDP that responded well to
dapsone. In the first case, dapsone at 100╯mg daily for 12
weeks resulted in regression of the active borders and central
hyperpigmentation. No new lesions developed. In the second
case, treatment with dapsone 100╯mg produced a significant
decrease in hyperpigmentation after 8 weeks and new lesions
did not appear. However, discontinuation of therapy resulted
in the recurrence of the eruption, which disappeared when
dapsone was reinstituted.
Commonly encountered pitfalls
The differential diagnosis of EDP as with many pigmentary
disorders, includes a drug eruption. A detailed history must be
taken to identify concomitant medications. A biopsy will dis-
tinguish between a drug eruption as well as lichen planus, as
some theorize that EDP is a variant of lichen planus. Addition-
ally, systemic conditions that have similar cutaneous presenta-
tions such as Addison’s disease and hemochromatosis should
not be overlooked.
Special management & counseling considerations
While EDP is a benign disorder, treatment presents special
management and counseling considerations. Clofazimine,
one of the few effective oral agents used to treat EDP has a
serious adverse event profile. They include ichthyosis and fatal
enteropathy. Therefore, topical steroids, phototherapy or lasers
should be utilized before clofazimine.
Since the prognosis differs according to age, and the condi-
tion tends to remit spontaneously in pre-pubertal children
(but not in adults), treatment is often unnecessary in this
population.7
References
1. Ramirez CO. Los cenicientos: problema clinica. Memoria del Primer
Congresso Centroamericano de Dermatologica 1957; 122–130.
2. Berger RS, et al. Erythema dyschromicum perstans and lichen planus:
are they related? J Am Acad Dermatol 1989; 21:438.
3. Silverberg NB, Herz J, Wagner A, Paller AS. Erythema dyschromicum
perstans in prepubertal children. Pediatr Dermatol 2003; 20(5):
398–403.
4. Torrelo A, Zaballos P, Colmenero I, Mediero IG, de Prada I, Zambrano
A. Erythema dyschromicum perstans in children: a report of 14 cases.
J Eur Acad Dermatol Venereol 2005; 19(4):422–426.
5. Correa MC, Memije EV, Vargas-Alarcon G, et al. HLA-DR association
with the genetic susceptibility to develop ashy dermatosis in Mexican
Mestizo patients. J Am Acad Dermatol 2007; 56(4):617–620.
6. Arbiser JL, Moschella SL. Clofazimine: a review of its medical uses and
mechanisms of action. J Am Acad Dermatol 1995; 32(2 Pt 1):241–
247.
7. Silverberg NB, Herz J, Wagner A, et al. Erythema dyschromicum
perstans in prepubertal children. Pediatr Dermatol 2003; 20(5):
398–403.

Exogenous ochronosis
First-Line Therapies

Removal of the offending agent.

Exogenous ochronosis (EO) is characterized by a bluish facial
pigmentation resulting from the application of hydroquinone
(HQ). First described in 1906, the etiology of EO is unknown,
although it is postulated that HQ inhibits homogentisic acid
oxidase, which leads to the development of ochronotic
pigment (Fig. 10.6).1,2,3
The etiology of EO is unknown, however several theories
exist.1 Hydroquinone (HQ) may inhibits homogentesic acid
oxidase in the dermis, leading to the development of dark
pigment or ochronotic pigmentation.2
EO typically occurs in dark skinned individuals; however,
it has been reported in Caucasians and Hispanics. Clinical
signs of ochronosis are enumerated in Box 10.1. While HQ is
foremost in causing EO, several agents can also cause the con-
dition; these include antimalarials and products with mercury,
picric acid and phenol.3
The Hull and Procter study illustrates that unlike many
other pigmentary disorders, the pathogenesis of EO requires
functioning melanocytes. A biopsy of a patient with ochrono-
sis and vitiligo, showed no melanocytes in the vitiliginous area
and ochronotic pigment in the areas with EO.4 Figure 10.6:╇ Distribution of exogenous ochronosis of the cheeks.

192

Box 10.1╇ Clinical signs of ochronosis
• Stage 1: Erythema and macular pigmentation
• Stage 2: Darker pigmentation, papules and atrophy
• Stage 3: Papulonodular, granulomatous or annular lesions
Exogenous ochronosis. Snider RL, Thiers BH. J Am Acad Der-
matol 1993; 28:662–664.
Snider and Thiers reported a case of exogenous ochronosis
in a 59-year-old black woman who has a 5-year history of
progressive darkening of the skin around her eyes. She had
been using 2-percent hydroquinone skin bleaching cream
once daily for many years. About 9 months before the exami-
nation she has used 3-percent hydroquinone twice daily for 3
months, then 4-percent hydroquinone with a sunscreen twice
daily for 3 months. Examination showed numerous pinpoint
blue-black spots around the eye area. A biopsy specimen
revealed multiple scattered, elongted, curved, and oval depos-
its of ochronotic pigment within the collagen bundles.
Second-Line Therapy
Topical tretinoin
Dermabrasion
CO2 laser
Probable coexisting exogenous ochronosis and mercurial
pigmentation managed by dermabrasion. Lang PG. J Am
Acad Dermatol 1988; 19:942–946.
A patient with blue-gray discoloration of the face is described
who used bleaching creams containing mercury and hydro�
quinone for many years. Biopsy showed deposits that were
compatible with both mercury deposition and exogenous
ochronosis. Dermabrasion was successfully employed to
remove these deposits.
Hydroquinone-induced localized exogenous ochronosis
treated with dermabrasion and CO2 laser. Diven DG, Smith
EB, Pupo RA, Lee M. J Dermatol Surg Oncol 1990;
16:1018–1022.
Localized exogenous ochronosis can result from the
repeated use of hydroquinone-containing creams, many of
which are available over the counter. This is a case that was
managed by dermabrasion and CO2 laser. The incidence and
10â•… Hyperpigmented Disordersâ•… •â•… Exogenous ochronosis
proposed etiologies of hydroquinone-induced exogenous
ochronosis are reviewed.
Commonly encountered pitfalls
Exogenous ochronosis is a rare disorder in the United States
with fewer than 50 case reports in the US literature. American
dermatologists erroneously associate the disorder with the use
of products with high concentrations of hydroquinone which
is seemingly the case with African patients. Patients emigrating
from Africa who present with facial dyspigmentation should
be evaluated for exogenous ochronosis. In the United States,
the majority of cases of exogenous ochronosis are a result of
the prolonged use of hydroquinone-containing products of
low concentrations (1–2%). Physicians should ask patients
about their use of low-dose hydroquinone-containing
products.
Exogenous ochronosis may be mistaken for the pigmentary
disorders melasma or post-inflammatory hyperpigmentation
and therapy with the causative agent, hydroquinone initiated.
A thorough history of over-the-counter or prescription hydro-
quinone use must be obtained. Furthermore, eliciting a history
of initial improvement in pigmentation with hydroquinone
therapy with subsequent worsening is supportive of the diag-
nosis of exogenous ochronosis.
E
E
Special management & counseling considerations
E Diagnosis of the majority of pigmentary disorders is clinical
and does not require a skin biopsy. However, given the diffi-
culty of diagnosing exogenous ochronosis, it may be appropri-
ate to perform a skin biopsy early to confirm the diagnosis.
Patients with pigmentary disorders, including exogenous
ochronosis, are reluctant to discontinue hydroquinone-
containing products. Therefore, the importance of educating
these patients that hydroquinone causes the problem, and
must be permanently discontinued, cannot be overempha-
sized. Furthermore, patients must be made aware that this
pigmentation may be permanent.
References
1. Touart DM, Sau P. Cutaneous deposition diseases. Part II. J Am Acad
Dermatol 1998; 39:527–546.
2. Burkhart CG, Burkhart CN. Ochronosis. Emedicine Specialties 1998.
3. Huerta Brogeras M, Sanchez-Viera M. Exogenous ochronosis. J Drugs
Dermatol 2006; 5:80–81.
4. Hull RB, Procter PR. The melanocyte: an essential link in hydroquinone-
induced ochronosis. J Am Acad Dermatol 1990; 22:529–531.
193
 Part 2 Pigmentary Disorders

Melanin pigmentation of the gingiva does not present a

Gingival medical problem although complaints of ‘black gums’ may

cause esthetic problems and embarrassment, particularly if the

hyperpigmentation pigmentation is visible while speaking or smiling.

Treatment of gingival hyperpigmentation by erbium-doped,

Few dermatoses can cause as much embarrassment and psy- yttrium, aluminum, and garnet laser for esthetic purposes.
chological damage as gingival hyperpigmentation. Abnormal Azzeh MM. J Periodontol 2007; 78:177–184.
melanocyte activity results in deposition of melanin in the In this clinical study, 6 White subjects with dark-brown to
basal layer and hyperpigmentation and discoloration of the black gingival hyperpigmentation (3 of whom were smokers)
gingiva.1,2 The causes of gingival hyperpigmentation include were treated with the Er:YAG laser (settings: 250╯mJ, 15╯Hz,
the following,3,4 (Fig. 10.7) using the defocused mode) without using anesthesia. Each
• Endocrine disturbance subject was initially treated for 20–25 minutes and then
• Albright’s syndrome underwent the same treatment 4 days later (same settings).
• Malignant melanoma With each treatment there were no signs of complications. All
• Antimalarial therapy wounds healed almost completely within the 4-day period
• Peutz–Jeghers syndrome prior to the second treatment. Follow-up visits were performed
• Trauma 6–18 months later. There were no signs of recurrence in the 6
• Hemochromatosis subjects.
• Chronic pulmonary disease
• Racial pigmentation. Treatment of gingival hyperpigmentation for esthetic pur-
poses by Nd:YAG Laser: report of 4 cases. Atsawasuwan P,
Dark skinned individuals and those of African, Asian, and
Greethong K, Nimmanon V. Periodontol 2000; 71:315–321.
Latino ancestry are genetically prone to exhibit gingival hyper-
In this study, 4 subjects with gingival hyperpigmentation
pigmentation.5,6 Interestingly, fair skinned individuals, despite
were treated with the Nd:YAG laser (settings: 6 watts, 60╯mJ,
having approximate numbers of gingival melanocytes, will not
100 pulses per second, 320 µm diameter fiber optic hand-
express the condition.7
piece). There were no complications. Complete ablation of the
hyperpigmented areas was achieved in all subjects. Follow-up
at 3–4 weeks then 11–13 months post procedure found the
First-Line Therapies gingiva to be healthy, pink, and firm.

Er:YAG laser D Gingival melanin pigmentation and its treatment with the
Nd:YAG laser D CO2 laser. Erdogan O, Esen E, Haytac MC, Karsli ED, Oz IA.
CO2 laser D Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;
98:522–527.
10 subjects with gingival melanin pigmentation were
treated using superpulsed CO2 laser (settings: 10 watts, 0.8╯mm
spot size, 20╯Hz, 10 milliseconds). Pigmented areas were
measured on pre- and post-operative standard digital images
by the aid of image-analyzing software. Statistical analysis of
the data was performed by Mann Whitney U test. Ablation of
the hyperpigmented gingiva was accomplished with minimal
carbonization and almost no bleeding. Post-operative healing
was uneventful. Two cases of partial repigmentation were
observed during 24-month follow-up. Statistical analysis of
the data revealed a significant difference between pre- and
post-operative measurements of pigmented area.

Commonly encountered pitfalls

Figure 10.7:╇ Gingival hyperpigmentation. Racial pigmentation of the gums.
(From Johnson, Moy, White: Ethnic Skin – Medical and Surgical, Mosby Inc.,
copyright Elsevier 1998.)
The differential diagnosis of gingival hyperpigmentation
is quite varied and includes both benign and malignant
conditions. Conditions associated with malignancy including
Peutz–Jeghers syndrome, oral melanoacanthoma and
melanoma. Gingival tattooing is a phenomenon seen in
certain cultures, thus it is important to obtain a tattoo history.9

194
 10â•… Hyperpigmented Disordersâ•… •â•… Melasma

Special management & counseling considerations
Cessation of smoking or discontinuation of an offending
agent can reverse hyperpigmentation in many cases. A visit
from a patient experiencing smoker’s melanosis would be a
very opportune time to initiate smoking cessation counseling.
Gingival hyperpigmentation can cause embarrassment in
patients with large gum lines or a ‘gummy smile’; these patients
should be offered treatment options.
References
1. Dummett CO. Overview of normal oral pigmentations. J Indiana Dent
Assoc 1980; 59(3):13–18.
2. Martini FH, Timmons MJ. Human anatomy. New Jersey: Prentice Hall;
1995.
3. Leston JM, Santos AA, Varela-Centelles PI, Garcia JV, Romero MA,
Villamor LP. Oral mucosa: variations from normalcy, Part II. Cutis
2002; 69(3):215–217.
4. Dummett CO, Sakumura JS, Barens G. The relationship of facial skin
complexion to oral mucosa pigmentation and tooth color. J Prosthet
Dent 1980; 43(4):392–396.
5. Fry L, Almeyda JR. The incidence of buccal pigmentation in caucasoids
and negroids in Britain. Br J Dermatol 1968; 80(4):244–247.
6. Tamizi M, Taheri M. Treatment of severe physiologic gingival pigmen-
tation with free gingival autograft. Quintessence Int 1996; 27(8):
555–558.
7. Esen E, Haytac MC, Oz IA, Erdogan O, Karsli ED. Gingival melanin
pigmentation and its treatment with the CO2 laser. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod 2004; 98(5):522–527.
8. Hoexter DL. Periodontal aesthetics to enhance a smile. Dent Today
1999; 18(5):78–81.
9. Rawal SY, Burrell R, Hamidi CS, et al. Diffuse pigmentation of maxil-
lary attached gingiva: four cases of the cultural practice of gingival
tattoo. J Periodontol 2007; 78(1):170–176.

The condition primarily affects women, particularly during

Melasma pregnancy or while using oral contraceptives.2 During preg-

nancy it is referred to as ‘melasma gravidarum’ or ‘mask of
pregnancy’ and has been reported in up to 80% of pregnant
Melasma is characterized by symmetrical hyperpigmented Mexican females. Melasma can also occur in men.3
patches that vary from light to dark brown in color. The lesions There are three recognized patterns of melasma (Table
are caused by both dermal and epidermal melanin deposition. 10.3):
This differentiation is critically important when assessing treat-
• Centrofacial, involving the cheeks, forehead, upper lips,
ment outcomes as dermal melasma is much more difficult to
nose and chin (accounting for 63% of the cases in one
ameliorate (Table 10.2). With clinical examination alone, it is
study);
difficult to differentiate between the different types of melasma.
• Malar, involving the cheeks and nose (21%);
Historically, Wood’s light examination was used for patients
• Mandibular, involving the mandible (16%) (Figs. 10.8,
with Fitzpatrick skin types I–IV to distinguish and highlight
10.9).4
changes of epidermal melasma. However, recent data indicate
that skin biopsy is required to distinguish between types of
melasma as the Wood’s light may be inconclusive.
Individuals with melasma display an exaggerated response
to UV light.1 Photosensitizing drugs, autoimmune thyroid dis-
orders, cosmetics and hormone therapy have all been linked
to melasma.

Table 10.2╇ Clinical features of melasma6

Type of melasma Clinical features

Epidermal • Well-defined border

• Dark brown color
• Appears more obvious under Woods light
• Responds well to treatment
Dermal • Ill-defined border
• Light brown color
• Unchanged under Woods light
• Responds poorly to treatment
Mixed • Combination of light and brown patches
• Partial improvement with treatment
Figure 10.8:╇ Male with Melasma.

195
 Part 2 Pigmentary Disorders
Figure 10.9:╇ Female with Melasma.
The incidence of melasma is thought to be higher in patients
with Fitzpatrick skin types V and VI. It is especially common
in Hispanics, African-Caribbeans and Asians. It is much more
prevalent in people who live in areas of intense UV exposure,
e.g. Southeast Asia.5,6
First-Line Therapy
Monotherapy A treat patients in each treatment group whose condition had
Combination therapy A completely cleared by week 8. Both studies demonstrated that
Retinoids (tretinoin) A
A double-blind, comparative, placebo-controlled study of
the efficacy and tolerability of 4% hydroquinone as a
depigmenting agent in melasma. Ennes SBP, Paschoalick RC,
Mota De Avelar Alchorne M. J Dermatolog Treat 2000;
11:173–179.
A total of 48 patients were randomly selected with 24
receiving hydroquinone 4%, and 24 placebo. Patients were
instructed to use and apply additional sunscreen. The 12-week
treatment period focused on evaluation of efficacy and toler-
ability with photographic assessment every 3 weeks. Efficacy
was classified into three categories: total improvement,
partial improvement, or failure. Tolerability was classified as
excellent, good, fair or poor. Results showed a statistically
significant difference between the efficacy of the hydroquinone
4% and placebo group. In the hydroquinone group, 40% of
the patients showed complete disappearance of spots at the
end of the treatment and there were no therapeutic failures
reported. In the placebo group, 10% of the patients showed
total improvement, while therapeutic failures occurred in 20%
196
Table 10.3╇ Characteristics of melasma
• Symmetrical facial hyperpigmentation
• Central facial distribution (most common)
• Malar distribution
• Mandibular distribution (least common)
• Can occur in non-facial sun exposed areas
• Increased melanin production but normal number of melanocytes
• May involve epidermis, dermis or both
• More common in women with Fitzpatrick skin type V and VI
• Exacerbated by sun exposure, pregnancy and oral contraceptives
of the patients. Both treatments were well tolerated, with no
serious adverse events reported.
Efficacy and safety of a new triple-combination agent for the
treatment of facial melasma. Taylor SC, Torok H, Jones T,
et╯al. Cutis 2003; 72:67–72.
The primary objective of two 8-week, multicenter, rando�
mized, investigator-blind studies was to compare the efficacy
and safety of a hydrophilic cream formulation containing
tretinoin 0.05%, hydroquinone 4.0%, and fluocinolone aceto-
nide 0.01% (RA + HQ + FA), with the dual-combination agents
tretinoin plus hydroquinone (RA + HQ), tretinoin plus fluoci-
nolone acetonide (RA + FA), and hydroquinone plus fluoci-
nolone acetonide (HQ + FA). All agents had the same drug
concentration and vehicle. A total of 641 adult patients, pre-
dominantly female, with Fitzpatrick skin types I through IV
and moderate to severe melasma were randomized. The
primary efficacy analysis involved the proportion of intent-to-
significantly more of the patients treated with RA + HQ + FA
(26.1%) experienced complete clearing compared with the
other treatment groups (4.6%) at the end of week 8 (p <
.0001). In addition, at week 8, a 75% reduction in melasma/
pigmentation was observed in more than 70% of patients
treated with RA + HQ + FA compared with 30% in patients
treated with the dual-combination agents. Erythema, skin
peeling, burning, and/or stinging sensation were among the
most common adverse reactions. The majority of treatment-
related adverse events were of mild severity.
Community-based trial of a triple-combination agent for
the treatment of facial melasma. Grimes P, Kelly AP, Torok
H, Willis I. Cutis. 2006; 77(3):177–184.
This was a phase IV community-based trial with 1290 sub-
jects with moderate to severe melasma and a Fitzpatrick skin
type of I–VI. The efficacy parameters were the Melasma Area
and Severity Index (MASI) score which was found to decrease
significantly at weeks 4 and 8 compared with baseline in the
overall study population (p < 0.001). By week 8, investigator
global evaluations showed that 75% of patients had moderate
or marked improvement or were almost clear or clear.
(p < 0.001).

The combination of glycolic acid peels with a topical
regimen in the treatment of melasma in dark-skinned
patients: a comparative study. Sarkar R, Kaur C, Bhalla M,
Kanwar AJ. Dermatol Surg 2002; 28:828–832.
The purpose of this comparative study was to determine if
serial glycolic acid peels provide additional improvement
when combined with a time-tested topical regimen, a modifi-
cation of Kligman’s formula (hydroquinone 5%, tretinoin
0.05%, hydrocortisone acetate 1% in a cream base). All
recruited subjects had epidermal melasma as detected by
Wood’s light examination. 40 melasma patients of Indian
descent were divided into two groups of 20 each. One group
received serial glycolic acid peel combined with a topical
regimen, modified Kligman’s formula. The control group
received modified Kligman’s formula alone. The results were
evaluated by a clinical investigator both subjectively and with
photographs taken at baseline, 12 (before the fourth peel),
and 21 (3 weeks after the sixth peel) weeks. For clinical evalu-
ation, the Melasma Area and Severity Index (MASI) was used.
Results showed a significant decrease in the MASI score from
baseline to 21 weeks in both groups (p < .001). The group
receiving the glycolic acid peels showed a trend toward more
rapid and greater improvement, with statistically significant
results (p < . 001). Only a few side effects were observed in the
peel group. This study demonstrates that serial glycolic acid
peels provide an additional effect to a topical regimen which
is a modification of the time-tested Kligman’s regimen for
treating melasma in dark-complexioned individuals, if used
judiciously and under supervision.
A comparison of triple combination cream and hydroqui-
none 4% cream for the treatment of moderate to severe
facial melasma. Cestari TF, Hassun K, Sittart A, Viegas ML.
Presented as a poster at the 63rd Annual Meeting of the
American Academy of Dermatology. New Orleans, February
18–22, 2005.
The goal of this study was to compare the efficacy and safety
of a triple combination (TC) cream and monotherapy with 4%
hydroquinone (HQ) cream in the treatment of moderate to
severe facial melasma. 120 patients were enrolled to one of
two groups: TC cream once daily or HQ cream twice daily for
8 weeks. Evaluations included static global severity assessment
of melasma, improvement of melasma over time, local toler-
ability, and adverse events. TC cream was significantly more
effective than HQ cream from week 4 onwards: lesions were
approximately equivalent to the surrounding skin in 35% of
all TC-treated patients, compared to 5% of those who used
HQ cream (p = 0.0001). Improvement of more than 75% was
achieved by 73% of TC cream patients and 49% of HQ cream
patients (p = 0.007). Both groups reported similar adverse
events, which included erythema, burning sensation, and
desquamation. Results concluded that TC cream was more
effective than the HQ cream for the treatment of moderate to
severe facial melasma.
Topical retinoic acid (tretinoin) for melasma in black
patients. A vehicle-controlled clinical trial. Kimbrough-
Green CK, Griffiths CE, Finkel LJ, et╯al. Arch Dermatol 1994;
130:727–733.
10â•… Hyperpigmented Disordersâ•… •â•… Melasma
This 10-month, randomized, vehicle-controlled clinical
trial investigated the efficacy of topical 0.1% all-trans retinoic
acid (tretinoin) in the treatment of melasma in black patients.
28 of 30 black patients with melasma completed the study in
which they applied either 0.1% tretinoin or vehicle cream
daily to the entire face. They were evaluated clinically using
MASI (Melasma Area and Severity Index), colorimetrically, and
histologically. After 40 weeks, there was a 32% improvement
in the MASI score in the tretinoin treatment group compared
with a 10% improvement in the vehicle group. Colorimetric
measurements showed lightening of melasma after 40 weeks
of tretinoin treatment vs vehicle. Lightening of melasma, as
determined clinically, correlated well with colorimetric meas-
urements. Histologic examination of involved skin revealed a
significant decrease in epidermal pigmentation in the tretinoin
group compared with the vehicle group. Side effects were
limited to a mild ‘retinoid dermatitis’ occurring in 67% of
tretinoin-treated patients. This controlled study demonstrates
that topical 0.1% tretinoin lightens melasma in Black patients,
with minimal side effects.
Topical tretinoin (retinoic acid) improves melasma. A
vehicle-controlled, clinical trial. Griffiths CE, Finkel LJ, Ditre
CM, Hamilton TA, Ellis CN, Voorhees JJ. Br J Dermatol 1993;
129(4):415–421.
This randomized, vehicle-controlled study, enrolled 38
women to one of two treatment groups: 0.1% tretinoin (n =
19) or vehicle cream (n = 19) once daily to the face for 40
weeks. At the end of treatment 13 (68%) of 19 tretinoin-
treated patients were clinically rated as improved or much
improved, compared with 1 (5%) of 19 in the vehicle group
(p = 0.0006). After 24 weeks of tretinoin treatment significant
improvement was first apparent. Colorimetry (an objective
measure of skin colour) demonstrated a 0.9 unit lightening of
tretinoin-treated melasma and a 0.3 unit darkening with
vehicle (p = 0.01); these results correlated with clinical lighten-
ing (r = 0.55, p = 0.0005). Histologically, epidermal pigment
was reduced by 36% following tretinoin treatment, compared
with a 50% increase with vehicle (p = 0.002). Reduction in
epidermal pigment also correlated with clinical lightening
(r = −0.41, p = 0.01). Moderate cutaneous side effects of ery-
thema and desquamation occurred in 88% of tretinoin-treated
and 29% of vehicle-treated patients. Results concluded that
topical 0.1% tretinoin produces significant clinical improve-
ment of melasma, mainly due to reduction in epidermal
pigment, but improvement is slow.
Melasma. Kauh YC, Zachian TF. Adv Exp Med Biol 1999;
455:491–499.
In this study, 40 Korean women were placed in an open
label study using 0.1% retinoic acid in combination with 3%
hydroquinone. The results rated the treatment as excellent or
good improvement. 96% of the subjects had mild to moderate
reaction to treatment.
Adapalene in the treatment of melasma: a preliminary
report. Dogra S, Kanwar AJ, Parsad D. J Dermatol 2002;
29(8):539–540.
197
 Part 2 Pigmentary Disorders
This study compared the treatment of melasma with ada-
palene 0.1% vs 0.05% tretinoin. A total of 30 subjects
from India were randomized in a 14-week trial where they
were assigned to either group. Results showed that subjects in
the adapalene group had a 41% reduction in melasma treat-
ment area and severity index versus 37% in the tretinoin
group. The difference between the two groups was not statisti-
cally significant. Adverse events were significantly higher for
tretinoin patients, 63% vs 22% in the adapalene treated
subjects.
Second-Line Therapies
Azelaic acid A 29 females with melasma were enrolled in this double-
Kojic acid B
Double-blind comparison of azelaic acid and hydroquinone
in the treatment of melasma. Verallo-Rowell VM, Verallo V,
Graupe K, Lopez-Villafuerte L, Garcia-Lopez M. Acta Derm
Venereol Suppl (Stockh) 1989; 143:58–61.
The goal of this randomized, double-blind study was to
evaluate the clinical efficacy of azelaic acid (20%) and hydro-
quinone creams (2%) in the treatment of melasma. 155
patients of Indo-Malay-Hispanic origin were assigned to either
treatment group and instructed to apply study medication
twice daily. A broad spectrum sunscreen was used concomi-
tantly. Over a period of 24 weeks, 73% of the azelaic acid
patients, compared with 19% of the hydroquinone patients,
had good to excellent overall results, as measured by the
reduction of melasma pigmentary intensity and lesion size.
Transient mild to moderate irritant reactions were initially
seen with both test drugs.
The treatment of melasma. 20% azelaic acid versus 4%
hydroquinone cream. Baliña LM, Graupe K. Int J Dermatol
1991; 30(12):893–895.
This 24-week, double-blind study evaluated the efficacy of
20% azelaic acid cream and 4% hydroquinone cream, both
used in conjunction with a broad spectrum sunscreen for
melasma. 329 women were enrolled and assigned to either
treatment group. Over the treatment period, azelaic acid cream
yielded 65% with good or excellent results; however, no sig-
nificant treatment differences were observed with regard to
overall rating, reduction in lesion size, and pigmentary inten-
sity. Severe side effects such as allergic sensitization or exoge-
nous ochronosis were not observed with azelaic acid.
Topical azelaic acid in the treatment of melasma: pharma-
cological and clinical considerations. In: Graupe K, Balina
LM. Melasma – new approaches to therapy. London: Martin-
Dunitz; 1995:19–41.
50 subjects with melasma were enrolled in this open-label,
randomized study for 24 weeks. Subjects were assigned to
receive either 20% azelaic acid or 20% azelaic acid with
tretinoin 0.05%. Results demonstrated the combination
group as having excellent results (34.8%) vs 5.3% of the
azelaic acid group with excellent results.
198
Third-Line Therapies
Glycolic acid D
Vitamin C D
Botanicals D
Laser treatment D
A randomized, double-blind, placebo-controlled trial of
vitamin C iontophoresis in melasma. Huh C, Seo K, Park J,
Lim J, Eun H, Park K. Dermatology 2003; 206:316–320.
blind, placebo-controlled trial. The purpose of this study was
to evaluate the efficacy of vitamin C iontophoresis for melasma
patients. For iontophoresis, a vitamin C solution was applied
to one side of the face, while distilled water was applied to the
other side as a control. The L (luminance) value was measured
by a colorimeter to obtain an objective pigmentation para�
meter. 12 weeks after iontophoresis, the colorimeter of the
treated site showed a significant decrease in the L value (from
4.60 to 2.78, p = 0.002), compared to that of the control site
(from 4.45 to 3.87, p = 0.142). The results showed that vitamin
C iontophoresis may be an effective treatment modality for
melasma.
Experience with a strong bleaching treatment for skin
hyperpigmentation in Orientals. Yoshimura K, Harii K,
Aoyama T, Iga T. Plast Reconstr Surg 2000; 105(3):1097–1108;
discussion 1109–10.
In this study, 136 Oriental patients were analyzed and fol-
lowed for more than 12 weeks. The treatment protocol was
composed of two steps: bleaching (2–6 weeks) and healing
(2–6 weeks); 0.1–0.4% all-trans retinoic acid aqueous gel
was originally prepared and applied concomitantly with
hydroquinone-lactic acid ointment for bleaching. After obtain-
ing sufficient improvement of the hyperpigmentation, a
corticosteroid was applied topically with hydroquinone and
ascorbic acid for healing. Improvement was evaluated with a
narrow-band reflectance spectrophotometer. The results were
successful in more than 80% of cases of senile lentigines and
post-inflammatory hyperpigmentation, especially on the face.
60% of cases of nevus spilus were also successfully treated.
Although the transient adverse effects of this treatment may be
more severe than conventional treatment, this strong bleach-
ing protocol improves a variety of hyperpigmented lesions,
including nevus spilus, with a higher success rate and a shorter
treatment period than conventional protocols.
Oral intake of proanthocyanidin-rich extract from grape
seeds improves chloasma. Yamakoshi J, Sano A, Tokutake S,
et╯al. Phytother Res 2004; 18(11):895–899.
This study investigated the reducing effect of proanthocya-
nidin, a powerful antioxidant, on chloasma in a one-year open
design study. 12 Japanese women received proanthocyanidin-
rich grape seed extract (GSE) orally. The treatment was admin-
istered to candidates with chloasma for 6 months between
 10â•… Hyperpigmented Disordersâ•… •â•… Mongolian spots
August 2001 and January 2002 and to 11 of these 12 for 5
months between March and July 2002. Clinical observation,
L* value (luminance) and melanin index, and size (length and
width) measurements of chloasma were performed through-
out the study period. The first 6 months of GSE intake improved
or slightly improved chloasma in 10 of the 12 women (83%,
p < 0.01) and the following 5 months of intake improved or
slightly improved chloasma in 6 of the 11 candidates (54%, p
< 0.01). L* values also increased after GSE intake (57.8 ± 2.5
at the start vs 59.3 ± 2.3 at 6 months and 58.7 ± 2.5 at the end
of study). Melanin index significantly decreased after 6 months
of the intake (0.025 ± 0.005 at the start vs 0.019 ± 0.004 at 6
months; p < 0.01), and also decreased at the end of the study
(0.021 ± 0.005; p < 0.05). GSE is effective in reducing the
hyperpigmentation of women with chloasma. The beneficial
effects of GSE were maximally achieved after 6 months and
there was no further improvement after this period. The latter
GSE intake for 5 months may prevent chloasma from becom-
ing worse prior to the summer season. GSE is safe and useful
for improving chloasma.
Combination treatment of melasma with pulsed CO2 laser
followed by Q-switched alexandrite laser: a pilot study.
Nouri K, Bowes L, Chartier T, Romagosa R, Spencer J. Dermatol
Surg 1999; 25(6):494–497.
The objective of this study was to compare pulsed CO2 laser
alone with the combination of pulsed CO2 laser followed by
Q-switched alexandrite laser in the treatment of dermal-type
melasma. 4 patients were randomly chosen for each treatment
arm. This combination is proposed to be effective by first
destroying the abnormal melanocytes with the pulsed CO2
laser and then selectively eliminating the dermal melanin with
the alexandrite laser. Patients received multiple follow-up
visits for examination by an objective blinded investigator. All
patients in the combination laser group showed complete
resolution, and 2 patients in the CO2 laser only group had
peripheral hyperpigmentation in the long-term follow-up
evaluation. The results showed that these laser therapies are
safe from scarring and infection. The combination laser
therapy was highly effective in removing the hyperpigmenta-
tion and all patients in this group showed complete resolution
without any peripheral hyperpigmentation.
Commonly encountered pitfalls
Pregnancy is commonly associated with melasma. Agents used
to treat melasma may be either teratogenic or insufficiently
Mongolian spots
Mongolian spots (MS), a type of dermal melanocytosis
involves the lumbosacral area of healthy infants (Fig. 10.10).1,2
The buttocks, flanks, and shoulders may be affected. The
studied to be considered safe during pregnancy or during
lactation.
Although lasers have been used to treat melasma, the
majority of studies show that lasers may exacerbate the
condition, minimally improve it, or produce unwanted post-
inflammatory hyperpigmentation. The physician should use
caution when considering laser treatment and select lasers
appropriate for the patient’s skin type.
Discontinuation of oral contraceptives is recommended as
an adjunct to treatment but it is imperative that another
method of contraception be suggested as an alternative.
Special management & counseling considerations
The psychosocial impact of melasma on the patient is an
aspect of the disease that requires close attention by clinicians.
Emotional support and reassurance are key. The patient must
understand that while treatment is available, improvement
may be incomplete and slow.
Management of melasma also includes the use of camou-
flaging cosmetics and sun protection in the form of sunscreen
and protective clothing. The use of broad-spectrum sunscreens
of at least SPF 30, applied daily and re-applied every 2 hours
is critically important for the treatment of melasma. Sun-
screens should be used on a daily basis. Abrasive cleansers
should also be avoided.
References
1. Ortonne JP, Bissett DL. Latest insights into skin hyperpigmentation.
J Invest Dermatol Symp Proc 2008; 13:10–14.
2. Draelos ZD. Melasma: introduction and disease background. In:
Flucinolone acetonide, hydroquinone and tretinoin: unique and
effective combination treatment for melasma. Virtual Symposium
CD-ROM, 2001.
3. Rendon MI. Utilizing combination therapy to optimize melasma out-
comes. J Drugs Dermatol 2004; 3(5 Suppl):S27–S34.
4. Sanchez NP, Pathak MA, Sato S, Fitzpatrick TB, Sanchez JL, Mihm MC.
Melasma: a clinical, light microscopic, ultrastructural, and immun-
ofluorescence study. J Am Acad Dermatol 1981; 4:698–710.
5. Grimes PE. Melasma. Etiologic and therapeutic considerations. Arch
Dermatol 1995; 131:1453–1457.
6. New Zealand Dermatological Society. Melasma. http://dermnetnz.org/
colour/melasma.html [accessed September 22, 2009].
lesions are almost always blue or gray in color. The diameter
of the lesions is usually several centimetres in diameter. One
macule or patch may be present, however, some patients may
have numerous lesions. Abnormal melanocyte migration has
been theorized as one cause of MS.
Mongolian spots are usually present at birth or appear
within the first weeks of life.1 Several ethnic groups are
199
 Part 2 Pigmentary Disorders

Table 10.4╇ Prevalence of skin manifestations*

School-aged Pre-school-aged
Skin manifestation children children

Dermatitis and/or eczema related

Xerosis 536 (37.8) 118 (8.3)
Dennie Morgan fold 143 (10.1) 48 (3.4)
Keratosis pilaris 220 (15.5) 53 (3.7)
Atopic dermatitis 73 (5.1) 32 (2.3)
†
Pityriasis alba 12 (0.8) 6 (0.4)
Others 23 (1.6) 11 (0.8)
Disorders of pigmentation
Figure 10.10:╇ Mongolian spot. (From Johnson, Moy, White: Ethnic Skin – Medical
Acquired melanocytic nevi 558 (39.4) 202 (14.3)
and Surgical, Mosby Inc., copyright Elsevier 1998.)
Mongolian spot‡ 0 103 (7.3)
‡
Café au lait macules 93 (6.6) 58 (4.1)
particularly prone to MS, with Asians as the highest among Congenital melanocytic nevi 47 (3.3) 39 (2.8)
them. It is observed in more than 90% of Asian infants. Laude Others 72 (5.1) 18 (1.3)
reports that over 95% of African-American babies have Mon-
golian spots (Table 10.4). Cutaneous infections
In a study of Nigerian children, 369 neonates and 484 Varicella scars 103 (7.3) 16 (1.1)
children aged 1 month to 14 years were evaluated for the pres- Viral 25 (1.8) 13 (0.9)
ence of MS. MS were present in over 381 children with an Bacterial 19 (1.3) 4 (0.3)
overall incidence of 44.7% (74.8% of neonates and 13.6% of
pre-school children). There was no sexual predilection. Traces Fungal 37 (2.6) 3 (0.2)
of MS disappeared with advanced age and no MS were found Disorders of the 343 (24.2) 0
in children over 6 years old.2 However, in some instances MS pilosebaceous unit
can persist for life (Fig. 10.11).3 Vascular lesions 37 (2.6) 58 (4.1)
Although MS are typically benign blue-gray discolorations, Hair disorders 46 (3.3) 3 (0.2)
extensive Mongolian spots can indicate possible inborn errors
of metabolism. There was a report of three infants with exten- Nail disorders 26 (1.8) 7 (0.5)
sive MS of whom two had GM1 gangliosidosis type 1, and a *Data are reported as number (percentage) of affected children.
third had an associated Hurler Syndrome. It is therefore †
Male predominance (p < .02).
important to diagnose extensive MS so that early treatment ‡
There is a significant correlation between coexistence of Mongolian spots and café au
may be possible.4 lait macules (p < .001).
In another observational report from Northern Italy, 620
healthy neonates were examined to study birthmarks and tran-
sient cutaneous lesions in newborns of different ethnic groups.
Hyperpigmentation in the genital area and MS were positively Laser treatment of 26 Japanese patients with Mongolian
associated with geographical area of origin and were more spots. Kagami S, Asahina A, Watanabe R et╯al. Dermatol Surg
common in non-European neonates. There was a positive cor- 2008; 34(12):1689–1694.
relation between melanocytic congenital nevi in Asian new- 26 patient study in which the Q-switched alexandrite laser
borns as well as a salmon patch on the nape of women who was used to treat MS with a good outcome. Of interest, the
were greater than 35 years of age.5 authors found that better outcomes were achieved when treat-
Since MS are benign lesions which may rapidly disappear, ments were started at a younger age. Therefore, a recommenda-
treatment is not necessary. However, if lesions of MS are exten- tion was made to begin treatment for sacral and extra-sacral
sive, the physician should examine the neonate for a possible MS before the age of 20.
genodermatosis.
Aberrant Mongolian spot. Kobayashi M, Kubota J, Ogo K.
Japanese J Plast Reconstr Surg 2001; 44:1193–1196.
First-Line Therapies The Q-switched Ruby laser and Q-switched Nd-YAG laser
were successful for treatment of aberrant Mongolian spots
Q-switched Ruby laser and Q-switched Nd-YAG laser D (lesions that persist past the age of 5 or 6). As in the above
study, treatment at a younger age is preferred.

200

Figure 10.11:╇ The Mongolian spot is found on the sacrum or low back at birth
and tends to fade, often disappearing completely within a few years. (From White &
Cox, Diseases of the Skin, A Color Atlas and Text, 2E, Mosby Inc, copyright Elsevier
2006.)
Special management & counseling considerations
Mongolian spots have been confused with ecchymotic lesions
resulting from child abuse. Parents of children with Mongo-
lian spots have been falsely accused of child abuse. In these
cases, the specialist must educate and provide clarification
about the differences between these lesions.6 Additionally, it
Nevus of Ota
The etiology of Nevus of Ota is unknown. It commonly occurs
on the face, namely the periocular skin and sclera, and repre-
sents dermal melanocytes in the epidermis.1 It is described
as a speckled, bluish-brownish and even grayish facial
patch. Of interest, its distribution has been known to follow
that of the first and second branches of the trigeminal nerve2
(Figs. 10.12, 10.13).
Pigmentation can be unilateral or bilateral and can also
involve the buccal mucosa.3 Histologically it is indistinguish-
able from a Nevus of Ito, except that the latter are found on
the shoulder and upper arms as opposed to the face.4 Its onset
occurs in the early years of life and lesions can multiply in
number and converge.5 The incidence of this condition is
common in Asian populations, with an estimated prevalence
in Japanese society of 0.2–1%.6
Disturbingly Nevi of Ota have been associated with deaf-
ness.7 Of even more concern, malignant transformations have
been reported.8,9
10â•… Hyperpigmented Disordersâ•… •â•… Nevus of Ota
is important to carefully document location and size of the
Mongolian spot.
Although parents should be reminded of the benign and
temporal nature of most lesions, they should also be encour-
aged to visit a pediatric endocrinology specialist to rule out a
metabolic disorder.
Commonly encountered pitfalls
Mongolian spots have been found in children with a multi-
tude of various diseases. Extensive, aberrant Mongolian spots
in children with mucopolysaccharidosis and GM1 ganglio�
sidosis have been reported and should merit evaluation by a
specialist well versed in inborn errors of metabolism.
References
1. Kibbi AG, Bahhady RF, Tannous Z, et al. Mongolian spot. http://
emedicine.medscape.com/article/1068732-overview [accessed Septem�
ber 15, 2009].
2. Onayemi O, Adejuyigbe EA, Torimiro SE, et al. Prevalence of Mon�
golian spots in Nigerian children in Ile-Ife, Nigeria. Niger J Med 2001;
10(3):121–123.
3. Cordova A. The Mongolian spot: a study of ethnic differences and a
literature review. Clin Pediatr (Phila) 1981; 20(11):714–719.
4. Rybojad M, Moraillon I, Ogier de Baulny H, et al. Extensive Mongolian
spot related to Hurler disease. Ann Dermatol Venereol 1999;
126(1):35–37.
5. Boccardi D, Menni S, Ferraroni M, et al. Birthmarks and transient skin
lesions in newborns and their relationship to maternal factors: a pre-
liminary report from northern Italy. Dermatology 2007; 215(1):
53–58.
6. Laude TA. Approach to dermatologic disorders in black children.
Semin Dermatol 1995; 14(1):15–20.
Cosmetic makeup can minimize the disfiguring facial pig-
mentation resulting from Nevus of Ota. Otherwise, topical
therapy is of no value in medical treatment. Some surgical
procedures have shown results in treating Nevus of Ota.
First-Line Therapies
Q-switched ruby laser.10,11,12,13 C
Pulsed Q-switched laser surgery is unquestionably the
current treatment of choice for Nevi of Ota and Ito. It works
via selective photothermal and photomechanical destruction
of dermal melanocytes and melanophages. High success rates
and minimal adverse effects have been reported with the
Q-switched ruby,3 Q-switched alexandrite,1,2 and Q-switched
Nd:YAG lasers.1 After 4–8 treatments, skin pigmentation is
reduced dramatically or removed in 90–100% of cases, with
< 1% risk of scarring.
201
 Part 2 Pigmentary Disorders
Figure 10.12:╇ Nevus of Ota in a black skinned child. (From Johnson, Moy, White:
Ethnic Skin – Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)
Figure 10.13:╇ Nevus of Ota-like macules. This condition is common in East-Asian
women and may be confused with sun damage. (From White & Cox, Diseases of
the Skin, A Color Atlas and Text, 2E, Mosby Inc., copyright Elsevier 2006.)
Nevus of Ota: treatment with high energy fluences of the
Q-switched ruby laser. Lowe NJ, Wieder JM, Sawcer D, et╯al.
J Am Acad Dermatol 1993; 29(6):997–1001.
A 16 patient study in which a Q-switched ruby laser was
used to treat Nevi of Ota. After two treatments, 44% of patients
showed > 50% improvement. With three treatments, 85% of
patients showed > 50% improvement. After four treatments,
100% of the patients showed > 50% improvement. No seque-
lae from the laser were noted.
Other surgical methods have been superseded by laser
surgery. They include:
202
• cryotherapy4
• microsurgery
• dermabrasion (alone or combined with other modalities,
such as carbon dioxide snow, autologous epithelial
grafting)
• sequential dry ice epidermal peeling.
Commonly encountered pitfalls
Malignant degeneration of Nevi of Ito and Ota have been
reported and the clinician should be mindful of changes that
are suggestive of melanoma. Furthermore, Nevi of Ota with
ocular involvement present an increased risk of choroidal
melanoma and glaucoma. Regular ophthalmic examinations
should be recommended.
Special management & counseling considerations
Nevi of Ota/Ita present cosmetic concerns to parents during
early childhood and to the patient from adolescence through
adulthood. Therefore, it is important to carefully discuss avail-
able cosmetics and surgical treatments.
References
1. Mishima Y. Melanocytic tumors. In: Zelickson AS, ed. Ultrastructure
of normal and abnormal skin. Philadelphia: Lea & Febiger; 1967:
388–424.
2. Carleton A, Biggs R. Diffuse mesodermal pigmentation with congeni-
tal cranial abnormality. Br J Dermatol Syphilol 1948; 60:10–33.
3. Dermnet NZ. Naevi of Ota and Ito. http://www.dermnet.org.nz/
lesions/naevus-ota-ito.html. [Accessed December 19, 2009].
4. Lui H, Zhou Y. Nevi of Ota and Ito. Emedicine. http://emedicine.
medscape.com/article/1058580-overview [Accessed December 19,
2009].
5. Fitzpatrick TB, Zeller R, Kukita A, et al. Ocular and dermal melanocy-
tosis. AMA Arch Ophthalmol 1956; 56:830–832.
6. Turnbull JR, Assaf Ch, Zouboulis C, Tebbe B. Bilateral naevus of Ota:
a rare manifestation in a Caucasian. J Eur Acad Dermatol Venereol
2004; 18(3):353–355.
7. Alvarez-Cuesta CC, Raya-Aguado C, Vázquez-López F, et al. Nevus
of Ota associated with ipsilateral deafness. J Am Acad Dermatol 2002;
47(5 Suppl):S257–S259.
8. Patterson CR, Acland K, Khooshabeh R. Cutaneous malignant
melanoma arising in an acquired naevus of Ota. Australas J Dermatol
2009; 50(4):294–296.
9. Dorsey CS, Montgomery H. Blue Nevus and its distinction from
Mongolian Spot and the naevus of ota. J Invest Dermatol 1954;
22:225–236.
10. Watanabe S, Takahashi H. Treatment of nevus of Ota with the
Q-switched ruby laser. N Engl J Med 1994; 331(26):1745–1750.
11. Chan HH, Leung RS, Ying SY, et al. A retrospective analysis of compli-
cations in the treatment of nevus of Ota with the Q-switched alexan-
drite and Q-switched Nd:YAG lasers. Dermatol Surg 2000; 26(11):
1000–1006.
12. Wang HW, Liu YH, Zhang GK, et al. Analysis of 602 Chinese cases of
nevus of Ota and the treatment results treated by Q-switched alexan-
drite laser. Dermatol Surg 2007; 33(4):455–460.
13. Chan HH, Leung RS, Ying SY, et al. A retrospective analysis of compli-
cations in the treatment of nevus of Ota with the Q-switched alexan-
drite and Q-switched Nd:YAG lasers. Dermatol Surg 2000; 26(11):
1000–1006.
 10â•… Hyperpigmented Disordersâ•… •â•… Pigmentary demarcation lines

Commonly encountered pitfalls

Pigmentary The development of pigmentary demarcation lines in a female

demarcation lines may signal pregnancy. Cases of hormonal imbalances in non-

pregnant women with sudden onset of pigmentary demarca-
tion lines are of interest but do not infer any medical problem.
Pigmentary demarcation lines (PDL), also known as Futcher’s
lines or Voight’s lines were first described by the Viennese
anatomist Christian A. Voight. Although there is no known
etiology, this condition is associated with pregnancy.1 Interest-
ingly, there is a recent case of a 51-year-old amenorrheic
Chinese woman who developed PDL which were attributed to
a hormonal imbalance.
PDL are more common in African and Japanese popula-
tions. There is no evidence that supports an age or sex predilec-
tion. The lines are classified into six different types based on
anatomical location: type A, B, C, D, E, and F.2
• Type A – lines run along the upper limb with variable
trans-pectoral extensions. They are commonly observed
in Japanese women as well as in Hispanics and Blacks
(Fig. 10.14).
• Type B – lines run along the lower limbs. They have
been observed in Japanese women and are accentuated
during pregnancy in Hispanic women with post-partum
resolution.
• Type C – lines present as paired median or paramedian
lines on the chest with midline abdominal extension. They
have been reported in African-American and Japanese
women.
• Type D – lines present on the posteromedial area of the
spine can mimic tinea versicolor, vitiligo and post-
A
inflammatory hypopigmentation.
• Type E – Hypopigmented macules located on the chest
extending from the clavicle to the periareolar skin; typically
bilaterally symmetrical.
• Type F – Lines on the face.

First-Line Therapy

Q-switched alexandrite laser E

Treatment of PDL may be considered a cosmetic problem.

However, patients have been treated with the Q-switched alex-
andrite laser.

Effective treatment of Futcher’s lines with Q-switched alex-

andrite laser. Bukhari IA. J Cosmet Dermatol 2005; 4(1):
27–28.
Case report of a young female patient who presented with B
type A pigmentary demarcation lines on the anterolateral
aspect of both arms, which were satisfactorily treated with a Figure 10.14:╇ Type A pigmentary demarcation lines. (From Johnson, Moy, White:
Q-switched alexandrite laser with no adverse effects. Ethnic Skin – Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)

203
 Part 2 Pigmentary Disorders

Special management & counseling considerations References

Commonly found in individuals with ethnic skin, these
benign findings should be of little concern to patients.
Camouflage with cosmetics and laser therapy can be offered
as treatment. Pregnant women whose development of PDL is
attributed to pregnancy can expect resolution after delivery.
1. James WD, Meltzer MS, Guill MA, Berger TG, Rodman OG. Pigmentary
demarcation lines associated with pregnancy. J Am Acad Dermatol
1984; 11:438–440.
2. Selmanowitz VJ, Krivo JM. Pigmentary demarcation lines. Comparison
of Negroes with Japanese. Br J Dermatol 1975; 93:371–377.

as keratinocytes may play an active part in the pathogenesis of

Post-inflammatory the condition.1 Cytokines and inflammatory mediators that

stimulate melanocytes2 and melanogenesis include: endothe-

hyperpigmentation (PIH)
Post-inflammatory hyperpigmentation (PIH) is a very common
disorder in black, Hispanics and Asian patients.1 It can occur
as sequela of virtually any inflammatory condition (Table 10.5,
Figs 10.15–10.17). Papulosquamous and vesiculobullous dis-
eases are also commonly associated conditions.1 The etiology
of PIH is unknown. However, the specific release of inflamma-
tory mediators and cytokines from inflammatory cells as well
lins, prostaglandin D2 and E2, interleukin 1 and 6, and tumor
necrosis factor alpha.3 A decrease in melanogenesis has been
reported to be caused by C4. Movement of melanocytes
can be caused by leukotriene, C4, and transforming growth
factor alpha.2 Mediators may be specific for each skin condi-
tion and responsible for either increased melanogenesis or

Table 10.5╇ Causes of post-inflammatory hyperpigmentation

• Allergic reactions
• Infections, trauma
• Phototoxic eruptions
• Acne excoriée
• Lichen planus
• Systemic lupus erythematosus
• Chronic dermatitis
• Cutaneous T-cell lymphoma
Figure 10.16:╇ Post-inflammatory hyperpigmentation from tinea corporis.

Figure 10.17:╇ Post-inflammatory hyper- and hypo-pigmentation secondary to a

Figure 10.15:╇ Post-inflammatory hyperpigmentation from arthropod bites. laser burn.

204
 10â•… Hyperpigmented Disordersâ•… •â•… Post-inflammatory hyperpigmentation (PIH)
decreased melanogenesis, leading to hyperpigmentation or
hypopigmentation.
The goal of therapy is treatment of the underlying disease
and prevention of PIH. It must be said that many of the treat-
ments that are effective for PIH are also effective for melasma,
thus consulting the section on melasma earlier in this chapter
is suggested.
First-Line Therapies
Hydroquinone B
Topical combination therapy:
Hydroquinone 4%, 0.05% tretinoin A
Hydroquinone 4% and retinol 0.15% C Topical azelaic acid
The effectiveness & safety of Lustra (hydroquinone USP
4%) in dyschromia. Rizer R, Sklar J, Hino P, et╯al. Skin &
Aging 1999; (Suppl 1):4–8.
Single-blind, randomized, controlled, 12-week study com-
paring the efficacy and tolerance of hydroquinone 4% vs
hydroquinone 3% vs hydroquinone cream 4% with sunscreens
SPF 17. The study included 69 female subjects (35–55 years
old) with relatively equal numbers of Caucasian, Asian, and
African-American individuals. Hydroquinone 4% had a faster
onset of activity and a greater decrease in pigmentation when
compared to the two other treatment arms. In addition, Lustra
showed improvement in fine lines, smoothness, and clarity
compared to the other agents.
Study of hydroquinone USP 4%, 0.05% tretinoin, and in
combination in UV-induced dyschromia with actinic photo-
damage. Swinyer LJ, Wortzman M. Cosmetic Dermatol 2000;
13:13–18.
Investigator-blind, randomized, controlled study compar-
ing the efficacy and safety of hydroquinone cream 4% cream
vs tretinoin emollient cream 0.05% vs hydroquinone cream
4% cream plus tretinoin emollient cream 0.05%. 42 subjects
with moderate-to-severe facial dyschromia and actinic photo-
damage were evaluated for 12 weeks. The cream was applied
twice daily and subjects were also provided with a sunscreen
(SPF 25) and a moisturizer. Investigators assessed blotchiness,
mottled hyperpigmentation, PIH, and surface roughness. The
group using hydroquinone cream 4% alone and the group
using tretinoin emollient cream 0.05% plus hydroquinone
cream 4% cream produced a more rapid and greater reduction
in mottled hyperpigmentation compared to tretinoin emol-
lient cream 0.05% alone.
A microsponge formulation of hydroquinone 4% and
retinol 0.15% in the treatment of melasma and post-
inflammatory hyperpigmentation. Grimes PE. Cutis 2004;
74(6):362–368.
25 patient open-label study of hydroquinone 4% and
retinol 0.15% applied twice daily for 12 weeks. Disease
severity, pigmentation intensity, lesion area, and colorimetry
assessments were evaluated. A broad-spectrum sunscreen was
applied once in the morning, 15 minutes after application of
the test product. Patients were evaluated at baseline and at 4,
8, and 12 weeks. HQ 4% and retinol 0.15% formulation pro-
duced improvement at all study endpoints. Improvement in
disease severity and pigmentation intensity was statistically
significant at weeks 4, 8, and 12 compared with baseline (p <
0.001). Lesion area and colorimetry measurements also were
significantly improved at each visit (p < 0.001). The treatment
was deemed safe and effective.
Second-Line Therapies
A
Kojic acid B
Chemical peels B
Azelaic acid 20% cream in the treatment of facial hyperpig-
mentation in darker-skinned patients. Lowe NJ, Rizk D,
Grimes P, et╯al. Clin Ther 1998; 20(5):945–959.
Multicenter, randomized, double-masked, parallel-group
study assessing the efficacy, safety, and tolerability of azelaic
acid 20% cream compared to vehicle for the treatment of facial
hyperpigmentation in darker-skinned patients, Fitzpatrick skin
types IV–VI. Subjects were treated for 24 weeks. Azelaic acid
produced significantly greater decreases in pigmentary inten-
sity than did vehicle as measured by both investigator’s subjec-
tive scale (p = 0.021) and chromometer analysis (p = 0.039).
There was significantly greater overall improvement with
azelaic acid than with placebo at week 24 (p = 0.008). Adverse
events experienced with the treatment arm included burning
and stinging.
Melanin hyperpigmentation of skin: melasma, topical treat-
ment with azelaic acid, and other therapies. Breathnach AS.
Cutis 1996; 57(1 Suppl):36–45.
Topical 20% azelaic acid is superior to 2% hydroquinone
and as effective as 4% hydroquinone in the treatment of post-
inflammatory hyperpigmentation. The effect of azelaic acid
can be attributed to its ability to inhibit the energy production
and/or DNA synthesis of hyperactive melanocytes, and par-
tially to its anti-tyrosinase activity.
The combination of glycolic acid and hydroquinone or kojic
acid for the treatment of melasma and related conditions.
Garcia A, Fulton JE. Dermatol Surg 1996; 22(5):443–447.
39 patients were treated with kojic acid on one side of the
face and hydroquinone in a similar vehicle on the other side
of the face. 51% of the patients responded equally to hydro-
quinone and kojic acid. 28% had a more dramatic reduction
in pigment on the kojic acid side; whereas 21% had a more
dramatic improvement with the hydroquinone formulation.
These results were not statistically different. The kojic acid
preparation was more irritating.
205
 Part 2 Pigmentary Disorders

Treatment of melasma using kojic acid in a gel containing

hydroquinone and glycolic acid. Teng Ee Lim J. Dermatol
Surg 1999; 25:282–284.
40 women with epidermal melasma were treated with 2%
kojic acid in a gel containing 10% glycolic acid and 2% hyd-
roquinone on one half of the face. The other half was treated
with the same application but without kojic acid. At 12 weeks,
more than half of the melasma cleared in 24/40 (60%) patients
receiving kojic acid compared to 19/40 (47.5%) patients
receiving the gel without kojic acid. Again, redness, stinging,
and exfoliation were observed side effects.
Many of the treatments that are effective for PIH are also effec-
tive for melasma and vice versa.

Glycolic acid peels for post-inflammatory hyperpigmenta-

tion in Black patients. A comparative study. Burns RL,
Prevost-Blank PL, Lawry MA. Dermatol Surg 1997;
23(3):171–175.
19 patients with Fitzpatrick skin type IV, V, or VI were ran-
domized to a control or peel group. The control group applied
2% hydroquinone/10% glycolic acid gel twice daily and 0.05%
tretinoin cream at night. The peel patients used the same
topical regimen and, in addition, received six serial glycolic Figure 10.18:╇ Halo of hypopigmentation from hydroquinone treatment.
acid peels (68% maximum concentration). The patients receiv-
ing the glycolic acid peels showed a trend toward more rapid
and greater improvement. The peel group also experienced
increased lightening of the normal skin.
Commonly encountered pitfalls
The safety and efficacy of salicylic acid chemical peels in Patients must be cautioned about the protracted nature of
darker racial-ethnic groups. Grimes PE. Dermatol Surg 1999; post-inflammatory hyperpigmentation which may take
25(1):18–22. months or years to resolve. Treatments may be partially effec-
25 patients with skin types V and VI, with various inflam- tive or in the case of dermal pigmentation, ineffective.
matory cutaneous disorders (including 5 with PIH) were pre- For patients with darker skin tones, a variety of surgical,
treated for 2 weeks with hydroquinone 4% prior to undergoing cosmetic or laser treatments may lead to post-inflammatory
a series of five salicylic acid chemical peels. The concentrations hyperpigmentation (Fig. 10.17). It is important to inform the
of the salicylic acid peels were 20% and 30%. The peels were patient prior to any of these procedures of this possible
performed at 2-week intervals. Moderate to significant improve- consequence.
ment was observed in 88% of the patients. Minimal to mild Treatment of post-inflammatory hyperpigmentation with
side effects occurred in 16%. products containing hydroquinone as the active ingredient
may result in a ‘halo’ of hypopigmentation surrounding
the treatment area (Fig. 10.18). The patient should be reas-
Third-Line Therapies sured that this halo will resolve spontaneously once the
hydroquinone-containing product is discontinued.
Q-switched ruby laser D

Special management & counseling considerations

Ineffective treatment of refractory melasma and postinflam-
matory hyperpigmentation by Q-switched ruby laser. Taylor
CR, Anderson RR. J Dermatol Surg Oncol 1994; 20(9):
592–597.
8 subjects with melasma or post-inflammatory hyperpig-
mentation refractory to traditional treatments were treated
with Q-switched ruby laser pulses. No permanent improve-
ment and, in some cases, darkening was seen in each type of
lesion. Several months later, epidermal pigmentation had
returned to baseline. This is an ineffective and sometimes
counterproductive treatment.
Sun protection and daily use of SPF 30 or higher sunscreens
are essential management strategies. Broad-spectrum sun-
screens must be used and re-applied every 2 hours. Patients
must be counseled on discontinuation of any offending
agent.
Patients should be warned about the use of corticosteroid-
containing products for the treatment of post-inflammatory
hyperpigmentation. These agents are often obtained from
beauty supply stores in major metropolitan areas. They have
been illegally imported into the United States.

206
 10â•… Hyperpigmented Disordersâ•… •â•… Solar lentigines

3. Morelli JG, Kincannon J, Yohn JJ, et al. Leukotriene C4 and TGF-alpha

References are stimulators of human melanocyte migration in vitro. J Invest
Dermatol 1992; 98(3):290–295.
1. Halder RM, Nootheti PK. Ethnic skin disorders overview. J Am Acad
Dermatol 2003; 48(6 Suppl):S143–S148.
2. Morelli JG, Norris DA. Influence of inflammatory mediators and
cytokines on human melanocyte function. J Invest Dermatol 1993;
100(2 Suppl):191S–195S.

Solar lentigines may show a linear increase in the melano-

Solar lentigines cytes at the dermato-epidermal junction.4 Characteristics of

solar lentigines are found in Table 10.6

Solar lentigines are usually well demarcated brown macules

which result from an increased number of melanocytes in the First-Line Therapies
epidermis.1 They may vary in color from light brown to black
and vary in size from a millimeter to a few centimeters.2 Solar
Photoprotection
lentigines can coalesce and are found in sun exposed areas,
e.g. hands, arms, shoulder and face (Figs. 10.19, 10.20). They Broad spectrum sunscreen
usually begin after the 4th decade of life and may occur after Protective clothing and hats
acute or chronic sun exposure. Retinoids B
There are certain diseases which may be associated with
lentigines:3 Phenolic compounds
Hydroquinone 2–4% C
• Lentigo simplex 2% 4-hydroxyanisone/tretinoin A
• Multiple lentigines syndrome (LEOPARD)
Hydroquinone/tretinoin B
• Peutz–Jeghers syndrome
• LAMB (name/myxoma) syndrome
• Centrofacial lentigines
• Nevus spilus
• Agminated lentigines
• Lentigo maligna
• Solar lentigines.

Figure 10.20:╇ Solar lentigines on the upper back.

Table 10.6╇ Characteristics of Solar Lentigines

Brown to black macules ranging in size from 1 mm to several

centimeters
Increase in melanin production, possible increased number of
melanocytes
Occurs only in the epidermis
Induced by UV light
More common in skin types I–III
Figure 10.19:╇ Solar lentigines.

207
 Part 2 Pigmentary Disorders
The combination of 2% 4-hydroxyanisole (mequinol) and
0.01% tretinoin is effective in improving the appearance of
solar lentigines and related hyperpigmented lesions in two
double-blind multicenter clinical studies. Fleischer AB Jr,
Schwartzel EH, Colby SI et╯al. J Am Acad Dermatol 2000;
42:459–467.
This study evaluated subjects that were either randomized
to treatment with topical 2% 4-HA / 0.01% tretinoin solution,
2% 4-HA or 0.01% tretinoin or vehicle (placebo). The 4-HA/
tretinoin combination was found to be superior to either of
the active components alone or placebo.
Topical tretinoin (retinoic acid) treatment for liver spots
associated with photodamage. Rafal ES, Griffiths CE, Ditre
CM, et╯al. N Engl J Med 1992; 326(6):368–374.
A 10-month randomized double-blind study of 58 patients
who applied either 0.1% tretinoin (28) or placebo cream daily
to the face, upper extremities, or both. After 1 month of treat-
ment, the patients treated with tretinoin had improvement of
hyperpigmented lesions as compared with the patients who
received placebo. After 10 months, 20 (83%) of the 24 patients
with facial lesions who were treated with tretinoin had lighten-
ing of these lesions, as compared with 8 (29%) of the 28
patients with facial lesions who received placebo. The results
for lesions of the upper extremities were similar.
Analytic quantification of solar lentigines lightening by a
2% hydroquinone-cyclodextrin formulation. Petit L, Piérard
GE. J Eur Acad Dermatol Venereol 2003; 17:546–549.
30 Asian adults applied a 2% hydroquinone-cyclodextrin
formulation (used as a novel delivery vehicle) once daily on
solar lentigines of one forearm, for 2 months; the other
forearm served as the control. The areas treated with 2%
hydroquinone showed improvement when compared to the
control area.
Experience with a strong bleaching treatment for skin
hyperpigmentation in Orientals. Yoshimura K, Harii K,
Aoyama T, et╯al. Plast Reconstr Surg 2000; 105:1097–1108;
discussion 1109–1110.
136 Asians were treated with a 0.1–0.4% all-trans retinoic
acid aqueous gel and hydroquinone-lactic acid ointment.
More than 80% of cases of solar lentigines improved though
a topical steroid had to be applied with hydroquinone and
Vitamin C to induce healing.
Second-Line Therapies
Chemical peels: trichloroacetic acid peels B Goldberg DJ, Marcus J. Dermatol Surg 2008; 22:841–844.
The use of chemical peelings in the treatment of different
cutaneous hyperpigmentations. Cotellessa C, Peris K, Onorati
MT, et╯al. Dermatol Surg 1999; 25:450–454.
20 patients with diffuse melasma were treated with a
solution composed of 50% glycolic acid and 10% kojic acid
peel, and 20 patients with lentigo were treated with 15–25%
208
trichloroacetic acid peel. Complete regression of localized
hyperpigmentations was observed in 8 of 20 patients (40%),
a partial regression in 10 of 20 patients (50%), and no regres-
sion in 2 of 20 patients (10%) treated with 15–25% trichloro-
acetic acid.
Third-Line Therapies
Cryosurgery B
Q-switched ruby laser A
Q-switched Nd-Yag AG A
CO2 B
Argon B
IPL (Intense Pulsed Light) B
Cryosurgery has been used for many decades with selective
destruction of melanocytes. However, cryosurgical destruction
may lead to hypopigmentation therefore treatment must be
judicious.
Efficacy and safety of cryotherapy vs trichloroacetic acid in
the treatment of solar lentigo. Raziee M, Balighi K, Shaban-
zadeh-Dehkordi H, et╯al. J Eur Acad Dermatol Venereol 2008;
22(3):316–319.
The study examined 25 women with solar lentigines of
the hands. They were either randomized to treatment with
cryotherapy or 33% trichloroacetic acid solution. Cryotherapy
demonstrated superior results when compared with trichloro-
acetic acid, especially in individuals with fair skin types. Post-
inflammatory hyperpigmentation was a complication in those
with darker skin types.
Q-switched ruby laser application is safe and effective for
the management of actinic lentigo (topical glycolic acid is
not). Kopera D, Hohenleutner U, Landthaler A, et╯al. Derm
Venereol 1996; 76:461–463.
10 female patients with actinic lentigines on the forearms
and dorsal aspects of their hands were treated with the
Q-switched ruby laser on the right side. A glycolic acid peel
was performed on the left side. 4 weeks after treatment with
the laser, total fading of the lesions was evident. However, the
glycolic acid peel did not clear the lesions and caused signifi-
cant adverse events such as burning, irritation and scaling.
The use of the frequency-doubled Q-switched Nd:YAG
laser in the treatment of small cutaneous vascular lesions.
Three-center trial examining the performance of the Nd:
YAG laser on 49 patients with benign pigmented lesions. Cuta-
neous lesions showed improvement with use of the laser, espe-
cially at the higher intensity setting.
Laser therapy versus cryotherapy of lentigines: a compara-
tive trial. Stern RS, Dover JS, Levin JA, et╯al. J Am Acad Der-
matol 1994; 30:985–987.
 10â•… Hyperpigmented Disordersâ•… •â•… Pediatric perspectives: Transient neonatal pustular melanosis
Randomized, controlled, prospective trial comparing liquid
nitrogen cryotherapy, argon laser and a carbon dioxide laser
irradiation in the treatment of solar lentigines at 99 sites in 13
patients. Researchers found that cryotherapy was more likely
to produce substantial lightening than either argon or CO2
laser treatment. The odds of an excellent results were about
50% higher with cryosurgery than with CO2 or argon laser
therapy.
IPL (intense pulsed light) uses light wavelength and shows
promise to treat lentigines with minimal side effects.5
Clinical improvement of solar lentigines and ephelides with
an intense pulsed light source. Kawada A, Shiraishi H, Asai,
M, et╯al. Dermatol Surg 2002; 28:504–508.
A study of intense pulsed light (IPL) was performed in
patients with solar lentigines and ephelides who received 3 to
5 treatments. 40% of patients with solar lentigines displayed
more than 50% improvement and 16% had more than 75%
Pediatric perspectives:
Transient neonatal
pustular melanosis
Candrice R Heath
First-Line Therapies
Observation
improvement. Patients with smaller lesions responded better
to this treatment modality than those with larger lesions.
References
1. Ortonne JP, Bahadoran P, Fitzpatrick TB, et al. Hypomelanoses and
hypermelanoses. In: Freedberg IM, et al, eds. Fitzpatrick’s dermatology
in general medicine. 6th edn. New York: McGraw-Hill; 2003:836–
881.
2. Hexsel DM, Mazzuco R, Bohn J, et al. Clinical comparative study
between cryotherapy and local dermabrasion for the treatment of solar
lentigo on the back of the hands. Dermatol Surg 2000; 26:457–462.
3. Cayce KA, McMichael AJ, Feldman SR. Hyperpigmentation: an over-
view of the common afflictions. Medscape Today [accessed August 27,
2009].
4. Bose S, Ortonne JP. Pigmentation: dyschromia. Cosmet Dermatol
1994; 277–298.
5. Rafal ES, Griffiths CE, Ditre CM, et al. Topical tretinoin (retinoic acid)
treatment for liver spots associated with photodamage. N Engl J Med
1992; 326(6):368–374.
Transient neonatal pustular melanosis. Ramamurthy RS,
Reveri M, Esterly NB, Fretzin DF, Pildes RS. J Pediatr 1976;
88(5):831–835.
This study evaluated 666 infants within 24 hours of birth.
The infants were examined for signs of transient neonatal
pustular melanosis (TNPM) (vesicular pustules, ruptured
vesiculopustules with collarette of scale surrounding a pig-
mented papule, or pigmented macules). There were 23 African-
American infants with TNPM of the 515 examined. There was
only 1 Caucasian infant of the 145 examined. Histopathologic
exam was performed on 6 specimens. Wright stain demon-
strated polymorphonuclear cells, cellular debris and few to no
eosinophils. The etiology of the disease was not established.
TNPM is a self-limited, benign condition requiring no therapy.
Reassure the parents. The remaining vesiculopustules will
resolve within 24–48 hours. However, the hyperpigmented
macules will fade slowly over the coming weeks to months.
209
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Part 2 Pigmentary Disorders
Hypopigmented Disorders
David A Rodriguez
Hypomelanosis of Ito . . . . . . . . . . . . . . . . . . . 211
Hypopigmented cutaneous T-cell lymphoma . . . . . . 212
Hypopigmented sarcoidosis . . . . . . . . . . . . . . . . 215
Pityriasis alba . . . . . . . . . . . . . . . . . . . . . . . 216
Vitiligo . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Pediatric perspectives: Vitiligo . . . . . . . . . . . . . . 221
Hypomelanosis of Ito
Hypomelanosis of Ito (HI), also known as ‘incontinentia pig-
menti achromians’ is a neurocutaneous disorder which mani-
fests as streaky, linear, coil-like or patchy macules that can
occur on any part of the body. Researchers believe the condi-
tion occurs as a result of various genetic anomalies within the
same individual; mosaicism, chimerism, post-zygotic muta-
tions, or X chromosome inactivations have all been impli-
cated.1 The lesions often follow the lines of Blaschko, which
are swirl-like patterns that form around the extremities and
trunk (Fig. 11.1).2 Diagnosis is typically made in infancy and
characterized by the aforementioned lesions. Clinical suspi-
cion should alert the physician to involvement of other organ
systems.3
Ruiz-Maldonado et╯al established diagnostic criteria for
Hypomelanosis of Ito:4
• Major criteria
– Congenital or early-acquired non-hereditary cutaneous
hypopigmented linear streaks or patches involving more
than two body segments
– One or more nervous system or musculoskeletal system
anomalies
©2011 Elsevier Ltd, Inc, BV
11â•…
• Minor criteria
– Two or more congenital malformations other than
nervous system or musculoskeletal system
– Chromosomal anomalies.
Diagnosis can be made with one major or minor criterion
or two minor criteria.
The major systemic manifestations of the disease are vast
and can be categorized into cutaneous and extra-cutaneous
which include cephalic, neurological, oral, musculoskeletal,
ophthalmologic, cardiac and urogenital. Neurologic abnor-
malities often accompany HI and have been reported in up to
40% of cases, though this number varies throughout the litera-
ture.5 Neurologic manifestations in HI have been attributed to
abnormal migration of nerve cells during development.6 In a
case series involving 76 children, the following central nervous
system abnormalities were noted:7
• mental retardation observed in 57%
• autistic behavior in 10%
• seizures in 49%
• infantile spasms in 8%
• macrocephaly and coarse facies in 15%
• microcephaly observed in 7%
• hypotonia with pes valgus/genu valgus in 18%
• only 22% had a normal intelligence level (IQ > 85).
Non-neurologic changes including multiple dental cusps
that protrude from the crowns of both deciduous and perma-
nent incisors are considered typical oral manifestations of IH.8
Changes in hair color, trichorrhexis and alopecia have been
reported.9
Treatment
Currently there is no specific treatment for HI. Camouflage
may be employed for cosmetic concerns. Camouflage make-up
found in the USA, that is water resistant includes Dermablend,
211
 Part 2 Pigmentary Disorders
Figure 11.1:╇ Hypomelanosis of Ito. Note the S-shaped pattern of the
hypopigmented streaks on the flank and abdomen because the lesions are
following Blaschko’s lines. (From Bolognia, Dermatology, 2e, Mosby Inc., copyright
Elsevier 2008.)
Covermark and Cover FX. In cases with extracutaneous mani-
festations, such as neurological involvement, follow-up with a
specialist is recommended.10 The skin lesions require no
special treatment.
Hypomelanosis of Ito. Olson LL, Maria BL. In: Maria BL, ed.
Current management in child neurology, 3rd edn. Hamilton
& London: BC Decker; 2005:476–478.
In this paper, Olsen et╯al specify that there is no particular
treatment for HI. However, referral to a neurologist for evalu-
ation and management is essential as almost 30% of patients
with HI have refractory epilepsy.
Hypomelanosis of Ito. Ratz J, Gross N. http://emedicine.
medscape.com/article/1068339-treatment [accessed Septem-
ber 15, 2009].
Ratz et╯al state that there is no specific treatment for the
cutaneous manifestations of HI. Specialty care and genetic
counseling should be part of a comprehensive management
plan.
Hypopigmented
cutaneous T-cell
lymphoma
Of the various types of cutaneous T-cell lymphoma, mycosis
fungoides (MF) is the most common. Clonally expanded, epi-
dermotrophic T lymphocytes on the skin characterize this dis-
order.1 The classic types of MF are patch, plaque, and tumor;
212
Commonly encountered pitfalls
Hypomelanosis of Ito may be confused with the condition
incontinentia pigmenti. Care must be taken to accurately
distinguish between these two disorders. The diagnosis and
management of this condition is multidisciplinary (involving
pediatricians, neurologists, dentists and geneticists) and it is a
primary role of the dermatologist to assist in accurate diag�
nosis of the condition. Since the cutaneous manifestations of
hypomelanosis of Ito pose no risk to the patient, the focus
must be upon the management of the extra-cutaneous
manifestations.
Special management & counseling considerations
The management of hypomelanosis of Ito is limited to cos-
metic camouflage of the lesions.
References
1. Donnai D, Read AP, McKeown C. Hypomelanosis of Ito: a manifesta-
tion of mosaicism or chimerism. J Med Genet 1988; 12:809–818.
2. Dermnet NZ. http://www.dermnet.org.nz/systemic/hypomelanosis-
ito.html [Accessed September 15, 2009].
3. Schwartz MF, Esterly NB, Fretzin DF, Pergament E, Rozenfeld IH.
Hypomelanosis of Ito (incontinentia pigmenti achromians): a neuro-
cutaneous syndrome. J Pediatr 1977; 90:236–240.
4. Ruiz-Maldonado R, Toussaint S, Tamayo L, Laterza A, Del Castillo V.
Hypomelanosis of Ito: diagnostic criteria and report of 41 cases.
Pediatr Dermatol 1992; 9(1):1–10.
5. Fleury P, Dingemans K, de Groot WP, Oranje AP, Voute PA, Woerdeman
MJ, et al. Ito’s hypomelanosis (incontinentia pigmenti achromians): a
review of four cases. Clin Neurol Neurosurg 1986; 88:39–44.
6. Fujino O, Hashimoto K, Fujita T, Enokido H, Komatsuzaki H, Asano
G, et al. Clinico-neuropathological study of incontinentia pigmenti
achromians – an autopsy case. Brain Dev 1995; 17(6):425–427.
7. Pascual-Castroviejoa I, Rochea C, Martinez-Bermejo A, Lopez-Martin
V, Tendero A, et al. Hypomelanosis of ITO. A study of 76 infantile
cases. Brain Dev 1998; 20:36–43.
8. Happle R, Vakilzadeh F. Hamartomatous dental cusps in hypomelano-
sis of Ito. Clin Genet 1982; 1:65–68.
9. Ruggieri M, Pavone L. Topical review. Hypomelanosis of Ito: clinical
syndrome or just phenotype? J Child Neurol 2000; 15:635–644.
10. Olson LL, Maria BL. Hypomelanosis of Ito. In: Maria BL, ed. Current
management in child neurology. 3rd edn. Hamilton & London: BC
Decker; 2005:476–478.
however, there are several atypical variants that exist. Some
examples of these are hypopigmented, psoriasiform, erythro-
dermic, follicular, noduloulcerative, ichthyosiform, poikilo-
dermatous, morphea and purpuric types.2 The cause of MF is
still unknown although a viral etiology is debated.3 Mycosis
fungoides has an estimated incidence of 0.4 per 100 000
persons.4
The hypopigmented variant of MF is characterized by the
presence of hypopigmented patches as the prime manifesta-
tion of the disease.5 It can also be associated with erythema-
tous patches, plaques, or tumors (Figs. 11.2, 11.3).3 Though
typically described in darker skinned individuals (Fitzpatrick
skin types IV–V), the disease has also been reported in
 11â•… Hypopigmented Disordersâ•… •â•… Hypopigmented cutaneous T-cell lymphoma
Figure 11.2:╇ Hypopigmented cutaneous T-cell lymphoma.
Figure 11.3:╇ Hypopigmented cutaneous T-cell lymphoma. (From Johnson, Moy,
White: Ethnic Skin – Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)
Caucasians.3 In a study in Pakistan, 21.3% of the MF patients
had the hypopigmented variety.2 Immunohistochemical
analysis of hypopigmented MF lesions demonstrates malig-
nant epidermotropic CD8+ T lymphocyte clone infiltration.2
First-Line Therapies
PUVA
Mechlorethamine (nitrogen mustard)
Imiquimod
Topical corticosteroids
Treatment of hypopigmented MF follows that of classic
early-stage MF (IA, IB). Modalities include topical corticoster-
oids, topical mechlorethamine, UVB, and PUVA.6 As opposed
to classic MF, the literature suggests that the treatment of
choice for the hypopigmented variant appears to be PUVA.
Hypopigmented variant of mycosis fungoides: demography,
histopathology, and treatment of seven cases. Lambroza E,
Cohen SR, Phelps R, et╯al. J Am Acad Dermatol 1995;
32:987–993.
Case report of 7 patients with brown or black skin (mean
age of 36) in whom 6 treated with PUVA had rapid induction
and complete repigmentation. The authors believe that PUVA
is first line treatment for hypopigmented MF.
Hypopigmented mycosis fungoides in a 20-year-old Saudi
woman with fair skin. Al-Ratrout JT, Al-Nazer M, Ansari NA.
Indian J Dermatol 2006; 51:115–117.
Case report of a Saudi woman with skin type IV who
responded well to PUVA therapy. The authors suggest close
follow-up as certain cases of hypopigmented MF can behave
aggressively.
Treatment of mycosis fungoides with photochemotherapy
(PUVA): long-term follow-up. Herrmann JJ, Hurria A, Kuzel
TM, et╯al. J Am Acad Dermatol 1995; 33:234–242.
A clinical trial in which the effectiveness and side-effect
profile of long-term use of PUVA to treat early-stage MF was
compared to previously reported topical therapies. 82 patients
with early-stage MF were treated with PUVA, followed by an
observation period of 2 months to 15 years (median, 43
months) in which clinical and histologic features were the
focus. 95% (78) of the subjects showed response, with 65%
(53 subjects) clearing of all clinical and histologic signs of
disease. In a non-randomized comparison with previously
reported data for other topical therapies, the efficacy and side-
effect profile of PUVA compared favorably.
Hypopigmented mycosis fungoides. Bahlouli Z, Blanchet-
Bardon C, Chemaly P, Dubertret L, Flageul B, Robert C. Ann
Dermatol Venereol 1995; 122:704–706.
In this rare clinical trial, a 28-year-old woman developed,
over a 10-year period, non-infiltrated hypopigmented and
discrete squamous macules throughout her entire body.
Based on pathologic evidence of epidermotropic lymphocyte
infiltration, the diagnosis of mycosis fungoides was made. The
subject was treated with PUVA laser therapy. The use of this
treatment lead to rapid regression of the lesions and proved
effective.
C
B Mechlorethamine
C Hypopigmented mycosis fungoides: a report of 7 cases and
B review of the literature. Stone ML, Styles AR, Cockerell CJ,
Pandya AG. Cutis 2001; 67:133–138.
Case report of 7 patients with hypopigmented MF treated
with mechlorethamine. The mean age was 35 years at disease
onset, with a mean of 5.5 years’ duration of illness before
presentation. All of the patients were Fitzpatrick skin type IV
or V. Treatment with topical nitrogen mustard produced
repigmentation in 4 of 6 patients.
213
 Part 2 Pigmentary Disorders
Topical mechlorethamine therapy for early stage mycosis
fungoides. Halperin PS, Ramsay DL, Zeleniuch-Jacquotte A.
J Am Acad Dermatol 1988; 19:684–691.
117 patients with mycosis fungoides were treated with
topical mechlorethamine hydrochloride. In subjects with stage
I disease, the probability of achieving a clinically apparent
remission was 75.8%; in subjects with stage II disease, 44.6%;
in subjects with stage III, 48.6%. The median time for relapse
was 44.5 months. Subjects with stage I achieved complete
remission sooner (median 6.5 months) than stage II (median
41.1 months) or stage III (median 39.1 months) disease. When
compared with the results of other treatments for early stage
MF, these findings were favorable.
Imiquimod
Treatment of patch and plaque stage mycosis fungoides
with imiquimod 5% cream. Aeling JL, Chapman JT, Deeths
MJ, Dellavalle RP, Zeng C. J Am Acad Dermatol 2005;
52:275–280.
6 patients with stage IA to IIB MF were treated with topical
imiquimod 5% cream 3 times per week for 12 weeks in this
open-label pilot study. Index lesions were biopsied pre- and
post-treatment, and up to 4 additional treated lesions were
monitored for 16 weeks. 3 of 6 patients had histologic clear-
ance of disease in index lesions, and also demonstrated sig-
nificant improvement in the clinical scores for all treated
lesions. A fourth patient had 2 of 4 lesions respond clinically.
Application site reactions were limited to those patients
responding to treatment.
Corticosteroids
Topical corticosteroids for mycosis fungoides. Zackheim HS,
Kashani-Sabet M, Amin S. Arch Dermatol 1998; 134:949–954.
79 patients with patch or plaque stage of mycosis fungoides
were treated with class I to III corticosteroids. 51 of these
patients were stage T1 (less than 10% of skin involved) and 28
were stage T2 (10% or more of skin involved). 75 patients had
patch-stage and 4 had plaque-stage disease as determined by
histological examination. Of the stage T1 patients, all used
class I corticosteroids, and 4 (8%) also used class II or III
corticosteroids. Of the stage T2 patients, 19 (68%) used class
I and 12 (43%) used class II or III compounds. Some patients
used more than one class of corticosteroid. 32 (63%) of stage
T1 patients achieved complete remission and 16 (31%)
achieved partial remission, for a total response rate of 48
(94%). The remission rates for stage T2 patients were 7 (25%),
16 (57%), and 23 (82%), respectively. 39 patients achieved
clinical clearing.
Second-Line Therapies
Narrowband ultraviolet B (UVB) C fungoides in Caucasian patients: a clinicopathologic study of 7 cases.
UVA-1 light E 4. Duvic M, Cather J. Emerging new therapies for cutaneous T-cell lym-
214
Narrowband ultraviolet B (UVB)
Narrowband ultraviolet B phototherapy to clear and main-
tain clearance in patients with mycosis fungoides. Ayhan M,
Boztepe G, Erkin G, Kolemen F, Sahin S. J Am Acad Dermatol
2005; 53:242–246.
The purpose of this study was to retrospectively evaluate the
data obtained from 14 subjects (10 male, 4 female; age range,
28–74 years) who received narrowband UVB to treat MF.
Although rapid recurrences after discontinuation of therapy
appear to interfere with its efficacy, optimal maintenance
schedules for prolonged relapse-free intervals are not discussed
in the literature. 78% (11 of 14 subjects) showed complete
response after a mean of 25 treatments. 10 of the 11 subjects
who showed complete response were followed for a median
of 22 months after showing signs of complete response. The
protocol outlined maintenance of narrowband UVB therapy
regimen lasting 18 months, which 8 subjects followed. No
subject showed signs or symptoms of a relapse during this
maintenance regimen.
Hypopigmented mycosis fungoides in a child successfully
treated with UVA1-light. Roupe G. Pediatr Dermatol 2005;
22:82.
Treatment with UVA-1 light has been used successfully in a
child to treat hypopigmented MF. Recently, NBUVB has also
proven to be a safe and easily administered alternative therapy
for early-stage MF. However, lower response rates have been
seen in patients with higher Fitzpatrick skin phototype, pos-
sibly because of the photoprotective effect of melanin and also
because of the longer disease duration in these patients.7
Commonly encountered pitfalls
Since MF is a disease that often progresses slowly, diagnosis
may require multiple biopsies over time. If histopathologic
findings are equivocal, close collaboration with the dermat-
opathologist is recommended.8
Special management & counseling considerations
This disease may follow a benign course.9 Patients may expect
a good response to therapy, though they must be warned that
recurrences are common.
References
1. Manzur A, Zaidi STH. Hypopigmented mycosis fungoides in a 10-year-
old boy. Dermatol Online J 2009; 12(6):21.
2. Shaikh ZI, Rahman SB. Clinicopathological spectrum of mycosis fun-
goides type cutaneous T-cell lymphoma. J Coll Physicians Surg Pak
2006; 16:171–174.
3. Ardigo M, Borroni G, Muscardin L, et al. Hypopigmented mycosis
J Am Acad Dermatol 2003; 49:264–270.
phoma. Dermatol Clin 2000; 18:147–156.
 11â•… Hypopigmented Disordersâ•… •â•… Hypopigmented sarcoidosis
5. Al-Ratrout JT, Al-Nazer M, Ansari NA. Hypopigmented mycosis fun-
goides in a 20-year-old Saudi woman with fair skin. Indian J Dermatol
2006; 51:115–117.
6. El-Shabrawi-Caelen L, Cerroni L, Medeiros LJ, et al. Hypopigmented
mycosis fungoides: frequent expression of a CD8+ T-cell phenotype.
Am J Surg Pathol 2002; 26(4):450–457.
7. Heald PW, Edelson RL. Lymphoma, pseudolymphoma and related
conditions. In: Fitzpatrick TB, Eisen AZ, Wolff K, et al ed. Dermatology
Hypopigmented
sarcoidosis
There are several distinct cutaneous manifestation of systemic
sarcoidosis including hypopigmented sarcoidosis (Chapter 5).
This variant presents as hypopigmented macules, papules
or nodules, typically found on the extremities (Fig. 11.4).
Although the etiology of sarcoidosis is unknown, an autoim-
mune etiology has been theorized. Hypopigmented sarcoido-
sis has been documented almost exclusively in individuals
of African lineage and its presence may herald systemic
sarcoidosis.1
Figure 11.4:╇ Hypopigmented, macular (Philadelphia) sarcoid. (From Johnson, Moy,
White: Ethnic Skin – Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)
in general medicine. 4th edn. New York: McGraw-Hill; 1993:
1285–1307.
8. Gathers RC, Scherschun L, Malick F, Fivenson DP, Lim HW. Narrowband
UVB phototherapy for early-stage mycosis fungoides. J Am Acad
Dermatol 2002; 47:191–197.
9. McNiff JM. Mycosis fungoides and variants. http://uscap.flsi.com/95th/
pdf/companion21h1.pdf [Accessed February 23, 2010].
Histologically, lesions can reveal the classic non-caseating
dermal granulomas typically found in sarcoidosis although
there are some lesions that do not reveal granulomas.2
Electron microscopy studies show possible damage to
melanocytes and questionable melanosome transfer abnor-
malities in areas of hypopigmented sarcoidosis.3
Diagnosis is clinical, though due to its rarity, a biopsy will
more than likely be required. More importantly, as Westerhof
et al points out,4 sarcoidosis should be suspected when a
patient presents with hypopigmented macules on the extremi-
ties and extradermal evidence of a systemic process such as
pulmonary abnormalities.4,5
Treatment
8-Methoxypsoralen and long wave ultraviolet light E
Treatment of hypopigmented sarcoidosis with 8-
methoxypsoralen and long wave ultraviolet light. Patterson
JW, Fitzwater JE. Int J Dermatol 1982; 21(8):476–480.
Case report of facial lesions treated three times per week
with 8-methoxypsoralen and UV light. The hypopigmented
areas re-pigmented after 8 months of therapy.
References
1. Mashek H, Kalb R. Hypopigmentation of the extremities. Arch
Dermatol 1998; 134:743–748.
2. Alexis JB. Sarcoidosis presenting as cutaneous hypopigmentation with
repeatedly negative skin biopsies. Int J Dermatol 1994; 33:44–45.
3. Patterson JW, Fitzwater JE. Hypopigmented sarcoidosis. J Tenn Med
Assoc 1978; 71:662–664.
4. Westerhof W, Njoo D, Menke HE, Relyveld G. Miscellaneous
hypomelanoses: hypopigmentation. In: Nordlund JJ, King RA, Ortonne
JP, Boissy RE, Hearing VJ, ed. The pigmentary system: physiology
and pathophysiology. 2nd edn. Malden, MA: Blackwell Publishing;
2006.
5. Patterson JW, Fitzwater JE. Treatment of hypopigmented sarcoidosis
with 8-methoxypsoralen and long wave ultraviolet light. Int J Dermatol
1982; 21(8):476–480.
215
 Part 2 Pigmentary Disorders
Pityriasis alba
Pityriasis alba has been referred to as a variant of atopic der-
matitis or eczema in its mild form. The condition is not limited
by race, but is more common and is cosmetically more appar-
ent and difficult to treat in darker skinned patients.1 A red,
pink or skin colored irregular plaque, that is rounded or oval
in shape, characterizes an individual pityriasis alba lesion.
These lesions typically have indistinct margins with fine lamel-
lar or branny scaling (Fig. 11.5). Lesions observed usually
range from 0.5 to 2╯cm in diameter, however it is not uncom-
mon to observe larger patches on the trunk. Pityriasis alba is
common among children (Fig. 11.6). In children it occurs
more commonly on the trunk and limbs; only 20% of children
diagnosed with the disorder have involvement of the arms,
neck or face.
Figure 11.5:╇ Pityriasis alba in a female patient.
Figure 11.6:╇ Pityriasis alba. (From Johnson, Moy, White: Ethnic Skin – Medical
and Surgical, Mosby Inc., copyright Elsevier 1998.)
216
Pigmented pityriasis alba is an uncommon variant usually
confined to the face, and associated with dermatophyte infec-
tion.2 The typical lesion is described as a central zone of hyper-
pigmentation, usually bluish, surrounded by a moderately
scaly halo.2 This halo varies in diameter.2
Extensive pityriasis alba is another uncommon variant of
pityriasis alba. This variant typically affects more females than
males. It is also differentiated by its lack of an inflammatory
phase prior to onset. As its name suggests, extensive pityriasis
alba is widespread and occurs symmetrically.3
Emollients and mild topical corticosteroids have a tendency
to speed up the repigmentation of lesions of pityriasis
alba, although their efficacy has been proven to be limited.4
First-Line Therapies
Tacrolimus ointment 0.1% B
Pimecrolimus cream 1% C
Tacrolimus ointment 0.1% in pityriasis alba: an open-label,
randomized, placebo-controlled study. Charissi C, Georgala
S, Gregoriou S, Kalogeromitros D, Kontochristopoulos G,
Rigopoulos D. Br J Dermatol 2006; 155:152–155.
In this clinical trial, 60 subjects (ages 6–21) with Fitzpatrick
skin phototype III or IV, were randomly assigned to two
separate groups. Group A received tacrolimus ointment 0.1%
(twice daily, 12 hours between doses, on all hypopigmented
macules) in combination with standard moisturizers that
included SPF 20 sunscreen. Group B received the sunscreen
and moisturizer combination. Subjects were evaluated at base-
line and weeks 0, 3, 6, and 9 for scaling, hypopigmentation
and pruritis (scale of 0–3) and patient satisfaction was also
measured on the same 0–3 scale. Both groups showed a
statistically significant improvement in hypopigmentation,
scaling and pruritis over the treatment period of 9 weeks.
Hypopigmentation resolved from a baseline score of 2.38 ±
0.64 to 1.15 ± 0.54 at week 3, 0.46 ± 0.51 at week 6 and 0.00
± 0.00 at week 9 for group A. The statistical difference between
both groups was significant on all three assessments for hypo-
pigmentation (p < 0.001), and for pruritis on week 6 and 9
assessments (p < 0.05). 11.5% of the subjects from group A
reported a mild transient sensation of burning. All subjects in
group A reported they were completely satisfied or just satis-
fied with the treatment, compared to only 50% of the subjects
from group B. Tacrolimus ointment 0.1% appears to be a effec-
tive and safe treatment for pityriasis alba.
An exploratory study to determine the efficacy of 1% pime-
crolimus cream in the treatment of pityriasis alba. Fujita
WH, McCormick CL, Parneix-Spake A. Int J Dermatol 2007;
46(7):700–705.
This open-label, single-arm study was designed to deter-
mine the efficacy and safety of 1% pimecrolimus cream in the
treatment of pityriasis alba. 10 subjects (ages 12–35) with
 11â•… Hypopigmented Disordersâ•… •â•… Vitiligo

Fitzpatrick skin types IV and V were enrolled into this 3-month
study and instructed to apply 1% pimecrolimus cream to the
hypopigmented areas twice daily for 3 months. Visit schedules
included a baseline visit and 3-, 6- and 12-week evaluations.
Subjects were also supplied facial moisturizers with SPF 15
sunscreen and mild soap-free cleansers to supplement their
treatment. 9 of 10 subjects completed the study and marked
improvement of uneven skin tone and complete resolution of
scaling were apparent at the 3-week visit. Near-complete reso-
lution of uneven skin tones was observed at the 12-week visit.
1% pimecrolimus cream was found to be safe and effective in
the treatment of pityriasis alba in children and adults.
Second-Line Therapies
2% coal tar, 1% di-iodohydroxyquinolin, 0.5% A
hydrocortisone
Oral methoxsalen photochemotherapy C References
Treatment of pityriasis alba with a combination of coal tar,
di-iodohydroxyquinolin and hydrocortisone. Gonzalez OA,
Vargas OF. Med Cutan Ibero Lat Am 1980; 8:69–72.
This double-blind trial compared the use of a combination
of 2% coal tar, 1% di-iodohydroxyquinolin, 0.5% hydrocorti-
sone to a placebo in 29 subjects. The subjects were asked to
apply the medication 3 times daily for 1 month. The combina-
tion therapy proved to have favorable results with a highly
significant difference compared with the placebo.
Oral methoxsalen photochemotherapy of extensive pityria-
sis alba. Jaber LA, Kurban AK, Zaynoun S. J Am Acad Dermatol
1986; 15:61–65.
In this study, 6 subjects with extensive pityriasis alba were
treated with oral methoxsalen in combination with exposure
to mid-day summer sun or exposure to phototherapy with
PUVA. Complete clearing or marked improvement was
obtained in 5 subjects in less than 4 weeks of treatment. The
6th subject, who had the most extensive skin involvement
of the cohort, achieved marked improvement after 15 weeks
of therapy.
1. Martin RF, Lugo-Somolinos A, Sanchez JL. Clinicopathologic study on
pityriasis alba. Bol Asoc Med P R 1990; 82(10):463–465.
2. du Toit MJ, Jordaan HF. Pigmenting pityriasis alba. Pediatr Dermatol
1993; 10(1):1–5.
3. Di Lernia V, Ricci C. Progressive and extensive hypomelanosis and
extensive pityriasis alba: same disease, different names? J Eur Acad
Dermatol Venereol 2005; 19(3):370–372.
4. Janniger CK, Lin RL. Pityriasis alba. Cutis 2005; 76:21–24.

vitiligo and the disease has an affinity for periorificial surfaces

Vitiligo in such cases (Fig. 11.8).5 Depigmentation of hair in vitiligi-
nous areas, (leukotrichia) may be seen (Figs. 11.9 & 11.10). Of
note, individuals with bilateral (typical) vitiligo have a low
Vitiligo is a progressive, hypopigmentary disorder character- incidence of leukotrichia, however those with unilateral (seg-
ized by the absence of epidermal melanocytes and melanin mental) vitiligo have a higher incidence of depigmented hair;
and thus absence of pigment. The scalp, neck and face are the
areas most commonly involved with vitiligo. Initial lesions
can be seen on the extremities, particularly the face, hands
and feet (Fig. 11.7). The condition can exact a heavy psycho-
logical toll on those afflicted, and is a common source of
embarrassment.
Vitiligo has a worldwide incidence of 1% and many patients
have a familial history of the disease.1,2 Curiously, involved
areas are ones routinely subjected to trauma with activities of
daily living.
Many of the common sites of occurrence are areas subjected
to repeated trauma or sun exposure such as:3
• Bony prominences
• Extensor forearm
• Ventral wrists
• Dorsal hands
• Digital phalanges.
The lesions can be unilateral and follow a dermatomal
distribution, though typically they present symmetrically.4 Figure 11.7:╇ Perioral vitiligo. (From Johnson, Moy, White: Ethnic Skin – Medical
Mucosal involvement can be seen, especially in generalized and Surgical, Mosby Inc., copyright Elsevier 1998.)

217
 Part 2 Pigmentary Disorders
Figure 11.8:╇ Vitiligo in a typical location. (From White & Cox, Diseases of the Skin,
A Color Atlas and Text, 2E, Mosby Inc., copyright Elsevier 2006.)
Figure 11.9:╇ Vitiligo with leukotrichia. Hairs with in patches of vitiligo often lose
their color. (From White & Cox, Diseases of the Skin, A Color Atlas and Text, 2E,
Mosby Inc., copyright Elsevier 2006.)
Figure 11.10:╇ Follicular repigmentation of vitiligo. When vitiligo repigments,
it often does so initially around the hair follicles. (From White & Cox, Diseases of
the Skin, A Color Atlas and Text, 2E, Mosby Inc., copyright Elsevier 2006.)
218
in the latter scenario the disease seems to be more resistant to
standard treatments.6
The disorder has been associated with various
conditions:4
• Thyroid disease
• Pernicious anemia
• Addison’s disease
• Diabetes mellitus
• Hypoparathyroidism
• Myasthenia gravis
• Alopecia areata
• Morphea and lichen sclerosus
• Halo nevus
• Malignant melanoma.
From examining associated diseases it could easily be sur-
mised that the condition probably has as autoimmune com-
ponent, and indeed several theories posit such a hypothesis.
Anti�bodies against specific organs have been found in higher
concentrations in the serum of individuals with vitiligo.7 The
autotoxicity theory proposed by Lerner blames a deficiency
of melanocytic autoprotective mechanisms, leading to the
destruction of the cell.1 Lerner also suggests that neurochemi-
cals might inhibit melanocytes.8 Moreover, abnormal concen-
trations of catecholamine metabolites have been found in
patients with the condition and this imbalance might lead to
depigmentation.9
Diagnosis is usually clinical. Patients can present with
symmetrical, or classic vitiligo, or in a unilateral, atypical
fashion. A Wood’s lamp can help differentiate vitiligo from
hypopigmentary disorders such as pityriais versicolor. A biopsy
is in order if diagnosis is unclear. Additionally, evaluation
of thyroid function and anemia is appropriate for vitiligo
patients.
Treatment
Treatment for vitiligo is directed at repigmentation and in
progressive or unstable vitiligo, arresting the depigmentation.
(Fig. 11.11). Therefore, treatment strategies for vitiligo must
address the type of vitiligo, generalized or localized, stable or
progressing, as well as the total amount of body surface area
involved. It should also take into consideration the part of the
body surface area involved.10
The development of guidelines for the treatment of vitiligo.
Njoo MD, Westerhof W, Bos JD. Arch Dermatol 1999;
135(12):1514–1521.
This is an extensive review of the literature regarding treat-
ment for vitiligo with evidence-based guidelines. Meta-analyses
were performed on all studies to date (1999), and showed that
class III corticosteroids and narrowband UVB (NBUVB) are the
most effective and safest therapy for localized and generalized
vitiligo.
It is interesting in these reviews that patients with vitiligo
regarded 75% repigmentation as a cosmetically acceptable level
of repigmentation.
 11â•… Hypopigmented Disordersâ•… •â•… Vitiligo

Determine site of involvement Figure 11.11:╇ The evaluation of first choice therapies for vitiligo.
BSA = Body Surface Area.

As appropriate:
Cosmetic camouflague
Psychological and social support

Exposed sites Unexposed sites

< 10% of BSA affected Observation vs.

*Topical calcineurin inhibitors BSA based
*Topical corticosteroid agents treatment approach
*Targeted UVB phototherapy
with or without calcipotriene; with or
without topical calcineurin inhibitors

11-80% BSA affected >81% of BSA

*NBUVB with or
Depigmentation
without calcipotriene;
therapy
Oral PUVA with or
*Topical agents: 20%
without calcipotriene
Monobenezyl Ether of
Hydroquinone cream
*Combination of topical
depigmentation agents
and Q-switch Ruby laser
treatment

and neck or both was seen in 68% of the patients (n = 13).

First-Line Therapies
Tacrolimus therapy may be helpful as adjunctive therapy for
vitiligo.
Topical corticosteroids A
Topical calcineurin inhibitors B
Second-Line Therapies

Treatment of vitiligo with 0.1% betamethasone 17-valerate Surgical treatment D

in isopropyl alcohol – a double-blind trial. Kandil E. Br J Phototherapy A
Dermatol 1974; 91:457–460. Combination tacrolimus and phototherapy A
In this study, 19 patients with symmetrically distributed Depigmentation with monobenzylether of hydroquinone C
patches of vitiligo were treated with topical corticosteroids. It
was the most effective treatment for localized vitiligo.
Meta-analysis of other studies showed that class III topical
There are many techniques for surgical treatment of refrac-
corticosteroid was the most effective treatment for localized
tory but stable vitiligo.10
vitiligo.

Topical tacrolimus therapy for vitiligo: therapeutic responses
and skin messenger RNA expression of proinflammatory
cytokines. Grimes PE, Morris R, Avaniss-Aghajani E, et╯al. J Am
Acad Dermatol 2004; 51(1):52–61.
In this prospective, non-randomized, uncontrolled study of
23 patients with vitiligo, variable repigmentation occurred in
81% of the patients (n = 17); 75% repigmentation of the face
Surgical approaches for stable vitiligo. Falabella, R. Derma-
tol Surg 2005; 31:1277–1284.
In the study, autologous mini grafts or punch grafts, 1.0–
1.2╯mm, were taken with a punch biopsy from selected pig-
mented areas. Re-pigmentation was noted in the grafted areas.
However, results may be technique-dependent, with areas of
‘cobble stoning’; less than 75% of lesions repigmented.

219
 Part 2 Pigmentary Disorders

A systematic review of autologous transplantation methods Randomized, controlled study to identify the optimal fre-
in vitiligo. Njoo MD, Westerhof W, Bos JD, et╯al. Arch Derma- quency of 308-nm excimer laser treatments. In this study of
tol 1998; 134:1543–1549. 14 patients, repigmentation was fastest when treatments were
The development of guidelines for treatment of vitiligo was administered three times a week.
based on three systematic reviews of the literature combined
with the results of two questionnaires, interviews with poten- The use of the 308-nm excimer laser for the treatment of
tial users of the guidelines, three interactive expert meetings vitiligo. Hadi SM, Spencer JM, Lebwohl M. Dermatol Surg
and one local expert meeting. 2004; 30:983–986.
This is a retrospective review of the literature that found that
Other forms of surgical repigmentation include autologous
lesions of the hands and feet did not exhibit > 75% repigmen-
suction blister grafting. The most successful of these methods
tation with excimer treatment. However, 71.5% of facial lesions,
was performed in stable segmental vitiligo. The highest success
60% of neck and scalp lesions, and 40% of truncal showed
rates were achieved with split-thickness skin.
> 75 % repigmentation using the 308-nm excimer laser.
The transplantation of monoculture in in-vitro cultures of
autologous epidermis or pure melanocytes involves trans-
Calcipotriene and vitiligo. Vásquez-López F, López-Escobar
planting auto�logous thin sheets of epidermis. This may involve
M, Pérez-Oliva. N. Arch Dermatol 2003; 139:1656–1657.
sheets of thin epidermal tissue, or pure melanocytic tissue
This was an open pilot study of 10 patients with vitiligo.
which have been previously cultured in-vitro. This is sub�
The efficacy and safety of PUVA with topical calcipotriene was
sequently followed by compression with bandages after
assessed. Repigmentation was not significant.
grafting.
In the study of culturing techniques, no significant results
Combination of narrowband UV-B and topical calcipotriene
can be drawn due to the small numbers of patients who
in vitiligo. Dogra S, Parsad D. Arch Dermatol 2003; 139:393.
have been enrolled. The transplantation method must take
A case report of a patient who was treated with NBUVB
into account disease characteristics such as disease stability
and calcipotriene in vitiligo of the lower extremities. The
and the expertise of the physician.
results of this single case demonstrated that NBUVB with cal-
cipotriene worked faster in repigmentation. Calcipotriene may
Randomized double-blind trial of treatment of vitiligo: act in vitiligo either by 1,25-dihydroxyvitamin D3 receptors on
efficacy of psoralen–UV-A therapy vs narrowband–UV-B melanocytes or by modifying defective calcium homeostasis
therapy. Yones SS, Palmer RA, Garibaldinos TM, Hawk JL. Arch in the epidermal unit.
Dermatol 2007; 143(7):906.
This was a randomized double-blind placebo control study Depigmentation of vitiligo should be reserved for refrac-
comparing narrowband UVB (NBUVB) with psolaren UVA tory, stable vitiligo of greater than 80% of body surface area
(PUVA) in 50 patients with vitiligo. At the end of the treatment (Fig. 11.12).
period (48 treatments), both PUVA and NBUVB demonstrated
excellent responses with repigmentation of vitiliginous areas
but NBUVB showed superior results to PUVA.
Targeted phototherapy has been available for the treatment
of vitiligo and includes the 308-nm excimer laser and UVB and
UVA targeted therapy.

Topical tacrolimus and the 308-nm excimer laser: a syner-

gistic combination for the treatment of vitiligo. Passeron
T, Ostovari N, Zakaria W, et╯al. Arch Dermatol 2004; 140:
1065–1069.
Randomized controlled study with 23 patients with a total
of 43 lesions treated with a 308-nm excimer laser alone (n =
4) or in combination with 0.1% tacrolimus ointment (n = 16).
24 treatments were performed and 100% repigmentation was
seen in the combination group, 85% repigmentation in the
excimer laser monotherapy group, and no repigmentation in
the control group. However, 75% or greater lesion repigmenta-
tion was seen in 70% of the combined laser and tacrolimus
group, but only 20% of the excimer laser monotherapy.

Optimal weekly frequency of 308-nm excimer laser treat-

ment in vitiligo patients. Hofer A, Hassan AS, Legat FJ, et╯al.
Figure 11.12:╇ Incomplete depigmentation with monobenzylether of hydroquinone.
Br J Dermatol 2005; 152:981–985.

220
 11â•… Hypopigmented Disordersâ•… •â•… Pediatric perspectives: Vitiligo
Monobenzylether of hydroquinone: a retrospective study of
treatment of 18 vitiligo patients and a review of the litera-
ture. Mosher DB, Parrish JA, Fitzpatrick TB. Br J Dermatol
1977; 97:669–679.
This was a retrospective study of 18 patients treated with 20%
monobenzylether of hydroquinone cream. 8 patients had com-
plete depigmentation, and 3 had dramatic hypopigmentation.
Depigmentation therapy in vitiligo universalis with topical
4-methoxyphenol and the Q-switched ruby laser. Njoo
MD, Vodegel RM, Westerhof W. J Am Acad Dermatol 2000;
42(5 Pt 1):760–769.
This was a retrospective study of the efficacy of
4-methoxyphenol (4-MP) cream and Q-switched ruby laser
in 16 patients with vitiligo universalis. Hypopigmentation
occurred in most patients.
Commonly encountered pitfalls
Inadequate evaluation of the vitiligo patient for underlying
systemic disorders is a common problem. Therefore, it is
important to rule out disorders such as endocrinopathies and
autoimmune disorders. The prudent clinician should be cog-
nizant of these associations and their evaluation. Referral to a
specialist may be considered.
Although effective, PUVA therapy for vitilgo is associated
with adverse events such as erythema, tenderness, burning,
post-inflammatory hyperpigmentation and cataracts. There-
fore, it is important to obtain informed consent prior to insti-
tuting this form of phototherapy.
Surgery for the treatment of vitiligo is a novel approach that
holds much promise for refractory disease. However, there
exists little consensus on the proper time to perform surgery.
Most experts recommend performing surgery when the disease
is ‘stable’, however the concept of stability is frustratingly neb-
ulous.8 Patients should be counseled that there is no optimal
time for surgery and that lesions that appear stable, may, in
fact, progress. This may lead to suboptimal surgical outcomes.
A thoughtful approach regarding this pitfall involves observing
lesions for 6 months to 2 years and/or performing ‘test’ grafts
and observing.9
Pediatric perspectives:
Vitiligo
Candrice R Heath
Thyroid abnormalities in pediatric patients with vitiligo in
New York City. Pagovich OE, Silverberg JI, Freilich E,
Silverberg NB. Cutis 2008; 81(6):463–466.
In this retrospective chart review, 67 pediatric patients with
vitiligo were tested for thyroid disease. Of the 67 vitiligo
Special management & counseling considerations
In patients with darker skin tones, vitiligo can have a devastat-
ing psychological impact. Therefore, referral to a mental health
professional is important for the patient who appears unable
to cope with the disease. Vitiligo support groups are also a
valuable resource. (National Vitiligo Foundation, Inc. http://
www.nvfi.org) Camouflaging techniques with water resistant
make-up are a useful tool to cover vitiligo. Agents available in
the USA include Dermablend, Covermark and Cover FX.
Summary
Vitiligo is a cosmetically disfiguring condition which is most
devastating to patients of color. Although no therapy is 100%
successful, physicians should utilize treatment strategies which
may help directly and lessen the degree of involvement.
References
1. Lerner AB. On the etiology of vitiligo and gray hair. Am J Med 1971;
51:141–147.
2. Forschner T, Buchholtz S, Stockfleth E. Current state of vitiligo therapy
– evidence-based analysis of the literature. J Dtsch Dermatol Ges 2007;
5(6):467–475.
3. Groisman V, Sami M. Vitiligo. Emedicine. http://emedicine.
medscape.com/article/1068962-overview [Accessed September 15,
2009].
4. Bleehen SS, Anstey AV. Disorders of skin colour. In: Burns T, Breathnacht
S, Cox N, Griffiths C, ed. Rook’s textbook of dermatology. Vol. 2. 7th
edn. Malden, MA: Blackwell Publishing; 2004:39–54.
5. Baum S, Barzilai A, Trau H. Vitiligo. In: Shoenfeld Y, Cervera R,
Gershwin ME, ed. Diagnostic criteria in autoimmune diseases. Totowa
NJ: Humana Press; 2008:353–358.
6. Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo.
Curr Dir Autoimmun 2008; 10:227–243.
7. Woolfson H, Finn OA, Macjie RM, et al. Serum anti-tumour antibodies
and auto-antibodies in vitiligo. Br J Dermatol 2006; 92:395–400.
8. Lerner AB. Vitiligo. J Invest Dermatol 1959; 32:285–310.
9. Morrone A, Picardo M, De Luca C, et al. Catecholamines and vitiligo.
Pigment Cell Res 1992; 5:65–69.
10. Lim HW, Hexsel CL. Vitiligo; to treat or not to treat. Arch Dermatol
2007; 143(5):643–646.
11. Parsad D, Gupta S. Standard guidelines of care for vitiligo surgery.
Indian J Dermatol Venereol Leprol 2008; 74:S37-S45.
patients, 53 had non-segmental types. Only 28 patients’
thyroid disease results were available. Active thyroid disease
was found in 7 (25%) of the 28 patients. Of these 7 patients,
none had segmental vitiligo. Although only a small cohort
of 28 patients was used, the importance of thyroid screening
for patients with generalized, non-segmental vitiligo was
highlighted.
An approach to the correlation between vitiligo and autoim-
mune thyroiditis in Chinese children. Yang Y, Lin X, Fu W,
Luo X, Kang K. Clin Exp Dermatol 2009; 35(7):706–710.
The aim of this prospective study was to evaluate the
correlation between pediatric vitiligo and other associated
221
 Part 2 Pigmentary Disorders
diseases with a focus on autoimmune thyroiditis. 363 pediatric
vitiligo patients (287 non-segmental and 76 segmental) and
93 healthy children were screened for autoimmune thyroiditis
and completed a questionnaire. Free tri-iodothyronine, free
thyroxine, thyroid-stimulating hormone, anti-thyroid peroxi-
dase antibody and anti-thyroglobulin antibody levels were
checked. Of the 363 patients, 43 (11.8%) had abnormal
thyroid results as compared to only 4 (4.3%) out of the 93
control patients. There were 21 cases of autoimmune thyroidi-
tis in the vitiligo group and 0 in the control group. The 21
cases of autoimmune thyroiditis consisted of 20 non-segmental
vitiligo patients and only 1 patient with segmental vitiligo. The
average age of children with autoimmune thyroiditis in this
study was 10.1 years. Since vitiligo usually appears before the
onset of thyroid disease, screening for thyroid function and
antibodies in all pediatric patients with vitiligo (especially
non-segmental) may be advantageous.
First-Line Therapies
Topical corticosteroids A
Topical tacrolimus or pimecrolimus A
A double-blind randomized trial of 0.1% tacrolimus vs
0.05% clobetasol for the treatment of childhood vitiligo.
Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB,
Ortiz CA, Torres-Rubalcava AB. Arch Dermatol 2003;
139:581–585.
20 children with vitiligo with an average age of 9.5 years
were included in this trial. Two symmetrical lesions of similar
size and evolution were selected in each patient for a 2-month
treatment period. Clobetasol was used on one lesion and tac-
rolimus was applied to the other. Some repigmentation was
noted in 18 of the 20 patients. Repigmentation was noted in
49.3% of the clobetasol treated lesions and in 41.3% of tac-
rolimus treated. Repigmentation was best on the face and areas
with high density of hair follicles. Neither clobetasol nor tac-
rolimus repigmented the lesions on the dorsal hands or areas
devoid of hair follicles. More than 75% repigmentation was
found in 5 patients (25%) treated with clobetasol and in
5 patients (25%) treated with tacrolimus. Clobetasol was
superior to tacrolimus in repigmenting the axillae, legs, and
abdomen. Tacrolimus is proven nearly as effective as clobeta-
sol propionate in repigmentation of vitiligo lesions in children
without the adverse affects of atrophy and telangiectasias.
Although, a burning sensation was noted in 2 patients using
tacrolimus, it did not preclude their continuation in the study.
Tacrolimus ointment promotes repigmentation of vitiligo
in children: a review of 57 cases. Silverberg NB, Lin P, Travis
L, et╯al. J Am Acad Dermatol 2004; 51(5):760–766.
This was a retrospective review of 57 pediatric patients with
vitiligo treated for at least 3 months with tacrolimus. Facial
segmental lesions responded best to treatment. A partial
response or greater was noted in 89% of participants with head
222
and neck lesions and 63% of participants with trunk and
extremity lesions. Topical tacrolimus ointment is an effective
treatment for pediatric vitiligo, especially for head and neck
lesions.
Topical immunomodulators are effective for treatment of
vitiligo. Choi CW, Chang SE, Bak H, et╯al. J Dermatol 2008;
35(8):503–507.
A retrospective review of 52 patients with vitiligo treated
with topical immunomodulators and 27 patients treated with
topical steroids. This review included 18 children; 9 in the
topical immunomodulator group and 9 in the topical steroid
group. The time to onset of repigmentation was significantly
shorter in the immunomodulator group. Patients with a
history of vitiligo for < 12 months had a higher response rate
than patients with disease duration > 12 months. Patients with
< 12-month history of vitiligo had a time to response of 2.3
± 1 month and patients with disease duration > 12 months
had a time to response of 3.6 ± 1.4 months. Topical
immunomodulators may be used as alternatives to topical
corticosteroids in the treatment of vitiligo.
Second-Line Therapies
Narrowband UVB B
Excimer laser B
Calcipotriene/Calcipotriol in combination with other B
treatments
Useful treatment of vitiligo in 10 children with UV-B nar-
rowband (311╯nm). Brazzelli V, Prestinari F, Castello M, et╯al.
Pediatr Dermatol 2005; 22(3):257–261.
10 children were treated with narrowband UVB two to three
times per week on non-consecutive days. The mean length of
treatment was 5.6 months. 5 patients had a repigmentation
level > 75% and three patients’ repigmentation levels were
between 26% and 75%. Overall, 80% of the study participants
had satisfactory response to phototherapy. The best repigmen-
tation results were found on the face and neck. Children with
recent onset vitiligo responded better. Narrowband UVB is safe
and valuable in the treatment of pediatric vitiligo.
Treatment of generalized vitiligo in children with narrow-
band (TL-01) UVB radiation therapy. Njoo MD, Bos JD,
Westerhof W. J Am Acad Dermatol 2000; 42(2 Pt 1):245–253.
51 children were treated with narrowband UVB twice per
week for up to 1 year. Repigmentation > 75% occurred in 53%
of the patients. In 80% of the patients, the vitiligo stabilized.
The better the patients responded to narrowband treatment,
the higher their quality of life scores on the Children’s Derma-
tology Life Quality Index. Narrowband UVB is safe and effec-
tive in pediatric vitiligo.
Artificial UV therapy delivered outside of the patient’s home
often leads to hours of missed school time.
 11â•… Hypopigmented Disordersâ•… •â•… Pediatric perspectives: Vitiligo
Combination of 308-nm excimer laser with topical pime-
crolimus for the treatment of childhood vitiligo. Hui-Lan Y,
Xiao-Yan H, Jian-Yong F, Zong-Rong L. Pediatr Dermatol 2009;
26(3):354–356.
Randomized (single-blinded) study of 49 patients (6–14
years old) evaluating the 308-nm excimer laser twice per week
with topical 1% pimecrolimus twice daily (group A) versus
excimer laser twice a week alone (group B). There were 17
patients with Fitzpatrick skin type II, 27 patients with skin type
III, and 5 patients with skin type IV. One patient did not com-
plete the study due to worsening vitiligo, but of the 48 who
completed the study, 71% of group A achieved grade 3 or 4
repigmentation versus 50% in group B after 30 weeks of treat-
ment. Combined therapy may lead to faster repigmentation
than monotherapy excimer laser for facial vitiligo lesions. The
combination of the 308-nm excimer laser with topical pime-
crolimus was statistically better than the excimer laser alone.
Third-Line Therapies
Camouflage D
Grafting C
Corrective camouflage in pediatric dermatology. Tedeschi A,
Dall’Oglio F, Micali G, Schwartz RA, Janniger CK. Cutis 2007;
79(2):110–112.
Of the 15 patients, 4 had vitiligo. The authors highlight that
the parents were pleased with the outcome and camouflage
should be considered as an adjunctive treatment.
Epidermal grafting for vitiligo in adolescents. Gupta S,
Kumar B. Pediatr Dermatol 2002; 19(2):159–162.
10 children with a total of 15 vitiliginous patches recalci-
trant to treatment, were treated with epidermal grafting. All of
the patients had Fitzpatrick skin type IV or V. The patients were
also treated with systemic PUVA for 3–6 months. Greater than
75% repigmentation was demonstrated in 13 of the 15 patches.
Initially, the color match was not accurate, but after 3–6
months, the lesions had a good to excellent match to the sur-
rounding skin.
223
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 PART 3
Follicular Disorders
and Alopecias
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Part 3 Follicular Disorders and Alopecias
Alopecias
Raechele Cochran Gathers
Alopecia areata . . . . . . . . . . . . . . . . . . . . . .
Alopecia mucinosa . . . . . . . . . . . . . . . . . . . .
Central centrifugal cicatricial alopecia . . . . . . . . . .
Dissecting cellulitis . . . . . . . . . . . . . . . . . . . .
Discoid lupus erythematosus . . . . . . . . . . . . . . .
Traction alopecia . . . . . . . . . . . . . . . . . . . . .
Traumatic alopecia: chemical, heat and mechanical . .
Trichotillomania . . . . . . . . . . . . . . . . . . . . . .
Alopecia areata
The lifetime risk of alopecia areata is reported to be 1.7% in
Americans, with a reported incidence of 0.1–0.2%.1 Alopecia
areata (AA) affects men and women equally, and there is no
known racial predilection. Though alopecia areata can occur
at any age, it is most common in the third and fourth decades
of life,2 and 20% of patients have a positive family history of
alopecia areata.3 Though the exact pathogenesis of alopecia
areata is not completely understood, it is widely accepted that
it is a T-cell mediated autoimmune disease. Associations have
also been reported with major histocompatibility complex
(MHC), cytokine and immunoglobin genes, suggesting that
the disease is multifactorial in origin. Patients with alopecia
areata have an increased frequency of other autoimmune dis-
eases, particularly thyroid disease and vitiligo. Other autoim-
mune diseases associated with alopecia areata include type I
diabetes mellitus, pernicious anemia, lupus erythematosus,
myasthenia gravis, lichen planus, autoimmune polyendocrine
syndrome type I and inflammatory bowel disease. Atopic der-
matitis and Down’s syndrome may also be associated with
alopecia areata at a higher rate than seen in the normal popu-
lation.4,5 Alopecia areata has been reported in association with
emotional and physical stress, as well as with environment
©2011 Elsevier Ltd, Inc, BV
12â•…
227 triggers.6,7 Evidence also suggests that alopecia areata has a
genetic predisposition, and about 20% of people with alopecia
232
areata may have a family history of the disease.3,8 Nail involve-
234 ment in alopecia areata is not uncommon, and may include
236 pitting, trachyonychia, Beau’s lines, onychomadesis, onychor-
rhexis, and punctate or transverse leukonychia.9
239
The diagnosis of alopecia areata is largely a clinical one. The
242 histology of early stage alopecia areata is typically character-
244 ized by an increased number of catagen and telogen hairs, as
well as a distinctive peribulbar lymphocytic infiltrate com-
246
monly termed ‘swarm of bees.’ Although routine tests are not
necessary, in patients with suggestive clinical signs or symp-
toms, or a family history of autoimmune disease, a CBC,
thyroid function tests, serum B12, autoantibody screening and
appropriate directed work-up should be considered. Up to
half of patients with alopecia areata will recover within one
year, although almost all will experience recurrence. The prog-
nosis of alopecia areata is usually better in patients with
limited disease. Those with widespread patch alopecia, alo-
pecia totalis (AT) and alopecia universalis (AU) typically fare
far worse. Full recovery from alopecia universalis is unlikely,
and has been reported as less than 10%.10,11 Other negative
prognosticators include childhood onset of disease, long dura-
tion of alopecia, family history, an ophiasis pattern of disease,
nail changes and history of atopy (Fig. 12.1).12
The differential diagnosis of alopecia areata includes tri-
chotillomania, tinea capitis, telogen effluvium, systemic lupus
and secondary syphilis. Additionally, in women of African
decent, traction alopecia involving the anterior and posterior
hairline may mimic alopecia areata in an ophiasis pattern.
Trichotillomania can be differentiated by the incomplete
nature of the hair loss, and the fact that broken hairs in
alopecic areas are still firmly attached to the scalp. Exclamation
point hairs are not seen in trichotillomania. Tinea capitis
usually differs from alopecia areata by the presence of clinical
inflammation, typically manifested as erythema or scaling of
the scalp. While diffuse alopecia in alopecia areata may mimic
telogen effluvium, the latter can usually be differentiated by
227
 Part 3 Follicular Disorders and Alopecias
Figure 12.1:╇ Alopecia areata, ophiasis pattern. (From Johnson, Moy, White: Ethnic
Skin – Medical and Surgical, Mosby Inc., copyright Elsevier 1998.)
patient history. Traction alopecia, systemic lupus and second-
ary syphilis may be differentiated by biopsy and appropriate
serology in the case of the later two.
First-Line Therapies
Reassurance
Topical corticosteroids
Intralesional corticosteroids
Contact immunotherapy
Because spontaneous remission may occur in up to 80% of
patients with limited hair loss and duration of less than one
year, treatment is not necessary for all patients.13 Instead, reas-
surance regarding the nature of the disease, coupled with
appropriate management of expectations, may suffice. Hair
regrowth may be expected within a few months of onset of
any individual alopecia patch.
Topical steroids
Potent topical steroids are widely used to treat patchy alopecia
areata, and are a reasonable choice, especially in children or
in those who cannot tolerate intralesional corticosteroids or
immunotherapy. Although there is little evidence that topical
corticosteroids actually promote hair regrowth, their ease of
application and favorable side effect profile make them a fre-
quent choice. Topical steroid treatment under occlusion may
also be considered.
Topical halcinonide in alopecia areata and alopecia totalis.
Montes LF. J Cutan Pathol 1977; 4:47–50.
The authors report successful treatment with twice daily
0.1% halcinonide cream in patients with alopecia areata and
alopecia totalis. Patients with alopecia areata were not
occluded, while those with alopecia totalis were. The authors
228
report that response time varied from 6 months to 18 months
of treatment to achieve full hair regrowth.
Clobetasol propionate 0.05% under occlusion in the treat-
ment of alopecia totalis/universalis. Tosti A, Piraccini BM,
Pazzaglia M, et╯al. J Am Acad Dermatol 2003; 49:96–98.
Authors reported a 28.5% response rate in patients with
either AT or AT/AU refractory to other topical treatments
using clobetasol propionate 0.05% ointment under occlusion
nightly for six months. 37.5% of responders experienced
relapses of AA and were unable to maintain hair regrowth,
even with treatment.
Intralesional corticosteroids
Triamcinolone acetonide in concentrations ranging from 2.5
to 10╯mg/mL have been reported to be of benefit for circum-
scribed alopecia areata affecting less than 50% of the scalp.14
Multiple 0.1╯mL injections, typically 1╯cm apart, are adminis-
tered into the deep dermis every 4–6 weeks. Intralesional
corticosteroids are not appropriate in extensive or rapidly pro-
gressive disease, and they are likely to be of little benefit in
chronic lesions.15
Intralesional triamcinolone acetonide in alopecia areata
amongst 62 Saudi Arabs. Kubeyinje EP. East Afr Med J 1994;
71:674–675.
62% of patients achieved full regrowth with monthly injec-
E tions of 40╯mg triamcinolone acetonide. Response was greatest
in patients with fewer than five patches of <3╯cm diameter.
B
B
B
Immunotherapy
Contact immunotherapy involves the induction of allergic
contact dermatitis on affected skin by applying contact aller-
gens.16 Popular contact allergens include squaric acid dibu�
tylester (SADBE) and 2,3-diphenylcyclopropenone (DPCP).
Diphencyprone has also been used as a contact allergen. Dini-
trochlorobenzene (DNCB) was the first sensitizer used for
alopecia areata, but is less popular secondary to its mutagenic
effects on Ames testing. Squaric acid dibutylester is of limited
usefulness secondary to its relative instability and need for
refrigeration. Owing to its efficacy and increased stability,
DPCP is currently the most popular choice for immuno-
therapy. Typically, the patient is sensitized with a 2% solution
of DPCP to affected areas of the scalp. Two weeks later, the
affected scalp is treated with a diluted solution of DPCP which
is left on for 1–2 days, and then washed off. Each week, a
progressively more concentrated dilution is utilized. Concen-
trations used are adjusted to maintain erythema and pruritus
to treated areas.17 Patients must avoid sun exposure and
bathing of the treated area for 48 hours. Side effects may
include severe dermatitis, dyspigmentation, fever and lym-
phadenopathy. Urticaria, anaphylaxis and vitiligo have also
been reported.
Prognostic factors in the treatment of alopecia areata with
diphenylcyclopropanone (DPCP). Van der Steen PHM, Van
Baar HMJ, Happle R, Boezeman JBM, Perret CM. J Am Acad
Dermatol 1991; 24:227–230.
 12â•… Alopeciasâ•… •â•… Alopecia areata

In this study of 139 patients, the authors report a 75% steroids are a less attractive option. Well documented side
response rate for those alopecia areata patients treated with effects, including adrenal insufficiency, hypertension, cata-
DPCP with scalp involvement of 40–90%. Patients with more racts, hyperglycemia, osteoporosis and others, severely limit
extensive hair loss had only a 40% response rate. systemic corticosteroids as a viable therapeutic choice.

Topical dinitrochlorobenzene for alopecia areata: revisited.
Mohan KH, Balachandran C, Shenoi SD, Raghavendra R,
Sripathi H, Prabhu S. Indian J Dermatol Venereol Leprol 2008;
74(4):401–402.
A total of 22 patients were included in the study of dinitro-
chlorobenzene (DNCB) with a duration of 6 months. Two
patients had only beard involvement, 8 only scalp involve-
ment, 3 ophiasis pattern alopecia areata, 5 alopecia totalis and
4 alopecia universalis. Complete hair growth was seen in 8
(36.36%) patients and no response in 4 patients. The remain-
ing 10 patients had a variable response. At 6 months, 2 patients
were lost to follow-up and 2 of the 20 patients with complete
hair growth developed patchy hair loss after 3 months.
Alopecia areata: topical immunotherapy treatment with
diphencyprone. Avgerinou G, Gregoriou S, Rigopoulos D,
et╯al. J Eur Acad Dermatol 2008; 22:320–323.
64 patients with extensive and/or long-lasting alopecia
areata were sensitized to 2% diphencyprone. During weekly
visits, patients were treated with gradually increasing concen-
trations of diphencyprone which maintained erythema
and pruritus for 48 hours. Response rates of 83.3% were
reported, with mean duration of treatment until maximum
response reported at 6.14 months. 68.9% of patients experi-
enced relapse during the follow-up period and required
retreatment.
Second-Line Therapies
Pulse methylprednisolone therapy for severe alopecia
areata: an open prospective study of 45 patients. Friedli A,
Labarthe MP, Engelhardt E, Feldmann R, Salomon D, Saurat
J-H. J Am Acad Dermatol 1998; 39:597–602.
This study evaluated the effectiveness of an intravenous
pulse of methylprednisolone (250╯mg b.i.d on 3 successive
days) at 1, 3, 6, and 12 months in 45 patients with AA (>30%
of scalp) of less than 12 months’ duration. Patients with multi-
focal AA (20) showed the best response rate (50–100%).
Relapse occurred in 7 patients. In patients with ophiasis AA
(10), 6 had no response and 4 had 20%–70% regrowth at 1
month with relapse at 3 and 6 months. In patients with uni-
versalis and totalis AA (15), 8 patients had no response, and
3 showed 50–90% regrowth at 1 month, with subsequent
improvement at 3 and 6 months. In 4 patients who did not
show an initial response, a significant number (90–100%)
showed delayed regrowth was observed between 9 and 16
months after the pulse therapy.
Systemic steroids with or without 2% topical minoxidil in
the treatment of alopecia areata. Olsen EA, Carson SC, Turney
EA. Arch Dermatol 1992; 128:1467–1473.
A randomized, controlled trial of 32 alopecia areata patients
(16 with alopecia totalis or universalis) who received a 6-week
taper of prednisone (starting at 40╯mg) followed by either 2%
topical minoxidil or vehicle applied t.i.d for an additional 14
weeks. At the end of 6 weeks of prednisone therapy, 47%
demonstrated more than 25% regrowth and the minoxidil was
felt to help limit post-steroid hair loss.

Systemic corticosteroids B
Anthralin
Anthralin C
PUVA B Anthralin (dithranol) is a contact irritant that is thought to
elicit hair growth through its irritant properties. While its exact
Minoxidil A
mechanism of action is unknown, it is believed to have immu-
Cyclosporin C nosuppressive and anti-inflammatory properties. Though only
Biologics C a small number of case reports show cosmetically acceptable
Hair transplant E results, anthralin may be a viable secondary treatment option.
Micropigmentation B Anthralin is applied topically in a 0.5–1% cream. Its useful-
Camouflage (wigs/hair piece) E ness is limited by dermatitis, staining of skin, hair and fabrics,
folliculitis and regional lymphadenopathy.14

Evaluation of anthralin in the treatment of alopecia areata.

Systemic corticosteroids
Daily systemic corticosteroid therapy may result in hair
regrowth in some patients, particularly those with extensive
patchy alopecia. Those with alopecia totalis, alopecia univer-
salis and an ophiasis like pattern of hair loss are less likely to
respond. Suggested dosages are 1╯mg/kg/day for adults and
0.1–1╯mg/kg/day for children.5
Treatment with pulsed methylprednisolone has also been
reported.18 Because of high relapse rates and the need for long
term treatment to maintain hair regrowth, systemic cortico�
Fiedler-Weiss VC, Buys CM. Arch Dermatol 1987; 123:
1491–1493.
68 patients with severe alopecia areata were treated with
anthralin cream 0.5–1.0%. Cosmetic response was observed
in 25% of the patients and was maintained during therapy in
71% of the cosmetic responders.
Treatment of alopecia areata by anthralin-induced dermati-
tis. Schmoeckel C, Weissmann I, Plewig G, Braun-Falco O.
Arch Dermatol 1979; 115:1254–1255.

229
 Part 3 Follicular Disorders and Alopecias
18 of 24 cases of alopecia areata and 2 of 8 cases of alopecia
totalis demonstrated a cosmetically good result when treated
with anthralin 0.2–0.8%.
PUVA
PUVA (psoralen plus UVA light) has been reported for the
treatment of alopecia areata in several uncontrolled studies. It
is thought that PUVA therapy decreases the perifollicular
inflammatory cell infiltrate seen in alopecia areata. Both oral
and topical psoralen, and local or whole body UVA have been
reported, though response is variable, and high relapse rates
have been reported. Side effects may include erythema and
burning, and PUVA therapy has also been associated with an
increased risk of melanoma.19
PUVA treatment of alopecia areata totalis and universalis: a
retrospective study. Whitmont K, Cooper A. Australas J Der-
matol 2003; 44:106–109.
Patients treated with 8-methoxypsoralen (8-MOP) at an
oral dose of 0.5╯mg/kg plus UVA radiation at 1╯J/cm2 demon-
strated complete hair regrowth in 53% of patients with alo-
pecia totalis, and regrowth in 55% of patients with alopecia
universalis, with a 21% relapse rate in 5.2 years mean follow-up.
PUVA treatment for alopecia areata: experience in a Turkish
population. Sahin S, Yalcin B, Karaduman A. Dermatol 1998;
197:245–247.
24 patients with extensive alopecia areata of more than one
year duration were treated with PUVA three times weekly.
37.5% experienced excellent hair regrowth, and the thera�
peutic efficiency was not related to age, sex, or disease duration
or extent.
PUVA treatment of alopecia areata partialis, totalis and uni-
versalis: audit of 10 years’ experience at St John’s Institute
of Dermatology. Taylor CR. Br J Dermatol 1995; 133(6):
914–918.
Review of 10-year experience of treating alopecia areata,
totalis and universalis with PUVA. The authors detail response
rates of 6.3% for alopecia areata, 12.5% for alopecia totalis
and 13.3% for alopecia areata universalis.
Minoxidil
Minoxidil, first used as an antihypertensive agent, has been
reported to be associated with hair regrowth when used in
concentrations ranging from 1% to 5%. Younger patients
have been reported to respond more favorably to minoxidil
therapy,20 and greater hair regrowth has been reported with the
5% solution.21
Minoxidil has also been reported to be useful in combina-
tion with topical betamethasone propionate.21 Minoxidil does
not appear to be of benefit in patients with extensive alopecia
areata, alopecia totalis, or alopecia universalis.
Response to minoxidil in severe alopecia areata correlates
with T lymphocyte stimulation. Fiedler-Weiss VC, Buys CM,
Br J Dermatol 1987; 117:759–763.
230
47 patients were treated with topical 5% minoxidil solution
twice daily. Terminal hair growth was observed in 85%.
Response to topical 5% minoxidil solution was found to
be significantly greater than response to 1% minoxidil
solution.
Double-blind, placebo-controlled evaluation of topical
minoxidil in extensive alopecia areata. Price VH. J Amer Acad
Dermatol 1987; 16(3):730–736.
This double-blind study evaluated the safety and efficacy of
3% topical minoxidil for alopecia areata, totalis and universa-
lis. Of 30 study subjects, minoxidil was found to be generally
well tolerated, with the exception of some minor itching and
dermatitis. Excellent hair regrowth was noted in 27.3% of the
treatment group, and in 7.1% of controls.
Cyclosporine A
Cyclosporine A, an immunosuppressive drug commonly used
in transplant patients, inhibits T-cell activation. Hypertrichosis
is a well known side effect. Cyclosporine A has proven useful
in the treatment of alopecia areata in several uncontrolled
trials,22 but its utility is limited by its drug interactions,
nephrotoxicity, hepatotoxicity and other clinically significant
side effects.
Oral cyclosporine for the treatment of alopecia areata. A
clinical and immunohistochemical analysis. Gupta AK,
Ellis CN, Gupta C, Voorhees, et al. J Am Acad Dermatol 1990;
22:242–250.
Six patients with alopecia areata, totalis and universalis
were treated with cyclosporine 6╯mg/kg/day for 12 weeks. Hair
regrowth in the scalp of all patients occurred within the second
and fourth weeks of therapy, followed by hair regrowth of the
face and chest (in the male patients), pubic area, extremities,
and axillae. The scalp was the best responder. Terminal hair
regrowth was deemed cosmetically acceptable in 3 of 6
patients. It should be noted, however, that ‘significant’ hair
loss occurred in all patients within 3 months of discontinua-
tion of cyclosporine therapy.
Biologics
Biologics, typically comprised of recombinant cytokines,
humanized monoclonal antibodies and molecular receptors
that bind target molecules, act by reducing pathogenic T cells.
Recently, efalizumab, a recombinant humanized monoclonal
anti-CD11a antibody, was reported to induce hair regrowth in
one patient with a long history of alopecia areata.23 The
usefulness of biologics is still uncertain.
Successful treatment of alopecia areata with efalizumab.
Kolde G, Meffert H, Rowe E. J Eur Acad Dermatol Venereol
2008; 22:1519–1520.
Efalizumab is a recombinant humanized monoclonal anti-
CD11a antibody that is known to block the migration of T cells
into the skin of psoriasis lesions. A 44-year-old woman with
a 3-year history of alopecia was treated with efalizumab at the
same protocol as used in psoriasis. Hair regrowth was observed

by 1 month, and by 8 months was reported at 80% at one
lesion and 100% at a second lesion. No relapse was observed
at 6 months.
Treatment of alopecia areata partim universalis with efali-
zumab. Kaelin U, Hassan AS, Braathen LR, Yawalkar N. J Am
Acad Dermatol 2006; 55:529–532.
The authors report a case of a 19-year-old man with a four
year history of extensive alopecia affecting all hair bearing
areas except for the eyebrows and eyelashes. He was treated
with efalizumab (initial dose, 0.7╯mg/kg/wk and 1.0╯mg/kg/
wk thereafter). After 6 months of therapy, he had 90% regrowth
of terminal pigmented scalp hairs, and 30–40% regrowth in
the pubic and axillary regions. The treatment was well toler-
ated with no reported side effects.
Etanercept does not effectively treat moderate to severe alo-
pecia areata: an open label study. Strober B, Siu K, Alexis A,
et╯al. J Am Acad Dermatol 2005; 52:1082–1084.
In this prospective, open-label pilot study, etanercept, a
TNF-α inhibitor, was used to treat 17 patients with moderate
to severe alopecia areata, alopecia totalis, or alopecia univer-
salis. Patients were treated with etanercept 50╯mg given sub�
cutaneously twice weekly. After 8–24 weeks of continuous
treatment, significant regrowth of hair was not shown in any
of the treated subjects.
Other treatments
Hair transplant has been previously reported in a patient with
eyebrow alopecia areata.24 More recently, successful scalp hair
regrowth has been reported following hair transplantation
from unaffected scalp, with no relapse of alopecia noted at a
10-month follow up.25
Successful hair transplant of eyebrow alopecia areata.
Barankin B, Taher M, Wasel N. J Cutan Med Surg 2005; 9(4):
162–164.
A 30-year-old male with chronic eyebrow alopecia was
treated with 85 mini and micrografts to the right eyebrow. The
patient remained free of eyebrow alopecia for eight months
following the transplant. However, after 8 months, relapse
ensued, requiring intralesional corticosteroids for mainte-
nance of hair growth.
Successful hair transplantation of recalcitrant alopecia
areata of the scalp. Unger R, Dawoud T, Albaqami R. Derma-
tol Surg 2008; 34:1589–1594.
A 62-year-old male patient with a 4-year history of localized
patchy alopecia areata affecting the scalp and eyebrows was
treated with hair transplants into areas of alopecia areata and
androgenetic alopecia. The areas of alopecia areata exhibited
more than double the amount of hair regrowth than was
expected, and at a 10-month follow-up, alopecia areata was
still found to be inactive.
Other options for patients include micropigmentation (tat-
tooing), particularly of the eyebrow, and the use of a wig or
hairpiece as camouflage.
12â•… Alopeciasâ•… •â•… Alopecia areata
Commonly encountered pitfalls
Common therapeutic regimens utilized in alopecia areata are
limited by their side effects. Skin of color patients may be
particularly susceptible to pigmentary sequelae from some
treatment options. Intralesional corticosteroids, and to a lesser
extent topical corticosteroids, may be associated with hypo�
pigmentation of the skin in treated areas. Likewise, allergens
and irritants, such as DPCP and anthralin, may have lasting
dyspigmentation as a side effect of brisk dermatitic reactions.
Patients should be appropriately forewarned.
Special management & counseling considerations
Although alopecia areata has no direct impact on general
health, it may be associated with significant psychological
sequelae. Patients with alopecia areata have been found to
have an increased prevalence of anxiety and mood and adjust-
ment disorders.25 Treatment of patients with alopecia areata
should include a frank discussion of the nature and prognosis
of the disease, as well as a review of available treatments. Due
to the psychosocial effects of the disease, which can be signifi-
cant in extensive disease and when treating young patients,
appropriate referral for psychological support is of benefit.
The National Alopecia Areata Foundation, as well as local
support groups, are likely to be helpful (www.naaf.org).
References
1. Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton LJ III. Incidence
of alopecia areata in Olmsted County, Minnesota, 1975–1989. May
Clin Proc 1995; 70:628–633.
2. Muller SA, Winkelmann RK. Alopecia areata. An evaluation of 736
patients. Arch Dermatol 1963; 88:290–297.
3. Shellow WV, Edwards JE, Koo JY. Profile of alopecia areata: a question-
naire analysis of patient and family. Int J Dermatol 1992; 31:186–
189.
4. Tan E, Tay YK, Goh CL, Chin GY. The pattern of alopecia areata in
Singapore – a study of 219 Asians. Int J Dermatol 2002; 41:748–753.
5. Tan E, Tay YK, Giam YC. A clinical study of childhood alopecia areata
in Singapore. Ped Dermatol 2002; 19:298–301.
6. McDonagh AJ, Tazi-Ahnini R. Epidemiology and genetics of alopecia
areata. Clin Exp Dermatol 2002; 27:405–409.
7. McMichael AJ. The genetic epidemiology of autoimmune pathogenesis
alopecia areata. J Eur Acad Dermatol Venereol 1997; 9:36–43.
8. McDonagh AJG, Messenger AG. The pathogenesis of alopecia areata.
Dermatol Clin 1996; 14:661–670.
9. Berker D, Baran D. RPR Handbook of diseases of the nails and their
management. Oxford: Blackwell Science; 2004.
10. Walker SA, Rothman S. Alopecia areata: a statistical study and consid-
eration of endocrine influences. J Invest Dermatol 1950; 14:403–
413.
11. Gip L, Lodin A, Molin L. Alopecia areata. A follow-up investigation of
outpatient material. Acta Derm Venereol (Stockh) 1969; 49:180–
188.
12. MacDonald Hull SP, Wood ML, Hutchinson PE, Sladden M, Messenger
AG, et al. Guidelines for the management of alopecia areata. Br J
Dermatol 2003; 149:692–699.
13. Ikeda T. A new classification of alopecia areata. Dermatologica 1965;
131:421–445.
14. Ross EK, Shapiro J. Management of hair loss. Dermatol Clin 2005;
23:227–243.
231
 Part 3 Follicular Disorders and Alopecias
15. Fiedler VC, Alaiti S. Treatment of alopecia areata. Dermatol Clin
1996; 14:733–737.
16. McMichael AJ. Topical sensitizers in alopecia areata. Dermatol Nurs
2004; 16:333–336.
17. Happle R, Hausen BM, Wiesner-Menzel L. Diphencyprone in the treat-
ment of alopecia areata. Acta Derm Venereol (Stockh) 1983; 63:
49–52.
18. Assouly P, Reygagne P, Jouanique C, Matard B, Marechal E, Reynert P.
Intravenous pulse methylprednisolone therapy for severe alopecia
areata. An open study of 66 patients. Ann Dermatol Venereol 2003;
130:326–330.
19. Stern RS, Nichols KT, Vakeva LH. Malignant melanoma in patients
treated for psoriasis with methoxsalen (psoralen) and ultraviolet
A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med 1997;
336:1041–1045.
Alopecia mucinosa
First described by Hermann Pinkus in 1957, alopecia muci-
nosa, also commonly referred to as follicular mucinosis, is
typically characterized by grouped follicular papules, nodules
and infiltrated plaques associated with alopecia. Lesions
may be isolated or multiple, and the face and scalp are most
commonly affected. Affected areas may demonstrate ery�
thema and scaling and mucinous material can sometimes
be manually expressed from active lesions. Lesions may dem-
onstrate prominent follicular orifices. Less common clinical
presentations of alopecia mucinosa include dermatitic, acnei-
form and hypo�pigmented forms.1,2,3,4 Though typically non-
scarring, scarring alopecia has been associated with alopecia
mucinosa.
Alopecia mucinosa has no known racial predilection. It
is thought to be more common in males. There are three
subtypes of alopecia mucinosa: a primary idiopathic form; a
malignancy associated form; and a form associated with
inflammatory conditions. The idiopathic form is further sub-
divided into a primary acute form of younger patients, and a
primary chronic form of older individuals. In the idiopathic
primary acute form, lesions are typically focal and limited to
the head, neck and shoulders. Patients are typically young,
with the pediatric population comprising the majority of
cases, and the remainder of patients being under forty. Lesions
typically resolve spontaneously within 2 months to 2 years.
In the idiopathic primary chronic form of alopecia muci-
nosa, patients have more generalized lesions and exhibit a
chronic and relapsing course. Patients in this group are typi-
cally between the fourth and sixth decades.
Malignancy associated alopecia mucinosa usually occurs
between 40 and 70 years, and mycosis fungoides is the most
commonly associated malignancy. Mycosis fungoides is recog-
nized at the time of diagnosis in 15–30% of patients with
alopecia mucinosa. It is important to note that the diagnosis
of malignancy may precede, coincide with or follow a diagno-
sis of alopecia mucinosa, thus careful physical investigation
and frequent follow-up are necessary. Other associated
232
20. Ranchoff RE, Bergfeld WF, Steck WD, Subichin SJ, Extensive alopecia
areata. Results of treatment with 3% topical minoxidil. Cleve Clin J
Med 1989; 56:149–154.
21. Fiedler VC. Alopecia areata: current therapy. J Invest Dermatol 1991;
96:69S.
22. Gupta AK, Ellis CN, Tellner DC, Voorhees JJ. Cyclosporine A in the treat-
ment of severe alopecia areata. Transplant Proc 1988; 20:105–108.
23. Ruiz-Doblado S, Carrizosa A, Garcia-Hernandez MJ. Alopecia areata:
psychiatric comorbidity and adjustment to illness. Int J Dermatol
2003; 42:434–437.
24. Bark-Lynn L, Min-Kyung S, Woo-Young S. Acute diffuse and total alo-
pecia: a new subtype of alopecia areata with a favorable prognosis.
J Am Acad Dermatol 2009; 60:85–93.
25. Wasserman D, Guzman-Sanchez DA, Scott K, McMichael A. Alopecia
areata. Int J Dermatol 2007; 46:121–131.
malignancies include Hodgkin’s lymphoma, leukemia cutis,
Kaposi’s sarcoma and various forms of leukemia.
Alopecia mucinosa can be associated with various inflam-
matory disorders, including angiolymphoid hyperplasia,
lupus erythematosus, sarcoidosis, lichen simplex chronicus
and HIV associated eosinophilic folliculitis.2,5,6,7,8 Recently,
drug-induced alopecia mucinosa has been associated with
adalimumab and imatinib.9,10
The etiology of alopecia mucinosa is unknown, but cell
mediated immunity is hypothesized to play a role in the
pathogenesis. Mucin deposition is thought to be secondary to
the interplay of T cells with the follicular keratinocytes.11
The diagnosis of alopecia mucinosa typically requires a skin
biopsy. As mycosis fungoides is commonly associated with
alopecia mucinosa, multiple skin biopsies may be necessary.
Immunohistochemistry and T-cell gene receptor analysis may
be helpful, though it should be noted that clonal expansion
can be seen in lymphoma-associated and benign forms of
alopecia mucinosa. Work-up should include a complete
history and physical, as well as directed studies to rule out
underlying associated disorders.
The differential diagnosis of alopecia mucinosa may include
alopecia areata, dermatitis, an acneiform eruption or folliculi-
tis. Histological evaluation will reveal the characteristic follicu-
lar degeneration and mucin accumulation within the follicular
epithelium and sebaceous glands.
First-Line Therapies
Treatment of underlying disorder, if present
Topical corticosteroids D
Intralesional corticosteroids D
Systemic corticosteroids E
Oral antibiotics E
Interferon E
Topical retinoids E
Oral retinoids E
PUVA E

There is no standard, uniformly effective therapy for alo-
pecia mucinosa. Because of its variable course and spontane-
ous resolution in some forms, the efficacy of any one therapy
can be difficult to assess. In variants associated with malig-
nancy or inflammatory disease, treatment is directed towards
the underlying disorder. To date, there are no known
published placebo-controlled treatment trials for alopecia
mucinosa. Commonly utilized primary therapies include
topical, intralesional and systemic corticosteroids. Other
primary treatments include minocycline, tetracycline, tretin-
oin, isotretinoin, and topical and systemic PUVA.12
Follicular mucinosis presenting as an acneiform eruption:
report of four cases. Wittenburg GP, Gibson LE, Pittelkow MR,
el-Azhary RA. J Am Acad Dermatol 1998; 38:849–851.
The authors report four cases of follicular mucinosis occur-
ring in early adulthood as an unusual acneiform eruption and
demonstrating a protracted course. They report a 22-year-old
woman treated with tretinoin gel 0.01% daily and pentoxifyl-
line 400╯mg t.i.d, with a 20% decrease in lesion size in one
month; a 21-year-old white female treated with tetracycline
and benzoyl peroxide gel, with 90% improvement at a 16-
year follow-up; a 31-year-old male with minor improvement
with minocycline 100╯mg/day for 4 months; and a 35-
year-old woman treated with isotretinoin 40╯mg/day and
clobetasol cream intermittently with significant improvement
over 3 months.
Alopecia mucinosa: report of a case and review. Anderson
BE, Mackely CL, Helm KF. J Cutan Med Surg 2003; 7(2):
124–128.
The authors report a 53-year-old white male with a 3-year
history of disease treated with minocycline 100╯mg b.i.d. They
report complete remission within 5 weeks. At 11 weeks, he was
tapered to minocycline 50╯mg b.i.d, and has remained in
remission at 7-month follow up.
Follicular mucinosis treated with PUVA. Kenicer KJA,
Lakshmipathi T. Br J Dermatol 1982; 107(22s):48–49.
The authors describe the successful treatment of a 79-year-
old woman with follicular mucinosis, which previously failed
to respond to both topical corticosteroids and radiotherapy,
which responded to PUVA with a total exposure dose of
454╯J/cm2.
Follicular mucinosis associated with early stage cutaneous
T-cell lymphoma: successful treatment with interferon
alpha-2b and acitretin. Kontochristopoulos GJ, Exadaktyloub
D, Hatziolou E, Tassidou A, Zakopoulou N. J Dermatol Treat
2001; 12:117–121.
Report of a case of secondary follicular mucinosis in which
cutaneous T-cell lymphoma was detected 6 years after the
initial eruption. Complete remission was achieved using com-
bination therapy of interferon alpha-2b at a dose of 6 million
U subcutaneously three times a week, and acitretin 35╯mg/day,
for 6 months.
12â•… Alopeciasâ•… •â•… Alopecia mucinosa
Second-Line Therapies
Topical nitrogen mustard E
Radiation therapy D
Dapsone E
Topical immunomodulators E
Indomethacin E
Photodynamic therapy E
Methotrexate E
Mepacrine E
Secondary treatments may include topical nitrogen mustard,
radiation therapy, dapsone,1 topical immunomodulators,
indomethacin,13 photodynamic therapy, methotrexate and
mepacrine.
A case of follicular mucinosis treated successfully with
pimecrolimus. Gorpelioglu C, Sarifakioglu E, Bayrak R. Clin
Exp Dermatol 2009; 34:86–87.
A 24-year-old man with facial follicular mucinosis recal�
citrant to topical corticosteroids responded to pimecrolimus
cream 1% b.i.d with complete remission after one month and
no disease recurrence at 7-month follow-up.
Primary follicular mucinosis: excellent response to treat-
ment with photodynamic therapy. Fernandez-Guarino M,
Castano AH, Carrillo R, Jaen P. J Eur Acad Dermatol Venereol
2008; 22:393–394.
The authors report a 79-year-old woman with a 4-year
history of primary follicular mucinosis treated with photody-
namic therapy (methylaminolaevulinic acid, and using red
light at 630╯nm for 7.5 minutes). They report good tolerance
of the treatment with only transient erythema, and cutaneous
lesion response in 6 to 7 days.
Atypical follicular mucinosis controlled with mepacrine.
Sonnex TS, Ryan TG, Dawber RPR. Br J Dermatol 1981;
105(19s):83–84.
Report of a 39-year-old male patient with facial follicular
mucinosis which responded to mepacrine 100╯mg b.i.d. The
patient developed lesion recurrence upon cessation of therapy.
Primary follicular mucinosis: excellent response to treat-
ment with photodynamic therapy. Fernández-Guarino M,
Harto Castaño A, Carrillo R, Jaén P. J Eur Acad Dermatol
Venereol 2007; 22:393–394.
A 79-year-old woman with a 4-year history of follicular
mucinosis, recalcitrant to topical corticosteroids, dapsone, and
narrowband UVB, was treated with photodynamic therapy
(topical methylaminolaevulinic acid occluded 3╯h), and after-
wards treated with red light as a founding source (630╯nm,
37╯J/cm2, 7.5╯min). The treated lesions cleared in 6–7 days
with no recurrence at 9-month follow-up.
233
 Part 3 Follicular Disorders and Alopecias
Commonly encountered pitfalls
Though most commonly associated with non-scarring alo-
pecia, alopecia mucinosa can also be associated with scarring
alopecia, and should be included in the differential diagnosis
of persons with scarring alopecia. Also, with hair shaft break-
age, alopecia mucinosa may display the ‘black dots’ commonly
associated with tinea capitis.
Special management & counseling considerations
Though spontaneous resolution of alopecia mucinosa can
occur in benign forms of the disease, patients may suffer con-
siderable morbidity from the cosmetic appearance of affected
skin. So, while observation alone may be advisable in some
cases, in others, clinically benign treatment measures should
be considered. Also, because of its association with lympho-
proliferative malignancies and mycosis fungoides, clinical
follow up and serial biopsies should be discussed.
References
1. Rustin MHA, Bunker CB, Levene GM. Follicular mucinosis presenting
as acute dermatitis and response to dapsone. Clin Exp Dermatol
1989; 14:382–384.
Central centrifugal
cicatricial alopecia
Among African-Americans, central centrifugal cicatricial alo-
pecia (CCCA) has been purported to be responsible for more
cases of scarring alopecia as compared to all other forms com-
bined.1 Clinically, CCCA develops as a scarring, roughly circu-
lar area of alopecia on the crown and/or vertex of the scalp
(Figs. 12.2A and B).2 With time, this scarred centralized area
progresses centrifugally. The affected scalp is in parts smooth,
shiny and illustrates massive follicular dropout (Fig. 12.2C).
Typically, a few short, brittle hairs remain within the scarred
expanse. Often, patients complain of dysesthesia (tenderness,
itching) in the affected area.2,3 Anecdotally, dysesthesias may
be associated with progression of the alopecia and active
inflammation.
While there is sparse epidemiologic data on the racial and
sex distribution of CCCA, the vast majority of reports describe
women of African ancestry. The etiology of CCCA remains
controversial. Etiologic hypotheses have included the early
degeneration of the inner root sheath (IRS), traction, chemical
insults and follicular stem cells injury. Recently, evidence has
shown a correlation between CCCA and the use of both sewn
and glued hair weaves, and the use of cornrow or braided
hairstyles with added extension hair.4
234
2. Zakon SJ, Gendleman M. Alopecia mucinosa. Arch Dermatol 1973;
110:653.
3. Wittenberg GP, Gibson LE, Pittelkow MR, el-Azhary RA. J Am Acad
Dermatol 1998; 38:849–851.
4. Locker E, Duncan C. Hypopigmentation in alopecia mucinosa. Arch
Dermatol 1979; 115:731–733.
5. Buezo GF, Fraga J, Abajo P, et al. HIV-associated eosinophilic folliculitis
and follicular mucinosis. Dermatology 1998; 197:178–180.
6. Hempstead RW, Ackerman AB. Follicular mucinosis: a reaction pattern
in follicular epithelium. Am J Dermatopathol 1985; 7(3):255–257.
7. Tupker RA, van der Meer JB, Croote D, et al. Urticaria-like follicular
mucinosis in a young female patient. Acta Derm Venereol 1997;
77:323–324.
8. Wolff HH, Kinney J, Ackerman AB. Angiolymphoid hyperplasia with
follicular mucinosis. Arch Dermatol 1978; 114:229–232.
9. Dalle S, Balme B, Berger F, Hayette S, Thomas L. Mycosis fungoides-
associated follicular mucinosis under adalimumab. Br J Dermatol
2005; 153(1):207–208.
10. Scheinfeld N. Imatinib mesylate and dermatology part 2: a review of
the cutaneous side effects of imatinib mesylate. J Drugs Dermatol
2006; 5(3):228–231.
11. Lancer HA, Bronstein BR, Nakagawa H, et al. Follicular mucinosis:
a detailed morphologic and immunopathologic study. J Am Acad
Dermatol 1984; 10:760–768.
12. Kenicer KJA, Lakshmipathi T. Follicular mucinosis treated with PUVA.
Br J Dermatol 1982; 107(22s):48–49.
13. Kodama H, Umemura S, Nohara N. Follicular mucinosis: response to
indomethacin. J Dermatol 1988; 15:72–75.
First-Line Therapies
Avoidance/limitation of traumatic hair grooming E
practices
Topical corticosteroids E
Intralesional corticosteroids E
Oral antibiotics E
Since CCCA is a progressive disease that may likely be tem-
pered with early intervention, prompt identification and treat-
ment of these patients is crucial. Avoidance of potentially
damaging hair care practices such as chemical relaxers, exces-
sive heat, traction and hardening gels and sprays should be
advised. Patients should be strongly counseled to discontinue
all chemical relaxers, as well as all hair styles which are likely
to be associated with excessive traction (cornrowing, braiding,
weaving, or other extensions).5 For patients in whom ceasing
use of chemical relaxers is not a viable option, it should be
recommended that chemical services be professionally
done (salon), that a base (usually petrolatum derivative)
be applied to the entire scalp prior to relaxer applications,
and that relaxers be applied no more frequently than every
8–12 weeks.2
Unfortunately, population based studies regarding the
response of CCCA to varying therapeutic regimens are lacking.
Many clinicians advocate a symptomatic treatment approach
 12â•… Alopeciasâ•… •â•… Central centrifugal cicatricial alopecia
A
B
C
Figure 12.2:╇ (A) Early stage CCCA. (B) CCCA. (C) Late stage CCCA. (Courtesy,
Susan Taylor, MD.)
for patients diagnosed with CCCA, instead of one based solely
upon objective and histopathologic evidence of inflammation.
Subjective symptoms of inflammation such as paresthesias,
itching, and tenderness warrant treatment. First-line therapies
include mid or high potency topical steroids and intralesional
corticosteroids. Topical steroids are initially utilized daily,
until stabilization, and then 3 days weekly for maintenance.5
Intralesional corticosteroids, ranging in potency up to 10╯mg/
mL are administered monthly for a period of at least 6 months,
and then symptomatically thereafter. For particularly aggres-
sive cases, oral antibiotics such as tetracycline, doxycycline or
minocycline are added for a duration of typically no less than
6 months, primarily for their anti-inflammatory properties.
Often, a seborrheic dermatitis treatment regimen is helpful in
decreasing pruritus and scaling.2 This includes increasing hair
washing frequency to at least once weekly. Anecdotally, these
aggressive anti-inflammatory treatments have been effective
for some patients, particularly those presenting with early
disease. Reversing existing scarring alopecia is not possible,
and should not be the goal of therapy. Therapy should be
directed at the periphery of the alopecic region, including the
surrounding normal appearing scalp, in an effort to thwart
progression of the inflammatory process. A significant response
to an anti-inflammatory regimen is often noted within a
few months, but many take up to 6 months. Once response
is achieved, treatment frequency may be gradually tapered
and then discontinued when remission is sustained for a
full year.6
Second-Line Therapies
Antimalarials E
Minoxidil E
Thalidomide E
Cyclosporine E
Mycophenolate mofetil E
Hair transplantation E
Camouflage E
Micropigmentation E
Other proposed treatments have included antimalarials,
minoxidil, thalidomide, cyclosporine, mycophenolate mofetil,
vitamins and various herbal treatments.7,8,9 For those individu-
als with end stage scarring, camouflage techniques such as
custom wigs, hair weaving, color sticks or crayons, and micro-
pigmentation (permanent tattooing) can be recommended.
Hair transplantation may be an option for some patients,
but it should be noted that the presence of recipient site
scarring presents a significant challenge and may decrease graft
survival rates.2
Commonly encountered pitfalls
Patient education regarding proper hair grooming techniques
and avoidance of traumatic hairstyling is paramount. When
discouraging certain hair care practices (e.g. braiding and
weaving) it is important that clinicians provide viable alterna-
tives to the patient. Patient expectations must be properly
managed, and it should be made clear that any existing scar-
ring alopecia is permanent, and the goal of therapy is to limit
additional hair loss. Patients treated with topical and intrale-
sional corticosteroids should be made aware of the potential
for dyspigmentation of the treated skin.
235
 Part 3 Follicular Disorders and Alopecias

Special management & counseling considerations References

Central centrifugal cicatricial alopecia is a chronic disorder, 1.
with etiologic factors still poorly defined. It is important that
2.
patients understand that the disease is likely to be chronic, and
periods of exacerbation may be expected. The importance of
follow-up and probable life long vigilance with gentle hair 3.
styling techniques should be emphasized. Many persons with
4.
African textured hair, particularly those with heat straightened
(pressed/hot combed) hair will prefer topical corticosteroid
treatment in an oil or ointment vehicle, as creams, lotions and 5.
gels may be drying to the hair and may cause reversion of
6.
straightened hair to its natural curled texture. Finally, clinicians
should be mindful of the significant psychosocial impact that 7.
the alopecia may have, and appropriate referral for counseling
should be considered. 8.
9.
Sperling LC, Cowper SE. The histopathology of primary cicatricial
alopecia. Semin Cutan Med Surg 2006; 25:41–50.
Callender VD, McMichael AJ, Cohen GF. Medical and surgical thera-
pies for alopecias in black women. Dermatol Ther 2004; 17:164–
176.
Sperling LC, Sau P. The follicular degeneration syndrome in black
patients. Arch Dermatol 1992; 128:68–74.
Gathers RC, Jankowski M, Eide M, Lim HWL. Hair grooming practices
and central centrifugal cicatricial alopecia. J Am Acad Dermatol 2009;
60(4):660–668.
Gathers RC, Lim HWL. Central centrifugal cicatricial alopecia: past,
present and future. J Am Acad Dermatol 2009; 60(4):574–578.
Ross EK, Tan E, Shapiro J. Update on primary cicatricial alopecias.
J Am Acad Dermatol 2005; 53:1–37.
McMichael AJ. Ethnic hair updates: past and present. J Am Acad
Dermatol 2003; 48:S127–S133.
Scott DA. Disorders of the hair and scalp in blacks. Dermatol Clin
1988; 6:387–395.
Price VH. The medical treatment of cicatricial alopecia. Semin Cutan
Med Surg 2006; 25:56–59.

The differential diagnosis of dissecting cellulitis includes

Dissecting cellulitis folliculitis decalvans, tinea capitis, folliculotropic mycosis fun-

goides, and acne keloidalis nuchae. Folliculitis decalvans is
characterized by perifollicular pustules, erythema, scaling and
Dissecting cellulitis (also known as perifolliculitis capitis smooth atrophic plaques of scarring alopecia. Tinea capitis
abscedens et suffodiens, Hoffman’s disease, dissecting [peri] and kerion can be differentiated by culture. Folliculotropic
folliculitis, and perifolliculitis capitis) is a chronic, relapsing mycosis fungoides can be differentiated by histopathology.
suppurative dermatitis of the scalp. It is characterized by a Acne keloidalis nuchae typically lacks fluctuant nodules and
destructive folliculitis that eventuates in multiple tender sinus tracts.
nodules, pustules, abscesses and intercommunicating sinuses The prognosis of dissecting cellulitis is guarded. This disease
(Fig. 12.3A, B and C). The vertex and occiput are most com- typically follows a chronic and relapsing course and may be
monly affected, and the scalp may have a distinctive cerebri- recalcitrant to many treatments.
form appearance. Inflammatory nodules may be firm or
fluctuant and may drain pus, blood and jelly-like serous fluid.
Shedding of hair is often noted from the surface of nodules,
and there is relative sparing between areas of inflammation.
Dissecting cellulitis commonly heals with patchy or confluent First-Line Therapies
scarring alopecia, and keloidal scars may also result.
Dissecting cellulitis is most common among black men in Antibiotic soaps E
the second to fourth decades, though there are rare reports of Oral antibiotics E
the disease in whites and females. Dissecting cellulitis, along Topical antibiotics E
with acne conglobata, hidradenitis suppurativa and pilonidal Topical corticosteroids E
cysts compose the follicular occlusion tetrad. Although the Intralesional corticosteroids E
exact etiology is unknown, it is widely accepted that dissecting
Isotretinoin E
cellulitis is secondary to follicular blockage, in which abnor-
mal follicular keratinization and retention of follicular mate�
rials results in follicular dilation and rupture. Consequent
keratin and follicular debris elicit a neutrophilic and granulo-
matous inflammatory response. For mild or early disease, antibiotic soaps, oral and topical
The diagnosis of dissecting cellulitis is often a clinical one. antibiotics and topical and intralesional corticosteroids
Work-up should include bacterial culture and sensitivity so are often utilized initially. Chlorhexidine and benzoyl perox-
that secondary infection may be treated. Staphylococcus aureus, ide cleansers may be used daily to ensure adequate scalp
Staphylococcus epidermidis and Staphylococcus albus are most hygiene. Topical antibiotics may be directed at bacterial culture
commonly cultured. The work-up may also include fungal, results, and broad spectrum systemic antibiotics such as tetra-
mycobacterial and viral cultures, particularly if the diagnosis cycline may reduce the inflammation associated with the
is unclear. disease.

236
 12â•… Alopeciasâ•… •â•… Dissecting cellulitis

Perifolliculitis capitis abscedens et suffodiens. Moscatelli P,

Ippoliti D, Bergama F, Piazza P. Eur J Dermatol 2001;
11(2):155–156.
The authors report a 25-year-old woman with dissecting
cellulitis of the scalp treated with doxycycline 200╯mg/day and
prednisone 50╯mg/day, with dose reduced every 2 weeks to an
eventual dosage of doxycyline 50╯mg/day and prednisone
5╯mg/day. Clinical improvement was noted a few weeks
after initiation of therapy, and within 3 months, complete
healing was reported. Treatment was discontinued after 4
months, with no disease recurrence reported at a 2-year
follow-up.
Ciprofloxacin has recently been reported to be of use in
dissecting cellulitis.

A Dissecting cellulitis of the scalp responding to oral quino�

lones. Greenblatt DT, Sheth N, Teixeira F. Clin Exp Dermatol
2007; 33(1):99–100.
A 28-year-old Indian male with recalcitrant disease was
treated with ciprofloxacin 250╯mg b.i.d. After 2 months, the
authors reported lesion flattening and resolution of purulent
discharge. The dosage was decreased to 250╯mg q.d, with good
disease control at 5 months follow-up.

Intralesional triamcinolone acetonide ranging in potency

from 5 to 40╯mg/mL may decrease inflammation in mild
disease, but is only a temporizing measure, with short term
benefit.
Isotretinoin is considered first line therapy for more severe
disease, and a long course of therapy is typically recommended.
Doses of 1╯mg/kg/day are recommended for a minimum of 4
months, with treatment continued for an additional 5–7
months after the disease appears inactive.
B

Dissecting cellulitis of the scalp: response to isotretinoin.

Khaded A, Zeglaoui F, Zoghlami A, Fazaa B, Kamoun MR. J Eur
Acad Dermatol Venereol 2007; 21(10):1430–1431.
The authors report a 25-year-old man with dissecting cel-
lulitis treated with oral isotretinoin 0.8╯mg/kg daily. After 4
weeks, they reported significant reduction of abscess formation
and nodule flattening. By 4 months of treatments, nodules had
completely flattened and there was evidence of hair regrowth.
After 12 months of therapy, the treatment was stopped, with
no relapse reported at a 6-month follow-up.

Perifolliculitis capitis abscedens et suffodiens success�

fully controlled with topical isotretinoin. Karpouzis A,
Giatromanolaki A, Sivridis E, Kouskoukis C. Eur J Dermatol
2003; 13(2):192–195.
The authors report successful treatment of a 20-year-old
C white male with isotretinoin gel (0.05%) and clindamycin
gel (1%). After 2 months of therapy, they report a dramatic
Figure 12.3:╇ (A) Dissecting cellulitis of the scalp. (B) Dissecting cellulitis of the decrease in cystic infiltration and diffuse hair regrowth over at
scalp with discharge. (C) Dissecting cellulitis of the scalp with severe scarring and least 50% of the disease plaques. No relapse was note 1 year
alopecia. after treatment.

237
 Part 3 Follicular Disorders and Alopecias
Second-Line Therapies
Oral corticosteroids E cellulitis treated with complete scalp excision and split-
Oral zinc E thickness graft from the anterior thighs. The scalp reportedly
Biologics E healed completely one month after surgery, and at a 10-month
Incision and drainage/Scalp excision of lesional skin E follow-up, the patient continued to be disease free and was
Laser E satisfied with the cosmetic results.
X-ray beam radiation therapy E Laser therapy, including the CO2 and long pulsed non-Q-
Alternate day prednisone therapy may be of benefit,1 and
combination prednisone and doxycycline therapy has been
reported in one case.
Oral zinc has also been reported to be of benefit.
Successful treatment of dissecting cellulitis and acne con-
globata with oral zinc. Kobayashi H, Aiba S, Tagami H. Br J
Dermatol 2001; 141(8)1136–1152.
The authors report the successful treatment of a 15-year-old
Japanese boy with oral zinc sulfate, ranging in dosage from
135╯mg t.i.d. to 135╯mg q.d. to b.i.d. They reported lesional
flattening, hair regrowth, no increase in the plasma zinc level
over the normal range or any side effects other than nausea at
initiation of therapy.
Recently, infliximab has been reported to be of benefit, with
a dosage of 5╯mg/kg every 8 weeks. Adalimumab has also been
reported to be helpful in cases refractory to antibiotics and
intralesional corticosteroids.
Perifolliculitis capitis abscedens et suffodiens successfully
controlled with infliximab. Brandt HRC, Malheiros APR,
Teixeira MG, Machado MCR. Br J Dermatol 2008; 159(2):
506–507.
Infliximab is a chimeric monoclonal antibody that binds
specifically to TNF-α. The authors report a 24-year-old man
with recalcitrant disease treated with infliximab 5╯mg/kg
infused at 8-week intervals over 12 months. They report an
excellent response with hair beginning to regrow after the
second infusion and response continuation over the 12-month
treatment period. No relapse was noted at a 1-year follow-up.
Refractory dissecting cellulitis of the scalp treated with adal-
imumab. Sukhatme SV, Lenzy YM, Gottlieb AB. J Drugs Der-
matol 2008; 7(10):981–983.
A case report detailing the successful treatment of a 39-year-
old white male with a 6-year history of dissecting cellulitis
with adalimumab, a tumor necrosis factor (TNF)-alpha
antagonist.
Surgical treatments including incision and drainage of fluc-
tuant lesions and scalp excision with split thickness skin grafts
have been reported.
Successful treatment of recalcitrant dissecting cellulitis of
the scalp with complete scalp excision and split thickness
238
skin graft. Bellew SG, Nemerofsky R, Schwartz R, Granick MS.
Dermatol Surg 2003; 29(10):1068–1070.
The authors report a 25-year-old black male with dissecting
switched ruby laser have been utilized.2,3 The 800╯nm diode
laser and long pulsed Nd-YAG laser have shown benefit in
some reports.4
Dissecting cellulitis treated with the long pulsed Nd:YAG
laser. Krasner BD, Hamzavi FH, Murakawa GJ, Hamzavi IH.
Dermatol Surg 2006; 32(8):1039–1044.
This observational study reported 4 African-American men
with long standing dissecting cellulitis treated with Nd-YAG
laser. Patients were treated with 3–7 monthly laser sessions. 3
of the 4 patients stopped or decreased their need for systemic
medications or therapy after the conclusion of treatment. 3
patients also experienced regrowth of terminal hairs within
treatment sites.
Modern X-ray beam radiation therapy has been reported for
severe refractory disease, though carcinogenic risk limits this
modality.
Modern external beam radiation therapy for refractory dis-
secting cellulitis of the scalp. Chinnaiyan P, Tena LB, Brenner
MJ, Welsh JS. Br J Dermatol 2005; 152(4):777–779.
3 African-American and 1 Hispanic male were treated 5
days weekly with electron or a combination of electrons and
photons to the entire scalp. The authors reported rapid resolu-
tion of pain in all patients with a regression of nodules and
decrease in discharge. Cosmesis was subjectively improved,
and no long-term toxicity was observed.
Commonly encountered pitfalls
Clinicians should be mindful of possible systemic associations
of dissecting cellulitis. In addition to the follicular occlusion
tetrad, which may coexist in one-third of cases, dissecting cel-
lulitis may also be associated with HLA B27 negative spondy-
loarthropathy, sternoclavicular hyperostosis and polyarticular
arthritis, marginal keratitis and the SAPHO syndrome
(synovitis, acne, palmoplantar pustulosis, hyperostosis and
osteitis).5,6 Complications of dissecting cellulitis may include
osteomyelitis and squamous cell carcinoma, especially in
chronic and relapsing cases.
Special management & counseling considerations
In addition to the pain associated with dissecting cellulitis,
patients may suffer considerable embarrassment and psycho-
logical distress due to the cosmetic appearance of the scalp.
 12â•… Alopeciasâ•… •â•… Discoid lupus erythematosus

Clinicians should be appropriately empathetic. Patients should
be counseled to expect a long course of therapy, and should
understand the chronic course and often poor prognosis of the
disease so that treatment expectations are appropriate. Patients
should also be aware of the potential for dyspigmentation
associated with intralesional corticosteroids, surgical modali-
ties and laser therapy. Patients should be informed that per-
manent epilation may result from some surgical, X-ray and
laser treatments.
References
2. Glass LF, Berman B, Laub D. Treatment of perifolliculitis abscedens
et suffodiens with carbon dioxide laser. J Dermatol Surg Oncol 1989;
15:673–676.
3. Chui Ct, Berger TG, Price VH, Zachary CB. Recalcitrant scarring folli�
cular disorders treated by laser-assisted hair removal: a preliminary
report. Dermatol Surg 1999; 25(1):34.
4. Boyd AS, Binhlam JQ. Use of an 800╯nm pulsed diode laser in the
treatment of recalcitrant dissecting cellulitis of the scalp. Arch Dermatol
2002; 138(10):1291–1293.
5. Ongchi DR, Fleming MG, Harris CA. Sternocostoclavicular hyperosto-
sis: two cases with differing dermatologic syndromes. J Rheumatol
1990; 17(10):1415–1418.
6. Ramasastry SS, Granick MS, Boyd JB, Futrell JW. Severe perifolliculitis
capitis with osteomyelitis. Ann Plast Surg 1987; 18(3):241–244.

1. Adrian RM, Arndt KA. Perifolliculitis capitis: successful control with

alternate day corticosteroids. Ann Plast Surg 1980; 4:166–169.

Discoid lupus
erythematosus
Discoid lupus erythematosus is a chronic, relapsing dermato-
sis characterized by the presence of sharply demarcated
atrophic plaques with scarring, often occurring on sun exposed
skin (Fig. 12.4). Discoid lupus accounts for 50–85% of all
cases of chronic cutaneous lupus erythematosus. Other forms
of chronic cutaneous lupus are lupus panniculitis (lupus pro-
fundus) and lupus tumidus. Clinically, the lesions of discoid
lupus are round or discoid in shape. The sharply marginated
lesions spread centrifugally, and may coalesce with one
another. Lesions of early disease are often erythematous or
A
hyperpigmented, and may also demonstrate hyperkeratotic
papules and areas of thickening with dense adherent scale. The
‘carpet tack’ sign is commonly described, in which retraction
of lesional scale demonstrates keratotic spikes corresponding
to areas of follicular plugging. Late lesions of discoid lupus are
usually atrophic, and commonly demonstrate telangiectasias,
hypopigmentation and depigmentation. In persons of color,
marked hyperpigmentation is often noted around the atrophic
plaques. The scalp is the most common site of involvement in
adults, and is usually the area where disease is first noted. Scalp
involvement has been associated with disease chronicity. In
addition to tenderness, patients may complain of pruritus,
stinging and shedding of scalp hairs. Discoid lupus eventuates
in scarring alopecia. Typically, disease activity concentrates in
the center of lesions. This is in contrast to most other causes
of scarring alopecia in which disease activity is noted at the
periphery of alopecic plaques. In addition to being induced by B
ultraviolet exposure, koebnerization is also a feature of discoid
lupus. Scratching, picking or aggressive hair styling may elicit Figure 12.4:╇ (A) Discoid lupus erythematosus. (B) Severe discoid lupus
the onset of lesions. erythematosus.

239
 Part 3 Follicular Disorders and Alopecias
In adults, discoid lupus appears to affect females more com-
monly than males, and the disease has been reported to be
more common among African-American women than in other
races. Discoid lupus typically affects younger women, most
commonly occurring between the ages of 20 and 40. While
it may occur in the setting of systemic lupus erythematosus,
children and adolescents with discoid lupus are more likely to
develop systemic lupus. Patients with disseminated lesional
plaques, both above and below the neck, high antinuclear
antibodies (ANA) titers, and leukopenia may be at greater risk
for significant systemic disease.
The etiology of discoid lupus is not completely understood,
but in addition to genetic and ultraviolet-mediated factors, it
is widely accepted that lymphocyte mediated cytotoxicity plays
a significant etiologic role in disease development. Immune
deposition and subsequent inflammatory response are patho-
genic factors.
Discoid lupus is often a clinical diagnosis. Histology is
usually diagnostic, and direct immunofluorescence may be
useful for confirmation. Though patients with discoid lupus
usually do not have significant systemic involvement, in addi-
tion to history and physical exam, work-up should include
CBC with differential, ANA, ESR, serum chemistries and uri-
nalysis. Serum should also be screened for Ro(SSA)/La(SSB)
antibodies.
While the clinical presentation of discoid lupus is fairly
diagnostic, especially when extracranial lesions occur, the
differential diagnosis may include psoriasis, tinea capitis, trau-
matic alopecia, alopecia mucinosa, and lichen planopilaris.
Pigmentary changes, tenderness, and atrophy will differentiate
discoid lupus from psoriasis and tinea capitis. Tinea capitis can
also be differentiated by fungal culture. Traumatic alopecia
may be differentiated by history. In lichen planopilaris, active
disease occurs at lesional periphery, as opposed to the lesion
center as seen in discoid lupus. Alopecia mucinosa can be dif-
ferentiated by histology.
The prognosis of discoid lupus is favorable due to the
relative infrequency of systemic disease. However, due to the
cosmetic impact of the disease, including significant scarring
alopecia and disfiguring dyspigmentation, aggressive treat-
ment is warranted, and lifelong photoprotective measures
should be anticipated.
First-Line Therapies
Evidence for photoprotection E chloroquine and quinacrine. The initial dose was: chloroquine
Topical corticosteroids B 100╯mg 3×/day and quinacrine 65╯mg 3×/day. The skin lesions
Intralesional corticosteroids B improved significantly or cleared totally in 10 patients. The
Antimalarials C
ILK E therapy, especially for subacute lupus erythematosus (LE).
There are three primary components to treatment: preven-
tion, topical treatments and systemic therapy. Prevention of
disease is paramount for all discoid lupus patients. Because
lesional activity is associated with ultraviolet exposure, pho-
240
toavoidance, broad spectrum sunscreen and photoprotective
clothing are necessary.
Phototesting and photoprotection in LE. Walchner M, Messer
G, Kind P. Lupus 1997; 6:167–174.
Photosensitivity and the induction of skin lesions following
UV radiation is a common characteristic of patients with cuta-
neous and systemic forms of lupus erythematosus. This review
gives an overview on the history, test procedure and test results
in patients with lupus erythematosus.
Topical treatments are useful in cases of limited disease, and
class I or II steroids are first line. Intralesional triamcinolone
acetonide, typically done monthly, may be a useful adjunct to
topical corticosteroids. It should be noted that hypopigmen�
tation is a risk of intralesional corticosteroids, particularly in
skin of color.
Successful treatment of chronic skin diseases with clobe�
tasol propionate and a hydrocolloid occlusive dressing.
Volden G. Acta Derm Venereol 1992; 72:69–72.
The lesions of 141 patients with chronic skin diseases unre-
sponsive to therapy were treated once a week with clobetasol
propionate lotion under occlusion. In 131 patients the lesions
resolved completely, while partial remission was observed in
the remaining 10. The mean interval for complete remission
in discoid lupus was 3.7 weeks.
Antimalarials, usually hydroxychloroquine and less fre-
quently chloroquine, are first-line systemic therapies. Hydro�
xychloroquine, given in doses of 200–400╯mg/day or 200╯mg
twice daily, is very effective for more progressive disease.
Patients treated with antimalarials should be monitored for
retinal toxicity in addition to the other adverse reactions that
may occur with this treatment modality. Because smoking
appears to decrease the efficacy of antimalarials, patients
should be referred for smoking cessation therapy. Because anti-
malarial therapy may not show full benefit for several months,
oral prednisone may be used as bridge therapy.
The association of the two antimalarials chloroquine and
quinacrine for treatment-resistant chronic and subacute
cutaneous lupus erythematosus. Feldmann R, Salomon D,
Saurat JH. Dermatology 1994; 189:425–427.
The authors report 14 patients with chronic and subacute
cutaneous lupus erythematosus who had responded poorly to
chloroquine or hydroxychloroquine who were treated with
authors suggest that a chloroquine-quinacrine therapeutic
regimen may be an alternative to the usual antimalarial mono-
Management of skin disease in lupus. Callen JP. Bull Rheum
Dis 1997; 46:4–7.
Summary of best practices for management of cutaneous
lupus with sunscreens, topical and intralesional corticoster-
oids, and anti-malarials as standard therapy.
 12â•… Alopeciasâ•… •â•… Discoid lupus erythematosus

R-Salbutamol has various anti-inflammatory effects,

Second-Line Therapies
inhibits proliferation and secretion of IL-2 and interferon
gamma in human T cells, and inhibits superoxide generation
Oral retinoids B and peroxidase release from stimulated human granulocytes.
Dapsone D 5 patients with treatment resistant DLE and 4 with SCLE used
Thalidomide D salbutamol cream b.i.d on affected skin. Patients with new and
Methotrexate B non-hypertrophic DLE lesions responded well, but to a lesser
Mycophenolate mofetil D degree than those patients with SCLE.
Gold compounds D Because recent studies have suggested evidence for a patho-
Azathioprine C genic role of type I interferons in cutaneous lupus, anti-
Interferon alpha D interferon alpha antibody therapy is a promising area for
Calcineurin inhibitors D treatment.3 Recently, efalizumab, a monoclonal antibody
Imiquimod E directed against CD11a, has been suggested as a novel treat-
ment alternative.
Salbutamol C
Biologics C
Efalizumab in the treatment of discoid lupus erythemato-
sus. Usmani N, Goodfield M. Arch Dermatol 2007; 143(7):
873–877.
Secondary systemic therapies include the oral retinoids Efalizumab is a monoclonal antibody directed against
isotretinoin and acetretin. Isotretinoin in doses of 1╯mg/kg/ CD11a. 13 patients received efalizumab 1╯mg/kg subcutane-
day is favored, as it has a shorter half-life and is less associated ously once per week, with an initial dose of 0.7╯mg/kg. Treat-
with telogen effluvium. Response to retinoids is rapid, though ment responses varied from good to excellent in 12 or 13
teratogenicity makes them a less desirable alternative. Dapsone, patients, with a significant reduction in the cutaneous lupus
typically given as 100╯mg/day is helpful for some patients. activity and severity score at the conclusion of therapy.
However, patients should be screened for glucose-6-phosphate
dehydrogenase deficiency prior to beginning therapy. Side Excision of chronic scarred lesions and laser treatment for
effects of dapsone may include hemolysis, methemoglobine- prominent telangiectasias has been described, but clinicians
mia and neuropathy. Other systemic medications that may be should be extremely wary of koebnerization and ensuing
an option for more extensive or refractory disease include disease reactivation.
thalidomide, methotrexate, mycophenolate mofetil, gold com-
pounds, azathioprine and subcutaneous interferon alpha-2a Commonly encountered pitfalls
and alpha-2b.
While discoid lupus is typically not associated with systemic
Efficacy and safety of methotrexate in recalcitrant cutaneous involvement, it is associated with severe cosmetic disfigure-
lupus erythematosus: results of a retrospective study in 43 ment owing to scarring, dyspigmentation and permanent alo-
patients. Wenzel J, Brahler S, Bauer R, Bieber T, Tuting T. Br J pecia. Clinicians must be aggressive in the early treatment of
Dermatol 2005; 153:157–162. discoid lupus to limit the cosmetic impact. While discoid
In this retrospective study of 43 patients (25% with DLE), lupus rarely progresses to systemic lupus, patients should be
42 patients showed improvement with methotrexate. The advised of the risk of systemic disease, and the importance of
greatest improvement was noted with patients with SCLE. regular clinical follow-up should be emphasized. For systemic
involvement, referral to rheumatology, nephrology, internal
Topical FK506 (tacrolimus) therapy for facial erythematous medicine and ophthalmology should be made as warranted.
lesions of cutaneous lupus erythematosus and dermato� Clinicians should also have a high index of suspicion for
myositis. Yoshimasu T, Ohtani T, Sakamoto T, Oshima A, squamous cell carcinoma development within chronic or
Furukawa F. Eur J Dermatol 2002; 12:50–52. scarred lesions. It has been reported that squamous cell carci-
Topical tacrolimus ointment 0.1% daily for four weeks noma of the scalp has a higher incidence in Black discoid
achieved marked improvement in 1 of 4 patients with facial lupus patients. Metastatic rates of 31% have been documented
DLE. Response was greatest in those with non-hyperkeratotic for squamous cell carcinoma in discoid lupus patients, with
lesions. mortality rates up to 10.5%.4
Imiquimod has been reported to successfully treat scalp
disease in one patient.1 Salbutamol cream, which inhibits IL-2 Special management & counseling considerations
and interferon gamma in T cells is a newer therapy which has
been reported to have therapeutic efficacy.2 Disease education is paramount in the treatment of discoid
lupus. Because the disease is exacerbated by photoexposure,
Discoid and subacute lupus erythematosus treated with sun protection and sun avoidance during peak hours is crucial.
0.5% R-Salbutamol cream. Wulf HC, Ullman S. Arch Derma- Many persons of color do not wear sunscreens, and mistakenly
tol 2007; 143(12):1589–1590. believe that they are not susceptible to sun damage. It is

241
 Part 3 Follicular Disorders and Alopecias

important to stress to skin of color patients that a darker skin
type will not obviate the need for photoprotection. Additional
protection of the scalp may be achieved by the use of hats,
caps and scarves. African-American women should be specially
counseled to avoid traumatic hair grooming practices which
may exacerbate scalp lesions.
2. Ross EK, Tan E, Shapiro J. Update on primary cicatricial alopecias.
J Am Acad Dermatol 2005; 53:1–37.
3. Wenzel J, Tuting T. Identification of type I interferon associated inflam-
mation in the pathogenesis of cutaneous lupus erythematosus opens
up options for novel therapeutic approaches. Exper Dermatol 2007;
16:454–463.
4. Sulica VI, Kao GF. Squamous cell carcinoma of the scalp arising in
lesions of discoid lupus erythematosus. Am J Dermatopathol 1988;
10:137–141.

References
1. Gerdsen R, Wenzel J, Uerlich M, Bieber T, Petrow W. Successful treat-
ment of chronic discoid lupus erythematosus of the scalp with imiq-
uimod. Dermatology 2002; 205:416–418.

Traction alopecia
Crystal Y Pourciau

Traction alopecia is a leading cause of hair loss, affecting

persons of several ethnic backgrounds. It is a biphasic, initially
non-cicatricial form of hair loss occurring secondary to pro-
longed and excessive tension placed on the hair. This form of
alopecia is typically most prominent along the frontal and
temporal scalp, but may be less commonly noted along the
occipital scalp margins as well. Prolonged use of ponytail hair-
styles, hair rollers, tight braids, locks and hair weaves have
been associated with traction alopecia (Fig. 12.5A and B).1
The initial phase of traction alopecia is of short duration
and is typically characterized clinically by pustules, scale, and
A
multiple, short, broken hairs. Prolonged tension and subse-
quent damage to the follicular unit produces perifollicular
erythema, although this may not be appreciated in darker-
skinned individuals. Chronicity of tension eventuates in
mechanical detachment of the shaft from the follicle, with
subsequent follicular atrophy. Follicular unit derangement
may predispose to increased incidence of scalp infections from
either bacteria or fungi thus increasing inflammation and con-
tributing to further hair loss. Other reported exacerbating
factors include occlusive scalp emollients, such as petrolatum
or mineral oil-based pomades.2
Scarring, peri-pilar casts and clinically apparent ‘follicular
drop out’ may be evident decades after the initial insult.
Untreated, chronic traction results in permanent alopecia.
Because of the popularity of certain hairstyles that are tight,
such as cornrows, braids, and weaves, in addition to poten-
tially traumatic grooming practices such as thermal straighten-
ing and chemical relaxers, traction alopecia is seen most
frequently in the black female populations in the United
States. Multiple studies performed by Khumalo et╯al3–5 in
Black African populations demonstrated a strong association
between traumatic grooming practices and hair loss. Addition- B
ally, traction alopecia is thought to have greater prevalence in
adult women as compared to younger girls, because of the Figure 12.5:╇ (A) Traction alopecia of the anterior and temporal scalp. (B) Traction
cumulative effects of damaging grooming practices.3 alopecia resulting from a long, heavy lock hairstyle.

242

Although there are limited controlled studies validating
treatment options for traction alopecia, there are various
case reports of management strategies as well as anecdotal
recommendations.
Specific investigations
The initial evaluation of traction alopecia requires a complete
and thorough history, including hair care products, grooming
practices, medical disorders, medications and relevant family
history.2
If an infectious etiology is suspected, Wood’s lamp exami-
nation, and bacterial and fungal cultures should be con�
sidered.2 Scalp biopsy should be performed if the clinical
presentation is not classic, or if other cutaneous stigmata are
noted on exam. In most cases, biopsy is not warranted, as the
physical exam and history strongly suggest the diagnosis.6
However, since alopecia areata in an ophiasis pattern may
mimic traction alopecia in the African American population,
there is an increasing need to perform a scalp biopsy to dis-
tinguish between these two entities.
Management strategy
Patient education is the mainstay of treatment. Realistic expec-
tations must be set, and particular emphasis should be placed
upon the importance of hair care practice modifications. Phy-
sicians must be able to recognize the disorder during the early
phase, before irreversible damage occurs.1,2,6,7 Most authors
agree that significant hair re-growth can occur, if alternative
hair care practices are utilized. Patients must discontinue the
traumatic grooming practices that contributed to the hair loss.
Braids and ponytails should only be worn if done in a loose
manner, and weaved hairstyles should not be tightly applied
and only used on a very infrequent basis.
First-Line Therapies
Topical corticosteroids
Intralesional corticosteroids
Oral antibiotics
Topical minoxidil E
During the early stages of traction alopecia, characterized
by prominent follicular inflammation, a brief course of oral
antibiotics with concomitant topical antibiotic ointment may
prevent super-infection and lessen folliculitis.7 However, no
randomized controlled studies have been published support-
ing this recommendation. Most published reports demon-
strated some efficacy during treatment but relapse of disease
occurs following cessation of treatment if hair care practices
are not modified.
Finally, minoxidil has been used as a treatment of hair loss
secondary to traction alopecia. In two case reports, significant
12â•… Alopeciasâ•… •â•… Traction alopecia
hair regrowth was noted after 9 months of twice daily use of
topical minoxidil in women assumed to have non-scarring
alopecia at the marginal scalp edges secondary to long-term
use of tight hairstyles.9
Second-Line Therapy
Hair transplantation E
In a review of medical and surgical therapies for alopecias
in black women, Callender et╯al9 reviewed various surgical
techniques, historically used for men with androgenic alo-
pecia, that now are thought to be potentially useful in female
populations with alopecia. Techniques reviewed include
punch grafting hair transplantation, follicular unit transplan-
tation, and micro- and mini- hair graft. The primary patient
selec�tion criteria for surgical procedures include a lack of
active/worsening disease, no history of keloids, access to an
appropriately sized donor site and, most importantly, realistic
expectations. While the greatest concern of most surgical prac-
titioners is the theoretical risk of keloidal scarring in African-
American populations, this has not proven problematic in the
authors’ clinical practice. In order to maintain a low incidence
of keloid formation, the authors recommend prophylactic
application of topical corticosteroid and antibiotic ointments
at the donor site for 2 weeks following the procedure.7
Case reports exist supporting surgical management of
traction alopecia. A 23-year-old Turkish woman presented
with pronounced, symmetric temporal alopecia after a 5-year
history of wearing a tight ponytail hairstyle almost daily. Hair
transplantation was performed using micrografts from the
occiput. Greater than 95% graft survival was noted at 1-year
follow-up. This patient had no adverse events associated with
the procedure. The authors reported self-resolving inclusion
cysts as the primary complication, with an incidence of 10%.10
Commonly encountered pitfalls
Alternative causes of hair fragility and breakage must be
excluded before reaching a diagnosis of traction alopecia.
These may include infectious sources such as tinea capitis,
traumatic or chemical alopecia, or systemic sequelae such as
telogen effluvium. The physical exam and history are key in
delineating the diagnosis.
Special management & counseling considerations
Counseling women of color with traction alopecia is often a
difficult task to tackle as strong cultural norms dictate hair-
styles and practices. Often women do not realize that the
discomfort they may feel from tight hairstyles is abnormal and
may lead to alopecia. It is helpful to ask the patient if she can
move her forehead or temples after braids with extensions or
cornrows are put in. Point out that if she cannot move these
areas normally, then the style is too tight. Cessation of high
tension hairstyle practices is therefore, requested along with
243
 Part 3 Follicular Disorders and Alopecias
suggesting alternative methods of hairstyling. Women often
ask if vitamins or diet will be of any benefit, and there are
some anecdotal reports of success with biotin supplementa-
tion. We also refer patients to internet resources for additional
tips on hair care practices as well as a source of support in
managing this disorder.
References
1. Hantash BM, Schwartz RA. Traction alopecia in children. Cutis 2003;
71:18–20.
2. Fox GN, Stausmire JM, Mehregan DR. Traction folliculitis: an under-
reported entity. Cutis 2007; 79:26–30.
3. Khumalo N, Jessop S, Gumedze F, Ehrlich R. Determinants of marginal
traction alopecia in African girls and women. J Am Acad Dermatol
2008; 59:432–488.
Traumatic alopecia:
chemical, heat and
mechanical
Traumatic alopecia may encompass alopecia secondary to
chemical, heat or mechanical insults. It is characterized by
broken hair shafts of uneven lengths; dry, split and thinned
hair ends; fragility and easy breakage. On examination, gentle
hair tug elicits many uneven, friable, and broken hairs. Unlike
naturally shed hairs, the broken hairs of traumatic alopecia do
not have visible hair bulbs, and the tips will appear weathered.
Traumatic alopecia may be either acute or chronic in nature.
Most commonly, traumatic alopecia is chronic, and secondary
to repetitive injury incurred during daily grooming. The cause
of the alopecia may be obvious or subtle, and a thorough hair
grooming history, including product use and frequency, should
be ascertained to delineate the offending agent or agents.
Traumatic alopecia is not uncommon, and hair loss has
been reported to be the fifth most common reason that
African-American patients present to a dermatologist.1 Among
African-American women, up to 20% may report a history of
alopecia, and 51% have been reported to cite hair loss or
thinning as their top hair care concern.2
Traumatic alopecia may be more commonly noted among
persons with African hair texture due to the unique structural
and physical properties of the hair fiber. African textured hair
is characterized by frequent twists, random curl direction
reversals and a flattened shape. These distinctive physical prop-
erties, in addition to prevalent grooming practices such as heat
application, chemical straighteners, and the use of drying
styling preparations, likely make this population more suscep-
tible to traumatic alopecia.
Common chemical insults leading to traumatic alopecia
include hair relaxers (colloquially referred to as ‘perms’), per-
244
4. Khumalo NP, Jessop S, Gumedze F, Ehrlich R. Hairdressing and
the prevalence of scalp disease in African Adults. Br J Dermatol 2007;
157:106–110.
5. Khumalo NP, Jessop S, Gumedze F, Ehrlich R. Hairdressing is associ-
ated with scalp disease in African schoolchildren. Br J Dermatol
2007; 157:106–110.
6. Schroeder TL, Levy ML. Treatment of hair loss disorders in children.
Dermatolog Ther 1997; 2:84–92.
7. Callender V, McMichael A, Cohen G. Medical and surgical therapies
for alopecias in black women. Dermatolog Ther 2004; 17:164–167.
8. Scott D. Disorders of the hair and scalp in Blacks. Dermatol Clin 1988;
6:387–395.
9. Khumalo NP. Traction alopecia: 2% topical minoxidil shows promise.
Report of 2 cases. J Eur Acad Dermatol Venereol 2007; 21:433–444.
10. Ozcelik D. Extensive traction alopecia attributable to ponytail hairstyle
and its treatment with hair transplantation. Aesth Plast Surg 2005;
29:325–327.
manent waves and hair dyes. Relaxers, which permanently
straighten the hair, are highly alkaline, and composed of
sodium hydroxide (lye) or guanidine, lithium or potassium
hydroxide (no lye) (Fig. 12.6). These chemical treatments may
be especially injurious if applied incorrectly or too frequently,
eventuating in digestion of the hair shaft and extreme hair
fragility and breakage with even gentle combing. Traumatic
alopecia from chemical application is often more prominent
at the nape or the frontal and temporal hairlines. Chemical
alopecia may be especially prevalent in patients who chemi-
cally straighten and color their hair, due to the compounded
action of these agents. Popular hair styling preparations, par-
ticularly those containing isopropyl alcohol, mineral oil or
petrolatum, coupled with infrequent washing, may further
exacerbate hair dryness and fragility. Both petrolatum and
mineral oil, while imparting a visible sheen to the hair, may
actually coat the hair shaft, keeping needed moisture from
entering.
Heat straightening, unlike chemical straightening, is tem-
porary and easily reversed by washing, humidity or perspira-
tion. It is typically accomplished by the use of a pressing comb,
blow dryer, curling iron, or flat iron, with temperatures ranging
Figure 12.6:╇ Chemical relaxer application to hair.
 12â•… Alopeciasâ•… •â•… Traumatic alopecia: chemical, heat and mechanical
Figure 12.7:╇ Hot comb, curling iron and electric stove used to heat these
implements.
from 300–500°F (Fig. 12.7). Though heat processing of the
hair, for the purposes of straightening or curling, is popular
among persons with various textures of hair, high heat require-
ments, coupled with the unique structure of the hair shaft and
higher hair fragility, makes those with African textured hair
particularly susceptible to injury. Hooded hair dryers and hot
rollers, with injudicious use, may also be associated with trau-
matic alopecia. Excessive heat may present as ‘bubble hair,’ in
which small globules of moisture within the hair shaft swell,
vaporize and cause bubbles. These bubbles lead to localized
areas of breakage.3 Mechanical insults leading to alopecia may
include excessive brushing and combing, particularly of
already infrequently washed and brittle hair. Excessive pulling
during styling, such as in tight ponytails, weaved and braided
hair styles, may also lead to alopecia.
First-Line Therapies
Eliminate/minimize traumatic grooming practices
Avoid excessive heat and frequent chemical
straightening
Wash hair no less frequently than every 2 weeks
The cornerstone of treatment for traumatic alopecia is elim-
ination or minimization of traumatic hair care practices. When
injury is due to chemical processing, it should be eliminated
or done less frequently. Chemical relaxers should be applied
no more frequently than every 8 to 12 weeks, and only to
previously unstraightened hair (new growth), instead of the
customary 4 to 6 weeks. While lye based relaxers may be more
irritating to the scalp, they are believed to be less drying to the
hair than their non-lye counterparts. Heat application should
be done no more frequently than once per week, and ceramic
appliances with dialed temperature control are preferable
which can be set on a low heat setting. Heat should preferably
be applied to only clean hair. Hair styling should not be
overzealous, so as to avoid fracture of the already fragile hair
shafts. When combed, a wide toothed comb is preferable.
Braided or weaved hairstyles should be done with care to avoid
excessive pulling and tearing of the hair, and drying styling
products should be eliminated. Hair washing should occur no
less than every 2 weeks (many women will not shampoo
for the duration of the braided or weaved style which may
be 8 or more weeks), and be followed by moisturizing
conditioners.
Second-Line Therapies
Damaged hair should be cut E
Excessively fragile and breaking hair should be cut at the
point of damage in order to minimize further breakage and
splitting. Over processing, excessive heat and infrequent
washing should be assiduously avoided as the hair regrows.
Commonly encountered pitfalls
While hair breakage and fragility is commonly due to trau-
matic causes, it is important to recognize that other diseases
common in persons of color may present a similar clinical
picture. Tinea capitis in adults may be characterized by hair
breakage, uneven hair length, and apparent fragility. Recent
studies indicate that up to 10% of cases of tinea capitis are
found in adults.4
Central centrifugal cicatricial alopecia, especially in its early
stages, may present with short, uneven and broken hairs, par-
ticularly at the crown. Similarly, excessive traction, particularly
when acute, may be characterized by broken and fragile hairs.
E Special management & counseling considerations
E
Many people of color, particularly those with African hair type,
may wash the hair infrequently, commonly monthly, owing
E
to the misconception that the hair is too dry and fragile to
wash more frequently. Infrequent washing may also occur in
order to preserve a straightened or sculpted hair style for a
longer period of time. When counseling patients with trau-
matic alopecia, it is important to emphasize that infrequent
washing, that is, once every 3 or 4 weeks, particularly when
compounded with the drying ingredients in many styling
agents, may exacerbate hair fragility and breakage. Particular
sensitivity is necessary when counseling those patients who
heat straighten their hair, as they may be hesitant to wash their
hair more frequently. Water exposure will lead to reversion to
the natural texture. Due to complexities of the hair shaft, hair
care time for African Americans is often consuming and con-
siderable time, money, and effort were likely expended in
245
 Part 3 Follicular Disorders and Alopecias

order to achieve a straight hairstyle.5 Often, one or two hours
are required to style African hair types, sometimes at a cost
between $40 and $100 for a professional hair stylist.
When purchasing hair products to aid in restoring hair
moisture and strength, patients should look for ingredients
such as panthenol, dimethicone, fatty alcohols (cetyl, stearyl)
and hydrolyzed proteins. Products containing isopropyl
alcohol, petrolatum and mineral oil should be used only
sparingly.
2. Pantene Relaxed & Natural External Relations ‘AA Statistics and Facts
Study,’ 2005 (conducted via the Internet among a statistically
representative sample of 1,000 U.S.-based African-American women,
age 18–64).
3. Whiting DA. Traumatic alopecia. Int J Dermatol 1999; 38(1):34–44.
4. Silverberg NB, Weinberg JM, DeLeo VA. Tinea capitis: focus on African-
American women. J Amer Acad Dermatol 2002; 46(2):S120–S124.
5. Draelos ZD. Understanding African-American hair. Dermatol Nursing
1997; 9(4):227–231.

References
1. Halder RM, Grimes PE, McLaurin CI, Kress MA, Kenney JA Jr. Incidence
of common dermatoses in a predominantly black dermatologic prac-
tice. Cutis 1983; 32:378–380.

or adolescence, and incidence has been reported as 1 in 200

Trichotillomania persons by age 18.2 Most cases of trichotillomania are chronic,
with periods of exacerbation and remission. Affected individu-
als may try to conceal their alopecia, and may avoid intimate
Trichotillomania is a compulsive, often unrelenting, urge to relationships or leisure activities that may expose their con�
pull the hair. Hair plucking is most commonly manifest on dition. Trichotillomania has been associated with impaired
the scalp, but affected individuals may also pull the hair from familial relationships and psychosocial stressors within the
the eyebrows, eyelashes, pubic area, trunk and extremities. First familial unit. It is also associated with major depression, psy-
described in 1889 by Hallopeau, patients with trichotilloma- chosis and dysthymia.4–7 The prognosis of trichotillomania is
nia pull their hair because of an irresistible urge and accom- guarded, as it is typically a chronic disease, characterized by
panying anxiety. The Diagnostic and Statistical Manual of exacerbations and remissions. Older females may be more
Mental Disorders (DSM IV) criteria for trichotillomania susceptible to chronicity.2,3
include recurrent pulling of hair, resulting in noticeable hair Upon microscopic exam, hairs emerging from affected areas
loss; an increasing sense of tension immediately before pulling often have blunt ends, and hair pluck tests reveal few telogen
out the hair or when attempting to resist hair pulling; and hairs, as these will have already been pulled, owing to the
pleasure and gratification upon pulling the hair. Additional fact that less force is required to remove them. Histologically,
DSM IV diagnostic criteria include that the hair pulling behav-
ior is not better accounted for by another mental disorder or
medical condition, and that the hair pulling provokes clini-
cally marked distress and/or impairment in occupational,
social or other areas of functioning.1,2 Trichotillomania usually
results in clinically apparent patchy hair loss. Patients may
exhibit small patches of baldness, thinning over the entire
head or full scalp alopecia (Fig. 12.8). Hair pulling is com-
monly performed in a ‘wave-like’ or centrifugal pattern, and
linear or circular areas of alopecia may result. Typically, areas
of alopecia have irregular borders, with hairs of variable length.
Upon examination, the scalp may exhibit a rough texture sec-
ondary to the short broken off hairs that result from pulling.
Some patients with trichotillomania may eat the pulled hairs,
and compulsive picking may result in traumatic injury to the
affected skin.
Trichotillomania is thought to occur more frequently in
females and is more common in children than in adults.
Adults affected by trichotillomania are more likely to suffer
from associated psychopathology and exhibit a poorer prog- Figure 12.8:╇ Trichotillomania. Classic findings with small areas of sparing.
nosis. Generally, the disease onset is noted in early childhood (From Bolognia; Dermatology 2e; Mosby, copyright Elsevier 2008.)

246

trichomalacia, follicular hemorrhage, pigment casts, high
catagen hair number, normal anagen follicles and an absence
of inflammatory cells will be noted.
The differential diagnosis of trichotillomania includes alo-
pecia areata, tinea capitis, traumatic or traction alopecia and
syphilitic alopecia. Alopecia areata may be distinguished by its
characteristic exclamation point hairs and frequent loss of hair
from the periphery of alopecic patches upon gentle tug. Fungal
infections can be differentiated by culture or microscopic
examination. Traumatic or traction alopecia can be differen�
tiated by pattern of hair loss on physical exam and history.
Syphilitic alopecia is differentiated by serology.
First-Line Therapies
Psychological/psychiatric referral D citalopram at a maximum dosage of 60 mg/day.
Behavior therapy/Hypnotherapy E
Clomipramine E Paroxetine treatment of trichotillomania in an adolescent.
The cornerstone of treatment is insight into concomitant
psychological comorbidities and psychosocial stressors that
may have triggered the behavior. In children, a thorough
history is necessary, and psychiatric referral prudent. Behavior
therapy, characterized by habit reversal, hypnotherapy, psycho-
therapy and pharmacotherapy may play a role.
Simplified habit reversal treatment for chronic hair pulling.
Rapp JT, Miltenberger RG, Long ES, Elliott AJ, Lumley VA. J
Appl Behav 1998; 31:299–302.
3 adolescents with trichotillomania were treated with
awareness training, competing response training and social
support. Treatment resulted in drastically decreased levels of
hair pulling, which were maintained from 18 to 27 weeks after
treatment.
Clomipramine treatment of trichotillomania: a follow-up
report on four cases. Pollard CA, Ibe IO, Krojanker DN,
Kitchen AD, Bronson SS, Flynn TM. J Clin Psychiatry 1991;
52(3):128–130.
4 patients with trichotillomania were treated with clomi-
pramine, and experienced drastic reduction in their symptoms.
By the 3-month follow-up, 3 of 4 patients had relapsed, though
still taking previously effective doses of clomipramine.
Hypnotherapy: an effective treatment modality for trichotil-
lomania. Cohen HA, Barzilai A, Lahat E. Acta Paediatrica 2007;
88:407–410.
3 children with trichotillomania were treated using hypno-
therapy technique (relaxation/mental imagery). All patients
were observed for 8 consecutive weeks and subsequently fol-
lowed for 12–18 months. 2 patients reported complete resolu-
tion of their complaints after 7–8 weeks and 1 patient after 16
weeks. During a mean follow-up period of 16 months, there
were no recurrences
12â•… Alopeciasâ•… •â•… Trichotillomania
Second-Line Therapies
Serotinergic reuptake inhibitors C
Neuroleptics E
Uncontrolled trials have suggested the use of serotinergic
reuptake inhibitors (SRIs) and neuroleptics. Paroxetine and
fluvoxamine may be effective.8,9 Haloperidol, pimozide or ris-
peridal may also be considered as adjunctive therapy.
Use of the selective serotonin reuptake inhibitor citalopram
in treatment of trichotillomania. Stein DJ, Bouwer C, Maud
CM. Eur Arch Psychiatry Clin Neurosci 1997; 247:234–236.
Of 14 patients who met DSM-IV criteria for trichotilloma-
nia, 30.5% were responders at week 12 with treatment with
Block C, West SA, Baharoglu B. J Child Adolesc Psychophar-
macol 1998; 8:69–71.
A case report of an adolescent with trichotillomania treated
with paroxetine. A significant reduction in symptoms was
noted after 2 weeks of treatment. The paroxetine dose was
gradually increased to 30╯mg per day, which was well tolerated
without any significant adverse events.
Low dose pimozide augmentation of serotonin reuptake
blockers in the treatment of trichotillomania. Stein DJ,
Hollander E. J Clin Psychiatry 1992; 53:123–126.
In a chart review study, 2 patients who had only moderate
response to clomipramine demonstrated marked improve-
ment after the addition of 1–2╯mg/day pimozide.
Commonly encountered pitfalls
Patients with trichotillomania may suffer from major depres-
sion, severe anxiety or other psychiatric disease. Appropriate
management necessitates recognition of the presence of
comorbid states and appropriate psychiatric referral.10 As
patients with trichotillomania may consume plucked hairs,
trichobezoar is a possible complication of the disorder, and
potentially life threatening intestinal or gastric obstruction
may ensue. Clinicians should also be aware of other complica-
tions of trichotillomania such as skin infection, blepharitis,
chronic neck or shoulder pain and carpal tunnel syndrome
(resulting from the ritualistic positioning associated with
plucking).
Special management & counseling considerations
In addition to appropriate psychiatric referral, patients should
be guided to support organizations and educational resources.
Clinicians should be especially mindful of the possibility of a
greater reluctance of persons of color to seek psychiatric evalu-
ation and counseling, owing to fear of social stigma.
247
 Part 3 Follicular Disorders and Alopecias
References
1. American Psychiatric Association. Diagnostic and statistical manual
of mental disorders. 4th edn. Washington: American Psychiatric
Association; 1994.
2. Hautmann G, Hercogova J, Lotti T. Trichotillomania. J Am Acad
Dermatol 2002; 46:807–821.
3. Christenson GA, MacKenzie TB, Mitchell JE. Characteristics of sixty
adult chronic hair pullers. Am J Psychiatry 1991; 148:365–370.
4. Sachdeva JS, Sidhu BS. Trichotillomania associated with depression.
J Indian Med Assoc 1987; 85:151–152.
5. Krishnan RR, Davidson J, Miller R. MAO inhibitor therapy in trichotil-
lomania associated with depression: a case report. J Clin Psychiatry
1984; 45:267–268.
248
6. Childers RT. Report of two cases of trichotillomania of long standing
duration and their response to chlorpromazine. J Clin Exp Psychopathol
1958; 19:141–144.
7. Sunkureddi K, Markovitz P. Trazodone treatment of obsessive compul-
sive disorder and trichotillomania. Am J Psychiatry 1993; 150:523–
524.
8. Ravindran AV, Lapierre YD, Anisman H. Obsessive-compulsive spec-
trum disorders: effective treatment with paroxetine. Can J Psychiatry
1999; 44:805–807.
9. Figgitt DP, McClellan KJ. Fluvoxamine. An updated review of its use in
the management of adults with anxiety disorders. Drugs 2000; 60:
925–954.
10. Fennessy J, Crotty CP. Trichotillomania. Dermatol Nurs 2008;
20(1):63.
Part 3 Follicular Disorders and Alopecias
Follicular Disorders
Raechele Cochran Gathers
Acne keloidalis nuchae . . . . . . . . . . . . . . . . . . 249
Folliculitis decalvans . . . . . . . . . . . . . . . . . . . 251
Pseudofolliculitis barbae . . . . . . . . . . . . . . . . . 254
Acne keloidalis nuchae
Acne keloidalis nuchae, also referred to as folliculitis keloidalis
or folliculitis nuchae, is a chronic inflammatory process, char-
acterized by the presence of firm, smooth papules, and some-
times pustules, along the occipital scalp and nape area. The
follicular papules of acne keloidalis nuchae (AKN) may coa-
lesce to form large keloidal plaques and nodules, sometimes
spanning the width of the nape. Though not significantly
symptomatic in its mild form, pustular lesions may be pruritic,
and more extensive disease may be associated with significant
discomfort. Chronic lesions may form painful and malodor-
ous abscesses and draining sinuses. Follicular destruction and
scarring alopecia within the affected areas are common seque-
lae, and the disease is of significant cosmetic concern. Though
there are reports of acne keloidalis in women, as well as in
white men following treatment with cyclosporine,1 and in an
epileptic patient on diphenylhydantoin and carbamazepine,2
acne keloidalis nuchae is almost exclusively found in men of
African descent, and the male to female ratio is approximately
20:1. The disease typically occurs in young men after puberty.
Onset after age 50 is rare. Acne keloidalis nuchae is not uncom-
mon, and has been estimated to account for 0.5% of all der-
matoses in African-Americans (Fig. 13.1).
The name ‘acne keloidalis nuchae’ is somewhat of a misno-
mer, as histologically the disease does not illustrate true
keloids, nor is there follicular occlusion as seen in acne vul-
garis. The exact etiology of acne keloidalis nuchae is unknown,
though it is widely held that closely cut hair at the nape grows
inward with subsequent penetration of the curved hair shaft
into the skin, thus inciting an inflammatory reaction. Other
©2011 Elsevier Ltd, Inc, BV
13â•…
hypothesized etiologies include chronic irritation from shirt
collars, and a chronic low-grade bacterial folliculitis.3
Due to its characteristic presentation, the diagnosis of acne
keloidalis nuchae is usually a clinical one. The differential
diagnosis may include sarcoidosis, dissecting cellulitis, simple
keloids and folliculitis. Besides clinical exam and histopatho�
logy, there are no specific tests for acne keloidalis. Periodic
bacterial cultures should be done of any pustular or draining
lesions, and appropriate antibiotic treatment rendered.
First-Line Therapies
Avoid close cropped hair E
Avoid use of razors when cutting hair E
Avoid excessive friction E
Topical corticosteroids E
Topical retinoids E
Topical antibiotics E
Oral antibiotics E
Intralesional corticosteroids E
In a clinical review published in 2003, Kelly provides an
extensive review of both the therapeutic and the counseling
approaches to the patient with acne keloidalis nuchae.4 Simi-
larly, in a 2007 issue of Dermatologic Therapy, several derma-
tologists discuss their ‘best practices’ for the treatment of acne
keloidalis nuchae.5 In individuals susceptible to acne keloi�
dalis nuchae, preventive measures are paramount. Patients
should be instructed to avoid closely cropped hair (fade
haircuts) at the occipital scalp and nape. The use of a razor,
typically done to give the hairline a sharp appearance at the
nape, should be avoided, and clippers should be utilized only
judiciously, with care to avoid excessive friction with the skin.
As friction is felt to exacerbate the disorder, stiff shirt collars,
249
 Part 3 Follicular Disorders and Alopecias
A removing small keloidal papules with a hair transplant
B Acne keloidalis nuchae: treatment with excision and second
Figure 13.1:╇ (A, B) Acne keloidalis nuchae.
tight fitting hats, and other sources of mechanical irritation to
the occipital scalp and nape areas should be avoided.
Topical corticosteroids, ranging in potency from class I to
III, may be of benefit depending upon the severity of the
disease. Kelly recommends class I or II corticosteroid gels
(Diprolene or Topicort) or foam (Olux) applied twice daily.
He also suggests using, in addition to the corticosteroid gel,
a topical retinoid every other night to relieve symptoms and
to aid in flattening keloidal lesions.4
Oral antibiotics such as doxycycline or minocycline, given
once to twice daily, may play both an antibacterial and an
anti-inflammatory role. Likewise, topical clindamycin, once to
twice daily, may be utilized in the presence of pustules or
other evidence of infection. Kelly utilizes topical antibiotics
twice daily until pustules and obvious signs of inflammation
abate.
Intralesional triamcinolone acetonide, 5–40╯mg/mL may
be injected into keloidal lesions at monthly intervals. Kelly
recommends injecting triamcinolone 40╯mg/mL at 3-week
intervals into active keloidal lesions.
250
Second-Line Therapies
Surgical excision of lesional skin C
Laser E
Cryotherapy E
Isotretinoin E
Imiquimod C
Pimecrolimus C
Surgical excision and laser therapy are popular treatment
modalities for extensive or recalcitrant disease. Kelly describes
punch and then leaving the postoperative site to close by
second intention or alternatively closing with sutures.4
The punch should extend past the deepest layer of the hair
follicle to minimize the risk of recurrence. Larger keloidal
nodules and plaques can be excised using a horizontal ellipse,
which can either be repaired primarily6 or allowed to heal
secondarily.7,8
Surgical excision of acne keloidlis nuchae with secondary
intention healing. Bajaj V, Langtry JAA. Clin Exp Dermatol
2007; 33:53–55.
Report of 2 men (Caucasian and South Asian) with chronic
acne keloidalis nuchae unresponsive to topical and oral
therapy. Both underwent excision with second intention
healing, with no report of recurrence of disease at 14 and 18
months postoperatively, respectively.
intention healing. Glenn MJ, Bennett RG, Kelly P. J Am Acad
Dermatol 1999; 33:243–246.
12 patients were treated with excision and subsequent
second intention healing. Wound healing was reported within
6–10 weeks with good to excellent cosmesis. 2 patients expe-
rienced recurrence.
The surgical management of extensive cases of acne
keloidalis nuchae. Gloster HM Jr. Arch Dermatol 2000;
136:1376–1379.
Report of 24 patients with AKN treated with excision with
direct closure. Two-thirds had disease recurrence within 4
months postoperatively, and a quarter developed hypertrophic
scarring requiring additional treatment.
Laser therapy using both the 810╯nm diode laser and
1064╯nm Nd-YAG lasers have shown good clinical response,
without permanent residual dyspigmentation.9,10 The CO2
laser may also be utilized, but secondary to potential adverse
effects, is a less popular option.11
Efficacy of diode laser for treating acne keloidalis nuchae.
Shah GK. Indian J Dermatol Venereol Leprol 2005; 71:31–34.
Report of 2 Indian patients (skin types IV and V) with acne
keloidalis nuchae treated with the diode laser. Lesions showed
90–95% clearance after four treatment sessions at 1 and 1.5

month intervals. No recurrence was observed during the
follow-up period of 6 months.
The use of cryotherapy and isotretinoin for the treatment
of AKN is anecdotal.12 However, there is a report of five sub-
jects treated with imiquimod and pimecrolimus with some
success.13
Use of imiquimod and pimecrolimus cream in the treat-
ment of acne keloidalis nuchae. Barr J, Friedman A, Balwin
H. J Am Acad Dermatol 2005; 52(3 Suppl 1):P64.
5 patients were randomly assigned treatment with either
imiquimod cream once daily for 8 weeks or pimecrolimus
cream twice daily for 8 weeks. The authors reported a significant
decrease in itching in all patients, and that both imiquimod and
pimecrolimus were objectively and subjectively effective in
decreasing lesion counts. They proposed the modalities as pos-
sibly useful as monotherapy or adjunctive therapy.
Commonly encountered pitfalls
While the clinical appearance of acne keloidalis nuchae is
fairly diagnostic, the differential diagnosis may include sar-
coidosis, dissecting cellulitis, keloids or folliculitis. In cases of
diagnostic uncertainty, biopsy is recommended. Hypopigmen-
tation and atrophic skin may be a consequence of both topical
and intralesional corticosteroid therapy, and patients should
be forewarned of these possible adverse effects of therapy.
Likewise, though newer laser modalities such as the Nd-YAG
show considerable safety profiles, patients should be fore-
warned of the possibility of dyspigmentation with laser
therapy. Surgical excision of affected skin should extend into
the deep subcutaneous tissue or muscular fascia (past the
deepest layer of the hair bulbs), as more superficial excisions
are associated with greater recurrence. Intralesional corti�
costeroids should be considered postoperatively and then
monthly for at least 6 months to reduce the chance of lesion
recurrence.
Special management & counseling considerations
Patient education regarding suspected etiologic associations of
acne keloidalis nuchae may be useful. Acne keloidalis nuchae
Folliculitis decalvans
Crystal Y Pourciau
Folliculitis decalvans is an inflammatory form of cicatricial
alopecia, typically involving the vertex and occipital scalp,
although it may appear on any hair-bearing area. Patients are
more often male, although both sexes can be affected. Some
studies suggest the disease occurs less frequently in Caucasian
than African-American populations, though epidemiologic
data are limited.1
13â•… Follicular Disordersâ•… •â•… Folliculitis decalvans
typically affects young men, in whom closely cropped hair-
styles may be favored. It is important to stress that hair at the
occipital scalp and nape be left longer, and that contact of the
skin with razors or clippers is to be limited and done only with
extreme care. When recommending topical corticosteroid
therapy, it is important to note that the hair of African-
Americans may be somewhat dry. As such, many patients may
prefer an ointment vehicle. Gels may exacerbate dryness.
Patients should be informed that because acne keloidalis
nuchae is a chronic disorder, long-term preventive practices
will be necessary, and the treatment period may take months
to years before the disease is satisfactorily quiescent.
References
1. Azurdia RM, Graham RM, Weismann K, Guerin DM, Parslew R. Acne
keloidalis in Caucasian patients on cyclosporine following organ trans-
plantation. Br J Dermatol 2000; 143:465–467.
2. Sperling LC, Homoky C, Pratt L, Sau P. Acne keloidalis is a form of
primary scarring alopecia. Arch Dermatol 2000; 136:479–484.
3. George AO, Akanji AO, Nduka EU, Olasode JB, Odusan O. Clinical,
biochemical and morphologic features of acne keloidalis in a black
population. Int J Dermatol 1993; 32:714–716.
4. Kelly AP. Pseudofolliculitis barbae and acne keloidalis nuchae.
Dermatol Clin 2003; 21:645–653.
5. Quarles FN, Brody H, Johnson BA, Badreshia S, Vause SE, Brauner G,
et al. Acne keloidalis nuchae. Dermatol Ther 2007; 20:128–132.
6. Gloster HM Jr. The surgical management of extensive cases of acne
keloidalis nuchae. Arch Dermatol 2000; 136:1376–1379.
7. Bajaj V, Langtry JAA. Surgical excision of acne keloidalis nuchae with
secondary intention healing. Clin Exp Dermatol 2007; 33:53–55.
8. Glenn MJ, Bennett RG, Kelly P. Acne keloidalis nuchae: treatment with
excision and second intention healing. J Am Acad Dermatol 1999;
33:243–246.
9. Shah GK. Efficacy of diode laser for treating acne keloidalis nuchae.
Indian J Dermatol Venereol Leprol 2005; 71:31–34.
10. Woolery-Lloyd H, Cook-Bolden F. Using lasers on ethnic skin. Skin
Aging 2004; 12(7).
11. Kantor GR, Ratz JL, Wheeland RG. Treatment of acne keloidalis nuchae
with carbon dioxide laser. J Am Acad Dermatol 1986; 14:263–267.
12. Goh M, Magee J, Chong AH. Keratosis follicularis spinulosa decalvans
and acne keloidalis nuchae. Austral J Dermatol 2005; 46(4):257–
260.
13. Barr J, Friedman A, Balwin H. Use of imiquimod and pimecrolimus
cream in the treatment of acne keloidalis nuchae. J Am Acad Dermatol
2005; 590:64.
In the initial phase of folliculitis decalvans, erythematous,
follicular-based papules are noted in addition to hyperkera-
totic, greasy scales around affected ostia. Intermittent erosions
of the scalp with subsequent bleeding and hemorrhagic crust-
ing may arise at the involved area. Papules and erosions even-
tually evolve to form scarred, indurated plaques of alopecia
with pustules interspersed, which is characteristic of the dis�
order (Fig. 13.2). Patients may also develop erythema, pain
and pruritus with disease progression. After inflammatory
damage of the follicular epithelium occurs, a larger, common
infundibulum is formed with many hairs emerging from
the same dilated follicular ostia. This phenomenon is
termed ‘tufted folliculitis’ and is frequently seen in folliculitis
251
 Part 3 Follicular Disorders and Alopecias
Figure 13.2:╇ Folliculitis decalvans with severe scarring.
decalvans, although the argument has been made that this
disorder is a separate entity.2 The differential diagnosis for fol-
liculitis decalvans includes other cicatricial alopecias such as
dissecting folliculitis. However, a primary distinguishing factor
is that no sinus tracts are present, as are demonstrated in dis-
secting folliculitis.
Research in dermatopathology has attempted to better
define the underlying pathogenesis of folliculitis decalvans’
phenotypic presentation. It has been proposed that genetic
predisposition leads to an altered immune response with an
exaggerated influx of neutrophils into the perifollicular dermis.
T-lymphocytes, in turn, are activated by innate markers and
bacterial ‘super-antigens’ (specifically derived from staphylo-
coccal aureus species), propagating pro-inflammatory and
pro-fibrotic pathways, with subsequent fibrosis and the clinical
appearance of scarring.2–4
Management strategy
Folliculitis decalvans is a chronic, relapsing disorder that is
notoriously difficult to treat.5 The initial work-up should
include a general medical history as well as detailed question-
ing of disease presentation and progression. All associated
symptoms should be identified. Trauma and potential for
zoonotic/geonotic infection should be excluded. Screening for
immunodeficiences or underlying inflammatory conditions
may also be pursued if suggested by history. Careful examina-
tion of the scalp with particular attention to follicular status
is indicated, with baseline measurements and photo�graphy of
scarred areas to better track disease progression.2
Pustules should be cultured for bacteria and fungi. Scalp
biopsy may be warranted if the clinical presentation is not
obvious, although some authorities argue that biopsy is a
requirement for definitive diagnosis. According to the 2001
Duke University scalp biopsy consensus guidelines, horizon-
tally sectioned, hematoxylin and eosin histoanalysis of a single
252
4-mm punch biopsy taken from an active lesion is the gold
standard.2 Likewise, other etiologies of alopecia can be
excluded by pathological review.
First-Line Therapies
Tetracyclines E
Erythromycin E
Co-trimoxazole E
Cloxacillin E
Vancomycin E
Sulfamethoxazole-Trimethoprim E
Rifampin/Clindamycin C
Dapsone E
Intralesional corticosteroids E
Isotretinoin E
Modification of hair styles E
Folliculitis decalvans. Otberg N, Kang H, Alzolibani AA,
Shapiro J. Dermatol Therapy 2008; 21:238–244.
This article provides a comprehensive analysis of folliculitis
decalvans including pathogenesis, presentation, diagnosis and
therapeutic options. Antibiotics, corticosteroids, isotretinoin,
dapsone and other medications are reviewed.
Folliculitis decalvans – a retrospective study in a tertiary
referred centre, over five years. Chandrawansa PH, Giam YC.
Singapore Med J 2003; 44:84–87.
A retrospective analysis of 6 patients which reviewed
treatment modalities. The use of systemic antibiotics in man-
agement of folliculitis decalvans was highlighted. Multiple
courses of antibiotics were used with varied success. The
authors noted disease flares after cessation of medication.
Regimens include: erythromycin 500╯mg t.i.d. then 500╯mg
b.i.d., doxycycline 100╯mg b.i.d., co-trimoxazole 480╯mg b.i.d.,
cloxacilliin 500╯mg daily, tetracycline 500╯mg b.i.d., dapsone
150╯mg daily, fusidic acid 500╯mg t.i.d. and zinc sulphate
200╯mg b.i.d.
Folliculitis decalvans: successful treatment with a combina-
tion of rifampicin and topical mupirocin. Kanwar AJ. J Der-
matol 2002; 29:180–181.
A single case report details successful treatment of follicu-
litis decalvans with rifampin 600╯mg daily and topical mupi-
rocin 2% daily for 10 weeks. No recurrence was demonstrated
at 6-month follow-up.
Folliculitis decalvans including tufted folliculitis clinical,
histological and therapeutic findings. Powell JJ, Dawber RP,
Gatter K. Br J Dermatol 1999; 140:328–333.
Successful clearance of active folliculitis decalvans was dem-
onstrated in 15 of 18 patients following a 10-week course of
oral rifampin 300╯mg twice daily with twice daily dosing of
clindamycin 300╯mg. 5 of the patients required more than one
course of antimicrobials.

Folliculitis spinulosa decalvans: successful therapy with
dapsone. Kunte C, Loeser C, Wolff H. J Am Acad Dermatol
1998; 39:891–893.
A patient was treated with 1 month of dapsone 100╯mg
daily with resolution of disease after failing previous
trials of oral antibiotics, isotretinoin and class IV topical
corticosteroids.
Primary cicatricial alopecias: clinicopathology of 112 cases.
Tan E, Martinka M, Ball N, Shapiro J. J Am Acad Dermatol
2004; 50:25–32.
Therapeutic management for 12 patients with folliculitis
decalvans was reviewed. The authors highlight first-line therapy
with systemic antibiotics as well as the use of isotretinoin in
refractory cases (1╯mg/kg/day for 9 months with tapering after
6 months).
Improvement of folliculitis decalvans following shaving of
the scalp. Walker SL, Smith HR, Lun K, Griffiths WD. Br J
Dermatol 2000; 142:1245–1246.
A 37-year-old man with recalcitrant folliculitis decalvans,
failing topical and systemic corticosteroids, rifampin and
isotretinoin, had remission after maintenance of a closely
shaved hairstyle.
Multiple treatment options are suggested in published case
reports, yet no controlled studies have been performed to date.
Systemic antimicrobial agents often are mentioned as the most
effective and most frequently employed first-line therapy. On
average, antibiotic courses last 10 months with a range of 6–24
months.6,7 However, relapse typically is seen after medication
cessation. Rifampin appears to provide the greatest sustained
results, although multiple courses may be required.3–6,8,9 Most
authorities warn that rifampin should not be used as mono-
therapy secondary to the high likelihood of resistance develop-
ing. Clindamycin is most commonly cited as the adjunct
therapy of choice.
Alternate management options with minimal associated
morbidities have been discussed. In a 5-year prospective study
performed in the United Kingdom,1 intralesional corticoster-
oids (triamcinolone acetonide 10mg/mL every 4–6 weeks)
were used as an adjunct to antimicrobials when acute inflam-
mation was found at presentation. Systemic corticosteroids
were given in exuberant flares of disease. In this same study,
isotretinoin was given as a trial in 9 patients at a dose of 1╯mg/
kg for at least 6 months, with an average duration of 9 months.1
The authors had success with this regimen, reporting delay in
relapse, similar to success in other reports of neutrophilic,
cicatricial alopecia.
Second-Line Therapies
Nd-YAG laser E 1. Tan E, Martinka M, Ball N, Shapiro J. Primary cicatricial alopecias:
Surgical excision E 2. Otberg N, Kang H, Alzolibani AA, Shapiro J. Folliculitis decalvans.
13â•… Follicular Disordersâ•… •â•… Folliculitis decalvans
Nd:YAG laser treatment of recalcitrant folliculitis decalvans.
Parlette EC, Kroeger N, Ross, EV. Dermatol Surg 2004;
30:1152–1154.
Remission was noted in an African-American man with
refractory folliculitis decalvans after 8 treatments with 1064-nm
Nd-YAG laser with dynamic cryogen cooling spray at a fluence
of 28╯J/cm2, pulse duration of 3msec and spot size of 12╯mm
at 4–6-week intervals.
Procedural modalities for the management of folliculitis
decalvans have been cited as well. In one case report, a 26-year-
old African-American man with Fitzpatrick skin type VI and
chronic history of refractory folliculitis decalvans had 6 month
remission of his disorder after eight treatments with the
Nd-YAG laser.10 Additionally, for limited, focal lesions, remis-
sion has been noted following surgical excision of scarred
plaques.
Commonly encountered pitfalls
In a Canadian study investigating primary cicatricial alopecias,
there was a predominance of cases in Middle Eastern and East
Indian patients (61%) in comparison to Caucasians (23%)
and African-Americans (15%). However, the overall, ethnic
distribution had few African-Americans at start, representing
0.5% of the total participants reviewed.
Among many African-American men, bald hairstyles are
seen as a popular and culturally acceptable hairstyle. This is a
management option that can be recommended as not just a
clinical benefit but a socially appropriate option to the patient
as well.11
The most likely adverse events of all proposed interventions
must be reviewed prior to initiating therapy. Specifically, as
corticosteroids are implemented frequently in the manage-
ment of folliculitis decalvans, it is important to review the
common side effects associated with their use, including but
not limited to dyschromia and atrophy, which may be more
notable in darker-skinned individuals. Additionally, prior to
exploring surgical procedures, the risk of dyspigmentation and
hypertrophic/keloidal scars must be reviewed, especially in
those persons with prior history of such adverse events.
Special management & counseling considerations
Neutrophilic cicatricial alopecias, and folliculitis decalvans in
particular, are notoriously difficult to treat. Sensitivity and
patience must be exercised when counseling affected persons.
A comprehensive approach from diagnosis to management is
key in caring for this population. For further information,
patients may be referred to online resources, such as
www.nahrs.org and www.carfintl.org.
References
clinicopathology of 112 cases. J Am Acad Dermatol 2004; 50:25–32.
Dermatol Therapy 2008; 21:238–244.
253
 Part 3 Follicular Disorders and Alopecias
3. Chiarini C, Torchia D, Bianchi B, Volpi W, Caproni M, Fabbri P.
Immunopathogenesis of Folliculitis Decalvans. Am J Clin Pathol
2008; 130:526–534.
4. Powell JJ, Dawber RP, Gatter K. Folliculitis decalvans including tufted
folliculitis clinical, histological and therapeutic findings. Br J Dermatol
1999; 140:328–333.
5. Brooke RCC, Griffiths CEM. Folliculitis decalvans. Clin and Exp
Dermatol 2001; 26:120–122.
6. Chandrawansa PH, Giam YC. Folliculitis decalvans – a retrospective
study in a tertiary referred centre, over five years. Singapore Med J
2003; 44:84–87.
7. Kunte C, Loeser C, Wolff H. Folliculitis spinulosa decalvans: successful
therapy with dapsone. J Am Acad Dermatol 1998; 39:891–893.
Pseudofolliculitis
barbae
Pseudofolliculitis barbae (PFB) is a chronic inflammatory
papular and pustular foreign body reaction of hair-bearing
areas. Most common on the beard and neck areas, pseudofol-
liculitis barbae may also be found on other commonly shaved
hair-bearing regions, such as the axillae or pubic area. Pseudo-
folliculitis barbae, often colloquially referred to as ‘shaving
bumps’ or ‘razor bumps,’ is characterized by multiple flesh-
colored, erythematous or hyperpigmented papules with a hair
shaft within their centers. The beard region and anterior
neck are most commonly affected, and the mustache and
side-burn areas are generally spared. Pustules, resulting
from secondary infections, are not uncommon, and abscess
formation may occur. Severe untreated disease may even�
tuate in severe hyperpigmentation, scarring or even keloids
(Fig. 13.3).
Pseudofolliculitis barbae is most commonly seen in Black
men with curly hair, and it has been estimated that 45–83%
A B
Figure 13.3:╇ (A) Pseudofolliculitis barbae. (B) Pseudofolliculitis barbae.
254
8. Kaur S, Kanwar AJ. Folliculitis decalvans: successful treatment with
a combination of rifampicin and topical mupirocin. J Dermatol
2002; 29:180–181.
9. Powell JJ, Dawber RP. Successful treatment regime for folliculitis decal-
vans despite uncertainty of all aetiological factors. Br J Dermatol
2001; 144:428–429.
10. Parlette EC, Kroeger N, Ross EV. Nd:YAG laser treatment of recalcitrant
folliculitis decalvans. Dermatol Surg 2004; 30:1152–1154.
11. Walker SL, Smith HR, Lun K, Griffiths WD. Improvement of folliculitis
decalvans following shaving of the scalp. Br J Dermatol 2000; 142:
1245–1246.
of Black men are affected by the disease.1 Though most
common in adult Black men, especially those who regularly
shave, pseudofolliculitis barbae may also affect Black women,
especially those who are more hirsute. Women may also be
more commonly affected in the pubic and axillary regions, as
these are common sites of hair removal. Plucking, tweezing,
waxing and electrolysis may all eventuate in pseudofolliculitis
barbae. Cyclosporine treatment has also been associated with
pseudofolliculitis barbae.
Pseudofolliculitis barbae results from the extrafollicular or
transfollicular penetration of sharp tipped hairs.2 These sharp
hairs most commonly result from shaving, but may also occur
secondary to plucking. It is widely accepted that pseudofol-
liculitis is more common in Black individuals because of the
coiled nature of the hair shaft, as well as the curved hair follicle
itself. Sharp tipped hairs curl back into the skin, causing epi-
dermal and dermal inflammation. Shaving against the grain
and pulling the skin taut during shaving can cause curved hairs
to retract below the skin when tension is released. Subse-
quently, the curved hair may grow into the follicle, eventually
penetrating the follicular wall and leading to inflammation.
Pseudofolliculitis barbae may be chronic in individuals
whose professional or personal dictates necessitate a clean
 13â•… Follicular Disordersâ•… •â•… Pseudofolliculitis barbae

shaven appearance. In individuals unwilling to stop shaving For patients that prefer to shave with a razor, a single-edged
or plucking the hair, improvement may occur with medical blade with a foil guard should be utilized to prevent hairs from
therapy, but cure is not likely. being trimmed too closely. Topical eflornithine may help to
The diagnosis of pseudofolliculitis barbae is typically a decrease the rate of hair growth, and its use often results in
purely clinical one. The differential diagnosis includes acne finer, less noticeable hairs.
vulgaris, tinea barbae, folliculitis and sarcoidosis. Unlike pseu-
dofolliculitis barbae, acne vulgaris is commonly characterized Combination laser and eflornithine HCL 13.9% cream: a
by comedones, and lesions are not limited to shaved areas. first line therapy for Fitzpatrick type IV–VI patients with
Tinea barbae is usually more confluent and may be unilateral. excessive facial hair. Callender V, Young CM. J Am Acad Der-
Culture or microscopy can be used for differentiation. Fol- matol 2005; 52:P209.
liculitis will be associated with a positive bacterial culture, A retrospective review of 80 randomly selected patients
whereas culture of pseudofolliculitis barbae lesions will be with excessive facial hair treated with combination eflorni-
positive only during secondary infection. Sarcoidal lesions can thine hydrochloride 13.9% and laser hair removal. Combina-
be differentiated by biopsy. tion therapy resulted in quicker and more complete results
than laser hair removal alone in eradication of both terminal
and vellus hairs.
First-Line Therapies
Some authors advocate the gentle brushing of the beard,
Cessation/limiting hair removal D followed by gentle lifting of any embedded hairs with a needle
Clippers, depilatories, single-bladed foil-guard razor D or toothpick.3 Extreme caution must be exercised with this
method however, to avoid trauma and secondary infection.
Eflornithine B
Low potency topical corticosteroids may be useful to reduce
Antibiotic soaps E inflammation, and topical retinoids, when used nightly, seem
Topical corticosteroids E to improve hyperpigmentation and hyperkeratosis, and may
Topical antibiotics C make hairs less likely to embed within the skin. Topical anti-
Oral antibiotics E biotics such as clindamycin and erythromycin, often com-
Intralesional corticosteroids E bined with a benzoyl peroxide preparation, are useful in
Topical retinoids D reducing skin bacteria and treating mild secondary infection.
Oral antibiotics, commonly tetracyclines, are useful for their
anti-inflammatory properties, as well as to treat pustular
lesions or abscesses. Intralesional corticosteroids, typically
Cessation of hair removal is likely to lead to cure of pseudo-
2.5–5╯mg/mL may be useful for more immediate relief of
folliculitis barbae. If complete cessation of hair removal is not
inflammatory papules, though caution should be exercised to
a viable option, discontinuation of shaving for up to 6 months
avoid hypopigmentation.
may lead to significant disease improvement. In cases where
Topical retinoids have been used in the treatment of PFB.
hair removal must continue, patients should be instructed on
hair removal options which are less likely to exacerbate the
Pseudofolliculitis of the beard and topically applied
disease. If possible, hair removal should occur with electric
tretinoin. Kligman AM, Mills OH. Arch Dermatol 1973; 107:
clippers, and the clippers should not be allowed to rub against
551–552.
the skin. Other means of hair removal may include beard trim-
Tretinoin solution 0.05% was evaluated in 11 early cases of
ming with scissors and chemical depilatories such as barium
moderately severe pseudofolliculitis of the beard and in 27
sulfide or calcium thioglycolate preparations. These chemicals
cases in older subjects, including some with long-standing
work by breaking the disulfide bonds in the hair, resulting in
cases of extreme severity. Daily application was beneficial in
hairs that are bluntly broken at the follicular opening. Chemi-
the early stages, producing good to excellent results within 8
cal depilatories may be associated with skin irritation and
weeks. Severe cases of pseudofolliculitis barbae were poor
chemical burns, and patients should be forewarned.
responders.
Surgical depilation for the treatment of pseudofolliculitis
or local hirsutism of the face: experience in the first 40 Second-Line Therapies
patients. Hage JJ, Bowman FG. Plast Reconstr Surg 1991;
88:446–451. Glycolic acid B
40 patients underwent surgical depilation over a 15-year Liquid nitrogen cryospray E
period for pseudofolliculitis barbae or local hirsutism of the Laser B
face. Affected skin was incised, everted, and a dermal-
subcutaneous plane containing hair bulbs was excised. The
operative method and its results and pitfalls are discussed. Side Glycolic acid peels may reduce sulfhydryl bonds in the hair
effects were significant, and this surgical method was not shaft and decrease hyperkeratosis and thickening of the
deemed the treatment of choice; however, it was proposed as stratum corneum, therefore allowing for straighter hair growth
an option when other therapy has not been successful. and less epidermal re-entry of hairs.

255
 Part 3 Follicular Disorders and Alopecias
Treatment of pseudofolliculitis barbae with topical glycolic
acid: a report of two studies. Perricone NV. Cutis 1993;
52:232–235.
Glycolic acid lotion was found to be significantly more
effective than placebo in treating pseudofolliculitis barbae in
these placebo controlled trials of 35 adult men. The author
reports a 60% reduction in lesions on treated areas.
Weekly liquid nitrogen cryosprays of 10–15 second thaw
times, which cause a mild peel of the skin, have been suggested
by Kelly as an adjunctive treatment.3 Patients should be advised
that both glycolic acid peel and cryospray may cause hypopig-
mentation of the skin.
Recently, lasers have been gaining in popularity in the treat-
ment of pseudofolliculitis barbae. Both the superlong pulsed
810╯nm diode laser4 and the 1064╯nm Nd-YAG laser have
shown promising results with skin of color.1
Treatment of pseudofolliculitis barbae in skin types IV, V,
and VI with a long-pulsed neodymium:yttrium aluminum
garnet laser. Ross EV, Cook LM, Cimko AL. J Am Acad Der-
matol 2002; 47(2):263–270.
The long pulsed Nd-YAG laser resulted in a decrease in
papule formation and a reduction of hair counts. Most sub-
jects had a return of normal hair regrowth after 6 months, but
2 of 20 subjects still had areas of permanent hair loss at the
12-month follow-up.
Treatment of pseudofolliculitis barbae using the long-pulse
Nd:YAG laser on skin types V and VI. Weaver SM, Sagaral EC.
Dermatol Surg 2003; 29(12):1187–1191.
20 male and female subjects with skin types V and VI were
given two treatments approximately 3–4 weeks apart, and
assessed at 1, 2 and 3 months after the final treatment. A sta-
tistically significant reduction in the quantity of papules/
pustules was reported at 1-, 2- and 3-month follow-ups. Side
effects included transient hyperpigmentation and hypopig-
mentation, mild erythema and itching.
Modified superlong pulse 810╯nm diode laser in the treat-
ment of pseudofolliculitis barbae in skin types V and VI.
Smith EP, Winstanley D, Ross EV. Dermatol Surg 2005;
31(3):297–301.
13 patients with skin types V and VI were treated three times
at 2-week intervals with varying fluences. The authors reported
a statistically significant improvement in lesion count. The
margin of safety was found to be greater in type V compared
to type VI skin.
256
Commonly encountered pitfalls
Clinicians should be aware that several of the treatments cur-
rently available for pseudofolliculitis barbae may be associated
with dyspigmentation. Extreme caution should be exercised
with intralesional corticosteroids, chemical peels, and cry-
ospray to avoid pigmentary changes. Patients that elect laser
therapy should be informed of the possibility of dyspigmenta-
tion, blistering and scarring. Patients should also understand
that epilation, perhaps permanent, will result. Patients should
be counseled that pseudofolliculitis barbae may be chronic,
and as long as hair removal techni�ques are employed, therapy
may yield improvement, but not complete cure.
Special management & counseling considerations
Patient education is the cornerstone of treatment. Patients
must be well informed of the causes and exacerbating factors
of the disease, and should understand that with continued
shaving or hair removal, complete cure is unlikely. When
counseling patients to avoid shaving, clinicians should be
especially sensitive to the fact that professional appearance
(e.g. military) may not allow for shaving avoidance. As such,
proper shaving technique is imperative. The beard areas should
be gently massaged with a soft toothbrush or wet sponge prior
to shaving. Next, warm water compresses should be applied
to the area to be shaved for 5 minutes.1 A shaving cream
should always be used, and the skin should never be pulled
taut. Shaving should always occur with the grain of the hair,
and a single-bladed razor, preferably one with a foil guard,
should be employed.
While pseudofolliculitis barbae has little impact on general
physical health, it is a significant cosmetic concern. Clinicians
should be mindful of the significant embarrassment and psy-
chosocial distress that the disorder can cause.
References
1. Bridgeman-Shah S. The medical and surgical therapy of pseudofol-
liculitis barbae. Dermatol Ther 2004; 17:158–163.
2. Chuh A, Zawar V. Epiluminescence dermatoscopy enhanced patient
compliance and achieved treatment success in pseudofolliculitis
barbae. Austral J Dermatol 2006; 47:60–62.
3. Kelly AP. Pseudofolliculitis barbae and acne keloidalis nuchae.
Dermatol Clin 2003; 21(4):645–653.
4. Greidanus TG, Honl B. Pseudofolliculitis of the beard. eMedicine.
http://emedicine.medscape.com/article/1071251. 2007.
 PART 4
Tumors Benign and Malignant
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Part 4 Tumors Benign and Malignant

Benign Tumors
Erica Mailler-Savage, Matthew Joseph Turner, David Robert Crowe, Erica Chon Davis
and Hugh Morris Gloster Jr 14â•…
Introduction . . . . . . . . . . . . . . . . . . . . . . . . 259 early diagnosis and proper treatment very important.2 Not
only are there differences in mortality rates, but there are also
Acrochordon . . . . . . . . . . . . . . . . . . . . . . . . 260
significant differences in the clinical presentation of skin
Dermatofibroma . . . . . . . . . . . . . . . . . . . . . . 260 cancers between light- and dark-skinned patients including the
Dermatosis papulosa nigra . . . . . . . . . . . . . . . . 261 location of the skin cancer (i.e. sun-exposed versus non-
sun-exposed or acral locations), the appearance of the tumor
Epidermal nevus . . . . . . . . . . . . . . . . . . . . . . 263
(i.e. non-pigmented versus pigmented), and the most common
Congenital melanocytic nevus . . . . . . . . . . . . . . 264 type of skin cancer in each group (Table 14.1).
Dysplastic nevus . . . . . . . . . . . . . . . . . . . . . 265
Epidermoid cyst . . . . . . . . . . . . . . . . . . . . . . 266
Keloid . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Table 14.1╇ Most common skin cancers by race/ethnicity

Race / ethnicity Skin cancer

White, Asian/Pacific Islander, Hispanic Basal cell carcinoma

Introduction Squamous cell carcinoma

Malignant melanoma
Black, Asian (Indian) Squamous cell carcinoma
The 2008 US Census Bureau estimated that racial and ethnic Basal cell carcinoma
minorities comprise approximately 34% of the total popula- Malignant melanoma
tion in the US.1 This percentage will likely continue to increase
in the future. Therefore, it is important as dermatologists to
become familiar with the presentation of cutaneous tumors in
skin of color patients as the appearance and clinical course of
tumors can vary. Benign lesions, such as keloids and dermato- References
sis papulosa nigra, occur more commonly in this population
and can often be more challenging to treat. 1. US Census Bureau: State and County QuickFacts. US Census
Bureau. http://quickfacts.census.gov/qfd/states/00000.html [Accessed
Although skin cancer is less common in patients with
November 13, 2009].
darker skin phototypes, malignant tumors are often associated 2. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol
with greater morbidity and mortality in these patients, making 2006; 55:741–760.

©2011 Elsevier Ltd, Inc, BV 259

 Part 4 Tumors Benign and Malignant
Acrochordon
Acrochordons (skin tags) are exceedingly common in the
general population with a reported incidence of approximately
46%. No data are available to suggest if the incidence is higher
or lower in ethnic skin. Skin tags are pedunculated, soft
papules, one to several millimeters in size, and most com-
monly occur on the neck, axillae, trunk and groin. They may
be tan, pink, or brown in color (Fig. 14.1). Histology demon-
strates a dome-shaped lesion with proliferation of collagen
and dilated capillaries. Obesity, diabetes, insulin resistance,
and atherosclerosis are frequently associated with skin tags,
but the presence of skin tags on a patient is not diagnostic of
these conditions. Acanthosis nigricans is frequently associated
with skin tags. The pathogenesis of skin tags has not yet been
elucidated, but growth of fibroblasts with insulin resistance
has been suggested. The presence of skin tags in Rabson–
Mendelhall syndrome, a rare autosomal recessive syndrome
associated with a defective insulin-receptor gene, further sug-
gests a related pathogenesis.
First-Line Therapies
Scissor excision E
Cryosurgery E New mechanical device for effective removal of skin tags in
Electrodessication E routine health care. Fredriksson CH, Ilias M, Anderson CD.
Flat adhesive patch B Dermatol Online J 2009; 15(2):9.
Mechanical clamping D A total of 177 skin tags were treated in 32 individuals with
Skin tags. Neville JA, Yosipovitch G. In: Arndt K, Hsu JTS,
eds. Manual of dermatologic therapeutics. 7th edn. Baltimore:
Lippincott, Williams & Wilkins; 2007:210–211.
Describes technique of excision of skin tags at base with iris
scissors and obtaining hemostasis with Monsel’s, aluminum
chloride, mild acids, or electrosurgery. Also describes cryo-
therapy and electrodessication.
Cryoanesthesia and electrosurgical treatment of benign skin
tumors. Spiller WF, Spiller RF. Cutis 1985; 35(6):551–552.
Report suggesting liquid nitrogen spray followed by light
electrodessication is a cosmetically acceptable method of treat-
ing skin tags.
Dermatofibroma
Dermatofibromas are common, benign, dermal papules and
nodules which usually occur on the trunk, buttocks, and
260
Figure 14.1:╇ Pigmented skin tag on a patient with Fitzpatrick skin type IV. Note
the dark brown color as opposed to the typical flesh-colored appearance. (Courtesy
of Valerie D. Callender, MD.)
Surgical pearl: a rapid technique for destroying small skin
tags and filiform warts. Goodheart HP. Dermatol Online J
2003; 9(5):34.
In this report, a hemostat, a non-toothed forcep, or a
needle holder was dipped into liquid nitrogen for 15 seconds,
and then used to grasp the stalk of each skin tag for about 10
seconds. Most lesions resolved within 7–10 days but some
lesions required multiple treatments.
a flat adhesive patch which applied pressure to the base of a
skin tag, leading to its removal within 3–6 days. Successful
outcome was highest (90%) for lesions up to 1╯mm in base.
For lesions up to 2╯mm, the rate of successful outcome
was 76%. The cosmetic outcome after removal was excellent.
Discomfort was assessed as minimal during all stages of the
procedure.
Surgical pearl: tissue forceps as a simple and effective instru-
ment for treating skin tags. Mukhtar M. Int J Dermatol 2006;
45(5):577–579.
Five patients with 37 skin tags were treated by clamping the
base of the skin tags with Kocher’s forceps for 10–15 seconds
for smaller tags and 2–30 seconds for larger tags. Discomfort
was rated as acceptable to the patients. After 4 weeks, all 37
tags had resolved.
extremities. They present as shiny or keratotic firm red, yellow
or brown papulonodules with dimpling on palpation (Fig.
14.2). Middle-aged women are most commonly affected. They
are proposed to form at sites of previous cutaneous injury
including insect bites, shaving and thorn pricks. Dermatofibro-
mas are usually asymptomatic but can be pruritic or painful.

Figure 14.2:╇ Dermatofibroma. (Courtesy of Valerie D. Callender, MD.)
Dermatofibromas are divided histologically into two main
subtypes composed mostly of fibroblastic cells (fibrous type)
and histiocytic cells (cellular type) with several other more rare
subtypes. Whether dermatofibromas are a true neoplasm or a
reactive hyperplasia is still not certain. Multiple eruptive der-
matofibromas have been described in the setting of autoim-
mune disease, treatment with immunosuppressive medications,
in HIV, and in neoplastic diseases. Treatment of these lesions
is unnecessary but may be undertaken for rapidly growing or
uncomfortable lesions.
Dermatosis papulosa
nigra
Dermatosis papulosa nigra (DPN) is a benign epithelial tumor
very common in the Black population with an estimated
incidence of 35–77%. DPN is considered to be a variant of
seborrheic keratoses with similar histologic findings of acan-
thosis and papillomatosis. DPN is more common in women,
presents in or after the second decade, and usually demon-
strates a familial predisposition. Lesions initially appear on the
face but may involve the neck or upper trunk, indicating that
they may be sun-related (Figs. 14.3 & 14.4). The lesions may
be papular or pedunculated and are brown to deep black in
color (Figs. 14.5 & 14.6).
14â•… Benign Tumorsâ•… •â•… Dermatosis papulosa nigra
First-Line Treatment
Excision
Second-Line Treatment
Cryosurgery B
Pulsed dye laser C
Cryosurgery in dermatologic office practice: special refer-
ence to dermatofibroma and mucous cyst of the lip. Spiller
WF, Spiller RF. South Med J 1975; 68:157–160.
Forty-five dermatofibromas, which varied in size from
4–15╯mm in diameter, were treated by cryosurgery, with 5
receiving a second treatment. In most cases, after the healing
occurred, there was residual hyperigmentation that lasted
several months. In 15 patients, the resultant scars were hypo-
pigmented. There was one atrophic scar but no hypertrophic
scars.
Treatment of dermatofibroma with a 600nm pulsed dye
laser. Wang SQ, Lee PK. Dermatol Surg 2006; 32:532–535.
A 600-nm pulsed-dye laser was used to treat 20 lesions from
18 Caucasian patients. Each lesion was treated three times at
6–8 week intervals at a fluence of 7╯J/cm2, a spot size of 7╯mm,
and a pulse duration of 1.5╯ms. Symptoms resolved in all
lesions that were symptomatic prior to treatment, 75% had an
improvement in the size of the lesion, and 60% had an
improvement in color.
Figure 14.3:╇ Dermatosis papulosa nigra. (Courtesy of Valerie D. Callender, MD.)
261
 Part 4 Tumors Benign and Malignant

Figure 14.4:╇ Dermatosis papulosa nigra on the neck of a Fitzpatrick skin type V
patient. (Courtesy of Valerie D. Callender, MD.)

First-Line Therapies
Figure 14.5:╇ Fitzpatrick skin type V patient with dermatosis papulosa nigra prior to
electrodessication. (Courtesy of Valerie D. Callender, MD.)
Electrodessication C
KTP laser C

A randomized, double-blind comparison of two topical

anesthetic formulations prior to electrodessication of der-
matosis papulosa nigra. Carter EL, Coppola CA, Barsanti FA.
Dermatol Surg 2006; 32:1–6.
Forty adults were randomly assigned to treatment with
either EMLA or LMX4 for 30 minutes under Tegaderm prior to
treatment with electrodessication. Both were comparable in
achieving tolerable anesthesia after a single 30-minute
application.

Comparison of electrodessication and potassium-titanyl-

phosphate laser for treatment of dermatosis papulosa nigra.
Kundu RV, Joshi SS, Suh KY, Boone SL, Huggins RH, Alam M,
et al. Dermatol Surg 2009; 35:1079–1083.
Fourteen subjects were randomized to receive two KTP laser
treatments 4 weeks apart to half of the face. The contralateral
half received two electrodessication treatments 4 weeks apart.
Difference in improvement between the two sides did not
reach statistical significance. Both treatments were well toler-
ated without significant adverse effects with KTP laser being
slightly more tolerable.
Figure 14.6:╇ Dermatosis papulosa nigra following electrodessication. (Courtesy of
Valerie D. Callender, MD.)
Second-Line Therapies
Treatment of dermatosis papulosa nigra with a 1064nm
Nd-YAG laser E Nd:YAG laser: report of two cases. Schweiger ES, Kwasniak L,
Curettage B Aires DJ. J Cosmet Laser Ther 2008; 10:120–122.
Non-ablative fractional laser E Two patients treated with Nd-YAG had resolution of lesions
with good cosmetic outcome.

262

A surgical approach for dermatosis papulosa nigra. Kauh
YC, McDonald JW, Rapaport JA, Ruschak PJ, Luscombe HA.
Int J Dermatol 1983; 22:590–592.
Describes 20 cases of DPN treated with light abrasive curet-
tage without local anesthesia. No postoperative scarring or
significant postoperative pigmentary change was present.
Dermatosis papulosa nigra treatment with fractional pho-
tothermolysis. Katz TM, Goldberg LH, Friedman PM. Derma-
tol Surg 2009; 35:1840–1843.
Epidermal nevus
Epidermal nevi (Fig. 14.7) are hamartomas characterized by
hyperplasia of the epidermis and adnexal structures. Verrucous
epidermal nevus, nevus sebaceous (Fig. 14.8), nevus come-
donicus, eccrine nevus, apocrine nevus, Becker’s nevus, and
white sponge nevus are all variants of epidermal nevi. Most
lesions are present at birth, enlarging slowly during childhood
and generally reaching a stable size at adolescence. Lesions
may be localized or diffuse. Linear configurations are common.
The histology of epidermal nevi varies depending on the
subtype but all variants share features of hyperkeratosis, acan-
thosis and papillomatosis.
Verrucous epidermal nevi may be associated with the
epidermal nevus syndrome, characterized by developmental
abnormalities of the skin and eyes, as well as the central
nervous, skeletal, cardiovascular, and urogenital systems.
Figure 14.7:╇ Epidermal nevus on the forehead of a skin of color patient. Note the
hyperpigmented, verrucous-like appearance. (Courtesy of Valerie D. Callender, MD)
14â•… Benign Tumorsâ•… •â•… Epidermal nevus
The authors report the case of a 50-year-old Pakistani
patient (Fitzpatrick skin type IV) with dermatosis papulosa
nigra who was successfully treated with the 1550-nm erbium-
doped laser. The patient received three treatments at 4- to
5-week intervals at fluences between 60 and 70╯mJ. After treat-
ment, the patient experienced a > 75% improvement without
post-treatment complications.
Rarely, malignant transformation to basal cell and squamous
cell carcinomas may be seen. The development of tumors in
nevus sebaceous is much more common. Syringocystadenoma
papilliferum, basal cell carcinoma and trichoblastomas have
all been reported to arise in nevus sebaceous. The risk of basal
cell carcinoma led to the common practice of prophylactic
excision of nevus sebaceous during childhood.
First-Line Therapies
Excision E
Full-thickness surgical excision for the treatment of inflam-
matory linear verrucous epidermal nevus. Lee BJ, Mancini
AJ, Renucci J, Paller AS, Bauer BS. Ann Plast Surg 2001;
47(3):285–292.
Figure 14.8:╇ Nevus sebaceous of the scalp in a Hispanic patient. (Courtesy of
Valerie D. Callender, MD.)
263
 Part 4 Tumors Benign and Malignant

Report of 4 patients with extensive inflammatory linear Successful therapy of an ILVEN in a 7-year-old girl with
verrucous epidermal nevus (ILVEN) treated successfully with calcipotriol. Böhm I, Bieber T, Bauer R. Hautarzt 1999;
full-thickness surgical excision. 50(11):812–814.
A child treated with calcipotriol 0.005% for 4 weeks with
nearly full resolution and no recurrence after a 25-week
follow-up.
Second-Line Therapies
Epidermal nevi treated by carbon dioxide laser vaporiza-
Acitretin E tion: a series of 25 patients. Paradela S, Del Pozo J, Fernandez-
Tretinoin and 5-fluorouracil E Jorge B, Lozano J, Martinez-Gonzalez C, Fonseca E. J
Calcipotriol E Dermatolog Treat 2007; 18:169–174.
Twenty-five patients were treated with the CO2 laser in
CO2 laser B
superpulsed mode, focalized at 2╯W/cm2. Patients with soft,
Erbium:YAG laser B flattened nevi obtained better results than patients with thick,
Ruby laser D keratotic nevi (good results in 92% and 33%, respectively).
The authors conclude that CO2 laser in superpulsed mode is
an effective treatment for verrucous epidermal nevi but
outcome is related to the thickness of the nevus.
Clinical investigation of acitretin in children with severe
inherited keratinization disorders in China. Zhang XB, Luo Er:YAG laser treatment of verrucous epidermal nevi. Park JH,
Q, Li CX, He YQ, Xu X. J Dermatolog Treat 2008; 19(4): Hwang ES, Kim SN, Kye YC. Dermatol Surg 2004; 30:378–381.
221–228. Er:YAG laser was used in the treatment of 20 patients with
Acitretin was given as a treatment dose of 0.77–1.07╯mg/ verrucous epidermal nevi. Fifteen patients experienced a suc-
kg/day (mean 0.86 ± 0.11) and maintenance dose of cessful elimination of nevi after a single treatment. Relapse
0–0.94╯mg/kg/day (mean 0.33 ± 0.26) to 28 children with occurred in 5 patients (25%) within 1 year after treatment.
severe inherited disorders of keratinization (including 3 Side effects included transient erythema, hypopigmentation,
patients with ILVEN). After 2–4 months of treatment, the clini- and post-inflammatory hyperpigmentation.
cal cure rate was 82.1% and the effectiveness rate was 17.9%.
Successful treatment of dark-colored epidermal nevus with
Topical tretinoin and 5-fluorouracil in the treatment of ruby laser. Baba T, Narumi H, Hanada K, et al. J Dermatol
linear verrucous epidermal nevus. Kim JJ, Chang MW, 1995; 22:567–570.
Shwayder T. J Am Acad Dermatol 2000; 43(1 Pt 1):129–132. Five patients with darkly pigmented epidermal nevi were
Treatment of a linear verrucous epidermal nevus using successfully treated with pulsed ruby laser. However, hypopig-
topical 0.1% tretinoin cream and 5% 5-fluorouracil in a young mentation occurred at the treatment site in 2 patients with
patient with significant improvement. darker skin.

Congenital melanocytic
nevus
Congenital melanocytic nevi are brown or black patches or
plaques that are present at birth or which develop in the first
year of life (Figs. 14.9 & 14.10). Approximately 1–6% of new-
borns are affected annually. Congenital melanocytic nevi are
characterized as small, medium, large or giant depending
upon their size (Fig. 14.11). Small nevi are 1.5 cm or less,
medium nevi are < 10╯cm, large nevi are between 10 and
20╯cm, and giant nevi are > 20╯cm. Small and medium nevi
are fairly common while giant nevi are rare. African-Americans
have a slightly higher occurrence of congenital melanocytic
nevi than Caucasians. The risk of malignant transformation of
small congenital melanocytic nevi into melanoma has been Figure 14.9:╇ Congenital nevus on the chest of skin phototype V patient. Note the
estimated to be approximately 1 in 2000 in African-Americans smaller, more heavily pigmented area versus the larger, more lightly pigmented
up to age 75.1 skin and surrounding speckled pattern. (Courtesy of Valerie D. Callender, MD.)

264

Figure 14.10:╇ Congenital melanocytic nevus on the neck. (Courtesy of Valerie D.
Callender, MD.)
Figure 14.11:╇ Congential melanocytic nevus. (Courtesy of Valerie D. Callender,
MD.)
Dysplastic nevus
Dysplastic nevi, also known as Clark’s nevi, BK moles, or
atypical nevi, are lesions usually > 5mm in diameter, irreg�
ular in shape, and are heterogenous in color (Fig. 14.12).
The estimated prevalence of clinically atypical nevi is
14â•… Benign Tumorsâ•… •â•… Dysplastic nevus
Approximately 10% of patients with giant congenital
melanocytic nevi are affected by neurocutaneous melanosis.
Neurocutaneous melanosis is characterized by numerous
abnormal melanocytes clustered in the brain and spinal cord,
resulting in seizures, hydrocephalus, and developmental delay.
The lifetime risk of developing melanoma within giant melano-
cytic nevi is approximately 5% and is slightly increased in
lesions that overlie the spine. Excision of at-risk lesions does
not decrease the risk of developing neurologic lesions. All
patients with giant congenital nevi should have annual cutane-
ous, lymph node, and neurological examination. Focal growths,
pigment changes, ulceration, and tenderness within lesions are
signs concerning for malignancy. Patients should be instructed
to avoid ultraviolet light to decrease their risk of developing
cutaneous malignancy. Routine MRIs are not suggested to
screen for neurocutaneous melanosis as no current treatment
is available but as a baseline may provide psychological relief
to patients and their families if they are negative.
First-Line Therapies
Excision C
Management of congenital nevocellular nevi. Mollitt DL,
Golladay ES. Am J Surg 1985; 150(6):669–671.
Seventeen children with localized nevi and those that
covered 5–50 percent of the total body surface area were
treated with primary removal or serial excision at an average
of 6 month intervals. Complete removal of nevi with good
cosmetic outcome was obtained without the need for skin
grafting.
Congenital melanocytic nevi: treatment modalities and
management options. Marghoob AA, Borrego JP, Halpern AC.
Semin Cutan Med Surg 2007; 26(4):231–240.
Prophylactic partial or complete excision of giant congenital
melanocytic nevi should be undertaken between 6 and 9
months of age and should be performed on a case by case basis.
Surgical removal can be simple or serial and can be accom-
plished with or without skin grafts or tissue expanders.
Reference
1. Shpall S, Frieden I, Chesney M, Newman T. Risk of malignant trans-
formation of congenital melanocytic nevi in blacks. Pediatr Dermatol
1994; 11:204–208.
7–18%. Dysplastic nevi may be located anywhere on the
skin and may be single or multiple in number. The dys�
plastic nevus syndrome is characterized by a triad of > 100
nevi, at least one nevus 8╯mm or larger in diameter, and
at least one nevus with clinically atypical features.
The histological diagnosis of dysplastic nevi is non-
universal but based on both architectural and cytologic
abnormalities.
265
 Part 4 Tumors Benign and Malignant
Figure 14.12:╇ The lesion on the left is a dysplastic nevus on the sole of a skin of
color patient. Note the irregular shape and heterogeneous color. The right-sided
lesion is a common acquired melanocytic nevus. (Courtesy of Valerie D. Callender,
MD.)
Epidermoid cyst
Epidermoid cysts are common lesions in the population. No
specific reports have denoted the incidence in dark-skinned
individuals. Epidermoid cysts are characterized by variably
sized skin-colored mobile subcutaneous nodules, sometimes
with an overlying punctum (Fig. 14.13). They may be located
anywhere on the body but are most common on the face
and trunk. Epidermoid cysts are associated with Gardner’s
syndrome and nevoid basal cell carcinoma syndrome.
Multiple lesions have also been reported in patients on
cyclosporine.
First-Line Therapies
Elliptical excision
Punch excision
Minimal excision
Comparison of the surgical outcomes of punch incision and
elliptical excision in treating epidermal inclusion cysts: a
prospective, randomized study. Lee HE, Yang CH, Chen CH,
Hong HS, Kuan YZ. Dermatol Surg 2006; 32(4):520–525.
Randomized, prospective study demonstrating no signifi-
cant difference in recurrence rate. Punch incision produces a
superior cosmetic result for cysts measuring 1–2╯cm on the
face or areas of cosmetic concern.
Removal of keratinous and pilar cysts with the punch inci-
sion technique: analysis of surgical outcomes. Mehrabi D,
Leonhardt JM, Brodell RT. Dermatol Surg 2002; 28(8):
673–677.
266
The incidence of melanoma is approximately 15 times
higher in patients with dysplastic nevi compared to the normal
population. Melanoma has been shown to occur in and sepa-
rate from pre-existing common and dysplastic nevi. Approxi-
mately 1 in 10 000 dysplastic nevi per year will progress to
melanoma and therefore prophylactic excision of dysplastic
nevi is not recommended. Close surveillance with annual skin
exams and monthly self exams is recommended, particularly
in patients with a personal or family history of melanoma.
Patients should be advised to avoid intense ultraviolet light
exposure to decrease risk. The routine use of dermoscopy
and full body photography for monitoring patients is
controversial.
Clinical practice. Dysplastic nevi. Naeyaert JM, Brochez L. N
Engl J Med 2003; 349(23):2233–2240.
Dysplastic nevi with changes concerning for melanoma
should be excised with a 2mm margin.
Retrospective chart review and patient survey over patient
data from 9 years demonstrating an 8.3% recurrence rate.
Subanalysis revealed a trend showing that inflamed cysts had
a lower recurrence rate. Back and ear had the highest recur-
rence rates (13.8% and 13.0%, respectively) compared to
those removed from other locations. Most cysts (54.5%)
recurred within the first year after punch incision removal.
A new method for facial epidermoid cyst removal with
minimal incision. Yang HJ, Yang KC. J Eur Acad Dermatol
Venereol 2009; 23(8):887–890.
Punch incision with dissection has been found to be equally
as effective as elliptical excision for 1–2╯cm lesions on the face
with less visible scarring. Yang describes removal with 3╯mm
incisions created with a No. 11 blade with subsequent removal
of the cyst contents and capsule followed by chemical cautery
and 20% trichloroacetic acid.
B
B
B
Figure 14.13:╇ Epidermoid cyst. Note the central punctum. (Courtesy of Valerie D.
Callender, MD.)

Keloid
Keloids are fibroproliferative tumors that rarely regress and
grow continuously and invasively beyond the confines of the
original margin of the scar, differentiating them from hyper-
trophic scars. They occur at sites of previous cutaneous injury
and may be found anywhere on the body, most commonly on
the upper back, shoulders, chest, back of the neck, and ear-
lobes (Figs. 14.14 & 14.15). Keloids rarely occur on the palms
or soles, which led some to postulate that sebaceous glands
may be involved in their pathogenesis.
Keloids can occur at any age but are more common between
the ages of 10 and 30 and in darkly-pigmented patients, with
a reported incidence of 4.5–15% in ethnic skin and < 1% in
Caucasians.1 The high rate of ear involvement following
ear piercing may account for the slightly higher female pre-
dominance. The high familial clustering of keloids and
Figure 14.14:╇ Multilobular keloid on the right earlobe. (Courtesy of Valerie D.
Callender, MD.)
Figure 14.15:╇ Multiple keloids on the chest of a skin phototype V patient.
(Courtesy of Valerie D. Callender, MD.)
14â•… Benign Tumorsâ•… •â•… Keloid
increased concordance in identical twins suggests a genetic
predisposition.
Keloids present as pink, skin-colored or hyperpigmented,
variably painful or pruritic, firm plaques that may have
overlying telangiectasias. They should be differentiated from
hypertrophic scars, which remain within the confines of the
original scar.
Histologically, keloids can be differentiated from hyper-
trophic scars. Keloids are characterized by haphazardly
arranged sheets of collagen with random orientation to the
epidermis whereas hypertrophic scars demonstrate wavy col-
lagen bundles running parallel to the epidermis.
The pathogenesis is still not well understood but transform-
ing growth factor beta (TGF-β), platelet-derived growth factor
(PDGF), and SMAD gene single nucleotide polymorphisms
(SNPs) are thought to be involved in the formation of keloids.
Collagen synthesis in keloids is approximately 20 times greater
than in normal, unscarred skin and three times greater than
in hypertrophic scars, with an elevated type I to type III col-
lagen ratio. Less synthesis of molecules that promote matrix
breakdown may also explain the lack of regression in keloids.
The management of keloids has remained a difficult chal-
lenge. No single or combination therapy has proven curative.
Though excision (Figs. 14.16 & 14.17) with adjuvant radiation
or intralesional steroids have been a mainstay of treatment,
neither is 100% effective, and intralesional steroids may be
complicated by development of hypopigmentation (Fig.
14.18), atrophy, and telangiectasias. For a systematic review of
the treatment of keloids, see the paper by Durani & Bayat.2
First-Line Therapies
Excision with adjuvant radiation B
Excision with adjuvant intralesional steroids B
Evaluation of various methods of treating keloids and
hypertrophic scars: a 10-year follow-up study. Darzi MA,
Chowdri NA, Kaul SK, Khan M. Br J Plast Surg 1992;
45:374–379.
Beta radiation alone was found to be effective in the eradi-
cation of symptoms (55% symptomatic relief), while results
in the reduction of size of lesions have been poor (11%
success rate). Surgery combined with postoperative beta
radiation therapy yielded a 67% success rate. The success rate
was 75% when radiation was delivered within 48 hours of
surgery. Preoperative radiation was found to be of no advan-
tage. Intralesional triamcinolone acetonide produced sympto-
matic relief in 72% and complete flattening in 64% of the
lesions.
Prevention of earlobe keloid recurrence with postoperative
corticosteroid injections versus radiation therapy: a rand-
omized, prospective study and review of the literature.
Sclafani AP, Gordon L, Chadha M, Romo T 3rd. Dermatol
Surg 1996; 22(6):569–574.
267
 Part 4 Tumors Benign and Malignant
Figure 14.16:╇ Keloid prior to excision.
Figure 14.17:╇ Keloid following excision and suprakeloidal flap.
Thirty-one keloids were treated and followed for a minimum
of 12 months. Two of sixteen keloids (12.5%) recurred after
surgery and radiation therapy, while 4 of 12 (33%) recurred
after surgery and steroid injections. No alteration of skin pig-
mentation, wound dehiscence, chronic dermatitis, or neoplas-
tic changes was observed in any patient in either group.
Although a statistically significant difference was not observed,
radiotherapy appeared to be more effective than steroid injec-
tions in preventing keloid recurrence.
Second-Line Therapies
Excision with compression therapy
Intralesional 5-FU
Bleomycin
Intralesional verapamil
Flashlamp pulsed-dye laser (PDL)
268
Figure 14.18:╇ Hypopigmentation along the angle of the mandible secondary to
corticosteroid injections for keloid formation from acne scarring. (Courtesy of Valerie
D. Callender, MD.)
Treatment of recurrent earlobe keloids. Rauscher GE, Kolmer
WL. Cutis 1986; 37:67–68.
Fifty-seven patients with recurrent earlobe keloids were
treated with steroid impregnated tape under pressure earrings.
Four recurrences occurred in the 4-year follow-up. Patients’
failure to use the recommended pressure earring and alteration
in endocrine balance were noted in 3 of the 4 patients with
recurrent keloids.
Intralesional triamcinolone alone or in combination with
5-fluorouracil for the treatment of keloid and hypertrophic
scars. Darougheh A, Asilian A, Shariati F. Clin Exp Dermatol
2009; 34(2):219–223.
At the 8-week and 12-week follow-up visits, both groups
showed an acceptable improvement in erythema, pliability,
length, width and height but the difference was more signifi-
cant in the triamcinolone plus 5-fluorouracil group. Pruritus
and percentage of itch reduction were not significantly differ-
ent. The overall efficacy of triamcinolone plus 5-fluorouracil
was comparable with intralesional triamcinolone alone.
Treatment of keloids and hypertrophic scars using bleomy-
cin. Aggarwal H, Saxena A, Lubana PS, Mathur RK, Jain DK.
J Cosmet Dermatol 2008; 7(1):43–49.
Bleomycin was administered through multiple superficial
puncture technique. Three applications were given at intervals
of 15 days each, followed by a fourth and final application 2
months after the last application. Complete flattening was
observed in 22 cases (44%), significant flattening in 11 cases
(22%), and adequate flattening was observed in 7 cases (14%).
Only 10 cases (20%) did not show any satisfactory flattening.
Pruritus was relieved completely in 40 patients (88.88%).
B
Recurrence was seen in 7 patients.
A
B Comparison of intralesional verapamil with intralesional
B triamcinolone in the treatment of hypertrophic scars and
C keloids. Margaret Shanthi FX, Ernest K, Dhanraj P. Indian J
Dermatol Venereol Leprol 2008; 74(4):343–348.

Vascularity, pliability, height and width of the scars were
reduced with both intralesional triamcinolone 40╯mg and int-
ralesional verapamil 2.5╯mg every 3 weeks until the scar flat-
tened or until a maximum of 6 months. Improvement was
noted after 3 weeks of treatment and was still present at 1-year
follow-up. Scar pigmentation was not changed desirably by
either drug. Length of the scars was also not altered signifi-
cantly by either drug. The rate of reduction in vascularity, pli-
ability, height and width of the scar with triamcinolone was
faster than with verapamil.
Treatment response of keloidal and hypertrophic sternot-
omy scars: comparison among intralesional corticosteroid,
5-fluorouracil, and 585nm flashlamp-pumped pulsed-dye
laser treatments. Manuskiatti W, Fitzpatrick RE. Arch Derma-
tol 2002; 138(9):1149–1155.
The 10 patients’ scars were randomly treated with one of
four different regimens: (1) laser radiation with a 585-nm PDL
(5╯J/cm2); (2) intralesional triamcinolone acetonide (TAC)
(20╯mg/mL); (3) intralesional 5-FU (50╯mg/mL); and (4) int-
ralesional TAC (1╯mg/mL) mixed with 5-FU (45╯mg/mL). One
segment of each scar received no treatment and served as a
control. Intralesional formulas resulted in faster resolution
than the PDL, scar induration responded better to intrale-
sional formulas, scar texture responded better to the PDL, and
scar erythema responded the same as the control with all treat-
ments. Adverse sequelae, including hypopigmentation, tel-
angiectasia, and skin atrophy, were observed in 50% (5/10) of
the segments that received corticosteroid intralesionally alone.
No long-term adverse sequelae were demonstrated in the seg-
ments treated with other modalities.
Third-Line Therapies
Excision with adjuvant imiquimod B
Silicon gel sheeting B course of treatment demonstrated reduction in size at the
Intralesional interferon C treated site with an average reduction in height of 30.4%
Treatment of keloid scars post-shave excision with imiqui-
mod 5% cream: a prospective, double-blind, placebo-
controlled pilot study. Berman B, Harrison-Balestra C, Perez
OA, Viera M, Villa A, Zell D, et al. J Drugs Dermatol 2009;
8(5):455–458.
Imiquimod 5% or vehicle cream was applied nightly for 2
weeks, and then given three times a week under occlusion for
14â•… Benign Tumorsâ•… •â•… Keloid
1 month. Tenderness and pain were significantly higher at
week 2 in the imiquimod group than for those treated with
vehicle cream. At 6 months, keloid recurrence rates were 37.5%
(3/8) in the imiquimod group and 75% (3/4) in the vehicle
group. Imiquimod was well tolerated, but there was not
enough statistical power to detect a significant difference in
6-month keloid recurrence rates between the two treated
groups.
Silicon gel sheeting for preventing and treating hypertrophic
and keloid scars. O’Brien L, Pandit A. Cochrane Database Syst
Rev 2006; 25(1):CD003826.
Thirteen trials compared adhesive silicon gel sheeting with
control, non-silicon gel sheeting, silicon gel plates with added
Vitamin E, laser therapy, triamcinolone acetonide injection,
and non-adhesive silicon gel sheeting. In the prevention
studies, when compared with a no treatment option, silicon
gel sheeting reduced the incidence of hypertrophic scarring
in people prone to scarring; however, these studies were
highly susceptible to bias. Silicon gel sheeting produced
a statistically significant improvement in scar elasticity, but
these studies were also highly susceptible to bias. There is
weak evidence of a benefit of silicon gel sheeting as a preven-
tion for abnormal scarring in high risk individuals but the
poor quality of research means a great deal of uncertainty
prevails.
A controlled trial of intralesional recombinant interferon-
gamma in the treatment of keloidal scarring. Clinical and
histologic findings. Granstein RD, Rook A, Flotte TJ, Haas A,
Gallo RL, Jaffe HS, et al. Arch Dermatol 1990; 126:1295–
1302.
Eight patients were treated by injection of either 0.01 or
0.1╯mg of recombinant human IFN-gamma into one lesional
site and diluent alone into another lesional site three times
per week for 3 weeks. Six of eight subjects who finished the
versus 1.1% for control sites.
References
1. English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol
Surg 1999; 25:631–638.
2. Durani P, Bayat A. Levels of evidence for the treatment of keloid
disease. J Plast Reconstr Aesthet Surg 2008; 61(1):4–17.
269
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Part 4 Tumors Benign and Malignant

Malignant Neoplasms
Erica Mailler-Savage, Matthew Joseph Turner, David Robert Crowe, Erica Chon Davis
and Hugh Morris Gloster Jr 15â•…
Basal cell carcinoma . . . . . . . . . . . . . . . . . . . 271 Management strategy
Cutaneous T-cell lymphoma (CTCL) . . . . . . . . . . . 273
The approach to management of BCC is essentially identical
Dermatofibrosarcoma protuberans (DFSP) . . . . . . . . 276
to that of squamous cell carcinoma and is dependent upon
Malignant melanoma . . . . . . . . . . . . . . . . . . . 277 risk of local recurrence. Aggressive histological subtype, size
Squamous cell carcinoma . . . . . . . . . . . . . . . . 279 > 2╯cm, tumor depth > 4╯mm, tumor location on the lip, ear,
temple, or genitalia, history of recurrence, and presence of
immunosuppression will place the patient at increased risk.

Basal cell carcinoma First-Line Therapies

Basal cell carcinoma (BCC) is an infrequent tumor in people
of color. Although BCC is estimated to compose about 60– Curettage and Electrodessication B
65% of skin cancers in the general population, only 1.8% of Excision A
skin cancers in African-Americans are BCC.1 This is likely due Mohs micrographic surgery A
to the relationship between ultraviolet light exposure and non- Radiation therapy A
melanoma skin cancers. Darker skin types have more melano- Imiquimod B
somes in a different aggregational pattern, likely giving them
Topical 5-fluorouracil B
more protection from ultraviolet light. While ultraviolet light
is the most common etiology of BCC, syndromes including
Gorlin’s (nevoid basal cell carcinoma syndrome), oculocuta-
neous albinism, and xeroderma pigmentosum should be con- Histological and immunohistochemical evaluation of basal
sidered as they can all occur in people of color. cell carcinoma following curettage and electrodessication.
There is debate about whether BCC is more common Filho LL, de Avelar Alchorne A de O, Pereira GC, Lopes LR, de
in sun-exposed versus non-sun-exposed skin in African- Carvalho TC. Int J Dermatol 2008; 47(6):610–614.
Americans, however the majority of studies suggest that sun- Twenty primary BCC outpatients were treated with two
exposed areas are more common (Fig. 15.1). In Blacks, BCC curet�tage and electrofulguration cycles and subsequently eval-
has been reported to occur in discoid lupus lesions, previously uated histologically with a surgical excision 2╯mm beyond the
irradiated areas, and stasis ulcers. visible bloody borders and in the base to the middle of sub-
The histologic subtypes of BCC in skin of color are similar cutaneous fat. There was evidence of persistent BCC in 25%
to those in lighter-skin patients; however, pigmented BCC (Fig. of cases.
15.2) may be slightly more common. Basal cell carcinoma in
people of color may be mistaken for seborrheic keratosis, Surgical excision versus Mohs’ micrographic surgery for
nevocellular nevus, malignant melanoma, or nevus sebaceous. primary and recurrent basal-cell carcinoma of the face: a
A biopsy is the most definitive diagnostic test for BCC. prospective randomised controlled trial with 5-years’

©2011 Elsevier Ltd, Inc, BV 271

 Part 4 Tumors Benign and Malignant
Figure 15.1:╇ Pigmented basal cell carcinoma on the scalp of a Fitzpatrick skin
type V patient. (Courtesy of Valerie D. Callender, MD.)
Figure 15.2:╇ Pigmented basal cell carcinoma.
follow-up. Mosterd K, Krekels GA, Nieman FH, Ostertag JU,
Essers BA, Dirksen CD, et al. Lancet Oncol 2008; 9(12):
1149–1156.
Of the 397 primary BCCs that were treated, 4.1% of recur-
rences occurred in patients treated with surgical excision and
2.5% occurred in patients treated with Mohs’ micrographic
surgery (MMS). Of the 202 recurrent BCCs that were treated,
2.4% of recurrences occurred in patients treated with MMS
versus 12.1% in patients treated with surgical excision,
suggesting that MMS should be performed on recurrent
BCCs but that MMS or excision are acceptable treatments for
primary BCC.
Basal cell carcinoma of the face: surgery or radiotherapy?
Results of a randomized study. Avril MF, Auperin A, Margulis
A, Gerbaulet A, Duvillard P, Benhamou E, et al. Br J Cancer
1997; 76(1):100–106.
A randomized trial to compare surgery and radiotherapy in
the treatment of primary BCC of the face measuring less than
4╯cm. The 4-year actuarial failure rate was 0.7% in the surgery
group compared with 7.5% in the radiotherapy. The cosmetic
272
results assessed by four of the five judges were significantly
better after surgery than after radiotherapy.
Recurrence rate of superficial basal cell carcinoma following
treatment with imiquimod 5% cream: conclusion of a 5-year
long-term follow-up study in Europe. Gollnick H, Barona
CG, Frank RG, Ruzicka T, Megahed M, Maus J, Munzel U. Eur
J Dermatol 2008; 18(6):677–682.
Five-year follow-up study to evaluate the recurrence rate of
superficial BCCs treated with imiquimod applied once daily 5
times per week for 6 weeks. The estimate of overall treatment
success for all treated patients at the end of follow-up was
77.9%. Most of the recurrences occurred early, indicating that
careful follow-up is important during the first year after
treatment.
5% 5-fluorouracil cream for the treatment of small superfi-
cial basal cell carcinoma: efficacy, tolerability, cosmetic
outcome, and patient satisfaction. Gross K, Kircik L, Kricorian
G. Dermatol Surg 2007; 33(4):433–439.
Thirty-one superficial basal cell carcinoma lesions on the
trunk or limbs were treated with 5% 5-fluorouracil (5-FU) cream
twice daily for up to 12 weeks. The lesional site was surgically
excised 3 weeks after the end of treatment for histologic evalu-
ation of cure. The histologic cure rate was 90% and the mean
time to clinical cure was 10.5 weeks. 5-FU cream was generally
well tolerated with a good cosmetic outcome.
Second-Line Treatment
Photodynamic therapy A
Curettage and cryotherapy B
Fractionated 5-aminolaevulinic acid-photodynamic therapy
vs surgical excision in the treatment of nodular basal cell
carcinoma: results of a randomized controlled trial. Mosterd
K, Thissen MR, Nelemans P, Kelleners-Smeets NW, Janssen RL,
Broekhof KG, et al. Br J Dermatol 2008; 154:864–870.
A randomized controlled trial in 173 primary nodular
BCCs treated with photodynamic therapy (PDT) twice on the
same day or surgical excision with a 3╯mm margin. A 3-year
interim analysis revealed that the cumulative incidence of
failure was 2.3% for excision and 0.3% for PDT.
Cryosurgery in difficult to treat basal cell carcinoma.
Jaramillo-Ayerbe F. Int J Dermatol 2000; 39(3):223–229.
Consecutive patients with 171 difficult to treat BCCs were
treated by the mixed technique of curettage followed by liquid
nitrogen application. After an average follow-up of 5.2 years a
cure rate of 91.8% was achieved. The treatment was well toler-
ated, widely accepted by the patients, of low cost, and with
good functional and cosmetic results.
Reference
1. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol
2006; 55:741–760.
 15â•… Malignant Neoplasmsâ•… •â•… Cutaneous T-cell lymphoma (CTCL)

dermatitis, vitiligo, or lichen planus. MF classically favors the

Cutaneous T-cell buttocks, breasts and intertriginous areas. It is also commonly
found on the trunk and extremities. It is rarely found on the

lymphoma (CTCL) palms, soles, or distal extremities.

MF is classified into four clinical stages based on the TNM
classification which is then utilized in a clinically-based staging
Cutaneous T-cell lymphoma (CTCL) encompasses a broad system broadly divided into early- and advanced-stage disease.
group of diseases characterized by a proliferation of skin Skin patches and plaques occur in stage I which is divided into
homing T-cells expressing cutaneous lymphoid antigen (CLA) IA (< 10% body surface area; BSA) or IB (≥ 10% BSA). The
and can be divided into two broad categories of mycosis fun- presence of clinically evident lymphadenopathy without path-
goides (MF)/Sezary syndrome and non-MF CTCLs. Over the ological nodal infiltration represents stage IIA, cutaneous
last 30 years, there has been a marked increase in the incidence tumors characterize stage IIB, generalized erythroderma char-
of CTCL, with a significantly higher incidence in Blacks.1 The acterizes stage III, and pathologically positive lymph nodes
first reports of CTCL in skin of color were of hypopigmented (IVA) and visceral disease characterize stage IVB.
MF (Fig. 15.3), and at the time were considered to be a rare Diagnosis of MF is based on a correlation between clinical
form of the disease. More current epidemiologic data, however, and histologic findings. The early diagnosis of MF is important
suggest that the overall incidence of CTCL is higher among because the appropriate management of stage IA disease leads
Blacks than Whites and other racial groups, regardless of
gender, with a smaller difference in incidence in advanced
ages. MF is 1.7 times more common in Blacks compared to
Whites, with the mortality being 2.4 times higher.
The pathogenesis of MF is not well understood. MF has
been shown by immunophenotyping to consist of epidermo-
tropic malignant CD4 helper T cells with reactive CD4 and
CD8 T cells in the papillary dermis. The lymphocytes express
the skin-homing protein CLA. Lymphocytes with CLA bind to
endothelial cells that express E-selectin 1 on their cell surfaces
to allow for extravasation from the blood vessels. It has been
suggested that CD8 lymphocytes are important in survival of
CTCL patients.
MF is polymorphic in its presentation. In its classic form it
presents with > 5╯cm, arcuate, poikilodermatous, scaly atrophic
patches or plaques. In skin of color, patches may be polymor-
phic in pigmentation (Fig. 15.4). Non-classic presentations
include hypo- or hyperpigmented patches, alopecia, erythro- Figure 15.4:╇ Active lesion of mycosis fungoides. Note the erythematous base,
derma or pruritus with associated lichenification (Fig. 15.5). white exudates, ulcerative areas, and hyper- and hypopigmented borders. (Courtesy
MF may be confused with dermatoses such as psoriasis, atopic of Valerie D. Callender, MD.)

Figure 15.5:╇ Hyperpigmented mycosis fungoides. (Courtesy of Valerie D.

Figure 15.3:╇ Hypopigmented mycosis fungoides. Callender, MD.)

273
 Part 4 Tumors Benign and Malignant
to a survival outcome comparable to the non-MF population.
CTCL is thought to follow a more aggressive course with
higher mortality rates in the Black population. A Howard Uni-
versity study of 16 Black patients demonstrated an overall
mortality rate of 44%, with 37.5% of the patients presenting
with stage IV or V disease.2
Given the incurable nature of CTCL, management should
focus on improving symptoms while limiting toxicity. Treat-
ment of early-stage disease (IA–IIA) typically involves skin-
directed therapies while systemic approaches are used for
recalcitrant early stage disease or advanced or transformed
disease. Drugs under active investigation include new histone
deacetylase inhibitors, forodesine, monoclonal antibodies,
proteasome inhibitors and immunomodulatory agents. It is
appropriate to consider patients for novel agents within clini-
cal trials if they have failed more typical therapies and before
chemotherapy is used.
Stage IA–IIA, First-Line Therapies
Topical corticosteroids B patients should receive a minimum surface dose of 20╯Gy,
PUVA or narrowband UVB B which offers excellent local control. Sequelae of therapy are
Topical carmustine B minimal.
Radiotherapy B
Topical corticosteroids for mycosis fungoides. Experience in
79 patients. Zackheim HS, Kashani-Sabet M, Amin S. Arch
Dermatol 1998; 134(8):949–954.
Patients were treated with topical class I to III corticoster-
oids. Of the stage T1 patients, all used class I corticosteroids,
and 8% also used class II or III corticosteroids. Of the stage T2
patients, 68% used class I and 43% used class II or III com-
pounds. Sixty-three percent of stage T1 patients achieved com-
plete remission and 31% achieved partial remission, for a total
response rate of 94%. The comparable figures for stage T2
patients were 25%, 57%, and 82%, respectively.
Narrowband UVB and psoralen-UVA in the treatment of
early-stage mycosis fungoides: a retrospective study. Died-
eren PV, van Weelden H, Sanders CJ, Toonstra J, van Vloten
WA. J Am Acad Dermatol 2003; 48(2):215–219.
A total of 21 patients were treated with narrowband UVB
(311-nm) and 35 patients were treated with PUVA. Narrow-
band UVB treatment led to complete remission in 81%, partial
remission in 19%, and none showed progressive disease.
PUVA treatment led to complete remission in 71%, partial
remission in 29%, and none showed progressive disease. The
mean relapse-free interval for patients treated with UVB was
24.5 months and 22.8 months for patients treated with PUVA.
When treating patients with early-stage MF it may be beneficial
to start with narrowband UVB therapy and, if there is progres-
sion or no response, switch to PUVA therapy.
Topical carmustine (BCNU) for mycosis fungoides and
related disorders: a 10-year experience. Zackheim HS, Epstein
274
EH Jr, McNutt NS, Grekin DA, Crain WR. J Am Acad Dermatol
1983; 9(3):363–374.
Complete remission was achieved in 84% of those with less
than 10% involvement (stage IA), and in 52% with greater
than 10% involvement (stage IB). The probability of freedom
from relapse for 1 year was 72% in stage IA and 37% in stage
IB. The hazard of bone marrow depression is slight and dose-
dependent. Erythematous reactions with pale centers and tel-
angiectasia are troublesome but have not been accompanied
by premalignant changes. Local side effects included ery-
thematous reactions with pale centers, telangiectasia and
hypopigmentation. The latter was seen in black patients and
in one patient it lasted for 2 years.
Local superficial radiotherapy in the management of
minimal stage IA cutaneous T-cell lymphoma (mycosis fun-
goides). Wilson LD, Kacinski BM, Jones GW. Int J Radiat
Oncol Biol Phys 1998; 40(1):109–115.
Patients with minimal stage IA mycosis fungoides may be
managed effectively with local superficial radiation alone
without adjuvant therapy. Distant failure is unusual and
Stage IA–IIA, Second-Line Therapies
Topical or oral bexarotene B
Interferon-alpha B
Methotrexate C
Phase 1 and 2 trial of bexarotene gel for skin-directed
treatment of patients with cutaneous T-cell lymphoma.
Breneman D, Duvic M, Kuzel T, Yocum R, Truglia J, Stevens VJ.
Arch Dermatol 2002; 138(3):325–332.
Bexarotene gel, 0.1%, 0.5%, and 1.0%, applied in incre-
mental dose adjustments from 0.1% gel every day to 1.0% gel
4 times daily or the maximal tolerated dose. Most patients
tolerated topical bexarotene at 1% gel twice daily for routine
use. Adverse events were generally mild to moderate in severity
and were confined to treatment sites. Treatment-limiting toxic
effects were associated with skin irritation and increased with
gel exposure. Patients achieved an overall response rate of 63%
and a clinical complete response rate of 21%.
Optimizing bexarotene therapy for cutaneous T-cell lym-
phoma. Talpur R, Ward S, Apisarnthanarax N, Breuer-Mcham
J, Duvic M. J Am Acad Dermatol 2002; 47(5):672–684.
Seventy patients with were treated with oral bexarotene as
monotherapy or in combination with other active agents.
Fifty-four patients receiving bexarotene monotherapy achieved
an overall response rate of 48%. Thirteen had stage IA–IIA
disease and 41 had stage IIB-IVB disease. Sixteen patients with
advanced disease treated with bexarotene (225–750╯mg/d) in
combination with other CTCL therapies achieved an overall
response rate of 69%. Bexarotene was safely combined with
 15â•… Malignant Neoplasmsâ•… •â•… Cutaneous T-cell lymphoma (CTCL)
PUVA plus IFN-alpha, with extracorporeal photopheresis
(ECP), with ECP/IFN-alpha, with ECP/IFN-alpha/PUVA, and
with IFN-alpha/PUVA/topical nitrogen.
Interferon alfa-2a in the treatment of cutaneous T cell
lymphoma. Olsen EA, Rosen ST, Vollmer RT, Variakojis D,
Roenigk HH Jr, Diab N, et al. J Am Acad Dermatol 1989;
20(3):395–407.
Twenty-two patients with Stages IA to IVA cutaneous T-cell
lymphoma were entered into a controlled study of interferon
alfa-2a (Roferon-A). Patients initially received either 3 million
IU interferon alfa-2a, or their dosage was increased to 36
million IU intramuscularly daily for a 10-week induction
period. At the end of induction, 64% of patients had an objec-
tive antitumor response. A complete response was noted in 3
patients, a partial response in 10 patients, and a minor response
in 1 patient. Side effects included acute flu-like syndrome,
malaise/fatigue, depression, anorexia, and weight loss.
Low-dose methotrexate to treat mycosis fungoides: a retro-
spective study in 69 patients. Zackheim HS, Kashani-Sabet M,
Macmillan A. J Am Acad Dermatol 2003; 49(5):873–878.
A retrospective analysis of 69 patients with patch/plaque
and tumor stage mycosis fungoides were treated with a median
weekly dose of 25╯mg with a maximum dose of 75╯mg. Twelve
percent of the patients achieved complete remission and 22%
achieved partial remission. Only 1 of 7 patients with tumor
stage disease responded.
Stage IIB–IVB, First-Line Therapies
Denileukin diftiox B A review of more than two-thirds of the allogeneic trans-
Histone deacetylase inhibitors B plant recipients in the literature who experienced long-term
Monoclonal antibodies C durable remissions of more than 3 years, which would appear
Pivotal phase III trial of two dose levels of denileukin difti-
tox for the treatment of cutaneous T-cell lymphoma. Olsen
E, Duvic M, Frankel A, Kim Y, Martin A, Vonderheid E, et al. J
Clin Oncol 2001; 19(2):376–388.
Overall, 30% of the 71 patients with CTCL treated with
denileukin diftitox had an objective and favorable response
(20% partial response; 10% complete response). Adverse
events consisted of flu-like symptoms, acute infusion-related
events, and a vascular leak.
FDA approval summary: vorinostat for treatment of
advanced primary cutaneous T-cell lymphoma. Mann BS,
Johnson JR, Cohen MH, Justice R, Pazdur R. Oncologist 2007;
12(10):1247–1252.
Open-label phase II trial that enrolled 74 patients with
stage IB and higher CTCL who had failed two systemic thera-
pies (one of which must have contained bexarotene). Patients
received vorinostat at a dose of 400╯mg orally once daily,
which could be reduced for toxicity to 300╯mg daily or 300╯mg
5 days a week. The objective response rate was 30%, the esti-
mated median response duration was 168 days, and the
median time to tumor progression was 202 days.
Low-dose intermittent alemtuzumab in the treatment of
Sézary syndrome: clinical and immunologic findings in 14
patients. Bernengo MG, Quaglino P, Comessatti A, Ortoncelli
M, Novelli M, Lisa F, et al. Haematologica 2007; 92(6):
784–794.
Fourteen patients were treated with 3╯mg alemtuzumab on
day 1, 10╯mg on day 3, then 15╯mg on alternating days or a
reduced dosage (3╯mg on day 1, then 10╯mg on alternating
days), with Sezary cells counted before every injection, until a
reduction to values of < 1000/mm. The median Sezary cell
count decreased by 95.5%. Overall, 85.7% achieved a clinical
response, with a 21.4% complete response rate. Infectious
complications occurred in 28.6% of patients, all included in
the group treated with 15╯mg. No patient in the group treated
with 1╯g developed hematologic toxicity or infections.
Stage IIB–IVB, Second-Line Therapies
Allogeneic stem cell transplant E
Extracorporeal photophoresis C
Chemotherapy
Haematopoietic stem cell transplantation for patients with
primary cutaneous T-cell lymphoma. Duarte RF, Schmitz N,
Servitje O, Sureda A. Bone Marrow Transplant 2008; 41(7):
597–604.
superior to the expected median survival for such patients.
Extracorporeal photopheresis for the treatment of Sézary
syndrome using a novel treatment protocol. Arulogun S,
Prince HM, Gambell P, Lade S, Ryan G, Eaton E, et al. J Am
Acad Dermatol 2008; 59(4):589–595.
Five-year retrospective analysis of 13 patients who were
treated with extracorporeal photopheresis consistently for a
minimum of 2 months. All patients received a modified pro-
tocol of one treatment per week for 6 sessions, one treatment
every 2 weeks for 6 sessions, and then one session per month.
The overall response rate was 62%: two patients achieved a
complete response and 6 patients achieved a partial response.
The median time to response was 10 months. The 2- and 4-year
predicted overall survivals were 82%.
References
1. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol
2006; 55:741–760.
2. Halder RM, Bang KM. Skin cancer in blacks in the United States.
Dermatol Clin 1988; 6:397–405.
275
 Part 4 Tumors Benign and Malignant

Dermatofibrosarcoma
protuberans (DFSP)
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally
aggressive tumor characterized by indolent growth, a low but
significant metastatic potential and a tendency for recurrence.
DFSP accounts for approximately 0.1% of malignant neo-
plasms and has been reported in all races, but is more common
in Blacks than Whites.1 Tumors usually present between the
3rd and 5th decades as slow growing skin-colored or hyper-
pigmented, indurated plaques and protuberant nodules on the
trunk and proximal extremities (Fig. 15.6). Histopathologi-
cally tumors consist of whorled collections of bland mono-
morphic spindle cells that by immunohistochemistry are
CD34(+) and Factor XIII(−).
The COL1A-PDGFβ fusion gene is a specific cytogenetic
abnormality present in more than 90% of tumors.2 This gene
constitutively expresses the growth factor PDGFβ, resulting in
autocrine stimulation of tumor cell proliferation via its cognate
receptor tyrosine kinase, PDGFRβ. PDGFβ-driven tumor pro-
liferation can be blocked with the small molecule tyrosine Figure 15.6:╇ Dermatofibrosarcoma protuberans of the lower back.
kinase inhibitor, imatinib (Gleevec), resulting in growth inhi-
bition and tumor cell apoptosis.
Retrospective analysis of 4 patients with locally advanced
or recurrent disease who received imatinib 400–80╯g daily for
3–7 months prior to MMS. Study demonstrated a reduction in
First-Line Therapies
tumor burden (18.9–61.6%) that was associated with 100%
local control for the full 1.5–4 years of follow-up.
Mohs micrographic surgery C
Imatinib D Dermatofibrosarcoma protuberans: treatment results of 35
Excision and radiotherapy B cases. Sun LM, Wang CJ, Huang CC, Leung SW, Chen HC, Fang
FM, et al. Radiother Oncol 2000; 57(2):175–181.
Retrospective analysis series of 35 consecutive patients with
A comparison between Mohs micrographic surgery and dermatofibrosarcoma protuberans treated with wide or local
wide surgical excision for the treatment of dermatofibrosar� surgical excision compared to those treated with excision plus
coma protuberans. Gloster HM Jr, Harris KR, Roenigk RK. adjuvant radiation therapy. At a median follow-up of 50
J Am Acad Dermatol. 1996; 35(1):82–87. months, 9/24 patients treated with excision alone developed
Case control series comparing rate of recurrence between a recurrence compared to 2/11 patients treated with excision
DFSP treated with MMS versus wide local excision. Analysis of and adjuvant radiation therapy.
data compiled from authors’ series plus those from previously
reported cases in the literature revealed a recurrence rate of References
1.6% (1/64 cases) with MMS versus 20% (100/489 cases) with
wide local excision. 1. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol
2006; 55:741–760.
2. Fiore M, Miceli R, Mussi C, Lo Vullo S, Mariani L, Lozza L, et al.
Neoadjuvant imatinib therapy for dermatofibrosarcoma Dermatofibrosarcoma Protuberans Treated at a Single Institution: A
protuberans. Han A, Chen EH, Niedt G, Sherman W, Ratner Surgical Disease With a High Cure Rate. J Clin Oncol 2005; 23:
D. Arch Dermatol 2009; 145(7):792–796. 7669–7675.

276
 15â•… Malignant Neoplasmsâ•… •â•… Malignant melanoma

secondary changes such as hyperkeratosis, which can lead to

Malignant melanoma misdiagnosis as plantar verruca or calluses. This often leads to

unsuccessful destructive therapy which further obscures mor-
phology and delays diagnosis.
The diagnosis of malignant melanoma in skin of color is Prognosis in darker-skinned individuals is poor (Table
uncommon, approximately 1 in 10╯000, with the actual inci- 15.2). Black patients are more likely to present with thicker
dence being inversely proportional to degree of skin pigmenta- primary tumors and ulceration. Asians, Blacks, and Hispanics
tion (Table 15.1).1,2 While risk factors such as ultraviolet light are all much more likely to be diagnosed after metastasis than
(specifically blistering sunburns), family history, and atypical Caucasian patients. In studies comparing early (stage 1 and 2)
nevi have been clearly established in Caucasians, predisposing disease, there seems to be a trend toward shorter survival times
factors are less clear in non-Caucasians. These risk factors in in Blacks as compared to Caucasians. Delay in diagnosis is
Blacks may include immunosuppression, radiation therapy, brought about by the atypical distribution and morphology of
and pre-existing pigmented lesions. Unlike the significant melanoma in skin of color as well as lack of appropriate
increases in incidence of melanoma among Caucasians, rates acknowledgement of risk to these populations by physicians.
of malignant melanoma incidence have been relatively stable
in most other ethnic populations over the last 30 years.1
In Caucasian patients, melanoma favors predominantly
sun-exposed areas, whereas the palms, soles, and nail bed in
Asians, Blacks, and dark-skinned Hispanics are more common.
Acral melanomas constitute 30–70% of melanomas in dark-
skinned individuals.1 The predominant histologic subtype is
acral lentiginous melanoma in Blacks and Asians, although
superficial spreading melanoma is more common than acral
lentiginous melanoma in Hispanics. The plantar surface of the
foot is the most common site involved (Fig. 15.7). When
subungual melanoma is considered, the thumb (Fig. 15.8)
and great toe are more likely to be involved. Mucosal melano-
mas are also over-represented in non-Caucasians, in particular
Asians and Blacks.
Differentiation of acral melanoma from acral nevi and
other benign lesions can be difficult. Acral nevi and hyperpig-
mented macules of the palmoplantar creases are more preva-
lent in African-Americans. Acral melanoma can also exhibit

Figure 15.7:╇ Acral lentiginous melanoma on the plantar surface of the foot in a
Table 15.1╇ 2002–2006 Incidence Rates (per 100,000) of Melanoma skin of color patient. (Courtesy of Beverly Johnson, MD.)
by Race/Ethnicity and Gender

35
30
25
20
15 Male
Female
10
5
0
White Black Asian/ American Hispanic
Pacific Indian/
Islander Alaska
Native
Race/Ethnicity

Horner MJ, Ries LA, Krapcho M, Neyman N, Aminou R, Howlader N, et al. SEER Cancer
Statistics Review, 1975–2006, National Cancer Institute. Bethesda, MD, http://seer.
cancer.gov/csr/1975_2006/. Figure 15.8:╇ Subungual melanoma of the thumb. Note the presence of
Hutchinson’s sign (periungual extension of pigmentation onto the proximal nail fold).

277
 Part 4 Tumors Benign and Malignant
Table 15.2╇ 2002–2006 Death Rates (per 100,000) from Melanoma
by Race/Ethnicity and Gender
5 Wide local excision and sentinel lymph node biopsy if
4.5
4
3.5
3
2.5
2 Male
1.5 Female
1 Although many small studies have quoted different recom-
0.5
0 emphasizes that excisional margins for melanoma subtypes
White Black Asian/ American Hispanic
Pacific Indian/
Islander Alaska
Native
Race/Ethnicity
Horner MJ, Ries LA, Krapcho M, Neyman N, Aminou R, Howlader N, et al. SEER Cancer
Statistics Review, 1975–2006, National Cancer Institute. Bethesda, MD, http://seer.
cancer.gov/csr/1975_2006/.
Management strategy
Management of melanoma at most sites is very similar regard-
less of race or ethnicity, with wide local excision being the
treatment of choice. Melanoma in situ, regardless of type,
requires excisional margins of 5╯mm. Margins of excision are
1╯cm for melanomas with Breslow thickness < 2╯mm, and
2╯cm for melanomas > 2╯mm thick. The utility of margins of
> 2╯cm in thicker melanomas has not been shown to improve
survival. If tumor thickness exceeds 1╯mm it is essential to
perform sentinel lymph node biopsy (SLNB), and it can also
be considered if ulceration or Clark level IV or V is present.
For melanoma in situ, in particular lentigo maligna (which
is rare in non-Caucasians), non-surgical treatments such as
imiquimod or radiation therapy can be considered for poor
surgical candidates. Radiation therapy can also be used as
adjuvant therapy with desmoplastic melanoma, or as primary
or adjuvant therapy for mucosal melanoma.
Management of metastatic melanoma is a rapidly growing
area of research with many different strategies of treatment,
and is beyond the scope of this review. While it may have a
role in unresectable limb melanoma, isolated limb perfusion
with melphalan is not recommended as a prophylactic or
adjuvant therapy for excised melanoma.
Treatment of both acral and subungual melanoma is a dif-
ficult balance of excising adequate margins and preserving
function, especially in regard to the upper extremity digits. It
is in this setting (as well as in the setting of extensive lentigo
maligna) that Mohs micrographic surgery may play an impor-
tant role. New studies continue to emerge regarding the
preservation of the function of digits while still preventing
recurrence and metastasis.
278
First-Line Therapies
Wide local excision with conventional margins A
B
tumor thickness > 1╯mm
Excision margins for primary cutaneous melanoma: updated
pooled analysis of randomized controlled trials. Lens MB,
Nathan P, Bataille V. Arch Surg 2007; 142(9):885–891.
mended margins for acral melanoma, this meta-analysis
have not been adequately evaluated in randomized controlled
trials. The recommended wide local excision for all types of
melanoma include 1╯cm margins for those < 2╯mm thick, and
2╯cm margins for melanomas that are > 2╯mm thick.
Sentinel-node biopsy or nodal observation in melanoma.
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff
R, Essner R, et al. N Engl J Med 2006; 355(13):1307–1317.
A total of 1269 intermediate-thickness melanoma patients
were randomized into 2 groups. One group was treated with
wide local excision and observation of lymph nodes, with
lymph node dissection if clinical nodal metastasis developed.
The second group received wide local excision with sentinel
lymph node biopsy followed by lymph node dissection if
micrometastases were present. This study reiterated the prog-
nostic and treatment implications of the practice of sentinel
lymph node biopsy with wide excision of intermediate-
thickness (1.2–3.5╯mm) malignant melanoma.
Second-Line Therapies
Conventional excision of subungual melanoma with C
functional amputation
Mohs micrographic surgery B
Subungual melanoma of the hand. Quinn M, Thompson J,
Crotty K, McCarthy WH, Coates AS, et al. J Hand Surg 1996;
21:506–511.
This retrospective analysis emphasized the importance of
amputation at the PIP joint of the finger and the neck of the
proximal phalanx of the thumb (‘functional amputation’).
Rates of recurrence in this retrospective study of 38 patients
revealed no difference in recurrence rates with ‘ablative ampu-
tation’ (amputation proximal to these points and loss of func-
tional digit).
Acral lentiginous melanoma: conventional histology vs
three-dimensional histology. Lichte V, Breuninger H, Metzler
G, Haefner HM, Moehrle M. Br J Dermatol 2009; 160:
591–599.
In 241 patients with stage I and II acral lentiginous
melanoma, excisional margins were reduced by two-thirds
 15â•… Malignant Neoplasmsâ•… •â•… Squamous cell carcinoma
using three-dimensional histology through Mohs micro-
graphic surgery as compared to conventional excision. While
overall survival was also significantly improved, local
recurrence rates were comparable. This study was performed
without the aid of immunohistochemical staining in either
method.
Third-Line Therapies
Imiquimod B follow-up). Two of the recurrent lesions were thick lentigo
Radiation therapy C maligna melanoma with subsequent nodal metastasis, and the
Laser therapy B remainder were local recurrences.
Treatment of lentigo maligna with topical imiquimod.
Naylor MF, Crowson, N, Kuwahara R, Teague K, Garcia C,
Mackinnis C, et al. Br J Dermatol 2003; 149(suppl 66):
66–70.
Thirty patients with lentigo maligna were treated with imi-
quimod 5% cream daily (applied to lesion and 2╯cm beyond
visible margins) for 3 months, followed by a four-quadrant
biopsy 1 month following treatment. Ninety-three percent of
the patients showed complete response. One-third of patients
required less frequent applications due to local side effects
after 1 month. Eighty percent were followed for 1 year without
clinical recurrence.
A retrospective study of 150 patients with lentigo maligna
and lentigo maligna melanoma using Grenz or soft x-rays.
Squamous cell
carcinoma
Squamous cell carcinoma (SCC; Fig. 15.9) is a malignant
epithelial tumor of the skin and mucous membranes typically
characterized by erythematous keratotic papules or nodules
that may become ulcerated (Fig. 15.10). Precursor lesions of
SCC, actinic keratoses, are rarely found in people of color. In
lighter skin, SCC is most commonly associated with chronic
sun exposure, but other precipitating factors include chronic
inflammation or scarring processes, chemical carcinogens
(arsenic, tobacco tar, hydrocarbons), human papilloma virus
(types 16, 18, 30, 33, 35), ionizing radiation (X-rays, gamma
rays, radium), and immunosuppression.
There are different subtypes of SCC, including keratoacan-
thoma and SCC in situ. SCC in situ has also been referred to
as Bowen’s disease or erythroplasia of Queyrat. Bowen’s disease
of the digits resembles verruca or chronic paronychia and has
been associated with human papillomavirus (HPV) 16 and 18
(Fig. 15.11). Bowen’s disease in Blacks is often pigmented.
Perianal SCC can arise in preexisting perianal warts. SCC that
arises in preexisting areas of disease may resemble the underly-
Farshad A, Burg G, Panizzon R, Dummer R. Br J Dermatol
2002; 146(6):1042–1046.
Ninety-three patients with lentigo maligna and 54 patients
with lentigo maligna melanoma (mean thickness 0.7╯m; 0.17–
3.06╯m) were treated with Grenz rays (mostly lentigo maligna
patients) and soft x-rays (mostly lentigo maligna melanoma
patients, deeper penetration) at 3–4-day intervals for 7–12
therapy sessions. This resulted in clinical resolution of lesions
with acceptable cosmetic results, with 7% disease recurrence
in the 101 patients followed for >2 years (8 year mean
Lentigo maligna – outcomes of treatment with Q-switched
Nd:YAG and alexandrite lasers. Madan V, August PJ. Dermatol
Surg 2009; 35(4):607–611.
QS-Nd-YAG and alexandrite lasers were used to treat lentigo
maligna in 22 patients who were poor surgical candidates.
Complete clinical response was achieved in 12/22 patients
after 1–4 treatments and a follow-up of 2–5 years after the last
treatment.
References
1. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol
2006; 55:741–760.
2. Byrd-Miles K, Toombs EL, Peck GL. Skin Cancer in Individuals of
African, Asian, Latin-American, and American-Indian Descent:
Differences in Incidence, Clinical Presentation, and Survival Compared
to Caucasians. J Drugs Dermatol 2007; 6:10–16.
ing disease. Invasive SCC can present as plaques, papules, and
ulcers with induration.
The incidence of SCC in African-Americans is reported to
be approximately 3.4 per 100╯000 in contrast to 100–150 per
100╯000 in Caucasians.1 Although basal cell carcinoma is
the most commonly diagnosed skin cancer in the United
States, SCC is the most commonly diagnosed skin cancer in
Figure 15.9:╇ Patient with skin phototype V and squamous cell carcinoma.
(Courtesy of Valerie D. Callender, MD.)
279
 Part 4 Tumors Benign and Malignant
Figure 15.10:╇ Ulcerated squamous cell carcinoma
Figure 15.11:╇ Pigmented Bowen’s disease of the fourth digit in a patient with skin
phototype IV.
African-Americans. A study of the incidence of SCC in Chinese,
Malays, and Indians living in Singapore was 3.2 per 100╯000
in men and 1.8 per 100╯000 in women.2
Most of SCCs in people of color develop in non-sun-
exposed skin. In a 1988 Howard University study, 65% of
patients diagnosed with SCC had leg involvement and 15%
were diagnosed with anal SCC.3 Penile and scrotal SCC were
also reported to occur at a higher rate than in Caucasians.
Squamous cell carcinomas occurring in sun-exposed skin are
in a similar distribution to that of Caucasians. Chronic inflam-
mation, scars, burns, chronic infections, leg ulcers, albinism,
chronic discoid lupus lesions, chronic radiation exposure, and
vitiligo are all clinical settings in which SCC has been described
in African-Americans. SCC of the nail bed has been most com-
monly reported in African-American women.
The factors for developing skin cancers in non-sun-exposed
areas are unknown. In areas of chronic inflammation, ulcera-
tion, and scarring, normal cell differentiation and apoptosis
of normal cells are altered, likely allowing for clonal expansion
280
of malignant cells. The p53 gene has been implicated in this
pathogenesis.
SCC in African-Americans is typically more aggressive and
carries a poorer prognosis. SCC developing within sun-exposed
areas has a better prognosis. An 18.4–29% mortality rate has
been reported in African-Americans diagnosed with SCC.4
Delay in diagnosis has been attributed to this higher mortality
rate. Underlying coexisting conditions may also contribute to
the difficulty in treatment.
Management strategy
Management of SCC is dependent upon risk of local recur-
rence and metastasis. Aggressive histological subtype, size
> 2╯cm, tumor depth > 4╯mm, tumor location on the lip, ear,
temple, or genitalia, history of recurrence, and presence of
immunosuppression all place the patient at increased risk.
Regional lymph node involvement is a poor prognostic sign.
Accurate histopathologic diagnosis is the critical first step
in effective management. Shave biopsy is usually sufficient for
diagnosis, however punch or incisional biopsy may be neces-
sary for recurrent or deeply indurated tumors. Regional lymph
node palpation should be performed at the time of initial
exam if a more aggressive tumor is suspected.
Small, superficial SCC in non-cosmetically sensitive areas
may be effectively treated with local destructive modalities
including cryosurgery and electrodessication and curettage.
Low risk SCCs may also be topically treated with imiquimod
or topical 5-fluorouracil. Well-demarcated, well-differentiated
SCC on the trunk or extremities may be treated with standard
surgical excision using 3–4╯mm margins. Tumors > 2╯cm in
size, ill-defined tumors, poorly differentiated tumors, recurrent
tumors, and tumors located on cosmetically or functionally
sensitive areas are best treated with Mohs micrographic surgery.
Adjuvant radiation therapy following Mohs surgery should be
considered for facial SCC > 2╯cm in diameter or with perineural
invasion (PNI) noted on Mohs sectioning. For extensive
tumors of the extremities, amputation may be necessary.
Patients who are poor surgical candidates or those of
advanced age who have uncomplicated tumors of the head
and neck may be primarily treated with radiation therapy.
Complications include hypopigmentation, telangiectasia,
loss of adnexae, radiation dermatitis, and tumor recurrence
after 10–20 years. Intralesional therapy with bleomycin,
5-fluorouracil or interferon, or systemic therapy with retinoids
has also been reported to be effective in non-surgical
candidates.
First-Line Therapies
Curettage and electrodessication B
Excision (elliptical, shave) B
Mohs micrographic surgery B
Radiation therapy C
Imiquimod C
Topical 5-fluorouracil B
 15â•… Malignant Neoplasmsâ•… •â•… Squamous cell carcinoma
Bowen’s disease: a four-year retrospective review of epideÂ�
miology and treatment at a university center. Hansen JP,
Drake AL, Walling HW. Dermatol Surg 2008; 34(7):878–883.
A total of 299 patients with 406 cases of Bowen’s disease
were treated with elliptical excision, Mohs micrographic
surgery, shave excision, cryotherapy, curettage and electrodessi-
cation, and topical 5-fluorouracil. Histologic recurrence was
seen in 4% of the cases, including one patient with an invasive
SCC. The highest recurrence rate was in patients treated with
cryotherapy, (5-year recurrence of 13.4%), followed by topical
5-fluorouracil (9%) and shave excision (9%). Curettage and
electrodessication (6.5%), MMS (6.3%), and elliptical excision
(5.5%) had the lowest 5-year recurrence rates.
Surgical margins for excision of primary squamous cell
carcinoma. Brodland DG, Zitelli JA. J Am Acad Dermatol
1992; 27:241–248.
Prospective study recommending minimal margins of
4╯mm around the visible borders of the squamous cell carci-
noma. Margins of 6╯mm or more were recommended for
tumors of 2╯cm or larger, moderately differentiated tumors,
invasive tumors or location in high risk areas.
Cutaneous squamous cell carcinoma treated with Mohs
micrographic surgery in Australia I. Experience over 10
years. Leibovitch I, Huilgol SC, Selva D, Hill D, Richards S,
Paver R. J Am Acad Dermatol 2005; 53(2):253–260.
Case series comprised 1263 patients in which 61.1% had a
primary tumor, and 38.9% had a recurrent tumor. Most of the
tumors (96.5%) were on the head and neck area. Recurrence
after MMS was diagnosed in 15 of the 381 patients (3.9%)
who completed the 5-year follow-up after MMS. The recur-
rence rate was 2.6% in patients with primary SCC and 5.9%
in patients with previously recurrent SCC.
What is the role of adjuvant radiotherapy in the treatment
of cutaneous squamous cell carcinoma with perineural
invasion? Han A, Ratner D. Cancer 2007; 109(6):1053–1059.
Literature review which demonstrated the local control rate
after Mohs surgery with or without radiation therapy was 92–
100% compared with a control rate of 38–100% after standard
excision with or without radiation therapy. A better prognosis
was associated with negative pre-treatment magnetic reso-
nance imaging or computed tomography findings than with
positive radiographic evidence of perineural invasion (PNI).
Primary SCC with PNI was associated with better local control
than recurrent SCC with PNI. When treatment outcomes were
stratified by PNI type, SCC with microscopic PNI and SCC
with extensive PNI had local control rates of 78–87% and of
50–55%, respectively. Adjuvant radiation therapy was associ-
ated in selected patients with 100% local control.
Surgical monotherapy versus surgery plus adjuvant radio-
therapy in high-risk cutaneous squamous cell carcinoma: a
systematic review of outcomes. Jambusaria-Pahlajani A,
Miller CJ, Quon H, Smith N, Klein RQ, Schmults CD. Derma-
tol Surg 2009; 35:574–585.
High cure rates are achieved in high-risk cutaneous SCC
when clear surgical margins are obtained. Current data are
insufficient to identify high-risk features in which adjuvant
radiation therapy may be beneficial. In cases of perineural
invasion, the extent of nerve involvement appears to affect
outcomes, with involvement of larger nerves imparting a worse
prognosis.
Imiquimod 5% cream in the treatment of Bowen’s disease
and invasive squamous cell carcinoma. Peris K, Micantonio
T, Fargnoli MC, Lozzi GP, Chimenti S. J Am Acad Dermatol
2006; 55(2):324–327.
Five Bowen’s disease lesions and 7 invasive SCC lesions
were treated with imiquimod once daily 5 times a week for a
maximum of 16 weeks in this open label design consisting of
10 patients. After 8–12 weeks of treatment, 4 of 5 Bowen’s
disease lesions (80%) and 5 of 7 invasive SCCs (71.4%)
showed complete clinicopathologic regression. Partial regres-
sion after 16 weeks of treatment was seen in the remaining 3
lesions. No recurrence has been detected after a follow-up
period of 24–38 months.
Topical treatment of Bowen’s disease with 5-Fluorouracil.
Bargman H, Hochman J. J Cutan Med Surg 2003; 7(2):
101–105.
Twenty-six biopsy-proven lesions of Bowen’s disease were
treated with topical 5-Fluorouracil cream and were followed
for periods of up to 10 years. Post-treatment biopsies were
performed in 18 of the 26 lesional sites. Two of the twenty-six
lesions treated topically recurred.
Second-Line Therapies
Intralesional 5-fluorouracil E
Intralesional interferon C
Cryosurgery C
Treatment of squamous cell carcinoma with intralesional
5-Fluorouracil. Morse LG, Kendrick C, Hooper D, Ward H,
Parry E. Dermatol Surg 2003; 29(11):1150–1153.
A patient with SCC of the face was treated with 8 weekly
injections of 5-FU. The doses ranged from 0.8 to 2.4╯L. After
completing the course of treatment, a repeat skin biopsy
revealed total clearance of the cancer. The patient has remained
free of recurrence during a 5-month follow-up period. This
treatment option provides cosmetic benefits in particular areas
of the face, such as the alar crease and nasolabial folds.
Treatment of advanced, recurrent, resistant to previous
treatments basal and squamous cell skin carcinomas with a
synergistic formulation of interferons. Open, prospective
study. Anasagasti-Angulo L, Garcia-Vega Y, Barcelona-Perez S,
Lopez-Saura P, Bello-Rivero I. BMC Cancer 2009; 9:262.
Sixteen patients with extensive, recurrent, resistant BCC or
SCC received the IFN formulation peri- and intralesionally,
three times per week for 3 weeks. Thirteen weeks after the end
281
 Part 4 Tumors Benign and Malignant

of treatment, the original lesion sites were examined for his-

tological evidence of remaining tumor. At the end of treatment Table 15.3╇ Differences in the Clinical Presentation of Skin Cancers by
47% of the lesions cleared, 40% were reduced in size, and 13% Race/Ethnicity
were unchanged.
Skin cancer Caucasians Non-caucasians
Cryosurgery for cutaneous malignancy. An update. Kuflik
EG. Dermatol Surg 1997; 23:1081–1087. Basal cell Translucent papule Pigmented (> 50%)
Review article discussing the advantages of cryotherapy carcinoma or nodule
including low cost and speed. Squamous cell Sun-exposed sites Non-sun-exposed
carcinoma (head, neck) sites (lower
Third-Line Therapies (Bowen’s disease) Erythematous, scaly extremities, anus)
patch Often pigmented
Systemic retinoids B Malignant Sun-exposed sites Non-sun-exposed
Systemic interferon-alpha B melanoma (trunk, legs) sites (mucous
Amputation E membranes and
acral areas)
Most common type: Most common type:
13-cis-retinoic acid and interferon alpha-2a: effective com- Superficial Acral lentiginous
bination therapy for advanced squamous cell carcinoma of spreading melanoma
the skin. Lippman SM, Parkinson DR, Itri LM, Weber RS, melanoma (Blacks, Asians)
Schantz SP, Ota DM, et al. J Natl Cancer Inst 1992; Typically more
84(4):235–241. advanced, thicker
Thirty-two patients with heavily pre-treated, advanced Typically earlier tumors at
inoperable cutaneous squamous cell carcinoma of the skin presentation presentation
were given a combination of oral 13-cRA (1╯mg/kg per day) Cutaneous T-cell Poikilodermatous, Hypopigmented
and subcutaneous recombinant human IFN alpha-2a (3 lymphoma scaly atrophic
million units per day) for at least 2 months, unless disease (Mycosis patches or
progressed earlier, in a phase II trial. Nineteen (68%) of the fungoides) plaques
twenty-eight assessable patients responded, seven (25%) of
whom had complete responses. Response rates were 93% in Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006; 55:
741–760.
patients with advanced local, 67% in patients with regional
disease, and 25% in patients with distant metastases (one
complete response). The major limiting side effect in this
elderly patient population was cumulative fatigue. confused with other clinical entities (Table 15.3). More serious
dermatologic conditions can be mistaken for common ones
Squamous cell carcinoma arising in osteomyelitis and which can delay proper treatment and impact prognosis. For
chronic wounds. Treatment with Mohs micrographic surgery example, hypopigmented mycosis fungoides can be clinically
versus amputation. Kirsner RS, Spencer J, Falanga V, Garland similar to tinea versicolor in this patient population (Figs.
LE, Kerdel FA. Dermatol Surg 1996; 22:1015–1018. 15.12 vs 15.13 vs 15.14). Differentiating between pigmented
Indicates that amputation may be necessary in cases where basal cell carcinoma (BCC), which may be the more common
Mohs micrographic surgery may leave the limb unstable. type of BCC in skin of color,1 and seborrheic keratosis, may
also be difficult and lead to misdiagnosis (Figs. 15.15 vs 15.16;
Table 15.4). Patients with acral lentiginous melanoma can be
References misdiagnosed as having an acral nevus, which is prevalent in
1. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol African-Americans,2 a subungual hematoma, or melanonychia
2006; 55:741–760. striata (Figs. 15.17 vs 15.18 vs 15.19). Dermatofibrosarcoma
2. Koh D, Wang H, Lee J, Chia KS, Lee HP, Goh CL. Basal cell carcinoma, protuberans can mimic keloids and benign dermatofibromas
squamous cell carcinoma and melanoma of the skin: analysis of the in early stages (Figs. 15.20 vs 15.21 vs 15.22) and Bowen’s
Singapore Cancer Registry data 1968–97. Br J Dermatol 2003;
148:1161–1166.
disease can look like an eczematous patch, verruca or sebor-
3. Halder RM, Bang KM. Skin cancer in blacks in the United States. rheic keratosis (Figs. 15.23 vs 15.24).
Dermatol Clin 1988; 6:397–405. Typically, skin cancers have been associated with fair-
4. Jackson BA. Nonmelanoma Skin Cancer in Persons of Color. Semin skinned individuals with chronic sun exposure; however, these
Cutan Med Surg 2009; 28:93–95. tumors do occur in skin of color with some frequency as well.
To appropriately recognize these conditions in dark-skinned
Commonly encountered pitfalls patients in a timely manner, it is important to know the
risk factors in this patient population and not exclude the
The presentation of certain cutaneous tumors in skin of color diagnosis based on racial/ethnic background alone (Table
can differ from the classical presentation of the disease and be 15.5). It is also important to have a high index of suspicion if

282
 15â•… Malignant Neoplasmsâ•… •â•… Squamous cell carcinoma

Figure 15.12:╇ Hypopigmented mycosis fungoides on

the leg. (Courtesy of Valerie D. Callender, MD.)

Figure 15.14:╇ Tinea versicolor on the chest. (Courtesy Figure 15.13:╇ Hypopigmented mycosis fungoides on
of Valerie D. Callender, MD.) the leg. (Courtesy of Valerie D. Callender, MD.)

Figure 15.15:╇ Pigmented basal cell carcinoma of the scalp in a skin phototype V
patient. (Courtesy of Valerie D. Callender, MD.) Figure 15.16:╇ Seborrheic keratosis on the face and scalp. (Courtesy of Valerie D.
Callender, MD.)

283
 Part 4 Tumors Benign and Malignant

Table 15.4╇ Commonly Mistaken Skin Cancers with Other Lesions

Mistaken skin cancer Other lesions

Basal cell carcinoma Seborrheic keratosis, nevocellular nevus, epidermal inclusion cysts, blue nevi, Bowen’s disease, lentigines,
(± pigmentation) malignant melanoma, nevus sebaceous
Squamous cell carcinoma Verruca, chronic paronychia, melanoma, psoriasis, eczema, seborrheic keratosis, infection, trauma
(Pigmented Bowen’s disease)
Malignant melanoma Plantar verruca, calluses, melanonychia, acral nevi, hematoma
Mycosis fungoides Tinea versicolor, psoriasis, atopic dermatitis, vitiligo, lichen planus, pityriasis alba, hypopigmented sarcoid,
(Hypopigmented) post-inflammatory hypopigmentation
Dermatofibrosarcoma protuberans Dermatofibroma, keloid
Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006; 55: 741–760.

Figure 15.17:╇ Subungual melanoma of the right great Figure 15.18:╇ Subungual hematoma of the right great Figure 15.19:╇ Melanonychia striata of the thumb
toe. Note the presence of Hutchinson’s sign. toe. (Courtesy of Valerie D. Callender, MD.) nailbed. (Courtesy of Valerie D. Callender MD.)

Figure 15.20:╇ Dermatofibrosarcoma protuberans Figure 15.21:╇ Small keloid. (Courtesy of Valerie D. Figure 15.22:╇ Dermatofibroma. (Courtesy of Valerie D.
confirmed by biopsy. (Courtesy of Valerie D. Callender Callender, MD.) Callender MD.)
MD.)

284
 15â•… Malignant Neoplasmsâ•… •â•… Squamous cell carcinoma

Table 15.5╇ Greatest Risk Factors for the Development of Skin

Cancers by Race/Ethnicity

Type of skin Racial/Ethnic

cancer Caucasian minorities

Basal cell UV radiation UV radiation

carcinoma Ionizing radiation Ionizing radiation therapy
therapy Genetic syndromes (e.g.
Genetic syndromes (e.g. XP, OC albinism)
XP, OC albinism) Chronic wounds
Chronic wounds
Squamous UV radiation Chronic scarring or
cell Chronic scarring or inflammation (e.g.
Figure 15.23:╇ Pigmented Bowen’s disease in a Fitzpatrick skin type V patient. carcinoma inflammation DLE lesions)
(Courtesy of Valerie D. Callender, MD.) Human papillomavirus Human papillomavirus
Chemical carcinogens Chemical carcinogens
(arsenic, tar) (arsenic, tar)
Ionizing radiation Ionizing radiation therapy
therapy Immunosuppression
Immunosuppression Genetic syndromes (e.g.
Genetic syndromes (e.g. XP, OC albinism)
XP, OC albinism)
Malignant UV radiation Pigmented lesions (e.g.
melanoma Pigmented lesions (e.g. Melanocytic nevi)
Melanocytic nevi) Genetic syndromes (e.g.
Family or personal XP, OC albinism)
history of melanoma Immunosuppression
Fitzpatrick skin types I
& II
Genetic syndromes (e.g.
XP, OC albinism)
Immunosuppression
XP = Xeroderma pigmentosum
OC albinism = Oculocutaneous albinism
Figure 15.24:╇ Seborrheic keratosis. (Courtesy of Valerie D. Callender, MD.)
DLE = Discoid lupus erythematosus
Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol. 2006; 55:
741–760.

the patient does not respond to appropriate therapy, and to
biopsy the lesion for definitive diagnosis.
Special management & counseling considerations
It is important to keep in mind when performing surgery on
patients with skin of color that this patient population is more
prone to keloid formation and hypertrophic scarring.3 Since
there is no completely curative treatment for keloids or hyper-
trophic scars to date, prevention is key in this group of patients.
A thorough medical history is necessary to determine
whether there is a personal or family history of keloids or
hypertrophic scarring. Whenever possible, avoid all non-
essential surgical procedures.3,4 In order to minimize keloid
formation, it is best if surgical incisions follow natural skin
creases, are undermined delicately, and are closed with everted
wound edges with minimal tension.3–5 Avoid creating inci-
sions over joint spaces and regions of the body that are more
prone to keloid formation like the deltoids, chest, and upper
back regions, if possible.3–5 Incisions that cross joint spaces
and skin creases at right angles are also more likely to form
hypertrophic scars.3 These incisions should lie parallel to joint
flexion and natural skin creases to decrease tension on the
wound.
Knowledge of the patient’s risk of keloids and appropriate
planning of the surgical incision may not completely prevent
keloid formation and hypertrophic scarring but should pos-
sibly produce a less severe and more aesthetically pleasing
outcome. It is also important to inform all skin of color
patients with and without a personal or family history of
keloids or hypertrophic scarring of their risk prior to the surgi-
cal procedure.

285
 Part 4 Tumors Benign and Malignant

3. English RS, Shenefelt PD. Keloids and Hypertrophic Scars. Dermatol

References Surg 1999; 25:631–638.
4. Wolfram D, Tzankov A, Pulzl P, Piza-Katzer H. Hypertrophic scars
1. Halder RM, Bridgeman-Shah S. Skin cancer in African-Americans. and keloids – a review of their pathophysiology, risk factors, and
Cancer 1995; 75:667–673. therapeutic management. Dermatol Surg 2009; 35:171–181.
2. Coleman WP, Gately LE, Krementz AB, Reed RJ, Krementz ET. 5. Kelly AP. Update on the management of keloids. Semin Cutan Med
Nevi, lentigines, and melanomas in blacks. Arch Dermatol 1980; Surg 2009; 28:71–76.
116:548–551.

286
 PART 5
Cosmetics
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Part 5 Cosmetics
Cosmetic Applications
Valerie D Callender and Erica Chon Davis
Hair cosmetics . . . . . . . . . . . . . . . . . . . . . . .
Shampoos . . . . . . . . . . . å°“. . . . . . . . . . . . å°“.
Hair moisturizers . . . . . . . . . . . .å°“ . . . . . . . . .
Chemical processing . . . . . . . . . . . .å°“ . . . . . . .
Hair dyes . . . . . . . . . . . . . . . . . . . . . . . . .
Glossary of terms . . . . . . . . . . . . . . . . . . . . .
Camouflage techniques . . . . . . . . . . . . . . . . . .
Skin cosmetics . . . . . . . . . . . . . . . . . . . . . .
Skin lightening agents . . . . . . . . . . . .å°“ . . . . . .
Photoprotection . . . . . . . . . . . . . . . . . . . . . .
Camouflage techniques . . . . . . . . . . . . . . . . . .
Hair cosmetics
Today, the hair care market in the United States is a multi-
billion dollar industry with a multitude of products created
specifically for ethnic consumers. Hair care products for
African-Americans, in particular, comprise a large number of
these ethnic hair products.1 Some items are sold only to
licensed hair stylists to be used in professional salons but there
are also many products created for home use. Therefore, it is
important as dermatologists to be familiar with a variety of
different hair care products and practices as patients may
present with questions or complications from home or even
professional use of these items. Without a fundamental under-
standing of the products and common hair customs used in
ethnic populations, it will be difficult to provide adequate or
even accurate counseling for healthy hair practices.
Franbourg et╯al2 state that there are three major categories
of human hair based on ethnic origin: Asian, Caucasian, and
African. Although the biochemical composition of hair is the
same among the three categories, each group displays different
©2011 Elsevier Ltd, Inc, BV
16â•…
289 hair characteristics.2 For example, hair of African origin is
typically more curly with lower tensile strength than Asian or
289
Caucasian hair, leading to increased hair breakage.2 However,
292 it is important to remember that these findings are generaliza-
293 tions, and that hair of African origin can vary tremendously
from very curly to little or no curl and have coarse, medium,
294
or fine textures. Therefore, individual hair care practices will
296 vary depending on the specific hair characteristics of the
301 patient and counseling should be tailored to the individual.
In this section, we will discuss several categories of ethnic hair
301
care products as well as review common hair practices of
301 ethnic patients in a glossary of terms.
306
306 Shampoos
Certain ethnic groups as well as Caucasians with straighter hair
shafts will typically shampoo daily or on a more frequent basis
to wash away product build-up, debris, and sebum from the
hair and scalp.3 African-American men with very short hair-
styles will also shampoo more frequently. However, depending
on hair style and texture, African-American women typically
shampoo only once a week or every other week for a number
of reasons. First, hair with tighter curl patterns is not as easily
coated with sebum as straight hair, which can lead to dryness,4
and secondly, the fragility of hair of African origin can easily
lead to breakage if the hair is washed, dried and styled too
often.5,6 In addition, African-American women typically visit
their hair stylist weekly and would prefer salon care over home
styling. Visiting the hair stylist more often would be too time
consuming and costly. However, the physician must empha-
size the importance of cleansing the hair of styling products
and other debris weekly, particularly in the presence of sebor-
rheic or irritant dermatitis (Fig. 16.1).7
For patients suffering from the above and other scalp con�
ditions, including dandruff and scalp psoriasis, there are a
number of shampoos available such as those containing anti-
fungals, corticosteroids, ciclopiroxolamine, zinc pyrithione,
selenium sulfide, and non-tar ingredients (Table 16.1). For
African-American women who use chemical relaxers on their
289
 Part 5 Cosmetics

Figure 16.1:╇ Patient with seborrheic dermatosis. Note the post-inflammatory

hypopigmentation along the hairline.

Figure 16.2:╇ Two over-the-counter shampoos containing zinc pyrithione that are
particularly well-tolerated by chemically relaxed hair.
Table 16.1╇ Medicated shampoos for dandruff and seborrheic
dermatitis available over-the-counter
hair, shampoos containing zinc pyrithione (available over-the-
Medicated counter) (Fig. 16.2), fluocinolone acetonide, and ciclopirox
shampoo Active ingredient Manufacturer may be the best and safest options.8 However, if the patient
is undergoing a chemical relaxing process, a neutralizing
Pantene Relaxed & 1% Zinc Pyrithione Procter & Gamble, shampoo should be used immediately after, instead of a medi-
Natural for Cincinnati, OH cated shampoo. In addition, there are also shampoos and
Women of Color other products specifically created for the care of weaves and
hair extensions.
KeraCare® Dry 1% Zinc Pyrithione Avlon Industries, Melrose
and Itchy Scalp Park, IL
Mane ‘n Tail 1% Zinc Pyrithione Straight Arrow Products, Treatment Options
Lehigh Valley, PA
Head & Shoulders 1% Zinc Pyrithione Procter & Gamble, Ketoconazole A
Cincinnati, OH
Ciclopirox A
Dr. Miracle’s 1% Zinc Pyrithione Dr. Miracle’s, New York, Zinc pyrithione A
NY
Clobetasol propionate A
Pert Plus 1% Zinc Pyrithione Innovative Brands, Non-tar shampoo A
Phoenix, AZ
Selenium sulfide A
Nizoral 1% Ketoconazole McNeil Consumer
Healthcare Division of
McNeil-PPC*, Fort
Of note, there is a paucity of clinical studies evaluating
Washington, PA
medicated shampoos in skin of color patients. The following
Selsun Blue 1% Selenium Chattem, Chattanooga, clinical trials either contain none or a very small percentage of
sulfide TN skin of color patients, or race/ethnicity was not mentioned in
Neutrogena T/Gel 0.5% Coal Tar Neutrogena Corporation*, the article.
Los Angeles, CA
Successful treatment and prophylaxis of scalp seborrhoeic
Glover’s 2.5% Coal Tar J. Strickland & Co., Olive dermatitis and dandruff with 2% ketoconazole shampoo:
Branch, MS results of a multicentre, double-blind, placebo-controlled
Sulfur 8 0.2% Triclosan J. Strickland & Co., Olive trial. Peter RU, Richarz-Barthauer U. Br J Dermatol 1995;
Branch, MS 132:441–445.
*Subsidiary of Johnson & Johnson This is a two-phased clinical trial to determine the
efficacy of 2% ketoconazole shampoo in the treatment and

290

prophylaxis of seborrheic dermatitis (SD) or dandruff. In
Phase I, 575 patients with moderate to severe seborrheic der-
matitis (SD) or dandruff were treated with 2% ketoconazole
shampoo twice weekly for 2–4 weeks. Eighty-eight percent of
patients experienced an excellent response to treatment. Of the
patients who responded to treatment, 312 entered Phase II
(prophylactic phase). Patients were divided into three groups
and treated with either ketoconazole 2% shampoo alone once
weekly (Group I), ketoconazole 2% shampoo once every other
week alternating with placebo (Group II), or placebo alone
once weekly (Group III). Relapse rates were 19%, 31%, and
47% for Groups I, II, and III, respectively. The difference in
relapse rates between Groups I and III and Groups II and III
were statistically significant (p < 0.0001 and p = 0.025, respec-
tively). However, there was no significant difference between
the two groups treated with ketoconazole either weekly or
every other week.
Treatment of seborrhoeic dermatitis with ketoconazole: I.
Response of seborrhoeic dermatitis of the scalp to topical
ketoconazole. Carr MM, Pryce DM, Ive FA. Br J Dermatol
1987; 116:213–216.
Randomized, double-blind, placebo-controlled cross-over
study of 20 patients to determine the efficacy of ketoconazole
2% shampoo in the treatment of scalp SD. Patients were
treated with either ketoconazole 2% shampoo or the shampoo
base as a placebo daily for 4 weeks. This was followed by a
4-week washout period with Johnson’s Baby Shampoo™ for all
patients. The two groups then crossed over and used the alter-
native medication. Seventy-four percent of patients improved
clinically on ketoconazole (p < 0.01). Linear analogue scores
also improved significantly for scalp scaling and itching on
ketoconazole (p < 0.05 and p < 0.01, respectively) but not with
placebo.
Safety and efficacy of ciclopirox 1% shampoo for the treat-
ment of seborrheic dermatitis of the scalp in the US popula-
tion: results of a double-blind, vehicle-controlled trial.
Lebwohl M, Plott T. Int J Dermatol 2004; 43(Suppl 1):17–20.
This is a randomized, double-blind, vehicle-controlled trial
of 499 patients with SD of the scalp to determine the efficacy
of ciclopirox. Patients were treated with either ciclopirox 1%
shampoo or vehicle twice weekly for 4 weeks. Twenty-six
percent of ciclopirox-treated patients versus 12.9% of vehicle-
treated patients achieved ‘effective treatment’ (based on disease
status, scaling, and erythema).
Treatment and prophylaxis of seborrheic dermatitis of the
scalp with antipityrosporal 1% ciclopirox shampoo. Shuster
S, Meynadier J, Kerl H, Nolting S. Arch Dermatol 2005; 141:
47–52.
Randomized, double-blind, vehicle-controlled trial of 949
patients to determine the safety and efficacy of ciclopirox in
the treatment and prophylaxis of SD of the scalp. Patients were
treated with either ciclopirox 1% once or twice weekly or
vehicle for 4 weeks. Response rates were 57.9%, 45.4%, and
31.6% for ciclopirox twice weekly, once weekly, and vehicle,
respectively. Of the following, 428 patients who responded to
16â•… Cosmetic Applicationsâ•… •â•… Hair cosmetics
treatment in the initial phase, they received ciclopirox 1% once
weekly or once every 2 weeks or vehicle. Relapse rates were
14.7%, 22.1%, and 35.5% for prophylactic ciclopirox once
weekly, every 2 weeks, and vehicle, respectively. Response rates
as well as relapse rates for the two ciclopirox-treated groups
were significantly better when compared to the vehicle-treated
group (all p < 0.001).
Clinical efficacy of a new ciclopiroxolamine/zinc pyrithione
shampoo in scalp seborrheic dermatitis treatment. Lorette
G, Ermosilla V. Eur J Dermatol 2006; 16:558–564.
This is a randomized, single-blinded, controlled clinical
trial of 189 patients with scalp SD. Patients were treated with
either ciclopiroxolamine 1.5%/zinc pyrithione 1% shampoo
(CPO/ZP), ketoconazole 2% foaming gel, or vehicle shampoo
twice weekly for 28 days. At day 14, the two antifungal treat-
ments were significantly better than vehicle in reducing
lesional score, erythema, and pruritus (p < 0.0001). In addi-
tion, the global efficacies of both antifungal treatments were
significantly better than vehicle at day 28 as assessed by inves-
tigator and patient. The authors suggest that CPO/ZP shampoo
is as effective as ketoconazole in the treatment of SD.
A double-blind randomized vehicle-controlled clinical
trial investigating the effect of ZnPTO dose on the scalp vs
antidandruff efficacy and antimycotic activity. Bailey P,
Arrowsmith C, Darling K, Dexter J, Eklund J, Lane A, et╯al. Int
J Cosmet Sci 2003; 25:183–188.
This is a randomized, double-blind, vehicle-controlled
trial of 53 patients with dandruff or mild to moderate SD.
Patients were treated with either a low-depositing zinc
pyrithione (0.5% ZnPTO) shampoo, a high-depositing zinc
pyrithione (1% ZnPTO) shampoo, or vehicle shampoo for 4
weeks. At week 1, both ZnPTO treatment groups had signifi-
cantly better efficacy in the treatment of dandruff and SD
compared to vehicle (p < 0.05). After cessation of treatment,
the two ZnPTO treatment groups continued to have lower
dandruff scores than vehicle for at least 3 weeks after and the
high-depositing shampoo group had lower dandruff scores
than the low-depositing shampoo and vehicle groups for up
to 6 weeks.
Clobetasol propionate shampoo 0.05% in the treatment of
seborrheic dermatitis of the scalp: results of a pilot study.
Reygagne P, Poncet M, Sidou F, Soto P. Cutis 2007; 79:
397–403.
This is a randomized, investigator-blinded, parallel-group
pilot study to determine the efficacy of clobetasol propionate
0.05% shampoo in the treatment of SD of the scalp. Fifty-five
patients were randomized to one of the following treatments
twice weekly for 4 weeks: clobetasol propionate 0.05%
shampoo for 2.5, 5, or 10 minutes; clobetasol propionate
vehicle for 10 minutes; or ketoconazole 2% foaming gel for 5
minutes. The mean percentage decrease of the total severity
score for all active treatment groups was significantly greater
to that of the vehicle (p < 0.01). There were no serious adverse
events. The authors suggest that clobetasol propionate is a safe
and effective treatment for SD.
291
 Part 5 Cosmetics
Clobetasol propionate shampoo 0.05%: a new option to
treat patients with moderate to severe scalp psoriasis. Jarratt
M, Breneman D, Gottlieb AB, Poulin Y, Liu Y, Foley V. J Drugs
Dermatol 2004; 3:367–373.
This is a randomized, double-blind, vehicle-controlled trial
of 142 patients to determine the safety and efficacy of clobeta-
sol propionate 0.05% shampoo in the treatment of scalp pso-
riasis. Patients were treated with either clobetasol shampoo or
vehicle shampoo daily for 4 weeks. Patients were instructed to
apply the study medication to dry scalp for 15 minutes before
lathering and rinsing. The success rates for the clobetasol
shampoo group were significantly higher than the vehicle
group at the Week 4 end point (p < 0.001) and the Week 6
follow up (p = 0.003). In addition, clobetasol was found to be
significantly superior to vehicle in reducing the total severity
(p < 0.001), pruritis, erythema, scaling, and plaque thickness
(p < 0.001) scores.
Comparative anti-dandruff efficacy between a tar and
non-tar shampoo. Piérard-Franchimont C, Piérard GE,
Vroome V, Lin GC, Appa Y. Dermatology 2000; 200:181–
184.
Randomized, double-blind clinical trial comparing the effi-
cacies of tar (0.5% coal tar) versus non-tar (2% salicylic acid,
0.75% piroctone olamine and 0.5% elubiol) shampoos for the
treatment of dandruff. Patients underwent a 3-week washout,
followed by 4 weeks of treatment then a 4-week post-treatment
regression phase. Patients used either the tar or non-tar
shampoo 3 times weekly throughout the study. Both sham-
poos were equally effective when assessed by clinical evalua-
tion (p < 0.001) and patient self-assessments. However, the
Malassezia spp. counts were significantly more reduced with the
non-tar shampoo than with the tar shampoo (p < 0.02) during
the treatment phase, and the non-tar shampoo also had a
greater reduction in the spontaneous increase in squamometry
values (p < 0.01) during the post-treatment phase.
A randomized, double-blind, placebo-controlled trial of
ketoconazole 2% shampoo versus selenium sulfide 2.5%
shampoo in the treatment of moderate to severe dandruff.
Danby FW, Maddin WS, Margesson LJ, Rosenthal D. J Am Acad
Dermatol 1993; 29:1008–1012.
This is a randomized, double-blind, placebo-controlled
trial of 246 patients to determine the safety and efficacy
of ketoconazole versus selenium sulfide in the treatment of
moderate to severe dandruff. Patients were randomized to
twice weekly treatments of either ketoconazole 2% shampoo,
selenium sulfide 2.5% shampoo, or placebo (ketoconazole
vehicle) shampoo for 4 weeks. Mean total adherent dandruff
score declined with both ketoconazole 2% and selenium
sulfide 2.5% shampoos significantly more than placebo at all
visits. Ketoconazole was statistically superior to selenium
sulfide at only one time point (day 8, p = 0.0026). Both keto-
conazole and selenium sulfide shampoos were significantly
better than placebo for reducing irritation, itching, and yeast
counts. There was an 11.1% increase in yeast with placebo. All
of the adverse events reported during the treatment phase
involved patients treated with selenium sulfide 2.5% shampoo.
292
The authors suggest that both ketoconazole 2% shampoo and
selenium sulfide 2.5% shampoo are effective in the treatment
of moderate to severe dandruff; however, ketoconazole 2%
shampoo may be better tolerated.
A randomized, controlled clinical trial of four anti-dandruff
shampoos. Rapaport M. J Int Med Res 1981; 9:152–156.
This is a randomized, controlled clinical trial of 194 patients
to determine the efficacy of four anti-dandruff shampoos.
Patients were randomized to twice weekly treatment with
either Selsun Blue (selenium sulfide 1%, Abbott Laboratories),
Head & Shoulders (zinc pyrithione, Procter and Gamble), Flex
(zinc pyrithione, Revlon), or Tegrin (coal tar extract-allantoin,
Reedco) for 4 weeks. Loose and adherent dandruff were
each rated on a scale of 0 to 20 at baseline and each week of
the study, and the mean total pre-study score for all patients
was 19.5. The mean improvement scores at the end of the
study were 16.2 for Selsun Blue, 14.6 for Head & Shoulders,
13.5 for Flex, and 13.1 for Tegrin. Selsun Blue achieved greater
(p < 0.05) and faster (p < 0.05) significant improvement
than any other shampoo and more patients had total scores
of zero on Selsun Blue than Tegrin or Head & Shoulders
(p < 0.05).
Hair moisturizers
Hair conditioners are important products that help to increase
manageability, particularly in hair of African origin. These
products work to soften and detangle hair for easier combing,
increase luster, decrease static electricity, seal damaged areas,
and protect against thermal injury.3,7,9 Draelos10 categorizes
conditioners as instant, leave-in, and deep. Instant condition-
ers are applied after shampooing then are rinsed off after brief
contact, whereas leave-in conditioners are applied to damp or
dry hair without rinsing (Table 16.2).10 Silicone and its deriva-
tives, quaternized proteins, and polymers are typically con-
tained in these leave-in conditioners and work to moisturize
and protect the hair from thermal damage.4,10 In fact, a study
by de Sá Dias et╯al11 showed the protective effects of condition-
ing agents, particularly silicone derivatives, on chemically
straightened hair leading to increased resistance to hair
breakage.
The presence of trichorrhexis nodosa or hair breakage (Fig.
16.3) can be determined by the pull test, where a gentle tug
of the hair may cause a significant number of hairs to break
either mid-shaft or even a few centimeters from the scalp in
certain racial/ethnic groups.8 This condition can be congenital
but is typically acquired from physical or chemical trauma
such as excessive heating or chemical relaxing in addition to
use of drying agents like hair gels and sprays.8 Therefore, the
best advice to patients with trichorrhexis nodosa is to keep
these practices and use of these products to a minimum and
encourage the use of products that will add and maintain
moisture, particularly oil moisturizers containing silicone and
dimethicone (Fig. 16.4) and less lanolin, which can be sensi-
tizing. Using satin pillow cases (Fig. 16.5) and wide-tooth
combs (Fig. 16.6) may also help decrease hair breakage.
 16â•… Cosmetic Applicationsâ•… •â•… Hair cosmetics

Table 16.2╇ Leave-in conditioners for trichorrhexis nodosa or added moisture

Leave-in conditioners Key ingredients Manufacturer

Barry Fletcher Water, avocado oil, glycerin, aloe vera, shea butter, rosemary, nettles, Barry Fletcher Products, District Heights, MD
silk protein, vitamins B & E
Carol’s Daughter Hair Milk Water, soybean oil, sweet almond oil, emulsifying wax Nf, cocoa seed Carol’s Daughter Holdings, Brooklyn, NY
butter, shea butter, apricot kernel oil, beeswax, essential oil of
lemongrass, jojoba seed oil, wheat germ oil, ascorbic acid
Creme of Nature Water, petrolatum, cyclomethicone, amodimethicone, peppermint leaf Colomer USA Ltd, Jacksonville, FL
extract, basil extract, sage leaf extract, thyme extract, rosemary leaf
extract, grapefruit seed extract, lemon grass extract, orange oil
KeraCare® Water, mineral oil, hydrolyzed wheat protein, panthenol, simethicone Avlon Industries, Melrose Park, IL
Mixed Chicks Water, glycerin, amodimethicone, hydrolyzed wheat protein, jojoba oil, Mixed Chicks, Los Angeles, CA
safflower oil, primrose oil
Motions Water, PEG-12 dimethicone, dimethicone PEG-8 lanolate, Alberto-Culver USA, Melrose Park, IL
amodimethicone, panthenol, hydrolyzed keratin, hydrolyzed
glycosaminoglycans, wheat germ acid, linoleic acid, linolenic acid,
sorbitol, wheat germ oil, jojoba oil, sulfur

Figure 16.3:╇ Trichorrhexis nodosa or hair breakage in the temporal scalp region.

In addition to conditioners and oil moisturizers, many

African-Americans also apply hair emollients to add shine
and moisture as well as improve manageability (Table 16.3).
These products include creams and pomades, which work to
protect the hair shaft by coating it, thereby becoming a water
barrier.7 In addition to applying these products to the hair
itself, petrolatum or other oils are also applied to the scalp for
lubrication and protection. However, daily use of these prod-
ucts without frequent washing can lead to build-up and
various scalp conditions. Not only can these products irritate
the scalp but they have also been shown to cause closed come-
dones on the forehead and temples, known as pomade acne
(Fig. 16.7).12
Figure 16.4:╇ Hair moisturizing product containing dimethicone.
Chemical processing
Permanents
At times, the term ‘perm’ is used interchangeably with the
word ‘relaxer.’ However, the two terms use different agents and
can produce different results. Perms use thioglycolic acid salts,
such as ammonium thioglycolate and calcium thioglycolate,
to produce a permanent curl in straight hair.3 This is the ‘curly

293
 Part 5 Cosmetics

perm’ for Caucasians, Asians, and Hispanics. However, a new

curl pattern can also be achieved in hair of African origin with
these perms and therefore, this process became popular among
African-Americans in the 1980s3 (Table 16.4). The perm is
applied to the hair then roller set. After 20–60 minutes, the
hair is neutralized with bromate or peroxide and dried. The
rollers are then removed and product is added to moisturize
and encourage the curl.

Figure 16.5:╇ Satin pillow cover which may help to decrease hair breakage.
Figure 16.6:╇ Wide-tooth combs decrease the probability of snagging on hair
knots, which leads to breakage.
Relaxers
Chemical relaxing or lanthionization is the process of chemi-
cally straightening curly hair. There are two categories of re��
laxers: lye-based, which contain sodium hydroxide, and no-
lye, which contain guanidine, calcium, lithium, or potassium
hydroxide that are available for home use (Table 16.5) or for
use by licensed professionals only (Table 16.6). These alkali
agents straighten hair by breaking cortical disulfide bonds to
create lanthionine.3,6 Given the high alkalinity of these agents,
they must be neutralized with an acidic shampoo to stop the
chemical reaction. These agents should only be applied to the
most proximal portions of hair ‘new growth’ that have not
been chemically processed before and at 6–8-week intervals.3
Overprocessing hair can lead to dry hair, alopecia, irrita-
tion, chemical burns, and hair breakage. Therefore, it is
important to either have chemical relaxing performed by a
licensed stylist or follow the instructions carefully for home
use as the complications can be serious. In fact, in 1994 there
was a nationwide outbreak of alopecia and scalp injuries from
an acidic but commercially available relaxer (Rio Hair Natural-
izer System, World Rio Corporation, Rio de Janeiro, Brazil).13
A few studies have investigated the relationship between
chemical relaxers and the development of central centrifugal
cicatricial alopecia (CCCA) but further studies are needed.14,15
Also available on the market are chemical relaxers specifically
for children’s hair, which are created to be less harsh although
some still contain sodium hydroxide (lye) (Table 16.7).
Texturizers
Texturizers (Table 16.8) are designed to loosen the natural curl
pattern without completely straightening the hair as a chemi-
cal relaxer would. They contain, as the active ingredient,
Sodium hydroxide or lithium hydroxide. Men who desire a
looser curl will typically choose texturizers over chemical
relaxers but many women prefer the opposite. As with
relaxers, texturizers are applied to the hair for a short period
of time and must also be neutralized with a shampoo.

Figure 16.7:╇ Pomade acne. Note the closed comedones.
Hair dyes
There is a wide range of possibilities when choosing to color
one’s hair. One can choose to color the entire surface of the
hair or alternatively, certain strands (highlights). In addition,
coloring can be temporary (rinses), semi-permanent, or per-
manent and the formulation of hair dyes is the same for all
types of hair (Table 16.9). Temporary hair dyes do not pene-
trate the cuticle but simply coat it with color whereas semi-
permanent dye molecules do penetrate the cortex of the hair

294

Table 16.3╇ Hair moisturizers
Oils
Aveda Light Elements™ Smoothing
Fluid
Carol’s Daughter Hair Milk
Fantasia Frizz Buster Serum
Long Aid k7 Essentials Extra Light
Oil Moisturizer
Pink ® Oil Moisturizer Hair Lotion
Roots of Nature Strengthening Oil
Moisturizer
Optimum Oil Therapy
Emollients
Barry Fletcher Press-N-Curl Wax
Blue Magic Hair & Scalp
Conditioner
Dr. Miracle’s Anti-Breakage
Strengthening Creme
Elasta QP Super Gro Hair
Strengthening & Scalp Treatment
Isoplus Castor Oil
Pink® Grocomplex 3000 Hairdress
Mane ‘n Tail Hair Dressing
Mizani Coconut Soufflé Light
Moisturizing Hairdress
Pantene Relaxed & Natural Oil
Cream Moisturizer
Smooth ‘N Shine Nourishing Balm
Roots of Nature Triple Repair
Hairdress
Sulfur 8 Fresh Oil Moisturizing
Creme
Ultra Sheen Original Formula Hair
Dress
*Subsidiary of Estée Lauder Companies
+
Subsidiary of L’Oréal USA
16â•… Cosmetic Applicationsâ•… •â•… Hair cosmetics
Key ingredients Manufacturer
Dimethicone, dimethiconol, phenyl trimethicone, dimethicone crosspolymer, Aveda Corporation*,
jojoba seed oil, rice bran oil, lavender oil, soybean oil Minneapolis, MN
Water, soybean oil, sweet almond oil, emulsifying wax, cocoa seed butter, Carol’s Daughter Holdings,
shea butter, apricot kernel oil, beeswax, essential oil of lemongrass, Brooklyn, NY
jojoba seed oil, wheat germ oil, ascorbic acid, xanthan gum
Cyclomethicone, dimethicone, trimethylsilamodimethicone Fantasia Industries
Corporation, Paramus, NJ
Water, mineral oil, petrolatum, isopropyl myristate, glycerin, lanolin, cetyl Keystone Laboratories,
alcohol, beeswax, aloe vera gel Memphis, TN
Water, mineral oil, lanolin, beeswax, petrolatum, provitamin B5, vitamin E, Luster Products, Chicago, IL
benzyl alcohol
Water, soybean oil, coconut oil, glycerin, isopropyl palmitate, sorbic acid, SoftSheen-Carson+, New
citric acid, avocado oil, shea butter, sunflower seed oil, dimethicone, York, NY
green tea, benzyl alcohol
Water, mineral oil, glycerin, petrolatum, lanolin, paraffin, phenoxyethanol, SoftSheen-Carson+, New
magnesium sulfate, lanolin alcohol, olive fruit oil, jojoba seed oil, coconut York, NY
oil, avocado oil
Carrot oil, soybean oil, beeswax, mink oil, shea butter, propylene glycol, Barry Fletcher Products,
indian hemp, vitamins B, E District Heights, MD
Petrolatum, lanolin, olive fruit oil, lecithin, isopropyl myristate J. Strickland & Co., Olive
Branch, MS
Water, menthol, safflower seed oil, hydrolyzed soy protein, hydrolyzed wheat Dr. Miracle’s, New York, NY
protein, sweet almond oil, castor seed oil, jojoba seed oil, lanolin,
paraffin, isopropyl palmitate, petrolatum, cetyl alcohol, PEG-12
dimethicone
Petrolatum, mineral oil, isopropyl myristate, dimethicone, cholesterol, Strength of Nature Co.,
Vitamin E Savannah, GA
Castor oil, coconut oil, essence oil J.M. Products, Little Rock, AR
Water, mineral oil, beeswax, provitamin B5, stearic acid, calcium oxide Luster Products, Chicago, IL
Petrolatum, isopropyl myristate, beeswax, lanolin, mineral oil, dimethicone Straight Arrow Products,
Lehigh Valley, PA
Coconut oil, camellina oil, rice bran oil Mizani+, New York, NY
Water, mineral oil, glycerin, petrolatum, cetearyl alcohol, coconut oil, jojoba Procter & Gamble, Cincinnati,
seed oil, dimethicone, paraffin OH
Petrolatum, mineral oil, coconut oil, jojoba seed oil, hydrolyzed wheat protein Henkel Consumer Goods,
Irvine, CA
Water, coconut oil, stearyl alcohol, glycerin, dimethicone SoftSheen-Carson+, New
York, NY
Water, mineral oil, petrolatum, glycerin, dimethicone, stearyl alcohol, cetyl J. Strickland & Co., Olive
alcohol Branch, MS
Petrolatum, mineral oil, lanolin, ceresin, benzyl benzoate, lauric acid, Johnson Products, Dallas, TX
tocopherol
295
 Part 5 Cosmetics

shaft. In permanent dyes, hydrogen peroxide decolorizes the
hair while aromatic amines and phenols provide the color.3
Although home dyes are available, it is important to use
caution with these products as they can produce not only an
aesthetically unpleasing result, but also skin reactions. Indi-
viduals can develop an allergic contact dermatitis to paraphe-
nylenediamine contained in the hair dyes (Fig. 16.8). DeLeo
et╯al16 conducted a study to evaluate the effect of race/ethnicity
on patch test results and found higher rates of sensitization to
paraphenylenediamine among Black patients compared to
Whites. It is also important to instruct the patient to wait at
least 2 weeks after chemical relaxing before dyeing their hair
to minimize hair damage and breakage.

Other ethnic hair products

Table 16.4╇ Permanents
Hair bonding glue (Fig. 16.9) is used to attach hair extensions
to the proximal portions of hair for increased fullness and
Permanents Active ingredients Manufacturer
length. Commercial bonding glues are composed of pigments,
antioxidants, and natural rubber latex.17 In general, most
Lustrasilk Lustra Ammonium Alleghany Pharmacal people tolerate the glue well but Cogen et╯al17 reported a case
Curl Gel Perm thioglycolate Corporation, Great of a patient who developed systemic anaphylaxis after repeated
Neck, NY exposure to hair bonding glue.
Care Free Curl Cold Ammonium SoftSheen-Carson*,
Wave Chemical thioglycolate New York, NY
Glossary of terms
Rearranger
Wave Nouveau® Sodium thioglycolate SoftSheen-Carson*, • “Basing the scalp”: Refers to the practice of applying a
Coiffure New York, NY thick, protective emollient evenly along the hairline or over
*Subsidiary of L’Oréal USA the entire scalp prior to chemical relaxing in an effort to
reduce scalp exposure to the chemicals.

Table 16.5╇ Chemical relaxers for home use

Chemical relaxer Active ingredient Manufacturer

Barry Fletcher Sodium hydroxide Barry Fletcher Products, District Heights, MD

Creme of Nature Calcium hydroxide Colomer USA Ltd, Jacksonville, FL
Dark and Lovely Moisture Calcium hydroxide SoftSheen-Carson*, New York, NY
Seal plus Shea Butter
Dr. Miracle’s Calcium hydroxide Dr. Miracle’s, New York, NY
Elasta QP Calcium hydroxide Strength of Nature Co., Savannah, GA
Gentle Treatment Calcium hydroxide, lithium hydroxide Johnson Products, Dallas, TX
Motions Sodium hydroxide Alberto-Culver USA, Melrose Park, IL
Optimum Care Anti-Breakage Therapy Calcium hydroxide SoftSheen-Carson*, New York, NY
Organic Root Stimulator Calcium hydroxide Namasté Laboratories, Blue Island, IL
PCJ Sodium hydroxide Luster Products, Chicago, IL
® ®
Pink Brand Smooth Touch Calcium hydroxide Luster Products, Chicago, IL
Renutrients™ Lithium hydroxide Luster Products, Chicago, IL
Silk Elements Calcium hydroxide Silk Elements, Atlanta, GA
Soft & Beautiful Calcium hydroxide Alberto-Culver USA, Melrose Park, IL
TCB Sodium hydroxide, calcium hydroxide Alberto-Culver USA, Melrose Park, IL
Ultra Sheen Calcium hydroxide Johnson Products, Dallas, TX
Vitale Olive Oil Calcium hydroxide AFAM Concept, Chicago, IL
*Subsidiary of L’Oréal USA

296
 16â•… Cosmetic Applicationsâ•… •â•… Hair cosmetics

Table 16.6╇ Chemical relaxers for professional use only

Professional use only Active ingredient Manufacturer

Affirm Sodium hydroxide, guanidine hydroxide Avlon Industries, Melrose Park, IL

Barry Fletcher Sodium hydroxide Barry Fletcher Products, District Heights, MD
Creme of Nature Calcium hydroxide Colomer USA Ltd, Jacksonville, FL
Design Essentials Sodium hydroxide McBride Research Laboratories, Decatur, GA
Elasta QP Soy Oyl Protein + Vitamins Sodium hydroxide, calcium hydroxide Strength of Nature Co., Savannah, GA
Mizani Sodium hydroxide, calcium hydroxide Mizani*, New York, NY
Motions Sodium hydroxide Alberto-Culver USA, Melrose Park, IL
Optimum Lithium hydroxide SoftSheen-Carson*, New York, NY
Organic Root Stimulator Sodium hydroxide Namasté Laboratories, Blue Island, IL
Olive Oil Professional
Syntonics Sodium hydroxide Syntonics International, Northlake, IL
Ultra Sheen Sodium hydroxide, calcium hydroxide Johnson Products, Dallas, TX
Vitale Pro Sodium hydroxide AFAM Concept, Chicago, IL
*Subsidiary of L’Oréal USA

Table 16.7╇ Products for children’s hair Table 16.8╇ Hair texturizers for home use

Shampoos and Chemical relaxers Hair texturizers Active ingredient Manufacturer

conditioners (active ingredient) Manufacturer
S-Curl Regular Sodium hydroxide Luster Products,
PCJ PCJ (Sodium hydroxide, Luster Products, Texturizer Chicago, IL
calcium hydroxide) Chicago, IL Silk Elements No-Lye Lithium hydroxide Silk Elements,
Motions for Kids Motions for Kids (Sodium Alberto-Culver USA, No-Mix Texturizer Atlanta, GA
hydroxide) Melrose Park, IL Soft & Beautiful Sodium hydroxide, Alberto-Culver USA,
Soft & Beautiful Soft & Beautiful Just for Alberto-Culver USA, Texturizer lithium hydroxide Melrose Park, IL
Just for me! me! (Calcium hydroxide) Melrose Park, IL

Table 16.9╇ Hair dyes for home use

Hair dyes Paraphenylenediamine Manufacturer

Temporary
Clairol Professional Jazzing No Procter & Gamble, Cincinnati, OH
Semi-Permanent
Clairol Professional Beautiful Collection No Procter & Gamble, Cincinnati, OH
Permanent
Creme of Nature Nourishing Permanent Hair Color Yes Colomer USA Ltd, Jacksonville, FL
Dark and Lovely Permanent Hair Color Yes SoftSheen-Carson*, New York, NY
*Subsidiary of L’Oréal USA

297
 Part 5 Cosmetics
Figure 16.8:╇ Patient who developed an allergic contact dermatitis of the left ear
due to contact with paraphenylenediamine in hair dye. Note the erythema, edema,
and small areas of superficial ulceration particularly over the superior aspect of the
helix.
Figure 16.9:╇ Hair bonding glue.
• Braids/Plaits: Popular hairstyle among African-American
women where three pieces of hair are woven together start-
ing at the scalp down to the tip of the hair. Often synthetic
or human hair is added for length or fullness. Microbraids
refer to significantly thinner braids that are of a longer
length. The process of hair braiding can take many hours
to complete depending upon the size and length of the
braids. In some cases, the hair is pulled very tightly and
frequent braiding can lead to traction folliculitis or alo-
pecia.6 Some African-American women believe that braids
help the hair grow longer likely due to decreased breakage
from combing. Braids should be removed after 6–8 weeks.6
• Brazilian keratin treatment: A method of temporary hair
straightening that uses a liquid keratin and formaldehyde
solution that is sealed into the hair shaft by the high heat
298
Figure 16.10:╇ Crimping or wave iron.
of a flat iron. The treatment typically lasts 2–3 months and
progressively washes out evenly.
• Cornrows: Popular with both men and women, cornrows
are braids that lay flat against the scalp. Similar to braids,
synthetic or human hair can be added for length or fullness
and traction folliculitis or alopecia can be sequelae of this
hairstyle.
• Crimping iron: Mechanical device that uses high heat to
temporarily add waves or crimps to hair. Crimping irons
are similar to curling irons except the cylinder of the curling
iron is replaced by two metal plates in the shapes of waves
or crimps that come together with the hair in the middle,
which gives it shape (Fig. 16.10).
• “Dominican blowout”: Method of temporary hair straight-
ening perfected by hairstylists of Dominican heritage. The
hair is shampooed then a setting lotion is applied and the
hair placed into large, plastic rollers. The hair is dried under
a hooded dryer. The hair stylist further straightens out the
hair using a large, roundbrush and a handheld hair dryer
with a nozzle piece to concentrate the heat to a specific area
working from root to tip.
• Dreadlocks/Locks: Type of irreversible hairstyle that
occurs when uncombed hair is allowed to tangle and
mat in clusters. Once the hair ‘locks,’ it can no longer be
combed out and must be cut off if a different hairstyle is
desired.4
• Durag: Also known as wave caps (Fig. 16.11). Typically
worn by African-American men to help relax the natural
curl of their hair and to keep certain hairstyles (e.g.
cornrows) in place while sleeping. However, these caps can
facilitate pomade acne, irritant dermatitis, infection, and
seborrhea, particularly when used with pomades or other
styling products, because of the occlusion from the cap.9
Therefore, mesh caps may be the best option if the patient
decides to continue use.
• Fade: Hairstyle typically worn by African-American men
where the hair is cut somewhat short on top then is cut

Figure 16.11:╇ Durag or wave cap.
Figure 16.12:╇ Men’s fade hairstyle.
progressively shorter and shorter as it continues down to
the end of the hair at the neck (Fig. 16.12).
• Finger waves: Type of sculpted hairstyle that uses a signifi-
cant amount of styling gel or spritz to hold the hair in a
wave formation closely against the scalp. Once dried,
these hairstyles become harder and more difficult to
manipulate.
• Flat iron: Type of handheld styling instrument that straight-
ens hair by compressing it between two heated flat metal
plates. Typically marcel flat irons are used with an oven to
reach very high temperatures and are generally reserved for
use by a licensed, professional stylist. However, there are a
number of companies that market electric flat irons to the
general public that do not reach the extreme temperature
16â•… Cosmetic Applicationsâ•… •â•… Hair cosmetics
Figure 16.13:╇ (Left to right) Electric curling iron, hot comb and ceramic flat iron.
of the marcel flat iron. Recently, ceramic flat irons have
become more popular due to their constant heat and quick
heat-up times (Fig. 16.13).
• “Greasing the scalp”: Typically involves any kind of mois-
turizing agent, including pomade, that is applied to the
entire scalp and proximal hair shafts to allow easier combing
and less hair breakage.9
• Hot comb: This type of handheld instrument is a metal
comb that is heated to temporarily straighten hair. Oil is
applied to the hair then the hot comb is passed through the
hair from root to tip. Excessive heat from this type of styling
can cause hair breakage.6,9 There has been some disagree-
ment over whether or not hot comb usage is the cause of
the scarring alopecia seen in some African-American female
patients.18,19
• “Japanese perm” or “Japanese hair straightening”: Also
called thermal reconditioning. This is a patented process to
straighten hair based on Japan’s Yuko System, which uses
a more gentle form of ammonium thyoglycolate that is lye-
free along with special straightening irons to restructure the
protein bonds in hair. The perm typically needs to be reap-
plied to the base of the hair shaft every 6 months. It is
important not to overlap onto previously treated hair;
however, not doing so is very difficult and it is these overlap
sections that are particularly prone to hair breakage.
These products are available to licensed, professional hair
stylists only.
• “Kiddie perm”: This term typically refers to a hair texturizer,
which is a mild hair relaxer that loosens the natural curl
pattern of the hair.
• Lace wigs: The wig hairs are hand-tied to a flesh-tone lace
base and placed over the head. This method gives the
appearance of hair growing out of your scalp to give a more
natural look. The hair can be parted anywhere and still
appear natural.
• Marcel curling iron: Metal curling iron that can reach very
high temperature (300–500° F) due to its use with a marcel
oven.
• “Pressing”: Method of straightening hair using heated
instruments such as hot combs or marcel irons.
• Roller set: Method used to achieve curls. The hair is sham-
pooed then while it is still damp, a setting lotion (used to
create hold) (Fig. 16.14) or slightly more water is sprayed
299
 Part 5 Cosmetics
Figure 16.14:╇ Setting lotion used with roller setting. Note its liquid consistency.
Figure 16.15:╇ Head wrap typically used during sleep to maintain hair style.
onto strands of hair, placed into rollers, and set under a
hooded hair dryer.
• “Touch up”: Refers to the application of a chemical relaxer
only to the base of the hair shaft that has not been previ-
ously treated (‘new growth’).
• Twists: Hairstyle that is formed when two pieces of hair are
wrapped around each other. This style can increase manage-
ability by decreasing the bulk of thick hair and can redefine
the natural curl pattern.9
• Weave: Another term for hair extensions. Weaves can be
made of synthetic or human hair and are attached by being
sewn on to a small, hidden cornrow, or glued to the hair
close to the scalp.
300
A
B
Figure 16.16:╇ Patient with CCCA before (A) and after (B) Toppik treatment.
Note some improvement in the appearance of hair loss after camouflaging.
• Wrap: Method of maintaining straight hair, typically during
sleep. The hair is combed in a direction where it wraps
around the head, then wrapped in a scarf or cap (Fig.
16.15). Some hair stylists also use the wrapping method
after shampooing. While the hair is still damp, it is combed
into a wrap, and a styling product may or may not be
applied to create a light hold. Then the hair is dried under
a hooded hair dryer.

Camouflage techniques
The fact that women take so much pride in their hair and
spend sizeable amounts of money and time in the care of their
hair can make conditions like CCCA, female pattern hair loss,
and traction alopecia psychologically devastating. There are
effective treatment options available such as topical and oral
medications that stimulate growth or hair transplantation.8
However, these options take time to reach maximum benefit.
In the meantime, patients can use other camoflage techniques
to cover areas of hair loss. For example, hair extensions can
provide temporary coverage; however, depending on the cause
of the hair loss, weaves can exacerbate the problem. Wigs,
particularly lace wigs, can cover large areas of hair loss without
inciting further hair damage. In addition, Toppik (Spencer
Forrest, Westport CT) is a camouflage product that uses
keratin fibers that are charged with static electricity so that they
intertwine with the patient’s own hair and bond securely.
The product is packaged in a bottle that is shaken over the
thinning areas (Fig. 16.16) and typically stays in place until
washed out.
Special management & counseling considerations
Ethnic hair care, particularly hair of African origin, is an area
that receives attention from consumers and hair product
manufacturers but there remains a paucity of literature on
most of these products. There have been some studies15,20 that
show the effects of particular hair practices and the develop-
ment of CCCA but further studies are needed to determine the
relationship not only between hair practices like braiding but
also between products like chemical relaxers and their contri-
bution to the development of certain scalp conditions.
References
1. Syed AN. Ethnic hair care products. In: Johnson DH, ed. Hair and hair
care. New York: Marcel Dekker; 1997:235–259.
Skin cosmetics
The majority of pharmaceutical and cosmeceutical agents
used in people of color address facial hyperpigmentation.
The most common conditions include melasma and post-
inflammatory hyperpigmentation (PIH). The mechanisms
involved in skin lightening include removing pigment from
the skin, decreasing the production of pigment by inhibiting
tyrosinase and preventing the transfer of melanin into epider-
mal keratinocytes. Photoprotection and camouflage are also
important in successful treatment of pigmentary changes. This
section will cover the most commonly used skin lightening
agents available through over-the-counter (OTC), prescription
16â•… Cosmetic Applicationsâ•… •â•… Skin cosmetics
2. Franbourg A, Hallegot P, Baltenneck F, Toutain C, Leroy F. Current
research on ethnic hair. J Am Acad Dermatol 2003; 48:S115–S119.
3. Holloway VL. Ethnic cosmetic products. Dermatol Clin 2003;
21:743–749.
4. Quinn CR, Quinn TM, Kelly AP. Hair care practices in African-American
women. Cutis 2003; 72:280–282, 285–289.
5. Grimes PE. Skin and hair cosmetic issues in women of color. Dermatol
Clin 2000; 18:659–665.
6. Grimes PE, Davis LT. Cosmetics in Blacks. Dermatol Clin 1991;
9:53–68.
7. Roseborough IE, McMichael AJ. Hair care practices in African-American
patients. Semin Cutan Med Surg 2009; 28:103–108.
8. Callender VD, McMichael AJ, Cohen GF. Medical and surgical thera-
pies for alopecias in black women. Dermatol Ther 2004; 17:164–
176.
9. Quinn CR. Hair care practices. In: Taylor SC, Kelly AP, ed. Dermatology
for skin of color. New York: McGraw Hill; 2009:217–226.
10. Draelos ZD. Understanding African-American hair. Dermatol Nurs
1997; 9:227–231.
11. de Sa Dias TC, Baby AR, Kaneko TM, Velasco VM. Protective effect of
conditioning agents on Afro-ethnic hair chemically treated with
thioglycolate-based straightening emulsion. J Cosmet Dermatol
2008; 7:120–126.
12. Plewig G, Fulton JE, Kligman AM. Pomade acne. Arch Dermatol
1970; 101:580–584.
13. Swee W, Klontz KC, Lambert LA. A nationwide outbreak of alopecia
associated with the use of a hair-relaxing formulation. Arch Dermatol
2000; 136:1104–1108.
14. Nicholson AG, Harland CC, Bull RH, Mortimer PS, Cook MG.
Chemically induced cosmetic alopecia. Br J Dermatol 1993; 128:
537–541.
15. Nnoruka NE. Hair loss: is there a relationship with hair care practices
in Nigeria? Int J Dermatol 2005; 44(Suppl 1):13–17.
16. DeLeo VA, Taylor SC, Belsito DV, Fowler JF, Fransway AF, Maibach HI,
et al. The effect of race and ethnicity on patch test results. J Am Acad
Dermatol 2002; 46:S107–S112.
17. Cogen FC, Beezhold DH. Hair glue anaphylaxis: a hidden latex allergy.
Ann Allergy Asthma Immunol 2002; 88:61–63.
18. LoPresti P, Papa CM, Kligman AM. Hot comb alopecia. Arch Dermatol
1968; 98:234–238.
19. Sperling LC. The follicular degeneration syndrome in Black patients:
‘hot comb alopecia’ revisited and revised. Arch Dermatol 1992;
128:68–74.
20. Gathers RC, Jankowski M, Eide M, Lim HW. Hair grooming practices
and central centrifugal cicatricial alopecia. J Am Acad Dermatol 2009;
60:574–578.
and office dispensing as well as photoprotection and cosmetic
camouflage.
Skin lightening agents
Treatment Options
Hydroquinone A
Retinoids
â•… tretinoin A
â•… adapalene B
â•… tazarotene A
301
 Part 5 Cosmetics

severity, lesion area, pigmentation intensity, and Melasma Area

Azaleic Acid A and Severity Index (MASI) score. In arm 2, cream A showed
Mequinol B similar improvements to cream C in overall disease severity,
Arbutin B lesion area, pigmentation intensity, MASI score, and global
evaluation of response to treatment at weeks 4 and 8. At week
Kojic acid A
12, cream A continue to show sustained improvements in
Licorice extract B outcome measures but cream C decreased because subjects
Ascorbic Acid A were switched to placebo for the last 4 weeks of treatment.
Soy B Based on the demonstrated efficacy of cream A, the author
N-acetyl glucosamine A suggests that non-steroidal products should be considered
Niacinamide A when long-term treatment is needed.

Safety and efficacy of 4% hydroquinone combined with 10%

Hydroquinone
Hydroquinone (HQ) remains the gold standard when treating
hyperpigmentaton. It is a phenolic compound that reduces
the conversion of DOPA to melanin by inhibiting tyrosinase.1
HQ is available over-the-counter (OTC) at a 2% concentration
and by prescription at a concentration between 3 and 4%.
However, there have been a number of studies that have shown
increased efficacy of hydroquinone when formulated in a
double (micro-encapsulated 4% HQ and retinol 0.15%; 4%
HQ and retinol 0.3%) or triple combination cream (4% HQ,
0.01% fluocinolone acetonide, and 0.05% tretinoin).2,3,4
Efficacy and Safety of a New Triple-Combination Agent for
the Treatment of Facial Melasma. Taylor SC, Torok H, Jones
T, Lowe N, Rich P, Tschen E, et al. Cutis. 2003; 72:67–72.
Two randomized, investigator-blinded studies were con-
ducted in 641 patients (Fitzpatrick skin types I-IV) to compare
the safety and efficacy of a triple combination (TC) agent
(tretinoin (RA) 0.05%, hydroquinone (HQ) 4.0%, and fluoci-
nolone acetonide (FA) 0.01%) to dual combination agents (RA
+ HQ; RA + FA; HQ + FA) in the treatment of moderate to
severe melasma. The results of both studies showed that more
patients treated with the triple combination agent experienced
complete clearing (26.1%) compared to other treatment
groups (4.6%) by the end of the 8-week study period (P <
0.0001). More than 70% of patients treated with the TC agent
experienced a 75% reduction in melasma/pigmentation by
8-weeks compared to 30% with the dual treatments. The
majority of side effects were mostly mild and included ery-
thema, skin peeling, burning, and stinging sensation.
An Efficacy Study of 3 Commercially Available Hydroqui-
none 4% Treatments for Melasma. Grimes PE. Cutis. 2007;
80:497–502.
Two-arm, single-blind, comparative study, to compare to
the safety and efficacy of 3 hydroquinone (HQ) 4%-containing
creams in the treatment of melasma in patients with Fitz-
patrick skin types III-V. Treatment arm 1 compared cream A
(microencapsulated HQ 4% and retinol 0.15% with antioxi-
dants) to cream B (HQ 4% and retinol 0.3% with antioxi-
dants) and arm 2 compared cream A to cream C (fluocinolone
acetonide 0.01%, HQ 4%, and tretinoin 0.05%). Treatment
arm 1 showed that at weeks 8 and 12, cream A showed statisti-
cally significant improvements over cream B in overall disease
glycolic acid, antioxidants, and sunscreen in the treatment
of melasma. Guevara IL, Pandya AG. Int J Dermatol 2003;
42:966–972.
This is a randomized, double-blind, controlled trial of 35
Hispanic patients (Fitzpatrick skin types III to V) to determine
the efficacy of 4% hydroquinone with 10% glycolic acid,
vitamins C and E, and sunscreen in treatment of epidermal
melasma. Patients were treated with either twice daily full-
face application of the study cream or with the cream contain-
ing sunscreen alone. There was a significant decrease in
pigmentation using the study cream by mexameter analysis
(p < 0.0001) as well as a significant reduction in the Melasma
Area and Severity Index (MASI) from baseline to 12 weeks
(p = 0.01).
A randomized controlled trial of the efficacy and safety of
a fixed triple combination (fluocinolone acetonide 0.01%,
hydroquinone 4%, tretinoin 0.05%) compared with hydro-
quinone 4% cream in Asian patients with moderate to
severe melasma. Chan R, Park KC, Lee MH, Lee ES, Chang SE,
Leow YH, et╯al. Br J Dermatol 2008; 159:697–703.
A randomized, single-blind, controlled clinical trial of 242
Asian patients (skin phototypes II to V) with melasma to
evaluate the efficacy of a fixed triple combination (TC) cream
compared with hydroquinone (HQ) alone. Patients were
treated with either nightly application of TC cream (fluoci-
nolone acetonide 0.01%, hydroquinone 4%, and tretinoin
0.05%) or twice daily 4% hydroquinone alone. More patients
treated with TC cream had a melasma global severity score of
‘none’ or ‘mild’ at 8 weeks than patients treated with HQ alone
(p < 0.001). Although there were more adverse effects with TC
cream, patient satisfaction was in favor of TC cream over HQ
(p = 0.005).
An open-label study of the efficacy and tolerability of micro-
encapsulated hydroquinone 4% and retinol 0.15% with
antioxidants for the treatment of hyperpigmentation. Cook-
Bolden FE, Hamilton SF. Cutis 2008; 81:365–371.
This is a 12-week open-label study of 19 patients (Fitz-
patrick skin types II to VI) with mild to moderate hyperpig-
mentation. The majority of patients had post-inflammatory
hyperpigmentation and were treated twice daily for 12 weeks
with microencapsulated hydroquinone 4%, retinol 0.15%
and antioxidants. Efficacy assessment results showed reduc-
tions in lesion size, darkness, and disease severity as early

302

as 4 weeks and remained significant throughout the study
(all p < 0.03). Sixty-three percent of patients had either
marked improvement (75%) or complete clearing (> 95%).
Retinoids
Tretinoin, a vitamin A analogue, has also been studied in the
treatment of dyschromias and has been shown to increase
epidermal cell turnover and inhibit tyrosinase transcription
and dispersion of keratinocyte pigment granules.5 Concentra-
tions range from 0.01% to 0.1%, although irritant dermatitis
can be a common side effect with higher concentrations.
Adapalene and tazarotene are synthetic retinoids, in which
studies have shown to be effective for the treatment of
hyperpigmentation.
Topical retinoic acid (tretinoin) for melasma in black
patients. a vehicle-controlled, clinical trial. Kimbrough-Green
CK, Griffiths CE, Finkel LJ, Hamilton TA, Bulengo-Ransby SM,
Ellis CN, et╯al. Arch Dermatol 1994; 130:727–733.
Twenty-eight African-American patients with moderate to
severe melasma were treated with either 0.1% tretinoin or
vehicle cream daily to the entire face in this randomized,
vehicle-controlled clinical trial. There was a significant reduc-
tion in MASI score in the treatment group compared to vehicle
(p = 0.03). Colorimetric analysis also showed a significant
lightening in the treatment and histologic exam confirmed an
8% decrease in epidermal pigmentation with tretinoin com-
pared to 55% increase with vehicle (p = 0.0007).
Topical tretinoin (retinoic acid) therapy for hyperpigmented
lesions caused by inflammation of the skin in black patients.
Bulengo-Ransby SM, Griffiths C, Kimbrough-Green CK, Finkel
LJ, Hamilton TA, Ellis CN, et╯al. N Engl J Med 1993; 328:
1438–1443.
This is a 40-week randomized, double-blind, vehicle-
controlled clinical trial of 54 African-American patients to
evaluate the efficacy of tretinoin in the treatment of post-
inflammatory hyperpigmentation. Patients applied either
0.1% tretinoin or vehicle cream to the face, arms, or both areas
every night for 40 weeks. There was significant improvement
in the hyperpigmentation in the tretinoin-treated group com-
pared to vehicle (p < 0.001). Colorimetric analysis confirmed
these results (p = 0.001). Side effects occurred in 50% of
the tretinoin-treated patients and included erythema and
desquamation.
Adapalene in the treatment of melasma: a preliminary
report. Dogra S, Kanwar AJ, Parsad D. J Dermatol 2002;
29:539–540.
Thirty Indian patients (Fitzpatrick skin type IV) with facial
melasma were randomized to treatment with either 0.05%
tretinoin cream or 0.1% adapalene gel. MASI scores were
decreased by 37% and 41% in the tretinoin-treated and
adapalene-treated groups, respectively. There was no signifi-
cant difference. Side effects were more common with tretinoin.
The authors suggest that adapalene has comparative efficacy
to tretinoin with fewer side effects.
16â•… Cosmetic Applicationsâ•… •â•… Skin cosmetics
Adapalene gel 0.1% for topical treatment of acne
vulgaris in African patients. Jacyk WK, Mpofu P. Cutis 2001;
68(Suppl):48–54.
This is an open-label study of 44 African patients to
determine the efficacy of adapalene in the treatment of acne
vulgaris. Patients applied 0.1% adapalene to the face nightly
for 12 weeks. After 12 weeks of treatment, there was a signifi-
cant improvement in the global acne grade (p < 0.01) as
well as significant improvements in PIH from baseline
(p < 0.01).
Tazarotene cream for post-inflammatory hyperpigmenta-
tion and acne vulgaris in darker skin: a double-blind, ran-
domized, vehicle-controlled study. Grimes PE, Callender VD.
Cutis 2006; 77:45–50.
Fifty-three patients (Fitzpatrick skin types III to VI) with
post-inflammatory hyperpigmentation were treated with
either tazarotene 0.1% cream or vehicle for up to 18 weeks in
this randomized, double-blind, vehicle-controlled trial. There
was a significant reduction in the overall disease severity score
(p = 0.01), the pigmentary intensity of hyperpigmented lesions
(p = 0.04), and the area of hyperpigmented lesions (p = 0.02)
in the treatment group compared to vehicle. Side effects, which
were trace to mild, included erythema, burning, peeling, and
dryness.
Azelaic acid
Azelaic acid (AZA) is a dicarboxylic acid originally isolated
from Pityrosporum ovale, the organism responsible for Pityriasis
versicolor.6 Azelaic acid was originally developed for the treat-
ment of acne and rosacea but is now used for the treatment
of PIH due to its ability to inhibit tyrosinase activity. AZA
works also by inhibiting DNA synthesis and mitochondrial
enzymes, thereby inducing direct cytotoxic effects toward
melanocytes. However, due to its selective affinity for abnor-
mal melanocytes, AZA has no depigmenting effects on nor-
mally pigmented skin.1
Double-blind comparison of azelaic acid and hydroquinone
in the treatment of melasma. Verallo-Rowell VM, Verallo V,
Graupe K, Lopez-Villafuerte L, Garcia-Lopez M. Acta Derm
Venereol (Stockh) 1989; 143(Suppl):58–61.
This is a randomized, double-blind clinical trial of 132
patients of Indo-Malay-Hispanic origin (Fitzpatrick skin types
II to V) with melasma. Patients were randomized to treatment
groups of either twice daily application of 20% AZA or 2% HQ
for 24 weeks. There was a significant reduction in pigmentary
intensity with AZA compared to HQ (p < 0.05) as well as
lesion size, and overall improvement (p < 0.001). Therefore,
the authors suggest that 20% AZA is more effective than 2%
HQ in the treatment of melasma in Asian patients.
Azelaic acid 20% cream in the treatment of facial hyperpig-
mentation in darker-skinned patients. Lowe NJ, Rizk D,
Grimes PE, Billips M, Pincus S. Clin Ther 1998; 20:945–959.
Forty-five patients (Fitzpatrick skin types IV to VI) with
hyperpigmentation were treated twice daily with either AZA
303
 Part 5 Cosmetics
20% or vehicle for 24 weeks in this randomized, double-blind,
parallel-group study. There was a significant reduction in
pigmentary intensity with AZA compared with vehicle by an
investigator’s subjective scale (p = 0.02) and by colorimetÂ�
ric analysis (p = 0.03). There was also greater global improve-
ment with AZA over vehicle at 24 weeks (p = 0.008). Side
effects were more common with AZA and included burning
and stinging.
Mequinol
Mequinol, 4-hydroxyanisole, is a skin lightening agent that is
derived from hydroquinone but has been found to be less
irritating than its parent compound. The exact mechanism of
action of mequinol is unknown; however, possible theories
include oxidation of mequinol by tyrosinase to melanotoxic
products, direct or selective melanotoxic effects, or inhibition
of melanin formation.7
The combination of 2% 4-hydroxyanisole (mequinol) and
0.01% tretinoin effectively improves the appearance of solar
lentigines in ethnic groups. Draelos ZD. J Cosmet Dermatol
2006; 5:239–244.
This is an open-label study of 259 patients of Asian, His-
panic, and African-American descent (Fitzpatrick skin types II
to V) to determine the efficacy of mequinol/tretinoin solution
in the treatment of solar lentigines. Patients were treated with
topical mequinol 2%/tretinoin 0.01% for 24 weeks. Over 80%
of patients responded to treatment assessed by the Overall
Lesion Pigmentation Index scores and the majority of these
patients maintained the clinical response 4 weeks after treat-
ment cessation.
Arbutin
Arbutin, a derivative of HQ and naturally occurring plant-
derived compound, inhibits tyrosinase activity as well as
melanosome maturation.5 The efficacy of arbutin is
concentration-dependent but higher concentrations can lead
to a paradoxical increase in pigmentation.8 Deoxyarbutin is a
synthetic compound and has greater tyrosinase inhibition
than arbutin.9 Arbutin is a component of numerous depig-
menting formulations marketed in the US and Japan.
Efficiency of ellagic acid and arbutin in melasma: a rand-
omized, prospective, open-label study. Ertam I, Mutlu B, Unal
I, Alper S, Kivcak B, Ozer O. J Dermatol 2008; 35:570–574.
This is a randomized, open-label clinical study of 29
patients (Fitzpatrick skin types II to IV) to determine the
efficacy of ellagic acid (EA) and arbutin in the treatment of
melasma. Patients were randomized into three treatment
groups: 1% arbutin, 1% ellagic acid (synthetic), 1% ellagic
acid from plant extracts containing natural EA. Pigment
density from baseline to study end point measured by
mexameter was significantly decreased in all three treatment
groups. However, the naturally occurring EA and arbutin
achieved greater decreases in pigmentation than synthetic EA
but this difference was not statistically significant.
304
Comparative efficacy and safety of deoxyarbutin, a new
tyrosinase-inhibiting agent. Hamed SH, Sriwiriyanont P,
deLong MA, Visscher MO, Wickett RR, Boissy RE. J Cosmet Sci
2006; 57:291–308.
Twenty-five patients (skin phototypes III to IV) were
exposed to UV light from a tanning bed for 10–20 minutes
daily for 7 consecutive days on three skin sites on their backs.
One site was left untreated and the other two sites were treated
with 3% deoxyarbutin (dA) and 4% HQ separately three times
per week for 5 weeks. The percentage of tan remaining was
44.6%, 37.3%, and 51.6% in the untreated site, dA site, and
HQ site, respectively. The percentage of tan remaining after
treatment with dA represents a significant decrease in the
hyperpigmentation over control, which suggests that dA accel-
erated the fading of the UV-induced tan.
Kojic acid
Kojic acid (KA) is an aromatic acid that occurs naturally as a
hydrophilic, fungal derivative of certain species of Acetobacter,
Aspergillus, and Penicillium.1 It is a potent inhibitor of tyrosi-
nase activity and acts by chelating copper at the active site
of the enzyme.10 KA had been widely used in skin care prod�
ucts in Japan but has since been removed from the market
as a consequence of long-term studies showing that kojic
acid has the potential for causing contact dermatitis and
erythema.1
Treatment of melasma using kojic acid in a gel containing
hydroquinone and glycolic acid. Lim JT. Dermatol Surg 1999;
25:282–284.
This is a randomized, double-blind, split-face comparison
study of 40 Chinese patients with epidermal melasma. Patients
applied 2% KA gel with 10% glycolic acid and 2% HQ on one
side of the face and the contralateral side of the face was
treated with the same application but without the KA. Sixty
percent of patients receiving KA versus 47.5% of patients not
receiving KA experienced a > 50% clearance of their melasma.
Side effects included erythema, stinging, and exfoliation.
Licorice extract
Licorice extract is a very common component in depigmenting
cosmetics and is used all over of the world. Glabridin, the
main component of the hydrophobic fraction of licorice
extract, inhibits tyrosinase activity.1 Other active compounds
in licorice include licochalcone A and liquiritin. Licorice
extract also causes depigmentation by dispersing melanin and
removing epidermal melanin.11
Topical liquiritin improves melasma. Amer M, Metwalli M.
Int J Dermatol 2000; 39:299–301.
Twenty patients with epidermal melasma were treated with
liquiritin cream on one side of the face and vehicle cream on
the other side twice daily for 4 weeks in this clinical study. On
the treatment side, 16 patients (80%) experienced an excellent
response with complete resolution of the hypermelanosis, 2
patients showed a good response, and 2 patients showed a fair
response with moderate pigmentation. In contrast, on the

vehicle-treated side, 18 patients (90%) showed a poor response
and 2 patients showed a fair response. Side effects included
erythema and burning.
Ascorbic acid
Ascorbic acid (AA), vitamin C, is a depigmenting agent that
suppresses melanin synthesis by its antioxidant properties.
To prevent the rapid oxidation of ascorbic acid in aqueous
solutions, ascorbate esters have been synthesized.5 Ascorbic
acid can be formulated in combination with hydroquinone for
skin lightening.
A double blind randomized trial of 5% ascorbic acid vs 4%
hydroquinone in melasma. Espinal-Perez LE, Moncada B,
Castanedo-Cazares JP. Int J Dermatol 2004; 43(8):604–607.
This is a randomized, double-blind, split-face clinical trial
of 16 patients (skin phototypes IV and V) to determine the
efficacy of AA versus HQ in the treatment of melasma. Patients
applied 5% AA to one side of the face and 4% HQ to the con-
tralateral side every night for 16 weeks. Ninety-three percent of
patients reported good to excellent results on the HQ-treated
side compared with 62.5% on the AA-treated side by patients’
subjective evaluations. However, colorimeter analysis showed
no statistically significant difference between the two treatment
sides. Side effects occurred in 68.7% and 6.2% with HQ and
AA, respectively. The authors suggest that although the treat-
ment response was better with HQ, AA may still have a role in
the treatment of melasma due to its safety profile.
Clinical efficacy of 25% L-ascorbic acid (C’ensil) in the treat-
ment of melasma. Hwang SW, Oh DJ, Lee D, Kim JW, Park
SW. J Cutan Med Surg 2009; 13:74–81.
Thirty-nine patients (Fitzpatrick skin types III to IV) with
melasma were treated with 25% L-ascorbic acid (C’ensil) in
this open-label trial of 16 weeks. Patients applied C’ensil twice
daily to the entire face. There was a significant reduction in
MASI scores and degree of pigmentation by mexameter analy-
sis with C’ensil from baseline to week 16 (p < 0.0001 for both).
Soy
Soy has also been studied in the treatment of hyperpig�
mentation. Certain soy proteins (serine trypsin inhibitor and
Bowman Birk inhibitor) inhibit protease-activated receptor
2 (PAR-2), which modulates melanosome transfer, thereby
inhibiting keratinocyte phagocytosis of melanosomes.11 Skin
lightening with a soybean extract has been demonstrated over
a 3-week period.11
Assessment of topical hypopigmenting agents on solar
lentigines of Asian women. Hermanns JF, Petit L, Piérard-
Franchimont C, Paquet P, Pierard GE. Dermatology 2002;
204:281–286.
This is an open-label, randomized trial of 30 patients of
South-East Asian ancestry with solar lentigines. Patients
applied a stabilized soy extract on the target lesion on one
limb twice daily for two months and similar lesions on the
other limb were left untreated as controls. There were signifi-
16â•… Cosmetic Applicationsâ•… •â•… Skin cosmetics
cant decreases in melanin density (p < 0.05) and melanin area
(p < 0.01) on the treated side compared to control.
N-acetyl glucosamine
N-acetyl glucosamine is an amino-monosaccharide that can
be found throughout nature and the human body. Its depig-
menting properties arise from its ability to inhibit tyrosinase
glycosylation, which is necessary for melanin production.12
N-acetyl glucosamine can be found in over-the-counter depig-
menting agents.
Reduction in the appearance of facial hyperpigmentation by
topical N-acetyl glucosamine. Bissett DL, Robinson LR,
Raleigh PS, Miyamoto K, Hakozaki T, Li J, et╯al. J Cosmet
Dermatol 2007; 6:20–26.
This is a randomized, double-blind, split-face, placebo-
controlled trial of Japanese patients with hyperpigmentation
(solar lentigines, chloasma, and freckles). The patients applied
a 2% N-acetyl glucosamine (NAG) formulation to one side of
the face and a vehicle control to the contralateral side. The
authors found that NAG was effective in improving facial
hyperpigmentation by computer image analysis.
Niacinamide
Niacinamide is a water-soluble derivative of niacin and has
been used in the treatment of acne. Studies show that niacina-
mide inhibits melanosome transfer by 35–68% without affect-
ing tyrosinase activity, melanin production, melanocyte
number, or cell viability.11 Niacinamide is also available in
some over-the-counter lightening agents.
The effect of niacinamide on reducing cutaneous pigmenta-
tion and suppression of melanosome transfer. Hakozaki T,
Minwalla L, Zhuang J, Chhoa M, Matsubara A, Miyamoto K,
et╯al. Br J Dermatol 2002; 147:20–31.
The authors report the results of two clinical trials, which
examine the efficacy of niacinamide in the treatment of hyper-
pigmentation. The first was a randomized, double-blind, split-
face trial of 18 Japanese patients with senile lentigines,
melasma, and freckles. Patients applied 5% niacinamide mois-
turizer to one side of the face and vehicle to the contralateral
side twice daily for 8 weeks. There was a significant reduction
in the area (p < 0.05) and level of pigmentation (p < 0.05) in
the niacinamide-treated sides compared to vehicle. The second
study was also a randomized, double-blind, split-face trial of
120 Japanese patients with moderate to deep facial tans.
Patients applied either vehicle moisturizer, sunscreen in a
vehicle moisturizer, or 2% niacinamide and sunscreen in a
vehicle moisturizer to one side of the face and another one of
the other study medications to the contralateral side twice
daily for 8 weeks. Although initially there was a significant
increase in skin lightness on the niacinamide and sunscreen-
treated side compared to the sunscreen only-treated side by
image analysis, this difference was not maintained at 8 weeks.
However, there was a significant difference between the niaci-
namide and sunscreen-treated side when compared to vehicle
only by visual assessment (p < 0.05).
305
 Part 5 Cosmetics
Emerging therapies
As there continues to be a demand for skin lightening agents
around the world, new products are currently in development.
A recent randomized, double-blind, vehicle-controlled clinical
trial of 30 patients showed that undecylenoyl phenylalanine
2% is effective in the treatment of solar lentigines.13 One
study14 showed that topical methimazole is safe for the use in
melasma patients. The efficacy of dioic acid was compared
with that of HQ in the treatment of melasma in an open-label
study of 96 Mexican patients.15 There was a significant decrease
in the MASI scores for both treatments but no significant dif-
ferences between the two treatments suggesting dioic acid as
an alternative in the treatment of melasma. Aloesin has been
shown in studies to suppress pigmentation by UV radiation.16
Other agents that require further research and development
include 4-(1-phenylethyl)1,3-benzenediol, paper mulberry,
ellagic acid, quinolines, piperlonguminine, luteolin, and
calycosin.
Photoprotection
The use of photoprotection in darker skin phototypes is an
issue that has not received much attention. This is likely due
to the inherent photoprotection in dark skin from the absorp-
tion of UV radiation by melanin pigment.17,18 However, the
risk of skin cancer in this patient population is not absent.
Furthermore, photoprotection may play a role in the preven-
tion of, as well as the improvement of, pigmentary disorders.
Public awareness campaigns and physician counseling have
typically been directed toward fair-skinned individuals because
these patients not only have the greatest risk but also a higher
incidence and prevalence of skin cancer. This may have led to
an attitude among ethnic patients and some physicians as well
that education about sun protection is not needed because
dark skin is fully protective.
One study by Briley et╯al19 looked at the attitudes and prac-
tices of sunscreen use in African-Americans in a beachside com-
munity in New York. Of the 50 patients included in the study,
37 (74%) had never used sunscreen. The majority of patients
who had used sunscreen previously used it only occasionally
when prolonged sun exposure was anticipated and only one
patient (8%) used it daily. Only 15% of sunscreen users and
11% of non-users had been advised either by a family member
or health care provider to use sunscreen. In addition, only 39%
of sunscreen users and 27% of non-users were aware that
African-Americans could develop skin cancer. Another study20
analyzed data from the 1992 National Health Interview Survey
of 1583 African-Americans regarding sun protection behaviors.
Only 9% of respondents were very likely to use sunscreen versus
81% who were unlikely to use it; 28% and 45% were very likely
to wear protective clothing or stay in the shade, respectively.
Therefore, with the knowledge that skin cancers in racial/ethnic
minorities are associated with greater morbidity and mortal-
ity,21 it is important as dermatologists to educate patients
regardless of skin color on the value of photoprotection.
306
Most over-the-counter sunscreens block solar radiation
through two mechanisms, reflection and absorption, by com-
bining two different active ingredients. Inorganic ingredients
such as zinc oxide and titanium dioxide reflect/scatter as well
as absorb ultraviolet (UV) radiation and organic components
also function to absorb it.22 The UVA spectrum ranges from
320 to 400╯nm and is absorbed by organic classes of UV filters
in sunscreens like avobenzone, ecamsule, and oxybenzone.
Octyl salicylate and octyl methoxycinnamate are also organic
UV filters that absorb UVB radiation, which covers the spec-
trum between 290 and 320╯nm.22 Typically, a sun protection
factor (SPF) of 30 is adequate for skin of color.23 However,
proper photoprotection involves not only topical sunscreens
but also avoidance measures. It is also important to educate
patients regarding the use of protective clothing, sun avoid-
ance during peak hours, and routine self examinations.
Camouflage techniques
Cosmetic camouflage is used to disguise deformities that are
not amenable to medical or surgical treatments. The goal is to
alleviate the patient’s suffering due to the untreatable disfig-
urement (Fig. 16.17). Several studies have shown that these
camouflage techniques significantly improve quality of life for
many of these patients.24,25 Indications for cosmetic camou-
flage include vascular lesions, pigmentary disorders like vitil-
igo, scars, chronic skin conditions like lupus erythematosus,
and for surgical patients in the post-operative period.26 Cam-
ouflage has been indispensable to patients with vitiligo par-
ticularly when very visible parts of the body are affected by the
disease like the face, neck, and hands.27
Before starting cosmetic camouflage, it is important to
obtain a thorough medical history. Important information
includes nature and duration of the condition to be camou-
flaged, any topical or systemic medications that may produce
further pigmentary changes and interfere with the proper color
match, any allergies or sensitivities to cosmetics, and any pre-
scribed skin care products. An adequate social history should
also be obtained from the patient as well including psycho-
logical impact of the condition, leisure activities (i.e. sports),
and work environment.26,28 It is also imperative to discuss the
patient’s expectations from cosmetic camouflage before start-
ing the coverage.
A good cosmetic cover must appear natural, and be grease-
less, opaque, waterproof, long-lasting, and easy to apply. It
should also be applicable to all skin types, non-irritating, and
non-comedogenic.29 There are four basic foundations: oil-
based (for dry skin), water-based (for dry to normal skin),
oil-free (for oily skin), and water-free (oil mixed with waxes
to form thicker creams that can incorporate higher pigment
concentrations).26 Cosmetic covers can be applied for subtle
coverage, full concealment, or color blending.28 A light
application of foundation is applied for moderate conceal-
ment in subtle coverage whereas full concealment is complete
coverage that extends beyond the affected sites. Color blending
matches a cream cover with the patient’s skin tone. Finally,
color correctors can be used under makeup foundations and
this involves using an opposite color to neutralize the color of

A and 0.01% tretinoin effectively improves the appearance of solar len-
B 513–515.
Figure 16.17:╇ Before and after cosmetic camouflage for post-inflammatory
hyperpigmentation.
a lesion.26 For example, a lesion with red discoloration would
be neutralized with a green color corrector.
The technique to apply cosmetic camouflage includes
cleansing the skin first, then applying a color corrector, if nec-
essary, followed by a cream cover to match the normal skin
tone of the patient’s face and neck. Once the cream cover has
dried, a translucent powder is applied and finally skin imper-
fections are created to avoid a ‘mask-like’ appearance.26
16â•… Cosmetic Applicationsâ•… •â•… Skin cosmetics
References
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2. Cestari CF, Hassun K, Sittart A, de Lourdes Viegas M. A comparison of
triple combination cream and hydroquinone 4% cream for the treat-
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meceuticals for women of color. J Drugs Dermatol 2007; 6:32–39.
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et al. Topical N-acetyl glucosamine affects pigmentation relevent genes
in in vitro genomics testing. Pig Cell Res 2006; 19:3009–3015.
13. Katoulis AC, Alevizou A, Bozi E, Makris M, Zafeiraki A, Mantas N,
et al. A randomized, double-blind, vehicle-controlled study of a prepa-
ration containing undecylenoyl phenylalanine 2% in the treatment of
solar lentigines. Clin Exp Dermatol Oct 23, 2009 [Epub ahead of
print].
14. Kasraee B, Safaee Ardekani GH, Parhizgar A, Handjani F, Omrani GR,
Samani M, et al. Safety of topical methimazole for the treatment of
melasma. Skin Pharmacol Physiol 2008; 21:300–305.
15. Tirado-Sanchez A, Santamaria-Roman A, Ponce-Olivera RM. Efficacy
of dioic acid compared with hydroquinone in the treatment of
melasma. Int J Dermatol 2009; 48:893–895.
16. Choi S, Park YI, Lee SK, Kim JE, Chung MH. Aloesin inhibits hyper-
pigmentation induced by UV radiation. Clin Exp Dermatol 2002; 27:
17. Antoniou C, Lademann J, Schanzer S, Richter H, Sterry W, Zastrow L,
et al. Do different ethnic groups need different sun protection? Skin
Res Techno 2009; 15:323–329.
18. Meinhardt M, Krebs R, Anders A, Heinrich U, Tronnier H. Effect of
ultraviolet adaptation on the ultraviolet absorption spectra of human
skin in vivo. Photodermatol Photoimmunol Photomed 2008; 24:
76–82.
19. Briley JJ, Lynfield YL, Chavda K. Sunscreen use and usefulness in
African-Americans. J Drugs Dermatol 2007; 6:19–22.
20. Hall HI, Rogers JD. Sun protection behaviors among African-Americans.
Ethn Dis 1999; 9:126–131.
21. Gloster HM, Neal K. Skin cancer in skin of color. J Am Acad Dermatol
2006; 55:741–760.
22. Nash JF. Human safety and efficacy of ultraviolet filters and sunscreen
products. Dermatol Clin 2006; 24:35–51.
23. Downie JB. Esthetic considerations for ethnic skin. Semin Cutan Med
Surg 2006; 25;158–162.
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24. Holme SA, Beattie PE, Fleming CJ. Cosmetic camouflage advice
improves quality of life. Br J Dermatol 2002; 147:946–949.
25. Kent G. Testing a model of disfigurement: effects of a skin camouflage
service on well-being and appearance anxiety. Psychol Health 2002;
17;377–386.
26. Antoniou C, Stefanaki C. Cosmetic camouflage. J Cosmet Dermatol
2006; 5:297–301.
27. Tanioka M, Miyachi Y. Camouflage for vitiligo. Dermatolog Ther
2009; 22:90–93.
28. Rayner VL. Camouflage Therapy. Dermatol Clin 1995; 13:467–472.
29. Roberts NG, Nordlund JJ, Wright C. The corrective cover or camouflage
clinic. Ear Nose Throat J 1989; 68:480–482.

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Part 5 Cosmetics
Cosmetic Treatments
Valerie D Callender, Vic A Narurkar and Erica Chon Davis
Introduction . . . . . . . . . . . . . . . . . . . . . . . .
Botulinum neurotoxin-A (BoNT-A) . . . . . . . . . . . .
Chemical peels . . . . . . . . . . . . . . . . . . . . . .
Fillers . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hair transplantation . . . . . . . . . . . . . . . . . . . .
Lasers, light sources and other devices . . . . . . . . .
Introduction
The field of cosmetic dermatology has grown tremendously
over the past decade. According to the American Society of
Aesthetic Plastic Surgery, the number of cosmetic surgery pro-
cedures in the skin of color population in the United States
has increased from 15% in 2000 to 20% in 2008.1 Hispanic
patients undergo 8% of these cosmetic procedures, African-
Americans 6%, Asians 4%, and other non-Caucasians 2% (Fig.
17.1). The five most common non-surgical cosmetic proce-
dures, regardless of race or ethnicity, include botulinum toxin
injections, laser hair removal, hyaluronic acid injections,
chemical peels and laser resurfacing (Fig. 17.2). This growth
arises from the need to enhance one’s appearance through
non-surgical facial rejuvenation methods rather than with
invasive plastic surgery.
Historically, cosmetic procedures in patients with pig-
mented skin have been performed reluctantly, mainly because
of the risk of dyspigmentation, hypertrophic and keloidal scar-
©2011 Elsevier Ltd, Inc, BV
17â•…
309 ring that can result from any form of cutaneous injury. These
adverse events can occur from a variety of cosmetic procedures,
311
such as chemical peels, microdermabrasion, laser hair removal
315 and hair transplantation (Fig. 17.3). However, recently there
321 have been more clinical studies performed involving skin
of color patients which have produced a greater understanding
326
of the safety profile for many of these procedures in this
332 population.
There are major differences between skin of color and white
skin. Although the number of melanocytes is the same among
the races, pigmented skin has more labile melanocytes, and
thus dyspigmentation is a common concern.2 In fact, melasma
(Fig. 17.4) and post-inflammatory hyperpigmentation (PIH)
(Fig. 17.5) are the third most common dermatoses seen in
people of color3 and treatments for these conditions often
include a combination of pharmaceuticals, cosmeceuticals
and chemical peel procedures. On the other hand, this increase
in melanin offers photoprotection, which allows less photo-
damage and wrinkles, and when these signs of aging do occur,
they occur later on in life.4 Therefore, cosmetic procedures
such as laser resurfacing are performed less often in skin of
color.
The desire to look younger and achieve healthy skin is
universal and global. Male and female patients with all skin
types seek these cosmetic procedures. They want non-surgical
facial rejuvenation that is less invasive with little or no down-
time. With a greater knowledge of the structural and physio-
logical differences in individuals with pigmented skin and a
greater understanding of potential side effects, cosmetic pro-
cedures in patients of color can be performed safely with
excellent cosmetic outcome and patient satisfaction.
309
 Part 5 Cosmetics

Other Non-
Caucasian
African Asian 4% 2%
American 6%
Hispanic 8%

Caucasian 80%

Figure 17.1:╇ Racial/ethnic distribution of patients undergoing all cosmetic

procedures (surgical and non-surgical) in 2008. (American Society for Aesthetic
Plastic Surgery. Cosmetic surgery national data bank statistics http:// Figure 17.4:╇ Skin phototype V patient with facial melasma.
www.surgery.org/professionals/index.php [Accessed May 30, 2009] or
www.surgery.org/download/2008stats.pdf. [Accessed May 30, 2009].)

2.5

2.0

1.5
Millions

1.0

0.5

0
Botulinum Laser hair Hyaluronic Chemical Laser skin
toxin removal acid fillers peels resurfacing
Figure 17.2:╇ Top five non-surgical cosmetic procedures for all races/ethnicities in
2008. (American Society for Aesthetic Plastic Surgery. Cosmetic surgery national
data bank statistics http://www.surgery.org/professionals/index.php [Accessed May
30, 2009] or www.surgery.org/download/2008stats.pdf. [Accessed May 30, 2009].)

Figure 17.5:╇ Patient with post-inflammatory hyperpigmentation secondary to acne

vulgaris.

Figure 17.3:╇ Skin of color patient with hypo- and hyperpigmentation as a result of
laser hair removal.
References
1. American Society for Aesthetic Plastic Surgery. Cosmetic surgery
national data bank statistics. http://www.surgery.org/professionals/
index.php [Accessed May 30, 2009] or www.surgery.org/
download/2008stats.pdf [Accessed May 30, 2009].
2. Taylor SC. Skin of color: biology, structure, function, and implications
for dermatologic disease. J Am Acad Dermatol 2002; 46:S41–S62.
3. Halder RM, Grimes PE, McLaurin CI, Kress MA, Kennedy JA Jr.
Incidence of common dermatoses in a predominately black dermato-
logic practice. Cutis 1983; 32:388–390.
4. Richards GM, Oresajo CO, Halder RM. Structure and function of
ethnic skin and hair. Dermatol Clin 2003; 21:595–600.

310
 17â•… Cosmetic Treatmentsâ•… •â•… Botulinum neurotoxin-A (BoNT-A)

Botulinum neurotoxin- Table 17.1╇ Cosmetic indications for BoNT-A

A (BoNT-A)
Indication Targeted muscle

FDA-approved Glabellar rhytides Procerus, corrugators

Aesthetic treatment with Botulinum neurotoxin type A Hyperhidrosis (axilla)
(BoNT-A) is the most commonly performed non-surgical Off-label Forehead rhytides Frontalis
cosmetic procedure in the United States (US), accounting
Lateral orbital rhytides Orbicularis oculi
for 2.4 million procedures in 2008.1 Currently, there are
(‘crow’s feet’)
two BoNT-A products that are FDA-approved for aesthetic
use in the US Onabotulinumtoxin A (Botox Cosmetic, Lateral brow lift
Allergan, Inc; Irvine, CA) has been approved for cosmetic use Nasal rhytids (‘bunny lines’) Transverse nasalis
since 2002 and abobotulinumtoxinA (Dysport, Medicis Aes- Infraorbital Inferior orbicularis
thetics; Phoenix, AZ) more recently in April 2009. They are oculi
both approved for the temporary improvement of glabellar
rhytides associated with procerus and corrugators muscle Gummy smile Levator labii superioris
activity and onabotulinumtoxin A for axillary hyperhidrosis. Vertical perioral rhytides Orbicularis oris
RimabotulinumtoxinB (Myobloc, Solstice Neurosciences, Inc; (‘smoker’s lines’)
South San Francisco, CA) is not FDA-approved for cosmetic Marionette lines Depressor angularis
use, but is currently used for the treatment of cervical oris
dystonia. Dimpled ‘golf ball’ chin Mentalis
BoNT-A are neurotoxins which are derived from the bacte-
rium Clostridium botulinum. There are seven different serotypes Mental crease
– A, B, Cα, D, E, F and G.2 Of these, only serotypes A and B Horizontal neck rhytids Superficial
are commercially available. BoNT-A exerts its effect by binding musculoaponeurotic
to receptor sites on motor nerve terminals, inhibiting the attachments
release of acetylcholine and blocking the neuromuscular Platysmal bands
motor transmission. Hyperhidrosis (palms, soles,
forehead, etc)

Indications
Table 17.1 lists the approved and unapproved cosmetic indica-
tions for BoNT-A.

Contraindications
The use of botulinum toxin is generally safe in all skin photo-
types; however, a complete medical history is necessary prior
to the procedure to identify contraindications. The procedure
should not be performed if an active skin infection is present
at the proposed injection site. Patients with allergies to the
toxin or any ingredients in the formulation as well as pregnant
or breast-feeding women (category C drug) should avoid
receiving BoNT-A. History of a neuromuscular disease, such as Figure 17.6:╇ ‘X’ denotes the five botulinum toxin injection sites for the glabellar
myasthenia gravis and amyotrophic lateral sclerosis, is a rela- region. The lateral corrugator injections should be placed at least 1╯cm above the
tive contraindication and treatment may exacerbate the disease. bony supraorbital ridge.
Care should also be taken if the patient is already taking a
medication that interferes with neuromuscular transmission, Technique (Fig. 17.6)
such as quinine and aminoglycosides, as these can potentiate
the effects of BoNT-A.3 The clinical use of Botox and Dysport is summarized in Table
In addition, abobotulinumtoxinA may contain trace 17.2. The units of Botox (BU) and Dysport (DU) are different
amounts of cow’s milk protein. Patients with a known and cannot be interchanged. Therefore, no true conversion
allergy to cow’s milk protein should not be treated with this factor exists; however, it has been stated that there is a dose
agent. ratio of 2.5â•›:â•›1 (Dysportâ•›:â•›Botox) for the two agents. The anatomy

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 Part 5 Cosmetics

Table 17.2╇ Cosmetic use of BoNT-A and dysport

Botox Dysport

Number of units/vial 100 BU 300 DU

Dilution 2.5╯mL 0.9% saline 1.5╯mL or 2.5╯mL
0.9% saline
Glabellar complex 4 BU (0.1╯mL) 10 DU (0.05╯mL)
5 sites injected 5 sites injected
20 BU total 50 DU total
Lateral brow lift 3–5 BU 6–12.5 DU
Forehead 12–20 BU 20–50 DU
Crow’s feet 2–5 BU 10 DU A
2–3 sites injected 2–3 sites injected
10–18 BU/side 20–30 DU/side
Bunny lines 2–4 BU 4–10 DU
Marionette lines 2–5 BU 4–12.5 DU
Perioral rhytides 1–4 BU 2–10 DU
Gummy smile 2–5 BU 4–10 DU
Dimpled chin, Mental 3–5 BU 6–12.5 DU
crease
Horizontal neck lines 1–2 BU 2–5 DU
5–10 BU/band 10–25 DU/band
10–20 BU total 20–50 DU total
Onset of action 5–7 days 3 days
Duration 4 months up to 4 months
Eyelid ptosis 2% B
Brow Ptosis less than 5% less than 5%
Figure 17.7:╇ Skin of color patient before (A) and after (B) injection of botulinum
Pregnancy category C C
toxin A into the glabellar region.
From Hexsel DM, Hexsel CL, Brunetto LT. Botulinum Toxin. In:Grimes, PE Ed.
Aesthetics and Cosmetic Surgery for Darker Skin Types. Philadelphia, PA: Lippincott
Williams & Wilkins. 2008:211–224. mally 1–2╯cm apart. Results are expected in 2–4 days and the
duration of effect can last up to 12 months.
and size of the muscle varies between patients and this will BoNT-A can also be used to treat palmar hyperhidrosis.
affect the location of the injection site and dosing. Anesthesia is recommended and consists of topical anesthetic
under occlusion; regional block of the median, ulnar and
Onabotulinumtoxin A radial nerves; ice application; and high intensity vibration. The
Botox Cosmetic is supplied in a sterile vial containing 100╯U injection technique is similar to the axilla; however, a dose of
of a vacuum-dried powder. It is reconstituted with an average 2–3 BU is used and spaced approximately 1–2╯cm apart. The
volume of 2.5╯mL of preservative-free4 or benzyl alcohol pre- results last from 6 to 12 months.
served (bacteriostatic) 0.9% sodium chloride solution. This
results in a solution containing 4U per 0.1╯mL. It is injected Abobotulinumtoxin A
into the belly of the active muscle in small amounts or units Dysport comes in a sterile 300 unit vial and is reconstituted
with a tuberculin or diabetic insulin syringe and a 30 gauge with 1.5╯mL of 0.9% sodium chloride preservative-free saline
needle. Results are usually seen within 3–5 days and peak in solution5 or benzyl alcohol preserved (bacteriostatic) normal
1–3 weeks. The duration varies from 3 to 6 months. saline (0.9%) to yield a solution of 10 DU per 0.05╯mL.
For the treatment of axillary hyperhidrosis with BoNT-A, Dysport can also be reconstituted with 2.5╯mL to yield a solu-
the recommended dilution is with 5╯mL of saline solution and tion of 10 DU per 0.08╯mL. Clinical studies have demonstrated
a total of 2.5╯mL (50 BU) is injected into each axilla with a a faster onset of action (3 days) with Dysport and a slightly
30╯g needle. Topical anesthesia can be used prior to the pro- wider field of effect, without an increase in adverse effects. The
cedure. The dose used is 2.5–4.0 BU and is placed intrader- duration of the two agents is similar (Figs. 17.7 & 17.8).

312
 17â•… Cosmetic Treatmentsâ•… •â•… Botulinum neurotoxin-A (BoNT-A)

A multicenter, double-blind, randomized, placebo-

controlled study of the efficacy and safety of botulinum
toxin type A in the treatment of glabellar lines. Carruther JA,
Lowe NJ, Menter MA, Gibson J, Nordquist M, Mordaunt J,
et╯al. J Am Acad Dermatol 2002; 46:840–849.
This is a prospective, randomized, double-blind, placebo-
controlled clinical trial of 262 patients to determine the effi-
cacy of BoNT-A in the treatment of moderate to severe glabellar
lines. Forty-one patients (16%) were racial/ethnic minorities.
Patients received intramuscular injections of 20╯U BoNT-A or
placebo into five glabellar sites. There was a significant reduc-
tion in glabellar line severity in the BoNT-A treatment group
compared with placebo (all measures, every follow-up visit;
p < 0.02). The treatment effect was maintained through day
120. Blepharoptosis occurred in 5.4% of BoNT-A patients.

A four-month randomized, double-blind evaluation of the

efficacy of botulinum toxin type A for the treatment of gla-
bellar lines in women with skin types V and VI. Grimes PE,
Shabazz D. Dermatol Surg 2009; 35:429–436.
Thirty-one African-American patients (Fitzpatrick skin types
A V and VI) with glabellar lines were treated with BoNT-A in this
randomized, double-blind clinical trial. Patients received
either 20╯U or 30╯U of BoNT-A into five glabellar sites. There
were no significant differences in the percentage of responders
at maximum frown between the two groups. Treatment effects
seemed to persist longer with 30╯U; however, the results were
not statistically significant. Side effects included tingling, mild
headache, and dull sensation.

An open-label, randomized, 64-week study repeating 10-

and 20-U doses of botulinum toxin type A for treatment of
glabellar lines in Japanese subjects. Kawashima M, Harii K.
Int J Dermatol 2009; 48:768–776.
This is a randomized, open-label study of 363 patients to
determine the efficacy of BoNT-A in the treatment of glabellar
lines in Japanese patients. Patients were treated with either
10╯U or 20╯U of BoNT-A for up to five treatments. Treatment
duration (p < 0.001) and subjective improvement (p < 0.05)
were higher in the 20╯U BoNT-A treatment group.

Evaluation of variable-dose treatment with a new U.S. botu-

linum toxin type A (dysport) for correction of moderate to
B severe glabellar lines: results from a phase iii, randomized,
double-blind, placebo-controlled study. Kane MA, Brandt F,
Figure 17.8:╇ Fitzpatrick skin type VI patient before (A) and after (B) Botox Rohrich RJ, Narins RS, Monheit GD, Huber MB, et╯al. Plast
injections into the frontalis muscle for horizontal forehead lines. Reconst Surg 2009; 124:1619–1629.
This is a Phase III, randomized, double-blind, placebo-
controlled study of 816 patients to determine the safety and
efficacy of dysport in the treatment of glabellar lines. The study
Efficacy and Results included 274 patients (33.5%) with Fitzpatrick skin types IV
to VI. Patients were randomized to either treatment with
Dysport or placebo. A single injection of Dysport was admin-
Glabellar brow furrow A
istered in a total volume of 0.4–0.6╯mL for women (50, 60, or
Horizontal frontalis forehead lines B 70 units) and 0.5–0.7╯mL for men (60, 70, or 80 units), based
Periocular crow’s feet A on procerus/corrugator muscle mass at five specific sites in the
Hyperhidrosis A glabellar region. At 1 month, 85% and 87% of Dysport-treated
patients were responders as assessed by blinded evaluator and

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 Part 5 Cosmetics
patient self-evaluation, respectively, compared with 3% and
5% of placebo-treated patients, respectively (p < 0.001).
Median duration of effect was 109 days for Dysport and 0 days
for placebo as assessed by a blinded evaluator. Response and
duration of action (117 days) were slightly higher in African-
American patients. The response rate at day 90 after treatment
was 70% for African-American subjects compared to 57% for
the whole Dysport-treated cohort.
Effect of botulinum toxin A on facial wrinkle lines in
Koreans. Lew H, Yun YS, Lee SY, Kim SJ. Ophthalmologica
2002; 216:50–54.
Twenty Korean patients with facial wrinkles were treated
with BoNT-A. Treatment sites included the glabellar, forehead,
and lateral canthus regions. The mean corrective effect follow-
ing treatment was 70% for at least 3 months post-treatment.
Side effects included tingling, edema, and lagophthalmos.
Bilateral, double-blind, randomized, comparison of three
doses of botulinum toxin type A and placebo in patients
with crow’s feet. Lowe NJ, Lask G, Yamauchi P, Moore D. J Am
Acad Dermatol 2002; 47:834–840.
This is a randomized, double-blind, split-face, placebo-
control trial of 60 patients to determine the efficacy of BoNT-A
in the treatment of crow’s feet. Twenty-three patients (38%)
were racial/ethnic minorities. Patients were treated with either
6, 12, or 18╯U of BoNT-A in the orbicularis oculi muscle on
one side of the face and placebo in the same muscle on the
contralateral side. All doses produced significantly higher
success rates than placebo at all time points (p < 0.03);
however, there were no significant differences among the three
BoNT-A treatment groups. The most common side effect was
bruising.
Botulinum toxin type A in the treatment of primary axillary
hyperhydrosis: a 52-week multicenter double-blind, rando�
mized, placebo-controlled study of efficacy and safety. Lowe
NJ, Glaser DA, Eadie N, Daggett S, Kowalski JW, Lai PY, et╯al.
J Am Acad Dermatol 2007; 56:604–611.
This is a randomized, double-blind, placebo-controlled
study of 252 patients with axillary hyperhidrosis to determine
the safety and efficacy of BoNT-A. Forty-nine patients (19.4%)
were racial/ethnic minorities. Patients were randomized into
treatment groups with either 50╯U BoNT-A, 75╯U BoNT-A, or
placebo for two treatments. Patients received the same treat-
ment under both arms. The percentage of responders was
significantly higher in the two treatment groups than in the
placebo group (p < 0.001). Patients in the BoNT-A treatment
groups also showed a significant improvement in the Hyper-
hidrosis Disease Severity Scale over placebo (p < 0.001).
Complications
In general, treatment with BoNT-A is a relatively safe cosmetic
procedure. Side effects usually occur as a result of injection of
314
the incorrect site or injection of large or high doses leading to
unintended paralysis of surrounding muscles. However, most
side effects are typically mild and transient, and can include
local skin reactions such as erythema, swelling, and bruising.
Some patients have also reported mild flu-like symptoms or
headache after the procedure.6
Eyelid and brow ptosis is an upper face complication that
a small percentage of patients might experience. The rate of
eyelid ptosis with Dysport is approximately 2.1%. However,
symptoms usually resolve within 2–4 weeks. If treatment is
required, Muller’s muscle can be stimulated to elevate the
eyebrow by alpha-adrenergic agonists – brimonidine tartrate
(Alphagan P, Allergan), 0.5% iopidine eye drops, apracloni-
dine 0.5% or phenylephrine 2–3 times per day.6,7 To help
reduce the risk of ptosis, it is important to inject a minimally
dilute solution 1╯cm or more above the brow and educate the
patient regarding proper postinjection care (i.e. remaining
upright for 6 hours without manipulating the injection site).
Diplopia can also result from unintended paralysis of the
upper eyelid levator or extraocular muscles. Patients can also
experience total paralysis of the frontalis muscle leading to an
expressionless appearance.3 Patients can appear to have exces-
sive elevation of the lateral eyebrow if only glabellar wrinkles
are treated without treating the frontalis muscle. Corneal
damage and dry eye can result if the lower eyelid is paralyzed
while treating crow’s feet.
Paralysis of perioral muscles is the most common mid- to
lower face complication.3 Patients can experience difficulties
with speaking, mastication, and swallowing as well as an
asymmetric smile. In Asia, the masseter muscle is injected with
toxin in an attempt to slim the face and this can lead also dif-
ficulties with mastication.6
Other complications include overparalysis of the platysma
leading to dysphagia and problems moving the neck as well
as weakness in the muscles of the hand after treatment for
hyperhidrosis.6
References
1. American Society for Aesthetic Plastic Surgery. Cosmetic surgery
national data bank statistics. http://www.surgery.org/professionals/
index.php [Accessed May 30, 2009] or www.surgery.org/
download/2008stats.pdf [Accessed May 30, 2009].
2. Callender VD, Young CM. Cosmetic procedures in skin of color: chem-
ical peels, mircrodermabrasion, hair transplantation, augmentation,
and sclerotherapy. In: Kelly AP, Taylor SC. Dermatology for skin of
color. New York, NY: McGraw Hill; 2009:513–528.
3. Hexsel DM, Hexsel CL, Brunetto LT. Botulinum toxin. In: Grimes PE,
ed. Aesthetics and cosmetic surgery for darker skin types. Philadelphia,
PA: Lippincott Williams & Wilkins; 2008:211–224.
4. Botox Cosmetic (package insert). Allergan, Inc., Irvine, CA.
5. Dysport (package insert). Medicis, Inc., Scottsdale, AZ.
6. Chan HH, Huh C. Potential adverse effects after procedures in ethnic
skin. In: Alam M, Bhatia AC, Kundu RV, et al, eds. Cosmetic
dermatology for skin of color. New York, NY: McGraw Hill; 2009:
16–25.
7. Pena MA, Alam M, Yoo SS. Complications with the use of botulinum
toxin A for cosmetic application and hyperhidrosis. Semin Cutan Med
Surg 2007; 26:29–33.

Chemical peels
Chemical peeling is the fourth most common non-surgical
cosmetic procedure performed in the United States.1 Patients
with skin of color typically undergo superficial or medium-
depth chemical peels. The most common indications include
dyschromias, such as post-inflammatory hyperpigmentation
(PIH) and melasma, acne vulgaris, acne scars, and rhytids.2
This procedure involves one or more peeling agents that are
applied to the skin for the purpose of exfoliating the epidermis
or dermis. The goal is to create a superficial wound that sub-
sequently re-epithelializes over several days.2 Deep chemical
peels are not recommended in darker skin types and are
seldom used, mainly due to the increased risk of dyspigmenta-
tion, hypertrophic scarring and keloid formation.3
Ethnic groups with Fitzpatrick skin types IV–VI may vary in
their response to chemical peeling and thus, the selection of
the peeling agent must be done with caution. A detailed
history, including ethnicity, dermatological conditions, current
oral and topical medications used, past reactions to other
cosmetic procedures, and a skin examination should be
obtained prior to performing a chemical peel procedure.
Indications
Two of the most common dermatologic conditions seen in
ethnic skin are acne vulgaris and pigmentary disorders includ-
ing PIH and melasma.4 PIH is an acquired excess of pigment
in the epidermis or dermis secondary to an inflammatory
process like acne vulgaris.5 Melasma is also an acquired hyper-
melanosis of unknown etiology, although genetic factors and
UV radiation exposure are thought to be important contribut-
ing factors.5 Melasma can be classified into epidermal-, mixed-,
or dermal-type. Typically, the superficial facial dermatoses
including acne, PIH, and melasma (epidermal-type) respond
well to superficial salicylic acid and glycolic acid peels.6
Conditions with dermal pigment deposition might
respond better to deeper chemical peels but a balance exists
between efficacy and adverse events. Other indications for
chemical peeling procedures include photoaging, rhytids, and
acne scars.2
Contraindications
Although there are few contraindications to most chemical
peels, it is important to obtain a thorough medical history
from the patient prior to the initial peel. General contraindica-
tions include active bacterial or viral infection, particularly
those with herpes simplex infection, atopic dermatitis, sun-
burned skin, delayed wound healing, history of keloidal or
other scarring, and salicylate allergy.2,7,8 Chemical peeling
should also be avoided in patients with inflammatory rosacea,
isotretinoin use within one year, and those who are pregnant
or breast-feeding.2,7,8
17â•… Cosmetic Treatmentsâ•… •â•… Chemical peels
Table 17.3╇ Superficial chemical peels in skin of color
Glycolic acid (GA)
Polyhydroxy acid (PHA)
Salicylic acid (SA)
Trichloroacetic acid (TCA)
Tretinoin
Jessner’s solution
Types of chemical peels
Superficial chemical peels
Superficial chemical peels (Table 17.3) penetrate the stratum
corneum into the papillary dermis.7 These peels are commonly
used in patients with darker skin tones because they are gener-
ally well tolerated with proven results in common dermato-
logic conditions including acne vulgaris, PIH, melasma, and
photoaging. Various types of chemical peels are discussed
below.
Glycolic acid (GA), found in sugarcane, is part of a family
of naturally occurring acids called alpha-hydroxy acids (AHA).7
GA works by inducing epidermolysis, disperses basal layer
melanin, and increases dermal collagen synthesis.9 Chemical
peeling with GA utilizes strengths ranging from 20% to 70%.
Neutralization with water or sodium bicarbonate is required
to terminate the peel.
Polyhydroxy acids (PHAs), including gluconolactone and
lactobionic acids, are a new generation of AHAs that provide
similar efficacy to older generation AHAs but are less irritating
and therefore can be used on sensitive skin.10 PHAs can be
used to treat acne and photoaging in all skin types.
Salicylic acid (SA), derived from willow tree bark, is a type
of beta-hydroxy acid.7 Its mechanism of action involves kera-
tolysis caused by disruption of intercellular lipid linkages
between epithelioid cells.5 Its lipophilic nature allows it to
penetrate into comedones. Efficacy in the treatment of acne in
dark-skinned patients has been demonstrated.11 Superficial SA
peels are usually performed with strengths ranging from 20%
to 30%. Neutralization is not required.
Trichloroacetic acid (TCA) has traditionally been known as
the gold standard for superficial chemical peels in terms of
efficacy. TCA causes cell necrosis by precipitating epidermal
proteins at strengths from 10% to 30% leading to a superficial
peel.7 Medium-depth TCA peels use concentrations of 35% or
greater.
Tretinoin has been shown to cause a decrease in stratum
corneum thickness while increasing epidermal thickness
causing an improvement in skin texture and appearance.2 One
study12 found tretinoin peels to be as effective as and less
irritating than a more commonly used superficial chemical
peel; however, it is important to note that the tretinoin peel
remained in contact with the skin for 4 hours versus a few
minutes with the other peel.
Jessner’s solution is a combination superficial chemical
peel containing 14╯g resorcinol (depigmenting agent), 14╯g
315
 Part 5 Cosmetics
Table 17.4╇ Medium-depth chemical peels in skin of color
TCA 35%–40%
Jessner’s solution + TCA 35%
GA 70% + TCA 35%
salicylic acid (BHA), 14╯g lactic acid (AHA) in 95% ethanol.
Jessner’s solution causes keratolysis by decreasing corneocyte
cohesion and was formulated as a combination peel to
decrease the concentration of any one component used in the
solution, thereby decreasing risk for side effects.2 The combi-
nation of the keratolytic components also produces a syner-
gistic effect.7 When using Jessner’s solution, exercise caution as
a study has shown increased exfoliation when compared to
other superficial chemical peeling agent.13
Medium-depth chemical peels
Medium-depth chemical peels (Table 17.4) penetrate the
stratum corneum and epidermis and exert their effect in the
upper reticular dermis.3 Indications for medium-depth peels
include dyschromias such as mixed- or dermal-type melasma,
photoaging, and acne scars. TCA can be used as a superficial
chemical peel or a medium-depth peel depending upon the
concentration of the solution used. Concentrations of 35–
40% will produce a medium-depth peel; however, exercise
caution when using 35% TCA or greater as this concentration
is thought to be melanotoxic and could lead to dyschromias.8
Multiple combination peels have been used to produce
medium-depth peels including Jessner’s solution or 70% gly-
colic acid followed by 35% TCA. The two peels are applied
sequentially with the thought that the initial application
causes a superficial peel by keratolysis and penetration through
the epidermis, allowing the following peel to penetrate more
deeply.14 88% phenol solution is also used for medium-depth
peels. However, due to its side effect profile including cardiac
and renal toxicity, this solution is generally not used as there
are other peels which are safe and effective.3
Deep chemical peels
Deep chemical peels, like Baker’s phenol, penetrate the stratum
corneum to the mid-reticular dermis and are usually reserved
for severely photoaged skin.15 However, these peels are mela-
notoxic and have an increased risk of dyspigmentation, hyper-
trophic scarring and keloid formation in Fitzpatrick skin types
IV–VI.3 Therefore, deep chemical peels are generally not per-
formed on dark-skinned patients. In addition, these solutions
have serious side effects including cardiac and renal toxicity
and also require the patient to be under heavy sedation or
general anesthesia for the peeling procedure.3
Technique
Peeling procedures are performed either alone or in combina-
tion with topical preparations, such as hydroquinone, topical
retinoids and various cosmeceuticals. A skin test is recom-
316
Figure 17.9:╇ Focal treatment of facial acne scars with 30% trichloroacetic acid.
Note the frosting indicating the end point of the peel.
mended for first-time patients, and as a general rule, it is best
to start with a lower concentration and titrate upward. The
frequency of application varies in general and can be per-
formed every 2–4 weeks.
Pre-peel preparation
Three to five days prior to the procedure, the patient should
be instructed to discontinue all topical retinoids and other
exfoliants. For glycolic acid and salicylic acid peels, this time
frame should be one week prior to the peel. Patients with
a positive history of herpes simplex infection should receive
oral prophylactic antiviral therapy (acyclovir, famcyclovir,
valcyclovir).9 The skin is cleansed with a gentle cleanser
to remove any makeup then the skin can be degreased
with 70% isopropyl alcohol or acetone. Apply petrolatum to
all sensitive areas including the corners of the eyes, lips,
and nasolabial folds to protect them from contact with the
chemical peeling agent.
Peel procedure
Using a sponge, gauze, or cotton-tipped applicator, apply the
peeling agent evenly across the face avoiding overlap. Spot
treatment of acne scars with TCA may produce frosting within
the treated area (Fig. 17.9). The patient may begin to experi-
ence a burning sensation; however, a hand-held fan can be
used to minimize this discomfort. A timer is useful for moni-
toring the duration of the peel. After the allotted time, glycolic
acid peels must be neutralized with water or a sodium bicar-
bonate solution; however, neutralization is not necessary with
most other peeling agents. A timer is useful for monitoring the
duration of the peel.
Post-peel care
After the skin is thoroughly cleansed of the peeling agent,
apply a bland emollient such as Aquaphor, Vaseline, or Biafine.
If the patient exhibits intense facial erythema, a topical
corticosteroid can be applied to the affected area. Finally,

a sunblock is applied to the skin and patient education on the
importance of sun protection should be given.
Efficacy & Results
Acne vulgaris B
Melasma B Excellent clinical results with a new preparation for chemi-
PIH B cal peeling in acne: 30% salicylic acid in polyethylene glycol
Acne scars B vehicle. Dainichi T, Ueda S, Imayama S, Furue M. Dermatol
Rhytids B
Acne vulgaris
Glycolic acid peels versus salicylic-mandelic acid peels in
active acne vulgaris and post-acne scarring and hyperpig-
mentation: a comparative study. Garg VK, Sinha S, Sarkar R.
Dermatol Surg 2009; 35(1):59–65.
Forty-four Indian patients with Fitzpatrick skin types IV to
VI with acne vulgaris, acne scarring, and post-inflammatory
hyperpigmentation (PIH) were treated with a series of six
peels at 2-week intervals. The patients were divided into two
groups: one group received 35% glycolic acid peels and the
other group 20% salicylic acid-10% mandelic acid (SMA)
peels. Although both agents produced statistically significant
improvements in inflammatory and non-inflammatory acne
lesions and PIH, the authors found a more rapid and greater
response in patients treated with SMA peels. There was minimal
improvement in acne scars. Dryness was more common with
SMA peels.
Glycolic acid versus Jessner’s solution: which is better for
facial acne patients? A randomized prospective clinical trial
of split-face model therapy. Kim SW, Moon SE, Kim JA, Eun
HC. Dermatol Surg 1999; 25(4):270–273.
Twenty-six Korean patients (Fitzpatrick skin type III and IV)
with mild to moderate acne were treated with a series of three
Jessner’s peels on one side of the face and 70% glycolic acid
peels on the contralateral side performed every 2 weeks. After
the final treatment, both sides showed improvement in the
acne grade score; however, there was no statistically significant
difference between the peels. Side effects included erythema,
acute eczema (on the glycolic acid side), and exfoliation,
which was noted to persist longer after the Jessner’s peel
(p < 0.01). Although both peels were noted to have equal
treatment effect, the authors recommended glycolic acid peels
over Jessner’s peel because of less exfoliation.
The effect of glycolic acid on the treatment of acne in Asian
skin. Wang CM, Huang CL, Hu CT, Chan HL. Dermatol Surg
1997; 23(1):23–29.
Forty Asian patients with moderate to moderately severe
acne and Fitzpatrick skin type IV were pretreated with a 15%
glycolic acid home product for one week followed by a series
of four glycolic acid peels. Patients with less facial oil received
35% glycolic acid peels while those with more facial oil
received 50% glycolic acid peels. There was a significant reduc-
17â•… Cosmetic Treatmentsâ•… •â•… Chemical peels
tion in the number of comedones, papules, and pustules as
well as improvement in skin texture and appearance, and
smaller pore size. Improvement in acne scars and cystic lesions
was less obvious. Only 5.6% of patients developed side effects
including post-inflammatory hyperpigmentation, mild local
herpes simplex infection, and mild skin irritation.
Surg 2008; 34:891–899.
A clinical study designed to evaluate the safety and efficacy
of a new formulation of 30% salicylic acid in polyethylene
glycol vehicle (SA-PEG) using mice and patients with acne and
photoaging. In the 44 patients with photoaging, 98% experi-
enced an improvement in skin texture, elasticity, and appear-
ance while skin barrier function remained intact. Of the 436
acne patients treated with SA-PEG peels, 42 patients com-
pleted a survey on adverse effects and perceived efficacy. There
was improvement in non-inflammatory and inflammatory
acne lesions and no patients complained of pain or burning
sensation during or after the peel. SA-PEG was also applied to
the skin of mice and subsequent histological exams showed
no inflammatory changes. PEG has a high affinity for SA;
therefore, a small amount of SA is released into the epidermis
accounting for the lack of burning and pain with application
of the peel. The authors concluded that SA-PEG is ideal for
chemical peeling in patients with skin of color, who are at
increased risk of developing post-peel hyperpigmentation,
given its safety and efficacy in photoaged skin and acne, and
minimal side effects.
Salicylic acid peels in polyethylene glycol vehicle for the
treatment of comedogenic acne in Japanese patients.
Hashimoto Y, Suga Y, Mizuno Y, Hasegawa T, Matsuba S, Ikeda
S, et╯al. Dermatol Surg 2008; 34:276–279.
Sixteen Japanese patients with comedogenic acne were
treated with a series of five 30% salicylic acid in polyethylene
glycol vehicle (SA-PEG) at 2-week intervals. There was a 75%
reduction (paired Student’s t-test, p = 0.001) in the comedone
count from baseline to the endpoint of the study and improve-
ment in the comedogenic acne severity grade in all patients.
Mild burning and erythema were noted in 3 patients during
the procedure but all symptoms resolved upon removal of the
peeling agent and application of an emollient.
Salicylic acid peels for the treatment of acne vulgaris in
Asian patients. Lee HS, Kim IH. Dermatol Surg 2003;
29(12):1196–1199.
Single-blind, non-controlled trial conducted on 35 Korean
patients (Fitzpatrick skin types III and IV) with mild to
moderate facial acne. All patients were treated with a series of
five 30% salicylic acid peels biweekly. The authors found
a significant reduction in both inflammatory and non-
inflammatory acne lesions. Over the course of the study, the
mean acne grade reduction was 1.29 (p < 0.01). Based on pre-
peel and multiple post-peel measures of stratum corneum
hydration, skin surface lipids, skin pH, and transepidermal
317
 Part 5 Cosmetics
water loss, skin barrier function was found to be uncompro-
mised by repeated peels. The most common side effect was
dryness but erythema, scaling, burning sensation, and crusting
were also noted.
The safety and efficacy of salicylic acid peels in darker racial-
ethnic groups. Grimes PE. Dermatol Surg 1999; 25(1):
18–22.
Twenty-five African-American and Hispanic patients with
Fitzpatrick skin types V and VI with acne (9), melasma (6),
post-inflammatory hyperpigmentation (PIH) (5), oily skin,
enlarged pores, and rough textural changes (5) underwent a
series of five salicylic acid peels (20% to 30%) at 2-week inter-
vals. Eighty-eight percent of patients experienced moderate to
significant improvement. There was a rapid resolution of
papules, pustules, and comedones in acne patients. All of the
patients with oily skin, enlarged pores, and rough textural
changes showed improvement. Moderate to significant
improvement occurred in 100% of patients with PIH and
66% of patients with melasma. Side effects were mild and
transient.
Melasma
Comparative evaluation of beneficiary effects of priming
agents (2% hydroquinone and 0.025% retinoic acid) in the
treatment of melasma with glycolic acid peels. Garg VK,
Sarkar R, Agarwal R. Dermatol Surg 2008; 34(8):1032–1039.
Discussion 1340.
Single-blind, randomized study of 50 Indian patients
(mostly Fitzpatrick skin type IV and V) with melasma. Patients
were randomized into three groups: Group I received glycolic
acid (GA) peels alone, Group II was primed with 0.025%
tretinoin followed by serial GA peels, and Group III was
primed with 2% hydroquinone then serial GA peels also.
Groups II and III also used the topical agents as a maintenance
regimen. GA peels were started at 20% concentration then
titrated up and occurred every 2 weeks for 3 months then once
a month for 3 months. There was a significant reduction in the
Melasma Area and Severity Index (MASI) from baseline to
endpoint for Groups II and III (p < 0.01). The peels-only group
had a significant reduction in MASI at 3 and 6 months but not
at the endpoint, 9 months. There was also a significant differ-
ence between Group III versus Groups I and II. Patients primed
with hydroquinone had greater improvement of their melasma
than all other patients. In addition, this group had the smallest
incidence of PIH.
The combination of glycolic acid peels with a topical
regimen in the treatment of melasma in dark-skinned
patients: a comparative study. Sakar R, Kaur C, Bhalla M,
Kanwar AJ. Dermatol Surg 2002; 28(9):828–832.
Forty Indian patients (Fitzpatrick skin types III–V) with
moderate to severe epidermal melasma were divided into two
groups. One group was only treated with modified Kligman’s
formula (0.05% tretinoin cream, 2% hydroquinone, and 1%
hydrocortisone cream) and the other group was treated with
a series of six glycolic acid peels (30–40%) at 3-week intervals
318
in addition to a modified Kligman’s formula as a daily main-
tenance regimen. The study found a significant reduction in
the MASI from baseline to 21 weeks in both treatment groups
(p < 0.001); however, the group receiving the peels saw a more
rapid and greater overall response (p < 0.001). Side effects were
more common in the peel group and included superficial
desquamation and vesiculation, herpes labialis, acneiform
eruptions, and erythema.
Safety and efficacy of glycolic acid facial peel in Indian
women with melasma. Javaheri SM, Handa S, Kaur I, Kumar
B. Int J Dermatol 2001; 40(5):354–357.
Twenty-three Indian patients with epidermal, mixed, and
dermal-type melasma and MASI of 15 or greater were treated
with a prepeel regimen of 10% glycolic acid lotion for 2 weeks
followed by 50% glycolic acid peels monthly for 3 months.
There was a significant reduction in MASI in 21 patients
(p < 0.01); however, a greater overall response was seen in
patients with epidermal-type melasma in comparison to
those with mixed-type (p < 0.05). No response to treatment
was seen in the one patient with dermal-type melasma. The
only side effect noted was mild, transient post-inflammatory
hyperpigmentation.
Glycolic acid peels in the treatment of melasma among
Asian women. Lim JT, Tham SN. Dermatol Surg 1997;
23(3):177–179.
Single-blind, right/left comparison study in which 10 Asian
patients (Fitzpatrick skin type IV and V) with moderate to
severe melasma were treated on both sides of the face with
10% glycolic acid and 2% hydroquinone cream followed by a
series of eight glycolic acid peels to only one side of the face
at 3-week intervals. The first peel was started at 20% then
titrated up to 70% in subsequent peels. The side of the face
receiving the peels had notable clinical improvement in the
melasma as well as fine wrinkling; however, the results were
not statistically significant. Side effects were transient hyper-
pigmentation, erythema, and burning sensation.
Tretinoin peels versus glycolic acid peels in the treatment
of melasma in dark-skinned patients. Khunger N, Sarkar R,
Jain RK. Dermatol Surg 2004; 30(5):756–760.
Prospective, split-face pilot study was conducted with 10
Indian women (Fitzpatrick skin types III–V) with moderate to
severe melasma. Tretinoin 1% peels were applied to one side
of the face and 70% glycolic acid peels were applied to the
contralateral side weekly for 12 weeks. There was a highly
statistically significant (p < 0.001) decrease in the modified
MASI from baseline to 6 weeks and from 6 weeks to 12 weeks
for both sides of the face. However, there was no difference
between the two sides. More side effects were noted on the
glycolic acid-treated side including erythema, superficial
desquamation, burning sensation, vesiculation, and post-
inflammatory hyperpigmentation. Side effects for the tretinoin
peel group were erythema and superficial desquamation.
Treatment of melasma with Jessner’s solution versus gly-
colic acid: a comparison of clinical efficacy and evaluation

of the predictive ability of Wood’s light examination.
Lawrence N, Cox SE, Brody HJ. J Am Acad Dermatol 1997;
36:589–593.
Sixteen patients (14 patients were Fitzpatrick skin types
III–VI) with melasma were pretreated with 0.05% tretinoin
followed by 1–3 chemical peels 1 month apart. Glycolic acid
70% was applied to one side of the face and Jessner’s solution
to the contralateral side. Tretinoin and hydroquinone were
used between peels. Colorimetric analysis (GA, p = 0.0031 and
Jessner’s, p = 0.0471) and average MASI (p = 0.0005) score
showed a significant improvement in melasma on both sides
of the face from baseline to the endpoint; however, there was
no difference between the two sides. Side effects only occurred
on the glycolic acid-treated side which included PIH,
crusting, persistent erythema, and extensive epidermolysis.
The authors also evaluated the ability of Wood’s light exam
to predict clinical response to treatment but they found no
correlation.
Combined trichloroacetic acid peel and topical ascorbic
acid versus trichloroacetic acid peel alone in the treatment
of melasma: a comparative study. Soliman MM, Ramadan
SA, Bassiouny DA, Abdelmalek M. J Cosmet Dermatol 2007;
6(2):89–94.
Thirty patients with Fitzpatrick skin types III and IV and
epidermal melasma were divided into two groups and treated
with 4–6 courses of 20% trichloroacetic acid (TCA) peels once
weekly. Both groups were primed with 0.05% tretinoin and
4% hydroquinone for 2 weeks prior to the initial peel. However,
Group B also used 5% ascorbic acid daily. There was noted
improvement in the MASI from baseline to the endpoint (16-
week follow-up) for both groups; however, Group B patients
using ascorbic acid had significantly better improvement in
MASI after the peel (p < 0.001) and at 16-weeks follow-up
(p < 0.003). Side effects were mild.
Post-inflammatory hyperpigmentation
Glycolic acid peels for post-inflammatory hyperpigmenta-
tion in black patients: a comparative study. Burns RL,
Prevost-Blank PL, Lawry MA, Lawry TB, Faria DT, Fivenson DP.
Dermatol Surg 1997; 23(3):171–174.
Sixteen African-American patients with Fitzpatrick skin
types IV–VI and facial post-inflammatory hyperpigmentation
were randomized to two groups. The control group was treated
with 2% hydroquinone/10% glycolic acid gel and 0.05%
tretinoin and the peel group was treated with the same topical
regimen in addition to a series of six glycolic acid peels (50–
68%) at 3-week intervals. Significant clinical improvement was
noted in the peel group using the Hyperpigmentation Area
and Severity Index (HASI) (p < 0.02); however, the difference
between the two treatment groups was not statistically signifi-
cant. Colorimetric analysis also showed a trend of more rapid
and greater improvement in the peel group but was of border-
line significance (p < 0.09). Also of note, the authors reported
a greater lightening of background pigmentation in the peel
group. Other side effects were minimal.
17â•… Cosmetic Treatmentsâ•… •â•… Chemical peels
Whitening effect of salicylic acid peels in Asian patients.
Ahn HH, Kim IH. Dermatol Surg 2006; 32(3):372–375.
Twenty-four Korean patients with post-inflammatory hyper-
pigmentation (PIH) from acne underwent 30% salicylic acid
peels every 2 weeks for 3 months. Colorimetric analysis
showed that the level of lightness from baseline to the first
post-peel period was significant (p < 0.02) but final levels were
not. In addition, there was a highly statistically significant
decrease in erythema (p < 0.0001) and clinical improvement
was also noted in greasiness, dryness, scaliness, and erythema
although results were not statistically significant.
Acne scars
Biweekly serial glycolic acid peels vs. long-term daily use of
topical low-strength glycolic acid in the treatment of
atrophic acne scars. Erbagci Z, Akcali C. Int J Dermatol 2000;
39:789–794.
Single-blind, placebo-controlled, randomized comparative
study of 48 patients with atrophic acne scars. Patients were
randomized into three groups: Group A received 20–70% gly-
colic acid (GA) peels bi-weekly, Group B used a home regimen
of 15% GA cream for 24╯weeks, and Group C used a placebo
cream for 24 weeks. There was a significant improvement in
scar severity from week 16 to week 24 for Group A (p < 0.0001)
(after application of 70% GA peels) as well as for Groups B
and C (p < 0.01). However, the investigators attribute this
finding to possible observer bias and there was also a statisti-
cally significant difference between percentage improvement
of Group A over Group B (p < 0.05) and Group B over Group
C (p < 0.05).
Histologic study of depressed acne scars treated with serial
high-concentration (95%) trichloroacetic acid. Yug A, Lane
JE, Howard MS, Kent DE. Dermatol Surg 2006; 32:985–990.
The investigators conducted a small pilot study of 3 patients
(Fitzpatrick skin type III) with acne scars treated with 95%
trichloroacetic acid (TCA) using the chemical reconstruction
of skin scars (CROSS) method. This method involves using a
wooden applicator to serially apply 95% TCA focally and with
pressure to acne scars including deep ‘ice pick’ scars until frost-
ing occurs. Each patient received six treatments at 6-week inter-
vals. There was clinical improvement in the appearance of the
scars. Punch biopsies were performed at the scar sites at base-
line and 1 year after the peel, which showed a decrease in scar
depth, increased collagen production, and fragmentation of
elastin fibers in the papillary dermis. There were no side effects.
Focal treatment of acne scars with trichloroacetic acid: chem-
ical reconstruction of skin scars method. Lee JB, Chung WG,
Kwahck H, Lee KH. Dermatol Surg 2002; 28(11):1017–1021.
Sixty-five patients (Fitzpatrick skin types IV and V) with
atrophic acne scars were divided into two groups and treated
with 3–6 courses of 65% or 100% trichloroacetic acid (TCA)
using the CROSS method. The majority (90%) of patients
experienced a good clinical response to treatment. The inves-
tigators found that improvement was greater in patients treated
with 100% TCA and that clinical improvement correlated with
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 Part 5 Cosmetics
the number of treatments received. This method can be used
to treat all types of deep acne scars. Side effects included mild
erythema, transient PIH, and a pustular eruption. Patients
treated with 100% TCA did not have an increased frequency
of side effects.
Medium-depth chemical peels in the treatment of acne scars
in dark-skinned individuals. Al-Waiz MM, Al-Sharqi AI. Der-
matol Surg 2002; 28(5):383–387.
Fifteen patients with acne scars (atrophic saucer or crater-
like form and pitted or ice-pick form) were treated with a
combination of Jessner’s peel followed by 35% TCA peel. The
majority of patients underwent a series of three peels at
monthly intervals. All but one patient had clinical improve-
ment. There was also greater improvement in patients with
mostly atrophic scars when compared with those with mainly
pitted scars. The majority of patients also developed transient
post-inflammatory hyperpigmentation and few patients devel-
oped persistent erythema.
Rhytids
The efficacy of glycolic acid for treating wrinkles: analysis
of newly developed facial imaging systems equipped with
fluorescent illumination. Funasaka Y, Sato H, Usuki A,
Ohashi A, Kotoya H, Miyamoto K, et╯al. J Dermatol Sci 2001;
27(Suppl 1):S53–S59.
Randomized, split-face comparison study of 97 patients
(Fitzpatrick skin types III and IV) with facial rhytids treated
with a series of four glycolic acid peels (35–70%) to one side
of the face at 2-week intervals. The investigators used computer-
assisted image analysis and found that a reduction in wrinkle
length correlates more closely with a clinically apparent
improvement in wrinkles, although both wrinkle number and
length can impact improvement. The wrinkle number
and length had significantly improved on the GA treated side
(p < 0.05) but there was no significant improvement on the
non-GA treated side or any difference between concentrations
of GA used (35%, 50%, and 70%).
Treatment of periorbital wrinkles by repeated medium-
depth chemical peels in dark-skinned individuals. Kadhim
DA, Al-Waiz M. J Cosmet Dermatol 2005; 4(1):18–22.
Twelve patients with Fitzpatrick skin type IV and V with fine
and/or medium-depth periorbital wrinkles were treated with
a 2-week pre-peel regimen of topical tretinoin, hydroquinone,
and sunscreen followed by 2–4 focal applications of a combi-
nation of Jessner’s peel then 35% trichloroacetic peels to the
periorbital area 1 month apart. All but one patient noted
improvement. The authors noted a 100% response rate of fine
wrinkles to peeling and a 60% response rate of medium wrin-
kles. Lower and upper eyelid fine wrinkles resolved faster and
required fewer peels than crow’s feet. Side effects included
post-inflammatory hyperpigmentation, persistent erythema,
and one patient developed a mild atrophic scar on the lower
eyelid.
320
Complications
Most chemical peeling agents are well tolerated by Fitzpatrick
skin types IV–VI. In general, side effects tend to be mild, tran-
sient, and depend on the depth of the peel and length of
exposure to the peeling agent. Common side effects include
erythema, burning sensation, post-inflammatory hyperpig-
mentation (PIH), reactivation of herpes simplex virus, super-
ficial desquamation and vesiculation.2 Persistent erythema and
transient PIH typically occur with medium-depth peels but can
also be a complication of superficial peels as well. Other com-
plications include hypopigmentation, hypertrophic scarring,
and keloid formation.
References
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brasion. Dermatol Surg 2004; 30:390–394.
10. Grimes PE, Green BA, Wildnauer RH, Edison BL. The use of polyhy-
droxy acids (PHAs) in photoaged skin. Cutis 2004; 73(2 Supp):
3–13.
11. Grimes PE. The safety and efficacy of salicylic acid peels in darker
racial-ethnic groups. Dermatol Surg 1999; 25(1):18–22.
12. Khunger N, Sarkar R, Jain RK. Tretinoin peels versus glycolic acid peels
in the treatment of melasma in dark-skinned patients. Dermatol Surg
2004; 30(5):756–760.
13. Kim SW, Moon SE, Kim JA, Eun HC. Glycolic acid versus Jessner’s
solution: which is better for facial acne patients? A randomized pro-
spective clinical trial of split-face model therapy. Dermatol Surg 1999;
25(4):270–273.
14. Monheit GD. The Jessner’s-trichloroacetic acid peel. An enhanced
medium-depth chemical peel. Dermatol Clin 1995; 13(2):277–283.
15. Bhutani T, Batra SR. Ablative dermal resurfacing in ethnic skin: laser,
deep peels, and dermabrasion. In: Alam M, Bhatia AC, Kundu RV,
et al, ed. Cosmetic dermatology for skin of color. New York,
NY: McGraw Hill; 2009:58–69.
 17â•… Cosmetic Treatmentsâ•… •â•… Fillers

Fillers Contraindications
As with most procedures, a thorough medical history is neces-
All patients regardless of race or ethnicity will experience some sary to identify risk factors for possible complications. A list
degree of facial aging as they grow older. The signs of facial of allergies should be obtained as hypersensitivity reactions,
aging in Caucasians differ from those seen in patients with albeit rare, can occur. For example, Hylaform (Inamed
skin of color. Facial aging in this population takes on a unique Aesthetics/Allergan, Santa Barbara, CA) contains avian pro-
pattern and is primarily localized to the midfacial region. teins from rooster combs, Zyderm (Inamed Aesthetics/
Intrinsic (midfacial) aging in skin of color is manifested by the
descent of malar fat pads, a tear trough deformity, infraorbital
hollowing, and deepening of the nasolabial folds (Fig. 17.10).1
These features are a result of gravity-dependent sagging, volu-
metric loss, and soft tissue and skeletal changes for which soft
tissue augmentation with dermal filler can produce an aes-
thetic improvement (Figs. 17.11, 17.12).

Indications
Treatment decisions are unique and specific for each patient
and should be individualized. There are three facial treatment
zones: (1) upper (glabellar rhytids, crow’s feet, forehead
rhytids and temporal depression), (2) mid (nasolabial folds,
marionette rhytids, hollowing of the cheeks and acne scars),
and (3) lower (lips, perioral vertical rhytids, chin and jowls).
In African-Americans, the lips tend to be larger and fuller, and
thus, lip augmentation is performed less commonly.

B
Figure 17.10:╇ Patient showing midface aging typical for patients with skin of
color. Note the descent of malar fat pads, tear trough deformity, infraorbital Figure 17.11:╇ Patient with skin phototype V before (A) and after (B) soft tissue
hollowing, and deepening of the nasolabial folds. augmentation of the nasolabial folds with Evolence.

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 Part 5 Cosmetics
A
B Many physicians would premix lidocaine into many fillers to
Figure 17.12:╇ African-American patient with skin phototype IV before (A) and
after (B) soft tissue augmentation with a hyaluronic acid filler into the nasolabial
folds. The patient also received filler on the sides of the chin.
Allergan, Santa Barbara, CA) contains lidocaine, and 5% of
patients may experience hypersensitivity to bovine collagen.2
Since injection of dermal fillers has the potential to cause
cutaneous inflammation, it should be used with extreme
caution in patients who have a history of scarring and hyper-
pigmentation. Use of fillers in patients with active infection or
inflammation at the intended injection site should also be
avoided.
FDA-approved agents
Table 17.53,4,5 lists FDA-approved dermal fillers.
Hyaluronic acid
Restylane and Perlane
Hyaluronic acid (HA) fillers, Restylane (Medicis, Scottsdale,
AZ) and Perlane (Medicis, Scottsdale, AZ), are approved by the
322
Food and Drug Administration (FDA) for the treatment
of moderate to severe facial rhytids and continue to be
some of the most widely used and studied (Restylane)
dermal fillers today.6,7 Both Restylane and Perlane are
Streptococcal bacteria-derived dermal fillers each containing
20╯mg/mL of HA and cross-linkage by butane-diol-diglycidyl
ether. However, the gel bead size is significantly larger in
Perlane (1000╯µm, 10╯000 units/mL) than in Restylane
(250╯µm, 100╯000 units/mL).8 Restylane has the advantage of
having a very natural look and feel as well as being easily
moldable. However, neither Restylane nor Perlane requires
skin testing due to their low allergic potentials, and both
fillers are relatively long-lasting (6–12 months).9 Safety with
Restylane and Perlane use has been demonstrated in skin
of color patients.3
Juvederm Ultra and Ultra Plus
Juvederm Ultra and Ultra Plus (Allergan, Irvine, CA) are also
FDA-approved hyaluronic acid fillers derived from Streptococ-
cus equi bacteria for moderate to severe facial wrinkles and
folds.10,11 As with most HA fillers, Juvederm Ultra is single
crossed-linked; however, Juvederm Ultra Plus is double
crossed-linked thereby possibly making it a better volume-
filling agent.9 Neither filler requires skin testing, and treatment
effect typically lasts between 6 and 12 months. Grimes et╯al4
has demonstrated that Juvederm can be safely used in darker-
skinned patients.
Prevelle Silk
Prevelle Silk (Mentor, Santa Barbara, CA) is another FDA-
approved, bacteria-derived HA filler; however, its major advan-
tage is its formulation already containing lidocaine anesthetic.
reduce the pain associated with its injection into the skin. In
the manufacturer’s clinical study,12 45 patients received Prev-
elle Silk in one nasolabial fold and Captique on the contral-
ateral side. Fourteen patients (31%) were Fitzpatrick skin types
IV–VI. Patients evaluated injection site pain at 15-minute
intervals for 1 hour after the injection using a Visual Analog
Scale (VAS). The mean value for all VAS pain assessments were
significantly lower (at least 50% lower) on the Prevelle Silk-
treated side than the Captique-treated side. The majority of
patients (29 of 42: 69%) who completed a questionnaire pre-
ferred Prevelle Silk of which 28 patients (96.6%) preferred
Prevelle Silk because it was less painful. However, treatment
effect is relatively short, lasting between 3 and 6 months.
Calcium hydroxylapatite
Radiesse
Radiesse (BioForm Medical, San Mateo, CA), a synthetic, semi-
permanent calcium hydroxylapatite filler, is FDA-approved for
the treatment of facial rhytids and folds as well as HIV-related
lipoatrophy.13 Once Radiesse is injected into the deep dermis,
it provides a scaffold on which collagenesis occurs. It is best
used as a volume filler for facial folds and soft tissue loss
but should be avoided for the correction of fine wrinkles
or lip augmentation. Radiesse is long-lasting (> 1 year) and
 17â•… Cosmetic Treatmentsâ•… •â•… Fillers

Table 17.5╇ FDA-approved dermal fillers for use in skin of color

Filler Classification Duration of treatment effect Complications Safety in skin of color

Restylane Non-animal-derived Temporary (6–12 months) Allergic reaction or inflammation, Taylor et╯al3
stabilized hyaluronic acid blue discoloration, misplacement,
lumps
Perlane Non-animal-derived Temporary (6–12 months) Allergic reaction or inflammation, Taylor et╯al3
stabilized hyaluronic acid blue discoloration, misplacement,
lumps
Juvederm Non-animal-derived Temporary (6–12 months) Allergic reaction or inflammation, Grimes et╯al4
Ultra stabilized hyaluronic acid blue discoloration, misplacement,
migration, lumps
Juvederm Non-animal-derived Temporary (6–12 months) Allergic reaction or inflammation, Grimes et╯al4
Ultra Plus stabilized hyaluronic acid blue discoloration, misplacement,
migration, lumps
Prevelle Silk Non-animal-derived Temporary (3–6 months) Allergic reaction or inflammation, None
stabilized hyaluronic acid blue discoloration, misplacement,
migration, lumps
Elevess Non-animal-derived Temporary (4–8 months) Allergic reaction or inflammation, None
stabilized hyaluronic acid blue discoloration, misplacement,
migration, lumps
Radiesse Synthetic calcium Semi-permanent (> 1 year) Nodules (especially in lips and Marmur et╯al5
hydroxylapatite periorbitally), misplacement with
demarcation of product
Zyderm, Bovine collagen Temporary (2–4 months) Allergic reaction, misplacement, None
Zyplast lumps
Cosmoderm, Human collagen Temporary (2–4 months) Allergic reaction, misplacement, None
Cosmoplast lumps
Evolence Porcine collagen Temporary (6–12 months) Allergic reaction or inflammation, None
injection site reaction, infection
Sculptra Synthetic poly-L-lactic acid Semi-permanent (> 1 year) Visible and palpable papules, None
Aesthetic injection site reactions

can be used safely with the proper technique in patients with
skin of color.5
To diminish pain associated with intradermal injection
and to enhance patient comfort, Radiesse can easily be mixed
with an anesthetic to provide a comfortable procedure. An
accessory kit is provided by the manufacturer that contains
a luer lock connector and a 3╯mL syringe. In a recent clinical
trial, 90% of patients had significant reduction in pain
when the filler was mixed with lidocaine.14 First, attach the luer
lock connector to the Radiesse syringe. The 3╯mL syringe is
filled with 2% lidocaine in the amount of either 0.02╯mL,
0.12╯mL or 0.26╯mL based on the Radiesse syringe size of
0.3╯mL, 0.8╯mL, or 1.5╯mL, respectively. The Radiesse syringe
is attached to the other end of the luer lock connector. The
lidocaine and the Radiesse are then mixed together by moving
the plungers back and forth, a minimum of 10 mixing passes.
The 3╯mL syringe and luer lock are then removed prior to
treatment and an injection needle is attached to the Radiesse
mixture.
Porcine collagen
Evolence
Evolence (Colbar Life Science, Ltd., Ortho Neutrogena, Morris
Plains, NJ) is composed of porcine collagen that was FDA-
approved in June 2008.15 Its allergic potential has been greatly
diminished by the enzymatic removal of the antigenic
N-terminus of the porcine collagen thereby eliminating the
need for skin testing.9 The collagen in Evolence is cross-linked
to ribose leading to a slower resorption rate and longer dura-
tion of effect.8 Therefore, the treatment effect of Evolence can
range between 6 and 12 months. Recently, Evolence was dis-
continued in the US but is still available in Europe.
Poly-L-lactic acid
Sculptra
Sculptra (Aventis Pharmaceuticals, Bridgewater, NJ), synthetic
poly-L-lactic acid, is used with FDA-approval for HIV-associated

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 Part 5 Cosmetics
lipoatrophy.16 Sculptra has also been used for age-related
volume loss in Europe. Each vial contains a freeze-dried
powder of Sculptra that should be reconstituted in 3–8╯mL of
sterile water and allowed to stand for at least 2 hours prior to
injection. A local anesthestic (1% lidocaine) can also be added
to the solution for pain control. Sculptra should be injected
deeper into the subcutaneous tissue using a 27 gauge needle
in a cross-hatching fashion.8
Volume correction is immediately apparent after injection
but diminishes over time as the aqueous solution is absorbed;
however, the treatment effect is restored after a few months
when the host produces collagen and fibrous tissue in response
to degrading Sculptra particles.9 Multiple treatment sessions
are typically required at 4–6 week intervals. Treatment effect
typically lasts for one year or longer.
In July 2009, Sculptra Aesthetic (Aventis Pharmaceuticals,
Bridgewater, NJ) was approved by the FDA for cosmetic use in
non-HIV patients.
Injection techniques
There are several injection techniques. These include linear
threading, fanning, serial puncture and cross hatching. The
number of injections needed for optimal correction must be
minimized in order to reduce the risk of post-inflammatory
hyperpigmentation.3,17
Efficacy and Results
Restylane A or keloids, and pigmentary changes were the same in non-
Perlane A Caucasian and Caucasian subjects. There were 12 reports
Juvederm A (7.5%) of discoloration lasting for 11 days or longer in the
Radiesse B non-Caucasian group which resolved by the end of the study.
Evolence B The second study was a randomized, open-label study of
Sculptra Aesthetic C
A randomized, double blind, multicenter comparison of the
efficacy and tolerability of restylane versus zyplast for the
correction of nasolabial folds. Narins RS, Brandt F, Leyden J,
Lorenc ZP, Rubin M, Smith S. Dermatol Surg 2003; 29:
588–595.
This is a randomized, double-blind clinical trial of 138
patients treated with a non-animal stabilized hyaluronic acid
gel and bovine collagen for the correction of nasolabial folds.
Eleven percent of patients were skin of color patients. Study
subjects received restylane (20╯mg/mL) in one nasolabial fold
and zyplast (35╯mg/mL) on the contralateral side. Treatments
were repeated at 2-week intervals until ‘optimal clinical result’
was obtained. Less injection volume was required for optimal
results with restylane than zyplast. In addition, Restylane
showed greater clinical improvement in the Wrinkle Severity
Rating Score (p < 0.0001) and the Global Aesthetic
Improvement Scale (p < 0.0001) than zyplast in a majority of
patients.
324
Safety of non-animal stabilized hyaluronic acid dermal
fillers in patients with skin of color: a randomized, evaluator-
blinded comparative trial. Taylor SC, Burgess CM, Callender
VD. Dermatol Surg 2009; 35:1653–1660.
This prospective, multi-center, randomized, evaluator-
blinded, split-face study compared the correction of moderate
to severe nasolabial folds in 150 patients with Fitzpatrick
skin types IV–VI. Two variable-particle non-animal stabilized
hyaluronic acid (NASHA) fillers were used and randomized to
either the left or the right nasolabial fold. Safety and efficacy
were monitored for 24 weeks. Adverse events included bruis-
ing, tenderness, edema, redness, itching, pain and changes in
pigmentation. Pigmentary changes developed in 6% and 9%
of patients injected with large- and small-particle NASHA gels,
respectively. Three patients developed mass formations, of
which two were infectious in nature. There were no reports of
keloid formation.
Safety and effectiveness of hyaluronic acid fillers in skin of
color. Grimes PE, Thomas JA, Murphy DK. J Cosmet Dermatol
2009; 8:162–168.
This paper summarizes two prospective, 24-week, multi-
center trials of patients with Fitzpatrick skin types IV–VI after
dermal injections of the nasolabial folds. The first study was a
randomized, double-blind clinical trial using one of three
highly concentrated HA fillers (Juvederm Ultra, Ultra Plus and
30) on one side of the face and Zyplast collagen on the con-
tralateral side. Of the 439 study patients, there were 160
patients (36.4%) with skin of color, mainly FST IV. Localized
side effects included pain, swelling, redness, induration and
nodules. There were no reported cases of hypertrophic scarring
119 patients with FST IV–VI. The nasolabial areas were injected
with one of three low-concentration fillers (Hylaform, Hyla-
form Plus and Captique) on both sides. There were no reported
cases of hypopigmentation, hypertrophic scarring or keloids;
however, three subjects (2.5%) developed hyperpigmentation.
Other site reactions were mild and transient.
In both studies, effectiveness was demonstrated by
the maintenance of a one point or greater improvement in
the NLF severity scores in the majority of subjects through
24 weeks.
A multicenter, 47-month study of safety and efficacy of
calcium hydroxylapatite for soft tissue augmentation of
nasolabial folds and other areas of the face. Sadick NS, Katz
BE, Roy D. Dermatol Surg 2007; 33(Suppl 2):S122–S127.
Forty-seven month safety and efficacy study of calcium
hydroxylapatite in 113 patients. The most commonly injected
site was the nasolabial folds and the majority (75 patients)
received only one treatment. At the 6-month follow-up visit,
both the mean patient evaluation and mean physician scores
were nearly perfect in regard to look and feel of the implant.
Only 7 patients reported adverse events including transient

ecchymosis, non-granulomatous submucosal nodules of the
lip, inflammation, and edema.
Six-month safety results of calcium hydroxylapatite for
treatment of nasolabial folds in Fitzpatrick skin types IV–VI.
Marmur ES, Taylor SC, Grimes PE, Boyd CM, Porter JP, Yoo JY.
Dermatol Surg 2009; 35:1641–1645.
This open-label 6-month study involved 100 patients with
Fitzpatrick skin types IV–VI with moderate to severe nasolabial
folds. Patients were treated with calcium hydroxylapatite
(CaHA) subdermally and examined at months 3 and 6. There
were no reports of hypo- or hyperpigmentation, hypertrophic
scars or keloid formation. The authors concluded that the lack
of pigmentary changes may be a result of a deeper injection
level as compared to hyaluronic acid fillers.
A randomized, multicenter study of the safety and efficacy
of dermicol-p35 and non-animal-stabilized hyaluronic acid
gel for the correction of nasolabial folds. Narins RS, Brandt
FS, Lorenc ZP, Maas CS, Monheit GD, Smith SR, et╯al. Derma-
tol Surg 2007; 33:S213–S221.
In this clinical study, 149 patients (19% Fitzpatrick skin
types IV and V) were randomized to receive Dermicol-
P35 (35╯mg/mL) or non-animal-stabilized hyaluronic acid
(NASHA) (20╯mg/mL) to contralateral nasolabial folds. Both
Dermicol and NASHA produced significant improvements in
the Modified Fitzpatrick Wrinkle Scale scores (p < 0.001) and
there were no significant differences between the two treat-
ments. Edema, pain, and bruising were more common with
NASHA; however, several patients experienced more indura-
tion at the Dermicol site.
A B
Figure 17.13:╇ (A) Skin phototype IV patient before soft tissue augmentation. (B) Patient immediately after injection of dermal filler into the nasolabial folds. Note the
erythema in these areas. (C) This is the patient 3 weeks after the procedure. Note the complete resolution of the erythema without the development of post-inflammatory
hyperpigmentation.
17â•… Cosmetic Treatmentsâ•… •â•… Fillers
Injectable poly-L-lactic acid: 3 years of aesthetic experience.
Lowe NJ, Maxwell CA, Lowe P. Dermatol Surg 2009; 35:
344–349.
This is a retrospective study of 221 patients who had been
previously treated with poly-L-lactic acid (PLLA). The patients
responded to a mailed questionnaire. Patients received between
1 and 5 injections and the nasolabial area was the most
common site injected. 68% of patients noticed beneficial
effects of PLLA after their first or second treatment, and 72%
of patients would plan for further PLLA injections if needed.
Side effects included edema, bruising, and discomfort. Grades
1, 2, and 3 papules or nodules developed in 14, 15, and 12
patients, respectively; 5 resolved spontaneously and 7 were
treated with either corticosteroids or excision. The authors
noted that the papules and nodules tended to occur in perioral
and periorbital regions. The duration of the treatment effect
was 24 months or greater in 32% of patients.
Complications
Complications from soft tissue augmentation with dermal
fillers can results from a number of factors including type of
filler used, sterility, and operator technique. Common side
effects include pain, erythema, edema, and bruising at the
injection site. Dark-skinned patients can develop mild ery-
thema after the procedure that typically resolves without
treatment (Fig. 17.13). However, if patients develop intense or
persistent erythema, then treatment with corticosteroids may
be warranted to prevent the occurrence of post-inflammatory
hyperpigmentation. Less common adverse reactions include
C
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 Part 5 Cosmetics
infection, granuloma formation, hypersensitivity reaction, and
even necrosis if filler is injected into a blood vessel.18 Hyaluro-
nidase (Vitrase, Ista Pharmaceuticals, Inc., Irvine, CA) can be
used to break down hyaluronic acid in unwanted areas. Simi-
larly, papules and nodules can develop from Sculptra Aesthetic
and treatment consists of intralesional corticosteroids and/or
excision.
References
1. Harris MO. The aging face in patients of color: minimally invasive
surgical facial rejuvenation – a targeted approach. Dermatol Ther
2004; 17:206–211.
2. Beddingfield F, Kim J. Fillers in ethnic skin. In: Grimes PE, ed. Aesthetics
and cosmetic surgery for darker skin types. Philadelphia, PA: Lippincott
Williams & Wilkins; 2008:225–240.
3. Taylor SC, Burgess CM, Callender VD. Safety of nonanimal stabilized
hyaluronic acid dermal fillers in patients with skin of color: a
randomized, evaluator-blinded comparative trial. Dermatol Surg
2009; 35:1653–1660.
4. Grimes PE, Thomas JA, Murphy DK. Safety and effectiveness of
hyaluronic acid fillers in skin of color. J Cosmet Dermatol 2009;
8:162–168.
5. Marmur ES, Taylor SC, Grimes PE, Boyd CM, Porter JP, Yoo JY.
Six-month safety results of calcium hydroxylapatite for treatment of
nasolabial folds in Fitzpatrick skin types IV to VI. Dermatol Surg 2009;
35:1641–1645.
Hair transplantation
According to the International Society of Hair Restoration
Surgery (ISHRS) 2009 practice census survey, the worldwide
number of hair transplantation (HT) procedures is approxi-
mately 252╯002, an increase from the 2006 statistics.1 Of these,
85% were males and 15% females. The number of hair trans-
plant surgeries in ethnic patients is currently not available;
however, cosmetic surgeons must be able to recognize the
racial differences in performing HT in response to the chang-
ing demographics.
Hair transplantation (HT) by punch grafting was first intro-
duced by Orentreich in the late 1950s and was based on the
theory of donor dominance.2 The procedure involved trans-
planting hair from the donor area of the scalp (donor site)
into an area of hair loss (recipient site). The transplanted hairs
would then grow without the hair characteristics (miniaturiza-
tion) of the balding area. In 1995, Bernstein and others devel-
oped follicular unit transplantation in order to achieve a more
aesthetic result. Instead of using larger round grafts or ‘hair
plugs’, natural-appearing transplanted hairs or ‘follicular units’
(FU) were implemented.3,4 More recently, there have been
major advances in surgical technique (follicular unit extrac-
tion, trichophytic closure), as well as with surgical instrumen-
tation.5,6 These new advances can also be used in the skin of
color population; however, racial differences that exist must
be taken in consideration prior to their use (Table 17.6).7
The hair morphology in patients of color differs.8,9 Indi-
viduals of African descent have a higher degree of curl, com-
326
6. Restylane (package insert). Medicis, Scottsdale, AZ.
7. Perlane (package insert). Medicis, Scottsdale, AZ.
8. Callender VD, Young CM. Cosmetic procedures in skin of color: chem-
ical peels, mircrodermabrasion, hair transplantation, augmentation,
and sclerotherapy. In: Kelly AP, Taylor SC, eds. Dermatology for skin
of color. New York, NY: McGraw Hill; 2009:513–528.
9. Wesley NO, Dover JS. The filler revolution: a six-year retrospective.
J Drugs Dermatol 2009; 8:903–907.
10. Juvederm Ultra (package insert). Allergen, Inc. Irvine, CA.
11. Juvederm Ultra Plus (package insert). Allergan, Inc. Irvine, CA.
12. Prevelle Silk (package insert). Mentor, Santa Barbara, CA.
13. Radiesse (package insert). Bioform Medical, San Mateo, CA.
14. Marmur E, Green L, Busso M. Controlled, Randomized Study of Pain
Levels in Subjects Treated with Calcium Hydroxylapatite Premixed
with Lidocaine for Correction of Nasolabial Folds. Dermatol Surg
2010; 36:309–315.
15. Evolence (package insert). Colbar Life Science, Ltd., Ortho Neutrogena,
Morris Plains, NJ.
16. Sculptra Aesthetic (package insert). Sanofi-Aventis, Bridgewater, NJ.
17. Glogau R, Kane M. Effect of injection techniques on the rate of local
adverse events in patients implanted with non-animal hyaluronic acid
gel dermal fillers. Dermatol Surg 2008; 34:S105–S109.
18. Chan HH, Huh C. Potential adverse effects after procedures in ethnic
skin. In: Alam M, Bhatia AC, Kundu RV, et al, eds. Cosmetic
dermatology for skin of color. New York, NY: McGraw Hill; 2009:
16–25.
Table 17.6╇ Racial differences in hair transplantation
Hair morphology
Hair density
Whorl pattern
Hair grooming practices
Indications – traction alopecia, central centrifugal cicatricial alopecia
Concomitant medications – topical corticosteroids, antifungal
shampoos
Contraindications – keloids, acne keloidalis, dissecting cellulitis
Pre- and post-operative counseling
Test session in scarring alopecia (CCCA)
Surgical instrumentation
Donor harvesting techniques
Hair line design
Recipient sites – larger
Complications – risk of hypertrophic and keloidal scarring
CCCA = Central centrifugal cicatricial alopecia
pared to wavy-straight hair of Caucasians and even straighter
hair of Asians. The curly nature of the hair increases the risk
of transection of hair follicle during donor harvesting and graft
dissection. Of note, it is important to remember that not all
patients of African descent with dark skin have curly hair and
close examination of the hair morphology is necessary for each
patient.10
In hair transplantation, the curly hair in patients of African
descent has some advantages as well. These include a greater
 17â•… Cosmetic Treatmentsâ•… •â•… Hair transplantation

Figure 17.14:╇ Male androgenetic alopecia. Figure 17.15:╇ Female androgenetic alopecia.

amount of coverage of surface area of scalp compared to

straight hair and less contrast between the dark hair color and
dark skin color.10 Both advantages provide these patients with
excellent cosmetic results.
Hair density in people of color can vary. Patients of African
descent have less hair density compared to Caucasians and
Asians.9,10 When performing hair transplantation, the hair
density in the donor area of scalp determines the aesthetic
outcome of the procedure.4

Indications and patient selection

The indications for hair transplantation in men and women
differ. There are also racial and gender differences. Clearly,
most procedures are performed on white males with androge-
netic alopecia (AGA). Racial differences also exist and women
of color present for surgical correction of their hair loss mainly
for traction alopecia and central centrifugal cicatricial alopecia
(CCCA).
In males regardless of race or ethnicity, AGA is the main
indication for hair restoration surgery (Fig. 17.14). Although
no true incidence exists on the number of HT performed in
women of color, cosmetic surgeons who treat these patients for
hair loss find that the most common reasons include AGA (Fig.
17.15), traction alopecia (Fig. 17.16) and CCCA (Fig. 17.17).
Contraindications
Contraindications for HT include limited donor area, active
inflammation, concurrent scalp disorders, such as acne keloi-
dalis (Fig. 17.18) and dissecting cellulitis (Fig. 17.19), mental
illness, pregnancy and a history of keloids (Fig. 17.20). Prior
to surgery, it is important to obtain a thorough medical history
and physical exam of the scalp and other areas that commonly
develop keloids to properly assess a patient’s risk for complica-
tions and appropriateness of surgery if certain risk factors are
present (Table 17.7).
Figure 17.16:╇ Traction alopecia in a patient with skin phototype IV.
Instrumentation
Table 17.8 outlines the surgical supplies and instrumentation
recommended for hair transplant surgery in patients of color
(Fig. 17.21). The major difference is the selection of the instru-
ment used in creating the recipient sites. These sites tend to be
larger in order to accommodate the larger grafts that contain
hair with a higher degree of curl. The site produced should be
greater than 1.5╯mm in size.11
Local anesthesia
Lidocaine 1–2% with epinephrine is the most common anes-
thetic used in hair transplantation. Bupivacaine is also used by
some surgeons because of its longer duration of action;
however, caution must be used because of the risk of cardio-
toxicity. Tumescence anesthesia with saline solution combined
with epinephrine is recommended for several reasons: (1)
vasoconstriction produces less bleeding during the procedure,

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 Part 5 Cosmetics
Figure 17.17:╇ Central centrifugal cicatricial alopecia.
Figure 17.18:╇ Acne keloidalis. Note the pustules.
(2) helps to prevent damage of the underlying larger vessels
by lifting the subcutaneous fat and (3) straightens the curved
hair shaft. The latter benefit helps to avoid transection of the
hair and hair follicle in people of color with curly hair.
Donor harvesting
The donor strip is meticulously excised from the scalp in the
area of the occipital protuberance (Fig. 17.22). This area is
used because it is relatively spared from male and female
pattern hair loss and CCCA. Loupe magnification is recom-
mended in order to better visualize the curl of black hair and
avoid transection (Fig. 17.23). The addition of saline tumes-
cence helps to increase skin turgor and straighten the hair
follicles. This allows more space between the follicles and
328
Figure 17.19:╇ Skin of color patient with dissecting cellulitis.
Figure 17.20:╇ Occipital scalp with large keloid.
minimizes transection. A single-bladed scalpel, rather than
multi-bladed, is recommended in patients with curly hair to
lessen the risk of transection. Also, the width of the strip
should be 1╯cm or less. Wider strips are associated with greater
wound tension with closure and wider resultant scars. In most
patients who wear their hair long, the scar is not visible;
however, if the hair is cut short, the scar is of cosmetic signifi-
cance. The size (width and length) of the strip is based on the
number of hair follicles needed for the recipient area and
donor density. It can easily be calculated by using a densito-
meter. A new technique, called trichophytic closure, is used to
close the donor area with minimal scarring.10 This procedure
involves trimming the epidermis of the lower surgical margin
 17â•… Cosmetic Treatmentsâ•… •â•… Hair transplantation

Table 17.7╇ Pre-operative counseling Table 17.8╇ Surgical instrumentation for performing hair
transplantation in Blacks
Obtain consent form
Laboratory studies – CBC with diff, platelet count, PT, PTT, CMP Donor harvesting Loupe magnification
Optional if clinically needed – Hepatitis screen, HIV and EKG Hair clips
Avoid alcohol, NSAIDS, ASA and Vitamin E prior to the surgery Electrical trimmer
Clinical photography Single bladed scalpel
Discussion on scar formation involving the donor area Curved No.10 or 15 blade
Donor hair density Tissue clamps
CBC = Complete blood count 3-0 or 4-0 Prolene (blue) suture
diff = Differential Graft preparation Stereomicroscope
PT = Prothrombin time
Fiberoptic box lighting
PTT = Partial thromboplastin time
CMP = Complete metabolic panel Straight or curved personna blade (DermaBlade)
HIV = Human immunodeficiency virus Petri dishes
EKG = Electrocardiogram Saline solution
NSAIDS = Non-steroidal anti-inflammatory drugs
ASA = Aspirin Recipient site Curved or straight microvascular forceps
and graft Spearpoint (SP) blades – 90 and 91
placement Minde knife – 1.3╯mm, 1.5╯mm
Nokor needles – 16 and 18 gauge
Punches – 2╯mm through 4╯mm
Modified from Callender VD, Young CM. Alopecia and hair restoration in women. In:
Grimes PE, ed. Aesthetics and cosmetic surgery for darker skin types. Philadelphia, PA:
Lippincott Williams & Wilkins 2008:293.

Figure 17.21:╇ Instruments used for donor harvesting during hair transplantation. (A) From left to right: 4-0 Prolene suture, needle holder, curved No. 15 blade scalpel,
forceps, small scissors, tissue clamp. (B) Electric shaver, hair clips, tape. (C) Loupe magnification, chlorhexidine gluconate solution.

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 Part 5 Cosmetics
Figure 17.22:╇ Shaved site on the occipital scalp for donor graft harvesting.
Figure 17.23:╇ Follicular unit from an African-American patient. Note the curved
nature of the hair follicles.
and exposing the tips of the hair shaft before closure. During
the healing process, these hairs will grow through the scar and
camouflage any scar tissue formed in that area.
Another advancement in harvesting donor grafts is called
follicular unit extraction (FUE).12 FUE involves the use of very
small punch excisions (1╯mm) to harvest individual follicular
units directly from the donor site. This technique was born out
of a concern for donor site complications like scarring after
conventional strip harvest. Rassman et╯al12 describe the tech-
nique of FUE as well as the Fox Test, which is used to deter-
mine which patients will be good candidates for FUE. For
the Fox Test, five or more biopsies are taken from the
occipital scalp and the integrity of the units is determined by
stereomicroscopic and/or histologic examination. Biopsies are
assessed on a scale of 1–5 based on whether the follicles are
intact (score of 1) versus significantly damaged (score of 5)
and differing levels in between. Patients in class 1 or 2 have
positive Fox Tests and are potential candidates for FUE. Class
3 patients are neutral (can be a candidate for the procedure if
330
Figure 17.24:╇ Instruments used for graft preparation during hair transplantation:
normal saline solution, petri dish, curved or straight microvascular forceps,
DermaBlade.
a strong indication for it exists), and class 4 and 5 patients
have negative Fox Tests and are not candidates for the
procedure.
Graft preparation
A stereomicroscope or loupe magnification is essential in pre-
paring follicular units and follicular grafts (Fig. 17.24) in skin
of color patients with curly hair. With the help of magnifica-
tion, the donor strip is divided into individual grafts of various
sizes. This step is accomplished using either a straight or
curved blade depending on the morphology of the hair folli-
cle. For African-Americans, in particular, a curved blade will
help avoid transection of the curved hair follicle.13 A straight
blade may be best for hair transplants in Asian patients given
the straight nature of the hair follicle. Each graft should contain
1–4 follicular units. The grafts should then be placed in a
saline solution until they are ready to be implanted into the
recipient sites.
Recipient site creation
Several different surgical instruments can be use to create
recipient sites (Fig. 17.25). In patients with curly hair, the sites
tend to be larger in order to accommodate the larger graft and
degree of curl. For patients with significant curvature of the
hair follicle, recipient sites can range from 1.2 to 2.0╯mm in
size. Fine blades, needles, or punches can be used to create
recipient sites based on the surgeon’s preference; however,
selection of the surgical instrument should be determined by
the size of the recipient site needed.
Complications
Postoperative scarring is rare; however, if it does occur, it
usually presents with a hypertrophic scar involving the occipi-
tal scalp at the donor site (Fig. 17.26). Keloid formation is rare.
 17â•… Cosmetic Treatmentsâ•… •â•… Hair transplantation

Figure 17.25:╇ Instruments used for graft placement into recipient site. From left to
right: Spearpoint blade (90), punch for recipient site creation, Nokor needle 16
gauge, 1.5╯mm punch, 2╯mm punch, Minde knife 1.3╯mm.

Figure 17.26:╇ Hypertrophic scar at the donor site on the occipital scalp.

Treatment involves class I topical corticosteroids twice daily

for 2–4 weeks and/or intralesional triamcinolone 20–30╯mg/
mL injected every 2–4 weeks until the area flattens.

Commonly encountered pitfalls
Cicatricial alopecia (CA) is characterized by permanent injury
of the stem cell region of the hair follicle. In addition, there is
replacement of the pilosebaceous unit with fibrous connective
tissue, which can occur by either primary or secondary causes.
Primary causes include lupus erythematosus (LE), lichen plan-
opilaris (LPP), and CCCA. Secondary causes include infiltra-
tive processes (granulomatous, neoplastic), trauma (chemical,
physical), infections (fungal, bacterial, viral) and autoimmune
(morphea, cicatricial pemphigoid, temporal arteritis).
Hair transplantation in CA poses therapeutic challenges
that are not confronted in non-scarring alopecias such as AGA.
Although most of the published literature focuses on HT in
B
Figure 17.27:╇ Before (A) and after (B) photos of a hair transplant test screen.
secondary forms of CA, such as traumatic scars or cosmetic
surgical scars, successful outcomes with primary CA are
lacking. For example, patients with CCCA (a primary CA) who
present for HT must be informed of the poor graft survival rate
and recurrence of their disease.
In scar tissue, there is a limited blood supply, thus the graft
survival rates are lower. Larger grafts and multiple smaller ses-
sions are recommended. A test session is strongly recom-
mended to determine if inflammation is present prior to the
procedure (Fig. 17.27).

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 Part 5 Cosmetics
Special management & counseling considerations
A discussion involving hair care practices must be undertaken
in order to prevent additional complications, such as the
development of an irritant contact dermatitis from hair chemi-
cals and infection. Chemical hair relaxers, hair coloring or
excessive use of hair gels or hair sprays should be avoided. It
is best to have the female patient wear a wig during the first 2
weeks postoperatively and avoid the hair salon. Normal hair
grooming can be resumed after the sutures are removed in
10–14 days after the procedure.
References
1. International Society of Hair Restoration Surgery 2009 Practice Census
Results. www.ishrs.org [Accessed August 2009].
2. Orentreich N. Autographs in alopecias and other selected dermatologi-
cal conditions. Ann NY Acad Sci 1959; 83:463–479.
3. Bernstein RM, Rassman WR, Szaniawski W, Halperin A. Follicular
transplantation. Int J Aesthet Rest Surg 1995; 3:119–132.
4. Bernstein RM, Rassman WR. The aesthetics of follicular transplanta-
tion. Dermatol Surg 1997; 23(9):785–799.
Lasers, light sources
and other devices
The theory of selective photothermolysis is the basis for most
device-based medicine which employs lasers, light sources and
radiofrequency devices. The two key components of selective
photothermolysis are the chromophore (of which there are
three biological chromophores – melanin, hemoglobin and
water) and the thermal relaxation time (TRT). The use of spe-
cific wavelengths of light to target chromophores and the selec-
tion of pulse durations of lasers that are shorter than the
thermal relaxation time of the target was the fundamental
concept in traditional lasers. However, it is becoming increas-
ingly evident that selective photothermolysis requires addi-
tional parameters, especially when considering the treatment
of skin of color. Expansion of selective photothermolysis
includes the concepts of thermokinetic selectivity, fractional
photothermolysis and photomodulation. This section will
explore how devices are being utilized with greater safety and
efficacy in skin of color using these expanded concepts of
selective photothermolysis.
Indications
Table 17.9 summarizes the most common use of lasers, light
sources and other devices. The most common procedures in
skin of color include: (1) laser and light-based hair reduction
(Figs. 17.28–17.30), (2) treatment of disorders of pigmenta-
tion including dyschromia, melasma and post-inflammatory
332
5. Unger WP, Shapiro R. Hair transplantation. 4th edn. New York: Marcel
Dekker; 2004.
6. Harris JA. Follicular unit extraction. Facial Plast Surg 2008;
24:404–413.
7. Callender VD. Hair transplantation for pigmented skins. In: Halder
RM, ed. Dermatology and dermatological therapy of pigmented skins.
London: Taylor and Francis; 2006:245–257.
8. Rook A. Hair II: Racial and other genetic variations in hair form. Br J
Dermatol 1975; 92:599–600.
9. Richards GM, Oresajo CO, Halder RM. Structure and function of
ethnic skin and hair. Dermatol Clin 2003; 21:595–600.
10. Shapiro R, Callender VD. Hair transplantation. In: McMichael A,
Hordinsky M, eds. Hair and scalp diseases: medical, surgical, and
cosmetic treatments. New York, NY: Informa Healthcare; 2008.
11. Callender VD. Alopecias and hair restoration in women. In:
Grimes PE, ed. Aesthetic and cosmetic surgery for darker skin
types. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:
287–295.
12. Rassman WR, Bernstein RM, McClellan R, Jones R, Worton E,
Uyttendaele H. Follicular unit extraction: Minimally invasive surgery
in hair transplantation. Dermatol Surg 2002; 28:720–728.
13. Callender VD, Young CM. Cosmetic procedures in skin of color: chem-
ical peels, mircrodermabrasion, hair transplantation, augmentation,
and sclerotherapy. In: Kelly AP, Taylor SC, eds. Dermatology for skin
of color. New York, NY: McGraw Hill; 2009:513–528.
hyperpigmentation, (3) treatment of acne, (4) treatment of
acne scarring, scars and keloids, and (5) treatment of laxity.
Advances in devices have made these treatments much safer in
skin of color.
Contraindications
The use of lasers in skin of color is generally safe and effective
if used properly. Patients with active skin infections should not
be treated during the acute disease; however, patients with a
history of HSV infection can receive laser therapy with con�
current use of anti-viral medications. A history of keloidal or
hypertrophic scarring is not an absolute contraindication to
laser therapy but these patients should be treated less aggres-
sively.1 Patients should cease taking isotretinoin for 6–12
months prior to a laser procedure as there is a risk of atypical
scarring after laser therapy with isotretinoin use.1 There is also
a risk of koebnerization after laser therapy in psoriasis and
vitiligo patients and a paradoxical darkening can occur if
Q-switched lasers are used in hair-bearing areas that overlie
light-colored tattoos.1
Procedures
Laser and light-based hair reduction
The initial basis of hair reduction employed lasers in the near
infra-red region such as the long-pulsed ruby and long-pulsed
alexandrite lasers.2 These devices were originally utilized in a
Q-switched fashion using nanosecond pulse durations to treat
pigmented lesions in light skin.3 The chromophore for both
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices

Table 17.9╇ Lasers and light-based devices in skin of color

Safety data for skin

Indication Device Wavelength Mechanism Side effects of color

Hair reduction Nd-YAG laser Long-pulsed Selective Post-inflammatory hyper- & Alster et╯al (FST IV-VI)13
1064-nm photothermolysis, hypopigmentation, Adrian et╯al (FST V, VI)14
Diode laser Long-pulsed 800-nm thermokinetic vesiculation, pain, scarring Lee et╯al (Korean)15
IPL with extended 500–1200╯nm selectivity Johnson et╯al (FST V, VI)16
pulse durations (550–590)
Dyschromia IPL with cooling 500–1200-nm Selective Post-inflammatory hyper- & Negishi et╯al (Japanese)17
and selective (550–590) photothermolysis hypopigmentation, Al-Otaibi et╯al (FST III-V)18
filters vesiculation, pain, scarring
Excimer laser 308-nm Targeted narrowband
(Vitiligo) UVB light
Melasma Non-ablative 1540-nm; 1550-nm Stamped and Post-inflammatory hyper- & Rokhsar et╯al (FST III-V)7
fractional lasers scanned fractional hypopigmentation, Lee et╯al (FST III, IV)19
photothermolysis- vesiculation, pain, scarring,
melanin shuttle melasma exacerbation
Acne Blue light 420-nm Photomodulation and Higher fluences – post- Tzung et╯al (FST III, IV)20
phototherapy destruction of P. inflammatory hyper- &
Photopneumatic 420-nm pulsed light acnes hypopigmentation,
therapy vesiculation, pain, scarring
Scars (acne, Nd-YAG laser Long-pulsed Neocollagenesis Post-inflammatory hyper- & Lee et╯al (FST IV, V)21
hypertrophic, 1064-nm through low hypopigmentation, Jones et╯al (FST VI)22
surgical, fluence heating vesiculation, pain, scarring Lee et╯al (FST IV, V)23
traumatic) Non-ablative 1540-nm; 1550-nm Fractional
fractional lasers photothermolysis
Skin laxity Radiofrequency No wavelength Neo-collagenesis Post-inflammatory hyper- & Kushikata et╯al (FST III,
Infra-red light 700–2000╯nm through bulk hypopigmentation, IV)24
(1100–1800) heating vesiculation, pain, scarring Chua et╯al (FST IV, V)25
Nd-YAG = neodymium:yttrium aluminum garnet
IPL = Intense pulsed light
UVB = Ultraviolet-B
Nm = Nanometers
P. acnes = Propionibacterium acnes
FST = Fitzpatrick skin types

A B

Figure 17.28:╇ Patient with hirsutism before (A) and after (B) laser hair removal.

333
 Part 5 Cosmetics

A B

Figure 17.29:╇ (A) & (B) Laser hair removal in the groin.

A B

Figure 17.30:╇ Patient with skin of color before (A) and after (B) laser hair removal in the axilla.

targets was melanin prevalent in melanosomes in the pig-
mented lesions and in the hair matrix and stem cells in the
hair follicle. The idea of different thermal relaxation times of
melanosomes versus hair follicles allowed the use of longer
pulse durations of these lasers to be more effective on hair.
However, it was evident that despite the extended pulse dura-
tions, if these lasers were utilized in skin of color, there was
still a very high risk of pigmentary alteration, both hypopig-
mentation and hyperpigmentation. This led to the develop-
ment of thermokinetic selectivity, where extremely long pulse
durations were used with near infra-red lasers and the use of
novel wavelengths such as the 800-nm diode laser with these
extended pulse durations.4 These very long pulse durations
allowed for safer treatment in skin of color.

334
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices

A B

Figure 17.31:╇ Male patient with pseudofolliculitis barbae (PFB) before (A) and after (B) laser hair removal.

A B

Figure 17.32:╇ Female patient with PFB before (A) and after (B) laser therapy. Note the reduction of unwanted hair as well as papules, inflammation, and
hyperpigmentation.

Further safety in skin of color was introduced with the
development of lasers which had the lowest coincidental
absorption of melanin, such as the long-pulsed 1064-nm laser.
This was particularly effective in the treatment of pseudofol-
liculitis barbae (PFB) and is the most gratifying treatment for
hair reduction in skin of color as in addition to hair reduction
there is a significant reduction in inflammation (Fig. 17.31).
Laser hair removal for PFB is a very common office procedure
not only in men but also in women with skin of color. This
problem can be psychologically disturbing for many female
patients. We find that many women are more concerned and
preoccupied with the post-inflammatory hyperpigmentation
from the folliculitis than the actual appearance of excess hair
over the face, axilla, and groin (Fig. 17.32). Therefore, the

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 Part 5 Cosmetics

Figure 17.33:╇ Patient with facial burns after Nd-YAG laser therapy without an
adequate cooling mechanism.

treatment goal of PFB is two-fold: hair removal and decreased

inflammation (and the subsequent pigmentary changes), both
of which tend to improve after laser hair removal.
The greatest advancement in the safety of all of these devices
was the expansion of contact cooling. Despite long pulse dura-
tions and very low coincidental absorption of melanin by
longer infra-red wavelengths, there was still a risk of develop-
ing complications from bulk heating, regardless of the wave-
length used. In fact, the long-pulsed 1064-nm laser with the
deepest penetration carries the highest risk of scarring if inad-
equate cooling is utilized (Fig. 17.33). Continuous contact
cooling is the safest modality to protect skin, regardless of the
color. The greatest controversy in laser and light-based reduc-
tion in skin of color is the number of treatments required
for adequate hair reduction. The general consensus is that B
darker skin requires significantly more treatments to achieve
Figure 17.34:╇ Female patient with hirsutism before (A) and after (B) laser hair
comparable results to lighter skin, but the exact ratio remains
removal. Endocrine diagnostic work-up revealed polycystic ovarian syndrome.
unknown. Finally, an unusual side effect of laser hair reduction
in darker skin is paradoxical hypertrichosis.5 This is typically
seen in facial hair and the theory is the lower fluences which hypertrichosis, the patient needs to be informed of the pos-
are often indicated in darker skin may inadvertently stimulate sibility of persistence of hair. Premedication with antivirals is
hair follicles. indicated if the patient gives a history of oral or genital herpes
simplex, or if hair reduction is to be performed in the facial
Patient selection and preparation or bikini areas. Pre-treatment with hydroquinones to the
For all skin types, a thorough history is warranted. This should affected area is indicated if the patient shows a high predispo-
include an assessment of whether the primary condition is sition to post-inflammatory hyperpigmentation, which is par-
hypertrichosis versus hirsutism (Fig. 17.34), as the latter will ticularly critical in facial skin and bikini areas. We always
warrant an endocrine work-up. If treatment is initiated for perform test spots to determine the adequate energy and

336
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices

Figure 17.35:╇ Patient with extensive leg burns after traditional pulsed light
therapy.

appropriate pulse duration of the laser and light source and A

wait 2–4 weeks before initiating treatments. Test sites are advis-
able in inconspicuous areas such as the sideburns and under
the chin for facial laser hair reduction. The main reason for
test spots is to determine if the patient will develop pigmentary
alterations. The other main reason is to assess the approximate
hair reduction which is feasible with each treatment, as this
varies between anatomic areas and skin types. As with all elec-
tive procedures, baseline photography and an informed
consent are indicated.

Treatment
The safest devices to use on skin of color, types IV–VI, are
the long-pulsed 1064-nm laser with contact cooling and the
extended-pulse (100–400╯msec) 800-nm laser with contact
cooling. The long-pulsed alexandrite laser can be used in skin
type IV but with extreme caution. The long-pulsed ruby laser
is not recommended for skin of color. Traditional pulsed light
is not safe in skin of color as significant pigmentary changes
can occur (Fig. 17.35). Newer generation pulsed light sources
with more selective filtrations and better cooling have been
developed to overcome these limitations but they are not
optimal.
The patient is advised to shave the day before treatment.
Topical anesthesia with 4% lidocaine is utilized prior to treat-
ment. Treatment intervals are spaced 4–6 weeks apart. Patients
generally question how many treatments are necessary. For
skin of color, the appropriate answer to this question is to give
a range, based on anatomic location. It is also imperative to
explain to the patient that the treatment may require ongoing
maintenance.
Lasers and light sources for disorders
of pigmentation
While lighter-skinned patients generally seek laser and light-
based treatments for pigmentation induced by photoaging,
darker-skinned patients generally seek these treatments for
B
Figure 17.36:╇ Patient with Fitzpatrick skin type V and DPN before (A) and after
(B) treatment with light electrodessication.
generalized dyschromia, post-inflammatory hyperpigmenta-
tion, dermatosis papulosa nigra and melasma. Lasers and light
sources have a limited role in the management of these condi-
tions, and often patients are inappropriately treated, leading
to disappointing results and/or worsening of the pre-existing
condition. Of all these entities, the only two that show modest
improvement in skin of color are generalized dyschromia
and melasma. Post-inflammatory hyperpigmentation is best
treated with hydroquinones and the tincture of time and der-
matosis papulosa nigra is best treated with light electrodessica-
tion (Fig. 17.36) or gradle excision.
Treatment of dyschromia is most effective in skin type IV
and a few skin type Vs. Very dark skin with dyschromia does
not fare well with devices. The newer generation pulsed light
sources with contact cooling are the first device utilized for this
condition and can effectively treat isolated lentigines and

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 Part 5 Cosmetics

mottled hyperpigmentation. Fluences need to be reduced by

30–50% and pulse durations need to exceed 20 milliseconds
for safe treatment. Therapy resistant melasma is the only indi-
cation for devices, regardless of skin type. The safest devices
for the treatment of melasma in skin of color are the non-
ablative fractional lasers. Fractional photothermolysis is an
extension of selective photothermolysis, whereby microscopic
wounds of damage are induced with rapid re-epithelialization.6
The rationale for the treatment of melasma is the creation of
‘melanin’ shuttles due to the deeper penetration of these
devices, thereby extruding some of this dermal pigment.7
Recently, some promise has also been shown using low fluence
Q-switched 1064-nm lasers8 which could achieve this result by
a photoacoustic effect.

Patient selection and preparation A

All patients must be started on topical hydroquinones, at least
4 weeks prior to treatment. A test site is always advisable and
performed after initiating hydroquinones. Melasma patients
are advised that this treatment is not a cure for melasma and
that there may be recurrence. For non-ablative fractional resur-
facing, patients are pre-medicated with antivirals regardless of
a history of oral herpes simplex.

Treatment
Three to five treatments are usually necessary for both dyschro-
mia and melasma (Fig. 17.37). If significant improvement is
seen with fewer treatments, laser therapy is terminated. After
the first treatment, it is advisable to see the patient in follow-up
before proceeding with additional sessions since if the treat-
ment is ineffective or if the treatment has worsened the pre-
existing condition, treatment should be terminated.
B

Device-based acne treatments
The treatment of acne with devices requires combination
therapy. Devices can jump start the treatment of acne but
maintenance regimens with topical and systemic agents are
necessary, as acne is a dynamic condition. The two targets for
acne with devices are the Propionibacterium acnes bacteria and
the sebaceous gland. Blue-green light sources target the former
while infra-red sources target the latter. The treatment of acne
in skin of color with traditional photothermal devices is risky,
as there is significant overlap with melanin, producing risks
of hypopigmentation and hyperpigmentation. The infra-red
devices which target sebaceous glands require cryogen cooling
which may also induce hypopigmentation. The safest devices
in treating acne in skin of color are non-thermal blue light
sources and devices employing photopneumatic therapy.9
Photodynamic therapy using 5-amino-levulinic acid can
augment these effects but the risk of post-inflammatory hyper-
pigmentation is greater and it should be used with caution.
Blue light sources, 420-nm, utilize low fluence light with
the primary mechanism being photomodulation leading to
the gradual diminution of Propionibacterium acnes bacteria.
Photopneumatic therapy employs very low fluence 420-nm
pulsed light with suction, allowing for more effective fluence
delivery to the desired dermal target.
Figure 17.37:╇ Before (A) and after (B) photos of a patient treated with fractional
photothermolysis for melasma.
Patient selection and preparation
The best candidates for device-based acne treatment are
patients with mild to moderate acne, patients who have
failed traditional acne treatments and patients who may
be candidates for more aggressive treatments such as
systemic cis-retinoic acid but there are contraindications or
hesitation to take systemic medications. Patients who desire to
get pregnant are also candidates for device-based acne
treatments.
Treatment
Treatment with 420-nm light requires a series of 8–10 treat-
ments spaced weekly. Photopneumatic therapy requires a
series of 3–6 treatments spaced 2–4 weeks apart (Fig. 17.38).
Specialized filters for darker skin and the use of lower fluences
have made this treatment safe and effective in skin
types IV–VI.

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 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices

A B

Figure 17.38:╇ Before (A) and after (B) photos of a patient treated with photopneumatic therapy for acne vulgaris.

A B

Figure 17.39:╇ Patient with some improvement of acne scars before (A) and after (B) treatment with a non-ablative fractional laser.

Laser therapy for scars Patient selection and preparation

Some of the biggest advances in device treatment of skin of
color have been the use of devices for scarring. Long-pulsed
1064-nm lasers with low fluences10 and non-ablative frac�
tional lasers using 1540-nm and 1550-nm wavelengths are
safe and effective for these treatments. The proposed mecha-
nism for long-pulsed 1064-nm treatment of scars is collagen
modulation using lower energy and the use of the 1064-nm
laser targeting water. Non-ablative fractional photothermolysis
uses a color blind wavelength and a fractional mode of energy
delivery to reduce bulk heating. The 1540-nm laser delivers
the energy in a stamped fashion while the 1550-nm laser
delivers the energy in a random scanned fashion. The results
are most impressive for acne scars, surgical scars and hyper-
trophic scars. True keloids will show subtle improvement
with lasers but traditional therapies such as intralesional injec-
tions are still warranted. Long-pulsed 1064-nm lasers have also
been successful in the removal of tattoos in patients with skin
of color.
All skin types can be treated safely with low fluence 1064-nm
lasers and non-ablative fractional lasers at 1540-nm and 1550-
nm. More impressive results are seen with non-ablative frac-
tional lasers (Fig. 17.39). Pre-treatment with hydroquinones
2–4 weeks prior to treatment is recommended.
Treatment
Three to five treatment sessions, spaced 4–6 weeks apart
are advisable. Post-treatment and intra-procedural treatment
with hydroquinones is recommended. Subtle scars respond
to low fluence long-pulsed and Q-switched 1064-nm laser
while a variety of scars (distensible, non-distensible, ice
pick and shallow) will respond to non-ablative 1540- and
1550-nm fractional laser resurfacing.11 The most extensively
studied and utilized device for these indications is the random
scanned 1550-nm non-ablative fractional laser. The treatment
of scars employs use of higher fluences, but lower treatment

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 Part 5 Cosmetics

densities. The lower treatment densities allow for safer treat-

ment in skin of color, while the higher fluences achieve deeper
penetration. When used for melasma, these devices should
be used with low fluences and low treatment densities.
For hypertrophic and surgical scars, high fluences and high
treatment densities are recommended, and, although there
may be some transient pigmentary anomalies, the results
are superior.
Radiofrequency and infra-red light treatment for
skin laxity
Regardless of skin type, skin laxity is an issue and patients are
seeking non-surgical alternatives. This indication shows the
most variable response to devices but use of this modality is
rapidly gaining momentum as treatment algorithms are being
maximized. Devices used for laxity include unipolar radio�
frequency, bipolar radiofrequency, combined unipolar and
bipolar radio�frequency, broadband infra-red light sources and
focused ultrasound. Unipolar radiofrequency is the most
extensively studied device for this indication.12 Safety in skin
of color has been studied with unipolar radiofrequency and
broadband infra-red light sources.
Patient selection and preparation
The most difficult component of device-based indication for
laxity is patient selection and setting realistic expectations.
During the consultation it is imperative to discuss the fact that
this modality is not a substitute for surgery. For facial laxity,
the ideal patient has mild to moderate laxity of the lower face
without prominent jowling. For off-face laxity, the ideal patient
has mild loose skin. Excessive adiposity and weight loss are
not indications.
Treatment
Unipolar radiofrequency is typically a single treatment, while
other modalities may require a series of treatments. Clinical
outcomes require up to 6 months to see results and this needs
to be emphasized during the consultation.
Efficacy & Results
Hair removal/pseudofolliculitis barbae
Nd-YAG laser B and 50╯J/cm2 for skin types IV, V, and VI, respectively. The
Diode laser C
Intense pulsed light B
Acne
Blue light photodynamic therapy B
Photopneumatic therapy C
Scars
Nd-YAG laser C
Nd-YAG laser (tattoos) C
Non-ablative fractional lasers B
Skin laxity
Radiofrequency B
Infra-red light B
Hair removal
Long-pulsed Nd:YAG laser-assisted hair removal in pig-
mented skin: a clinical and histological evaluation. Alster TS,
Bryan H, Williams CM. Arch Dermatol 2001; 137:885–889.
Twenty women with Fitzpatrick skin types IV–VI and dark
brown to black terminal hair on the face, axillae, and legs were
treated with a series of three long-pulsed (50 millisecond)
1064-nm Nd-YAG laser treatments at fluences ranging from 40
to 50╯J/cm2. Prolonged hair loss was noted at the 1-year
follow-up visit (70–90% hair reduction). Axillary hair was
noted to be more responsive to laser therapy than facial or leg
hair. Adverse events were treatment pain, vesiculation, and
transient pigmentary changes.
Treatment of pseudofolliculitis barbae in skin types IV, V,
and VI with long-pulsed neodymium:yttrium aluminum
garnet laser. Ross EV, Cooke LM, Timko AL, Overstreet KA,
Graham BS, Barnette DJ. J Am Acad Dermatol 2002;
47:263–270.
Two-phase observational study of 37 patients (skin types
IV–VI) to determine the safety and efficacy of long-pulsed
Nd-YAG laser in the treatment of pseudofolliculitis barbae
refractory to conservative therapy. In phase I, one treatment
with a Nd-YAG laser was performed on adjacent areas of the
thigh with three light doses (50, 80, and 100╯J/cm2) plus an
untreated area for control. In phase II, the highest dose toler-
ated by the epidermis from phase I was applied to a small
submental region with an adjacent untreated area for control.
The highest doses tolerated by the epidermis were 100, 100,
mean papule count was significantly decreased (p < 0.001)
after 3 months follow-up.

Dyschromias 800 nanometer diode laser hair removal in African-American

Intense pulsed light
Non-ablative fractional lasers (melasma)
Non-ablative fractional lasers (DPN)
Non-ablative fractional lasers (PIH)
Excimer laser (vitiligo)
patients: a clinical and histologic study. Adrian RM, Shay KP.
B
J Cutan Laser Ther 2000; 2:183–190.
B
This is a clinical study to determine the efficacy of 800-nm
E diode lasers at different pulse durations in hair removal in
E African-American patients with skin types V and VI. Face, neck,
B and axillary regions were treated. Fluences used at 30╯msec
pulse duration ranged from 15 to 25╯J/cm2 in skin type V

340
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices
patients and from 15 to 20╯J/cm2 in skin type VI patients.
However, fluences at 100╯msec pulse duration were 30%
higher: 20–35╯J/cm2 in skin type V and 20–30╯J/cm2 in skin
type VI. The authors suggest that both pulse durations can be
used safely in skin types V and VI; however, the diode laser at
the longer pulse duration was able to deliver higher fluences
with good efficacy and minor side effects.
Modified superlong pulse 810╯nm diode laser in the treat-
ment of pseudofolliculitis barbae in skin types V and VI.
Smith EP, Winstanley D, Ross EV. Dermatol Surg 2005;
31:297–301.
Thirteen patients with skin types V and VI and pseudofol-
liculitis barbae (PFB) were treated with a modified 810-nm
superlong pulse diode laser at varying fluences (23–34╯J/cm2)
a total of three times at 2-week intervals. There was a signifi-
cant reduction in the PFB lesion count from baseline to the
end of therapy on the laser-treated side (p < 0.05) but not on
the control side.
Photoepilation results of axillary hair in dark-skinned
patients by IPL: a comparison between different wavelength
and pulse width. Lee JH, Huh CH, Yoon HJ, Cho KH, Chung
JH. Dermatol Surg 2006; 32:234–240.
Forty-eight Korean patients were treated with either HR (IPL
600–950╯nm filter, 14.9╯J/cm2) or HR-D (IPL 645–950╯nm
filter, 17.1╯J/cm2) in the axillary area for a total of four treat-
ments at 4–6-week intervals. Longer pulse widths were used
with HR-D treatment. All study patients experienced a signifi-
cant hair reduction after treatment (p < 0.001) and the HR-D-
treated group showed a greater response to treatment than the
HR-treated group (p < 0.001). The average clearance of hair
was 52.8% and 83.4% for HR and HR-D, respectively.
Intense pulsed light treatment of hirsutism: case reports of
skin phototypes V and VI. Johnson F, Dovale M. J Cutan Laser
Ther 1999; 1:233–237.
The authors report three cases of hirsutism in female
patients with skin phototypes V and VI that were successfully
treated with IPL. Patients were treated on the face with energy
ranges 28–45╯J/cm2 for 5–7 sessions monthly. All three patients
showed clearance of unwanted facial hair without pigmentary
changes.
Dyschromias
Photorejuvenation by intense pulsed light with objective
measurement of skin color in Japanese patients. Negishi K,
Kushikata N, Takeuchi K, Tezuka Y, Wakamatsu S. Dermatol
Surg 2006; 32:1380–1387.
Twenty-five Japanese women received a series of three IPL
treatments to evaluate its efficacy in skin rejuvenation. The
majority of patients showed a subjective improvement of 50%
or more in pigmentation. The mean value of lightness (L*) by
spectrophotometric analysis increased significantly from base-
line to 3-month follow-up (p = 0.001).
A comparison of Q-switched alexandrite laser and intense
pulsed light for the treatment of freckles and lentigines in
Asian persons: a randomized, physician-blinded, split-face
comparative trial. Wang CC, Sue YM, Yang CH, Chen CK. J
Am Acad Dermatol 2006; 54:804–810.
Fifteen Asian patients with freckles and 17 patients with
lentigines were treated randomly with one session of
Q-switched alexandrite laser (QSAL) on one cheek and two
sessions of IPL on the other cheek at 4-week intervals. All
patients experienced improvement (p < 0.0001). Patients with
freckles showed greater improvement with QSAL than IPL
(p = 0.04). The improvement rates were similar between the
two treatment groups for patient with lentigines; however,
8 of these patients (47%) treated with QSAL developed post-
inflammatory hyperpigmentation (PIH) versus none of the
patients treated with IPL. In a subgroup analysis, of the patients
who developed PIH, improvement rates were significantly
higher with IPL (p < 0.04).
Fractional photothermolysis treatment for resistant melasma
in Chinese females. Naito SK. J Cosmet Laser Ther 2007;
9:161–163.
Six patients (skin phototypes III and IV) with refractory
melasma were treated with 3–4 sessions of fractional photo-
thermolysis (FP) at 4-week intervals. Three patients experi-
enced 50% improvement, 2 had 30% improvement, and the
remaining patient showed 20%. One patient developed PIH.
The treatment of melasma with fractional photothermoly-
sis: a pilot study. Rokhsar CK, Fitzpatrick RE. Dermatol Surg
2005; 31:1645–1650.
This is a clinical study of 10 patients (Fitzpatrick skin types
III–V) with refractory melasma successfully treated with FP.
Patients received 4–6 treatments at 1–2-week intervals.
Wavelengths of 1535- and 1550-nm were used. Sixty percent
of patients achieved 75–100% clearance by physician evalua-
tion. One patient developed PIH but no hypopigmentation
was seen.
Treatment of melasma in Asian skin using a fractional
1,550-nm laser: an open clinical study. Lee HS, Won CH, Lee
DH, An JS, Chang HW, Lee JH, et╯al. Dermatol Surg 2009;
35:1499–1504.
Twenty-five patients (Fitzpatrick skin type III and IV) with
melasma received four monthly fractional photothermolysis
(FP) treatments. The mean Melasma Area and Severity Index
(MASI) decreased significantly from baseline to 36 weeks
follow-up (p = 0.03). However, the mean melanin index
showed a statistically significant decrease after the first two
sessions but increased in subsequent follow-up visits. There-
fore, the authors recommend judicious use of FP for the treat-
ment of melasma in Asian patients.
Dermatosis papulosa nigra treatment with fractional photo�
thermolysis. Katz TM, Goldberg LH, Friedman PM. Dermatol
Surg 2009; 35:1840–1843.
The authors report the case of a 50-year-old Pakistani
patient (Fitzpatrick skin type IV) with dermatoses papulosa
nigra who was successfully treated with the 1550-nm erbium-
doped Fraxel laser. The patient received three treatments at
341
 Part 5 Cosmetics
4–5-week intervals at fluences between 60 and 70╯mJ. After
treatment, the patient experienced a > 75% improvement
without post-treatment complications.
Fractional photothermolysis for the treatment of post-
inflammatory hyperpigmentation. Katz TM, Goldberg LH,
Firoz BF, Friedman PM. Dermatol Surg 2009; 35:1844–1848.
The authors report a case of a 50-year-old patient (Fitz-
patrick skin type IV) with post-inflammatory hyperpigmenta-
tion (PIH) on the left lateral neck successfully treated with
the 1550-nm erbium-doped Fraxel laser. The patient under-
went three treatments at 4–8-week intervals at fluences of
15╯mJ and experienced a near complete resolution (> 95%) of
PIH after treatment.
Using a 308-nm excimer laser to treat vitiligo in Asians.
Al-Otaibi SR, Zadeh VB, Al-Abdulrazzaq AH, Tarrab SM, Al-
Owaidi HA, Mahrous R. Acta Dermatovenerol Alp Panonica
Adriat 2009; 18:13–19.
This is a prospective, controlled clinical trial of 29 patients
(skin phototypes III–V) to determine the efficacy of the
308-nm excimer laser in the treatment of vitiligo in Asian
patients. Lesions were treated twice weekly for 13 weeks start-
ing at 50–100╯mJ/cm2 and increasing by 50╯mJ/cm2 every
session until erythema appeared. Eighteen patients (62%)
achieved 50% or more repigmentation. The most responsive
lesions were on the face and lesions on the hands and feet
were least responsive to treatment. The authors noted a cor-
relation between skin type and response to treatment. The
percent ages of repigmentation were 10%, 45%, and 62% in
skin types III, IV, and V, respectively.
Treatment of vitiligo using the 308-nm excimer laser. Hadi
S, Tinio P, Al-Gaithi K, Al-Qari H, Al-Helalat M, Lebwohl M,
et╯al. Photomed Laser Surg 2006; 24:354–357.
This is a retrospective chart review of 97 patients to evaluate
the efficacy of the 308-nm excimer laser in the treatment of
vitiligo. Of the 221 patches treated, 64.3% showed 50% rep-
igmentation or more, and 25 patients achieved 100% repig-
mentation. The authors found facial lesions to be the most
responsive to treatment and hands and feet to be the least
responsive. Like the above study, the authors also found that
patients with higher skin phototypes were more responsive to
excimer laser therapy.
Acne
Blue light phototherapy in the treatment of acne. Tzung TY,
Wu KH, Huang ML. Photodermatol Photoimmunol Pho-
tomed 2004; 20:266–269.
Twenty-eight patients (Fitzpatrick skin types III and IV)
with facial acne were treated with blue light on one side of the
face twice weekly for 4 weeks. The contralateral side of the face
was left untreated as a control. Compared to the mean percent-
age improvement in the untreated side, the blue light-treated
side showed a significant improvement (p < 0.001). However,
nodulocystic acne tended to worsen despite treatment. The
authors suggest that blue light phototherapy is effective in the
treatment of acne other than the nodulocystic type.
342
Photopneumatic technology for the treatment of acne vul-
garis. Shamban AT, Enokibori M, Narurkar V, Wilson D. J
Drugs Dermatol 2008; 7:139–145.
This is a retrospective study of 56 patients with mild to
severe acne who were successfully treated with 2–4 sessions of
photopneumatic therapy that delivers broadband light (400–
1200-nm). The median physician-rated clearance increased
from 50% (first treatment) to 90% (fourth treatment). Eleven
patients were evaluated by photography and showed improve-
ments in median papule and pustule counts, median acne
severity, median erythema, and median acne clearance. Side
effects included mild erythema.
Scars
Comparison of a 585-nm pulsed dye laser and a 1064-nm
Nd:YAG laser for the treatment of acne scars: a randomized
split-face clinical study. Lee DH, Choi YS, Min SU, Yoon MY,
Suh DH. J Am Acad Dermatol 2009; 60:801–807.
This is a 14-week, single-blinded, randomized, comparative
split-face study of a 585-nm pulsed dye laser (PDL) and
1064-nm Nd:YAG laser in the treatment of acne scars. Eighteen
patients (Fitzpatrick skin types IV and V) received four treat-
ments of PDL or Nd-YAG (50–70╯J/cm2) laser at 2-week inter-
vals. The clinical evaluation scale for acne scarring (ECCA)
scores were significantly reduced after PDL and Nd-YAG laser
treatments (p = 0.005 and p = 0.01, respectively). Both treat-
ments were effective in treating superficial rolling and boxcar
scars but ice-pick and deep scars were relatively resistant to
both treatments. However, ice-pick scars tended to improve
more after PDL and deep boxcar scars tended to improve more
with Nd-YAG.
Non-ablative 1064-nm Nd:YAG laser for treating atrophic
facial acne scars: histologic and clinical analysis. Keller R,
Junior WB, Valente NY, Rodriguez CJ. Dermatol Surg 2007; 33:
1470–1476.
Twelve patients (Fitzpatrick skin types II–V) with mild to
moderate atrophic facial acne scars received five monthly treat-
ments with 1064-nm Nd:YAG laser. Most patients experienced
mild to moderate clinical improvement by physician evalua-
tion and all patients were satisfied. Biopsies were taken before
treatment and 1 month after the last session. There was a
significant increase in the median quantity of collagen
(p < 0.05).
The Q-switched ND:YAG laser effectively treats tattoos in
darkly pigmented skin. Jones A, Roddey P, Orengo I, Rosen
T. Dermatol Surg 1996; 22:999–1001.
This is a clinical study to determine the efficacy of
Q-switched Nd-YAG laser for tattoo removal in 8 patients
(Fitzpatrick skin type VI) with a total of 15 amateur tattoos.
Patients received 3–4 treatments on average at 8-week inter-
vals. Dosages ranged from 3.2 to 8.3╯J/cm2. After treatment, 8
of 15 tattoos were 75–90% cleared, 5 were 50% cleared and
2 were 25% cleared. Thirteen of fifteen tattoos were removed
without any pigmentary changes in the involved skin and the
other two tattoos were removed with only a slightly lightening
of the skin.
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices
Laser treatment of tattoos in darkly pigmented patients:
efficacy and side effects. Grevelink JM, Duke D, van Leeuwen
RL, Gonzalez E, DeCoste SD, Anderson RR. J Am Acad Derma-
tol 1996; 34:653–656.
This is a clinical study to determine the safety and efficacy
of Q-switched ruby (QSRL) and Nd-YAG (QSYAG) lasers for
tattoo removal in darkly pigmented patients. All 5 patients
were Fitzpatrick skin type VI but 4 of the 5 patients were of
Ethiopian descent with tattoos on the face and neck composed
of charcoal injected into the skin, which had been present for
9–12 years. Three patients were treated initially with QSRL
(4.5–6╯J/cm2) but switched to QSYAG (4.5–7.3╯J/cm2) after
pigmentary changes. The remaining two patients were treated
with QSYAG alone. Patients received between 3 and 8 treat-
ments at intervals ranging from 4 weeks to 6 months. The
majority of patients showed at least a 50% clearance after
treatment. The authors recommend the use of QSYAG over
QSRL for tattoo removal in darkly pigmented patients.
Fractional resurfacing for the treatment of atrophic facial
acne scars in asian skin. Hu S, Chen MC, Lee MC, Yang LC,
Keoprasom N. Dermatol Surg 2009; 35;826–832.
Forty-five patients (Fitzpatrick skin types III and IV) with
atrophic facial acne scars were treated with a 1550-nm erbium
doped Fraxel laser at either 15–20╯J/MTZ or 30–40╯J/MTZ.
Fifty percent of patients experienced good to excellent results
by physician evaluation. Side effects included erythema,
edema, skin dryness, PIH, and acneiform eruption.
Fractional photothermolysis for the treatment of acne scars:
a report of 27 Korean patients. Lee HS, Lee JH, Ahn GY, Lee
DH, Shin JW, Kim DH. J Dermatolog Treat 2008; 19:45–49.
Twenty-seven Korean patients (skin phototypes IV and V)
with moderate to severe facial acne scars were treated with 3–5
sessions of FP (1550-nm erbium doped Fraxel) treatment at
3–4-week intervals. Most patients reported a significant to
excellent improvement in the appearance of ice-pick, boxcar,
and rolling scars as well as a reduction in scar depth.
Skin laxity
Non-ablative skin tightening with radiofrequency in
Asian skin. Kushikata N, Negishi K, Tezuka Y, Takeuchi K,
Wakamatsu S. Lasers Surg Med 2005; 36:92–97.
Clinical study of 85 Japanese patients (skin phototypes III
and IV) to determine the efficacy of radiofrequency for skin
tightening in the areas of the nasolabial folds, marionette
lines, and sagging jowls with 6 months follow-up. The patients
were treated once with dosages ranging from 74 to 124╯J/cm2.
The overall improvement rates by objective physician evalua-
tion at 6 months post-treatment were 89% jowls, 89%
marionette lines and nasolabial folds, and 83.8% other facial
wrinkles. Complications included edema, burn (1 patient),
vesiculation (1 patient), and hyperpigmentation. All compli-
cations healed completely without permanent sequelae. The
authors state that the burn and vesiculation were likely due to
delivery of excessive heat and/or incomplete or non-uniform
contact of the treatment tip with the target skin.
Figure 17.40:╇ Skin of color patient who developed post-inflammatory
hypopigmentation after laser therapy.
Non-ablative infrared skin tightening in type IV to V Asian
skin: a prospective clinical study. Chua SH, Ang P, Khoo LS,
Goh CL. Dermatol Surg 2007; 33:146–151.
Twenty-one patients (Fitzpatrick skin types IV and V) with
facial and neck skin laxity received three treatments of non-
ablative infrared laser therapy at 4-week intervals. Wavelengths
ranged from 28 to 40╯J/cm2. At 6 months after treatment, 86%
of patients showed an observable lifting of sagging skin folds
by physician evaluation. Side effects included superficial vesic-
ulation and post-inflammatory hyperpigmentation.
A prospective, split face, single-blinded study looking at the
use of an infrared device with contact cooling in the treat-
ment of skin laxity in Asians. Chan HH, Yu CS, Shek S, Yeung
CK, Kono T, Wei WI. Lasers Surg Med 2008; 40:146–152.
This is a prospective, single-blind, split-face comparative
study of 13 patients (Fitzpatrick skin types III and IV) to deter-
mine the efficacy of an infra-red device in the treatment of skin
laxity. Patients were treated on one side of the face with the
infra-red device at 36–46╯J/cm2 for two monthly sessions and
the contralateral side was left untreated as a control. 41% of
patients were identified as having some degree of improve-
ment on the treated side at 3 months follow-up by objective
assessment. The treated side showed a significant improve-
ment compared to the untreated side (p = 0.03). One patient
experienced superficial vesiculation, which completely resolved
by the 3 month follow-up visit.
Complications
The most common complication of laser and light-based hair
reduction in skin of color is post-inflammatory hyperpigmen-
tation, followed by hypopigmentation (Fig. 17.40). Devices
which employ poor cooling can produce bulk heating, leading
to full thickness scars (Fig. 17.41). Pain sensation often is a
good predictive factor if a significant complication is going to
343
 Part 5 Cosmetics
occur. A Nikolsky sign is an early indication of complication
and if blister formation is evident, the treatment needs to be
terminated. A test site is always advisable as it can be a guide
to setting appropriate parameters. Management of hyperpig-
mentation is with topical hydroquinones and sunscreens.
Hypopigmentation may be permanent. Extensive areas can be
treated with a non-ablative fractional laser (Fig. 17.42). Full
thickness scarring is usually preceded by the formation of a
blister. At the first sign of a blister, aggressive wound care must
be instituted to achieve adequate epithelialization. If this still
produces a scar, treatment options include non-ablative frac-
tional resurfacing and the use of dermal fillers.
Post-inflammatory hyperpigmentation is the most common
complication of the treatment of dyschromia and melasma
with pulsed light and non-ablative fractional resurfacing. Test
sites and pre-treatment with hydroquinones can help to
prevent this. Exacerbation of melasma with non-ablative frac-
Figure 17.41:╇ Full thickness scars on the forearm of patient who received laser
therapy without adequate cooling.
A B
Figure 17.42:╇ Before (A) and after (B) photos of a patient with hypopigmentation on the forearm treated with a non-ablative fractional laser.
344
tional resurfacing can also be seen (Fig. 17.43) and this is
managed with hydroquinones and the tincture of time. The
greatest patient complaint with devices for this indication is
the disappointment with results and therefore it is imperative
to discuss realistic outcomes with patients when employing
devices for these indications.
No adverse effects have been seen with blue light laser (420-
nm). Transient suction marks have been seen with photopneu-
matic therapy which resolves spontaneously. Higher fluences
may induce the same risks seen with traditional light-based
treatments for acne, including pigmentary changes and blister-
ing. Scarring has not been reported.
With the 1064-nm laser, inadvertent bulk heating may
produce pigmentary anomalies such as hypopigmentation
(Fig. 17.44) and full thickness scarring. Non-ablative frac-
tional resurfacing is the safest mode of treating skin of color
Figure 17.43:╇ Exacerbation of melasma after non-ablative fractional resurfacing.
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices
Figure 17.44:╇ Hypopigmentation after treatment with Nd-YAG laser due to bulk
heating in a Fitzpatrick skin type V patient.
Figure 17.45:╇ Burn resulting from bulk heating with infra-red light.
for these indications, as the chromophore is “color blind” and
the laser delivery is fractional, thereby reducing the risk of
bulk heating. Post-inflammatory hyperpigmentation may still
ensue, but can be prevented by pre-treatment with hydroqui-
nones. Hypopigmentation and scarring have not been reported
with non-ablative fractional lasers. Ablative fractional resurfac-
ing is generally not recommended in skin of color.
While in theory radiofrequency and infra-red light devices
are ‘color blind’ as the chromophore is water, they are still
delivering very high energies to the skin. Therefore, optimal
cooling to protect the epidermis is critical. The older protocols
of unipolar radiofrequency reported complications such as
subcutaneous atrophy and scarring, which is now rarely seen
with the newer protocols which utilize lower energies and
multiple passes. Bulk heating with infra-red light sources
is still a risk and can produce permanent scars (Fig. 17.45).
These complications require the use of resurfacing and dermal
filler.
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14. Adrian RM, Shay KP. 800 nanometer diode laser hair removal in
African American patients: a clinical and histologic study. J Cutan Laser
Ther 2000; 2:183–190.
15. Lee JH, Huh CH, Yoon HJ, et al. Photoepilation Results of Axillary Hair
in Dark-skinned Patients by IPL: A Comparison Between Different
Wavelength and Pulse Width. Dermatol Surg 2006; 32:234–240.
16. Johnson F, Dovale M. Intense pulsed light treatment of hirsutism: case
reports of skin phototypes V and VI. J Cutan Laser Ther 1999;
1:233–237.
17. Negishi K, Kushikata N, Takeuchi K, et al. Photorejuvenation by
Intense Pulsed Light with Objective Measurement of Skin Color in
Japanese Patients. Dermatol Surg 2006; 32:1380–1387.
18. Al-Otaibi SR, Zadeh VB, Al-Abdulrazzaq AH, et al. Using a 308-nm
excimer laser to treat vitiligo in Asians. Acta Dermatovenerol Alp
Panonica Adriat 2009; 18:13–19.
19. Lee HS, Won CH, Lee DH, et al. Treatment of Melasma in Asian Skin
Using a Fractional 1,550-nm Laser: An Open Clinical Study. Dermatol
Surg 2009; 35:1499–1504.
20. Tzung TY, Wu KH, Huang ML. Blue light phototherapy in the
treatment of acne. Photodermatol Photoimmunol Photomed 2004;
20:266–269.
21. Lee DH, Choi YS, Min SU, et al. Comparison of a 585-nm pulsed dye
laser and a 1064-nm Nd:YAG laser for the treatment of acne scars: A
randomized split-face clinical study. J Am Acad Dermatol 2009;
60:801–807.
22. Jones A, Roddey P, Orengo I, et al. The Q-switched ND:YAG Laser
Effectively Treats Tattoos in Darkly Pigmented Skin. Dermatol Surg
1996; 22:999–1001.
23. Lee HS, Lee JH, Ahn GY, et al. Fractional photothermolysis for the
treatment of acne scars: A report of 27 Korean patients. J Dermatolog
Treat 2008; 19:45–49.
24. Kushikata N, Negishi K, Tezuka Y, et al. Non-Ablative Skin Tightening
With Radiofrequency in Asian Skin. Lasers Surg Med 2005;
36:92–97.
25. Chua SH, Ang P, Khoo LS, et al. Nonablative Infrared Skin Tightening
in Type IV to V Asian Skin: A Prospective Clinical Study. Dermatol Surg
2007; 33:146–151.
345
 Part 5 Cosmetics

tion and hypertrophic scarring, it is important to obtain a

Commonly encountered pitfalls thorough medical history prior to the initial treatment,
The response of skin of color patients to cosmetic procedures perform a skin test and above all, exercise caution. It is best to
can be variable (Table 17.10). In an effort to avoid complica- start at lower concentrations and fluences and titrate up once
tions like hypopigmentation, PIH, or burns, which can be it is known how the patient will respond to treatment.
particularly obvious in dark-skinned patients, careful selec- In treating conditions of the scalp and hair in patients with
tion, with the skin of color patient in mind, of the chemical skin of color, particularly African-American patients, it may
peeling agent or laser should be performed. Also, given the prove beneficial to become familiar with the hair care products
skin of color patient’s propensity toward keloidal scar forma- and grooming practices used by this population to ensure
proper and competent counseling. It is also important to
Table 17.10╇ Commonly encountered pitfalls in cosmetic treatments remember the differences in the morphology of the hair
for skin of color follicle between patients of African descent and Caucasian
patients (curved versus straight, respectively) when performing
hair transplantation to avoid transection of the hair follicle.
Cosmetic
procedure Dyschromia* HTS/Keloids Others
Special management & counseling considerations
Chemical peels +++ +
Erythema after chemical peeling is almost always transient but
BoNT-A – –
typically should be treated with topical corticosteroid therapy
Fillers + – to minimize the development of PIH, which patients with skin
Hair – + Follicle of color are more prone to develop.1 PIH in dark-skinned
transplantation transection patients can be prevented and treated with topical depigment-
Laser surgery ++ + ing agents such as hydroquinone as part of the pre-peel
and maintenance regimens.2 Daily use of a sunscreen or
*Post-inflammatory hyper- or hypopigmentation
sunblock and other sun protection measures including avoid-
HTS = Hypertrophic scars
BoNT-A = Botulinum toxin type A ance are also important ways to prevent peel-induced PIH
(Table 17.11).

Table 17.11╇ Special management and counseling considerations in skin of color

Cosmetic procedure Considerations

Chemical peels Titrate concentration

Perform a test session
Adjunctive skin lightening agents
Post-procedure topical corticosteroids to decrease inflammation
Sun protection
BoNT-A None
Fillers Lessen the number of injections to minimize trauma and sequelae – PIH
Deeper injection
Post-injection application of a topical corticosteroid cream to decrease inflammation
Hair transplantation Magnification for better visualization of curved hair shaft and follicle – donor harvesting and graft creation
Proper selection of surgical instruments
Topical and intra-lesional corticosteroids to minimize or treat scar formation in the donor area
CCCA patients – perform a test session and confirm an absence of inflammation via scalp biopsy
Postoperative hair grooming
Laser surgery Proper selection of laser parameters – lower fluences (energy), longer wavelengths and longer pulse durations
Skin cooling
Post-treatment application of a topical corticosteroid cream to decrease inflammation
BoNT-A = Botulinum toxin type A
PIH = Postinflammatory hyperpigmentation
CCCA = Central centrifugal cicatricial alopecia

346
 17â•… Cosmetic Treatmentsâ•… •â•… Lasers, light sources and other devices
Using dermal fillers in patients with skin of color is typi-
cally safe and effective. Keloid formation and hypertrophic
scarring are very uncommon with this procedure. However,
any procedure that could provoke an inflammatory response
could lead to dyschromias. The incidence of pigmentary
changes (hyper- and hypopigmentation) at the injection site
in patients with skin of color has been reported to be from 6%
to 15%.3,4 Post-injection application of a mid- to high topical
corticosteroid, especially if erythema is appreciated, may
decrease the risk of dyspigmentation in skin of color. Several
studies have demonstrated the absence of keloid formation.
In hair transplantation, as with any other surgical proce-
dure, there is an increased risk of hypertrophic scarring and
keloid formation in patients with skin of color. Therefore, in
males, who typically cut their hair short, the location of the
donor scar should be discussed and carefully selected.
It is also important to use caution during donor harvesting
and graft preparation, particularly in African-American
patients. The morphology of the hair follicle in most Black
patients is curved, which leads to an increased risk of transec-
tion of the hair follicle when using a straight blade.5 In CCCA,
reactivation of the inflammatory process may occur with trans-
plantation. Therefore, multiple scalp biopsies demonstrating
the absence of inflammation preoperatively and intraopera-
tively should be performed. In traction alopecia, hair groom-
ing modification must include the discontinuation of hairstyles
that cause traction including tight ponytails, braids, and hair
extensions.
The use of lasers can be a safe and effective mode of treat-
ment in patients with skin of color when used properly. It is
important to perform skin tests prior to the initial treatment
and work at lower fluences than would normally be used in
fair-skinned patients to possibly avoid complications like
hyper- or hypopigmentation, erythema, and scarring. Typically
the safest lasers to use in dark-skinned patients are those with
longer wavelengths and pulse durations, and cooling mecha-
nisms to allow for greater penetration depth and slower
heating of the epidermis.6 The majority of complications in
skin of color are due to pigmentary anomalies and bulk
heating. The former can be controlled with adequate pre- and
post-treatment use of hydroquinones. The latter can be con-
trolled with optimal cooling, fractional modes of laser delivery
and photomodulation.
References
1. Sarkar R. Medium-depth chemical peels and deep chemical peels.
In: Grimes PE, ed. Aesthetics and cosmetic surgery for darker
skin types. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:
170–178.
2. Burns RL, Prevost-Blank PL, Lawry MA, Lawry TB, Faria DT, Fivenson
DP. Glycolic acid peels for post-inflammatory hyperpigmentation in
black patients: a comparative study. Dermatol Surg 1997; 23(3):
171–174.
3. Grimes PE, Few JW. Injectable fillers in skin of color. In: Carruthers J,
Carruthers A, eds. Procedures in cosmetic dermatology series:
soft tissue augmentation. 2nd edn. Philadelphia: WB Saunders; 2007:
143–150.
4. Taylor S, Burgess C. Assessment of adverse experiences, keloid forma-
tion, and pigmentary changes in subjects with Fitzpatrick skin types 4,
5, or 6 injected with hyaluronic acid gel dermal fillers. Plast Reconstr
Surg 2007; 120(4S):104.
5. Callender VD. Hair transplantation for pigmented skins. In: Halder
RM, ed. Dermatology and dermatological therapy of pigmented skins.
London: Taylor and Francis; 2006:245–257.
6. Soriano T, Beynet D, Carranza DC. Laser hair removal in darker racial
ethnic groups. In: Grimes PE, ed. Aesthetics and cosmetic surgery for
darker skin types. Philadelphia, PA: Lippincott Williams & Wilkins;
2008:303–309.
347
This page intentionally left blank
 PART 6
Complementary and
Alternative Medicine
This page intentionally left blank
Part 6 Complementary and Alternative Medicine
An Overview of
Complementary and
Alternative Medicine
Janet L Nelson and Sonia Badreshia-Bansal
Introduction . . . . . . . . . . . . . . . . . . . . . . . .
Acne . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Alopecia . . . . . . . . . . . . . . . . . . . . . . . . . .
Eczema / Atopic dermatitis . . . . . . . . . . . . . . . .
Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction
Patients are seeking complementary and alternative medicine
(CAM) in unprecedented numbers, especially those with skin
conditions.1 According to government estimates, Americans
spend $34 billion dollars annually on complementary and
alternative medicine.2 Research into the reasons for this choice
indicates that patients often turn to alternative approaches as
a result of dissatisfaction with conventional medicine, or after
running out of options with orthodox therapies.3 These
patients may have responded less than satisfactorily to stand-
ard treatment, or experienced significant and unwanted side
effects.3 Some patients have a preference for modalities which
emphasize a mind-body connection not found in conven-
tional medicine.3 Other reasons identified for choosing CAM
therapies include a desire for a more natural therapy, the view
that CAM is less toxic or safer than conventional treatment,
and a desire to try any and all possible therapies.3,4,5 CAM use
by adults with dermatologic disorders in the US has been
estimated at between 50% and 62%.5
What is complementary and alternative medicine?
The National Center for Complementary and Alternative
Medicine (NCCAM) describes complementary and alternative
©2011 Elsevier Ltd, Inc, BV
18â•…
351 medicine (CAM) as a diverse group of medical and health care
systems, practices, and products that are not currently consid-
357
ered part of mainstream medicine.6 Complementary medicine
361 is any therapy that is used as an adjunct to conventional medi-
364 cine while alternative medicine is used in place of conven-
tional medicine.7 Alternative medicines come from a variety of
368
countries, and form the backbone of basic medical care for
much of the global population. To this day, medicinal plants
are the most commonly used form of traditional medication
worldwide, and medicinal herbs are central to alternative
therapies for dermatology.5 As alternative therapies become
increasingly integrated into mainstream medicine their
standing will be considered more complementary and less
alternative.
CAM therapies, as defined by the NCCAM, are divided into
the following four categories: alternative medical systems
which include Chinese medicine, Ayurveda, and homeopathy;
biologically-based therapies such as herbal products, nutri-
tion, megavitamin therapy, and non-vitamin, non-mineral
natural products; mind-body therapies such as biofeedback,
hypnosis, yoga, meditation, Qi Gong, Tai Chi, and Reiki; and
manipulative, body-based therapies such as chiropractic, and
massage6 (Table 18.1).
Heading the list of CAM modalities are the two oldest
medical systems still in use today: traditional Chinese medi-
cine (TCM) which includes acupuncture and herbal medicine,
and Indian Ayurveda which uses meditation, herbs, and diet
in combinations based on body type. Both are ancient healing
traditions that have been used safely and successfully in their
respective cultures for millennia. The foundation of alternative
therapies and one reason they hold such appeal is they take
into account the whole person – the physical, mental, emo-
tional, and spiritual aspects. These therapies follow a patient-
oriented approach with a high degree of interaction between
patient and practitioner.
351
 Part 6 Complementary and Alternative Medicine
Table 18.1╇ CAM therapies6
Alternative medical systems
• Traditional Chinese Medicine (TCM)
– Acupuncture
– Herbal medicine
• Ayurveda (India’s traditional healing system)
• Homeopathy
• Naturopathic medicine
Biologically-based therapies
• Herbal products
• Nutrition
• Megavitamin therapy
• Non-vitamin, non-mineral natural products
• Diet-based therapies
Mind-Body therapies
• Biofeedback
• Hypnosis
• Yoga
• Meditation
• Qi Gong
• Tai Chi
• Reiki
Manipulative, body-based therapies
• Chiropractic
• Massage
Given the rise in CAM use and its place as a significant
modality in the public’s eye, it has become increasingly impor-
tant for dermatologists to familiarize themselves with current
information on the most popular CAM therapies and their
efficacy. Dermatologists must also be aware of CAM usage by
their patients, many of whom don’t readily divulge this infor-
mation. Studies have reported that less than 40% of patients
using CAM discussed it with their doctor.8 It is therefore essen-
tial that physicians initiate these discussions and foster an
environment of open, non-judgmental communication which
respects their patient’s treatment choices. With knowledge of
CAM modalities, dermatologists can provide informed and
balanced advice to their patients. Physicians must also be
aware of how much a patient’s psyche can be affected by their
skin problems. Several studies have made a therapeutic con-
nection between addressing a patient’s psychological land-
scape and clinical success in treatment.9–11
In light of growing demand and widespread use, many
doctors now incorporate a variety of alternative modalities
along with their standard treatments (integrative dermato�
logy) and frequently collaborate with skilled, specialist prac�
titioners of alternative medicine to provide a multi-prong
approach of comprehensive care that optimizes treatment.
Recognizing that many disorders, especially chronic ones, have
a variable and often complex mix of physical, social, psycho-
352
90
80
70
60
50
40
$20 million
$12 million
30
$7.3 million
$5.4 million
$3.5 million
$3.5 million
$69.2 million
20
$2 million
$50 million
$69 million
10
0
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Figure 18.1:╇ CAM funding shows significant increases.12
logical, environmental, and genetic factors, applying a multi-
prong approach is therapeutically sound. This is not a new
idea. Rather, it is one put forth since ancient times when
Socrates warned that treating only one part of the body would
not have good results.
While critics maintain that alternative medicine falls behind
in rigorous scientific evidence, it nonetheless has a huge
amount of experience-based knowledge which many consider
to be of equal, if not greater value. It must be noted that
until recently there has been a lack of funding and little
financial incentive for conducting scientific studies using
natural substances and ancient modalities that are not
patentable or profit-generating. In recent years, NCCAM has
begun increasing its funding for CAM research (Fig. 18.1) and
since 1999 has funded more than 2200 studies.12 Even so, a
lack of evidence should not at this point be equated as evi-
dence for a lack of efficacy. In fact, there is no shortage of
published literature in Asia on the efficacy and safety of herbal
medicine, acupuncture, and other medical sciences. But this
vast amount of data will likely never get the exposure it
deserves in the West, as it remains to be translated into the
English language.13
This chapter was written to provide the dermatologist with
an overview of some of the most common, successful, and
promising forms of complementary and alternative treatment
as well as some popular but unproven methods. Before cover-
ing individual disorders, it is important to first discuss the
ethnic groups that use CAM, and review the top three CAM
modalities. The remainder of the chapter will focus on com-
monly seen disorders with supporting evidence as well as
anecdotal information.
Who uses CAM?
Recently, the NCCAM compiled statistics showing CAM use by
race/ethnicity (Fig. 18.2), with the highest use by American
Indian/Alaskan Native. Other studies demonstrate CAM use to
be highest among Hispanics and Asians.14–17 The use of com-
plementary and alternative medicine can vary considerably
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Introduction
60
50.3%
50
43.1%
39.9%
40
30
25.5%
20
10
0
American White Asian Black
Indian/
Alaskan
native
Figure 18.2:╇ CAM use by race/ethnicity among adults.14–17
Table 18.2╇ Most commonly used CAM modalities
CAM modality
1. Herbal medicine/herbal supplementation
2. Homeopathy
3. Traditional Chinese medicine (TCM)
4. Nutritional supplements and vitamins
among racial/ethnic groups because it is often used in relation
to cultural and health beliefs.18 While CAM is used by people
of all backgrounds, the studies agree that it is used more fre-
quently by women and those with higher levels of education
and income.18,19
On a global scale, herbal medicine and acupuncture are the
most widely-used therapies according to the World Health
Organization (WHO), with published reports of their clinical
efficacy. In addition, WHO reports that up to 80% of the
popu�lation of developing countries use traditional medicine
or CAM as a cost-effective source of comprehensive primary
health care.13,20,21
Herbal medicine and herbal supplements are the most
popular CAM modality in the U.S., and the most pertinent to
dermatology, yet many healthcare providers lack adequate
knowledge about herbs. A survey of CAM use by patients with
psoriasis showed that those reporting skin problems were
more likely to use CAM than those who did not.5 In addition,
CAM patients, on average, used two or more CAM modalities
for their treatment. According to the same survey, the next
most often used therapy after herbal medicine (and specifically
for skin disorders) is homeopathy, followed by traditional
Chinese medicine (TCM), and nutritional supplements (Table
18.2).4,5 It should be noted that diet-based therapies such as
vegetarian, high-protein, and macrobiotic diets were counted
in the percentages of CAM use in this survey (20.8%). However,
they were not used specifically for skin problems; therefore,
they will not be included with the therapies which were used
specifically for skin problems.
Herbal medicine
23.7%
Of the available alternative modalities, treatment with Chinese
herbal medicine (CHM) ranks high in terms of clinical success
in dermatology. The medicinal strength of plants has been
known for thousands of years and numerous clinical trials
confirm its efficacy. From an apothecary of hundreds
Hispanic of medicinal plants, herbal medicine utilizes all parts of the
plant from the flower, fruit, seed, bark, leaf, and stem, to the
root, all of which contain numerous chemical constituents,
many still unrecognized. A host of modern drugs, such as
aspirin and alkaloids, are the highly concentrated synthetic
forms of these natural constituents. An astonishing 25% of
pharmaceutical drugs continue to be derived from plant
sources. The TCM materia medica utilizes substances not only
from China’s own folk medicine, but from other parts of the
world including India, the Middle East, Southeast Asia, and
Users the Americas.
The fundamental element of treatment with CHM is that
although the symptoms manifest on the skin, they reflect an
64.6%
internal or systemic problem. Skin disorders are best resolved
18.8% when treated from the inside out, with both an oral (internal)
18.8% and topical (external) herbal prescription. Treatment with
12.5% herbs is highly individualized and first requires a clear diag-
nosis by a trained Chinese medicine physician to determine
the root cause of the condition. An effective herbal prescrip-
tion constitutes not the use of a single herb in isolation, as is
common in western herbology, but rather a complex combina-
tion of selected medicinal herbs, often up to a dozen or more,
which together address a multitude of underlying factors. The
properties and actions of each separate herb and their syner-
gistic effects when combined must be well understood. Once
the patient’s pattern has been correctly identified, using diag-
nostic principles inherent to the practice of Chinese medicine,
an herbal formula can be compounded from either raw herbs,
to be decocted into a tea, an elixir, or a topical solution; or
from powdered, pre-decocted herbs that can be taken by the
spoonful, made into capsules, or added to a cream or other
type of base for external application.
Successful oral administration of herbs is complex and
requires a solid comprehension of Chinese herbal pharma�
cology. Administration should only be undertaken by fully
trained experts, with the requisite knowledge and background,
in accordance with a traditional individualized diagnosis.
Chinese herbal medicine is safe and effective when adminis-
tered in this manner. Adverse effects, although very rare, can
and do happen. It is primarily a problem of inappropriate use
by unskilled individuals. There have also been instances of
heavy metal contamination and unlabeled pharmaceutical
additives found in prepared formulas imported from
China.13,22,23 To avoid potential additives and contaminants, it
is suggested that physicians use only those herbal products
353
 Part 6 Complementary and Alternative Medicine
that have been manufactured in the U.S. and purchased from
reputable companies that adhere to Good Manufacturing
Practice (GMP).
Because of the complex nature of prescribing oral medicinal
herbs, it is recommended that the dermatologist only use
topically-based herbal products, or if oral Chinese herbs are
desired, the dermatologist should refer to the appropriately
trained professional. Topical herbal formulas are often effica-
cious, easy to use and readily available.
Numerous Western herbs and botanicals are also used in
dermatology and some have been shown to be very effective.
Western herbs are used individually (unlike CHM) and most
patients purchase them from a health food store. A few of the
herbs used specifically in dermatology include aloe vera, garlic,
chamomile, ginger, curcumin, and capsaicin (cayenne). They
can be used in many forms including as a tea, a tincture, in
powdered form, in creams and lotions, capsules, or tablets.
Patients commonly use herbs they have heard about, and for
the layperson, unfortunately, much misinformation exists.
Homeopathy
The practice of homeopathy, one of the most controversial of
the alternative healing systems, was developed by a German
doctor, Samuel Hahnemann, more than 200 years ago. While
homeopathic treatment has often been of significant benefit
for many disorders, no one can really explain how and why it
works, hence the reason for its sometimes questionable prac-
tice. Despite this fact, homeopathy is becoming increasingly
popular worldwide, where a substantial following of people
rely at least in part, on its use. In recent years, homeopathic
medicines have been subjected to rigorous scientific evalua-
tion. The result has been a growing body of double-blind,
placebo-controlled trials which suggest homeopathy may be
clinically effective.24 In the US the number of patients under-
going homeopathic care quadrupled from 1991 to 1997.25
Homeopathy dates back to the late eighteenth century
when Hahnemann began experimenting with cinchona bark
(the source of the drug quinine), and upon ingesting a thera-
peutic dose, observed that it quickly gave his healthy body all
the symptoms of malaria. After this experience he reasoned
that a substance that could create symptoms in a healthy body
could effectively treat similar symptoms in an ill body. Thus,
he began the idea of ‘treatment by similars.’
The principle behind homeopathy is to stimulate the body’s
defensive reaction by taking infinitesimal amounts of sub-
stances called remedies. These extremely small concentrations
(in the 10−6 to 10−1000 range) are given to resolve or prevent an
illness or condition.26 The more dilute the concentration, the
more powerful it is said to be. Sometimes the dilutions are so
small they exceed Avogadro’s number.
Homeopathic medicines are not just diluted. They are also
shaken vigorously or ‘potentized’ which is believed to help
transfer the essence of a substance to the water in which it is
diluted. Homeopathic remedies are individualized to each
patient and a practitioner treats according to symptoms,
emotional/mental state, lifestyle and other factors.
354
Homeopathic remedies are known by Latin names or Latin
abbreviations of their active ingredients. For example, a patient
who has poison ivy will be given a homeopathic preparation
called Rhus toxicodendron, made from the actual oleoresin
found in the poison ivy plant. This is a classic example of
homeopathic treatment where ‘like treats like.’ Another well
known homeopathic remedy is arnica, which is typically given
to patients in pill form sublingually right after surgery, trauma,
or as needed to promote healing, reduce pain and swelling.
With homeopathy there are reportedly no side effects and it is
a very cost effective therapy. Homeopathic remedies are sold
as over-the-counter medicine exempt from the government
regulations applied to pharmaceuticals.
Traditional chinese medicine
The most well-known of the CAM medical systems, traditional
Chinese medicine (TCM) is a complete system of health care
originating in China more than 3000 years ago. It encom-
passes a wide range of practices from acupuncture and herbal
medicine to nutritional food cures and moxibustion (thera-
peutic burning of the herb mugwort). The strength of Chinese
medicine comes from its long history of accumulated knowl-
edge and wisdom, of treating and preventing illness, and pro-
moting health and longevity. Little is known about TCM prior
to the writing of one of the oldest major medical texts, The
Yellow Emperor’s Classic of Internal Medicine (The Huang Di Nei
Jing), which was compiled and written by unknown scholars
around 200 B.C., and based on discussions which took place
nearly 2000 years prior between Emperor Huang Di (the
Yellow Emperor) and his physician Qi Bo (circa 2697–2205
B.C.). These discussions, passed down through the tradition of
oral re-telling, became the seminal text upon which the foun-
dations of Chinese medicine were built. The Nei Jing, as it is
usually abbreviated, contains fundamental theories of TCM as
well as information crucial to the development of medicinal
herbal formulas. It also covers acupuncture, physiology,
anatomy, pathology, diagnosis, and treatment.
The difference that sets the practice of Chinese medicine
apart from non-CAM treatment is its focus on treating the root
cause of the condition, along with providing uniquely indi-
vidualized treatment for each patient, emphasizing prevention
(rather than disease), and promoting the body’s self-healing
mechanism. It is understood that good health is fundamen-
tally related to balance and harmony – to Yin and Yang –
which proper treatment aspires to restore. Over the centuries,
TCM doctors have gained a wealth of knowledge and experi-
ence in the etiologic, diagnostic, and clinical treatment of
various syndromes and diseases. As often happens in chronic
conditions, a patient will present with numerous symptoms
that the Chinese physician uses to identify an individualized
diagnostic pattern. In difficult to treat conditions, a patient will
often have a minimum of three or more simultaneous pat-
terns. For complete resolution of the disorder the correct
pattern(s) must be identified and appropriately treated. The
WHO supports traditional Chinese medicine and its efficacy
in healing many diseases.21
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Introduction
Table 18.3╇ Skin conditions treated with acupuncture27
• Acne
• Alopecia
• Dermatitis
• Eczema
• Pompholyx eczema
• Rosacea
• Pruritis
• Melasma (chloasma)
• Seborrheic dermatitis
• Psoriasis
• Urticaria
• Systemic lupus erythematosus
• Herpes Zoster
• Impetigo
• Vitiligo
• Tinea
• Leprosy
Acupuncture
The use of acupuncture in dermatology is also a common
practice, where it has been used to treat a number of skin
disorders27 (Table 18.3) Acupuncture is a popular modality,
used in an estimated 78 countries and practiced not only by
licensed acupuncturists and TCM doctors, but also by conven-
tional physicians who must undergo additional, specialized
training.21 Designated therapeutic acupuncture points are
found in hundreds of locations on the body, face, hands, ears,
and feet, where they follow pathways known as ‘meridians.’
Meridians create an unseen network that connects every part
of the body. Because this network is extensive, almost any area
from head to toe can be used as a site for acupuncture, even
though it may not be an actual, designated point. When points
are used in this manner they are called ‘Ah-shi’ points. It is
worth noting that in many clinical trials of acupuncture, ‘sham’
acupuncture points are used for treatment on patients that do
not receive treatment at the actual therapeutic points. The
‘sham’ points used can include both random points and ‘Ah-
shi’ points. Because acupuncture points and ‘Ah-shi’ points are
found everywhere on the body, the ‘sham’ acupuncture may
in fact be causing its own therapeutic effect, thus leading to a
less significant and often inconclusive difference between
patient groups. In light of this, it may be reasoned that utiliz-
ing ‘sham’ points is perhaps not the best gauge of the effective-
ness of acupuncture, and better methods of assessing clinical
efficacy should be sought.
Acupuncture, as with Chinese herbal medicine, treats the
whole person and can offer something for almost every disor-
der. It is an individualized treatment, and no two patients will
receive the same acupuncture prescription – even if they both
present with what appears to be the same condition. For most
chronic disorders, Chinese medicinal herbs are the standard
of care, with acupuncture providing an effective adjunct treat-
ment. At the very least, acupuncture can effectively control the
disorder while it aims for a complete cure. The practice of
acupuncture is different in the Western world than it is in
China. In the West, patients typically come for acupuncture
treatment on average 2 to 4 times per month, while in China
they are given treatment one or more times per day. Closely
spaced treatments, as a rule, tend to be more effective than
once weekly treatments.
Skin disease and psychology/psychodermatology
Skin disease can have a devastating effect on the life of
a patient. Many patients who live with a chronic disorder
find it to be emotionally taxing. This psychological stress
can exacerbate any number of skin conditions. Recent litera-
ture has found that depression in dermatological patients is
significantly more prevalent compared with the general popu-
lation.12,28 An approach called psychodermatology, or psycho-
cutaneous medicine, looks at the clinical relationship between
the skin and the mind in the onset and progression of assorted
dermal disorders.29–31 Psychodermatology helps address the
psychological sequelae involved in these disorders, however, it
is not designed to substitute psychotherapy for medical treat-
ment. Instead, it aims to recognize that emotional issues may
be involved in many cases where conventional treatment alone
does not resolve a skin problem.
Psychodermatological disorders have been classified into
three groups: psychophysiologic disorders (common skin
problems elicited or aggravated by emotional factors), derma-
tologic disorders with simultaneous psychiatric symptoms
i.e. those with a disfiguring component such as vitiligo, and
primary psychiatric disorders with concurrent dermatologic
symptoms such as trichotillomania (Table 18.4).31,32 A signifi-
cant and well-substantiated incidence of psychosocial and psy-
chiatric comorbidity exists in more than 30% of skin disease
patients.33 Actual levels may be higher as suggested by esti-
mates which place it between 40% and 80%.34 Left untreated,
comorbid psychological disorders may cause patients to be
less responsive to standard dermatological treatment.33
For patients suffering with chronic skin conditions, many
have feelings of anxiety, low self-esteem, or helplessness,
fearing their condition may never improve, or perhaps even
worsen. Many will withdraw socially rather than face reactions
by others to their condition. Situations like these serve to
underscore the increasing importance for physicians of under-
standing the dynamics inherent in living with a chronic or
cosmetically disfiguring skin disorder. There is much to be
therapeutically gained when a physician can incorporate a
compassionate approach; choosing optimistic words when
consulting and treating patients, and who can convey a sense
of acceptance and support.31 Several studies demonstrate the
importance of addressing the psychological component
involved in skin disorders, and that clinical success is enhanced
and more easily attained when these aspects are undertaken
as part of routine treatment (Fig. 18.3).9–11
Therapeutic modalities frequently recommended by
psychodermatologists include anxiety-decreasing therapies
such as acupuncture, meditation, hypnosis, and massage to
counteract the stress response which can worsen any skin
355
 Part 6 Complementary and Alternative Medicine

80
Table 18.4╇ Classification of psychodermatologic disorders9–11
70
Psychophysiologic disorders
• Psoriasis 60
• Atopic dermatitis/eczema

• Urticaria
• Rosacea
• Pruritis
• Acne excoriee
• Hyperhidrosis
• Herpes Simplex virus infection
• Seborrheic dermatitis
• Apthosis
Dermatologic disorders with psychiatric symptoms
• Alopecia areata
• Vitiligo
• Chronic eczema
• Generalized psoriasis
• Albinism
Psychiatric disorders with dermatologic symptoms
• Trichotillomania
• Obsessive-compulsive disorder
• Body dysmorphic disorder
• Dermatitis artefacta
• PTSD (post-traumatic stress disorder)
• Neurotic excoriations
• Social phobia (social anxiety disorder)
• Delusions of parasitosis
• Eating disorders
• Phobic states
• Psychogenic pruritis
problem.12,31,35 These modalities are used in combination with
conventional dermatological treatment.
Conclusion
More than one-third of US adults currently use complemen-
tary and alternative medicine (CAM) but less than 40% tell
their physicians. With patients of all backgrouds seeking out
CAM in growing numbers, it makes sense for physicians and
dermatologists to become knowledgeable in CAM modalities.
While CAM use varies by ethnicity and race, women are more
likely to use CAM, as are those with a higher level of education
and income. Patients typically use two or more CAM modali-
ties, with herbal medicine being the most popular CAM choice
worldwide. CAM therapies are increasingly incorporated into
conventional medicine in the form of integrative dermatology.
The most effective clinical results come from using a multi-
prong approach and addressing emotional and psychological
issues along with conventional treatment. With well-designed
CAM studies in short supply in the English literature, there
remains a greater need for such studies in order to guide and
better inform clinical decision making.
% clinical improvement
50
40
30
20
10
0
Traditional Psychocutaneous Combined
techniques
dermatological therapy
therapy
Figure 18.3:╇ Enhanced clinical improvement with combined therapy.31
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dermatology. Arch Dermatol 1998; 134(11):1437–1441.

Acne
Many CAM modalities are available for the treatment of acne
including botanical ingredients, topical essential oils, certain
homeopathic remedies, diet, nutrition, and vitamins. However,
most of these therapies are thought to be primarily anecdotal
due to an absence of published evidence or poorly designed
and conducted trials. In addition, numerous studies published
in Asian medical journals demonstrate that herbal medicine,
acupuncture, and moxibustion are likewise effective therapies
but supporting evidence is rarely trans�lated into English and
thus is inaccessible to the Western physician. There is a need
for more well controlled studies in the English literature in
order to draw appropriate conclusions.
Summary of Advocated CAM Therapies for Acne
Alternative Medical Systems
â•… Chinese herbal medicine
â•… Indian/Ayurvedic herbal medicine
â•… Acupuncture & moxibustion
â•… Topical herbs/plants
â•… Homeopathy
â•… Topical essential oils/aromatherapy
Biologically Based Therapies
â•… Diet/nutrition
â•… Vitamins/minerals
Chinese Herbal Medicine
Like all skin conditions, the etiology of acne can be attributed
to a combination of internal and external factors. In much the
same way that conventional thinking views acne as caused by
infection with P. acnes, excess sebum secretion, and androgenic
hormones (to name a few), Chinese medicine views things
similarly, but uses terminology and concepts foreign to main-
stream medical thinking. While acknowledging infection and
inflammation of lesions, acne is considered to be an internal
imbalance of excess heat, dampness, and toxins, with the occa-
sional congealing or stasis of blood as a secondary manifesta-
tion. The aim of treating acne from a Chinese medical
perspective (using TCM terms) is to ‘clear heat’, ‘dry dampness’,
‘resolve toxins’, and/or ‘move blood’ (i.e. break up stasis).
Conducting a thorough visual inspection of lesions is one
essential part of determining the underlying pathology and
dominant pattern upon which correct diagnosis and treatment
will be based. For example, it is readily apparent that redness
and inflammation of lesions indicates heat and the presence
of infection – more redness equals more heat. Lesions with
Variable white matter and pus are a sign of dampness. Oily, greasy skin
Variable combined with yellowish pus indicates a combination of
Variable dampness and heat (damp-heat). Deep, inflamed nodules and
Variable pus-filled cysts typical of cystic acne have a combined syn-
drome of heat, dampness, and toxins. Some lesions exhibit a
Anecdotal
purplish colour which signifies that blood stasis is part of the
Anecdotal pattern. The presence of any combination of the above-named
patterns/syndromes can be part of the acne most commonly
Anecdotal seen in practice.
Anecdotal The physician’s goal is to clear and resolve the patholoÂ�
gies which lie at the root of the condition. This is readily

357
 Part 6 Complementary and Alternative Medicine
Table 18.5╇ Topical Chinese herbal formula – ‘Three Yellows Powder’
(San Huang San)*
Scientific name Chinese name Therapeutic action
Cortex Phellodendri Huang Bai Antibiotic, anti-inflammatory
Radix Scutellaraie Huang Qin Antibiotic, anti-inflammatory
Baicalensis
Radix Et Rhizoma Da Huang Antibiotic, clears heat
Rhei
Radix Sophorae Ku Shen Antibiotic, antifungal, stops
Flavenscentis itching
*Grind ingredients into a fine powder. Dissolve equal amounts in water (or oil) and
apply twice per day. Therapeutic action: Clears heat and dries dampness, stops itching
(for acne, eczema, allergic dermatitis)
accomplished by treating the patient with a combination of
Chinese medicinal herbs utilizing two different formulas: one
for internal (oral) use and a second for external (topical)
application. A correct diagnosis steers the doctor toward the
specific herbs to use. A typical oral formula will consist of
10–12 different herbs which are known to be pharmacologi-
cally antibacterial, anti-inflammatory and skin regenerating.
These properties are well-documented in the Asian pharmaco-
poeia. As with all internal formulas, they should be prescribed
by professionals with the appropriate knowledge and exper-
tise, who understand herbal pharmacology. Many of the prin-
cipal Chinese herbs used for acne have a high content of
berberine, as found, for example, in Rhizoma Coptidis (Huang
Lian) and Cortex Phellodendri Chinensis (Huang Bai), both of
which are highly anti-bacterial as well as anti-inflammatory
(Table 18.5).
Chinese herbal medicine in the treatment of 58 cases of
acne. Zhong Z. New J Chinese Med 2001; 4:33–34.
58 patients with acne were given a standard oral Chinese
herbal formula called Qing Fei Yi Rou Tang, but adjusted
according to the morphology of the lesions and the constitu-
tion of the patient. After treatment ranging from 2 to 6 months,
the following results were recorded: 46 cases were classified as
clinically cured (all papules, pustules, nodules and cysts
cleared, with no recurrence); 10 cases were classified as
improved (reduction in all lesions, but mild recurrence on
stopping the herbs); and 2 cases were unchanged.
Clinical observation in 86 cases of acne vulgaris treated with
compound Oldenlandis mixture. Liu W, Shen D, Song P, Xu
X. China Academy of Traditional Chinese Medicine, Beijing.
86 patients with acne were treated with the Chinese herbal
compound Oldenlandis mixture and 34 patients were assigned
to a control group using a different herbal formula. Of the
treatment group, 73% showed marked improvement, com-
pared with 47% of the control group.
The medicinal action of androgens and green tea epigallo-
catechin gallate. Liao S. Hong Kong Med J 2001; 7(4):
369–374.
358
A specific green tea catechin, (-)epigallocatechin-3-gallate,
can modulate the production and biological actions of andro-
gens and other hormones when administered orally. No
mention was made of a study in conjunction with these
findings.
Indian/Ayurvedic herbal medicine
Along with Chinese herbal medicine, treatment with Indian
herbs (a specific formula of five herbs including turmeric) has
been shown effective in the treatment of P. acnes and
inflammation.
Inhibition of Propionobacterium acnes-induced mediators of
inflammation by Indian herbs. Jain A, Basal E. Phytomedi-
cine 2003; 10:34–33.
A combination of five herbs from the Indian materia medica
have been shown to significantly suppress the capacity of
P. acnes-induced reactive oxygen species (ROS) and pro-
inflammatory cytokines. (The herbs included Rubia cordifolia,
Curcuma longa, Hemidesmus indicus, Azadirachta indica, and
Sphaeranthus indicus).
All of these herbs have anti-inflammatory properties.
Treatment of acne vulgaris with new polyherbal formula-
tions. Sachidanand YN, Anand KBH. Indian J Dermatol 2000;
45; i3:138–141.
An open clinical trial of 105 patients with active acne lesions
who were administered an oral, multiple herb formula (purim)
in tablet form twice daily for 4 weeks. Simultaneously, they
applied an herbal cream (Clarina) twice daily on affected acne
areas for 4 weeks. The response to treatment was excellent for
Grade I and II acne after 4 weeks. For severe acne the response
was significant for healing of the papules and pustules. There
were no local or systemic side effects reported.
Nodulocystic acne: oral gugulipid versus tetracycline.
Thappa DM, Dogra J. J Dermatol 1994; 21(10):729–731.
20 patients were followed for 3 months and randomly
assigned to receive either tetracycline or oral gugulipid, an
Ayurvedic herbal preparation. Both therapies achieved compa-
rable results with the tetracycline group noting a 65% reduction
in acne lesions, and the gugulipid group, a 68% reduction.
A topical, extracted version of the Indian mukul myrrh tree,
gugulipid (guggul) can be applied three times daily to help acne.
Acupuncture and moxibustion
Acupuncture may also be used as an adjunct treatment along
with herbal medicine to further support the body’s ability to
clear pathogens and relieve stasis in the acne condition. The
following is a review of several published papers where acu-
puncture and moxibustion were used in acne treatment.
Evaluation of therapeutic effect and safety for clinical ran-
domized and controlled trials of treatment of acne with
acupuncture and moxibustion. Li B, Chai H, Du YH, Xiao L,
Xiong J. Zhongguo Zhen Jiu 2009; 29(3):247–251.
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Acne
An analysis of 17 papers, including 1613 cases, eva�
luated the therapeutic effect and safety of acupuncture and
moxibustion for treatment of acne against a control of routine
Western medicine. The analysis concluded acupuncture and
moxibustion to be safe and effective, and possibly better than
routine Western medicine, but further research is needed.
Homeopathy
Common homeopathic remedies for acne include: Thuja,
Hepar sulfuris, Silicea for whiteheads, Kali muriaticum for
lesions with thick white pus, and Graphites for lesions with
yellow pus.
Effect of homeopathic treatment of 60 Japanese patients
with chronic skin disease. Itamura R. Complement Ther Med
2007; 15(2):115–120.
60 patients with chronic skin diseases including severe
acne, received individualized homeopathic treatments in addi-
tion to conventional dermatological treatments. 6 patients had
a 100% improvement, 23 had 75% improvement, 24 patients
had 50% improvement and 7 patients had 25% improvement.
A total of 88.3% of patients reported over 50% improvement.
Individualized homeopathic treatment can provoke a good
response in those with chronic skin disorders and may be a
useful therapy alongside conventional treatment.
Topical CAM Therapies
Topical CAM therapy for acne
Ayurvedic herbal medicine Variable
Chinese herbal medicine Variable
Topical herbs/plants Variable
â•… Aloe vera
â•… Green tea
Topical essential oils/aromatherapy Variable
â•… Tea tree oil
â•… Rosemary
â•… Citrus oils
Typical Chinese herbs that are used for acne (topical and
oral) include those that clear heat, dry dampness, and elimi-
nate toxins such as Forsythia suspensa (Lian Qiao), Rhubarb /
Radix et Rhizoma Rhei (Da Huang), Honeysuckle / Flos Lonicera
(Jin Yin Hua), Sophora flavescens (Ku Shen), and Rhizoma Cop-
tidis (Huang Lian). See Table 18.5 for a classical topical herbal
formula.
Antibacterial and anti-inflammatory effects of Jeju medici-
nal plants against acne-inducing bacteria. Kim SS, Kim JY,
Lee NH, Hyun CG. J Gen Applied Microbiol 2008; 54(2):
101–106.
Four Asian medicinal plants had value against two pus-
forming bacteria that trigger inflammation in acne. Ethanol
extracts of the plants were topically applied and tested for
antimicrobial activity against Propionibacterium acnes and Sta-
phyloccus epidermidis. Anecdotally, aloe vera applied to the face
as a gel is beneficial due to its action of clearing heat (cooling).
Pharmacological research shows that aloe vera contains
emodin glycosides which are anti-inflammatory and anti-
bacterial, as well as saccharides, amino acids, vitamins, and
trace minerals. Aloe not only has the ability to permeate the
deeper layers of the skin but it helps with tissue regeneration
while at the same time killing bacteria and removing toxins.
Green tea (Camellia sinensis) and Tea tree oil (Melaleuca
alternifolia) are botanical ingredients which can be applied
topically to reduce acne lesions. Tea tree essential oil works as
an antiseptic that can be topically applied to breakouts (utiliz-
ing 100% pure oil). A possible adverse event is contact
dermatitis.
The efficacy of topical 2% green tea lotion in mild-to-
moderate acne vulgaris. Elsaie ML, Abdelhamid MF, Elsaaiee
LT, Emam HM. J Drugs Dermatol 2009; 8(4):358–364.
20 patients with acne vulgaris were given 2% green tea
lotion to apply twice daily for 6 weeks. At the end of the trial
total lesions count (TLC) showed a reduction of 58.3%.
Treatment of acne vulgaris with 2% topical tea lotion.
Sharquie Ke, Al-Turfi IA, Al-Shimary WM. Saudi Med J 2006;
27(1):83–85.
60 patients in a single-blind, randomly-controlled study
were equally divided into two groups. Group A used freshly
prepared 2% tea lotion twice daily for 2 months, while group
B used a control solution. 49 patients completed the study.
Group A had significantly reduced lesions after 2 months. The
response of patients to treatment was complete in 64%, partial
in 24%, and no response in 12%. Group B showed no signifi-
cant reduction in lesions after 2 months. No side effects were
reported.
The efficacy of 5% topical tea tree oil gel in mild to moder-
ate acne vulgaris: a randomized, double-blind placebo-
controlled study. Enshaieh S, Jooya A, Siadat AH, Iraji F.
Indian J Dermatol Venereol Leprol 2007; 73(1):22–25.
50 patients divided into two random groups were treated
with topical 5% tea tree oil gel or a placebo for 45 days.
Response to treatment was evaluated by the total acne lesions
count (TLC) and acne severity index (ASI). There was a sig�
nificant difference between tea tree oil gel and placebo in the
improvement of the TLC and ASI.
A comparative study of tea-tree oil versus benzoyl peroxide
in the treatment of acne. Bassett IB, Pannowitz DL, Barnetson
RS. Med J Aust 1990; 153(8):455–458.
This single-blind randomized clinical trial with 124 patients
evaluated the efficacy and skin tolerance of 5% tea-tree oil gel
in the treatment of acne when compared with 5% benzoyl
peroxide lotion. Results showed that both 5% tea-tree oil and
5% benzoyl peroxide had a significant effect in reducing the
number of open and closed comedones, although the effects
were slower to occur with the tea-tree oil. Fewer side effects
were experienced with tea-tree oil patients.
359
 Part 6 Complementary and Alternative Medicine

Biological activities of Korean Citrus obovoides and Citrus

natsudaidai essential oils against acne-inducing bacteria. Table 18.6╇ Acne Pathogenesis and Dietary Interventions in Acne1–8
Kim SS, Baik JS, Oh TH, Yoon WJ, Lee NH, Hyun CG. Biosci
Biotechnol Biochem 2008; 72(10):2507–2513. Increased keratinocyte proliferation caused by
Two citrus oils, Citrus obovoides (Geumgamja) and Citrus Hyperinsulinemia
natsudaidai (Cheonyahagyul) were evaluated in vitro for anti- High glycemic index
acne activity against Propionibacterium acnes and Staphylococcus Increased androgen-mediated sebum production caused by
epidermis which are involved in acne. The Geumgamja and Hyperinsulinemia
Cheonyahagyul oils exhibited antibacterial activity against High glycemic index
both P. acnes and S. epidermidis. Their potential usefulness in Inflammation caused by
future cosmetic products was also assessed and found to have Polyunsaturated fatty acids (vegetable oils, processed foods)*
low cytotoxicity. In addition, they reduced P. acnes-induced Cereal grains*
secretion of interleukin-8 (IL-8) and tumor necrosis factor Dairy products*
alpha (TNF-alpha) in THP-1 cells, an indication of anti- Refined sugar*
inflammatory effects. Therefore, based on these results, Beneficial foods for acne
Geumgamja and Cheonyahagyul essential oils are attractive Unprocessed fresh fruits/vegetables:
acne-mitigating candidates for topical application. – Watermelon
– Cucumbers
Investigation of antibacterial activity of rosemary essential – Celery
oil against Propionibacterium acnes with atomic force micro- – Carrots
scopy. Fu Y, Chen L, Efferth T, Liang H, Liu Z, Liu W. Planta – Cherries
Med 2007; 73(12):1275–1280. – Raspberries
The antibacterial activity of rosemary (Rosmarinus officinalis – Papaya
L. labiatae) essential oil against Propionibacterium acnes was – Pears
observed with atomic force microscopy (AFM). Significant – Mung beans
changes in morphology and size of P. acnes were observed by – Squash
AFM in response to essential oil treatment, eventually leading Protein
to cell wall damage and bacterial death. – Mung beans
– Lean meats
– Fish
– Seafood
Diet
*controversial
Despite the fact that Western medicine largely maintains that
diet is not a causative factor for acne, a growing body of evi-
dence now shows the influence that diet may directly or indi- Data from previous studies suggest possible associations
rectly have on acne. Chinese medicine definitely makes a between Western diet and acne. Data from the Nurses Health
correlation between fatty foods including dairy products Study II were retrospectively examined and evaluated to deter-
(which contain IGF-1 and other endocrine-disrupting hor- mine whether intake of dairy foods during high school were
mones), red meat, deep-fried foods and its association to associated with physician-diagnosed severe teenage acne.
dampness. In addition, eating stimulating substances such as Results found a positive association with acne for intake of
spicy food, peppers, sugar, coffee (an alkaloid which stimulates milk, whole, low-fat, and skim, and cottage cheese, cream
the sebaceous glands to produce large amounts of sebum), and cheese, sherbet and instant breakfast drink. The study hypo�
drinking alcohol or smoking all cause excess internal heat. In thesized that the association with milk may be because of the
most cases of acne, there are varying proportions of heat and presence of hormones and bioactive molecules in milk.
dampness to contend with. Recommended foods to add to Adhering to a low glycemic diet seems to improve acne
one’s diet are foods that are ‘cooling’ and have a high water lesions by beneficially influencing sebum production. It has
content, i.e. watermelon, cucumbers, celery, carrots, cherries, been hypothesized that there are positive endocrine effects
raspberries, pears, mung beans, bok choy and squash, to name including improving insulin sensitivity, as high levels of
just a few. Also helpful are foods which ‘dry dampness’ includ- insulin may cause a higher-than-normal production of andro-
ing asparagus, pumpkin, papaya, and aduki bean. gens. Sebaceous gland activity is heightened by androgens
Patients with acne need to monitor the amounts of iodine such as DHEA and testosterone.
they consume because large amounts can aggravate the
condition. Iodine is found in many foods including dairy The effect of a high-protein, low glycemic-load diet versus
products (Table 18.6). a conventional, high glycemic-load diet on biochemical
parameters associated with acne vulgaris: a randomized,
High school dietary dairy intake and teenage acne. investigator-masked, controlled trial. Smith RN, Mann NJ,
Adebamowo CA, Spiegelman D, Danby FW, Frazier AL, Willett Braue A, Mäkeläinen H, Varigos GA. J Am Acad Dermatol
WC, Holmes MD. J Am Acad Dermatol 2005; 52(2):207–214. 2007; 57(2):247–256.

360
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Alopecia
43 male patients modified their diet over 12 weeks to incor-
porate a low-glycemic-load diet. At 12 weeks, total lesion
counts had decreased more in the experimental group com-
pared with the control group. The results suggest that increases
in dietary glycemic load may augment the biological activity
of sex hormones and IGF-I, suggesting that these diets may
aggravate potential factors involved in acne development.
Vitamin and mineral therapy
Adequate, but not excessive dosages, of specific vitamins and
minerals may be helpful in clearing acne. Vitamin A helps
reduce sebum levels when used in daily doses of 10,000╯IU.
The mineral selenium helps to control inflammation in the
recommended twice-daily dose of 200╯mcg.
Dietary zinc supplements at 100╯mg daily for 12 weeks reduce
the level of the androgenic hormone dihydrotesto�sterone
(DHT), which is associated with causing more breakouts than
other androgens. Zinc may also help with skin healing.
Chromium at 200╯mcg twice a day stabilizes insulin levels
and may help promote more effective utilization of essential
fatty acids and thus help with acne clearing.
Pantothenic acid in the treatment of acne vulgaris ‘a medical
hypothesis’. Leung LH. J Orthomolec Med Nov 1997; 12.
100 patients with acne were given 10 grams of pantothenic
acid (vitamin B5) per day (divided into four doses) and simul-
taneously applied a 20% pantothenic acid topical cream four
to six times per day. A prompt decrease in sebum secretion
occurred within 2–3 days. Regression of lesions occurred
Alopecia
Alopecia can arise from a multitude of causes including
reduced blood flow to the scalp, stress, depression, hypo�
thyroidism, chemical exposure, androgenic hormones, chemo-
therapy, and autoimmune factors. The symptoms of alopecia
can cause a patient substantial emotional distress which must
not be overlooked. Evidence suggests that utilizing mind-body
therapies adjunctively to standard treatment can be very effec-
tive. Several CAM/alternative therapies are used to treat alo-
pecia including herbal medicine, topical treatments with a
variety of substances (garlic, onions, green tea), aromatherapy,
diet (Table 18.7) and hypnosis.
Summary of CAM therapies for alopecia
Alternative Medical Systems
â•… Chinese herbal medicine Variable
â•… Topical botanical ingredients Variable
Mind-Body Therapies
â•… Hypnotherapy Anecdotal
â•… Diet Anecdotal
â•… Aromatherapy Variable
within 2 weeks and the development of new ones slowed. Pore
size became smaller and skin more refined over several months.
In moderate acne, the condition was controlled in about 8
weeks. For severe acne, the study suggests increasing the dose
of pantothenic acid to 15–20 grams a day for a gradual and
steady improvement, while certain dietary restrictions are fol-
lowed (avoiding high fat, oily foods).
While this was not a well designed or executed study, the author
makes some interesting points which are worth further study.
References
1. Kaimal S, Thappa DM. Diet in dermatology: revisited. Indian J
Dermatol Venereol Leprol 2010 Mar-Apr; 76(2):103–115.
2. Thiboutot DM, Strauss JS. Diet and acne revisited. Arch Dermatol
2002; 138:1591–1593.
3. Simpson NB, Cunliffe WJ. Disorders of the sebaceous glands. In: Burns
T, Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of derma-
tology. 7th ed. Massachusetts: Blackwell science; 2004. p. 431–475.
4. Zaenglein AL, Graber EM, Thiboutot DM, Strauss JS. Acne vulgaris and
acneiform eruptions. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA,
Paller AS, Leffell DJ, editors. Fitzpatrick’s Dermatology in General
Medicine. 7th ed. New York: McGraw Hill; 2008. p. 690–702.
5. Tan JK, Vasey K, Fung KY. Beliefs and perceptions of patients with acne.
J Am Acad Dermatol 2001; 44:439–445. Back to cited text no. 22
6. Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J.
Acne vulgaris: a disease of western civilization. Arch Dermatol 2002;
138:1584–1590.
7. Cordain L. Implications for the role of diet in acne. Semin Cutan Med
Surg 2005; 24:84–91.
8. Anderson PC. Foods as the cause of acne. Am J Fam Pract 1971;
3:102–103.
Chinese herbal medicine
Chinese medicine is a commonly used modality for alopecia
that utilizes acupuncture and herbal medicine. Alopecia is
interpreted by doctors of Chinese medicine to be a result of
‘blood’ deficiency which causes the hair follicles to be under-
nourished and to fall out. Chronic illness, anemia, poor diet,
the aging process, and excessive use of drugs can all be causes
of a blood deficiency. The condition can be exacerbated by
complications of Chinese diagnostic syndromes known as
‘blood stagnation’ and ‘heat in the blood.’ The first step in
treating hair loss is to improve the quality of the blood. To
achieve this, a Chinese physician will utilize one of several
standard ingested herb formulas that nourish and build the
blood and promote new hair growth. Additional herbs can be
added to the primary formula as needed to address other
residual or underlying factors (Table 18.8).
Topical agents
Many advocates of CAM feel that Chinese herbal medicine
provides effective topical treatment for hair loss. Several
approaches may be utilized. A primary approach is to use
strong stimulants such as ginseng, ginger, or hot pepper rubbed
daily on the scalp to increase circulation. Acupuncture may
also be used on the scalp for this purpose. Another approach
361
 Part 6 Complementary and Alternative Medicine

Table 18.7╇ Dietary deficiencies and hair loss1–5 Table 18.9╇ Hair generating tincture (Sheng Da Fing) (topical treatment)

Iron deficiency* Scientific name Chinese name Amount used

High risk
– Vegetarians Radix Polygoni multiflori He Shou Wu 200╯g
– Vegans
Fructus Psoraleae Corylifoliae Bu Gu Zhi 200╯g
High iron content
– Lean meats Rhizoma Zingiberis Officinalis Gan Jiang 100╯g
– Nuts Flos Carthami Tinctorii Hong Hua 100╯g
– Seeds Rhizoma Ligustici Chuanxiong Chuan Xiong 100╯g
– Legumes
Cortex Cinnamomi Cassiae Rou Gui 100╯g
– Bean products
– Raisins Fructus Cnidii Monnieri She Chuang Zi 100╯g
– Dark green leafy vegetables The dried, raw herbs are cut up and crushed, then steeped in 3000╯ml of a 75%
– Whole grains alcohol solution for 2 weeks. The liquid is strained off for application to affected areas
– Iron-fortified cereals two or three times daily. Results are purportedly seen after 2 months.

Protein deficiency (less than 0.8╯g/kg protein and less than

1200╯Kcal per day)
High risk
Topical botanical treatments for alopecia
– Malnutrition
– Starvation
– Eating disorders Chinese herbal medicine Variable
– Crash diets Green tea Anecdotal
– Rigorous caloric restriction Garlic Anecdotal
Zinc deficiency* Onions Anecdotal
Biotin deficiency*
*controversial
Development and evaluation of polyherbal formulation for
hair growth-promoting activity. Roy RK, Thakur M, Dixit VK.
Table 18.8╇ Herbs that nourish the blood and promote new hair J Cosmet Dermatol 2007; 6(2):108–112.
growth (Oral treatment) Three Chinese-Ayurvedic herbs traditionally known for
their hair growth-promoting activity were used topically and
Scientific name Chinese name English name compared to a control of minoxidil 2% solution. The herbs
Cuscuta reflexa, Citrullus colocynthis, and Eclipta alba were used
Radix Polygoni Multiflori He Shou Wu Fleece-flower root as an extract on the shaved skin of rats. Hair growth initiation
time was markedly reduced by one-third for the herb formula
Fructus Lycii Gou Qi Zi Wolfberry fruit
compared to the control. The time required for complete hair
Radix Angelica Sinensis Dang Gui Chinese angelica growth was reduced by 32%. Post-treatment analysis of hair
root growth cycles showed a greater number of hair follicles in
Radix Rehmannia Glutinosae Shu Di Huang Processed anagen phase compared with control.
Rehmannia root
Radix Paeonia Lactiflorae Bai Shao White peony root The hair growth promoting effect of Asiasari radix extract
and its molecular regulation. Rho SS, Park SJ, Hwang SL, Lee
Herba Eclipta Prostratae Han Lian Cao Eclipta
MH, Kim CD, Lee IH, Chang SY, Rang MJ. J Dermatol Sci 2005;
Semen Cuscutae Tu Si Zi Dodder seed 2:89–97.
Fructus Ligustri Lucidi Nu Zhen Zi Glossy privet fruit 45 plant extracts that have been traditionally used in Asian
Radix Astragali Seu Hedysari Huang Qi Milk vetch root medicine for treating hair loss were tested on 6-week-old
female mice. The extracts were applied daily for 30 days and
45 days respectively. Of the tested plant extracts, the extract of
is to use “blood vitalizing” herbs, (like those used in oral Asiasari radix showed the most potent hair growth stimulation.
therapies) to nourish the blood and promote microcircula- This may be due to its regulatory effects on both cell growth
tion. Herbs to stimulate hair or reduce 5-alpha-reductase (for and growth factor gene expression.
cases of androgenic alopecia) may be incorporated. Table 18.9
shows an example of a simple topical herbal formulation The hair growth promoting effect of Sophora flavescens
which nourishes the blood, promotes circulation, and stimu- extract and its molecular regulation. Roh SS, Kim CD, Lee
lates hair growth. There is a paucity of studies in humans but MH, Hwang SL, Rang MJ, Yoon YK. J Dermatol Sci 2002;
proof-of-concept studies on mice have been published. 30(1):43–49.

362
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Alopecia
The extract of Sophora flavescens root, a Chinese herb, was
found to have outstanding hair growth promoting effect when
used topically on C57BL/6╯mice. RT-PCR analysis showed the
extract induced mRNA levels of growth factors such as IGF-1
and KGF in dermal papilla cells. In addition, Sophora extract
was found to possess potent inhibitory effect on type II 5
alpha-reductase activity.
Treatment of 8324 cases of alopecia with 101 Hair Regener-
ating Alcohol. Zhao Zhangguang (Journal of Traditional
Chinese Medicine) 1988; 29(9):693–694.
The largest clinical evaluation of a topical treatment for
alopecia involved over 8300 patients. The treatment consisted
of a liquid herbal hair regenerating tonic, applied 2–3 times
per day, for 2–3 months. It included energizing, and circulation-
enhancing ingredients such as the roots of fresh ginger, Zin-
giberis officialis recens (Sheng Jiang) and panax ginseng (Ren
Shen) in addition to herbs Angelica sinensis (Dang Gui), Salvia
miltiorrhizae (Dan Shen), Ligusticum (Chuan Xiong), Astragalus
membranaceus (Huang Qi), Prunus persica (Tao Ren), and
Carthamus tinctorius (Hong Hua), and some additional undis-
closed ingredients. The liquid goes by the name ‘101 Hair
Regenerating Alcohol’ and can be found in some Chinese
shops in the US The study claims that the cure rates for alo-
pecia areata were 91.7%, for alopecia totalis 83.4%, and for
alopecia universalis 62.1%. Less than 6% of patients in each
category failed to respond to the treatment.
Androgenic alopecia
A randomized, double-blind, placebo-controlled trial to
determine the effectiveness of botanically derived inhibitors
of 5-alpha-reductase in the treatment of androgenic alo-
pecia. Prager N, Bickett K, French N, Marcovici G. J Altern
Complement Med 2002; 8(2):143–152.
This placebo-controlled, double-blind study of males with
androgenetic alopecia (AGA) showed a highly positive response
to botanical compounds liposterolic extract of Serenoa repens
(LSESr) and beta-sitosterol. One contributing factor to andro-
genic alopecia is the conversion of testosterone to dihydrotes-
tosterone (DHT) via the enzyme 5-alpha reductase (5AR). The
study established the effectiveness of botanical compounds
containing naturally occurring 5AR inhibitors against AGA.
60% (6/10) study subjects dosed with the active study formula-
tion were rated as improved at the end of the study. Larger trials
are recommended to further study this effect.
The extract of Thujae occidentalis semen inhibited 5-alpha-
reductase and androchronogenetic alopecia of B6CBAF1/j
hybrid mouse. Park WS, Lee CH, Lee BG, Chang IS. J Dermatol
Sci 2003 Apr; 31(2):91–98.
The topically-applied medicinal plant extract of Thujae occi-
dentalis semen (TOS) has a demonstrated inhibitory activity
for 5-alpha-reductase type 2 and its biological action in two
animal models. TOS extract showed higher inhibition activity
than that of gamma-linoleic acid, but lower than that of fin-
asteride. Results suggest that TOS extract would be an effective
agent for modifying androgen conversion in male pattern
baldness.
Essential oils and low-intensity electromagnetic pulses in
the treatment of androgen-dependent alopecia. Bureau JP,
Ginouves P, Guilbaud J, Roux ME. Adv Ther 2003; 20(4):
220–229.
This double-blind randomized study demonstrated the
positive effect on hair loss and hair re-growth of a pulsed
electromagnetic field in combination with essential oils over
26 weeks on healthy patient volunteers vs placebo. The treat-
ment group exhibited a decrease in hair loss in 83% of volun-
teers and a more than 20% hair count increase over baseline
in 53% of patients. A histological examination correlated with
the clinical study. There were no reported adverse effects.
Alopecia areata
The therapeutic use of naturally aromatic essential plant oils
(aromatherapy) is another often utilized topical modality for
alopecia. The use of aromatherapy dates back to ancient times
when most major civilizations extracted the oils from the
flowers, leaves, and stems of selected plants for use in medical,
religious, and social practices. The oils are dissolved in alcohol,
emulsifiers, or fat, which allow them to penetrate the skin.
Many of the oils have innate antiviral, anti-inflammatory, anti-
bacterial, pain-relieving, and antidepressant properties. Essen-
tial oils can contain as many as 100 chemical components,
which may include monoterpenes, aldehydes, esters, phenols,
ketones, coumarins, or oxides.
Randomized trial of aromatherapy. Successful treatment for
alopecia areata. Hay IC, Jamieson M, Ormerod AD. Arch Der-
matol 1998; 134:1349–1352.
This randomized, double-blind controlled trial followed 86
patients with alopecia areata who received daily scalp massage
treatments for seven months. There were two arms of the trial.
The treatment group of 43 patients used essential oils of lav-
ender, thyme, rosemary, and cedarwood (all of which have
hair-growth promoting properties) in carrier oils of grapeseed
and jojoba. The control group of 43 patients received their
scalp massage treatment with carrier oils only. At the end of
the trial, 19 (44%) of 43 patients in the essential oil group
grew hair, compared to only 6 (15%) in the control group.
Combination of topical garlic gel and betamethasone valer-
ate cream in the treatment of localized alopecia areata: a
double-blind randomized controlled study. Hajheydari Z,
Jamshidi M, Akbari J, Mohammadpour R. Indian J Dermatol
Venereol Leprol 2007; 73:29–32.
In this randomized, double-blind, controlled clinical trial,
40 patients divided into two groups applied topical 5% garlic
gel or a placebo twice daily for 3 months in addition to using
topical corticosteroid betamethasone cream 0.1% in isopropyl
alcohol. At the conclusion of the study, 19 (95%) patients of
the active group had a good response with the remaining
patient having a moderate response. This was significantly
better than the control group. There were no adverse effects
reported. This study concluded that the use of garlic gel in
conjunction with topical betamethasone valerate significantly
adds to the therapeutic efficacy in the treatment of alopecia
areata.
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 Part 6 Complementary and Alternative Medicine
Onion juice (Allium cepa L.), a new topical treatment for
alopecia areata. Sharquie KE, Al-Obaidi HK. J Dermatol 2002;
29:343–346.
62 patients with patchy alopecia received either a twice-
daily topical application of crude onion juice or topical appli-
cation of tap water for 2 months. After 8 weeks, 23 patients in
the active group finished treatment and full regrowth was seen
in 20 (86.9%). By contrast, only 2 (13%) of the 15 patients
in the control group showed hair regrowth at 8 weeks of
treatment.
Human hair growth enhancement in vitro by green tea
epigallocatechin-3-gallate (EGCG). Kwon OS, Han JH, Yoo
HG, Chung JH, Cho KH, Eun HC. Phytomedicine 2007;
14:551–555.
This study measured the effect of EGCG (the active compo-
nent in green tea) on hair growth in vitro and its effect on
human dermal papilla cells (DPCs) in vivo and in vitro. 10%
EGCG in ethanol was applied topically to the scalp and found
to stimulate hair growth via its proliferative and antiapoptotic
effects on DPCs, as well as possible prolongation of the anagen
phases of hair growth.
Hypnotherapy
Hypnotherapeutic management of alopecia areata.
Willemsen R, Vanderlinden J, Deconinck A, Roseeuw D.
J Am Acad Dermatol 2006; 55(2):233–237.
Hypnosis was used in 28 patients with extensive alopecia
areata who were refractory to previous conventional treat-
ments. In all, 21 patients, 9 with alopecia totalis or alopecia
universalis and 12 with extensive alopecia areata were ana-
Eczema / Atopic
dermatitis
Eczema, also termed atopic dermatitis or atopic eczema (terms
which will be used interchangeably in this chapter), is a
common inflammatory skin disease whose etiology involves
numerous internal and external factors. This disorder causes
erythematous or hyperpigmented scaly plaques, papules or
vesicules which may lead to exudates and crusting.
In traditional Chinese medicine (TCM), the pathology of
eczema is similarly complex and involves an interaction of
factors such as stress, gastrointestinal disorders, infection,
contact with chemicals, environmental exposure, profuse
sweating, friction, and even certain aggravating foods. Eczema
may be considered a delayed allergic reaction causing an
inflammatory skin reaction.
Some eczema lesions will have a dry, red, and flaky appear-
ance with inflammation, heat, and dehydration. TCM calls this
manifestation ‘blood heat’ and treats it with cooling and mois-
tening herbs such as Chinese foxglove (Rehmanniae) and Red
Peony root (Paeoniae Rubra) as part of a larger herbal formula
364
lyzed during a 5-year period. After treatment, all patients
had a significantly lower score for anxiety and depression.
Scalp hair growth of 75–100% was seen in 12 patients after
3–8 sessions of hypnotherapy. Total growth occurred in 9 of
these 12 patients, including 4 patients with alopecia universa-
lis and 2 with ophiasis. In 5 patients, a significant relapse
occurred. Hypnotherapy may improve clinical outcome of
patients with alopecia and improve their psychological
well-being.
Hypnotherapy for alopecia areata [letter]. Harrison PV,
Stepanek P. Br J Dermatol 1991; 124:509–510.
5 patients with extensive alopecia areata underwent medical
hypnotherapy in this small clinical trial. 1 patient showed a
significant increase in hair growth. 3 patients had a slight
increase in hair growth, and one had no change. Hypnosis
improved the psychological parameters in all 5 patients and is
suggested as a complementary supportive treatment to address
the emotional impact of having alopecia areata.
References
1. Kaimal S, Thappa DM. Diet in dermatology: revisited. Indian J
Dermatol Venereol Leprol 2010 Mar-Apr; 76(2):103–115.
2. Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron
deficiency and its potential relationship to hair loss. J Am Acad
Dermatol 2006; 54:824–844.
3. Goette DK, Odom RB. Alopecia in crash dieters. JAMA 1976;
235:2622–2623.
4. Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol
2002; 27:396–404.
5. Shrivastava SB. Diffuse hair loss in an adult female: Approach to diag-
nosis and management. Indian J Dermatol Venereol Leprol 2009;
75:20–28.
consisting of 12–16 herbs. Another manifestation of eczema
consists of wet, fluid-filled blisters or oozing lesions with ery-
thema, which indicates a ‘damp-heat’ condition. The herbs
used for this type of eczema will likely be Scutellaria baicalensis,
Moutan, and Alismatis orientalis along with a handful of others
which clear heat and eliminate dampness. Chinese herbal
medicine is felt to be safe for oral use when prescribed by
practitioners who are experienced in the pharmacology and
synergy of compounding formulas consisting of a dozen or
more herbs, and understanding their interactions.
It is commonly held that patients with atopic dermatitis
have altered fatty acid metabolism which seemingly contri�
butes to their compromised skin barrier function. This has led
to the use of supplemental dietary essential fatty acids such as
those found in the botanical lipids of evening primrose oil
(EPO) and flaxseed oil. The oils gamma linolenic acid in EPO
and alpha linoleic acid in flaxseed oil, respectively, can help
replenish and correct the essential fatty acid imbalance.
There are numerous therapeutic options for treating atopic
dermatitis both topically and systemically. The majority of
clinical trials cover the efficacy of Chinese herbal medicines.
Studies on a few other alternative modalities have also been
conducted. Diet (Table 18.10), homeopathy, massage, hypno-
therapy, and psychotherapy have also shown some benefit.
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Eczema / Atopic dermatitis
Table 18.10╇ Diet advocated for atopic dermatitis
Antigen avoidance* (only in highly selected patients with specific
elevations in IgE)
Eggs
Cow’s milk
Probiotics**
Lactobacillus
Bifidobacterium
*caution must be excercised to avoid nutritional deficiency
**controversial
Summary of CAM therapies for eczema
Alternative Medical Systems
â•… Chinese herbal medicine (oral and topical)
â•… Acupuncture with herbal medicine
â•… Evening Primrose Oil (EPO)
â•… Lactobacillus GG
â•… Homeopathy
â•… Topical vitamin B12
â•… Topicals
â•…â•… Herbs
â•…â•… Relieva
â•…â•… St John’s Wort
Mind Body Therapies
â•… Hypnotherapy
â•… Psychotherapy
Manipulative Body-Based Therapies
â•… Massage Therapy
Systemic Chinese herbal medicine therapy
The following clinical studies assess the efficacy of Chinese
herbal medicine in treating eczema (atopic eczema and atopic
dermatitis.) Many Chinese herbs are chosen for their therapeu-
tic effect on the production of white blood cells which affect
the immune system, thus reducing allergic responses and alle-
viating inflammation. These studies have reportedly shown no
adverse effects.
A controlled trial of traditional Chinese medicinal plants in
widespread non-exudative atopic eczema. Sheehan MP,
Atherton DJ. Br J Dermatol 1992; 126:179–184.
Placebo-controlled double-blind trial of an oral medicinal
herb prescription formulated specially for non-exudative
atopic eczema. 47 children started the study and were given
active treatment or placebo in random order, each for 8 weeks,
with an intervening 4-week wash-out period. 37 children com-
pleted the study. Response to active treatment was superior to
response to placebo, and was clinically significant. There were
no reported adverse effects to the treatment.
One year follow-up of children treated with Chinese medici-
nal herbs for atopic eczema. Sheehan MP, Atherton DJ. Br J
Dermatol 1994; 130:488–493.
A longer-term investigation analyzed the results of 37
children suffering from atopic eczema. 10 patients withdrew
from the study early because of inadequate response; 4
patients withdrew because of the unpalatable taste of the treat-
ment herbs. Conducted over a 1-year period, 18 out of 23
patients (78%) demonstrated a 90% reduction in the severity
of their eczema by the end of the study; 7 of the children
were able to discontinue treatment without relapse. Of the
remaining children, 16 still required treatment to maintain
control of their eczema, though their treatments were reduced
from once each day to once every 5 days. A reversible asymp-
tomatic elevation of the transaminase level was seen at 7–14
times normal in 2 patients during treatment. Normal levels
were regained shortly after concluding treatment. Chinese
medicinal herbs provide a therapeutic option for children
Variable with atopic eczema which has failed to respond to other
B treatments.
B Modulation by Chinese herbal therapy of immune mecha-
A nisms in the skin of patients with atopic eczema. Xu XJ,
B Banerjee P, Rustin MH, Poulter LW. Br J Dermatol 1997;
A 136(1):54–59.
Variable 10 patients with atopic eczema received oral Chinese
medicinal herbs for 2 months from a formula called Zema-
phyte. Chinese herbal therapy was clinically efficacious and
improvement was associated with a significant reduction in
antigen-presenting cells expressing CD23.
C Efficacy of traditional Chinese herbal therapy in adult atopic
Anecdotal dermatitis. Sheehan MP, Rustin MHA, Atherton DJ, Buckley
C, Harris DW, Brostoff J, Ostlere L, Dawson A. Lancet July 4,
1992; 340(8810):13–17.
C Double-blind, placebo-controlled crossover study with 40
patients randomly allocated to receive either the active treat-
ment consisting of 10 Chinese medicinal herbs to decoct and
drink daily for 8 weeks followed by a 4-week wash-out period,
an identically packaged placebo for 8 weeks, or the same treat-
ments in the reverse order. The chosen herbs were selected
for their known pharmacological actions, each herb having
either anti-inflammatory, antimicrobial, immunosuppressive,
or sedative effects. Patients in both treatment sequences
showed a rapid and continued improvement in both erythema
and surface damage scores during the time they consumed the
Chinese herbal remedy. No side effects were reported by either
group although many patients did not care for the taste of the
decoction.
The effectiveness of combined Chinese herbal medicine and
acupuncture in the treatment of atopic dermatitis. Salameh
F, Perla D, Solomon M, Gamus D, Barzilai A, Greenberger S,
Trau H. J Altern Complement Med 2008; 14(8):104–108.
20 patients were given a combined treatment of acupunc-
ture and Chinese herbal medicine. Patients received acupunc-
ture treatment twice a week and an oral Chinese herbal
formula three times daily for 12 weeks. Assessments were per-
formed before treatment and every 3 weeks thereafter. The
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 Part 6 Complementary and Alternative Medicine

primary outcomes were defined as the changes in the Eczema

Area and Severity Index (EASI), Dermatology Life Quality Table 18.11╇ Components of Chinese herbal formula for atopic
Index (DLQI) and patient assessment of itch measured on a dermatitis*
visual analogue scale (VAS). After 12 weeks of treatment, 100%
of patients had an improvement in EASI when compared with Scientific Name Chinese Name Action
baseline. The median percentage of decrease was 63.5%. More-
over, 78.8% of patients experienced a reduction in DLQI and Gypsum Fibrosum Shi Gao Anti-inflammatory
VAS compared to baseline. No adverse effects were reported. Radix Rehmannia Sheng Di Huang Anti-pyretic,
Glutinosae anti-inflammatory
Efficacy and tolerability of a Chinese herbal medicine con-
Radix Angelica Dang Gui Promotes blood
coction for treatment of atopic dermatitis: a randomized,
Sinensis circulation
double-blind, placebo-controlled study. Hon KLE, Leung
TF, Ng PC, Lam MC, Kam WY, Wong KY, Lee KC, Sung YT, Rhizoma Atractylodis Cang Zhu Harmonizes water
Cheng KF, Fok TF, Fung KP, Leung PC. Br J Dermatol 2007; metabolism
157:357–363. Radix Ledebouriellae Fang Feng Relieves itching, relieves
85 children with moderate to severe atopic dermatitis pain
were followed in this randomized, double-blind, placebo- Akebia Caulis Mu Tong Harmonizes water
controlled study over 12 weeks. 42 of the children were given metabolism
a twice-daily, oral herbal formula consisting of five traditional
Rhizoma Zhi Mu Sedative,
Chinese herbs (a widely-used ancestral formula). The herbs
Anemarrhenae anti-inflammatory
when combined in exact proportions have the effect of reduc-
ing inflammation, alleviating itching, and controlling allergic Radix Glycyrrhizae Gan Cao Antitoxic, sedative,
response. The remaining 43 children were given placebos. By protects digestive
the end of the study, the conditions of the children on the system
herbs were significantly improved and their need for topical Radix Sophorae Ku shen Anti-inflammatory,
corticosteroids was also significantly reduced by one-third. The relieves itching
formula was well tolerated with no serious adverse effects Herba Schizonepetae Jing Jie Anti-inflammatory,
observed by either group. relieves pain, itching
The pharmacology of Chinese herbs is complex and fasci- Fructus Arctii Lappae Niu Bang Zi Anti-bacterial, relieves
nating. In recent years more texts have become available to itching
explain the extensive pharmacological constituents inherent in Semen Sesami Indici Hei Zhi Ma Moistens, nourishes
medicinal herbs. Table 18.11 shows an example of an oral
Periostracum Cicadae Chan Tui Sedative, relieves itching
herbal prescription that can be used for atopic dermatitis
(eczema). It is proported to be excellent for skin rashes, urti- *Xiao Feng San (Powder for Dispersing Wind)
caria, and psoriasis with red discoloration, severe itching and
leakage of fluids upon scratching.

Additional systemic therapies

Evening Primrose Oil (EPO)
Evening primrose oil is effective in atopic dermatitis: a ran-
domized placebo-controlled trial. Senapati S, Banerjee S,
Gangopadhyay DN. Indian J Dermatol Venereol Leprol 2008;
74:447–452.
25 patients with atopic dermatitis receiving a daily 500╯mg
capsule of evening primrose oil (EPO) were evaluated after
completing 5 months of trial versus placebo. At the end of the
study, 24 (96%) patients in the evening primrose oil group
and 8 (32%) patients in the placebo group showed improve-
ment. The difference in outcome of treatment between the two
groups was significant. No adverse events were reported by the
patient during the trial.
The active ingredient in evening primrose oil is gamma lino-
lenic acid.
Improving AD: adding Lactobacillus GG boosts treatment.
Viljanen M, et╯al. Allergy 2005; 60(4):494–500.
A randomized, double-blind, placebo-controlled study of
230 infants with atopic dermatitis showed improvement after
treatment with Lactobacillus GG. Improvement occurred in
the subgroup of patients who had high IgE levels at the begin-
ning of the study.
Homeopathic therapy
Effect of homeopathic treatment of 60 Japanese patients
with chronic skin disease. Itamura R. Complement Ther Med
2007; 15(2):115–120.
60 patients with chronic skin diseases including eczema
and atopic dermatitis received individualized homeopathic
treatments in addition to conventional dermatological
treatments. 6 patients had a 100% improvement, 23 had 75%
improvement, 24 patients had 50% improvement and 7
patients had 25% improvement. A total of 88.3% of patients
reported over 50% improvement. Half of the patients with
atopic dermatitis and eczema reported greater satisfaction in
daily life.

366
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Eczema / Atopic dermatitis
Homoeopathic versus conventional treatment of children
with eczema: a comparative cohort study, Keil T, Witt CM,
Roll S, et╯al. Complement Therap Med 2008; 16(1):15–21.
Homeopathic treatment was administered to 118 children
by physicians in primary care and found to be equally as
effective as conventional therapy in relieving symptoms and
improving quality of life.
The authors conducted their study in a primary care setting,
which they said gave a ‘more realistic picture’ of eczema therapy
than that seen in a placebo-controlled, randomized controlled
trial.
Topical therapy
While topical corticosteroids are the gold standard for treat-
ment of eczema, a variety of natural and botanical ingredients
can be used adjunctively for dryness, inflammation, and
itching. A number of topical and botanical ingredients show
promise in the treatment of atopic dermatitis: however, scien-
tific evidence tends to be limited. Licorice and feverfew can
help manage inflammation and oatmeal and is helpful in
restoring the cutaneous barrier.
Herba saxifragae cream in treatment of chronic eczema: a
randomized controlled trial. Xu R, Li F, Zhang L, Song X, Zhu
J, Li B. J Chinese Integrative Med Volume 2008; 6(12).
42 patients with chronic eczema were randomized into two
groups and treated with a topical herbal cream containing
herba saxifragae or hydrocortisone. 22 patients received herbal
cream, 20 patients received hydrocortisone. Each group applied
their respective topical treatment twice a day for 4 weeks. At
the end of the trial, the total response in the herbal group
was 86.4% and in the hydrocortisone group it was 85.0%.
Treatment with herba saxifragae cream is found to have the
same effect as hydrocortisone in treating chronic eczema and
there were no side effects.
Topical vitamin B12 – a new therapeutic approach in atopic
dermatitis-evaluation of efficacy and tolerability in a
randomized placebo-controlled multicentre clinical trial.
Stucker M, Pieck C, Stoerb C, Niedner R, Hartung J, Altmeyer
P. Br J Dermatol 2004; 150(5):977–983.
This study involved 49 patients who, for 8 weeks, applied
topical vitamin B12 cream twice daily to one side of the body
and a placebo preparation to the contralateral side. The final
results showed a significant superiority of vitamin B12 cream
over the placebo with regard to the reduction of the extent and
severity of atopic dermatitis. The treatment was well tolerated
by patients and posed a very low safety risk.
Evaluation of topical vitamin B(12) for the treatment of
childhood eczema. Januchowski R. J Altern Complement Med
2009; 15(4):387–389.
Topical vitamin B12 is thought to decrease nitric oxide
production and thus reduce symptoms in eczema. It has been
shown to successfully treat atopic dermatitis in adults. 21
patients completed this double-blinded, randomized, placebo-
controlled, 4-week study. By study’s end, skin treated with
topical vitamin B12 improved significantly more than placebo
treated skin. Topical vitamin B12 should be considered as a
treatment option in children with eczema.
Relieva, a Mahonia aquifolium extract for the treatment of
adult patients with atopic dermatitis. Donsky H, Clarke D.
Am J Ther 2007; 14(5):442–446.
This open-label trial of 42 patients with atopic dermatitis
(eczema) who were treated for 12 weeks with Relieva cream (a
homeopathic product containing Psorberine, a proprietary
Mahonia aquifolium extract) demonstrated significant improve-
ments in Eczema Area and Severity Index scores and a Subject
Reported Evaluation of Treatment. Patients indicated a sub-
stantial benefit when rating effectiveness, itching, and appear-
ance as a result of using the preparation. Relieva cream is a
safe and effective treatment for adult patients with atopic der-
matitis (eczema).
Topical treatment of atopic dermatitis with St. John’s wort
cream – a randomized, placebo controlled, double blind
half-side comparison. Schempp CM, Windeck T, Hezel S,
Simon JC. Phytomedicine 2003; 1(Suppl 4):31–37.
This study compared the efficacy of Hypericum perforatum L.
(St. John’s Wort) cream to placebo in 21 patients who received
twice daily topical treatments for 4 weeks. 18 patients com-
pleted the study. The hypericum cream was significantly supe-
rior to placebo; however, further studies with a larger patient
base were suggested.
Massage therapy, hypnotherapy,
and psychotherapy
Atopic dermatitis symptoms decreased in children follow-
ing massage therapy. Schachner L, Field T, Hernandez-Reif
M, Duarte AM, Krasnegor J. Pediatr Dermatol 1998; 15(5):
390–395.
One small, controlled trial found positive results and a
reduction in clinical symptoms in children with atopic derma-
titis. The study randomized a group of 20 children to receive
either 20 minutes of massage daily from a parent or caregiver
or standard topical care for 1 month. At the end of the trial,
the children in the massage treated group had improved sig-
nificantly in the clinical severity of their symptoms.
Hypnotherapy as a treatment for atopic dermatitis in adults
and children. Steward AC, Thomas SE. Br J Dermatol 1995;
132(5):777–783.
18 patients who had no clinical success with dermatologi-
cal treatment of their atopic dermatitis were offered 3 to 4
hypnotherapy sessions emphasizing relaxation. Significant
reduction in severity of symptoms was seen in 16 of 18
patients, who also reported improvement in non-dermatologic
quality-of-life measures. More clinical research is needed to
assess the therapeutic value of hypnosis.
Treatment of atopic dermatitis: a comparison of psychologi-
cal and dermatological approaches to relapse prevention.
Ehelers A, Stangier U, Gieler U. J Consult Clin Psychol 1995;
63:624–635.
367
 Part 6 Complementary and Alternative Medicine
10 adult patients with atopic dermatitis were given group
psychotherapy in addition to their regular medical regimen.
All 10 patients showed a significant reduction in targeted
symptoms.
References
1. Kaimal S, Thappa DM. Diet in dermatology: revisited. Indian J
Dermatol Venereol Leprol 2010 Mar-Apr; 76(2):103–115.
2. Oranje AP, de Waard-van der Spek FB. Atopic dermatitis and diet. J Eur
Acad Dermatol Venereol 2000; 14:437–438.
3. Bath-Hextall F, Delamere FM, Williams HC. Dietary exclusions for
established atopic eczema. Cochrane Database Syst Rev 2008 Jan 23;
(1):CD005203.
Psoriasis
Psoriasis is a complex disorder involving genetic predisposi-
tion, immunologic, metabolic, and endocrine factors. Along
with these, certain medications (beta-blockers, lithium), strep-
tococcal infection, folate and vitamin B12 deficiencies, alco-
holism, and smoking can increase the risk of developing
psoriasis.1,2
With no known cure, the reality of living with psoriasis can
exert a heavy toll on a patient’s psychological status and quality
of life. Those who have the disease often feel hopeless and
depressed. Stress plays a vital role in psoriasis, as it can trigger
or exacerbate the condition.
Many factors contribute to the etiology of psoriasis and
there are several CAM approaches to the condition. One
thought is that it is an inflammatory disorder rooted in the GI
tract where poor function leads to increased intestinal perme-
ability (leaky gut syndrome). In this scenario, molecules of
incompletely digested food cross into the bloodstream where
an inflammatory cascade is triggered as the immune system
attempts to counteract these food-borne antigens.
Complementary and alternative medicine (CAM) is in��
creasingly used by patients with psoriasis.3 While treatment
methods vary from Chinese herbal medicine (oral and topical)
to hypnotherapy, meditation, and diet, several studies suggest
that adjunctive psychological therapies can be effective in the
clinical management of psoriasis. However, the best results are
obtained when both the physical and psychosocial aspects of
the psoriasis are addressed.
Many patients turn to traditional Chinese medicine (TCM)
and its natural approach as a last resort after using conven-
tional therapies that simply suppress symptoms or produce
unwanted side-effects. Chinese medicine subtypes psoriasis
into three main categories: blood-heat, blood deficiency-
dryness, and blood stasis. The underlying pathology of each
subtype is slightly different and the resulting lesions vary in
appearance. Each subtype is treated accordingly with a differ-
ent compounded formula of medicinal herbs, usually num-
bering 10 or more. Each formula is individualized to the
patient’s underlying condition. If prescribed by a physician
who has a clear diagnosis of the subtype and who knows the
368
4. Devlin J, David TJ, Stanton RH. Elemental diet for refractory atopic
eczema. Arch Dis Child 1991; 66:93–99.
5. Isolauri E, Arvola T, Sütas Y, Moilanen E, Salminen S. Probiotics in the
management of atopic eczema. Clin Exp Allergy 2000; 30:1604–
1610.
6. Laitinen K, Isolauri E. Management of food allergy: vitamins, fatty
acids or probiotics? Eur J Gastroenterol Hepatol 2005; 17:1305–
1311.
7. Boyle RJ, Bath-Hextall FJ, Leonardi-Bee J, Murrell DF, Tang ML.
Probiotics for treating eczema. Cochrane Database Syst Rev 2008 Oct
8; (4):CD006135.
pharmacology of Asian herbs, the probability of adverse effects
from an oral formula is minimized.
‘Blood-heat’ lesions can be either bright or dark red papules
or patches that often occur with the onset of psoriasis. ‘Blood
deficiency-dryness’ lesions are dark red, brownish-red, or
pale red and present as patches or rings which are dry, crack
easily, can be itchy, and are covered by a layer of silvery-whitish
scale that is difficult to peel off. ‘Blood stasis’ lesions, which
can occur when the disease is of a relatively long duration, are
dull red, hard and thick. In this situation, Chinese herbal
medicines which ‘invigorate the blood’ and ‘transform blood
stasis’ are used. Primary treatment for psoriasis with Chinese
herbal medicine is designed to suppress the proliferation of
cells, reduce tissue inflammation, and relieve itching. Specific
herbs with these actions are used in varying combinations to
address these issues. Examples of several such herbs include,
but are not limited to: Oldenlandia diffusa (Bai Hua She She
Cao), Isatis tinctoria (Da Qing Ye), Sophora flavescens (Ku Shen),
Paeonia suffruticosa (Mu Dan Pi), Glycyrrhiza uralensis (Gan
Cao), Polygonum multiflorum (He Shou Wu), and Polygonum
cuspidatam (Hu Zhang). In general, the longer the patient has
suffered from psoriasis, the longer the length of treatment.
Alternative therapies for psoriasis are as follows.
Summary of CAM therapies in psoriasis
Alternative Medical Systems
â•… Chinese herbal medicine Variable
â•…â•… Various formulas
â•…â•… Herose
â•…â•… Curcumin
â•… Topical botanicals Variable
Biologically Based Therapies
â•… Diet Variable
Mind Body Therapies
â•… Meditation E
â•… Psychotherapy E
â•… Hypnosis E
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Psoriasis
Systemic Chinese herbal medicine therapy
Effect of Chinese herbal medicine combined with acitretin
capsule in treating psoriasis of blood-heat syndrome type.
Zhang LX, Bai YP, Song PH, You LP, Yang DQ. Chin J Integr
Med 2009; 15(2):141–144.
80 patients with blood-heat type psoriasis were randomly
assigned to either Group A (39 patients) or Group B (41
patients). Both groups were treated with Chinese herbal medi-
cines that actively clear heat, cool blood and remove toxic
substances. In addition, Group A was given acitretin for 8
weeks. The effectiveness of Group A was 84% and Group B
was 68%. The clinical effect of Chinese herbal medicine com-
bined with acitretin capsule was superior to Chinese medicine
alone, but it was felt that the adverse reaction of acitretin could
be alleviated by adjusting the herbs used.
Influence of traditional Chinese anti-inflammatory medici-
nal plants on leukocyte and platelet functions. Prieto JM,
Recio MC, Giner RM, Manez S, Giner-Larza EM, Rios JL.
J Pharm Pharmacol 2003; 55(9):1275–1282.
The enzymes 5-lipoxygenase and elastase are therapeutic
targets in dermatological disorders such as psoriasis. Several
extracts from traditional Chinese medicinal plants used to
treat topical inflammations were studied for their inhibitory
effect on lipoxygenase, cyclo-oxygenase, and elastase activity
in intact leukocytes and platelets. The herbs Forsythia suspensa
(Lian Qiao), Astragalus membranaceus (Huang Qi), and Poria
cocos (Fu Ling) were all effective in inhibiting 5-lipoxygenase.
Elastase was inhibited by Angelica dahurica (Bai Zhi), Angelica
pubescens (Du Huo), Lian Qiao, and Huang Qi. Results indi-
cate that several of the herbs studied are potentially valuable
in the management of skin pathologies involving chronic
inflammation.
The Chinese medical treatment of psoriasis. Flaws B.
Townsend Letter for Doctors and Patients 2003; May:p50(3).
68 patients with long-term psoriasis were treated with a
Chinese medicinal formula. 49 of these patients had previ-
ously been treated with corticosteroids or immune-suppressing
medications. One month before participating in this study
they discontinued pharmaceutical medications and photo-
therapy. The patients were divided into four Chinese medical
patterns with all patients receiving a basic Chinese medicinal
formula, in addition to individual herbal formulas modified
according to their pattern. Cure was defined as complete reso-
lution of symptoms or at least 80% improvement. Improve-
ment was defined as 30% recession in skin lesions or more
and a marked decrease in symptoms. No effect meant that the
lesions did not decrease in size by 30% and there was not a
marked change in symptoms. Based on these criteria, 20 cases
were judged as cured, 35 as improved, and 13 cases obtained
no beneficial effect.
This clinical trial was originally published in a Chinese lan-
guage journal and then translated into English.
Efficacy of TCM for psoriasis – a scientific review. Hsiao ELC,
Vinjamury SP, Hsiao LS, Li JT, Wu WS. The American Acupunc-
turist. Winter 2008.
A review of 21 controlled clinical trials studying the efficacy
of acupuncture and Chinese herbal medicine specifically for
psoriasis; 19 of the studies were translated into English, after
being published in China. The authors concluded that tradi-
tional Chinese medicine (TCM) may be of benefit to patients
suffering from psoriasis.
Review of a treatment for psoriasis using Herose, a botanical
formula. Yugi TT. J Dermatol 2005; 32(12):940–945.
A Chinese herbal formula known as Herose was used in an
open-label trial of 15 subjects. All subjects took four Herose
capsules (450╯mg each) three times daily for 10 months.
Herose consists of seven Chinese herbs including: Astragalus,
ginger root, white peony root, cinnamon twig, codonopsis
root, coix seeds, and salvia root. Each patient’s PASI and thera-
peutic response to treatment was evaluated. The conclusion
was that Herose may be an effective and safe treatment for
moderate to severe plaque psoriasis.
According to TCM, this formula warms the yang and promotes
blood circulation. Therefore, it would only address psoriasis in
those patients where this is the issue.
Oral curcumin in the treatment of moderate to severe pso-
riasis vulgaris: a prospective clinical trial. Kurd SK, Smith N,
Van Voorhees A, Troxel AB, Badmaev V, Seykora JT, Gelfand
JM. J Am Acad Dermatol 2008; 58(4):625–631.
This phase II, open-label trial of oral curcumin had a small
sample size and no placebo group. It showed a low response
rate. There were no adverse effects reported. Larger placebo-
controlled studies were recommended to establish further
efficacy.
Curcumin has anti-inflammatory properties which inhibit phos-
phorylase kinase in the epidermis.
Topical therapy
Various topical remedies are now popular for the treatment of
skin disorders and many are thought to be quite effective, even
while they are considered anecdotal.
Aloe vera is a frequently used topical agent chosen prima-
rily for its cooling and skin regenerating effects. It also contains
salicylic acid, a keratolytic, which helps in the desquamation
of psoriatic plaques. It is well-tolerated, which makes it all the
more popular.
Capsaicin, derived from the cayenne pepper plant, has been
used in skin creams where it is associated with a reduction in
scale and erythema.
Indigo is a COX-2 inhibitor which can decrease inflamma-
tion. Used in a topical cream it modulates epidermal kerati-
nocytes and improves lesions.
Climatotherapy comprises topical alternative treatment
methods which are based on the healing capacities of natural
resources such as bathing in the Dead Sea. Magnesium salts
369
 Part 6 Complementary and Alternative Medicine
are the prevalent minerals in Dead Sea water and are known
to bind water, influence epidermal proliferation and differen-
tiation, reduce inflammation, and enhance permeability
barrier repair.4 It is considered a safe and efficient alternative
to conventional therapeutic modalities.
An ongoing battle with scaliness can be a concern for many
patients with psoriasis and a decreased level of epidermal
ceramides may be one reason.5 Ceramides are lipid molecules
made of fatty acids and sphingosine which regulate the skin’s
water-holding capacity and homeostatic balance. Patients can
benefit from using emollient creams containing ceramides to
help reduce water loss and scaliness while increasing skin
barrier function.
Topical herbal therapies for psoriasis
â•… Aloe vera A ment of plaque psoriasis. Gulliver WP, Donsky HJ. Am J Ther
â•… Capsaicin A 2005; 12(5):398–406.
â•… Mahonia aquifolium B This review summarizes three recent clinical trials and
â•… Indigo B worldwide clinical experience with Mahonia aquifolium in
Climatotherapy B patients with psoriasis. Study 1 was an open-label study to
Management of psoriasis with Aloe vera extract in a
hydrophilic cream: a placebo-controlled, double-blind
study. Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH,
Afzal M. Trop Med Int Health 1996; 1(4):505–509.
60 patients with chronic plaque-type psoriasis were
randomized into two groups in this double-blind, placebo-
controlled study that evaluated topical 0.5% Aloe vera extract
in a hydrophilic cream. Patients self-administered the medica-
tion topically at home 3 times daily for 5 consecutive days per
week (maximum 4 weeks active treatment) versus placebo. The
study was scheduled for 16 weeks with 12 months of follow-up
on a monthly basis. By the end of the study, the Aloe vera
extract cream had cured 25/30 patients (83.3%) compared to
the placebo cure rate of 2/30 (6.6%). PASI scores decreased to
a mean of 2.2. The treatment was well tolerated by all patients
with no adverse symptoms.
Effects of topically applied capsaicin on moderate and
severe psoriasis vulgaris. Bernstein JE, Parish LC, Rapaport M,
et╯al. J Am Acad Dermatol 1986; 15:504–507.
44 patients with moderate and severe psoriasis vulgaris who
used capsaicin cream for 6 weeks had significant reductions in
scaling and erythema.
A double-blind evaluation of topical capsaicin in pruritic
psoriasis. Ellis CN, Berberian B, Sulica VI, Dodd WA, Jarratt
MT, Katz HI, Prawer S, Krueger G, Rex IH Jr, Wolf JE. J Am Acad
Dermatol 1993; 29:438–442.
197 patients with pruritic psoriasis used the cream four
times daily and found that the scaling, thickness, erythema,
and pruritis were all significantly reduced over 6 weeks.
370
The antipsoriatic Mahonia aquifolium and its active constitu-
ents; II. Antiproliferative activity against cell growth of
human keratinocytes. Muller K, Ziereis K, Gawlik I. Planta
Med 1995 Feb; 61(1):74–75.
The extract of the bark of Mahonia aquifolium is an inhibitor
of keratinocyte growth with an IC50 of 35 microM. Of its main
alkaloids tested, berberine inhibited cell growth to the same
extent as did the Mahonia extract, while the benzylisoquino-
line alkaloids berbamine and oxyacanthine were more potent
inhibitors by a factor of three.
Mahonia aquifolium is an ornamental shrub whose bark, roots,
and stems contain alkaloids (berberine) which have been found
to have an anti-inflammatory and anti-proliferative effect that
is useful in treating psoriasis.
A report on three recent clinical trials using Mahonia aqui-
folium 10% topical cream and a review of the worldwide
clinical experience with Mahonia aquifolium for the treat-
evaluate the safety of Mahonia aquifolium in 39 patients treated
for 12 weeks. The results indicate statistically significant
improvements in PASI score and Dermatology Life Quality
Index. The improvement continued one month after the con-
clusion of treatment.
Study 2 was a clinical trial of 32 patients who used Mahonia
on one side of the body and standard treatment (i.e. Dovonex
cream) on the other; 84% of patients rated the response to
Mahonia-treated psoriasis as good to excellent. When com-
pared with standard treatment, 63% of patients rated Mahonia
equal to or better than standard psoriatic treatment.
Study 3 was an open-label clinical trial for one month with
33 patients who used Mahonia cream on one side of the body
and vehicle cream on the other side. The side treated with
Mahonia did as well or better than the side treated with the
vehicle cream. Improvement was seen after one week of
treatment.
Results from these three clinical trials are in agreement that
Mahonia aquifolium is a safe and effective treatment for mild
to moderate psoriasis.
The efficacy and safety of topically applied indigo naturalis
ointment in patients with plaque-type psoriasis. Lin YK,
Wong WR, Chang YC, Chang CJ, Tsay PK, Chang SC, Pang JH.
Dermatology 2007; 214:155–161.
14 patients with plaque-type psoriasis applied indigo natu-
ralis ointment or vehicle ointment daily for 8 weeks. Results
suggest that topical application of indigo naturalis is a safe and
effective therapy that modulates the proliferation and differ-
entiation of keratinocytes in the epidermis and inhibits the
infiltration of T-lymphocytes and inflammatory reactions in
psoriatic lesions.
While more research is needed, topical indigo ointment is
nonetheless felt to be a safe treatment which may prove effective
in some patients.
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Psoriasis
Clinical assessment of patients with recalcitrant psoriasis in
a randomized, observer-blind, vehicle-controlled trial using
indigo naturalis. Lin YK, Chang CJ, Chang YC, Wong WR,
Chang SC, Pang JH. Arch Dermatol 2008; 144:1457–1464.
In this comparison study over 12 weeks, 42 patients with
chronic plaque psoriasis applied an ointment containing the
dark blue powder made from Indigo, a Chinese herb, on
lesions on one side of their body and on the other side applied
a mixture of petroleum jelly, wax, and olive oil to a corre-
sponding lesion. By the end of the study, the indigo-treated
areas showed an 81% improvement and there were no reported
side effects.
The Chinese medical action of Indigo (Qing Dai), is to clear
heat, eliminate toxins, cool blood, and disperse stagnation.
Effectiveness of climatotherapy at the Dead Sea for psoriasis
vulgaris: a community-oriented study introducing the ‘Beer
Sheva Psoriasis Severity Score’. Cohen AD, Van-Dijk D,
Naggan L, Vardy DA. J Dermatol Treat 2005; 16(5–6):
308–313.
A total of 70 patients with psoriasis were treated with cli-
matotherapy at the Dead Sea (CDS). All patients were evalu-
ated before treatment using PASI score and Beer Sheva Psoriasis
Severity Score (BPSS). There was a 75.9% reduction in PASI
scores after treatment. There was a 57.5% reduction in BPSS,
which indicates that CDS is an effective treatment for patients
with psoriasis vulgaris.
Climatotherapy at the Dead Sea is a remittive therapy for
psoriasis: combined effects on epidermal and immunologic
activation. Hodak E, Gottlieb AB, Segal T, Politi Y, Maron L,
Sulkes J, et al. J Am Acad Dermatol 2003; 49(3):451–457.
27 patients with chronic plaque-type psoriasis bathed in
the Dead Sea for 4 weeks, resulting in a decrease of PASI of
81.5%. Complete clearance was achieved in 48% of the
patients and moderate to marked improvement in 41%. The
average duration of remission was 3.3 months. Histologically,
there was a 78% decrease in keratinocyte hyperplasia and
almost total elimination of T-lymphocytes from the epidermis,
with a low number remaining in the dermis. Climatotherapy
at the Dead Sea (CDS) is a highly effective treatment for plaque
psoriasis, leading to a reversal of both pathologic epidermal
and immunologic activation.
Climatotherapy at the dead sea for pediatric-onset psoriasis
vulgaris. Ben-Amitai D, David M. Pediat Dermatol 2009;
26(1):103–104.
Climatotherapy at the Dead Sea (CDS) is highly effective
and safe for adults. This study examined the efficacy and safety
of the same modality for children with psoriasis vulgaris. More
than 75% improvement in the PASI was noted in 35% of the
patients with no side effects reported.
Diet
To fully address the multifactorial etiologies of psoriasis, der-
matologists should acknowledge the role that diet and nutri-
tion may play in the final outcome of their patient’s treatment.
Table 18.12╇ Dietary autoimmune triggers in psoriasis6–13
Avoidance of the following triggers
• Cow’s milk dairy products (cheese, milk, yogurt, ice cream)
• Shellfish (crab, lobster, clams, musse’s meat, egg yolks)
• Nightshades (tomatoes, eggplant, potatoes, bell peppers, paprika)
• Peanuts, sunflower seeds
• Fried or Hot and spicy food
• Wheat (and other gluten-containing grains)
• Vegetable oils (corn, soy, sunflower, safflower high in omega-6 fatty
acids)
• Soft drinks
• Artificial sweeteners (saccharine, aspartame, Nutrasweet, Splenda,
Equal)
• All processed foods (chips, crackers, frozen dinners)
• Sugar
• Alcohol
• Tobacco
• High calorie diet
• High body mass index
• Beneficial diet
– Vegetarian
– Low calorie diet
– Fasting periods
– Fresh vegetables and fruits
– Fish (mackerel, herring, sardine, salmon)
– Linseed
– Walnut oil
– Spices (ginger, garlic, cloves, turmeric)
In the midst of busy lives, foods are often eaten for conven-
ience, without consideration of their content. Many patients
consume large amounts of processed foods which are laden
with artificial ingredients, chemicals, and substances that can
cause a hyperresponse of the immune system (Table 18.12).
There is adequate evidence of an autoimmune etiology for
psoriasis and food choices made can have far reaching effects.
Foods that are known autoimmune triggers and/or those that
promote an inflammatory response should be eliminated from
the diet. For example, one dietary promoter of inflammation is
an excessive amount of omega-6 fatty acids which are found in
vegetable oils such as corn, soy, sunflower, and safflower.6
Many psoriasis patients improve on a gluten-free or vegetar-
ian diet, as well as those who are fasting or following a low-
calorie diet (Patients with psoriasis have been found to have
increased sensitivity to gluten via elevated serum IgA and/or
IgG antibodies to gliadin.7,8). But rather than resort to a strict
diet, the key is to simply follow a wholesome diet consisting
of a variety of fresh, organic vegetables and fruits; meat, fish
and poultry that has been raised without hormones or antibi-
otics; omega-3 fatty acids from sources such as fish oils, wild
salmon, flaxseed, hemp seeds, and pumpkin seeds.14
Of significant note are the benefits of adding vitamin D3
(cholecalciferol) to the diet and maintaining serum 25(OH)D
371
 Part 6 Complementary and Alternative Medicine

levels in a high-normal range of 70-100╯ng/mL. It is well

documented that Vitamin D is an important immune system Table 18.13╇ Complementary and alternative medicine use in
modulator, especially of T-cell mediated inflammatory psoriasis1
responses. In addition, it has antiproliferative effects.3 Defi-
ciency of vitamin D has become a worldwide problem where Evidence
an estimated 1 billion people have insufficient levels.11,12 Sur- Modality level P value Adverse events
prisingly, despite ample evidence, it is seldom recognized by
physicians. With higher levels of melanin, ethnicities with Vitamin D A NS* none
darker skin are more likely to be vitamin D deficient.11–14 Most Inositol C .015 none
psoriasis patients require 5,000–10,000╯IU of vitamin D3 per
Zinc A NS not studied
day to achieve and maintain a beneficial serum level.11 Clinical
evidence shows no adverse effects with extended supplementa- Selenium A NS none
tion at these levels. Patients with psoriasis who undergo pho- Neem A < .001 none
totherapy show an increase in their serum vitamin D levels Aloe Vera A NS dryness, stinging,
and a marked improvement in their psoriasis. Clinical research erythema
shows the greatest improvement from exposure to broadband
Vitamin B12 C NS pruritus
UVB (BUVB, 280–315╯nm), the wavelength most similar to
sunlight.21 Avocado oil C NS pruritus
Selenium supplementation may also be of value in psoria- Mahonia aquifolium A .01 staining
sis due to its antiproliferative and immunomodulating proper- Oleum horwathiensis A NS irritation
ties. Patients with low levels of selenium may be at greater risk
Fish Oil B NS, <.05 fishy smell/taste,
of developing the disease or have greater severity related to the
diarrhea
disease.22
Inflammatory compounds known as leukotrienes are Climatotherapy B NS, <.001 erythema, burning/
much more prevalent in individuals with psoriasis.16 Fish oils stinging
are known to bind to receptor sites, inhibit production of Chinese Medicine C <.05 none provided
leukotrienes, and reduce the rapid replication and build up of Mind/Body B NS, <.01 none reported
skin cells.17
*Not significant (p > .05)
Several herbs used as seasonings contain phytochemicals
that can block nuclear factor-kappaB (NFkB) activation of
inflammatory cytokines. Therefore, adding cloves, ginger, tur-
meric, anise, cumin, garlic, rosemary, red pepper, fennel, basil,
and pomegranate to the diet can be very beneficial.18 32╯ng/mL.19,20 Surprisingly, it is a problem seldom recognized
It is recommended that physicians make information avail- by physicians, despite ample evidence. There is a greater inci-
able to patients on suggested dietary guidelines or work dence of vitamin D deficiency in ethnicities with darker skin
in tandem with, or refer out to a trusted nutritionist or a due to higher amounts of melanin.19–22 While a portion of
traditional Chinese medical physician who is versed in one’s daily vitamin D3 requirement can be produced in the
dietary therapy and can guide the patient in a new, improved skin from adequate exposure to solar UVB radiation (30
way of eating (Table 18.13). Prevention is a better strategy minutes of full-body exposure on a summer day produces in
than attempting to cure a difficult disorder. excess of 10,000╯IU), the increased use of sunscreen and rigor-
Lastly, it is recommended that patients drink fresh, filtered ous sun protection measures may inadvertently contribute to
water in place of soft drinks and fruit juices (which are a source an ongoing insufficiency.19,20,22 Most patients require vitamin
of sugar). D supplementation at 5,000–10,000╯IU (severe cases may
require 20,000╯IU) per day to achieve and maintain beneficial
serum levels of 70–100╯ng/mL.19 Clinical evidence shows no
Vitamin/Mineral Therapies adverse effects from extended oral supplementation at these
dosages.23,24 Serum 25(OH)D levels should be checked twice
Patients with psoriasis often have very low levels of certain yearly. Concerns of toxicity are largely a non-issue unless oral
vitamins and minerals, thus supplementation with vitamin doses of 40,000–IU/day have been reached.19,23–27 When sup-
D3, B12, folate, selenium, and zinc should be undertaken.15 plementing a deficiency, it is important to use vitamin D3
Of significant note are the benefits of adding vitamin D3 (cholecalciferol) rather than vitamin D2 (ergocalciferol).
(cholecalciferol) to the diet and maintaining serum 25(OH)D Studies show that ergocalciferol is not as effective at raising
levels in a high-normal range of 70–100╯ng/mL. It is well serum 25(OH)D levels.27,28 Moreover, vitamin D3 is notably
documented that Vitamin D is an important immune system non-calcemic and safe, unlike vitamin D2 and other vitamin
modulator, especially of T-cell mediated inflammatory D analogs.24
responses. In addition, it has antiproliferative effects.7 Defi- Patients who undergo phototherapy show an increase in
ciency of vitamin D has become a worldwide problem where their serum vitamin D levels and a marked improvement
an estimated 1 billion people have insufficient levels below in their psoriasis. Clinical research shows the greatest

372
 18â•… An Overview of Complementary and Alternative Medicineâ•… •â•… Psoriasis
improvement from exposure to broadband UVB (BUVB, 280–
316╯nm), the wavelength most similar to sunlight.29
Supplementation with selenium may also be of value in
psoriasis due to its antiproliferative and immunomodulating
properties. Patients with inadequate levels of selenium may be
at greater risk of developing the disease or have greater severity
related to the disease.30
Psychological and meditative therapy
Meditation and stress reduction are a very important part of
complementary treatment for psoriasis.
Influence of a mindfulness meditation-based stress reduc-
tion intervention on rates of skin clearing in patients with
moderate to severe psoriasis undergoing phototherapy
(UVB) and photochemotherapy (PUVA). Kabat-Zinn J,
Wheeler E, Light T, Skillings A, Scharf MJ, Cropley TG, Hosmer
D, Bernhard JD. Psychom Med 1998; 60:625–632.
Psoriasis patients who listened to a guided meditation tape
while undergoing artificial ultraviolet light treatments cleared
four times faster than those who received only phototherapy.
37 patients with moderate to severe psoriasis received light
therapy (either UVB or PUVA) three times per week for approx-
imately 13 weeks while listening to stress reduction/relaxation
tapes. They avoided the use of any oral or topical psoriasis
treatments during this time except emollients and 1% hydro-
cortisone cream for skin areas not exposed to light. Results
showed that of the 37 subjects in the study, 19 achieved clear-
ing, 4 did not, and 14 subjects prematurely discontinued treat-
ment. Results suggest that the rate of skin clearing can be
accelerated when subjects listen to a guided meditative stress-
reduction intervention during their UVB or PUVA photother-
apy treatment sessions.
Depression in dermatology: an integrative perspective.
Filakovic P, Biljan D, Petek A. Psychiatr Danub 2008; 20(3):
410–425.
In dermatological patients, depression occurs significantly
more frequently, approximately 30%, as compared to patients
in general practice where it is 22%. The authors found a strik-
ing similarity between depression and psoriasis including
elevated concentrations of proinflammatory cytokines and
acute phase proteins in both disorders, indicating that
both disorders can be considered immunologically mediated,
inflammatory states with similar comorbidity.
A pilot study of hypnosis in the treatment of patients with
psoriasis. Tausk F, Whitmore SE. Psychother Psychosom 1999;
6(4):221–225.
This 3-month randomized, single-blind, controlled trial
studied hypnosis in adult patients with plaque-type psoriasis.
This study had a limited number of patients but the results
showed significantly greater improvement in highly hypnotiz-
able subjects than moderately hypnotizable subjects. This sug-
gests that hypnosis can be a useful therapeutic modality for
those with psoriasis but further studies are recommended.
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alternative medicine for psoriasis: a qualitative review of the clinical
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26. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentra-
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Index
A laser treatment, 333t
abobotulinumtoxin A (Dysport), 311–314,
312t
abscesses, S. aureus, 132
acanthosis nigricans, 183–185
N-acetyl glucosamine, 305
acetylsalicylic acid see aspirin
aciclovir (acyclovir), erythema multiforme,
105–106
acitretin
bullous pemphigoid, 112
cutaneous lupus erythematosus
chronic, 49–50
subacute, 53
epidermal nevus, 264
follicular mucinosis associated with
cutaneous T-cell lymphoma, 233
lichen amyloidosis, 150–151
lichen planus, 156
psoriasis, 171
combined with Chinese herbal
medicine, 369
acne, 3–13, 317–318
chemical peel, 317–318
complementary therapy, 357–361
device-based treatments, 316, 338, 342
efficacy and results, 340t
pediatric, 13–14
pomade, 12–13, 273f, 274
scars, 5–6, 5f, 10, 319–320, 342–343
steroid-associated, 13
vulval apocrine, 20
acne conglobata, 238
acne keloidalis nuchae, 249–251, 327, 328f
acne rosacea, 14–18
acne vulgaris, 3–14
1st-line therapies, 6b
2nd-line therapies, 8b
3rd-line therapies, 10b
algorithm, 5f
commonly encountered pitfalls, 11
cosmetic products, 285
diagnosis, 3
differential diagnosis, 3–4
epidemiology, 3
psoriasis, 175–176
postinflammatory hyperpigmentation trichotillomania, 247
(PIH), 310f Ah-Shi points, 355
special management and counselling alefacept, psoriasis, 173
considerations, 11 alemtuzumab, Sézary syndrome, 275
acneiform disorders, 3–23 alexandrite laser
follicular mucinosis presenting as, 233 Futcher’s lines, 203
acral melanoma (incl. acral lentiginous lentigenes and freckles, 341
melanoma), 277 lentigo maligna, 279
diagnostic difficulties, 277, 282 melasma, 199
histology, 278–279 minocycline-induced hyperpigmentation,
treatment, 278 189–190
acrochordon, 260 allergic contact dermatitis, 69–74, 85
acropustulosis, infantile, 32–33 induction in alopecia areata treatment,
actinic lentigo (solar lentigo), 207–209, 228–229
277–278, 285 paraphenylenediamine dyes, 275
actinic lichenoid eruption, summertime, secondary, risk in nummular eczema,
153–154 91
actinic photodamage, 205 allergic disorders, 101–118
acupuncture, 355 Allium cepa juice, alopecia areata,
indications, 355t 363–364
acne, 358–359 all-trans-retinoic acid see tretinoin
alopecia, 361–362 aloe vera
urticaria, 118 acne, 359
acute leukemia, oral candidiasis prevention psoriasis, 369–370
in chemotherapy-treated patients, aloesin, 278
120 alopecia (hair loss; baldness), 227–248,
acyclovir, erythema multiforme, 105–106 361–364
adalimumab (anti-TNF MAb) androgenetic see androgenetic alopecia
dissecting cellulitis, 238 cicatricial see cicatricial alopecia
erythema nodosum, 110 complementary therapy, 361–364
granuloma annulare, 96 discoid lupus erythematosus, 51
psoriasis, 171 scarring, 234
sarcoidosis, 98 tinea capitis, 143
adapalene traction, 242–244, 327f
acne vulgaris, 4, 6, 285 traumatic, 244–246
infants, 14 alopecia areata, 227–232
melasma, 197–198, 285 complementary therapy, 363–364
adjuvant therapy alopecia follicularis (folliculitis decalvans),
dermatofibrosarcoma protuberans, 251–254
276 alopecia mucinosa, 232–234
squamous cell carcinoma, 281 5-alpha-reductase inhibition by herbs in
adolescents (teenagers) androgenic alopecia, 361–363
acne and dairy intake, 360 alternative medicine see complementary and
folliculitis, 131 alternative medicine
375
Index
American College of Rheumatology
classification
scleroderma, 62t
systemic lupus erythematosus, 54, 54t
5-aminolaevulic acid (5-ALA) see
photodynamic therapy
amiodarone-associated pigmentation
disorders, 190, 190t
ammonium lactate, acanthosis nigricans,
184
amorolfine, candidal onychomycosis, 148
amoxicillin, C. trachomatis, 125
amoxicillin/clavulanate (co-amoxiclav;
Augmentin)
cellulitis and erysipelas, 121
impetigo, 31t
amputation
squamous cell carcinoma arising in
osteomyelitis or chronic wounds,
282
subungual melanoma of hand, 271
amyloidosis
lichenoid, 149–151
primary localized cutaneous (PLCA),
149, 151
anakinra, cold urticaria, 118
analgesics, fixed drug eruptions caused by,
103t
androgen(s)
antagonists see antiandrogens
green tea effects on, 358
androgenetic alopecia, 327, 327f
complementary therapy, 363
anesthesia
local, hair transplantation, 327–328
topical (before removal)
dermatosis papulosa nigra, 262
skin tags, 259–260
angioedema, 115, 118
angiotensin II receptor antagonist,
Raynaud’s phenomenon in
scleroderma, 64
annular seborrheic dermatitis, 177,
180
annular subacute cutaneous lupus
erythematosus, 53
anogenital lesions
lichen sclerosus, 161
lymphogranuloma venereum, 136t
warts, 133–135, 134t
anorectal syndrome, lymphogranuloma
venereum, 136t
anosacral amyloidosis, 151
anthralin see dithranol
antiandrogens (androgen antagonists)
acne vulgaris, 4, 9
hidradenitis suppurativa, 21
antibacterial activity of herbal medicines,
358–360
antibiotics (referred to sometimes as
antimicrobials or antibacterials)
acne keloidalis nuchae, 250
acne vulgaris, 4, 6–9
infants, 13–14
376
atopic dermatitis with associated S.
aureus colonization, 79
bullous pemphigoid, 27
cellulitis and erysipelas, 121–122
chancroid, 124, 137
Chlamydia trachomatis, 125–126
types L1-L3 (lymphogranuloma
venereum), 136–137,
136b–137b
confluent and reticulated papillomatosis,
187–188
dissecting cellulitis, 236–237
donovanosis (granuloma inguinale),
127b, 128
fixed drug eruptions caused by, 103t
folliculitis, 130–131
folliculitis decalvans, 252–253
furunculosis, 132
hidradenitis suppurativa, 19–21
and surgery, 20
impetigo, 29–31
lupus erythematosus (cutaneous), 50
perioral dermatitis, 22–23
rosacea, 16–18
scarlet fever (S. pyogenes), 130
scleroderma
diffuse, 66–67
localized, 60
syphilis, 139t, 141, 141t
traction alopecia, 243
antibody see autoantibodies;
immunoglobulin, intravenous;
monoclonal antibodies
anticonvulsants, fixed drug eruptions caused
by, 103t
antifungal agents
atopic dermatitis, 79
candidiasis
intertriginous/cutaneous, 120
oral, 119–120
children, 143–144
confluent and reticulated papillomatosis,
188
dandruff, 272, 274
fixed drug eruptions caused by, 103t
pityriasis (tinea) versicolor, 137b,
138–139
seborrheic dermatitis
face, 178
scalp, 179–180, 272–273
tinea capitis, 143–144
tinea corporis, 145–146
tinea unguium, 146, 148
antihistamines (H1 receptor antagonists)
atopic dermatitis, 75–76, 79
bedbug bites, 101
infantile acropustulosis, 32
pityriasis rosea, 167
urticaria, 117–118
anti-inflammatory drugs see non-steroidal
anti-inflammatory drugs; steroids
anti-inflammatory herbal medicines
acne, 359
psoriasis, 369
antimalarials
cutaneous lupus erythematosus, 49, 52,
240
effects of smoking, 49, 51–52
erythema nodosum, 109
pigmentation disorders caused by, 189,
190t
polymorphous light reaction, 113–114
sarcoidosis, 98–99
systemic lupus erythematosus, 56
antimycotic agents see antifungal agents
antinuclear antibody (ANA)
systemic lupus erythematosus, 56
systemic sclerosis, 61–62
antioxidants
melasma, in combination cream, 282
nickel-induced hypersensitivity reactions,
72
antiplatelet agents, livedoid vasculopathy, 45
antipruritics
lichen simplex chronicus, 89
nummular eczema, 91
antipsychotics, pigmentation disorders with,
190t
antituberculous agent, lichen nitidus, 153
apocrine acne, vulval, 20
arbutin, 304
aromatherapy see essential oils
arthritis, psoriatic, 171
arthropod bites, 101–102
ascorbic acid see vitamin C
ashy dermatosis (erythema dyschromicum
perstans), 191–192
Asiasari radix extract, alopecia, 362
aspirin (acetylsalicylic acid)
erythema nodosum, 109
livedoid vasculopathy, 45
atopic dermatitis, 74–81, 85, 88, 364–368
complementary therapy, 364–368
impetigo predisposition, 29
postinflammatory hyperpigmentation,
204f
atorvastatin, Raynaud’s phenomenon in
scleroderma, 64
atrophic acne scars, 319, 343
atrophic papulosis, malignant, 46
atrophie blanche (livedoid vasculopathy),
44–47
atrophy, discoid lupus erythematosus, 51
Augmentin see amoxicillin/clavulanate
auranofin, discoid lupus erythematosus, 51
autoantibodies
systemic lupus erythematosus, 56
systemic sclerosis, 61–63, 67, 67t
autoimmune disorder(s)
blistering disorders, 33–38
collagen vascular diseases, 53–58, 61–67
psoriasis as, and effects of diet, 371
autoimmune thyroiditis and granuloma
annulare, 93
axillary hair removal, 334f, 341
axillary hyperhidrosis, botulinum toxin A,
314
Ayurvedic medicine see Indian
 Index

azathioprine mycosis fungoides (associated with localized scleroderma, 60

bullous pemphigoid, 27, 112 parapsoriasis), 164–165 lupus erythematosus (cutaneous), 241
diffuse systemic sclerosis, 65 seborrheic dermatitis of scalp, 179 see also pimecrolismus; tacrolismus
erythema multiforme, 106 vitiligo, 219 calcinosis
lupus erythematosus bexarotene, cutaneous T-cell lymphoma, juvenile dermatomyositis, 39–44
cutaneous, 50, 53 274–275 livedoid vasculopathy, 44
systemic, 57 Sézary syndrome, 112 calcipotriol (calcipotriene)
nummular eczema, 91 bifonazole, pityriasis versicolor, 138 acanthosis nigricans (for hyperkeratosis
parthenium dermatitis, 72 biologic agents, alopecia areata, 230–231 of nipple), 184
pemphigus vulgaris, 36–38 see also monoclonal antibodies inflammatory linear verrucous epidermal
psoriatic erythroderma, 112 biopsy nevus (ILVEN), 264
azelaic acid, 303–304 benign melanonychia, 186 lichen amyloidosis, 150
hyperpigmentation, 205, 285 donovanosis (granuloma inguinale), 128t localized scleroderma, 60
melasma, 198, 205, 285 Haemophilus ducreyi, 123 psoriasis, 169
rosacea, 16 scalp children, 175
azithromycin alopecia mucinosa, 232 vitiligo, 220
chancroid, 124, 137 folliculitis decalvans, 252 calcitriol (1,25-dihydroxyvitamin D3)
Chlamydia trachomatis, 125–126 see also histology psoriasis, children, 175
Chlamydia trachomatis, types L1-L3 bipenicillin, erysipelas, 121 scleroderma (localized), 59, 61
(lymphogranuloma venereum), birth control pills see contraceptive pills calcium channel blockers
136–137 BK mole, 265 keloids, intralesional, 268–269
confluent and reticulated papillomatosis, bleaching agents livedoid vasculopathy, 46
188 hyperpigmentation Raynaud’s phenomenon in systemic
donovanosis (granuloma inguinale), melasma, 198 sclerosis, 63–64
127b, 128 Orientals, 198, 208 calcium hydroxide, relaxers containing,
rosacea, 17–18 irritant contact dermatitis, 84f 275t–276t
syphilis, 141 bleomycin, keloids, 268 calcium hydroxylapaptite, 322–325
blisters see bullae Camellia sinensis (green tea) and acne,
blood (in Chinese medicine) 358–359
B alopecia and, 361 camouflage
bacterial exanthems, 129t psoriasis and, 368 hair, 282, 301
see also antibacterial activity; antibiotics blood-heat, 368–369 skin, 306–307
baldness see alopecia blue-light phototherapy, 342 CAMPATH-1H, monoclonal antibody to
basal cell carcinoma, 271–272, 281–282 boil (furunculosis), 131–133 (=alemtuzumab), Sézary
diagnostic difficulties, 282, 284t bonding glue (hair), 275, 283f syndrome, 275
pigmented, 271, 272f, 282, 283f bosentan, Raynaud’s phenomenon in cancer, 271–286
presentation commpared to other skin systemic sclerosis, 64 cutaneous, 271–286
cancers, 282t botanicals see herbal medicine alopecia mucinosa predisposition to,
risk factors by race/ethnicity, 285t botulinum toxin A, 311–314 232
basing the scalp, 275 complications, 314 benign melanonychia leading to, 185
BCNA (carmustine), mycosis fungoides, 274 contraindications, 311 diagnostic difficulties, 282, 284t
bedbugs, 101–102 indications (face/neck etc.), 311t discoid lupus erythematosus
behavioral treatment dyshidrotic hand eczema, 83 predisposition to, 51
neurodermatitis, 88 technique, 311–314 hidradenitis suppurativa
trichotillomania, 247 Bowen’s disease (squamous cell carcinoma predisposition to, 21
benign tumors, 259–269 in situ), 271, 282, 282t lichen sclerosus predisposition to,
benzoyl peroxide pigmented, 280f, 285f 160
acne, 4, 7, 359 treatment, 281 Ota’s nevus leading to, 202
infants, 13–14 braids, 275 non-cutaneous/in general
neonates, 14 Brazil, lichen amyloidosis, 151 acanthosis nigricans associated with,
dissecting cellulitis, 236 Brazilian keratin treatment, 275 185
rosacea, 17 brow ptosis complicating botulinum toxin dermatomyositis predisposition to,
benzylpenicillin (penicillin G) A use, 314 40
cellulitis, 121 bullae/blisters HPV vaccine in prevention of cervical
localized scleroderma, 60 bedbug bites causing, 101–102 neoplasia, 135
syphilis, 141 disorders causing, 25–38 see also specific histological types
beraprost sodium, livedoid vasculopathy, 46 bullosis diabeticorum, 25–26 candidiasis, 119–120
berberine, psoriasis, 370 butenafine, tinea corporis, 145 fingernail, 148
beta radiation, keloids, 267 capsaicin
betamethasone lichen simplex chronicus, 89
alopecia areata, 363 C pruritic psoriasis, 369–370
atopic dermatitis, 77–78 calcineurin inhibitors carbon dioxide laser
irritant contact dermatitis, 77–78 atopic dermatitis, 75–76 epidermal nevus, 264
lichen amyloidosis, 150 irritant contact dermatitis, 84 HPV lesions, 134t

377
Index
hyperpigmentation
gingival, 194
hydroquinone-induced (=exogenous
ochronosis), 193
melasma, 199
carcinoma see basal cell carcinoma;
squamous cell carcinoma
carcinoma in situ, squamous cell see
Bowen’s disease
cardiovascular disease, systemic lupus
erythematosus, 54–55
carmustine, mycosis fungoides, 274
caseating granulomatous variant of rosacea,
15, 18
Castellani’s paint, intertriginous/cutaneous
candidiasis, 120
catechin (in green tea) and acne, 358
alopecia areata, 364
CD2-targeting drug (=alefacept), psoriasis,
173
CD4+ T lymphocytopenia, 112
CD11a-targeting monoclonal antibody see
efalizumab
CD20-targeting monoclonal antibody see
rituximab
CD52-targeting monoclonal antibody
(=alemtuzumab), Sézary
syndrome, 275
cefazolin, cellulitis and erysipelas, 121–122
cefdinir, folliculitis, 131
cefotaxime, cellulitis and erysipelas, 122
ceftriaxone
cellulitis and erysipelas, 121–122
chancroid, 124
syphilis, 141
cefuroxime
impetigo, 31t
subacute cutaneous lupus erythematosus,
53
celecoxib, systemic lupus erythematosus, 56
cell adhesion and activation molecules and
erythema dyschromicum perstans,
191
cellular dermatofibroma, 261
cellulitis, 121–122
dissecting, 236–239, 327, 328f
central centrifugal cicatricial alopecia,
234–236, 245, 328f
hair transplantation, 327
central nervous system disorders see
neurological disorders
cephalexin
folliculitis, 131
impetigo, 31t
methicillin-resistant S. aureus-related
abscesses, 132
secondarily-infected dermatitis, 30
ceramide-containing/ceramide-dominant
emollients
atopic dermatitis, 76–77
psoriasis, 370
cervical neoplasia prevention, HPV vaccine,
135
cervicitis, chlamydial, 125–126
378
cetirazine
atopic dermatitis, 79
urticaria, 117
chancre, 140t
chancroid, 123–124, 137
chelating agents, nickel-induced
hypersensitivity reactions, 72
chemical alopecia, 244–246
chemical peels, 315–320
acne, 317–318
agents used, 315–316, 315t
see also specific agents
complications, 320, 344–345
contraindications, 315
deep, 316
hyperpigmentation, 208
melasma, 197, 208, 318–319
postinflammatory, 206, 319
solar lentigo, 208
indications, 315–320
medium depth, 316
pseudofolliculitis barbae, 255–256
rhytides, 320
special management and counselling
considerations, 346, 346t
superficial, 315–316
technique, 316–320
chemical processing of hair, 293–294
chemotherapy (cytotoxic drugs)
acute leukemia, oral candidiasis
prevention, 120
pigmentation disorders due to, 190t
see also specific agents
chickenpox, 129t
children
abuse, Mongolian spots mistaken for
ecchymotic lesions of, 201
acne, 13–14
allergic contact dermatitis, 70f
atopic dermatitis, 76–78
Chinese medicine, 365–366
evening primrose oil, 366
homeopathy, 367
hypnotherapy, 367
massage therapy, 367
nasal S. aureus colonization,
78–79
risk in Black children, 79
vitamin B12, 367
epidermal nevus, 264
erythroderma associated with
immunodeficiency, 112
hair products, 282t
lichen sclerosus, 157–158, 160–161
localized scleroderma, 60
Nigerian, Mongolian spots,
199–201
perioral dermatitis, 22–23
pityriasis alba, 216
psoriasis, 174–176
tinea capitis, 142–144
trichotillomania, 247
see also adolescents; infants; juvenile
dermatomyositis; neonates
Chinese medicine, traditional (incl. herbs
and acupuncture), 351, 354
acne, 358–359, 358t
alopecia, 361–362
eczema/atopic dermatitis, 364–368,
366t
historical background, 354
psoriasis, 368–373
see also acupuncture; herbal medicine;
moxibustion
Chinese populations
allergic contact dermatitis, 71
lichen amyloidosis, 151
pediatric atopic dermatitis and nasal S.
aureus colonization, 78–79
Chlamydia trachomatis, 124f, 125–126
L1-L3 types (causing lymphogranuloma
venereum), 135–137
chloramabucil, granuloma annulare, 96
chlorhexidine, dissecting cellulitis, 236
chloroquine
hyperpigmentation associated with,
189
lupus erythematosus
cutaneous, 52, 240
systemic, 56
sarcoidosis, 99
chromium administration, acne, 361
chronic wounds, squamous cell carcinoma
arising in, 282
cicatricial alopecia
central centrifugal see central centrifugal
cicatricial
hair transplantation, 331
inflammatory form (folliculitis
decalvans), 251–254
ciclopirox and ciclopiroxolamine
pityriasis versicolor, 139
seborrheic dermatitis
face, 178
scalp, 179, 272–273
toenail onychomycosis, 148
ciclosporin see cyclosporine
cilastin, cellulitis and erysipelas, 122
Cimex lectularias (bedbug), 101–102
ciprofloxacin
cellulitis and erysipelas, 122
chancroid, 124
dissecting cellulitis, 237
donovanosis (granuloma inguinale),
127b, 128
circumcision, lichen sclerosus et atrophicus
causing phimosis, 157–158
cisaprost, Raynaud’s phenomenon in
systemic sclerosis, 64
13-cis-retinoic acid see isotretinoin
citalopram, trichotillomania, 247t
Citrullus colocynthis, alopecia, 362
citrus oils, acne, 360
clarithromycin, confluent and reticulated
papillomatosis, 188
Clark’s nevus (mole), 265
clavulanate/amoxicillin see amoxicillin/
clavulanate
 Index

climatotherapy, psoriasis, 369–371 eczema/dermatitis, 364–368 cyclodextrin–hydroquinone, solar lentigenes,

clindamycin allergic contact, 74 208
acne keloidalis nuchae, 250 atopic, 364–368 cyclophosphamide
acne vulgaris, 7–8 nummular exzema, 91 dermatomyositis with refractory
dissecting cellulitis, 237–238 funding of research, 352 cutaneous vasculitis, 40
folliculitis decalvans, 252–253 psoriasis, 368–374 diffuse systemic sclerosis, 65–66
hidradenitis suppurativa, 19–20 urticaria, 118 pemphigus vulgaris, 36
rosacea, 17 users of, 352–353 systemic lupus erythematosus, 57
clioquinol, nickel-induced hypersensitivity conditioners, hair, 275t, 292–293 cyclosporine (ciclosporin)
reactions, 72 children, 282t alopecia areata, 230
clobetasol propionate confluent and reticulated papillomatosis (of irritant contact dermatitis, 86
alopecia totalis, 228, 243 Gougerot and Carteaud), 187–188 pemphigus vulgaris, 37
chronic cutaneous lupus erythematosus, congenital melanocytic nevus, 264–265 psoriasis, 172
49, 240 connective tissue (collagen vascular) children, 176
granuloma annulare (associated with diseases, 39–67 systemic lupus erythematosus, 57
autoimmune thyroiditis), 93 contact cooling (laser/light devices), 336 toxic epidermal necrolysis, 107
lichen simplex chronicus, 88 infrared device, 343 urticaria, 118
psoriasis, 169 contact dermatitis cyproterone acetate, hidradenitis
adolescents, 175 allergic see allergic contact dermatitis suppurativa, 6, 21
scalp, 274 irritant, 71, 84–87, 89 cyst, epidermoid, 266
seborrheic dermatitis of scalp, contact immunotherapy, alopecia areata, cytotoxic drugs
273–274 228–229 anticancer see chemotherapy
clobetasone butyrate, pemphigus foliaceus, continuous contact cooling see contact immunosuppressive see
34 cooling immunosuppressive cytotoxic
clofazimine contraceptive (birth control) pills drugs
discoid lupus erythematosus, 50 discontinuation with melasma, 199
erythema dyschromicum perstans, use, acne vulgaris, 4, 9–10
191–192 cooling, contact see contact cooling D
side-effects, 192 cornrows, 275 dairy intake and teenage acne, 360
clomipramine, trichotillomania, 247 corticosteroids see steroids danazol, livedoid vasculopathy, 46
clotrimazole cosmetic procedures, 309–347 dandruff, 273–274
candidiasis cosmetic products, 289–308 dapsone
intertriginous/cutaneous, 120 hair, 276 dermatomyositis, 43
oral, prophylactic, 119–120 skin, 301–308 erythema dyschromicum perstans,
pityriasis (tinea) versicolor, 138 perioral dermatitis associated with, 191–192
tinea corporis, 145 22 erythema multiforme, 106
coal tar Cosmoderm and Cosmoplast, 323t folliculitis decalvans, 253
dandruff shampoo, 274 co-trimoxazole see trimethoprim/ granuloma annulare, 95
pityriasis alba, 217 sulfamethoxazole infantile acropustulosis, 32
psoriasis, 170 coxsackie virus A16 and hand, foot and lupus erythematosus (cutaneous)
and UV, children, 175 mouth disease, 129t chronic, 50, 241
co-amoxiclav see amoxicillin/clavulanate crimping iron, 275 subacute, 53
cobalamin (vitamin B12), eczema/atopic crow’s feet, botulinum toxin A treatment, urticaria, 117–118
dermatitis, 367 314 daptomycin, cellulitis and erysipelas, 122
cobalt, dietary restriction in dyshidrotic cryoanesthesia, skin tags, 259–260 dark ground illumination, T. pallidum,
eczema, 82 cryosurgery 142t
COL1A-PDGFβ fusion gene and basal cell carcinoma, 272 Dead Sea bathing, psoriasis, 369–371
dermatofibrosarcoma protuberans, dermatofibroma, 261 demarcation lines, pigmentary, 203–204
276 granuloma annulare, 94 denileukin diftitox, cutaneous T-cell
colchicine, erythema nodosum, 109–110 HPV, 134t lymphoma, 275
cold urticaria, 118 nodular neurodermatitis, 89 deoxyarbutin, 285
collagen, 309 pseudofolliculitis barbae, 256 depilation/epilation (hair reduction/
porcine, 323 solar lentigenes, 208–209 removal)
collagen vascular diseases, 39–67 squamous cell carcinoma, 282 device-based (lasers and light sources),
coloring agents (hair dyes), 285t, culture 332–337, 333t, 340–341
294–296 H. ducreyi, 123 complications, 310f, 343–344
combs, wide-tooth, 273f, 274 K. granulomatis (granuloma inguinale), efficacy and results, 340t
comedogenic acne 128t in pseudofolliculitis barbae, surgical,
comedone extraction, 5 curcumin, psoriasis, 369 255
salicylic acid peels, 317 curettage depression and psoriasis, 373
complementary medicine, 351–374 basal cell carcinoma, 271 dermabrasion
acne, 357–361 HPV lesions, 134t hydroquinone-induced exogenous
alopecia (hair loss; baldness), 361–364 curling iron, Marcel, 276 ochronosis, 193
defining, 351–352 Cuscuta reflexa, alopecia, 362 rosacea, 18

379
Index
dermatitis (eczema), 69–91, 364–368
allergic contact see allergic contact
dermatitis
atopic see atopic dermatitis
complementary therapy see
complementary medicine
dyshidrotic, 81–83, 86–87
exfoliative see erythroderma
irritant contact, 71, 84–87, 89
nummular, 90–91
perioral, 21–23
seborrheic, 177–180
secondarily-infected, cephalexin, 30
see also neurodermatitis
dermatofibroma, 260–261
dermatofibrosarcoma protuberans, 276,
284f
diagnostic difficulties, 282, 284t
dermatomyositis, 39–44
dermatophytosis see tinea
dermatosis papulosa nigra, 261–263
fractional photothermolysis, 263,
341–342
laser treatment, 262, 337
postinflammatory hyperpigmentation,
342
Dermicol-P35, 325
dermis
fillers see fillers
in melasma, features, 195t
dermographism, 117
desloratadine, urticaria, 117–118
desmoglein-1
pemphigus foliaceus and, 33
pemphigus vulgaris and, 35, 38
desmoglein-3 and pemphigus vulgaris, 35,
38
dexamethasone
pemphigus vulgaris, 36
Stevens–Johnson syndrome and toxic
epidermal necrolysis, 107
diabetes mellitus
bullous disorder, 25–26
cellulitis and erysipelas in, 122
lichen simplex chronicus in
postmenopausal women with,
88–89
diaper (napkin) candidiasis, 119
dichlorodifluoromethane (Refrigerant 12),
nodular neurodermatitis, 89
dicloxacillin, impetigo, 31t
dietary management
acne, 360–361
atopic dermatitis, 80
dyshidrotic eczema, 82
nickel allergy, 72
psoriasis, 371–372
diffuse systemic sclerosis, 61–62, 62t
treatment, 65–66
digits (incl. fingers)
granuloma annulare, 95
subungual melanoma, amputation, 271
ulcers, systemic sclerosis, 64
see also toe
380
1,25-dihydroxyvitamin D3 see calcitriol durag, 275
di-iodohydroxyquinoline, pityriasis alba, dye, hair, 285t, 294–296
217 dye laser, pulsed see pulsed dye laser
dimethicone, hair moisturizer, 273f, 274 dyschromia
dimethicone and glycerin (Pro-Q) aerosol device-based treatment, 333t, 337–338,
foam, hand dermatitis, 71, 85 341–342
dimethyl sulfoxide (DMSO), lichen complications, 344
amyloidosis, 150–151 efficacy and results, 340t
dinitrochlorobenzene postinflammatory see postinflammatory
alopecia areata, 229 hyperpigmentation
lichen nitidus, 153 dyshidrotic eczema, 81–83, 86–87
diode laser dysplastic nevus (mole), 265
acne keloidalis nuchae, 250–251 Dysport (abobotulinumtoxin A), 311–314,
hair removal, 340–341 312t
pseudofolliculitis barbae, 256 dystrophic onychomycosis, total, 146
dioic acid, 278
diphencyprone, alopecia areata, 229
diphenylcyclopropenone, alopecia areata, E
228–229 earlobe, keloid, 267–268
diphtheria toxin/interleukin-2 conjugate eberconazole, intertriginous/cutaneous
(denileukin difitox), cutaneous candidiasis, 120
T-cell lymphoma, 275 ecchymotic lesions of child abuse,
dipyridamole, livedoid vasculopathy, 45 Mongolian spots mistaken for, 201
discoid lupus erythematosus, 39, 239–242 Eclipta alba, alopecia, 362
alopecia, 51 eczema see dermatitis
management, 49–51, 53, 240–242 eczema herpeticum, 79–80, 80f
special management and counseling EDTA, nickel-induced hypersensitivity
considerations, 51–52 reactions, 72
dissecting cellulitis, 236–239, 327, 328f efalizumab (anti-CD11a)
disulfiram, hand dermatitis, 72 alopecia areata, 230–231
dithranol (anthralin) discoid lupus erythematosus, 51, 241
alopecia areata, 229–230 eflornithine, pseudofolliculitis barbae, 255
psoriasis, 169 EGF cream, pemphigus foliaceus, 34
children, 175 electromagnetic pulses, low-intensity,
DMSO (dimethyl sulfoxide), lichen androgenic alopecia, 363
amyloidosis, 150–151 electrosurgery (incl. electrodesiccation)
Dominican blowout, 275 basal cell carcinoma, 271
donovanosis, 126–128 dermatosis papulosa nigra, 262
doxepin, dermatitis, 89 skin tags, 259–260
doxycycline Elevesse, 323t
acne keloidalis nuchae, 250 ellagic acid, melasma, 285
acne vulgaris, 4, 9 elliptical excision, epidermoid cyst, 266
C. trachomatis, 125–126 emollients and moisturizers
cervicitis, 126 allergic contact dermatitis, 71
dissecting cellulitis, 237–238 atopic dermatitis, 75–77
donovanosis (granuloma inguinale), hair see conditioners
127b irritant contact dermatitis, 71, 85, 89
methicillin-resistant S. aureus-related skin nummular eczema, 90
and soft tissue infection, 131 pityriasis rosea, 167
rosacea, 16 psoriasis, 170
dreadlocks, 275 endothelin receptor antagonist, systemic
dressings sclerosis, 64
hydrocolloid see hydrocolloid dressings enteroviruses and hand, foot and mouth
in toxic epidermal necrolysis, 107 disease, 129t
drospirenone + ethinyl estradiol, acne ephelides, 209
vulgaris, 9–10 epidermal growth factor cream, pemphigus
drug-induced conditions foliaceus, 34
dermatomyositis, 40 epidermis
erythema multiforme, 104, 105t irritant reactivity and water loss across, 86
erythema nodosum, 109t in melasma, 195t
exfoliative dermatitis, 111t nevus, 263–264
fixed eruption, 102–104 in psoriasis, climatotherapy effects, 371
hyperpigmentation, 189–190, 192–193 in vitiligo, grafts, 223
lupus-like syndrome, 56 epidermoid cyst, 266

epigallocatechin-3-gallate (in green tea)
acne, 358
alopecia areata, 364
erbium:YAG laser
gingival hyperpigmentation, 194
verrucous epidermal nevus, 264
erythema dyschromicum perstans,
191–192
erythema multiforme, 104–108
erythema nodosum, 106, 108–110
chronic variant, 108
erythroderma (exfoliative dermatitis),
111–113
erythromycin
acne vulgaris, 4
infants, 14
C. trachomatis, 125–126
chancroid, 124
confluent and reticulated papillomatosis,
188
donovanosis (granuloma inguinale),
127b
impetigo, 29–30
perioral dermatitis, 22
essential oils (aromatherapy)
acne, 360
alopecia areata, 363
androgenic alopecia, 363
etanercept (anti-TNF agent)
alopecia areata, 231
erythema nodosum, 110
psoriasis, 172–174
children, 176
ethinyl estradiol
cyproterone acetate and, hidradenitis
suppurativa, 21
progestogen and see contraceptive pills
ethnicity see race
ethylenediaminetetra-acetic acid, nickel-
induced hypersensitivity reactions,
72
etretinate
lichen amyloidosis, 150–151
psoriasis, children, 176
evening primrose oil, atopic eczema, 366
Evolence, 323t
exanthems, 128–130
excimer laser, vitiligo, 220, 314–315
exfoliative dermatitis see erythroderma
extensions, hair, 276, 282
extracorporeal photochemotherapy
(photopheresis)
CD4+ T lymphocytopenia, 112
localized scleroderma, 61
Sézary syndrome, 275
systemic scleroderma, 66
eye see ocular involvement
eyelid and brow ptosis complicating
botulinum toxin A use, 314
F HPV, 134t
face
basal cell carcinoma, 271–272
cosmetic procedures
botulinum toxin A treatment see
botulinum toxin A
chemical peels see chemical peels
dermal fillers see fillers
wrinkles see wrinkles
epidermoid cyst removal, 266
hyperpigmentation, 205, 278
melasma, 195–196
pseudofolliculitis barbae, 255
psoriasis in children, 176
seborrheic dermatitis, 177–179
factor V Leiden, livedoid vasculopathy with,
45–46
fade, 275
familial primary localized cutaneous
amyloidosis (familial PLCA),
151
favus, 143
FDA approval
botulinum toxin A, 311, 311t
dermal fillers, 322–324
vorinostat in cutaneous T-cell
lymphoma, 275
females, hair loss, 327, 327f
fibrous dermatofibroma, 261
fifth disease, 129t
fillers (dermal), 321–326
special management and counselling
considerations, 346t, 347
finger see digits
finger waves, 275
fingernail, candidal onychomycosis, 148
fish oils, psoriasis, 372
Fitzpatrick skin type
botulinum toxin A (for glabellar lines)
and, 313
chemical peels and, 315
infrared and skin tightening, 343
intense pulsed light treatment of
hirsutism and, 341
laser hair removal and, 341
melasma and, 195–196
nasolabial fold augmentation, 325
pseudofolliculitis barbae and, 255–256
fixed drug eruptions, 102–104
FK506 see tacrolismus
flat iron, 275
flexural candidiasis, 119
flucloxacillin, cellulitis, 121
fluconazole
oropharyngeal candidiasis in HIV-
infected patients, 120
pityriasis (tinea) versicolor, 138–139
tinea capitis, children, 144
tinea corporis, 146
tinea unguium, 147–148
fluocinolone acetonide, melasma treatment,
196, 282
5-fluorouracil (5-FU) cream
basal cell carcinoma, 272
keloids, 268
squamous cell carcinoma, 281
Index
squamous cell carcinoma in situ
(Bowen’s disease), 281
verrucous epidermal nevus, 264
flurandrenolone tape, lichen simplex
chronicus, 88
foam products, irritant contact dermatitis,
71, 85
follicular mucinosis, 232–234
follicular unit extraction, 326
folliculitis, 130–131
dissecting (dissecting cellulitis),
236–239, 327, 328f
tufted, 251–252
folliculitis decalvans, 251–254
folliculitis keloidalis/nuchae (acne
keloidalis), 249–251, 327, 328f
follicullar disorders (in general), 249–256
foot ulcers, bullosis diabeticorum, 25
footwear dermatitis, India, 69–71
forceps removal of skin tags, 260
fractional photothermolysis, 337–338
dermatosis papulosa nigra, 263,
341–342
melasma, 337–338, 341
scars, 339, 343
freckles, device-based treatment in Asian
persons, 341
fulminating rosacea conglobata (rosacea
fulminans), 15
fumaric acid esters, granuloma annulare, 96
fungal infections, 119–120, 137–139
atopic dermatitis associated with, 79
dermatophyte see tinea
see also antifungal agents
furunculosis, 131–133
fusidic acid and sodium fusidate
confluent and reticulated papillomatosis,
188
folliculitis, 131
impetigo, 30
Futcher’s lines, 203–204
G
Galderma International triple combination
study in melasma, 196
garlic gel, alopecia areata, 363
G-CSF, necrotizing cellulitis, 122
genetic factors
atopic dermatitis, 80
urticaria, 118
genital-anorectal syndrome,
lymphogranuloma venereum, 136t
genitalia
lichen sclerosus, 159–161
psoriasis, 170
warts (anogenital warts), 133–134
gentamicin sulfate and surgery, hidradenitis
suppurativa, 20
German measles, 129t
gingival hyperpigmentation, 194–195
glabellar lines, botulinum toxin A, 312f,
313
glucocorticoids see steroids
381
Index

glucose-6-phosphate deficiency and infantile loss see alopecia
acropustulosis, 32 pulling out see trichotillomania
glue, hair bonding, 275, 283f removal/reduction see depilation;
glycemic load and acne, 360–361 shaving
glycerin and dimethicone (Pro-Q) foam transplantation, 326–332
aerosol, 71, 85 alopecia areata, 231
glycolic acid, 315 commonly encountered pitfalls, 331
acne vulgaris, 317 complications, 330–331, 347
actinic lentigo, 206, 208 contraindications, 327
melasma (and related conditions), 197, donor harvesting, 328–330, 329t
206, 208 graft placement, 329t
in combination preparations, graft preparation, 329t, 330
205–206, 282, 285, 318–319 indications and patient selection,
priming agents, 318 327–332
postinflammatory hyperpigmentation, instrumentation, 327
319 local anesthesia, 327–328
pseudofolliculitis barbae, 255–256 recipient site creation, 329t, 330
wrinkles, 320 special management and counseling
Goeckerman regimen, pediatric psoriasis, considerations, 332, 346t, 347
175 traction alopecia, 243
gold compounds, discoid lupus hair products in traumatic alopecia, 246
erythematosus, 51 hairstyles and traction alopecia, 242
gonorrhea (N. gonorrhoea) and C. halcinonide
trachomatis coinfection, 125 alopecia areata and totalis, 228
Gougerot–Carteaud syndrome, 187–188 dyshidrotic eczema, 82
grafts see transplants and grafts halobetasol propionate
granulocyte colony stimulating factor lichen simplex chronicus, 88
(G-CSF), necrotizing cellulitis, 122 plaque psoriasis, 175
granuloma annulare, 93–97 hand
generalized, 95–97 dermatitis/eczema, 72, 85–86
localized, 93–95 dyshidrotic eczema, 82–83
granuloma inguinale, 126–128 subungual melanoma, 277–278
granulomatous disorders, 93–100 hand, foot and mouth disease, 129t
granulomatous variant of rosacea, caseating, heat application causing traction alopecia,
15, 17 244–245
grape juice extract, melasma, 198–199 Helicobacter pylori
greasing, 275 nummular eczema and, 90
green tea rosacea and, 14
acne, 358–359 hematopoietic growth factors, necrotizing
alopecia areata, 364 cellulitis, 122
see also tea lotion hematopoietic stem cell transplantation,
Grenz rays, lentigo maligna melanoma, 279 cutaneous T-cell lymphoma, 275
griseofulvin henna dermatitis, 73
tinea capitis, 143–144 heparin, livedoid vasculopathy, 45
children, 143–144 hepatic transplant patients,
tinea corporis, 145–146 immunosuppressed, oral
tinea unguium, 147 candidiasis prophylaxis, 119–120
groin, hair removal, 334f hepatitis B and lichen planus, 157
gugulipid, nodulocystic acne, 358 hepatitis C and lichen planus, 154–155, 157
gums, hyperpigmentation, 194–195 herald patch, pityriasis rosea, 166
Herba saxifragae cream, eczema, 367
herbal medicine (phytomedicines; plant
H medicines), 353–354
habit reversal acne, 358, 358t
neurodermatitis, 88 alopecia, 361–362
trichotillomania, 247 androgenic, 363
Haemophilus ducreyi infection (chancroid), eczema/atopic dermatitis, 364–368
123–124, 137 psoriasis, 369–373
hair, 276 Western products, 354
breakage (trichorrhexis), 271t, 274 see also Chinese medicine
cosmetics, 276 Herose, psoriasis, 369
growth-promoting complementary herpes simplex-associated conditions
therapies, 361–364 eczema (eczema herpeticum), 79–80, 80f
ingrown see pseudofolliculitis barbae erythema multiforme, 105
HHV6 and HHV7, 129t
hidradenitis suppurativa, 19–21
hirsutism
intensive pulsed light, 341
laser treatment, 336–337, 336f
Hispanic populations, allergic contact
dermatitis, 71
histamine and urticaria, 115–116
histamine H1 receptor antagonists see
antihistamines
histochemistry, lichen amyloidosis,
149–150
see also immunohistochemistry
histology
basal cell carcinoma, 271
lichen nitidus, 152
lichen planus, 155
lymphogranuloma venereum, 136t
mycosis fungoides, 213
sarcoidosis (hypopigmented), 215
squamous cell carcinoma, 280
see also biopsy
HIV infection
atopic-like dermatitis, 80
erythema nodosum, 110
oropharyngeal candidiasis, 120
HLA and subacute cutaneous lupus
erythematosus, 52
Hoffman’s disease (dissecting cellulitis),
236–239, 327, 328f
homeopathy, 354
acne, 359
eczema/atopic dermatitis, 366–367
Hong Kong, allergic contact dermatitis,
71
hot comb, 275
HPV see human papilloma virus
human herpes virus 6 and 7, 129t
human immunodeficiency virus see HIV
infection
human papilloma virus (HPV), 133–135
squamous cell carcinoma in situ and,
279
hyaluronic acid fillers, 322
nasolabial folds, 324–325
hydrocolloid dressings/membranes
discoid lupus erythematosus, 240
nummular eczema, 90
psoriasis, 169
ulcers in scleroderma, 64
hydrocortisone
atopic dermatitis with associated S.
aureus colonization, 79
nickel-induced hypersensitivity reactions,
72
perioral dermatitis, 22
pityriasis alba, 217
seborrheic dermatitis, 178
hydroquinone, 302–306
hyperpigmentation
exogenous ochronosis, 192–193
melasma see subheading below
postinflammatory, 205–206
solar lentigenes, 208

382
 Index

melasma treatment, 196, 198, 205, 282,
318
in combination preparations,
196–197, 205–206, 285
vitiligo, 221
4-hydroxyanisole see mequinol
hydroxychloroquine
cutaneous lupus erythematosus, effects
of smoking, 49
erythema nodosum, 109
systemic lupus erythematosus, 56
hyperbaric oxygen, livedoid vasculopathy,
46
hyperhidrosis, axillary, botulinum toxin A,
314
Hypericum perforatum cream, atopic
dermatitis, 367
hyperkeratosis of nipple in acanthosis
nigricans, 185
hyperpigmentation, 183–209
cosmetic agents used, 272, 280–282,
302–306
drug-induced, 189–190, 192–193
gingival, 194–195
laser treatment see laser treatment
in lichen planus, 157
in lichen sclerosus, 160
post-pemphigus foliaceus, 34
postinflammatory see postinflammatory
hyperpigmentation
hypersensitivity disorders, 101–118
hypertrichosis, laser treatment, 336–337
hypertrophic lupus erythematosus, 47
treatment, 49
hypertrophic scars, 267–269, 285
hypnosis/hypnotherapy
alopecia areata, 364
nummular exzema, 91
psoriasis, 373
trichotillomania, 247
hypomelanosis, Ito’s, 211–212
hypopigmentation, 211–223
cutaneous T-cell lymphoma (incl.
mycosis fungoides), 212–215, 273,
283f
sarcoidosis, 215
seborrheic dermatitis, 177–178, 180
I sarcoidosis, 99
iloprost, Raynaud’s phenomenon in
systemic sclerosis, 63–65
imatinib, dermatofibrosarcoma protuberans,
276
imipenem, cellulitis and erysipelas, 122
imiquimod
acne keloidalis nuchae, 251
basal cell carcinoma, 272
discoid lupus erythematosus, 51
granuloma annulare, 94
HPV, 134t
keloids, 269
lentigo maligna, 279
localized scleroderma, 60
mycosis fungoides, 214
squamous cell carcinoma, 281
immune effects
Chinese herbal therapy in atopic eczema,
352–353
climatotherapy in psoriasis, 371
immunodeficiency, pediatric, erythroderma,
112
immunoglobulin
intravenous
bullous pemphigoid, 28
dermatomyositis, 42–43
livedoid vasculopathy, 46
lupus erythematosus (cutaneous), 53
pemphigus vulgaris, 28
Stevens–Johnson syndrome and toxic
epidermal necrolysis, 106–107
subcutaneous, dermatomyositis, 42
immunohistochemistry
basal cell carcinoma, after curettage and
electrodessication, 271
psoriasis remission and relapse, 169
immunomodulators
acne keloidalis nuchae, 251
atopic dermatitis, 77
bullous pemphigoid, 27
dermatomyositis, 43, 241
juvenile, 41–42
dyshidrotic eczema, 82
follicular mucinosis, 233
granuloma annulare, 95
irritant contact dermatitis, 85
lichen nitidus, 152
lichen sclerosus, 159
anogenital, 161
lichen simplex chronicus, 88–89
lichen striatus, 162
lupus erythematosus (cutaneous)
chronic, 49, 241
subacute, 53
mycosis fungoides (associated with
parapsoriasis), 164
nickel-induced contact allergy, 72
pemphigus foliaceus, 34
perioral dermatitis, 23
pityriasis alba, 216–217
psoriasis, 170
children, 176
rosacea, 17
scleroderma (localized), 60
seborrheic dermatitis, 178–179
vitiligo, 219
with excimer laser, 220
immunosuppression
oral candidiasis prophylaxis, 119–120
sunlight-induced, broad-spectrum
sunscreen protection, 114
immunosuppressive cytotoxic drugs
alopecia areata, 230
bullous pemphigoid, 27–28, 112
dermatomyositis, 40
erythema multiforme, 106
erythema nodosum, 110
granuloma annulare, 96
irritant contact dermatitis, 86
lupus erythematosus
cutaneous, 50, 53, 241
systemic, 57
nummular eczema, 91
parthenium dermatitis, 72
pemphigus vulgaris, 36–38
polymorphous light reaction, 113–114
psoriasis, 172, 173b
children, 176
erythroderma, 112
scleroderma
localized, 59–60
systemic, 63, 65–66
toxic epidermal necrolysis, 107
urticaria, 118
immunotherapy, alopecia areata, 228–229
impetigo, 29–31
incontinentia pigmenti, hypomelanosis of
Ito vs, 212
incontinentia pigmenti achromians,
211–212
India
allergic contact dermatitis, 69–71
urticaria as malaria presentation, 118
Indian (Ayurvedic) medicine, 351
acne, 358
indigo (naturalis), psoriasis, 369–371
indomethicin, erythema nodosum, 109
infants
acne, 13–14
acropustulosis, 32–33
atopic dermatitis, 77, 79
Lactobacillus GG, 366
newborn see neonates
seborrheic dermatitis, 177
infections, 29–31, 119–148
erythema nodosum caused by, 109t
pustular disorders caused by, 33t
in systemic lupus erythematosus causing
death, 57
inflammation, suppression see anti-
inflammatory drugs; anti-
inflammatory herbal medicines
infliximab (anti-TNF MAb)
dermatomyositis, 43
dissecting cellulitis, 238
erythema nodosum, 110
granuloma annulare, 96
psoriasis, 173
children, 176
sarcoidosis, 98
infrared treatment (of skin tightening), 340,
343
complications, 345
inguinal region (groin), hair removal, 334f
inguinal syndrome, lymphogranuloma
venereum, 136t
injection technique, dermal fillers, 324–325
injury (trauma), alopecia due to, 244–246
insect bites, 101–102
insulin resistance and acanthosis nigricans,
183, 185

383
Index

intense pulsed light (IPL) sources comedogenic acne, 317 KTP (potassium-titanylphosphate) laser,
axillary hair removal, 341 glabellar lines and botulinum toxin A dermatosis papulosa nigra,
hirsutism, 341 treatment, 313 262
lentigenes, 341 Mongolian spots, 200 kumkum, 73
solar lentigenes and ephelides, 209 photorejuvenation by intense pulsed
photorejuvenation, 341 light, 341
interferon psoriasis, 174 L
discoid lupus erythematosus, 241 toxic epidermal necrolysis, 107 lace wigs, 276
HPV lesions, 134t Japanese perm (Japanese hair straightening), Lactobacillus GG, infant atopic dermatitis,
squamous cell carcinoma, 281 276 366
interferon alpha 2a Jeju medicinal plants, acne, 359 Lamisil cream and Lamisil DermGel,
cutaneous lupus erythematosus, 51, 53 Jessner’s solution, 315–316 pityriasis versicolor, 138
cutaneous T-cell lymphoma, 275 acne vulgaris, 317 lanthonization see relaxers
squamous cell carcinoma, 282 scars, 320 large plaque parapsoriasis (LPP),
interferon alpha 2b melasma, 318–319 163–164
CD4+ T lymphocytopenia, 112 periorbital wrinkles, 320 treatment, 164, 164b
follicular mucinosis associated with Juvederm Ultra and Ultra Plus, 322, 323t laser treatment, 332–347
cutaneous T-cell lymphoma, 233 juvenile dermatomyositis, 39–44 acne keloidalis nuchae, 250–251
interferon gamma treatment, 42–43 acne vulgaris, 333t, 340t
granuloma annulare, 95 complications, 343–345, 347
keloids, 269 contraindications, 332
interleukin-1 receptor antagonist, cold K dermatofibroma, 261
urticaria, 118 Kaposi’s varicelliform eruption (eczema dermatosis papulosa nigra, 262,
interleukin-2/diphtheria toxin conjugate herpeticum), 79–80, 80f 337
(denileukin difitox), cutaneous keloid (keloid scars), 267–269, 285, 328f dissecting cellulitis, 238
T-cell lymphoma, 275 acne and risk of, 3 dyschromia, 333t, 337–338, 340t,
intertriginous areas hair transplantation contraindicated, 341–342
candidiasis, 119–120 327 post-inflammatory hyperpigmentation
psoriasis, children, 176 surgery and risk of, 285 following, 344
intravenous immunoglobulin see keloid folliculitis (acne keloidalis), epidermal nevus, 264
immunoglobulin, intravenous 249–251, 327, 328f folliculitis decalvans, 253
iontophoresis, vitamin C, with melasma, keratin, liquid (Brazilian keratin treatment), granuloma annulare, 94–95
198 275 hair reduction/removal, 332–337, 333t,
irritant contact dermatitis, 71, 84–87, 89 keratinocytes, Mahonia aquifolium extract 340–341, 340t
isoniazid, lichen nitidus, 153 effects, 370 HPV, 134t
isotretinoin (13-cis-retinoic acid; keratinous cysts, 266 hyperpigmentation, 312, 338
Roaccutane) keratoacanthoma, 279 actinic lentigo, 208–209
acanthosis nigricans, 184 keratosis, seborrheic see seborrheic keratosis Futcher’s lines, 203
acne vulgaris, 4–5, 10 kerion, 143–144 gingival, 194
dissecting cellulitis, 237–238 ketoconazole hydroquinone-induced (=exogenous
granuloma annulare, 95 confluent and reticulated papillomatosis, ochronosis), 193
hidradenitis suppurativa, 20 188 melasma see melasma
lichen planus, 156 dandruff, 272, 274 minocycline-induced, 189
lupus erythematosus (cutaneous), 50, 241 seborrheic dermatitis Mongolian spots, 200
pseudofolliculitis barbae, 255 face, 178 postinflammatory, 206, 337, 342
sarcoidosis, 98 scalp, 179–180, 272 indications, 332
squamous cell carcinoma, 282 tinea capitis, children, 144 keloids, 269
Israel, allergic contact dermatitis, 71 tinea corporis, 145 laxity of skin, 333t, 340, 340t
Ito’s hypermelanosis, 211–212 tinea (pityriasis) versicolor, 138–139 lentigo maligna, 279
itraconazole kiddie perm, 276 Ota’s nevus, 201–202
atopic dermatitis, 79 kidney disease, lupus, 54–55 pseudofolliculitis barbae, 255–256,
candidal onychomycosis, 148 Klebsiella granulomatis infection (granuloma 314, 335–336, 335f, 340–341,
lichen nitidus or planus, 153 inguinale), 126–128 340t
tinea capitis, children, 143–144 Kocher’s forceps removal of skin tags, rosacea, 17–18
tinea corporis, 146 260 scars see scars
tinea unguium, 147 kojic acid, 304 special management and counselling
tinea versicolor, 138 melasma, 205–206, 208, 285 considerations, 346t, 347
Korea vitiligo, 220–221
acne latex glove allergy, 70f
J citrus oil treatment, 360 laxity, skin, device-based treatment, 311,
Japan scars, 343 340, 343
acne, homeopathy, 359 atopic dermatitis, 77 efficacy and results, 340t
atopic dermatitis, 77–78 glabellar lines and botulinum toxin A leflunomide, dermatomyositis,
homeopathy, 366 treatment, 314 43

384

lentigines
device-based treatment in Asian persons,
341
solar, 207–209, 277–278, 285
lentigo maligna (lentiginous melanoma),
278–279
acral see acral melanoma
treatment, 279
lentigo maligna melanoma, 279
leukemia, acute, oral candidiasis prevention
in chemotherapy-treated patients,
120
leukocyte function (in psoriasis), Chinese
herbal medicine effects, 369
leukocytoclastic vasculitis, cutaneous, 50, 53
leukotrichia, vitiligo with, 217–218, 218f
leukotriene receptor antagonist, urticaria,
117
levamisole, nodulocystic acne, 9
levocetirazine, urticaria, 117
levofloxacin, C. trachomatis cervicitis, 126
lichen amyloidosis, 149–151
lichen nitidus, 152–154
lichen nitidus actinicus, 153–154
lichen planus, 153–158
lichen planus pigmentosus, 157
lichen sclerosus, 158–161
pediatric, 157–158, 160–161
lichen simplex chronicus, 87–89
lichen striatus, 161–162
licorice extract, 304
light eruptions, polymophous, 113–115
light sources, 332–347
complications, 343–345
indications, 332
acne, 338
pigmentation disorders, 337–338
skin laxity, 340, 340t
lightening creams/cosmeceuticals, 10, 277,
285
new products, 278
perioral dermatitis and, 23
linear morphea, 58
treatment, 60–61
lipid mixtures
atopic dermatitis, 76–77, 85
irritant and allergic contact dermatitis,
85
liquiritin, 285
lithium gluconate, seborrheic dermatitis,
178
livedoid vasculopathy, 44–47
liver transplant patients,
immunosuppressed, oral
candidiasis prophylaxis, 119–120
local anesthesia, hair transplantation,
327–328
locks (dreadlocks), 275
Lofgren’s syndrome, erythema nodosum,
110
losartan, Raynaud’s phenomenon in
scleroderma, 64
low-intensity electromagnetic pulses,
androgenic alopecia, 363
Index
lung disease, systemic lupus erythematosus, melanoma in situ, 278
54–55 melanonychia (benign), 185–187
lupus erythematosus melanosis, transient neonatal pustular, 209
chronic cutaneous, 47–52, 239–242 melasma, 195–199, 205–206, 208, 318–319
see also discoid lupus erythematosus chemical peels, 197, 208, 318–319
hypertrophic see hypertrophic lupus cosmetic products, 277, 282, 285
erythematosus laser treatment, 199, 206, 311, 337–338
subacute cutaneous, 52–53 fractional photothermolysis,
systemic, 53–58 337–338, 341
lupus-like syndrome, drug-induced, 56 postinflammatory hyperpigmentation
lupus miliaris disseminatus faciei (caseating following, 344
granulomatous variant of rosacea), men, androgenetic alopecia, 311–312, 327f
15, 17 mepacrine, follicular mucinosis, 233
lupus panniculitis, 48 mequinol (4-hydroxyanisole), 304
lupus profundus panniculitis, 48 solar lentigenes, 208, 304
lupus timidus, 48 mercurial pigmentation and exogenous
lymecycline, acne vulgaris, 8–9 ochronosis, 193
lymph node management, melanoma, 278 meropenem, cellulitis and erysipelas, 122
lymphogranuloma venereum, 135–137 metastatic melanoma, 278
lymphoma, cutaneous T-cell see T-cell metformin, acanthosis nigricans, 184
lymphoma methicillin-resistant S. aureus (MRSA), 31,
131
community-acquired (CR-MRSA), 30–31
M furuncle-like lesions and abscesses, 132
macular amyloidosis, 150 methimazole, 278
Mahonia aquifolium extract (and Relieva methotrexate
cream) bullous pemphigoid, 28
atopic dermatitis, 367 dermatomyositis, 41
psoriasis, 370 lupus erythematosus
malar rash, systemic lupus erythematosus, 54f cutaneous, 50, 241
malaria presenting as urticaria, 118 systemic, 57
Malassezia mycosis fungoides, 275
pityriasis versicolor and, 137–138 parthenium dermatitis, 72
seborrheic dermatitis and, 177 psoriasis, 172
males, androgenetic alopecia, 327, 327f children, 176
malignant atrophic papulosis, 46 sarcoidosis, 98–99
malignant tumors see cancer scleroderma
mandelic acid–salicylic acid peel, acne localized, 60
vulgaris, 317 systemic, 63, 65
Marcel curling iron, 276 4-methoxyphenol, vitiligo, 221
massage therapy, atopic dermatitis, 367 methoxypsoralen/methoxysalen + UVA see
mast cells photochemotherapy
urticaria and, 115–116 methylprednisolone
measles, 129t alopecia areata, 229
mechanical alopecia, 244–246 pemphigus vulgaris, 36
mechanical device, skin tag removal, 260 metronidazole
mechlorethamine, mycosis fungoides lichen planus, 156
hypopigmented, 213–214 perioral dermatitis, 22
parapsoriasis-associated, 164–165 children, 22–23
medicated shampoos, 271 rosacea, 16–17
meditation, psoriasis, 373 Mexico, erythema dyschromicum perstans,
melanocytic nevus, congenital, 264–265 191
melanoma (malignant), 277–279, 310f miconazole, intertriginous/cutaneous
acral see acral melanoma candidiasis, 120
benign melanonychia leading to, 185 micrographic surgery see Mohs micrographic
diagnosis, 277 surgery
difficulties, 282, 284t Microsporum canis, tinea capitis, 144
dysplastic nevi and progression to, 266 mineral supplements, acne, 361
presentation commpared to other skin minocycline
cancers, 282t acne keloidalis nuchae, 250
prognosis, 277 acne vulgaris, 4, 8–9
risk factors by race/ethnicity, 285t alopecia mucinosa, 233
subungual see subungual melanoma confluent and reticulated papillomatosis,
superficial spreading, 277 188
385
Index
diffuse scleroderma, 66–67
hyperpigmentation associated with, 189
minoxidil
alopecia areata, 229–230
traction alopecia, 243
Mohs micrographic surgery
basal cell carcinoma, 271–272
dermatofibrosarcoma protuberans, 276
melanoma, 278
squamous cell carcinoma, 281
arising in osteomyelitis or chronic
wounds, 282
moisturizers see emollients and moisturizers
mole see nevus
mometasone furoate
dyshidrotic eczema, 82
irritant contact dermatitis, 85
Mongolian spots, 199–201
monoclonal antibodies
alopecia areata, 230–231
bullous pemphigoid, 28
dermatomyositis, 43
discoid lupus erythematosus, 51, 241
dissecting cellulitis, 238
erythema nodosum, 110
granuloma annulare, 96
pemphigus vulgaris, 37–38
psoriasis, 171, 173
children, 176
Sézary syndrome, 275
montelukast, urticaria, 117
morphea (localized scleroderma), 41,
58–61, 66
moxibustion, acne, 358–359
mucinosis, follicular, 232–234
mucosal involvement
lichen planus, 156–157
Stevens–Johnson syndrome and toxic
epidermal necrolysis, 107
multiple endocrine neoplasia type 2A (MEN
2A), lichen amyloidosis, 149
mupirocin
atopic dermatitis with associated S.
aureus colonization, 79
folliculitis, 130–131
impetigo, 30–31
muscles in botulinum toxin A treatment
targeted for paralysis, 309
unintended paralysis, 314
mycobacteria in footbath, furunculosis due
to, 132
Mycobacterium tuberculosis see tuberculosis
mycophenolate mofetil
bullous pemphigoid, 27
diffuse systemic sclerosis, 65
erythema nodosum, 110
lupus erythematosus
pemphigus vulgaris, 37
mycosis see fungal infections
mycosis fungoides, 212–215, 273
alopecia mucinosa predisposition to,
232
diagnosis, 273–274
diagnostic difficulties, 284t
386
hypopigmented, 212–215, 273, 283f
parapsoriasis-associated, 163
treatment, 164–165
pathogenesis, 273
presentation commpared to other skin
cancers, 282t
staging, 273
tinea versicolor vs, 282
myiasis, 132
Myobloc, 311
N Raynaud’s phenomenon in systemic
nails
dark dyspigmentation, 185–187
fungal infections see onychomycosis
see also entries under subungual
napkin candidiasis, 119
naproxen, erythema nodosum, 109
nasolabial folds, soft tissue augmentation,
321f, 324–325
Nd:YAG laser see neodymium:YAG laser
necrobiosis lipoidica and granuloma
annulare, 94
necrotizing cellulitis, 122
Neisseria gonorrhoeae and C. trachomatis
coinfection, 125
neoadjuvant therapy, dermatofibrosarcoma
protuberans, 276
neodymium:YAG (Nd:YAG) laser
acne scars, 342
dermatosis papulosa nigra, 262
dissecting cellulitis, 238
facial burns with inadequate cooling,
336f
folliculitis decalvans, 253
gingival hyperpigmentation, 194
hair removal, 340
lentigo maligna, 279
Mongolian spots, 200
pseudofolliculitis barbae renal disease,
pseudofolliculitis barbae, 256
tattoos, 342–343
neonates
acne, 14
pustular disorders, differential diagnosis,
33t
transient pustular melanosis, 209
neoplasms see cancer; tumors
nephritis, lupus, 54–55
nerve, squamous cell carcinoma invasion of
space around, 281
neurodermatitis (lichen simplex chronicus),
87–89
neurological (mainly central nervous
system) disorders
hypomelanosis of Ito, 211
syphilis, 139t–140t
systemic lupus erythematosus, 54–55
nevus (mole)
congenital melanocytic, 264–265
dysplastic/Clark’s/atypical/BK, 265
epidermal, 263–264
Ota’s, 201–202
nevus sebaceous, 263
newborns see neonates
NFκB inhibition in psoriasis by
phytochemicals, 372
niacinamide (nicotinamide), 278
bullous pemphigoid, 27
hyperpigmentation, 305
nickel allergy, 69, 70t, 71–72
child, 70f
nicotinamide see niacinamide
nifedipine
livedoid vasculopathy, 46
sclerosis, 63–64
Nigerian children, Mongolian spots,
199–201
nipple, hyperkeratosis in acanthosis
nigricans, 185
nitric oxide, inducible, systemic lupus
erythematosus and, 54
nodular basal cell carcinoma, 272
nodular neurodermatitis, 89
nodulocystic acne, 8–9, 13–14
complementary therapy, 358
non-steroidal anti-inflammatory drugs
(NSAIDs)
erythema nodosum, 109
pigmentation disorders caused by,
190t
systemic lupus erythematosus, 56
norgestimate + ethinyl estradiol, acne
vulgaris, 9–10
nuclear antigens, autoantibodies to see
antinuclear antibody
nuclear factor kappaB inhibition in psoriasis
by phytochemicals, 372
nucleic acid amplification tests (incl. PCR)
C. trachomatis, 125
types L1-L3 (lymphogranuloma
venereum), 136t
donovanosis (granuloma inguinale),
128t
nummular eczema, 90–91
nystatin, oral candidiasis, 119–120
O
obesity
acanthosis nigricans and, 184
psoriasis and, 173
ochronosis, exogenous, 192–193
ocular involvement
psoriasis, 174
rosacea, 15
Stevens–Johnson syndrome and toxic
epidermal necrolysis, 107
ofloxacin, C. trachomatis cervicitis, 126
Ofuji papuloerythroderma, 111–112
oils, hair, 275t
Oldenlandis mixture, acne, 358
onabotulinumtoxin A (Botox), 311–312,
312t
101 Hair Regenerating Alcohol, 363
onion juice, alopecia areata, 363–364
 Index

onychomycosis (fungal infections of scarlet fever (S. pyogenes), 130 polymorphous light reaction
nailfold/plate) scleroderma (localized), 60 differentiated from other types,
candidal, 119 syphilis, 141 114–115
dermatophyte (tinea unguium), penicillin G see benzylpenicillin photodynamic therapy (incl. use of 5-ALA)
146–148 pentoxifylline follicular mucinosis, 233
oral cavity granuloma annulare, 96 granuloma annulare, 94
candidiasis, 119–120 livedoid vasculopathy, 45 perioral dermatitis, 23
lichen planus, 155 sarcoidosis, 98 photoepilation, 341
see also perioral region perifolliculitis capitis (dissecting cellulitis), photopheresis see extracorporeal
oral contraceptives (birth control pills) see 236–239, 327, 328f photochemotherapy
contraceptive pills perineural invasion, squamous cell photopneumatic therapy, acne, 321, 338,
orbit carcinoma, 281 339f, 342
botulinum toxin A unintended paralysis perioral region photoprotectants see sunscreen/sunblock
of muscle around, 314 dermatitis, 21–23 photorejuvenation by intense pulsed light,
chemical peels for wrinkles around, 320 vitiligo, 217f 341
Orientals, bleaching agents for periorbital muscles, botulinum toxin A photosensitivity rash, systemic lupus
hyperpigmentation, 198, 208 unintended paralysis, 314 erythematosus, 55f
OSMR mutation and familial primary periorbital wrinkles, chemical peels, 320 photosensitivity testing in discoid lupus
localized cutaneous amyloidosis Perlane, 322, 323t erythematosus, 240
(familial PLCA), 151 permanents (perms), 273–275, 275t phototherapy
osteomyelitis, squamous cell carcinoma Japanese, 276 blue-light, acne, 342
arising in, 282 phenytoin UVA
Ota’s nevus, 201–202 cutaneous lupus erythematosus, 50 atopic dermatitis, 78
oxygen, hyperbaric, livedoid vasculopathy, pigmentation disorders caused by, 190, dyshidrotic eczema, 82
46 190t granuloma annulare, 95
phimosis, lichen sclerosus et atrophicus localized scleroderma, 59–60
causing, 157–158 mycosis fungoides, 214
P phosphodiesterase V inhibitor, Raynaud’s pityriasis rosea, 167
panniculitis, lupus, 48 phenomenon in systemic sclerosis, small plaque parapsoriasis, 164
Panton–Valentine leukocidin gene, 132 64 systemic scleroderma, 66
pantothenic acid, acne, 361 photochemotherapy (PUVA; methoxysalen/ UVB
papillomatosis, confluent and reticulated psoralen + UVA) allergic contact dermatitis, 72
(Gougerot–Carteaud syndrome), alopecia areata, 230 atopic dermatitis, 78
187–188 atopic dermatitis, 78 irritant contact dermatitis, 85–86
papular amyloidosis, 150 CD4+ T lymphocytopenia, 112 lichen nitidus, 153
papular atopic dermatitis, 75f dyshidrotic eczema, 82 lichen planus, 155–156
papuloerythroderma, Ofuji, 111–112 extracorporeal see extracorporeal mycosis fungoides, 274
papulopustular rosacea, 15 photochemotherapy mycosis fungoides, hypopigmented,
papulosis, malignant atrophic, 46 follicular mucinosis, 233 214
papulosquamous disorders, 163–180 granuloma annulare, 94 polymorphous light reaction,
paraphenylenediamine dye irritant contact dermatitis, 85–86 114
allergic contact dermatitis caused by, 275 lichen amyloidosis, 150 psoriasis, 171, 173–174, 373
products containing, 285t lichen nitidus, 153 psoriasis, children, 176
parapsoriasis, 163–165 lichen planus, 155–156 urticaria, 117
paronychia, candidal, 119 livedoid vasculopathy, 46 vitiligo, 218, 220
paroxetine, trichotillomania, 247 mycosis fungoides, 213, 274 vitiligo, with calcipotriene, 220
parthenium dermatitis, 72 Ofuji papuloerythroderma, with retinoid, photothermolysis
parvovirus B19, 129t 111 dermatosis papulosa nigra, 263
patch testing, allergic contact dermatitis, 69 pityriasis alba, 217 fractional see fractional photothermolysis
PDGFβ/COL1A fusion gene and polymorphous light reaction, selective, 332
dermatofibrosarcoma protuberans, 114 phymatous rosacea, 15
276 psoriasis, 171 phytomedicines see herbal medicine
pediatrics see children and meditation-based stress pigmentary disorders see hyperpigmentation;
pemphigoid, bullous, 26–28, 112 reduction, 373 hypopigmentation
pemphigus foliaceus, 33–36 sarcoidosis (hypopigmented), 215 pigmented basal cell carcinoma, 271, 272f,
pemphigus vulgaris, 35–38 scleroderma 282, 283f
PEMPULS trial, 36 localized (morphea), 59, 61, 66 pigmented Bowen’s disease, 280f, 285f
D-penicillamine systemic, 66 pilar cysts, 266
localized scleroderma, 61 T-cell lymphoma (cutaneous), 112 pimecrolismus
systemic sclerosis, 63 vitiligo, 220–221 acne keloidalis nuchae, 251
diffuse, 66 photodermatoses atopic dermatitis, 77
penicillin(s) mechanisms of phototherapy follicular mucinosis, 233
cellulitis, 121 and photochemotherapy, irritant contact dermatitis, 85
erysipelas, 121–122 114 lichen striatus, 162

387
Index

lupus erythematosus (chronic prednisolone melasma, 199

cutaneous), 49 bullous pemphigoid, 26 pseudofolliculitis barbae, 256
perioral dermatitis, 23 diffuse systemic sclerosis, 65–66 psoriasis, 168, 373
pityriasis alba, 216–217 lichen planus, 156 vitiligo, 221
rosacea, 17 pemphigus vulgaris, 37 psychosocial stressors (in etiology or
seborrheic dermatitis, 178–179 tinea capitis, 144 exacerbation), 355
pimozide, trichotillomania, 247 vulval apocrine acne, 20 trichotillomania, 246–247
pityriasis alba, 69, 216–217 prednisone, 238 ptosis complicating botulinum toxin A use,
variants, 216 acne vulgaris, 4–5 314
pityriasis rosea, 166–167 alopecia areata, 229 pulmonary disease, systemic lupus
pityriasis versicolor (tinea versicolor), diffuse systemic sclerosis, 65 erythematosus, 54–55
137–139 pemphigus vulgaris, 36 pulsed carbon dioxide laser, melasma,
mycosis fungoides vs, 282 systemic lupus erythematosus, 56 199
plaits, 275 pregnancy pulsed diode laser
plant medicines see herbal medicine C. trachomatis in, 125–126 hair removal, 341
plaque morphea, 58 cervicitis, 126 pseudofolliculitis barbae, 256
treatment, 60 dermatomyositis treatment in, 42–43 pulsed dye laser, 269
plaque parapsoriasis, 163–165 mask of (melasma), 195 dermatofibroma, 261
plaque psoriasis, 168–176 syphilis, 141 granuloma annulare, 94–95
children, 175–176 pressing (hair), 276 rosacea, 17
complementary therapies, 370–371 Prevelle Silk, 322, 323t scars, 342
plasmapheresis, toxic epidermal necrolysis, proanthocyanidin-rich grape juice extract, pulsed Nd:YAG laser
107 melasma, 198–199 dissecting cellulitis, 238
platelet function (in psoriasis), Chinese probenecid (with cephalosporin), cellulitis hair removal, 340
herbal medicine effects, 369 and erysipelas, 121–122 pulsed Q-switched laser, Ota’s nevus, 202
platysma, botulinum toxin A over-paralysis, progestogen + oestrogen see contraceptive punch grafting (hair), 326
314 pills punch incision, epidermoid cyst, 266
podophyllin resin, HPV, 134t Propionobacterium acnes, Indian herb effects, pustular disorders, 25–38
podophyllotoxin, HPV, 134t 358 neonatal, differential diagnosis, 33t
polycystic ovary syndrome and hidradenitis propylene glycol, tinea versicolor, 139 pustular melanosis, transient neonatal, 209
suppurativa, 21 Pro-Q aerosol foam (dimethicone and PUVA see photochemotherapy
polyherbal formulations glycerin), 71, 85 pyoderma faciale, 15
acne, 358 prostacyclin analog
alopecia, 362 livedoid vasculopathy, 46
poly-L-lactic acid, 323–325 Raynaud’s phenomenon in systemic Q
polymerase chain reaction see nucleic acid sclerosis, 63–65 Q-switched laser
amplification tests protein, dietary, acne and, 360–361 actinic lentigo, 208
polymorphous light eruptions, 113–115 prurigo nodularis and chronic prurigo, 89 dyschromias (freckles and lentigenes),
pomade acne, 12–13, 273f, 274 pruritic psoriasis, capsaicin, 369–370 341
pompholyx, 81–83, 86–87 pruritus, drug therapy see antipruritics Futcher’s lines, 203
porcine collagen, 323 pseudofolliculitis barbae (shaving/razor lentigo maligna, 279
postinflammatory hyperpigmentation bumps), 254–256 melasma, 199, 206
(PIH), 5–6, 5f, 10–11, 204–207, device-based treatments, 255–256, minocycline-induced hyperpigmentation,
319 335–336, 335f, 340–341 189–190
acne vulgaris, 310f efficacy and results, 340t Mongolian spots, 200
chemical peels complicated by, 346 psoralen + UVA see photochemotherapy Ota’s nevus, 201–202
chemical peels for, 206, 319 psorberine, atopic dermatitis, 367 postinflammatory hyperpigmentation,
cosmetic products for, 285, 307f psoriasis, 168–176, 368–374 206
insect bites, 102 children, 174–176 tattoos, 342
laser treatment complicated by, 309, 316, complementary therapies, 368–374 vitiligo, 221
343–344 erythroderma, 112 quinacrine, cutaneous lupus erythematosus,
laser treatment of, 206, 337, 342 plaque see plaque psoriasis 52, 240
psoriasis, 168, 184f postinflammatory hyperpigmentation, quinolone antibiotics, dissecting cellulitis,
postmenopausal women with diabetes 168, 184f 237
mellitus, lichen simplex chronicus scalp, 274
in, 88–89 psychodermatology (psychocutaneous
potassium iodide medicine), 355–356 R
erythema multiforme, 106 classification of disorders, 356t race/ethnicity
erythema nodosum, 109 psychological therapies allergy and, 73
potassium-titanylphosphate laser, atopic dermatitis, 367–368 patch test for, 69, 70t
dermatosis papulosa nigra, psoriasis, 373 cosmetic procedures and, 309, 310f
262 psychosocial impact hair transplantation and, 309
prazosin, Raynaud’s phenomenon in alopecia areata, 231 irritant reactivity and, 86
systemic sclerosis, 65 dissecting cellulitis, 238–239 sarcoidosis and, 99–100

388

skin tumors (incl. cancer) and
clinical presentation, 282t
epidemiology, 259t
risk factors, 285t
systemic lupus erythematosus clinical
features and, 55–56
systemic sclerosis clinical features, 62–63
radiation therapy (radiotherapy)
basal cell carcinoma, 272
dermatofibrosarcoma protuberans,
adjuvant, 276
dissecting cellulitis, 238
keloids, 267–268
melanoma in situ, 278
mycosis fungoides, 274
squamous cell carcinoma, 280
adjuvant, 281
Radiesse, 322–323, 323t
radiofrequency treatment (of skin laxity),
340, 343
complications, 345
Raynaud’s phenomenon in systemic
sclerosis, 63
treatment, 63–65
razor bumps see pseudofolliculitis barbae
5α-reductase inhibition by herbs in
androgenic alopecia, 361–363
Refrigerant 12, nodular neurodermatitis, 89
relaxers (for lanthonization), 271, 275t
children, 282t
home use, 271
professional use, 271
Relieva cream see Mahonia aquifolium extract
renal disease, lupus, 54–55
restriction fragment length polymorphism
(RFLP) lymphogranuloma
venereum, 136t
Restylane, 322, 323t
nasolabial folds, 324
retapamulin, impetigo, 30
retinoic acid see isotretinoin; tretinoin
retinoids (vitamin A derivatives), 303
acanthosis nigricans, 184
acne vulgaris, 4–6, 10, 285
infants, 13–14
bullous pemphigoid, 112
confluent and reticulated papillomatosis,
188
dissecting cellulitis, 237–238
epidermal nevus, 264
follicular mucinosis associated with
cutaneous T-cell lymphoma,
233
granuloma annulare, 95
hidradenitis suppurativa, 20
lichen amyloidosis, 150–151
lichen planus, 156
lupus erythematosus (cutaneous)
chronic, 49–50, 241
subacute, 53
melasma, 196–198, 205, 282–285
Ofuji papuloerythroderma, with PUVA,
111
pseudofolliculitis barbae, 255
Index
psoriasis, 169, 171 scalp
children, 176 basing the, 275
with Chinese herbal medicine, 369 biopsy see biopsy
sarcoidosis, 98 discoid lupus erythematosus, 51
scleroderma (localized), 59, 61 dissecting cellulitis, 236–239, 327, 328f
solar lentigenes, 208 hair loss see alopecia
squamous cell carcinoma, 282 psoriasis, 274
T-cell lymphoma (cutaneous), 274–275 seborrheic dermatitis, 179–180
Sézary syndrome, 112 shampoos, 180, 271t, 272–274
UV-induced dyschromia, 205 shaving in folliculitis decalvans, 253
retinol 0.15[percent], melasma, 205, tinea see tinea
282–285 scar(s), 342–343
rhinophyma, 15–16, 18 acne, 5–6, 5f, 10, 319–320, 342–343
rhytides see wrinkles in hair transplantation, postoperative,
rifamp(ic)in, folliculitis decalvans, 252–253 330
rimabobotulinumtoxin B (Myobloc), 311 hypertrophic, 267–269, 285
rituximab (anti-CD20) keloid see keloids
bullous pemphigoid, 28 laser treatment, 317, 333t, 339–340,
dermatomyositis, 43 340t, 342–343
pemphigus vulgaris, 37–38 fractional photothermolysis, 339, 343
Roaccutane see isotretinoin scarlet fever, 129t, 130
roller set, 276 scarring alopecia, alopecia mucinosa
rosacea, 14–18 associated with, 234
roseola infantum, 129t scleroderma, 58–67
rosiglitazone, acanthosis nigricans, 184 localized (morphea), 41, 58–61, 66
roxithromycin, erysipelas, 122 systemic (=systemic sclerosis), 40
rubella, 129t sclerosis
rubeola, 129t cutaneous, 65–67
ruby laser systemic, 40
actinic lentigo, 208 Sculptra/Sculptra Aesthetic, 323–324, 323t
epidermal nevus, 264 sebaceous nevus (nevus sebaceus), 263
melasma, 206 seborrheic dermatitis, 177–180
minocycline-induced hyperpigmentation, seborrheic keratosis
190 dermatosis papulosa nigra as variant of,
Mongolian spots, 200 261–263
Ota’s nevus, 202 pigmented basal cell carcinoma vs, 282
postinflammatory hyperpigmentation, shampoos, 180, 271t, 272–274
206 secondary intension healing, acne keloidalis
tattoos, 343 nuchae, 250
vitiligo, 221 segmental hyalinizing vasculitis (livedoid
vasculopathy), 44–47
selective serotonin reuptake inhibitor,
S trichotillomania, 247t
St John’s wort cream, atopic dermatitis, 367 selenium and acne, 361
salbutamol cream, discoid and subacute selenium sulfide
lupus erythematosus, 241 confluent and reticulated papillomatosis,
salicylic acid, 315 188
acne vulgaris, 7, 317–318 dandruff, 274
with mandelic acid, 317 pityriasis (tinea) versicolor, 138
in polyethylene glycol, 317 seborrheic dermatitis of scalp, 179–180
postinflammatory hyperpigmentation, tinea capitis, 144
206, 319 senile (solar) lentigo, 207–209, 277–278,
psoriasis, 170 285
seborrheic dermatitis of scalp, 179 sentinel node biopsy, melanoma, 278
see also aspirin; sulfur and salicylic acid Serenoa repens extract, androgenic alopecia,
shampoo 363
sand flea and tungiasis, 132 serological tests
sarcoidosis, 97–100, 215 K. granulomatis (granuloma inguinale),
extracutaneous and systemic, 100 128t
hypopigmented, 215 lymphogranuloma venereum, 136t
see also Lofgren’s syndrome T. pallidum, 142t
satin pillow cases, 273f, 274 sexually-transmitted infections (STIs; STDs),
scabies, infantile acropustulosis and history 123–128, 135–137, 139–142
of, 32 Sézary syndrome, 112, 273, 275–276
389
Index
shampoos, 289–292
children, 282t
medicated products, 271
seborrheic dermatitis of scalp, 180, 271t,
272–274
shaving
folliculitis decalvans improvement, 253
in pseudofolliculitis barbae,
discontinuation/avoidance,
255–256
shaving bumps see pseudofolliculitis barbae
shoewear (footwear) dermatitis, India,
69–71
sildenafil, Raynaud’s phenomenon in
systemic sclerosis, 64
silicone gel sheeting, keloids, 269
sindhoor, 73
Singapore
allergic contact dermatitis, 71
atopic dermatitis, 74–75
psoriatic eye complications, 174
Sipple syndrome, lichen amyloidosis, 149
sixth disease (roseola infantum), 129t
Sjögren’s syndrome and subacute cutaneous
lupus erythematosus, 52
skin laxity, device-based treatment, 311, 340,
343
skin tags, 260
small plaque parapsoriasis (SPP), 163, 164b
treatment, 164
smear
donovanosis (granuloma inguinale),
128t
Haemophilus ducreyi, 123–124
smoking
cutaneous lupus erythematosus
treatment and, 49, 51–52
hyperpigmentation reversal with
discontinuation, 195
sodium fusidate see fusidic acid and sodium
fusidate
sodium hydroxide, relaxers containing,
275t–276t
sodium lauryl sulfate irritant contact
dermatitis, 71
sodium sulfacetamide, pityriasis versicolor,
138
sodium sulfacetamide and sulfur cream
perioral dermatitis, with hydrocortisone,
22
rosacea, 17
soft tissue augmentation with dermal fillers
see fillers
solar lentigines, 207–209, 277–278, 285
solar urticaria, 114
Sophora flavenscens extract, alopecia,
362–363
soy, 305
spironolactone, acne vulgaris, 4, 9
squamopapular disorders, 163–180
squamous cell carcinoma, 279–282
diagnostic difficulties, 282, 284t
discoid lupus erythematosus
predisposition to, 51
390
hidradenitis suppurativa predisposition
to, 21
lichen sclerosus predisposition to, 160
presentation commpared to other skin
cancers, 282t
risk factors by race/ethnicity, 285t
squamous cell carcinoma in situ see Bowen’s
disease
staging, mycosis fungoides, 273
Staphylococcus aureus
atopic dermatitis and skin and nasal
colonization by, 78–79
decolonization of nasal carriage, 132t
furuncle-like lesions and abscesses,
132
methicillin-resistant see methicillin-
resistant S. aureus
statins, Raynaud’s phenomenon in
scleroderma, 64
stem cell transplantation, hematopoietic,
cutaneous T-cell lymphoma, 275
steroids (corticosteroids; glucocorticoids)
acne keloidalis nuchae, 250
intralesional, 250–251
acne vulgaris induced by, 13
acne vulgaris treatment, 4–5, 8
alopecia areata
intralesional, 228
systemic, 229
topical, 228–231, 363
atopic dermatitis, 75–77, 175
with associated S. aureus
colonization, 79
rebound phenomenon, 78
bedbug bites, 101–102
bullous pemphigoid, 26
central centrifugal cicatricial alopecia,
235
dermatomyositis, 44–47
dissecting cellulitis, 237
dyshidrotic eczema, 82
folliculitis decalvans, 253
granuloma annulare
associated with autoimmune
thyroiditis, 93
associated with necrobiosis lipoidica,
94
hair transplant-related scars, 331
hidradenitis suppurativa, 20
infantile acropustulosis, 32
irritant contact dermatitis, 84–86
keloids
intralesional, 268–269
postoperative use, 267–268
recurrent, 267–268
lichen amyloidosis, 150
lichen planus, 155
lichen sclerosus, 159–160
children, 160
lichen simplex chronicus, 88
lupus erythematosus
cutaneous, 48–49, 240
melasma (in triple combination cream),
196, 282
mycosis fungoides, 214, 274
associated with parapsoriasis,
164–165
nickel-induced contact allergy, 71–72
nummular exzema, 90
pemphigus foliaceus, 33–34, 36
pemphigus vulgaris, 36–37
perioral dermatitis induced by, 21, 23
perioral dermatitis treatment with, 22
pityriasis alba, 217
pityriasis rosea, 166
postinflammatory hyperpigmentation,
206
psoriasis, 169–170
children, 175
scalp, 274
rosacea induced by, 17
sarcoidosis, 98
scleroderma
localized, 60
systemic, 65–66
seborrheic dermatitis
face, 178
scalp, 179, 273–274
Stevens–Johnson syndrome and toxic
epidermal necrolysis, 107
systemic lupus erythematosus, 56
tinea capitis, 144
vitiligo, 218–219
Stevens–Johnson syndrome (SJS), 104
commonly encountered pitfalls, 107
management, 106–107
medications causing, 105t
special management and counseling
considerations, 107
Streptococcus pyogenes and scarlet fever, 129t,
130
streptomycin, donovanosis, 128
stress reduction, psoriasis, 373
subcutaneous immunoglobulin,
dermatomyositis, 42
suberoylanilide hydroxamic acid (SAHA;
vorinostat), cutaneous T-cell
lymphoma, 275
subungual melanoma, 277–278, 277f
benign melanonychia vs, 186
hematoma vs, 282
subungual onychomycosis, 146
sulfamethoxazole/trimethoprim see
trimethoprim/sulfamethoxazole
sulfasalazine
atrophie blanche, 46
discoid lupus erythematosus, 51
lichen planus, 156
sulfur, seborrheic dermatitis, 179
sulfur and salicylic acid shampoo, tinea
versicolor, 138
sulfur and sodium sulfacetamide see sodium
sulfacetamide and sulfur cream
summertime actinic lichenoid eruption,
153–154
sunlight
immunosuppression due to, sunscreen
protection, 114

polymorphous light reaction as recurrent
and delayed reaction to, 113
see also ultraviolet and entries under
actinic; solar
sunscreen/sunblock (photoprotectants), 306
broad-spectrum, sunlight-induced
immunosuppression and
protective effects of, 114
lupus erythematosus, cutaneous
chronic, 48
subacute, 52
melasma, 282
polymorphous light reaction, 113–114
postinflammatory hyperpigmentation,
206
rosacea, 10, 17–18
surgery
acne keloidalis nuchae, 250–251
acne vulgaris, 5
cancer see Mohs micrographic surgery
cancer
basal cell carcinoma, 271–272
dermatofibrosarcoma protuberans,
276
melanoma, 278
melanoma in situ, 278
squamous cell carcinoma, 280–281
squamous cell carcinoma in situ
(Bowen’s disease), 281
therapy after or before see adjuvant
therapy; neoadjuvant therapy
congenital melanocytic nevus, 265
dermatosis papulosa nigra, 263
dysplastic nevus, 266
epidermoid cyst, 266
granuloma annulare, 95
hidradenitis suppurativa, 19–21
HPV lesions, 134t
for keloid, 267
keloid risk with, 285
Ota’s nevus, 202
pseudofolliculitis barbae, 255
skin tags, 260
traction alopecia, 243
verrucous epidermal nevus, 263–264
vitiligo, 219, 221
see also cryosurgery; laser treatment
syphilis, 139–142
systemic diseases
erythema nodosum in, 109t
exfoliative dermatitis, 111t
granuloma annulare in, 97
systemic lupus erythematosus, 53–58
systemic sclerosis, 40
T see also specific derivatives
T-cell lymphoma, cutaneous, 112, 212–215,
273–275
follicular mucinosis associated with,
233
hypopigmented, 212–215, 273, 283f
large plaque parapsoriasis progression
to, 163–164
presentation commpared to other skin
cancers, 282t
see also mycosis fungoides; Sézary
syndrome
T lymphocytopenia, CD4+, 112
tacrolismus (FK506)
atopic dermatitis, 77
bullous pemphigoid, 27
dermatomyositis, 241
dyshidrotic eczema, 82
granuloma annulare, 95
irritant contact dermatitis, 85
lichen nitidus, 152
lichen sclerosus, 159
anogenital, 161
lichen simplex chronicus, 89
lichen striatus, 162
localized scleroderma, 60
lupus erythematosus (chronic
cutaneous), 49, 241
mycosis fungoides (associated with
parapsoriasis), 164
nickel-induced contact allergy, 72
pemphigus foliaceus, 34
pityriasis alba, 216
psoriasis, 170
children, 176
sarcoidosis, 99
seborrheic dermatitis, 178
vitiligo, 219
tags, skin, 260
tar see coal tar
tattoos, laser treatment, 342–343
tazarotene
acne vulgaris, 6, 10, 285
confluent and reticulated papillomatosis,
188
postinflammatory hyperpigmentation,
285
psoriasis, 169
tea lotion in acne vulgaris, 8, 359
see also green tea
tea tree oil, acne, 359
teenagers see adolescents
terbinafine
tinea capitis, children, 143
tinea corporis, 145–146
tinea unguium, 146–147
tetracycline and derivatives
acne keloidalis nuchae, 250
acne vulgaris, 4, 8–9, 16, 359
bullous pemphigoid, 27
diffuse scleroderma, 66–67
donovanosis, 128
folliculitis, 131
perioral dermatitis, 22
texturizers, 294
home use, 284t
Thailand, allergic contact dermatitis, 71
thalidomide, 113–114
cutaneous lupus erythematosus, 50–51
erythema multiforme, 106
sarcoidosis, 98
Index
thermal reconditioning (Japanese perm),
276
Three Yellows Powder, acne, 358t
thrombomodulin upregulation in livedoid
vasculopathy treatment, 46
Thujae occidentalis semen, androgenic
alopecia, 363
thumb, subungual melanoma, 277
thyroiditis, autoimmune, granuloma
annulare and, 93
tigazon, localized scleroderma, 61
tinea (dermatophytosis)
body (tinea corporis) and crural region
(tinea cruris), 145–146
nummular eczema resembling, 90
nails (tinea unguium), 146–148
scalp (tinea capitis), 142–144
alopecia areata vs, 227–228
children, 142–144
traumatic alopecia vs, 245
tinea versicolor see pityriasis versicolor
tioconazole
tinea unguium (onychomycosis), 148
tinea versicolor, 138
tissue plasminogen activator, livedoid
vasculopathy, 45
TNF-alpha inhibitors see tumor necrosis
factor-alpha inhibitors
TNM staging, mycosis fungoides, 273
α-tocopherol see vitamin E
tocoretinate, localized scleroderma, 60
toe
subungual melanoma, 284f
tinea infection of nail, 147–148
see also digits
Toppik, 282
touch up, 276
toxic epidermal necrolysis (TEN), 104
commonly encountered pitfalls, 107
management, 106–107
medications causing, 105t
special management and counseling
considerations, 107
traction alopecia, 242–244, 327f
traditional Chinese medicine see Chinese
medicine
transepidermal water loss and irritant
reactivity, 86
transient neonatal pustular melanosis,
209
transplants and grafts
hair see hair
hematopoietic stem cell, cutaneous T-cell
lymphoma, 275
liver, oral candidiasis prophylaxis (in
immunosuppressed patients),
119–120
skin (incl. cultured cells)
dissecting cellulitis, 238
vitiligo, 220, 223
traumatic alopecia (hair loss; baldness),
244–246
Treponema pallidum and syphilis,
139–142
391
Index

tretinoin (all-trans-retinoic acid), 315 U localized scleroderma, 59–61

acanthosis nigricans, 184 ulcers (cutaneous) psoriasis, 169
acne vulgaris, 6 bullosis diabeticorum, foot, 25 children, 175
melasma, 196–198, 282, 285, 318 chancroidal, 123 vitiligo, 220
solar lentigenes, 208 in systemic sclerosis, 63–65 vitamin E (α-tocopherol)
UV-induced dyschromia, 205 ultraviolet A nickel-induced contact allergy, 72
triamcinolone alone see phototherapy with sunblock, in polymorphous light
acne keloidalis nuchae, 250 with psoralen see photochemotherapy reaction, 113–114
alopecia areata, 228 ultraviolet B phototherapy see phototherapy vitiligo, 217–221
discoid lupus erythematosus, 240 ultraviolet–coal tar (Goeckerman regimen), excimer laser, 220, 314–315
dissecting cellulitis, 237 pediatric psoriasis, 175 Voight’s lines, 203–204
folliculitis decalvans, 253 ultraviolet-induced conditions vorinostat, cutaneous T-cell lymphoma, 275
granuloma annulare associated with dyschromia, 205 vulva
necrobiosis lipoidica, 94 immunosuppression, 114 apocrine acne, 20
hair transplant-related scars, 331 lupus erythematosus, 52 lichen simplex chronicus, 88–89
keloids, 268–269 see also sunlight
lichen sclerosus, 159–160 undecylenoyl phenylalanine, 278
sarcoidosis, 98 unipolar radiofrequency, skin laxity, 340 W
trichloroacetic acid urethritis, chlamydial, 125–126 warfarin, livedoid vasculopathy with factor
acne scars, 319–320 urticaria, 115–118 V Leiden mutation, 45–46
HPV, 134t bedbug bites masquerading as, 101 warts
hyperpigmentation, 208 bullous pemphigoid lesions resembling, anogenital, 133–134
medium-depth peel, 316 28 plane/simple, 133
melasma, 319 solar, 114 water loss, transepidermal, irritant reactivity
periorbital wrinkles, 320 urushiol contact dermatitis, 89 and, 86
solar lentigenes, 208 wave caps, 275
superficial peel, 315 wave (crimping) iron, 275
trichophytic closure, 328–330 V weave (extensions), 276, 282
trichorrhexis, 274, 274t vaccine, HPV, 135 Whitfield ointment, pityriasis (tinea)
trichotillomania, 246–248 vancomycin, cellulitis and erysipelas, 122 versicolor, 138
alopecia vs, 227–228 varicella, 129t wigs, 282
trimethoprim/sulfamethoxazole vascular rosacea, 15 lace, 276
(co-trimoxazole) vasculitis women, hair loss, 327, 327f
donovanosis (granuloma inguinale), cutaneous Wood’s light examination in melasma,
127b, 128 in dermatomyositis, 40 clinical response evaluation,
methicillin-resistant S. aureus-related skin leukocytoclastic, 50, 53 318–319
and soft tissue infection, 131 segmental hyalinizing (=livedoid wrap, 282
tuberculosis (M. tuberculosis infection) vasculopathy), 44–47 wrinkles/rhytides
erythema nodosum and, 110 vasodilator therapy in Raynaud’s botulinum toxin A, 311–314
lichen nitidus and, 153 phenomenon in systemic sclerosis, chemical peels, 320
tufted folliculitis, 251–252 resistance to, 64
tumor(s) (neoplasms) verapamil, keloids, intralesional, 268–269
benign, 259–269 verrucous epidermal nevus, 263–264 Y
malignant see cancer vesicular dyshidrotic eczema, 82 yeast infections, 119–120
tumor necrosis factor-alpha inhibitors (incl. viral exanthems, 129t Yellow Emperor’s Classic of Internal Medicine,
monoclonal antibodies) vitamin A 354
dermatomyositis, 43 derivatives see retinoids
erythema nodosum, 110 sebum levels and, 361
granuloma annulare, 96 vitamin B5 (pantothenic acid), acne, 361 Z
psoriasis, 171, 173–174 vitamin B12, eczema/atopic dermatitis, zinc pyrithione shampoo
children, 176 367 products containing, 271
sarcoidosis, 98, 172–173 vitamin C (ascorbic acid), 305 seborrheic dermatitis, 179, 272–273
tungiasis, 132 melasma, 277, 285 tinea versicolor, 138
Turkey iontophoresis, 198 zinc sulfate pill, dissecting cellulitis, 238
allergic contact dermatitis, 71 with trichloroacetic acid, 319 zinc sulfate solution, acne vulgaris, 8
alopecia areata, 230 nickel-induced contact allergy, 72 zinc supplements, acne, 361
twists, 276 vitamin D derivatives Zyderm, 323t
tyrosinase inhibition acanthosis nigricans (for hyperkeratosis Zyplast, 323t
arbutin, 285 of nipple), 184 nasolabial folds, 324
azelaic acid, 285 inflammatory linear verrucous epidermal
licorice extract, 285 nevus (ILVEN), 264
N-acetyl glucosamine, 278 lichen amyloidosis, 150

392