Atlas of Dermatology - Motta - 2022

Atlas
of Dermatology
Inflammatory, Infectious and
Tumoral Skin Diseases
Adriana Motta
Luis Fernando González
Gonzalo García
Jennifer Guzmán
Lorena Prada
Hugo Herrera
Mariam Rolon
123
Atlas of Dermatology
Adriana Motta • Luis Fernando González
Gonzalo García • Jennifer Guzmán
Lorena Prada • Hugo Herrera • Mariam Rolon
Atlas of Dermatology
Inflammatory, Infectious and Tumoral Skin
Diseases
Adriana Motta Luis Fernando González
Dermatology Dermatology
El Bosque University El Bosque University
Bogotá, Colombia Bogotá, Colombia
Gonzalo García Jennifer Guzmán

Lorena Prada Hugo Herrera

Mariam Rolon
Dermatology
El Bosque University
Bogotá, Colombia
ISBN 978-3-030-84106-5 ISBN 978-3-030-84107-2 (eBook)

https://doi.org/10.1007/978-3-030-84107-2
© Springer Nature Switzerland AG 2022

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Contents
Part I Inflammatory Skin Diseases

1 Papulosquamous and Eczematous Dermatoses: Dermatitis�� 3
Contact Dermatitis �� 4
Atopic Dermatitis�� 12
Asteatotic Dermatitis �� 15
Nummular Dermatitis�� 18
Seborrheic Dermatitis�� 21
Vesicular Palmoplantar Dermatitis�� 27
Disseminated Eczema (Autosensitization Dermatitis)�� 32
Herpetic Eczema�� 34
Infective Dermatitis�� 36
Gravitational Dermatitis�� 37
Lichen Simplex Chronicus�� 39
Nodular Prurigo �� 41
Juvenile Plantar Dermatosis�� 46
References�� 50
2 Papulosquamous and Eczematous Dermatoses: Psoriasis �� 53
Psoriasis �� 54
References�� 79
3 Papulosquamous and Eczematous Dermatoses: Lichen�� 81
Lichen Planus�� 82
Lichenoid Drug Eruption �� 102
Fixed Pigmented Erythema�� 103
Lichen Nitidus�� 108
Lichen Striatus �� 109
Erythema Dyschromicum Perstans�� 112
Lichen Sclerosus et Atrophicus�� 117
References�� 128
v
vi Contents
4 Other Papular, Erythematous, and Scaly Diseases �� 131

Lichenoid Pityriasis �� 131
Pityriasis Rubra Pilaris�� 136
Axillary Granular Parakeratosis�� 140
5 Inflammatory Diseases of the Hair Follicle �� 143
Alopecia Areata�� 144
Temporal Triangular Alopecia �� 146
Androgenetic Alopecia�� 149
Telogen Effluvium �� 152
Trichotillomania�� 154
Traction Alopecia�� 155
Lichen Planopilaris�� 156
Discoid Lupus�� 161
Acne Keloidalis Nuchae�� 164
Folliculitis Decalvans�� 165
Dissecting Folliculitis�� 166
Hidradenitis Suppurativa�� 170
6 Inflammatory Diseases of the Sebaceous and Apocrine Glands�� 177
Acne �� 178
Rosacea�� 191
Perioral Dermatitis �� 200
7 Inflammatory Skin Diseases Induced by Drugs�� 205
Morbilliform Drug Eruption�� 205
Erythema Multiforme�� 208
Stevens-Johnson Syndrome �� 209
Toxic Epidermal Necrolysis�� 211
Drug Reaction with Eosinophilia and Systemic Symptoms�� 218
Acute Generalized Exanthematous Pustulosis�� 219
8 Inflammatory Diseases of the Blood Vessels with Cutaneous
Compromise�� 223
Leukocytoclastic Vasculitis�� 224
Granulomatosis with Polyangiitis�� 227
Polyarteritis Nodosa�� 229
Acute Hemorrhagic Edema of Childhood�� 231
Septic Vasculopathy �� 234
Cryoglobulinemia�� 235
Contents vii
9 Inflammatory Diseases Affecting Melanocytes �� 253

Post-inflammatory Hyperpigmentation�� 254
Melasma�� 255
Erythema Ab Igne�� 258
Confluent and Reticulated Papillomatosis of Gougerot and Carteaud�� 259
Vitiligo �� 261
Post-inflammatory Hypopigmentation�� 265
Pityriasis Alba�� 266
10 Vesiculobullous Inflammatory Diseases�� 279
Pemphigus Vulgaris�� 280
Pemphigus Foliaceus �� 284
Dermatitis Herpetiformis �� 286
Linear Iga Bullous Dermatosis�� 287
Bullous Pemphigoid�� 292
11 Inflammatory Skin Diseases Presenting with Erythema,
Urticaria, and Purpura�� 301
Urticaria �� 302
Erythema Annulare Centrifugum�� 304
Erythema Gyratum Repens�� 310
Erythema Marginatum �� 313
Pigmented Purpura�� 314
12 Inflammatory Connective Tissue Diseases�� 323
Cutaneous Lupus Erythematosus�� 324
Dermatomyositis�� 334
Scleroderma �� 339
Morphea �� 347
Relapsing Polychondritis �� 351
Graft-Versus-Host Disease�� 356
13 Granulomatous Inflammatory Diseases�� 383
Sarcoidosis �� 383
Granuloma Annulare�� 387
Necrobiosis Lipoidica�� 389
Melkersson-Rosenthal Syndrome�� 390
14 Inflammatory Diseases Induced by Ultraviolet Radiation�� 395
Polymorphic Light Eruption�� 396
Actinic Prurigo�� 399
Chronic Actinic Dermatitis�� 401
viii Contents
Photocontact Dermatitis�� 403

Congenital Erythropoietic Porphyria �� 405
Porphyria Cutanea Tarda�� 410
Erythropoietic Protoporphyria �� 411
15 Neutrophilic and Eosinophilic Inflammatory Diseases�� 415
Sweet Syndrome�� 415
Pyoderma Gangrenosum�� 418
Behcet’s Disease�� 425
Eosinophilic Pustular Folliculitis�� 428
16 Inflammatory Diseases of the Subcutaneous Adipose Tissue�� 437
Erythema Nodosum �� 438
Lupus Panniculitis�� 441
Lipodermatosclerosis �� 446
Part II Infectious Skin Diseases

17 Bacterial Infections�� 459
Staphylococcal and Streptococcal Infections
of the Skin �� 459
Impetigo �� 459
Erysipelas�� 460
Cellulitis�� 462
Necrozing Fascitis�� 464
Folliculitis, Forunculum, Carbunculum �� 465
Botriomycosis�� 467
Staphylococcal and Streptococcal Toxin Syndromes�� 468
Staphylococcal Scald Skin Syndrome �� 468
Erysipeloid �� 471
Erythrasma �� 472
Keratolysis Punctata�� 472
Gram-Negative Infections�� 473
Gangrenous Ecthyma �� 473
Bacillary Angiomatosis�� 474
18 Mycobacterial Infections �� 479
Leprosy (Hansen’s Disease)�� 479
Cutaneous Tuberculosis �� 486
Non-tuberculosis Mycobacteria �� 491
Contents ix
19 Fungal Infections�� 493

Superficial Mycosis�� 493
Dermatophytosisor Ringworm�� 493
Mucocutaneous Candidiasis�� 495
Onychomycosis�� 499
Pityriasis Versicolor �� 504
Tinea Nigra�� 505
Deep Mycoses�� 507
Sporotrichosis�� 507
Systemic Mycoses�� 509
Histoplasmosis �� 509
Paracoccidioidomycosis�� 510
20 Virus Infections�� 515
Herpesvirus�� 515
Herpes Simplex Type 1 (HHV1) and Type 2 (HHV2)�� 515
VHH 3 Congenital Varicela Syndrome�� 518
VHH 3 Varicela and Herpes Zoster�� 519
VHH 4 (Epstein–Barr) Leucoplasia Vellosa�� 522
VHH 4 (Epstein–Barr): Lipschutz Ulcers�� 523
VHH 5 Cytomegalovirus �� 526
VHH7 Herpes Virus Type 7 Pytiriasis Rosea�� 529
VHH 8 Sarcoma of Kaposi�� 530
Papillomavirus �� 534
Viral Warts and Flat Warts �� 534
Condylomas and Bowenoid Papulosis�� 544
Poxvirus �� 547
Molluscum Contagiosum �� 547
Other Virus Diseases�� 552
HTLV Infective Dermatitis�� 552
Parbovirus B19 Infectious Erythema �� 556
21 Sexually Transmitted Diseases�� 559
Syphilis�� 559
Lymphogranuloma Venereum�� 563
22 Infections by Parasites�� 567
Protozoa �� 567
Leishmaniasis�� 567
Helminths�� 571
Larva Migrans Cutaneous�� 571
x Contents
Infestations�� 573
Scabies �� 573
Pediculosis �� 575
Cutaneous Myasis�� 577
Part III Neoplastic Skin Diseases

23 Benign Neoplasms�� 583
Benign Epidermal Tumors �� 583
Seborrheic Keratosis�� 583
Porokeratosis�� 589
Dermatosis Papulosa Nigra�� 594
Skin Horn �� 595
Clear Cell Acanthoma�� 597
Epidermal Nevus�� 599
Verrucous Epidermal Nevus�� 600
Comedonal Nevus�� 602
Acanthosis Nigricans �� 604
Cysts�� 609
Epidermoid Cyst�� 610
24 Skin Adnexal Neoplasms �� 617
Nevus Sebaceous of Jadassohn�� 617
.Trichoepitheliomas�� 618
Pilomatrixoma�� 621
.Sebaceous Hyperplasia �� 622
.Sebaceous Carcinoma �� 622
.Syringomas �� 626
.Eccrine Poroma�� 627
.Hidradenoma�� 630
Syringocystadenoma papilliferum �� 632
.Spiradenoma �� 634
.Cylindroma �� 637
25 Muscle, Adipose Tissue, and Cartilaginous Neoplasms�� 641
Lipoma �� 641
26 Vascular Malformations�� 645
Capillary Malformations�� 645
Arterial �� 647
Angiohistiocytoma�� 647
Venous Malformations �� 654
Contents xi
Lymphatic Malformations�� 654

Arteriovenous Malformations�� 655
Other Vascular Disorders �� 655
Cherry or Cherry Angioma�� 656
Telangiectatic Granuloma�� 657
Infantile Hemangioma �� 661
27 Fibrous and Fibrohistiocytic Proliferations of Skin and Tendons�� 667
Dermatofibroma �� 667
Angiofibromas�� 669
Lax Fibroids (Skin Tags)�� 670
Superficial Fibromatosis-Plantar Fibromatosis�� 672
Atypical Fibroxanthoma�� 674
Dermatofibrosarcoma Protuberans�� 675
Low Differentiation Fibromyxoid Sarcoma�� 676
28 Congenital and Acquired Melanocytic Nevus �� 679
Congenital Melanocytic Nevus, Acquired Nevus and Others�� 679
Solar Lentigo�� 689
29 Neural and Neuroendocrine Neoplasms�� 693
Neurofibroma �� 693
Neurotechoma�� 695
Schwannoma�� 697
Merkel Cell Carcinoma�� 699
30 Disorders of Cells of Langerhans and Macrophages�� 703
Non-Langerhans Cell Histiocytosis �� 703
Xanthomas �� 707
Differential Diagnosis�� 710
31 Malignant Neoplasms�� 713
Actinic Keratoses �� 713
Basal Cell Carcinoma�� 715
Basosquamous Carcinoma �� 726
Keratoacanthoma �� 729
Erythroplasia of Queyrat�� 732
Squamous Cell Carcinoma�� 733
Sebaceous Carcinoma�� 742
Mastocytosis�� 743
Melanoma�� 749
Cutaneous Metastases�� 758
xii Contents
Breast and Extramammary Paget Disease �� 762

Lymphoproliferative Disorders Cd30�� 765
Lymphomatoid Papulosis�� 765
T-Cell Leukemia-Lymphoma �� 766
Mycosis Fungoid�� 767
Histopathology Will Depend on the MF Subtype�� 770
B-Cell Lymphoma�� 772
B-Cell Lymphoma of the Primary Cutaneous Marginal Area�� 772
32 Other Lymphoproliferative Disorders �� 775
Plasmacytoid Dendritic Cell Neoplasia �� 775
Index�� 777
Part I
Inflammatory Skin Diseases
Chapter 1
Papulosquamous and Eczematous
Dermatoses: Dermatitis
In this group of dermatological diseases are all the entities that present clinically as
papules or plaques in association with erythema, desquamation, and lichenification.
Among the most frequently cited diseases are dermatitis or eczema, psoriasis, lichen
planus, and lichenoid reactions. The most common dermatitis- or eczema-related
conditions are documented in this chapter:
A. Contact dermatitis.
(i) Allergic contact dermatitis.
(ii) Irritant contact dermatitis.
B. Atopic dermatitis.
C. Asteatotic dermatitis.
D. Nummular dermatitis.
E. Gravitational dermatitis.
F. Seborrheic dermatitis.
G. Vesicular palmoplantar dermatitis.
(i) Pompholyx.
(ii) Chronic vesiculobullous hand dermatitis.
(iii) Hyperkeratotic dermatitis of the hand.
(iv) Ide reaction.
H. Disseminated eczema (autosensitization dermatitis).
I. Herpetic eczema or Kaposi’s varicelliform rash.
J. Infective dermatitis.
K. Lichen simplex chronicus.
L. Nodular prurigo.
M. Juvenile plantar dermatosis.
© Springer Nature Switzerland AG 2022 3

A. Motta et al., Atlas of Dermatology,
https://doi.org/10.1007/978-3-030-84107-2_1
4 1 Papulosquamous and Eczematous Dermatoses: Dermatitis
Contact Dermatitis
• Definition: Contact dermatitis (also known as contact eczema) represents the

most frequent occupational dermatosis in industrialized countries. It is character-
ized as a disease of chronic fluctuating course with relapses and remissions [1].
• Pathogenesis: There are two presentations of contact dermatitis depending on the
pathophysiological mechanism involved. Reactions can be immunologically
mediated (allergic contact dermatitis) or mediated via direct damage via the
exposed substance to the skin (irritant contact dermatitis) [1]. Allergic contact
dermatitis occurs in response to a delayed type IV hypersensitivity reaction to
external chemicals (allergens) (Figs. 1.1, 1.2, and 1.3). The inflammatory pro-
cess occurs secondary to a previous sensitization phase that can take 10 to 14
days. Subsequent re-exposure to the allergen after this phase results in more
rapid and severe disease activity [2]. Irritant contact dermatitis is a nonspecific
and immunologically mediated localized reaction secondary to external physi-
cal, mechanical, or chemical agents that cause direct damage to the keratinocyte
and its components [2] (Fig. 1.4).
• Clinical presentation: In acute injuries, it is common to find papules, vesicles,
blisters, edema, and erythema (Figs. 1.5, 1.6, and 1.7). In subacute lesions, pap-
ules that converge forming plaques can be observed, accompanied by scales as
well as eroded areas secondary to the rupture of vesicles and blisters, serous
crusts, and exudation (Figs. 1.8 and 1.9). Lichenification and hyperkeratosis are
typical of chronic eczemas whereby the inflammatory process leads to epidermal
hyperplasia in response to local damage (Figs. 1.10, 1.11, 1.12, 1.13, 1.14, 1.15,
and 1.16).
• Diagnosis: The diagnosis of contact dermatitis is based on patient history, physi-
cal examination, and response to corticosteroids and, in some cases, is supported
Fig. 1.1 Allergic contact

dermatitis: Desquamative
erythematous plaque with
well-defined regular edges
in contact with a metal
handle (allergen) on the
back of the right wrist
Contact Dermatitis 5

dermatitis: Erythematous
plaque with fine superficial
scaling on the left wrist
and in contact with a metal
handle (allergen)

dermatitis: In the
suprapubic region, a scaly
erythematous plaque is
observed with some
excoriated areas, secondary
to contact with a metal belt
(allergen)
Fig. 1.4 Erythematous

irritative dermatitis
Sevestre-Jacquet’s
posterosive syphilitic
dermatitis: In the perianal
region of an older infant
with a history of anal
sphincter failure (with
chronic exposure to
irritants from fecal matter),
erythematous plaques and
nodules with well-defined
regular edges are observed
Fig. 1.5 Acute contact

dermatitis: Multiple
vesicles and blisters with
irregular borders are
observed in the distal third
of the forearm
by patch tests to confirm and identify the specific allergenic agent. Skin biopsy
in eczema is indicated to rule out diseases such as psoriasis, lichen planus, or
chronic eczema which can often present similarly to the initial stages of cutane-
ous T-cell lymphoma (mycosis fungoides). The histopathology findings of aller-
gic contact dermatitis compared to irritant contact dermatitis reveal increased
spongiosis in the allergic variant, while in the contact variant, the histopathologi-
cal findings will depend on the chemical composition and concentration of the
irritant, the type and time of exposure, and the severity of the response at the time
the sample is taken [3].
• The histopathological and clinical characteristics of contact dermatitis vary
depending on whether the disease is acute or chronic. In the acute state, spongio-
sis (intercellular edema that generates rupture of the cell-to-cell junction bridges)
is observed along with the consequent formation of epidermal vesicles. There is
Fig. 1.6 Acute contact

dermatitis: Tense blisters
on an erythematous
macular base are observed
on the dorsums of the
hands in a patient with a
history of exposure to a
chemical

dermatitis in the acute
phase: Eroded and
exudative erythematous
plaques with significant
edema in the eyelids are
seen on the lateral aspect
of the neck and pinna

dermatitis in the subacute
phase: On the forehead,
eyelids, malar region, and
nasal dorsum,
erythematous papules are
observed which converge,
forming a large plaque
with a degree of serous
crusting and excoriations

dermatitis in the subacute
phase: On the forehead and
extending to the eyelids,
multiple erythematous
papules are observed that
coalesce, forming a large
plaque with serous crusting
on its surface
Fig. 1.10 Chronic contact

dermatitis: Patient with
erythematosus and
lichenified plaques that
compromise the entire
surface of the palms. Note
the presence of fissures in
the fingertips

dermatitis: Chronic
dermatitis lesions can
generate retraction of the
nail bed with subsequent
deformation of the nail
plate. Exaggerated
curvature of the nail lamina
is observed

dermatitis: Fissured
palmar hyperlinearity are
observed in the fingertips

plaques with increased
skin cross-linking and loss
of dermatoglyphics
Fig. 1.14 Contact

dermatitis on the hands:
Presence of scaly
erythematous and
hyperkeratotic plaques
with some cracked areas
Fig. 1.15 Chronic allergic

contact dermatitis: On the
dorsums of the feet,
lichenified and scaly
violaceous plaques are
observed, likely secondary
to chronic contact with
synthetic shoe material
Fig. 1.16 Chronic allergic

contact dermatitis: A large,
erythematous, scaly, and
lichenified plaque with
well-defined irregular
edges is observed on the
dorsum of the left foot
variable infiltration of the epidermis by lymphocytes with an increase in epider-

mal mitotic activity leading to acanthosis. In the subacute phase of the disease, a
decrease in spongiosis and vesiculation is observed with an increase in acantho-
sis and the formation of a parakeratotic corneal layer that contains coagulated
plasma and pyknotic nuclei of inflammatory cells. In chronic eczema, hyperkera-
tosis is gradually replaced by parakeratosis with a predominance of acanthosis
and little or no spongiosis. The epidermal infiltrate is less evident, and the dermal
changes are more prominent with an elongation of the dermal papilla that, added
to the epidermal changes, are findings typical of lichenification [4].
• The diagnosis of allergic contact dermatitis is confirmed by the patch test in
which the individual is exposed to specific concentrations of particular antigens
in order to induce inflammation at the site of application in susceptible individu-
als. These tests are indicated in patients with allergic contact dermatitis, espe-
cially with therapeutic failure; chronic hand or foot eczema; persistent or
intermittent eczema of the face, eyelids, and perineum; and in some cases gravi-
tational eczema [5].
• Differential diagnosis: The most important differential diagnosis of irritant con-
tact dermatitis is allergic contact dermatitis. Similarly, the differential diagnosis
also depends on the location of the lesions. On hands and plantar surfaces of the
feet, plantar psoriasis should be ruled out, while in photo-exposed sites, a photo-
contact dermatitis should be ruled out. In some cases, it is important to exclude
atopic dermatitis or seborrheic dermatitis on the face. Dermatophytosis, fixed
drug eruption, and phytophotodermatitis are also relevant differential diag-
noses [6].
Atopic Dermatitis
• Definition: Atopic dermatitis is a chronic and inflammatory skin disease caused

by an alteration in the barrier function of the epidermis that generates dry skin
and IgE-mediated sensitization to different allergens [7].
• Pathogenesis: Atopic dermatitis is an inflammatory condition of the skin second-
ary to the defect of essential proteins involved in the structural and functional
integrity of the stratum corneum [8]. The genetically derived epidermal barrier
dysfunction combined with other environmental factors (e.g., Staphylococcus
aureus enterotoxin and topical allergens) can trigger an immune response in sus-
ceptible infants and adults [7, 8].
• Clinical presentation: Atopic dermatitis affects all population groups with a pre-
dominance in children. The clinical presentation of the disease varies according
to the age of the patient as determined by its distribution and morphology of
lesions in infants, children, adolescents, and adults [8, 9]. Infant atopic dermati-
tis presents as exudative and erythematous plaques that can be accompanied by
meliceric crusts secondary to serous secretion or in some cases bacterial superin-
fection [6]. Lesions are mainly located on the face and cheeks (respecting the
nasolabial folds), the extensor areas of the extremities, and, to a lesser extent, the
trunk (Figs. 1.17 and 1.18). In this age group, the diaper area is usually preserved
[9]. From 2 years of age or childhood atopic dermatitis, atopic dermatitis pres-
ents with polymorphic lesions with involvement mainly on the flexor areas and
folds that can extend to further include the trunk and extremities (Figs. 1.19 and
1.20). Atopic dermatitis in adolescents and adults presents as lichenified and
excoriated plaques in flexor areas, wrists, ankles, and eyelids [9] (Fig. 1.21).
Some adults with atopic dermatitis may develop allergic contact dermatitis on
the hands or additional sites including the retroauricular region, the neck, and the
chest. Any presentation of atopic dermatitis can manifest as erythema associated
with desquamation of more than 90% of the body surface (erythroderma), where
a thorough differential diagnosis must be made to rule out other causes of eryth-
roderma and establish immediate treatment [8] (Figs. 1.22, 1.23, and 1.24).
Atopic Dermatitis 13
Fig. 1.17 Atopic

dermatitis of the infant:
Erythematous plaques
covered with serous crusts
in the malar region and
forehead without
compromise of the
nasogenian sulcus
–– Besnier prurigo: Chronic lesions due to atopic dermatitis occur with licheni-
fication, in some cases producing infiltrated plaques and nodules that resem-
ble nodular prurigo. The association of prurigo with atopic dermatitis is called
Besnier prurigo or atopic prurigo [10] (Fig. 1.25).
• Diagnosis: There are no specific laboratory or histopathology findings for the
diagnosis of atopic dermatitis. Different diagnostic criteria have been proposed,
such as those of Hanifin and Rajka in 1980, with difficulty for clinical validity
due to the low specificity of some criteria. Until 2003, the American Academy of
Dermatology proposed different essential characteristics to make the diagnosis
such as the presence of itching associated with chronic and recurrent eczema that
affects typical areas according to the affected age group. The above added to
important characteristics at the time of diagnosis such as early age of onset of
disease, personal or family history of atopy, IgE hyperreactivity, and associated
xerosis are all important features aiding the diagnosis of atopic dermatitis [11].
• Differential diagnosis: The main entities to rule out are scabies, seborrheic der-
matitis (especially in infants), contact dermatitis (allergic or irritative), ichthyo-
sis, psoriasis, cutaneous T-cell lymphoma, photosensitivity dermatitis, and
immunodeficiency diseases, among others [10].
Fig. 1.18 Atopic

dermatitis: A 2-year-old
patient with erythematous
exudative plaques and
serous crusts in the
bilateral malar region.
Note the presence of the
Dennie-Morgan
infraorbital double eyelid
fold, a clinical sign
frequently associated with
atopic dermatitis
Fig. 1.19 Childhood

atopic dermatitis: A
5-year-old patient with
lichenified excoriated
erythematous plaques in
bilateral popliteal fossae
Asteatotic Dermatitis 15
Fig. 1.20 Childhood

atopic dermatitis: Multiple
erythematous papules that
coalesce to form a large
excoriated plaque in the
cubital fossa
Asteatotic Dermatitis
• Definition: Asteatotic dermatitis or eczema craquelé is a special variant of irritant

dermatitis present in older adult patients or in patients using oral retinoids [12].
• Pathogenesis: Although the pathogenesis is not entirely elucidated, it is sug-
gested that the alteration of skin lipids and a decrease in the quantity of the natu-
ral moisturizing factor from the keratohyalin granules are triggers of the disease.
In the case of the elderly, this dermatitis is triggered by very frequent baths asso-
ciated with the use of detergent soaps or passing prolonged periods in rooms
with high temperatures and low humidity [12, 13]. In young adults, it can be
related to oral retinoid intake and rarely associated with endocrinopathies such
as hypothyroidism or Sjögren’s syndrome [11, 12].
Fig. 1.21 Adult atopic

plaques with fine flaking
that involve the eyelids,
perioral region, and neck
• Clinical presentation: Xeroderma and ichthyosiform plaques present on the skin

that are prone to exacerbation by repetitive and frequent baths at low t emperatures
with detergent [14] (Figs. 1.26 and 1.27). The plaques are pruritic in nature and
typically involve the legs, arms, and hands, often with relapses in cold cli-
mates [11].
• Diagnosis: The diagnosis is clinical, and in relatively few cases, a skin biopsy is
necessary. The classically observed histopathological characteristics are those of
subacute eczema with a variable dermal infiltrate [11].
• Differential diagnosis: Irritant or allergic contact dermatitis, nummular dermati-
tis, gravitational dermatitis, or ichthyosis may have similar characteristics with
eczema craquelé [12].
Asteatotic Dermatitis 17
Fig. 1.22 Erythroderma

due to atopic dermatitis:
Adolescent patient with a
history of difficult-to-
manage atopic dermatitis
with the presence of
erythema and scaling of
more than 90% of the total
body surface

Adult patient with
more than 90% of the total
body surface. The patient
has a history of atopy and
asthma since childhood

On the back of a young
adult, erythema and scaling
are observed with few
areas of healthy skin
Fig. 1.25 Besnier prurigo:

A 10-year-old chronic
atopic dermatitis patient
with multiple lichenified
and excoriated
erythematous-violaceous
papules and plaques on the
trunk and extremities
Nummular Dermatitis
• Definition: Nummular dermatitis, also called discoid eczema or microbial

eczema, is characterized by its presentation of oval or circular eczematous
plaques with a well-defined and regular border, unlike other types of eczema [15].
• Pathogenesis: Its etiology is unknown, and for some authors, it is a form of
endogenous primary eczema with particular characteristics [11]. It has been
Nummular Dermatitis 19
Fig. 1.26 Asteatotic

dermatitis: Older adult
with erythematous and
cracked plaques that
involve the anterior aspect
of the legs
Fig. 1.27 Eczema

craquelé: Ichthyosiform
plaques with irregular
edges in the middle third
of the right leg
related in some cases to bacterial superinfection or contact sensitization.

Similarly, it can be associated with xerosis and venous hypertension [15].
• Clinical presentation: Dermatologic examination reveals oval or coin-sized
plaques (hence the nummular name) covered by serous or meliceric crusts
(Fig. 1.28). The most frequently affected sites are the legs in men and the fore-
arms and back of hands in women [16] (Fig. 1.29).
• Diagnosis: Based on clinical findings. Histopathology shows subacute dermatitis
indistinguishable from other forms of eczema, accompanied by spongiotic vesi-
cles and a lymphohistiocytic infiltrate in the superficial dermis [14] (Figs. 1.30,
1.31, 1.32, 1.33, and 1.34).
• Differential diagnosis: Nummular eczema can be difficult to distinguish from
other entities that present with scaly plaques that are sometimes oval, such as
superficial dermatophytosis, contact dermatitis, psoriasis, the initial presentation
of a mycosis fungoides, impetigo, and benign familial pemphigus [17].
Fig. 1.28 Nummular

dermatitis: On the back of
the arm surrounding the
elbow, erythematous
nummular plaques with
serohematic crusts are
observed
Fig. 1.29 Nummular

dermatitis: On the back of
the arm and forearm,
observed, which converge
forming a number of
plaques covered with
serohematic crust, some of
which have central
clearance
Seborrheic Dermatitis 21
Fig. 1.30 Nummular dermatitis: 20x H&E-stained skin biopsy with epidermal acanthosis and a
superficial perivascular inflammatory infiltrate with edema in the papillary dermis
Seborrheic Dermatitis
• Definition: It is considered a chronic dermatitis that involves areas rich in seba-

ceous glands such as the scalp, face, and upper trunk. It is proposed that the
common “dandruff” (fine desquamation of the scalp) is a precursor lesion of
seborrheic dermatitis that subsequently progresses to redness, irritation, and des-
quamation [18].
• Pathogenesis: Its cause is unknown; however, it is suggested that the fungus
Pityrosporum ovale could be related to seborrheic dermatitis [19]. This evidence
is based on the growth of P. ovale from scales of patients with seborrheic derma-
titis and the satisfactory response to therapy with antifungals such as ketocon-
Fig. 1.31 Nummular dermatitis: 40x H&E-stained skin biopsy with foci of spongiosis at the der-
moepidermal junction with perivascular inflammatory infiltrate
azole or itraconazole. Similarly, it is believed that seborrhea (excess sebum)

favors seborrheic dermatitis, which is why the lesions are located in the anatomi-
cal sites with the greatest number of folliculosebaceous units. Seborrheic derma-
titis is more common in neurological disorders including Parkinson’s disease and
infections such as human immunodeficiency virus (HIV) [20]. (Figs. 1.35
and 1.36).
• Clinical presentation: There are two peaks of disease presentation: (1) in the first
3 months of life and (2) in the second to fourth decades of life [19]. The clinical
Fig. 1.32 Nummular dermatitis: H&E-stained skin biopsy with evidence of epidermal hyperplasia
and a superficial perivascular inflammatory infiltrate
presentation of the disease often varies according to the age of presentation.

Infantile seborrheic dermatitis presents as erythematous plaques covered with a
fine, oily scale that involves the scalp, the trunk folds, and the diaper area [19]
(Figs. 1.37, 1.38, 1.39, and 1.40). In adults, seborrheic dermatitis begins with a
fine desquamation of the scalp without major erythema or infiltration called pity-
riasis simplex capillitii or also commonly known as “dandruff”. Erythematous
plaques with oily scales can be seen on the forehead, between the eyebrows, and
on the upper eyelids, nasolabial folds, retroauricular area, occiput, and neck
(Figs. 1.41 and 1.42). Similarly and less frequently, involvement of the anterior
thorax can be observed (Fig. 1.43), and seborrheic dermatitis is even known to
manifest in an erythrodermic form [21].
Fig. 1.33 Nummular dermatitis: H&E-stained skin biopsy with evidence of epidermal hyperplasia
with some foci of spongiosis and a superficial perivascular inflammatory infiltrate
• Diagnosis: It is normally a clinical diagnosis as per the clinical findings of the

lesions, with the presence of slightly scaly erythematous plaques in areas rich in
sebaceous glands such as the scalp, forehead, ears, and presternal region,
although it can rarely present folds [20].
• Differential diagnosis: Childhood seborrheic dermatitis should be differentiated
from childhood atopic dermatitis, being less pruritic and inflammatory in the first
entity. Similarly, childhood seborrheic dermatitis should be differentiated from
irritant diaper area dermatitis, candidiasis, childhood psoriasis, Langerhans cell
Fig. 1.34 Nummular dermatitis: H&E-stained skin biopsy at higher magnification with evidence
of epidermal hyperplasia with some foci of spongiosis and presence of subcorneal pustule
Fig. 1.35 Seborrheic

dermatitis in a patient with
HIV immunosuppression:
Middle-aged male patient
with multiple erythematous
scaly plaques with
irregular edges in the
nasogenian sulcus and
beard area
histiocytosis, and tinea capitis [20]. In adult seborrheic dermatitis, the lesions
can mimic psoriasis of the scalp. If the lesions affect the face, it must be
differentiated from rosacea, systemic lupus erythematosus, contact dermatitis,
and perioral dermatitis. On the contrary, if the lesions are located on the trunk, a
pityriasis rosea, pityriasis versicolor, subacute cutaneous lupus, and psoriasis in
the eruptive phase should all be ruled out [20].

dermatitis in a patient with
HIV immunosuppression:
Adult patient with
multiple, well-defined
irregular scaly
erythematous plaques that
compromise the beard area
and extend to nasogenian
furrows
Fig. 1.37 Infantile

seborrheic dermatitis: A
2-month-old patient with
erythematous scaly plaques
with irregular edges that
involve the bilateral
parietal region and vertex
Vesicular Palmoplantar Dermatitis 27
Fig. 1.38 Infantile

seborrheic dermatitis:
Infant with erythematous
plaques containing fine
oily scales that
compromise the forehead
and the malar region
Vesicular Palmoplantar Dermatitis
• Definition: Also called pompholyx or dyshidrotic eczema, it represents an acute

or chronic dermatitis that affects the palms and soles. Endogenous dermatitis
distinct from dermatitis caused by exogenous factors is considered [22].
• Pathogenesis: The etiology is not entirely clear. Genetic and environmental com-
ponents are believed to trigger the pompholyx [23]. This condition has been
frequently related in patients with a history of atopy as well as those with posi-
tive patch tests for perfumes, medications, or topical corticosteroids [22].
Likewise, exacerbation of the lesions has been documented during hot climates
or in summer without being able to identify an inflammation or structural altera-
tion of the eccrine glands as initially thought [17–19]. In the case of hyperkera-
totic dermatitis of the hands, there is no relationship with allergens identified by
patch tests, nor is there a higher incidence of psoriasis or atopy found in these
patients [22]. On the other hand, ide reactions are triggered by a fungal antigen
during the inflammatory process of infection which generates distant clinical
lesions [ 17–19].
• Clinical presentation: Four categories are identified: the pompholyx, the chronic
vesiculobullous dermatitis of the hands, the hyperkeratotic dermatitis of the
hands, and the ide reactions [21].
Fig. 1.39 Infantile

Infant with erythematous
plaques with yellowish
scales in the frontal and
ciliary region
–– The most acute presentation of the disease is the pompholyx which appears as
a vesiculobullous eruption that affects palms, soles, and lateral aspect of the
fingers. The cheiropompholyx and podopompholyx are terms used for the
involvement of the disease in the hands and feet, respectively [24]. Desiccation
of the vesicles or blisters leaves exudative erosions that can become
infected [21].
–– Chronic vesiculobullous dermatitis of the hands or dyshidrotic eczema is the
most common presentation and difficult to manage given the recalcitrant
course of the disease. Clinically, it appears as small vesicles with clear content
on the lateral aspect of fingers, palms, and soles. Chronic lesions can fissure
and become hyperkeratotic [21] (Figs. 1.44 and 1.45).
–– Hyperkeratotic dermatitis of the hand presents as erythematous and keratotic
plaques which are generally pruritic and located on the central part of the
palms more frequently than the soles. This condition occurs frequently in
middle-aged men and is generally refractory to treatment [21] (Fig. 1.46).
–– The ide reaction appears as erythematous-based vesicles on the lateral aspect
of the fingers. The lesions appear suddenly and are accompanied by pruritus.
The ide reaction is proposed to be an allergic response to a fungal infection or
Fig. 1.40 Infantile

Infant with multiple
erythematous papules,
some of which coalesce,
forming plaques on the
trunk and face
to a particular antigen created during the inflammatory process of the infec-

tion [21] (Fig. 1.47).
• Diagnosis: The diagnosis is made according to the clinical history and the find-
ings on physical examination and sometimes with histopathology [21]. Optical
microscopy shows a thickened corneal stratum corneum with intraepidermal
spongiotic vesicles that do not compromise the acrosyringium and associated
with a mild mixed infiltrate in the superficial dermis [25]. In the case of hyper-
keratotic dermatitis of the hands, chronic spongiotic dermatitis with psoriatic
hyperplasia, compact orthokeratosis, and chronic cellular inflammatory infiltrate
is observed [24].
• Differential diagnosis: The differential diagnoses of dermatoses that affect palms
and soles are very broad, sharing similar clinical characteristics. One of the most
analogous differential diagnoses is contact dermatitis which, unlike vesicular
vesicular palmoplantar dermatitis with erythematous plaques that can compro-
mise the back of the hands. Tinea manuum is generally unilateral with plaques
Fig. 1.41 Adult seborrheic

dermatitis: Middle-aged
patient with poorly defined
erythematous plaques with
thin superficial scales that
compromise the eyebrows,
nasolabial folds, and
beard area

dermatitis: Middle-aged
adult patient with poorly
defined erythematous
plaques with fine scales in
the bilateral ciliary region

dermatitis: Male patient
with erythematous scaly
edges in the anterior chest
Fig. 1.44 Chronic

vesiculobullous dermatitis
of the hands: Patient with
presence of frustrating
vesicles on hands with
negative KOH for fungi
with fine desquamation, while the tinea pedis appears very similar to the pom-
pholyx. In some cases, it is useful to perform a scraping of the lesions for myco-
logical examination with KOH [20]. In palmoplantar psoriasis, no vesicles are
seen, and the lesions resemble erythematous plaques covered with a thick silver
scale. Keratolysis exfoliativa occurs as areas of local exfoliation [23]. Other enti-
ties that affect palms and soles include palmoplantar pustulosis, Bazex paraneo-
plastic acrokeratosis, and epidermolysis bullosa [21].
Fig. 1.45 Chronic

vesiculobullous dermatitis
of the hands: Patient with a
clinical picture of several
years’ evolution of
multiple plaques with a
desquamative halo and
some frustrating vesicles
Fig. 1.46 Ide reaction to

tinea pedis: (a) On the a
palmar aspect of the foot,
plaques with a scaly halo
are observed, secondary to
frustrating vesicles and
blisters. (b) Scaly plaques
with an active edge in a
patient with tinea pedis
Disseminated Eczema (Autosensitization Dermatitis)
• Definition: Disseminated eczema or generalized dermatitis secondary to an

exogenous agent, being more frequent in patients with allergic contact dermatitis
and gravitational dermatitis [26].
Disseminated Eczema (Autosensitization Dermatitis) 33
Fig. 1.47 Hyperkeratotic

dermatitis of the hand:
Erythematous plaque
and some frustrating
perilesional vesicles in the
palmar region
Fig. 1.48
Autosensitization
dermatitis: Older adult
scaling plaques with
irregular edges on the face,
upper extremities, and
trunk
• Pathogenesis: The relationship of endogenous spread with eczema was described

by Whitfield. Although it has not been very clearly elucidated, it is suggested that
the ingestion of certain allergens, for example, nickel, can trigger dermatitis or
eczema spread in sensitized patients [25].
• Clinical presentation: Disseminated eczema presents as very itchy erythematous
plaques with fine scaling on the extremities and face with less trunk involvement
[25] (Figs. 1.48 and 1.49). The lesions may be similar to those found in circum-
scribed allergic contact dermatitis, gravitational dermatitis [33], or eczema
craquelé in older adults.
• Diagnosis: The detailed medical history and the physical examination are essen-
tial to make the diagnosis. Histopathology findings can be elicited from acute or
subacute dermatitis [25].
Fig. 1.49 Generalized

eczema or autosensitization
dermatitis: Affecting the
back and posterior aspect
of the arms, a large
erythematous scaly plaque
with irregular edges is
observed, with some areas
• Differential diagnosis: Disseminated eczema must be differentiated from other

eczemas that can present as disseminated lesions such as contact dermatitis by
airborne substances, atopic dermatitis, photoallergic dermatitis, and tumor enti-
ties such as mycosis fungoides and Sézary syndrome [25].
Herpetic Eczema
• Definition: Herpetic eczema (also known as “Kaposi’s varicelliform rash”) is an

acute dermatitis caused in most cases by infection of the herpes simplex virus
type I (HSV-1) on the skin affected by pre-existing dermatosis (atopic dermatitis,
psoriasis, burn, etc.) [27].
• Pathogenesis: Although the pathogenesis has not been fully elucidated, it is sug-
gested that there is structural damage to the skin barrier and immunodeficiency
that favor viral infection. It has been argued that the growth of herpes simplex
virus type I is faster in patients with atopic dermatitis and psoriasis [28].
• Clinical presentation: After an incubation period of 5 to 10 days, a disseminated
and pruritic vesiculopustular eruption occurs. Vesicular lesions have central
umbilication and tend to converge. Later, the lesions tend to become covered
with hemorrhagic crusts on their surfaces [29]. (Figs. 1.50, 1.51, and 1.52).
• Diagnosis: The diagnosis should be suspected in all patients who present an
alteration of the basic skin barrier and present an acute vesiculopustular eruption.
The Tzanck test is useful to confirm the herpetic infection of the lesions. The
sensitivity of this test can reach up to 70% depending on the integrity of the
lesion. Skin biopsy shows histopathological changes due to herpes simplex
(nucleated giant cells with keratinocyte ballooning and intracellular eosinophilic
inclusions) [30].
Herpetic Eczema 35
Fig. 1.50 Herpetic

eczema: Patient with a
history of Darier’s disease
who has multiple vesicles
and umbilicated papules
covered with a central
hemorrhagic crust in the
left half face
Fig. 1.51 Herpetic

eczema: Multiple
umbilicated vesicles with
central serohematic crust
in the left half face
• Differential diagnosis: The main differential diagnoses are infections with the
varicella zoster virus (VZV) and impetigo. PCR tests are available in cases of
high clinical suspicion of VZV infection to differentiate it from HSV-1 infec-
tions. Culture of the lesions should be performed if a bacterial infection is sus-
pected [29].
Fig. 1.52 Herpetic

eczema: Multiple vesicles
with central serohematic
crust are seen in the palmar
region
Infective Dermatitis
• Definition: It is a rare dermatological entity that affects children, adolescents,

and even less so adults, related to HTLV-1 lymphotropic virus infection [31].
• Pathogenesis: The HTLV-1 lymphotropic virus has the ability to infect T lym-
phocytes, B lymphocytes, and monocytes with consequent spontaneous cell pro-
liferation without exogenous stimulation. The said proliferation favors the
expression of different pro-inflammatory cytokines such as interferon gamma,
IL-5, and IL-10 [30].
• Clinical presentation: Infective dermatitis appears in early childhood and some-
times in adulthood. It presents clinically as exudative dermatitis and crusted
eczematous dermatitis that mainly affects the scalp, armpits, groin, ears, perineal
skin, eyelid margin, and neck [30, 32] (Figs. 1.53 and 1.54).
• Diagnosis: Le Granade et al. proposed different diagnostic criteria for patients
with suspected infectious dermatitis. The main criteria are (1) a crusted eczema
of the scalp, (2) the armpits, (3) the retroauricular region, (4) the eyelids, (5) the
perinasal area, and (6) the neck in addition to a (7) watery nasal discharge with-
out signs of rhinitis, beginning in childhood, and (8) seropositivity for HTLV-1.
Among the minor criteria are (1) positive cultures for Staphylococcus aureus or
beta-hemolytic streptococcus of the perinasal skin, (2) a generalized papular
rash, (3) anemia with high sedimentation rate, (4) hypergammaglobulinemia,
and (5) high CD4+ and CD8+ T-cell counts. To establish the diagnosis, four of
the major criteria plus HTLV-1 seropositivity must be met [31, 33].
• Differential diagnosis: A differential diagnosis should be made with atopic der-
matitis, seborrheic dermatitis, and impetigo [30].
Gravitational Dermatitis 37
Fig. 1.53 Infective

dermatitis: Elderly patient
with scaly plaques covered
with serohematic crust
with compromised eyelids,
ears, scalp, and
perinasal skin
Gravitational Dermatitis
• Definition: Gravitational dermatitis or stasis dermatitis is a common entity that

affects the lower extremities due to venous hypertension that generates a gravita-
tional syndrome characterized by edema, inflammation, induration, ulceration,
and fibrosis of the skin [34].
• Pathogenesis: The venous circulation of the lower limbs is made up of the deep,
superficial, and intercommunicating (perforating) venous system that together
with the contraction of the gastrocnemius and soleus muscles allow venous
return. When any component of this system is altered, venous hypertension is
generated that results in the distension and elongation of the capillary loops that
allow the deposition of fibrin into the endothelial pores that limit the diffusion of
oxygen and other nutrients [33]. It is suggested that the inflammation of the skin
results from the sequestration of leukocytes in the venules with the consequent
release of proteolytic enzymes and free radicals that cause tissue damage [35].
Fig. 1.54 Infective

dermatitis: Elderly patient
with scaly plaques with
some serohematic crusts in
the pinna, neck, and scalp
• Clinical presentation: It appears as erythematous, scaly, and exudative plaques,

usually on the ankles or middle third of the legs (Fig. 1.55). Likewise, excess
skin lesions can be observed on the abdomen of patients with obesity and in
association with arteriovenous fistulas in the upper extremities. In addition to
eczematous changes, gravitational dermatitis can be associated with cutaneous
alterations secondary to venous hypertension due to superficial varicose dilation
(Figs. 1.56 and 1.57), edema, purpura, hemosiderin deposits, ulceration, or small
white atrophic plaques with scars and telangiectasia (white atrophy) [34]
(Fig. 1.58). These patients may present with allergic contact dermatitis second-
ary to different topical agents or to the elastic used to manage venous insuffi-
ciency. In some cases, self-sensitizing dermatitis may be triggered [33, 34].
• Diagnosis: In most cases, it is clinical. The use of imaging such as venous
Doppler is useful to assess the state of the venous system. Biopsy is indicated
only for those cases refractory to treatment where the clinical diagnosis is
doubtful.
• Differential diagnosis: In children and young adults, atopic dermatitis can gener-
ate lichenified erythematous plaques on the ankles or popliteal fossae. Similarly,
nummular dermatitis, asteatotic dermatitis, and allergic contact dermatitis can
Lichen Simplex Chronicus 39
Fig. 1.55 Gravitational

dermatitis: Desquamative
serous crusting is observed
on the right leg and
extending to the dorsum of
the foot in a patient with
chronic venous
insufficiency
manifest with leg injuries. In some cases, dermatophyte infections present as

erythematous plaques with a scaly border. Hypertrophic lichen planus presents
as a hyperkeratotic or lichenified plaque on the legs. Psoriasis also affects the
legs, depicted as erythematous and infiltrated plaques covered with a silver
scab [34].
Lichen Simplex Chronicus
• Definition: A chronic eczematous response to chronic friction and scratching of

a localized area of the
skin. It is also known as “neurodermatitis” [36].
• Pathogenesis: Lichenification occurs secondary to repetitive excoriation or
scratching. This can be presented as a manifestation of an atopic state. It has been
considered that in predisposed individuals, emotional stress can worsen and per-
petuate the condition [37].

dermatitis: Patient with a
history of venous
hypertension presenting
with an erythematous scaly
plaque with irregular edges
in the middle and distal
third of the right leg. Note
the dilation of the
superficial venous
capillaries
• Clinical presentation: The main symptom of patients with chronic lichen sim-
plex is pruritus. Clinically, plaques are observed in circumscribed areas that can
be scaly and scabby, sometimes with fissures and with the usual features of
lichenification (e.g., hyperlinearity of the skin). This condition frequently occurs
on the nipple, neck, scalp, thighs, vulva, pubis, scrotum, and extensor areas of
the forearms [36] (Figs. 1.59 and 1.60).
• Diagnosis: An underlying dermatosis such as atopic eczema, lichen planus, or
amyloid lichen should be ruled out, which can present with similar lichenified
plaques. In some cases, histology can orientate the clinician to the diagnosis. The
main findings are acanthosis with varying degrees of hyperkeratosis that can be
accompanied by spongiosis with areas of parakeratosis and a chronic inflamma-
tory infiltrate in the dermis with collagen verticalization [36] (Figs. 1.61
and 1.62).
Nodular Prurigo 41

scaly plaques with
irregular edges are
observed on the lateral
aspect of the legs.
N.B. there is presence of
varicose dilation
• Differential diagnosis: Any condition characterized by pruritus and the conse-

quent scratching leading to lichenified lesions such as in patients with atopic
dermatitis, chronic eczema, psoriasis, lichen planus, and occasionally tinea
[35, 36].
Nodular Prurigo
• Definition: A relatively uncommon chronic idiopathic dermatitis that affects

middle-aged women and sometimes children [38].
• Pathogenesis: Its etiology is unknown, but a relationship with neurological, trau-
matic, and metabolic factors is postulated. It is not known whether itching or
excoriation appears first [37].
• Clinical presentation: The lesions are hard, round, and keratotic nodules that
present a depressed surface with some lichen plaques. Excoriations and post-
inflammatory hyperpigmentation can be observed (Fig. 1.63). The distribution is
generally symmetrical with a predominance of the extensor surfaces of the
Fig. 1.58 White atrophy

due to chronic venous
insufficiency: A
scleroatrophic plaque is
observed with some
telangiectasias and
venulectasias on the medial
malleolus of the left leg
Fig. 1.59 Lichen simplex

chronicus: Multiple
papules are observed on
the back of the neck,
converging to form a large
lichenified erythematous
plaque with well-defined
irregular edges
Nodular Prurigo 43
Fig. 1.60 Lichen simplex

chronicus: An
erythematous scaly plaque
with lichenified areas and
poorly defined borders is
observed on the dorsum of
the foot
Fig. 1.61 Lichen simplex chronicus: H&E-stained skin biopsy with evidence of psoriasiform epi-
dermal hyperplasia with compact hyperkeratosis and mild superficial perivascular inflammatory
infiltrate
Fig. 1.62 Lichen simplex chronicus: H&E-stained skin biopsy at higher magnification with col-
lagen verticalization in the superficial dermis
Fig. 1.63 Nodular

prurigo: Erythematous-
violaceous nodules and
papules with excoriated
centers and infiltrated
edges
Nodular Prurigo 45
Fig. 1.64 Nodular

prurigo: Multiple papules
and nodules with a
keratotic center are
observed in the trunk,
leaving hyperpigmented
macules and some atrophic
scars
Fig. 1.65 Nodular

prurigo: On the posterior
region of the arm and
forearm, multiple slightly
infiltrated papules and
erythematous nodules are
observed, some of which
are keratotic and
excoriated
extremities, although compromise of the sacral region and abdomen has been
observed in 50% and 44% of patients [37] (Figs. 1.64, 1.65, 1.66, 1.67, and 1.68).
• Diagnosis: The diagnosis is clinical and supported by the findings on histopa-
thology. Biopsies from patients with nodular prurigo show histological changes
secondary to scratching such as thick compact orthokeratosis, pseudoepithelio-
matous hyperplasia, surface erosions, fibrosis of the papillary dermis with
collagen verticalization, and perivascular or interstitial superficial inflammatory
infiltrate [38] (Figs. 1.69 and 1.70). Similarly, the formation of neuromas
(Pautrier’s neuroma) secondary to nerve fiber hyperplasia has been docu-
mented [39].
• Differential diagnosis: Lichen simplex chronicus, hypertrophic lichen planus,
multiple keratoacanthomas, and rare entities such as nodular pemphigoid and
pruritic epidermolysis bullosa [37].
Fig. 1.66 Nodular

and violaceous infiltrated
nodules with a lichenified
surface are observed on the
left leg
Fig. 1.67 Nodular

and nodules with
excoriated centers and
hyperpigmented macular
borders are observed in the
pretibial region
Fig. 1.68 Nodular

prurigo: Infiltrated plaques
with poorly defined and
hyperpigmented edges
with an excoriated center
covered with squamous
scab are observed
Juvenile Plantar Dermatosis
• Definition: A frequent dermatosis in patients with atopic diathesis that involves

the plantar region of the feet [40].
Juvenile Plantar Dermatosis 47
Fig. 1.69 Simple prurigo: 20x H&E-stained skin biopsy showing the epidermis with foci of spon-
giosis and superficial perivascular infiltrate
• Pathogenesis: It occurs in patients with a predisposition to atopy who expose

themselves to exogenous factors such as rubber or plastic (materials used in foot-
wear) that favor antigenic presentation and are capable of forming a local inflam-
matory reaction [40].
• Clinical presentation: Affecting the plantar area of the feet, juvenile plantar der-
matosis typically presents with shiny scaly erythematous plaques that can fissure
and be associated with pain. Generally, the dorsum of the foot and the interdigital
spaces are preserved [40] (Figs. 1.71 and 1.72).
• Differential diagnosis: Juvenile plantar dermatosis must be distinguished from
allergic contact dermatitis, an alternative pathogenesis secondary to the chemi-
cals present in leather and rubber, as well as infectious diseases such as tinea
pedis [40].
Fig. 1.70 Simple prurigo:

40% H&E-stained skin
biopsy. In the initial stages
of prurigo, spongiosis and
hyperkeratosis with a
superficial perivascular
infiltrate are observed
Juvenile Plantar Dermatosis 49
Fig. 1.71 Juvenile plantar

dermatosis: In the plantar
region of the feet, bright
lichenified areas and
fissuring with irregular
borders are observed
Fig. 1.72 Juvenile plantar

dermatosis: Shiny
areas of lichenification are
seen in bilateral plantar
metatarsal regions of
the feet
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9. Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;12:1109–22.
10. Rodríguez BA. Prurigo nodular: conceptos básicos. Revista Médica de Costa Rica y
Centroamerica. 2016;618:157–9.
11. Eichenfield LF, et al. Guidelines of care for the management of atopic dermatitis: section 1.
Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70:338–51.
12. Eczema BJJ. Lichenification, Prurigo and Erythroderma: asteatotic eczema. In: En Burns T,
Wiley-Blackwell; 2010. p. 23.6
13. Wolff K, Johnson RA. Trastornos de la piel y las mucosas: dermatitis aesteatótica. In: En
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14. Cohen DE, De Souza A. Irritant contact dermatitis. In: En Bologna JL, Jorizzo JL, Rapini RP,
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Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of dermatology, vol. 1. 8th ed.
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16. Reider N, Fritsch PO. Other eczematous eruptions. In: En Bologna JL, Jorizzo JL, Rapini RP,
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17. Wolff K, Johnson RA. Trastornos de la piel y las mucosas: eccema nummular. In: En Fitzpatrick
Atlas en Color y Sinopsis de Dermatología Clínica. Sexta edición, editorial panamericana;
2010. p. 46.
18. Eczema BJJ. Lichenification, Prurigo and Erythroderma: Seborrheic dermatitis. In: En Burns
T, Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of dermatology, vol 1. 8th ed.
19. Du Vivier A. Eczema: Adult seborrheic dermatitis. In: En Du Vivier A, editors, Atlas of clinical
dermatology,4th ed; 2013. p. 52.
20. Plewig G, Jansen T. Seborrheic dermatitis. In: En Wolff K, Goldsmith L, Katz S, Gilchrest B,
Paller A, Leffell D, editors. Fitzpatrick’s Dermatology in general medicine, 7th ed. McGraw-
Hill; 2010. p. 219–223.
21. Reider N, Fritsch PO. Other eczematous eruptions: seborrheic dermatitis. In: En Bolognia JL,
Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2. London: Mosby; 2010. p. 219–21.
22. Doshi DN, Kimball AB. Vesicular palmoplantar Eczema. In: En Wolff K, Goldsmith L, Katz
S, Gilchrest B, Paller A, Leffell D, editors. Fitzpatrick’s Dermatology in general medicine, 7th
ed. McGraw-Hill; 2010. p. 162–5.
23. Berth-Jones J. Eczema, Lichenification, Prurigo and Erythroderma: pompholyx. In: En Burns
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24. Du Vivier A. Eczema: pompholyx Wdyshidrotic eczema. In: En Du Vivier A, editors, Atlas of
clinical dermatology, 4th ed; 2013. p. 56.
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skin pathology, 4th ed. Churchill-Livingstone; 2016. p. 126.
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Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D, editors. Fitzpatrick’s Dermatology in
general medicine, 7th ed. McGraw-Hill; 2010. p. 152.
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Revisión de la literatura a propósito de un caso. Rev Chil Infectol (online). 2009;26:356–9.
31. Reider N, Fritsch PO. Other eczematous eruptions: infective dermatitis. In: En Bolognia JL,
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Dermatol. 2014;22:67–73.
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logic, and immunologic features of human T lymphotrophic virus type I-associated infective
dermatitis in children. Arch Dermatol. 1998;134:439–44.
34. Du Vivier A. Skin manifestations of disordered circulation: gravitational/stasis eczema and
ulceration. In: En Du Vivier A, editors, Atlas of clinical dermatology, 4th ed; 2013. p. 581.
35. Eczema BJJ. Lichenification, Prurigo and Erythroderma: venous eczema. In: En Burns T,
36. Du Vivier A. Eczema: Lichen simplex. In: En Du Vivier A, editors, Atlas of clinical dermatol-
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Wiley-Blackwell; 2010. p. 23.39–40.
38. Accioly-Filho LW, Nogueira A, Ramos-e-Silva M. Prurigo nodularis of Hyde: an update. J Eur
Acad Dermatol Venereol. 2000;14:75–82.
39. Weigelt N, Metze D, Ständer S. Prurigo nodularis: systematic analysis of 58 histological crite-
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40. Reider N, Fritsch PO. Other Eczematous Eruption: Juvenile plantar dermatosis. In: En Bolognia
JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 1. London: Mosby; 2010. p. 228–9.
Chapter 2
Dermatoses: Psoriasis
In this group of dermatological diseases are all entities that present clinically with
papules or plaques due to erythema, desquamation, and lichenification. One of the
representative entities of this group is psoriasis. There are different presentations of
this same entity grouped as follows:
A. Plaque or vulgar psoriasis
B. Guttate psoriasis
C. Pustular psoriasis
(a) Localized
(i) Palmoplantar pustulosis
(ii) Acrodermatitis continua of Hallopeau
(b) Generalized
(i) Generalized acute pustular (von Zumbusch)
(ii) Pustular annular
D. Inverse psoriasis
E. Psoriasis of the scalp
F. Psoriasis of the genitals
G. Erythrodermic psoriasis
H. Nail psoriasis
I. Psoriatic arthropathy1
J. Psoriasis associated with HIV1
1
Diseases not documented in this atlas.

https://doi.org/10.1007/978-3-030-84107-2_2
54 2 Papulosquamous and Eczematous Dermatoses: Psoriasis
Psoriasis
• Definition: Psoriasis is a common chronic inflammatory disease that affects 2%

of the population [1]. The origin is unknown, but it is suggested that there is a
dominant genetic transmission in most cases with variable penetrance. Psoriasis
has a chronic and fluctuating disease progression characterized by exacerbations
and remissions that are emotionally and physically debilitating for the patient [2].
• Pathogenesis: It is considered a hyperproliferative and autoimmune disorder as a
result of the activation of mature T cells which secrete cytokines that induce
vascular changes and modification in keratinocytes as well as an increase in pro-
liferation and a decrease in cell maturation [3]. Psoriasis is a multifactorial dis-
ease with intrinsic and extrinsic factors that trigger the disease. The role of
genetic susceptibility is the main intrinsic factor associated with psoriasis. This
observation is supported by different genomic studies that associate HLA-Cw6
with the locus of susceptibility for psoriasis 1 (PSORS1) as well as different
specific mutations in the interleukins (such as IL-17, IL-23, and IL-12, among
others) that mediate the inflammatory process [3, 4]. Among the extrinsic factors
are local trauma (given by Koebner phenomenon) (Figs. 2.1 and 2.2) which can
trigger psoriasis lesions, exposure to certain medications (beta-blockers, lithium,
antimalarials), and infections (HIV and streptococcal pharyngitis) [4].
• Clinical presentation: Psoriasis can present with a wide clinical spectrum, and
different variants can coexist in the same individual [5]. However, all lesions
share three key clinical features: erythema, thickening, and scales.
–– Plaque or vulgar psoriasis: Plaque psoriasis is the most common clinical
form of psoriasis characterized by the presence of erythematous plaques with
whitish scales and regular borders distributed symmetrically. The degree of
skin involvement varies from limited to extensive injuries. Frequently involved
sites are the scalp, elbows, knees, presacral area, as well as hands and feet [1]
(Figs. 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 2.10, 2.11, and 2.12).
Fig. 2.1 Koebner

phenomenon: Patient with
scaly erythematous plaques
with irregular edges
slightly infiltrated in the
nostrils secondary to local
trauma on blowing.
Psoriasis lesions can
appear at sites of repetitive
trauma
Psoriasis 55
Fig. 2.2 Koebner

phenomenon: Patient who,
after trauma to the knee,
presents an erythematous
plaque with a silver crust
on its surface and an
infiltrated base with regular
edges compatible with
vulgar psoriasis
Fig. 2.3 Psoriasis:

Slightly infiltrated
thick silver scale involving
the hemithorax and left
flank
Fig. 2.4 Plaque or vulgar

psoriasis: In the abdomen,
plaques with well-defined
regular edges and thick
silver scales are observed
on their surface. Some
hemorrhagic crusts are
observed secondary to the
detachment of the
superficial thick scale due
to the formation of
punctiform bleeding
(Auspitz sign)
Fig. 2.5 Plaque psoriasis:

Erythematous and
infiltrated plaques covered
with thick white scales
with well-defined regular
edges are observed in the
lower extremities involving
the anterior aspect of the
thighs, knees, and legs
–– Guttate psoriasis: This form of psoriasis occurs suddenly with multiple,

slightly scaly erythematous plaques that in some cases resemble rashes and
tends to resolve spontaneously. This entity occurs in young adults after a pha-
ryngeal strep infection. Rarely, (less than 2%) chronic plaque psoriasis can
progress [6] (Figs. 2.13 and 2.14).
–– Inverse psoriasis: Unlike classic vulgar psoriasis that affects extensor areas
such as the knees and elbows, inverse psoriasis presents as slightly scaly ery-
thematous plaques on flexor and crease surfaces such as the perineal, interglu-
teal, intermammary, inframammary, axillary, and inguinal areas [2–5]
(Figs. 2.15, 2.16, and 2.17).
–– Pustular psoriasis: There are different types of pustular psoriasis (Fig. 2.18),
among which are the generalized variant or von Zumbusch type, annular pus-
tular psoriasis, and impetigo herpetiformis. Within the group of localized
pustular psoriasis are acrodermatitis continua of Hallopeau and palmoplantar
Psoriasis 57

In the back and lumbar
region, erythematous and
infiltrated plaques with
silvery whitish scales and
are observed

Erythematous plaques with
silver scales and well-
defined regular edges are
observed on the posterior
aspect of the forearms
psoriasis. However, the presence of SAPHO syndrome, which corresponds to

the acronym for synovitis, acne, pustulosis, hyperostosis, and osteitis, has
been described as a complication of pustular psoriasis in children [1–3].
• Generalized von Zumbusch-type pustular psoriasis: Generalized pustular
psoriasis is a rare and acute clinical variant of psoriasis characterized by
the presence of multiple sterile pustules associated with systemic symp-
toms such as fever, myalgia, nausea, leukocytosis, and painful erythema-
tous skin [7] (Fig. 2.19).

Comprising 70% of the
body surface, erythematous
plaques covered with silver
scale with infiltrated
• Annular pustular psoriasis: A rare clinical variant of psoriasis character-

ized by the presence of pustules grouped in an annular or circinate form
and may be the beginning of a generalized pustular psoriasis [1] (Figs. 2.20
and 2.21).
• Acrodermatitis continua of Hallopeau (ACH): A rare manifestation of
psoriasis, usually recurrent, affecting the fingers or toes [8, 9]. Clinically,
it is characterized by the presence of sterile pustules followed by desqua-
mation and crusting on the distal part of the fingers and sometimes of the
feet, forming lakes of pus that, when broken, leave a shiny erythematous
skin in which new pustules appear [10]. The pustules can also compromise
the nail bed, generating incapacitating lesions caused by atrophy, onycho-
dystrophy, osteolysis, and anonychia [11] (Figs. 2.22 and 2.23).
• Palmoplantar psoriasis: Also called Palmoplantar pustulosis (PPP) of
palms and soles, it is characterized by the presence of sterile pustules in the
palmoplantar areas (Fig. 2.24) that can be accompanied by erythematous
Psoriasis 59

Involvement of extensor
areas of the knees, thighs,
and legs in a male patient
with plaque psoriasis
and scaly plaques (Figs. 2.25, 2.26, 2.27, 2.28, 2.29, 2.30, and 2.31). The
disease course is chronic and localized in distribution, and in some cases,
it may be associated with auto-inflammatory syndromes such as SAPHO
(synovitis, acne, pustulosis, hyperostosis, and osteitis) [5].
–– Nail psoriasis: Nail involvement by psoriasis is frequent with a prevalence
ranging between 10% and 78%. Psoriasis can affect the nail bed or matrix
with different clinical manifestations depending on the anatomical structure
involved [12]. Nail involvement by psoriasis is associated with an increased
risk of psoriatic arthropathy. When the nail matrix is compromised
by foci of
parakeratosis, alterations are observed in the nail lamina as “pits” or cavities.
The presence of leukonychia (whitish coloration of the nail lamina) occurs
due to compromise of the middle portion of the nail matrix (Figs. 2.32, 2.33,
2.34, and 2.35).
Changes in the nail bed due to psoriasis present clinically as “oil drop spots”
due to leukocyte exocytosis in this area. Additionally, splinter hemorrhages
and subnail hyperkeratosis with onycholysis (detachment of the nail lamina)
can be observed secondary to parakeratosis of the distal end of the nail bed [5,
7, 8] (Figs. 2.32, 2.33, 2.34, and 2.35).
Fig. 2.10 Plaque

psoriasis: Middle-aged
man who, on elbows and
extending to the arm and
forearm, presents
erythematous plaques
covered with thick silver
scale with regular
well-defined edges
–– Psoriatic erythroderma: Psoriatic erythroderma represents the most severe

form of psoriasis characterized by a significant inflammatory state of the skin
with erythema accompanied or not with exfoliation of more than 90% of the
body surface. There are different etiologies of erythroderma with psoriasis
being the cause in 23% and with a prevalence of 1–2.2% in patients with pso-
riasis [13]. Erythroderma, independent of its etiology, clinically manifests as
intense erythema, edema, and superficial desquamation, which can be accom-
panied by hair loss, nail dystrophy, and pruritus. Whatever the cause of eryth-
roderma, these patients can present severe systemic changes that can trigger a
skin failure syndrome with a risk of mortality (Figs. 2.36, 2.37, and 2.38).
Psoriasis 61
Fig. 2.11 Plaque

psoriasis: Erythematous
plaques covered by thick
whitish scale with
are seen in the elbow
extensor area
Fig. 2.12 Plaque

plaque with thick silver
scale on its surface with
is observed in the
periumbilical region
Fig. 2.13 Guttate

psoriasis: Compromising
the abdomen, erythematous
plaques with borders
smaller than 1 cm are
observed with silver scales
on their surface
Fig. 2.14 Guttate

psoriasis: On the lateral
aspect of the right arm and
upper trunk, erythematous
plaques are observed with
scales on their surface that
leave residual hypochromic
macules
Psoriasis 63
Fig. 2.15 Inverse

psoriasis: Patient with
slightly scaly erythematous
plaques in the intergluteal
fold. Note the presence of
vulgar psoriasis plaques on
the buttocks
Fig. 2.16 Inverse

psoriasis: Elderly female
with slightly scaly shiny
erythematous plaques in
the left armpit
Fig. 2.17 Inverse

psoriasis: Comprising the
folds, erythematous and
infiltrated plaques with
regular borders are
observed in a patient with
inverse psoriasis
Fig. 2.18 Pustular

psoriasis: Multiple
pustules are observed on
the neck of a middle-aged
woman, some of which
coalesce to form lakes of
pus that, upon drying,
leave erythematous scaly
plaques

pustular psoriasis:
Compromising the thorax,
abdomen, neck, and
forearms, multiple pustules
are observed, which
converge to form
Fig. 2.20 Annular

psoriasis: Multiple
erythematous papules can
be seen on the back, neck,
and back of the arms,
converging to form annular
scaly plaques and a
circinate border.
Histological findings
confirm psoriasis
Psoriasis 65
Fig. 2.21 Annular

pustular psoriasis:
Middle-aged woman who
presents with pustules that
converge annularly and
some circinate on an
erythematous macular base
Fig. 2.22 Acrodermatitis

continua of Hallopeau
(ACH): Chronic
desiccation of the pustules
in a patient with ACH can
lead to the formation of
crusted tumor-like lesions
in the nail bed
Fig. 2.23 Acrodermatitis

continua of Hallopeau
(ACH): Anonychia of the
third finger of the right
hand secondary to damage
to the nail bed by the
drying of pustules in a
patient with ACH
Fig. 2.24 Localized

palmoplantar pustular
psoriasis: Isolated pustules
on an erythematous plaque
are seen on the soles and
internal lateral aspect of
the right foot. The pustules
resolve leaving a scaly
collarette.
Histopathological findings
confirm pustular psoriasis
There are two clinical forms of psoriatic erythroderma: acute and subacute-
chronic presentation [13]. The first, also called unstable psoriasis, occurs de
novo in patients with no previous medical history of psoriasis or in patients
with plaque psoriasis as a consequence of exposure to a drug or infection. The
subacute-chronic presentation is characterized by a progressive worsening of
a more or less stable plaque psoriasis in patients who have not received treat-
ment. Clinically, psoriasis plaques are observed, which coalesce to form more
extensive plaques with some areas of healthy skin [14].
Psoriasis 67
Fig. 2.25 Plantar

psoriasis: Patient with
fissured and keratotic
histopathological findings
compatible with plantar
psoriasis
Fig. 2.26 Plantar

psoriasis: On the plantar
region with involvement of
the lateral aspect of the left
foot, a keratotic
well-defined and regular
borders is observed with
compatible with psoriasis
• Scalp psoriasis: Scalp involvement is the most frequent site, affecting 79% of
psoriasis patients. The lesions present as erythematous plaques, slightly indu-
rated and scaly (Figs. 2.39, 2.40, 2.41, and 2.42). Patients refer to itching and
desquamation as the most frequent symptoms. In many of the cases, the lesions
are nearly indistinguishable from severe seborrheic dermatitis, and both condi-
tions can even occur in the same patient [13].
Fig. 2.27 Plantar

psoriasis: Compromising
bilateral plantar aspects of
the feet, fissured scaly
observed
Fig. 2.28 Plantar

psoriasis: On the middle
third of the bilateral plantar
aspects of the feet, scaly
observed with additional
perilesional satellite
plaques
Psoriasis 69
Fig. 2.29 Palmoplantar

plaques with regular and
well-defined borders along
with additional scale and
fissured areas that involved
the palmar and plantar
regions, compatible with
psoriasis
• Genital psoriasis: Skin involvement of the genital area by psoriasis is rare and
occurs in only 2–5% of patients with psoriasis. This compromise may be associ-
ated with reverse psoriasis lesions (Fig. 2.43). Clinically they present as regular-
bordered erythematous plaques with very little desquamation limited to
keratinized areas [15].
• Psoriatic arthropathy: Joint compromise due to psoriasis occurs in 30% of
patients. Skin lesions precede the onset of joint involvement by up to 10 years.
Clinically, it presents as a heterogeneous arthritis with asymmetric oligoarthritis,
dactylitis, and enthesitis. In 2006, the psoriatic arthritis classification group pro-
posed CASPAR criteria for the diagnosis of the disease, which include a family
or personal history of psoriasis, nail dystrophy secondary to psoriasis, rheuma-
toid negative factor, dactylitis, and the presence of new formation of juxta-
articular bone evidenced on radiographs [16].
Fig. 2.30 Palmoplantar

psoriasis: On bilateral
palmar and plantar regions
of the hands and feet,
erythematous and scaly
borders and fissured areas
are observed
• Diagnosis: The diagnosis is often clinical but can be confirmed with the histo-
pathological findings. Clinically, it is typical to observe pinpoint bleeding after
detachment of the whitish scales from the plaques (Auspitz sign) [7]. Classically,
pathological examination shows psoriatic hyperplasia (regular acanthosis with
uniform elongation of the dermal ridges) with confluent parakeratosis, neutro-
phils in the stratum corneum (Munro microabscesses), and hypogranulosis.
Dilated tortuous vessels with papillary edema and a mixed neutrophilic mono-
nuclear infiltrate are observed in the dermis. In pustular psoriasis, the initial his-
topathological findings involve the presence of subcorneal neutrophilic pustules
with a moderate lymphoplasmacytic dermal infiltrate, and in chronic lesions on
biopsy of the nail matrix, moderate acanthosis with exocytosis of neutrophils and
lymphocytes with spongiosis is common [17] (Figs. 2.44 and 2.45).
Psoriasis 71
Fig. 2.31 Plantar

psoriasis: Patient with an
thick scales and irregular
borders on the heel
• Differential diagnosis: Guttate psoriasis should be distinguished from chronic

lichenoid pityriasis, viral rashes, secondary syphilis, and disseminated cutaneous
histoplasmosis. Plaque psoriasis can be confused with seborrheic dermatitis
when located on the scalp, tinea cruris, or candidal intertrigo if located on the
folds and with contact dermatitis when lesions on the hands are observed. Other
entities that clinically share characteristics with psoriasis are hypertrophic lichen
planus, hyperkeratotic hand eczema, pityriasis rubra pilaris, Mibelli’s porokera-
Fig. 2.32 Nail psoriasis:

Trachyonychia (sandpaper
appearance) with
onycholysis of the nail
lamina in a patient with
nail psoriasis

Patient with subnail
hyperkeratosis and oil drop
spots on the fingernail
plate
Psoriasis 73
Fig. 2.34 Psoriatic

onycholysis: Distal
detachment of the nail
lamina, oil drop spots, and
subnail hyperkeratosis in a
patient with nail psoriasis

Distal onycholysis with
trachyonychia (sandpaper
appearance) of the nail
lamina in a patient with
nail psoriasis
Fig. 2.36 Psoriatic

erythroderma: Comprising
more than 90% of the body
surface, erythema and
desquamation are observed
with histopathological
findings compatible with
erythroderma due to
psoriasis
Fig. 2.37 Psoriatic

erythroderma: Patient with
more than 90% of body
surface with
compatible with psoriasis
Fig. 2.38 Psoriatic

erythroderma: Elderly
adult patient with
involvement of the entire
body surface with
erythema and scaling with
some lichenified areas
tosis, Bowen’s disease, extramammary Paget’s disease, and penile erythroplasia.

In annular lesions, it must be distinguished from figurate erythemas such as
centrifugal annular erythema and migratory necrolytic erythema. Pustular pso-
riasis should be differentiated from other entities with pustules such as subcorneal
pustular dermatosis, IgA pemphigus, transient neonatal pustular melanosis,
acute generalized exanthematous pustulosis (AGEP), and childhood
acropustulosis.
Psoriasis 75
Fig. 2.39 Psoriasis of the

scalp: Slightly
a silvery scale on their
surface that involves the
scalp with extension to the
skin of the frontal region

scalp: Adult patient with
irregular edges and thick
silver scales that extend to
the forehead skin

scalp: Adult patient with
covered with silver scales
that compromise the scalp
with extension to the
retroauricular region

scalp: In the parietal and
involving the scalp, an
erythematous plaque
covered with whitish scale
is observed in a patient
with psoriasis. Note that
psoriasis lesions are not
associated with alopecic
areas
Psoriasis 77
Fig. 2.43 Genital

psoriasis associated with
reverse psoriasis:
Comprising the pubis,
scrotum, foreskin, and
inner thighs, brightly
infiltrated erythematous
regular borders are
psoriasis
Fig. 2.44 Acrodermatitis continua of Hallopeau (ACH): 40× skin biopsy with evidence of psoria-
siform hyperplasia and significant telangiectasias in superficial and deep dermis with subepithelial
lymphoplasmacytic infiltrate
References 79
Fig. 2.45 Acrodermatitis continua of Hallopeau (ACH): 80× skin biopsy with evidence of psoria-
siform hyperplasia with numerous clusters of neutrophils in the epidermis, stromal telangiectasias,
and lymphoplasmacytic infiltrate in the superficial dermis
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10. Iijima S, Okazaki Y, Watanabe S, Maruyama Y. Case of acrodermatitis continua of Hallopeau
following psoriasis with atypical clinical presentation. J Dermatol. 2014;41:1006–8.
11. Wolff K, Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D. Pustular eruptions of palms and
soles: acrodermatitis continua (Hallopeau). Fitzpatrick’s dermatology in general medicine. 7th
ed. USA: McGraw-Hill; 2008. p. p217–8.
12. Sánchez-Regaña M y Umbert P. Aspectos diagnósticos y terapéuticos de la psoriasis ungueal.
Actas Dermosiliogr. 2008;99:34–43.
13. Johnson MA, Armstrong AW. Clinical and histologic diagnostic guidelines for psoriasis: a
critical review. Clin Rev Allergy Immunol. 2013;44:166–72.
14. Ferrándiz C, Carrascosa JM, Bielsa I. Eritrodermia psoriásica. Piel. 2011;26:18–24.
15. Meeuwis KA, de Hullu JA, Massuger LF, van de Kerkhof PC, van Rossum MM. Genital
psoriasis: a systematic literature review on this hidden skin disease. Acta Derm Venereol.
2011;91:5–11.
16. Durham LE, Taams LS, Kirkham BW. Psoriatic arthritis. Br J Hosp Med (Lond).
2016;77:C102–8.
17. Patterson JW. The psoriasiform reaction pattern. In: Patterson JW, editor. Weedon’s skin
pathology. 4th ed. Churchill-Livingstone; 2016. p. 81.
Chapter 3
Dermatoses: Lichen
In this group of dermatological diseases are entities that present clinically with pap-
ules or plaques with associated erythema, peeling, and lichenification. Within this
group are lichen and lichenoid reactions grouped as follows:
A. Lichen planus
(a) Lichen planopilaris
(b) Oral lichen planus
(c) Actinic lichen planus
(d) Lichen planus pigmentosus
(e) Acute exanthematous lichen
(f) Inverse lichen planus
(g) Genital lichen planus
(h) Hypertrophic lichen planus
(i) Bullous or lichen planus pemphigoides
(j) Annular lichen planus
(k) Linear lichen planus
(l) Nail lichen planus
(m) Ulcerative lichen planus
B. Lichenoid drug eruption
C. Fixed pigmented erythema
D. Lichen nitidus
E. Lichen striatus
F. Erythema dyschromicum perstans
G. Chronic lichenoid keratosis

https://doi.org/10.1007/978-3-030-84107-2_3
82 3 Papulosquamous and Eczematous Dermatoses: Lichen
Lichen Planus
• Definition: An idiopathic inflammatory disease that affects the skin, mucosa, and
adnexa. It is also known as red lichen planus [1].
• Pathogenesis: Lichen planus is a T-cell-mediated autoimmune disease causing
the destruction of keratinocytes in the basal layer in response to abnormal expres-
sion of autoantigens. There is evidence that viruses (hepatitis C, herpes 6 and 7),
medications (e.g., nonsteroidal anti-inflammatory drugs), vaccines, bacteria, and
contact allergens are precipitating factors for lichen planus [1].
• Clinical presentation: Classically, it appears as pink papules that become viola-
ceous with a polygonal configuration that coalesce to form plaques that are asso-
ciated with pruritus [2] (Fig. 3.1). Some of the lesions may display a fine whitish
network on the surface called “Wickham striae” or small gray-white spots that
correspond to focal hypergranulosis of the epidermis [1] (Figs. 3.2 and 3.3). Like
other categories of inflammatory dermatoses such as psoriasis and vitiligo,
patients with lichen planus may experience the Koebner phenomenon (an iso-
morphic response) where the lesion develops after local trauma [1] (Fig. 3.4).
Lesions may be associated with residual post-inflammatory hyperpigmentation
(Fig. 3.5).
• Lichen planus lesions can develop anywhere on the body with the possibility of
classifying in different clinical subtypes according to the distribution of the
lesions, along with their morphological features (Fig. 3.6). Within these clinical
subtypes, we can find:
–– Lichen planopilaris: It is considered a follicular variant of lichen planus in
which three clinical variants are distinguished: classic lichen planopilaris,
frontal fibrosing alopecia (FFA), and Graham-Little-Piccardi-Lasseur syn-
drome [3]. Clinically, lichen planopilaris presents as follicular keratotic pap-
ules that clump together forming plaques on the scalp but can also involve
Fig. 3.1 Lichen planus:

Violaceous papules and
regular edges are seen on
the anterior wrists
Lichen Planus 83

Violaceous papules that
coalesce forming
irregularly edged plaques
with associated Wickham
striae (white-gray striae)
on their surface

Violaceous plaques with
Wickham striae (whitish
streaks) on their surfaces
other hairy areas such as the eyebrows and armpits [4]. The local inflamma-
tory process produces scarring alopecia and, in the case of frontal fibrosing
alopecia, a loss of the hairline which extends posteriorly. In Graham-Little-
Piccardi-Lasseur syndrome, there is alopecia due to lichen planopilaris on the
scalp, eyebrows, armpits, and pubis associated with follicular hyperkeratosis
[5] (Figs. 3.7, 3.8, 3.9, and 3.10).
–– Oral lichen planus: In the oral cavity, lichen planus has a different clinical
manifestation characterized by white-grayish papules and plaques that are

Situated on the dorsum of
the hand and distal third of
the forearm, numerous
linear papules and
violaceous plaques are
observed at the site of
previous trauma (Koebner
phenomenon)

Multiple subtly raised
violaceous papules with
whitish streaks on their
surface. Note the presence
of residual brownish-
violaceous macules
(post-inflammatory
hyperpigmentation)
Fig. 3.6 Lichen planus: A

violaceous plaque with
well-defined regular
keratotic edges is observed
in the first interdigital
space of the hand
Lichen Planus 85
Fig. 3.7 Lichen

planopilaris: Frontal and
temporal alopecic area
with loss of the hairline in
a patient with frontal
fibrosing alopecia-type
lichen planopilaris
Fig. 3.8 Lichen

planopilaris: Alopecic
areas on the forehead and
bitemporal and brow
regions with loss of some
follicular ostium
l inear, reticular, or annular [6]. The lesions are generally asymptomatic, bilat-
eral, and symmetrical with distribution frequently in the oral mucosa, tongue,
lips, and gingival mucosa [5] (Figs. 3.11, 3.12, 3.13, 3.14, 3.15, and 3.16).
These lesions can appear before skin lesions [5].
Fig. 3.9 Lichen

cicatricial areas are
observed on bilateral
temporal regions in a
patient with a long-
standing history of lichen
planopilaris
Fig. 3.10 Follicular lichen

planus: Multiple follicular
violaceous papules are
observed on brown-
violaceous macules with
irregular edges
–– Actinic lichen planus: This variant occurs in photo-exposed areas in the form
of annular-shaped erythematous-brownish plaques [7] (Figs. 3.17 and 3.18).
In some cases, hyperpigmented plaques with a melasma-like appearance can
be observed [6] (Fig. 3.19). This form of lichen planus respects the mucosa [6].
–– Lichen planus pigmentosus: This is a rare variant of lichen planus that pres-
ents as brownish or grayish-brown macules and plaques in areas frequently
exposed to the face and neck [8] (Figs. 3.20 and 3.21).
–– Acute exanthematous lichen planus: Given the wide and rapidly disseminat-
ing distribution of classic lichen planus lesions, this variant is the eruptive or
exanthematous form of lichen [1] (Figs. 3.22 and 3.23). It mainly affects the
trunk, the anterior part of the wrists, and the dorsum of the feet with a self-
limiting course that leaves residual hyperpigmented macules [1] (Fig. 3.24).
Lichen Planus 87
Fig. 3.11 Oral lichen

planus: Reticulated whitish
plaques on the jugal
mucosa

planus: A whitish
reticulated plaque is
observed on the left jugal
mucosa

planus: Multiple white-
observed which coalesce to
form a large plaque that
involves the ventral aspect
of the tongue

planus: Violaceous plaques
with irregular edges and
superficial erosion are
observed on the ventral
aspect of the tongue and
free edge
Lichen Planus 89
Fig. 3.15 Lichen planus

on mucosa: A slightly
plaque eroded at its center
is observed on the lower lip

on mucosa: An
plaque with poorly defined
irregular edges, compatible
with lichen planus, is seen
on the lower lip
Fig. 3.17 Actinic lichen

with well-defined irregular
edges on the temporal and
frontal region

planus: Young adult patient
with multiple violaceous
regular edges on the
forehead

planus: On the malar
region and with extension
to the forehead, dark
violaceous macules with
irregular edges are
observed
Lichen Planus 91

pigmentosus: Violaceous
macules with well-defined
regular edges that comprise
the malar region, nasal
dorsum, and upper lip skin
are observed

pigmentosus: Violaceous
macules are observed on
the back of the hands
Fig. 3.22 Acute eruptive

lichen planus: Violet
papules and plaques with
superficial whitish streaks
are observed on the
pretibial region
Fig. 3.23 Acute eruptive

lichen planus:
Erythematous-violaceous
papules and plaques
involving the upper
extremities and trunk

Violaceous plaques are
observed on the back,
some of which possess
follicular violaceous
papules that leave residual
hyperpigmented macules
Lichen Planus 93
Fig. 3.25 Inverse lichen

planus: Violaceous papules
that converge forming
plaques on the bilateral
axillary region
Fig. 3.26 Inverse lichen

planus: Some linear purple
plaques in the axillary
region
–– Inverse lichen planus: This clinical presentation typically affects the armpits,
groin, submammary region, and flexor surfaces of the extremities [9]
(Figs. 3.25 and 3.26). Lesions consist of erythematous or pigmented plaques
with poorly defined edges with occasional lichenified areas [8].
–– Genital lichen planus: In men, this variant presents as subtly raised papules
on the glans or coronal sulcus [10] (Figs. 3.27 and 3.28). Eroded plaques are
frequently found in women, which can sometimes compromise the oral
mucosa in addition to the genitals, hence classifying this condition as
“vulvovaginal-gingival syndrome” [1] (Fig. 3.29).
–– Hypertrophic lichen planus: Also known as verrucous lichen planus or hyper-
keratotic lichen planus, hypertrophic lichen planus presents as brown, grayish-
brown, or erythematous papules or plaques that affect the pretibial region and
less often the arms or trunk [8] (Figs. 3.30 and 3.31).
–– Bullous lichen planus or lichen planus pemphigoides: Clinically presents
with the formation of tense blisters prior to the evolution of more classic
lichen planus lesions with a wide distribution that favors the lower limbs [1,
8]. Bullous lichen planus shares histological and immunofluorescence find-
Fig. 3.27 Genital lichen

planus: White-violet
plaque with an irregular
and ulcerated edge that
compromises the foreskin
and the balano-preputial
junction, histologically
compatible with lichen
planus

planus: Violet papules with
whitish striae are seen on
the surface of the penile
shaft
Lichen Planus 95

with irregular edges that
compromise the genitalia
and perineal region
secondary to lichen planus
Fig. 3.30 Hypertrophic

lichen planus: On the
pretibial region, infiltrated
violaceous plaques with
edges are observed
ings with bullous pemphigoid, revealing extensive epidermal damage with an

intense lichenoid infiltrate [1].
–– Annular lichen planus (ALP): Although this variant is frequent in the mucosa,
it can also affect the trunk, extremities, and scrotum. It appears as annular
erythematous-violaceous plaques with centrifugal growth [8] (Figs. 3.32,
3.33, and 3.34).
–– Linear lichen planus: This variant is frequently found in children as violet flat
papules with usually a linear or zosteriform distribution that follows the lines
of Blaschko [8] (Figs. 3.35 and 3.36).
–– Nail lichen planus: It occurs in 10% of patients with lichen planus with clini-
cal features including thinning of the nail plate, longitudinal striae, onycho-
schizia, onychorrhexis, subungual hyperkeratosis, and pterygium [2]. Lesions
can be chronic and destroy the nail matrix with consequent anonychia [1]
(Figs. 3.37, 3.38, and 3.39).
–– Ulcerative lichen planus: This variant of lichen planus is typified by a singu-
lar or multiple erosions or ulcers situated habitually on the feet with regular
raised edges. Lesions tend to favor the interdigital spaces and frequently lead
to difficulties in patient ambulation [8].
Fig. 3.31 Hypertrophic

lichen planus: Multiple
violaceous hypertrophic
plates with well-defined
irregular edges are seen
Fig. 3.32 Annular lichen

planus: Slightly infiltrated
violaceous plaque in a
patient with
histopathological changes
compatible with lichen
planus

planus: On the back of the
proximal fourth phalanx,
annular violaceous plaques
with a depressed center are
observed, compatible with
lichen planus
Lichen Planus 97

planus: On the forehead,
nasal dorsum, and perioral
region, brown plaques are
contain an annular
configuration compatible
with lichen planus
Fig. 3.35 Linear lichen

that converge, forming a
horizontal linear plaque on
the lateral region of the
abdomen
Fig. 3.36 Linear lichen

planus: Multiple
distributed in a linear
manner
Fig. 3.37 Nail lichen

planus: On the nail lamina
and eponychium,
pterygium is observed that
extends to the lamina with
associated
onychodystrophy

planus: Onychodystrophy
with anonychia secondary
to nail lichen planus is
seen in toenails
Lichen Planus 99

planus: On the nail lamina
of the great toe of both
feet, onychodystrophy is
observed with isolated
violaceous papules on the
anterior aspect of the
metatarsals
Fig. 3.40 Palmar lichen

planus: Fissured
hyperkeratotic plaques
flattened erythematous
papules are seen on the
palmar aspects of the
hands. Note some of the
papules are distributed
linearly on the anterior
aspects of the wrists which
are compatible with classic
lichen planus
–– Palmoplantar lichen planus: This rare variant of lichen planus presents as

hyperkeratotic, erythematous, and pruritic plaques with well-defined edges,
most commonly involving the plantar surfaces of the feet followed by the
palmar surfaces of the hands. Plantar lesions usually affect the arch of the sole
of the foot [11] (Figs. 3.40, 3.41, 3.42, and 3.43).
–– Lichen planus-lupus overlap syndrome: The coexistence of lichen planus and
lupus is uncommon and rarely reported. This condition is diagnosed via the
combination of clinical, histological, and immunopathological characteristics
of both diseases in the same patient or the same lesion. Clinically, the lesions
resemble chronic cutaneous lupus erythematosus and are similar to discoid
lupus [1, 12] (Figs. 3.44, 3.45, and 3.46).

edges compatible with
lichen planus are seen in
the palmar region

planus: Some papules with
regular edges compatible
with lichen planus

edges are seen on the
palmar and wrist regions
Lichen Planus 101
Fig. 3.44 Lichen

planus-lupus overlap:
Adult patient with
erythematous plaques,
some with verrucous-
appearing keratoses with
well-defined irregular and
hyperpigmented edges that
leave residual hypochromic
areas
Fig. 3.45 Lichen

Older adult patient with a
edges and a hypochromic
center that involves the lips
in addition to affirmative
paraclinical criteria for
lupus erythematosus
• Diagnosis: The diagnosis is usually ascertained via a degree of clinical suspicion

that is supported by subsequent histopathological and laboratory findings.
Among the histological characteristics are an epidermal hyperplasia with com-
pact orthokeratosis and some foci of focal hypergranulosis [10]. Significant dam-
age to the basal layer of keratinocytes can be observed with some of them
necrotic either in an isolated fashion or in groups (colloid bodies or Civatte bod-
ies) [10] (Figs. 3.47 and 3.48). Likewise, an important inflammatory lympho-
cytic infiltrate can be observed at the dermoepidermal junction that can extend to
the acrosyringium or hair follicle, resembling a similar process to that of the
follicular variant of lichen planus [13].
• Differential diagnosis: Other inflammatory conditions that must be distinguished
from lichen planus are lupus erythematosus, lichen nitidus, lichen striatus, lichen
sclerosus et atrophicus, pityriasis rosea, erythema dyschromicum perstans, pso-
riasis, lichenoid reactions, and secondary syphilis [1, 2, 4].
Fig. 3.46 Lichen

Elderly patient with
violaceous plaques
containing hypochromic
centers with some keratotic
areas that comprise the
right ear helix
Lichenoid Drug Eruption
• Definition: The lichenoid drug eruption is considered a lichen planus-like derma-

titis secondary to the intake of certain drugs or contact with certain chemicals [4].
• Pathogenesis: There is a period of latency between exposure to the drug and the
development of lichenoid reactions that ranges from a few months to years [4].
The most frequently reported medications are gold salts, beta-blockers, antima-
larials, thiazide-type diuretics, furosemide, spironolactone, and penicillamine [4].
• Clinical presentation: Lichenoid drug eruptions affect both men and women
equally with an average age of presentation of 66 years [1]. It manifests as post-
inflammatory hyperpigmentation and alopecia, in which the lesions lack the clas-
sic Wickham striae [4]. The rash is generally symmetrical with involvement of
the trunk and the extremities, rarely involving the flexor areas as does classic
lichen planus. Distribution patterns have been described in areas exposed to the
Fixed Pigmented Erythema 103
Fig. 3.47 Lichen planus: H&E-stained skin biopsy with evidence of regular epidermal hyperpla-
sia with hyperkeratosis with foci of parakeratosis coupled with hypergranulosis with lymphocytic
band infiltrate in the superficial dermis
sun and in mucosa [4] (Figs. 3.49, 3.50, 3.51, 3.52, 3.53, 3.54, 3.55, 3.56,
and 3.57).
• Diagnosis: The diagnosis is suspected clinically and confirmed with the findings
on histopathology. Microscopy shows various degrees of plasma cell infiltration,
a deep eosinophilic infiltrate, and parakeratosis [1].
• Differential diagnosis: Other forms of lichen planus, lichenoid reactions in the
context of graft-versus-host disease, contact lichenoid reactions, photocontact
dermatitis, and post-inflammatory hyperpigmentation, among others, should be
ruled out [1, 4, 8, 10].
Fixed Pigmented Erythema
• Definition: Represents a localized toxicoderma, characterized by nummular or

bullous plaques on skin or mucous membranes, which always appear in the same
location following the re-exposure to the causal drug [14].
Fig. 3.48 Lichen planus: H&E-stained skin biopsy with epidermal hyperplasia and orthokeratosis
with some foci of parakeratosis with hypergranulosis and a lymphocytic infiltrate in the superfi-
cial dermis
Fig. 3.49 Lichenoid drug

eruption: Violaceous
plaques in a reticulated
pattern on the anterior and
lateral sides of the neck
with extension to the trunk
and chin
• Pathogenesis: It occurs as a delayed cell-mediated response 1–2 weeks after the

intake of the causative drug [15]. The lesions reappear within 24 hours after
repetitive exposure of the implicated drug. Related drugs include
trimethoprim-sulfamethoxazole, nonsteroidal anti-inflammatory drugs, tetracy-
clines, and pseudoephedrine [11].

eruption: Violaceous
plaques are observed on
the malar and chin regions,
converging to form a large
plaque. Note the
distribution in areas
exposed to the sun

eruption: Adult patient
with multiple grayish
macules with poorly
defined irregular edges in
the periocular and perioral
region

eruption: On the face and
neck of a young adult,
grayish macules with
poorly defined irregular
edges are observed

eruption: Female patient
with a large cross-linked
macula in the left malar
region compatible with a
lichenoid reaction

eruption: Elderly adult
female patient with
multiple grayish macules
that compromise the face
• Clinical presentation: It appears as one or more erythematous-edematous

plaques with well-defined regular edges and a clear violaceous center that can
blister [11]. Fixed pigmented erythema affects any part of the body, often favor-
ing the lips, face, hands, feet, and genitals. The lesions can disappear in a few
weeks and leave post-inflammatory hyperpigmentation. Plaques can be erythem-
atous, especially when the fixed pigmented erythema is caused by pseudoephed-
rine [11] (Figs. 3.58, 3.59, 3.60, 3.61, 3.62, and 3.63).
• Diagnosis: The causal relationship with the drug is crucial to make the diagnosis
in addition to the clinical presentation. Histopathology shows a superficial and
deep interstitial infiltrate as well as a perivascular infiltrate composed of lympho-
cytes, eosinophils, and some neutrophils [10, 11]. Similarly, necrotic keratino-
cytes can be seen in the epidermis [10] (Figs. 3.64 and 3.65).

eruption: Female patient
with multiple grayish
macules with irregular
edges on the malar region
• Differential diagnosis: When the lesions are multiple, it can be confused with
erythema multiforme or Steven-Johnson syndrome. Herpes simplex infection
should be ruled out in lesions that affect the genitals [11].
Lichen Nitidus
• Definition: It is a rare condition that shares histopathological characteristics with

idiopathic lichen planus [16].
• Pathogenesis: Its etiology is unknown, but there are immunophenotyping studies
that relate it to lichen planus despite the fact that several authors consider it as a
separate entity [12].
• Clinical presentation: Clinically, it appears as small euchromatic papules, some
donut-shaped and others more planar, which can last weeks to years [12]
Lichen Striatus 109
Fig. 3.56 Lichenoid

reaction: Older adult
patient with multiple
grayish macules with some
peripheral plaques on the
temporal and malar region
and posterolateral aspect of
the neck
(Figs. 3.66, 3.67, 3.68, 3.69, 3.70, 3.71, 3.72, 3.73, 3.74, 3.75, 3.76, 3.77,
and 3.78).
• Diagnosis: On histopathology, it is characteristic that the papule is made up of an
intense subdermal and contains a well-circumscribed infiltrate composed of lym-
phocytes and histiocytes with some giant Langhans cells [12].
• Differential diagnosis: In 25–30% of patients, lichen nitidus may be associated
with lichen planus. However, it must be differentiated from lichen scrofulosorum
and keratosis pilaris [12].
Lichen Striatus
• Definition: Lichen striatus belongs to the category of papulosquamous d ermatoses

with a linear distribution that in many cases follows the lines of Blaschko [17].
• Pathogenesis: The etiology is unknown; however, it is considered that there are
environmental, viral, or genetic factors that may be related to the disease. One of
the etiological hypotheses proposes a cell-mediated immune disorder that elimi-
Fig. 3.57 Vitiligo

lichenoid reaction:
Adolescent patient with
grayish macules that leave
a residual hypochromic
center on the forehead,
malar region, and left
nasofacial angle
nates mutant keratinocytes by following the migration pathways of cells in utero

(Blaschko lines) [13].
• Clinical presentation: Clinically, it appears as papules that converge in a linear
distribution that can extend from a few to several centimeters in length. It mainly
affects children from 5 to 15 years old, most frequently involving the trunk or
face but may also include the extremities [13] (Figs. 3.79 and 3.80).
• Diagnosis: The clinical findings are usually suggestive of the diagnosis, but in
some cases, histopathological confirmation is necessary, where the findings will
depend on the evolution of the lesion [14]. Spongiotic dermatitis has been docu-
mented to be more frequent than the lichenoid component associated with
necrotic keratinocyte band infiltrate at the dermoepidermal junction. Additionally,
granulomatous inflammation can be observed with a dense infiltrate around the
sweat glands and the acrosyringium, these findings being distinctive of lichen
planus [18].
Lichen Striatus 111
Fig. 3.58 Fixed pigmented

erythema: A violaceous
plaque containing a
circular erythematous halo
lateral malleolus

erythema: On the posterior
aspect of the forearm, a
violaceous macula with
is observed

erythema: A hyperpig
mented macula with
is observed at the right
suprascapular level in a
patient with a history of
fixed pigmented erythema

erythema: On the dorsal
lumbar area, there are
violaceous plaques with an
erythematous border
• Differential diagnosis: Differential diagnosis should be made with entities that

have a linear distribution such as inflammatory linear verrucous epidermal nevi
(ILVEN), linear lichen planus, linear psoriasis, and even viral warts [13].
Erythema Dyschromicum Perstans
• Definition: Also called ashy dermatosis, it was described by Ramírez in 1957 and
is included in lichenoid dermatoses [19].
• Pathogenesis: The etiology is unknown; it occurs mainly in Central and South
America. Its course is chronic and refractory to treatment [13]. Parasitic infec-
tions, chemicals such as ammonium nitrate and barium sulfate, and environmen-
Erythema Dyschromicum Perstans 113

erythema:An erythematous-
violaceous macula is
observed on the left axilla
of a patient with a fixed
drug eruption

erythema: A violaceous
macula with well-defined
regular edges
tal allergens are suggested to be potential causes of erythema dyschromicum

perstans.
• Clinical presentation: The condition is generally asymptomatic affecting chil-
dren and young adults [20]. In the acute phase of the disease, grayish macules
appear with an erythematous border that involves the trunk and extremities [13].
In the later stages, residual brownish-gray pigmentation is observed (Figs. 3.81,
3.82, 3.83, 3.84, 3.85, 3.86, 3.87, 3.88, and 3.89).
Fig. 3.64 Fixed pigmented erythema: 20× H&E-stained skin biopsy with lichenoid infiltrate asso-
ciated with basal dropsical degeneration, pigment incontinence (arrow), and Civatte bodies
Fig. 3.65 Fixed pigmented erythema: H&E-stained skin biopsy at 40× magnification shows vacu-
olar change or hydropic degeneration of the basement membrane (thick arrows) and the presence
of apoptotic keratinocytes or Civatte bodies (thin arrow)
Erythema Dyschromicum Perstans 115
Fig. 3.66 Lichen nitidus:

Brown papules that cluster
to form a stone-like plaque

Multiple keratotic papules,
some of which are
digitiform, grouped
together in a
hyperpigmented plaque

Multiple follicular
hypopigmented papules are
seen on the trunk and
abdomen
• Diagnosis: Although clinical findings are relevant, the histopathological findings

are also highly supportive in the diagnosis. At the inflammatory border, an epi-
dermis with hyperkeratosis with slight atrophy and vacuolar degeneration of
basal cells with some formation of cytoid bodies associated with pigment incon-
tinence in the dermis and perivascular infiltrate can be observed. Also, a dermal
lymphocytic lichenoid infiltrate in the superficial dermis can be found [14].
• Differential diagnosis: It should be distinguished from post-inflammatory hyper-
pigmentation and other lichenoid dermatitis such as lichen planus, lichen planus
pigmentosus, lichenoid reaction, graft-versus-host disease, and fixed drug erup-
tion [10].
Lichen Sclerosus et Atrophicus 117

Multiple follicular
euchromatic papules are
seen on the trunk
Lichen Sclerosus et Atrophicus
• Definition: It is a chronic inflammatory mucocutaneous disease that frequently

affects prepubertal and postmenopausal women [21].
• Pathogenesis: The etiology is unknown; however, it has been associated with
genetic factors, autoimmune mechanisms, infectious agents (Borrelia burgdor-
feri infection, HPV), and trauma [15].
• Clinical presentation: Clinically, it presents as silvery white plaques with atro-
phic or thickened areas of the skin with bruising or hemorrhages secondary to
repetitive scratching [16]. The white color and wrinkled appearance of the skin

Multiple follicular
observed on the suprapubic
and glans region
Fig. 3.71 Adult lichen

nitidus: Multiple
euchromatic and
erythematous follicular
papules are seen on the
forearm

A 5-year-old patient with
multiple follicular
euchromatic papules on
the back

Multiple follicular
euchromatic papules

Compromising the arm and
forearm, multiple follicular
observed in adults with
lichen nitidus

Multiple follicular
seen on the posterior
aspect of the forearm and
elbow

multiple euchromatic
follicular papules

Multiple erythematous and
grouped together on the
back of the foot

Multiple follicular
seen on the back
Fig. 3.79 Lichen striatus:

On the lateral and anterior
aspect of the left knee,
multiple pink papules are
observed that converge
forming a linearly
distributed plaque that
leaves residual achromic
macules
Fig. 3.80 Lichen striatus:

On the lateral aspect of the
knee with extension toward
the thigh, hypopigmented
papules are observed,
which converge forming a
linear distribution plate
that follows the lines of
Blaschko
Fig. 3.81 Erythema

dyschromicum perstans: A
brown macula with
edges is seen on the lateral
aspect of the shoulder
Fig. 3.82 Erythema

dyschromicum perstans:
On the back, there are
gray-brown macules with
edges
on the genitals is classic for this entity [16]. In chronic lesions, scarring can be
observed with resorption of the genital lips that erodes the clitoris and decrease
vaginal introitus [16]. Although it is rare in men, urethral narrowing can be found
in chronic injuries [22] (Figs. 3.90, 3.91, and 3.92).
• Diagnosis: The diagnosis is clinical, and the skin biopsy is reserved for those
cases that are difficult to differentiate from other conditions or those that require
additional microscopic study to rule out underlying malignancy. Histopathological
findings will depend on the time and location of the specimen collection [17]. In
the initial findings, vacuolization of the basement membrane can be identified
with occasional necrotic keratinocytes and a band lymphocytic infiltrate in the
superficial dermis. In the most stable lesions, epidermal atrophy with edema is
observed in the papillary dermis with sclerosis and hyalinization of the collagen
bands [23].
• Differential diagnosis: Within the differential diagnosis are psoriasis (sometimes
it may be associated), lichen planus, chronic simplex lichen, vitiligo, and mucous
membrane pemphigoid [17].
Fig. 3.83 Erythema

Gray macules with
irregular erythematous
borders are seen on the
anterior thorax and trunk
Fig. 3.84 Erythema

Comprising the arm,
forearm, and antecubital
fossa, grayish macules
with poorly defined
irregular edges are
observed
Fig. 3.85 Erythema

On the anterior side of the
neck, extending to the
anterior thorax, grayish
macules with poorly
defined irregular edges are
witnessed
Fig. 3.86 Erythema

Compromising the neck
and “V”-like distribution
of the neckline, grayish
macules with erythematous
edges are observed
Fig. 3.87 Erythema

Grayish macules with
edges are seen on the
forearm
Fig. 3.88 Erythema

Grayish macules with
well-defined regular and
erythematous borders are
observed on the
supraclavicular region
Fig. 3.89 Erythema

Grayish-violet macules
with a slightly
erythematous border are
seen on the arm and
forearm
Fig. 3.90 Lichen sclerosus

et atrophicus:
Compromising the labia
majora and labia minora of
the female genitalia, a
hypochromic
scleroatrophic plaque with
is observed

et atrophicus: In the
genital area of a middle-
aged woman,
scleroatrophic areas with
synechia of the labia
majora and minora are
observed

et atrophicus plus lichen
planus: Multiple
violaceous plaques, one
with a scleroatrophic
center
References
1. Shiohara T, Kano Y. Lichen planus and lichenoid dermatoses. In: Bolognia JL, Jorizzo JL,
Rapini RP, editors. Dermatology, vol. 1. London: Mosby; 2010. p. P183–93.
2. Rodríguez M, Carbajal P. Liquen plano: revisión de la literatura. Rev Cent Dermatol Pascua.
2006;15:203–7.
3. Baibergenova A, Donovan J. Lichen planopilaris: update on pathogenesis and treatment.
Skinmed. 2013;11:161–5.
4. Pittelkow MR, Daoud MS. Lichen planus. In: Wolff K, Goldsmith L, Katz S, Gilchrest B,
Paller A, Leffell D, editors. Fitzpatrick’s dermatology in general medicine. 7th ed. McGraw-
Hill; 2010. p. 244–53.
5. Fernández MI, et al. Síndrome de Graham-Little frente a liquen plano folicular. Actas
Dermosifiliogr. 2001;92:229–32.
References 129
6. Gupta S, Jawanda MK. Oral lichen planus: an update on etiology, pathogenesis, clinical pre-
sentation, diagnosis and management. Indian J Dermatol. 2015;60:222–9.
7. Salman SM, Kibbi AG, Zaynoun S. Actinic lichen planus. A clinicopathologic study of 16
patients. J Am Acad Dermatol. 1989;20:226–31.
8. Rieder E, Kaplan J, Kamino H, Sanchez M, Pomeranz MK. Lichen planus pigmentosus.
Dermatol Online J. 2013;19:20713.
9. Wagner G, Rose C, Sachse MM. Clinical variants of lichen planus. J Dtsch Dermatol Ges.
2013;11:309–19.
10. Zendell K. Genital lichen planus: update on diagnosis and treatment. Semin Cutan Med Surg.
2015;34:182–6.
11. Abreu Velez AM, Howard MS, Pereyo N. Palmar and plantar lichen planus: a case report and
review of the literature. An Bras Dermatol. 2015;90:175–7.
12. Demirci GT, Altunay IK, Sarıkaya S, Sakiz D. Lupus erythematosus and lichen planus over-
lap syndrome: a case report with a rapid response to topical corticosteroid therapy. Dermatol
Reports. 2011;25(3):e48.
13. Patterson JW. The lichenoid reaction pattern (‘interface dermatitis’): lichen planus. In:
Patterson JW, editor. Weedon’s skin pathology. 4th ed. Churchill-Livingstone; 2016. p. 39–40.
14. Núñez NMM, Rodas EAF. Generalized fixed drug eruption. Med Cutan Ibero Lat Am.
2014;42(1–3):54–6.
15. Revuz J, Valeyrie-Allanore L. Drug reactions: fixed drug eruption. In: Bolognia JL, Jorizzo JL,
Rapini RP, editors. Dermatology, vol. 2. London: Mosby; 2010. p. 345–7.
16. Breathmach SM. Lichen planus and lichenoid disorders: lichen nitidus. In: Burns T,
Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of dermatology, vol. 1. 8th ed.
17. Zhang Y, McNutt NS. Lichen striatus. Histological, immunohistochemical, and ultrastructural
study of 37 cases. J Cutan Pathol. 2001;28:65–71.
18. James WD, Berger TG, Elston DM. Lichen planus and related conditions: lichen striatus. In:
Andrews’ diseases of the skin. 4th ed. Elsevier; 2016. p. 220–1.
19. Zaynoun S, Rubeiz N, Kibbi AG. Ashy dermatoses - a critical review of the literature and a
proposed simplified clinical classification. Int J Dermatol. 2008;47:542–4.
20. Falabella R. Pigmentary disorders in Latin America. Dermatol Clin. 2007;25:419–30.
21. Heymann WR. Lichen sclerosus. J Am Acad Dermatol. 2007;56:683–4.
22. Murphy R. Lichen sclerosus. Dermatol Clin. 2010;28:707–15.
23. Barchino-Ortiz L, et al. Dermatosis inflamatorias vulvares. Actas Dermosifiliogr.
2012;103:260–75.
Chapter 4
Other Papular, Erythematous, and Scaly
Diseases
In this group of dermatological diseases are all the entities that present clinically
with papules or plaques usually secondary to erythema, desquamation, and licheni-
fication, where the pathophysiology is of inflammatory origin and cannot be classi-
fied in the previous groups. Among the most frequent diseases are:
A. Lichenoid pityriasis
(a) Acute lichenoid and varioliform pityriasis
(b) Chronic lichenoid pityriasis
(c) Leukomelanoderma
B. Pityriasis rubra pilaris
C. Pityriasis rosea
D. Pityriasis rotunda*
E. Axillary granular parakeratosis
Lichenoid Pityriasis
• Definition: A group of papular-erythematous scaly conditions of unknown etiol-

ogy that presents in children and young adults [1].
• Pathogenesis: Unknown. However, it has been suggested that it presents as a
hypersensitivity response to a bacterial, parasitic, or viral agent.
• Clinical presentation: There are three clinical presentations of the disease:
–– Pityriasis lichenoides et varioliformis acuta (PLEVA or Mucha-Habermann
disease): Presents as an acute eruption consisting of vesicles or erythematous
papules that become umbilicated and leave a central hemorrhagic crust. The
*
Pathologies not included in this atlas

https://doi.org/10.1007/978-3-030-84107-2_4
132 4 Other Papular, Erythematous, and Scaly Diseases
Fig. 4.1 Pityriasis

lichenoides et varioliformis
acuta: A 2-year-old patient
papules, some with a
central hemorrhagic crust
that compromise the trunk
lesions affect the trunk and the proximal region of limbs with a greater repre-
sentation in folds. The skin rash may be accompanied by systemic symptoms
[1, 2] (Fig. 4.1).
–– Pityriasis lichenoides chronica: Starts with an erythematous papule that dark-
ens over time and scales in layers secondary to friction via scraping without
leaving residual bleeding. Lesions affect the trunk and extremities, with little
involvement of the palms, soles, face, and scalp [1] (Figs. 4.2, 4.3, 4.4, 4.5,
4.6, 4.7, and 4.8).
–– Leukomelanoderma lichenoid pityriasis: Clinically presents as hypochromic
macules with minimal scaling component that involves the neck and upper
arms [1].
• Diagnosis: The diagnosis requires an adequate clinical-pathological correlation.
Histopathological findings of all three forms share certain characteristics and
depend on the stage of the disease. In acute lichenoid and varioliform pityriasis,
it is possible to find a superficial perivascular interface dermatitis associated with
Lichenoid Pityriasis 133
Fig. 4.2 Pityriasis

lichenoides chronica:
multiple plaques and
erythematous scaly papules
containing well-defined
irregular edges that involve
the trunk and upper
extremities
Fig. 4.3 Pityriasis

multiple papules and
erythematous and scaly
plaques on the lower limbs
parakeratosis with epidermal necrosis, erythrocyte extravasation, and lympho-

cytic vasculitis [2] (Figs. 4.9 and 4.10).
• Differential diagnosis: In the acute form of pityriasis lichenoides, the main dif-
ferential diagnoses include lymphomatoid papulosis, drug eruption, arthropod
reactions, small vessel vasculitis, and chicken pox. In the chronic form, the main
differential diagnoses include small plaque parapsoriasis, guttate psoriasis,
lichen planus in its exanthematous form, secondary syphilis, pityriasis rosea,
papular dermatitis, drug eruptions, and lymphomatoid papulosis [1, 2].
Fig. 4.4 Pityriasis

scaly erythematous plaques
on the eyelids,
histopathologically
compatible with chronic
lichenoid pityriasis
Fig. 4.5 Pityriasis

Patient with multiple
brownish-erythematous
plaques with a fine
superficial scale
Fig. 4.6 Pityriasis

Multiple erythematous and
hypochromic plaques with
fine superficial scales are
seen on the back
Lichenoid Pityriasis 135
Fig. 4.7 Pityriasis

Comprising the trunk and
upper extremities, multiple
scaly brown plaques with
irregular edges are
observed. The skin biopsy
confirms a chronic
lichenoid pityriasis
Fig. 4.8 Pityriasis

multiple brown and
superficial fine scale
Fig. 4.9 Pityriasis lichenoides chronica: 40× H&E-stained skin biopsy displaying irregular epi-
dermal hyperplasia and inflammatory infiltrate in the superficial dermis with extension to the der-
moepidermal junction. The stratum corneum contains some foci of parakeratosis
Pityriasis Rubra Pilaris
• Definition: Pityriasis rubra pilaris is a condition of unclear etiology initially

described in 1835. Today, it is considered a papular-erythematous desquamative
disease [3].
• Pathogenesis: Its cause is unknown; however, vitamin deficiency has been raised
as a possible related cause given the clinical response of the lesions with retinoid
treatment. Similarly, it has been related to autoimmune diseases and as an immu-
Pityriasis Rubra Pilaris 137
Fig. 4.10 Pityriasis lichenoides chronica: H&E-stained skin biopsy at higher magnification with
foci of vacuolar degeneration in the basement membrane, extravasation of red blood cells to the
epidermis, and parakeratosis in the stratum corneum
nological response to particular antigens when associated with infections such as

HIV and malignancies [3].
• Clinical presentation: There are different clinical variants that share a diagnostic
sign given by the presence of follicular hyperkeratosis on an erythematous base.
It presents with erythematous follicular papules and salmon squamous plaques
that coalesce while leaving patches of unaffected skin, which is a distinctive
feature of this disease [4]. Palmar involvement is typical, consisting of
erythematous-orange plaques that do not compromise the dorsum of the hands.
There are six clinical variants of the disease: pityriasis rubra pilaris classic adult
or type I (most frequent), type II or atypical of the adult, juvenile type III or clas-
sic, juvenile type IV or circumscribed, juvenile type V or atypical, and type VI or
associated with HIV [4] (Figs. 4.11, 4.12, 4.13, and 4.14).
Fig. 4.11 Pityriasis rubra

pilaris: Scaly brownish-
yellowish plaques are seen
on the hands

pilaris: In the trunk
compromising the
intermammary region,
multiple papules are
observed, converging to
form plaques with
edges
• Diagnosis: Requires clinical and histological correlation. Although the histologi-

cal findings are not pathognomonic, skin with regular acanthosis and thickened
and shortened papular ridges plus hypergranulosis can be evidenced. A classic
finding of the disease is where there are areas of orthokeratosis that alternate
with areas of parakeratosis vertically and horizontally giving the “chessboard”
appearance [3, 4].
• Differential diagnosis: The main differential diagnosis is psoriasis followed by
lichen spinulosus, Darier’s disease, and seborrheic dermatitis. In its initial stages,
pityriasis rubra pilaris can resemble Kawasaki disease, scarlet fever, and, in the
case of the generalized variant, other erythroderma causes [3, 4].
Pityriasis Rubra Pilaris 139
Fig. 4.13 Pityriasis rubra pilaris: Erythematous and scaly plaques with irregular edges are
observed on the hands

pilaris: Elderly patient
with scaling and erythema
that involves more than
90% of the body surface
(erythroderma) compatible
with pityriasis rubra pilaris
Fig. 4.15 Axillary

granular parakeratosis:
Erythematous plaque with
some lichenified areas and
borders is observed in the
axillary region
Axillary Granular Parakeratosis
• Definition: Considered a benign condition that mainly affects the axillary region;
however, it has been reported in other body regions [5].
• Pathogenesis: Although its etiology is uncertain, it has been proposed that there
is a defect in the processing of prophylagrin to filaggrin which generates reten-
tion of the keratohyalin granules in the stratum corneum during cornification.
Alternatively, some authors support the allergic theory or a direct irritant reaction
secondary to the use of deodorants or occlusive preparations [5].
• Clinical presentation: Classically affects women and presents as brown or
erythematous-crusted plaques or papules with well-defined irregular edges with
some maceration or lichenification changes that compromise the axillary folds
unilaterally or bilaterally [5] (Fig. 4.15).
• Diagnosis: Diagnosis requires an adequate clinical-pathological correlation.
Histopathological findings can reveal psoriatic hyperplasia with thickening of
the stratum corneum and retention of keratohyalin granules and parakera-
tosis [5].
• Differential diagnosis: It should be distinguished from acanthosis nigricans,
Bowen’s disease, confluent and reticulated papillomatosis, erythrasma, and
extramammary Paget’s disease [5].
References
1. Pérez J, Charro L, Grasa MP, Carapeto FJ. Pitiriasis liquenoide crónica. Med Cutan Ibero Lat
Am. 2007;35:167–73.
2. Wood GS, Reizner GT. Other papulosquamous disorders: pityriasis lichenoides et variolifor-
mis acuta and pityriasis lichenoides chronica. In: Bolognia JL, Jorizzo JL, Rapini RP, editors.
References 141
3. Wood GS, Reizner GT. Other papulosquamous disorders: pityriasis rubra pilaris. In: Bolognia
JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 1. London: Mosby; 2010. p. 159–162-165.
4. Lombardi V, Rossi MM, Minvielle AI. Pitiriasis rubra pilaris. Arch Argent Dermatol.
2013;63:254–61.
5. Shah SA, Azhar AF, Altman K. Granular Parakeratosis. December 13, 2019. Available online:
https://emedicine.medscape.com/article/1108677-overview.
Chapter 5
Inflammatory Diseases of the Hair Follicle
The pilosebaceous unit is composed of the hair follicle, the erector muscle of the
hair, the sebaceous gland, and the apocrine gland [1]. This chapter describes the
inflammatory diseases that affect the hair follicle, mainly represented by both scar-
ring and non-scarring alopecia. Similarly, hidradenitis suppurativa, an inflammatory
disease that affects the pilosebaceous unit, is explored and illustrated.
A. Alopecia
(a) Non-scarring
(i) Alopecia areata
1. Alopecia areata universalis
2. Alopecia areata totalis
3. Alopecia areata in patches
(ii) Androgenetic alopecia
(iii) Telogen effluvium
(iv) Trichotillomania
(v) Traction alopecia
(vi) Temporal triangular alopecia
(b) Scarring
(i) Central centrifugal cicatricial alopecia*
(ii) Lichen planopilaris
1. Lichen planopilaris classic
2. Frontal fibrosing alopecia
3. Graham-Little-Piccardi syndrome
(iii) Mucinous alopecia
*
Pathologies no ilustrated in this atlas

https://doi.org/10.1007/978-3-030-84107-2_5
144 5 Inflammatory Diseases of the Hair Follicle
(iv) Discoid lupus

(v) Acne keloidalis nuchae
(vi) Folliculitis decalvans
(vii) Dissecting folliculitis
B. Inflammatory folliculitis
(a) Pseudofolliculitis barbae*
(b) Other follicular disorders
C. Hidradenitis suppurativa
Alopecia Areata
• Definition: Alopecia areata is an autoimmune disease characterized by non-

scarring hair loss that affects 0.7–3.8% of the population [2].
• Pathogenesis: Represents an autoimmune disease affecting the hair bulb due to
loss of immune privilege and with the consequent activation of cellular immu-
nity mediated by TH1 cells and production of autoantibodies directed against
specific follicular components [3]. The above is supported by the clinical
response of patients to immunosuppressive and immunomodulatory therapies
(Fig. 5.1).
• Clinical presentation: Appears as circumscribed alopecic areas without epider-
mal change [2] (Fig. 5.2). Alopecia areata can affect any part of the body with
Fig. 5.1 Therapeutic response to alopecia areata: Patient with diffuse alopecia areata in whom
management with prednisolone and azathioprine was established with evidence of repopulation of
alopecic areas in more than 90%
Alopecia Areata 145
Fig. 5.2 Alopecia areata

in patches: In the posterior
and occipital parietal
region, there are four
alopecic areas with some
white-gray hairs in their
center (leukotrichia)
hair follicles, the scalp being the most affected site in 90% of patients [4]. The
onset is usually rapid with small circular or oval alopecic areas in hairy distribu-
tions (Figs. 5.2, 5.3, and 5.4) until complete hair loss in the scalp (alopecia tota-
lis or total) (Fig. 5.5) or complete loss of whole body hair (alopecia universalis
or universal) (Figs. 5.6 and 5.7) [4].
• There are rare clinical variants such as “ophiasic” alopecia in which a band of
alopecia compromises the temporo-occipital region and “sisaipho” or “inverse
ophiasis” alopecia whereby alopecic areas are distributed in the frontoparietal
area. Some individuals have an androgenic pattern alopecia clinically seen as
diffuse alopecia areata, which presents as a decrease in global hair population
with predominance in the vertex [3].
• In addition to the hair follicle, alopecia areata can involve the nail apparatus with
different manifestations such as cavities or nail pitting (small pin-sized depres-
sions of the nail plate), trachyonychia (multiple longitudinal lines on the nail
plate causing the appearance of sandpaper), fragile nails, onycholysis (detach-
ment of the distal end of the nail plate), koilonychia (anterior oblique deforma-
tion of the nail plate that gives the appearance of a spoon), and, rarely,
onychomadesis (detachment of the nail plate in its proximal part) [1].
• Diagnosis: The clinical and dermatoscopic characteristics of the alopecic areas
are of great diagnostic utility. Biopsy of the scalp is reserved for cases where it is
imperative to rule out alopecia from another origin or different prognosis such as

in patches: In the right
occipital region, alopecic
areas with well-defined
irregular edges are
observed
scarring alopecia [3]. Histopathological findings will depend on the clinical stage
of the disease and the intensity of the inflammation [3].
• Differential diagnosis: The main differential diagnoses of alopecia areata are
tinea capitis, trichotillomania, temporal triangular alopecia, traction alopecia,
secondary syphilis, and loose anagen hair syndrome. Similarly, diffuse variants
must be differentiated from telogen effluvium and androgenetic alopecia where
trichoscopy is very useful although in some cases biopsy is necessary [1].
Temporal Triangular Alopecia
A. Definition: Also called congenital triangular alopecia and is a circumscribed,

asymptomatic, and permanent non-cicatricial alopecia that affects one or several
areas of the frontotemporal region of the scalp [5].
Temporal Triangular Alopecia 147
Fig. 5.4 (a) Alopecia

areata in patches: In the a
occipital region, there is an
allopathic area with
edges with some white-
gray hairs in its center
(leukotrichia). (b) Alopecia
areata in patches: In the
occipital region, there is a
nummular area of alopecia
without epidermal changes

totalis: Extensive alopecic
area in the scalp with
preservation of hairy zones
in eyebrows, armpits, and
genitals in a patient with
alopecia totalis
B. Pathogenesis: The etiology is unknown; however, it has been suggested that

temporal triangular alopecia represents a genetic mosaicism [5, 6] or may be
due to an acquired form of post-zygotic loss of a wild-type allele in a disease
carrier [7].
Fig. 5.6 Universal

alopecia areata: Extensive
alopecic area in the scalp
and eyebrows with
involvement of axillary and
genital area (not shown) in
a patient with universal
alopecia
Fig. 5.7 (a) Universal

alopecia areata: Extensive a
alopecia in the scalp with
extension to eyebrows,
eyelashes, armpits, and
genitals. (b) Universal
alopecia areata: Alopecic
areas in the scalp,
eyebrows, and eyelashes in
a boy
C. Clinical presentation: Presented as a triangular alopecic area in the frontotem-

poral region in more than half of patients since birth (Fig. 5.8). The alopecic
area is mainly triangular (48%) followed by an oval shape (38%) (Fig. 5.8) and
finally in the form of a blade (12%) [5]. Unilateral compromise is the most fre-
Androgenetic Alopecia 149
Fig. 5.8 Temporal

triangular alopecia: In the
right temporal region, there
is an alopecic area with
regular circumscribed
borders, oval in shape and
without epidermal changes.
Note the presence of hair
shafts of different sizes
within the alopecic area
quent and presents in 93% of cases, while bilateral involvement is significantly

less frequent in only 6.7% of cases.
D. Diagnosis: The diagnosis is clinical and often supported by trichoscopy findings
whereby thin white hairs (leukotrichia), diversity in the diameter of the hair
shaft, hairs surrounded by terminal hair, empty follicles, and white spots can be
observed. The latter features are present in more than 50% of cases, while other
features such as the arboriform vascular pattern, yellow spots, epidermal scales,
broken hairs, cadaverous hair, and black spots are present in a smaller propor-
tion of patients [5].
Androgenetic Alopecia
• Definition: Androgenetic alopecia is an androgen-dependent non-scarring alope-

cia with a hereditary component that results in the conversion of terminal hair
into vellus hair with the consequent miniaturization of the hair shaft [8].
• Pathogenesis: There is a genetic predisposition with an alteration in the andro-
gen and aromatase receptors (the aromatase receptor is responsible for the con-
version of testosterone to estradiol). In men, the expression of androgenetic
alopecia is linked to the activation of the enzyme 5α-reductase which is respon-
sible for converting testosterone to dihydrotestosterone. In women, it is sug-
gested that there is a similar pathophysiology dependent on androgens in
genetically susceptible patients [8].
• Clinical presentation: Clinically, androgenetic alopecia presents in clearly estab-
lished male and female patterns. In men, it is typical to find recession of the
hairline and baldness of the vertex of the scalp (Figs. 5.9 and 5.10). The hair
shafts are miniaturized until they disappear completely with a consequent
decrease in hair density (Figs. 5.10 and 5.11). The evolution of these changes
was classified by Hamilton-Norwood [8] (Fig. 5.12). In women, there is a
Fig. 5.9 Androgenetic

male alopecia: Middle-
aged man with a decrease
in hair population in the
temporal region with
retraction of the hairline

aged male patient with hair
shaft miniaturization and
decrease in hair density in
scalp vertex
decrease in the density of the hair shaft with compromise of the crown and fron-
tal area of the
scalp without loss of the hairline (Figs. 5.13, 5.14, and 5.15). These
progressive changes were classified by Ludwig [8, 9].
• Diagnosis: The diagnosis is clinical, and in some cases, skin biopsy may be use-
ful to rule out other causes of alopecia. On a histopathological level, an increase
in the number of miniaturized hairs, telogen follicles, and increased dermal
fibrosis can be observed [10].
Androgenetic Alopecia 151

alopecia: In the scalp, hair
shafts of different diameter
with a tendency to
miniaturization are
observed

aged male patient with
biparietal recession of the
hairline associated with
miniaturization of the hair
shaft in the vertex

alopecia female pattern:
Middle-aged woman with
reduced hair population in
the frontoparietal region
with miniaturization of
hair shafts

alopecia female pattern: In
the vertex and interparietal
regions, there is a decrease
in the hair population with
associated miniaturization
of the hair shaft

alopecia female pattern: In
the frontoparietal region,
miniaturization of hair
shafts and reduction of hair
density are observed
• Differential diagnosis: The most important differential diagnosis especially in

androgenetic alopecia that affects women is diffuse alopecia areata and telogen
effluvium. There are some cases in which two conditions can occur in the same
patient [1].
Telogen Effluvium
A. Definition: Telogen effluvium is a form of non-cicatricial alopecia characterized

by diffuse hair loss usually of acute onset due to metabolic or hormonal
stress [11].
B. Pathogenesis: There are different stages of the hair growth cycle known as the
anagen (growth phase), the catagen (involution), and the telogen phase (resting
Telogen Effluvium 153
phase) [11]. There is an unknown mechanism in which the anagen phase ends
and the catagen/telogen phase begins [12]. Metabolic alterations such as
pregnancy, malnutrition, and other stressful conditions can trigger abnormally
large number of hair follicles to enter the telogen phase simultaneously [12].
After about 2–3 months of initial insult, there is excessive hair shedding [12].
C. Clinical presentation: Two clinical presentations can be distinguished accord-
ing to duration: acute telogen effluvium lasting less than 6 months (Fig. 5.16)
and chronic telogen effluvium greater than 6 months [13]. Although the physical
changes are not very noticeable, the patient reports a constant hair shedding
(Fig. 5.17). The physical examination can be documented a decrease in the hair
population with the presence of some growing hairs [11].
D. Diagnosis: The diagnosis is clinical, while skin biopsies are reserved for cases
in which it is useful to rule out other causes of alopecia [14]. Histopathology can
Fig. 5.16 Acute telogen

effluvium: Young adult
patient in the postpartum
period with decreased hair
density in the right
frontoparietal region
Fig. 5.17 Chronic telogen

effluvium: In the frontal
region, there is a slight
decrease in hair density
with some short growing
stems
be documented with transverse cuts and an increase in the percentage of folli-

cles in the catagen and telogen phase in more than 25% of the follicles [15].
E. Differential diagnosis: Telogen effluvium should be distinguished from diffuse
forms of alopecia areata, anagen effluvium, androgenetic alopecia, secondary
syphilis, scarring alopecia, and trichotillomania [11].
Trichotillomania
• Definition: Trichotillomania represents an impulse control disorder secondary to

hair traction most frequently observed in children. Although it does not represent
the prototype of inflammatory alopecia, trichotillomania is a differential diagno-
sis of importance in alopecia [16, 17].
• Pathogenesis: Classified by the American Psychiatric Association [16] as an
impulse control disorder that can occur in patients with personality disorders,
body dysmorphic disorder, intellectual disability, and psychosis. Lesions occur
due to hair traction that occurs in childhood more frequently in boys compared
to girls [16, 17].
• Clinical presentation: Clinically, patients with trichotillomania have patchy alo-
pecia or complete scalp alopecia, although it may compromise other hairy areas
such as the eyebrows (Fig. 5.18), eyelashes, limbs, face, and pubic region. The
alopecic areas have irregular borders and shapes with multiple hair shafts of dif-
ferent lengths, giving patients the “rough” appearance or brush shape [16, 17].
• Diagnosis: Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
[16], this disorder was part of obsessive-compulsive and related disorders. There
are diagnostic criteria for trichotillomania [17], including (1) recurrent pulling
out of one’s hair, resulting in hair loss; (2) repeated attempts to decrease or stop
hair pulling; (3) hair pulling that causes clinically significant distress or impair-
ment in social, occupational, or other important areas of functioning; (4) hair
pulling or hair loss that is not attributable to another dermatological condition;
Fig. 5.18
Trichotillomania: Alopecic
areas in eyebrows and
eyelashes with hair stems
of different lengths
Traction Alopecia 155
and (5) hair pulling that is not better explained by the symptoms of another men-
tal disorder [16, 17].
• Differential diagnosis: The differential diagnoses include tinea capitis, alopecia
areata, and monilethrix [18].
Traction Alopecia
• Definition: Traction alopecia is hair loss due to repetitive tension on the hair shaft
frequently observed in Afro-descendant patients with spiral or frizzy hair [18].
• Pathogenesis: Traction alopecia is the only alopecia that is “biphasic” in its clini-
cal behavior with an initially reversible non-scarring disease with subclinical
follicular inflammation that leads to permanent follicular loss with chronic scar-
ring [18].
• Clinical presentation: High clinical suspicion is required in addition to the pres-
ence of alopecic areas that frequently occur at the margin of the hairline in the
frontal, temporal, and occipital areas with presence of the “fringe sign” (retained
hairs along the frontal and/or temporal rim) (Fig. 5.19) near the alopecic area by
traction [18] (Fig. 5.20).
• Diagnosis: Given the biphasic nature of this condition, in early lesions, tricho-
malacia histopathology can show an increase in the number of hairs in telogen
and catagen with a conserved number of terminal follicles and preservation of
sebaceous glands. In chronic lesions, there is a decrease in the number of termi-
nal follicles which are replaced by fibrous tracts with mild or absent inflamma-
tion [18].
• Differential diagnosis: The main differential diagnoses are ophiasis-type alope-
cia areata or frontal fibrosing alopecia [18].
Fig. 5.19 Traction

alopecia: Afro-descendant
woman with an alopecic
band in the frontotemporal
region with occipital
extension and “fringe sign”
(thin hairs) prior to
alopecic area
Fig. 5.20 Traction

alopecia: In the occipital
region, there is an alopecic
area; note the presence of
dense frizzy hair in an
Afro-descendant patient
Fig. 5.21 Lichen

planopilaris: In the
occipital region, multiple
follicular erythematous
papules with peripheral
desquamation and residual
alopecia compatible with
lichen planopilaris are
observed
Lichen Planopilaris
• Definition: Like classical lichen planus, this form of lichen represents an inflam-
matory disease of lymphocytic origin with follicle involvement [19].
• Pathogenesis: Although its etiology is unknown, it is proposed that there is a fol-
licular autoimmune disorder with the consequent activation of the T lymphocyte
against follicular antigens [19].
• Clinical presentation: There are three clinical presentations of the disease: lichen
planopilaris classic, frontal fibrosing alopecia, and Graham-Little-Piccardi-
Lassueur syndrome [18–20]. In the classical form of the disease, follicular ery-
thematous papules with peripheral hyperkeratosis can be found at the vertex of
the head or parietal areas (Figs. 5.21 and 5.22). The follicular inflammatory pro-
cess leads to the fusion of follicular units manifesting clinically as “plume hairs”
or “trichostasis” (Fig. 5.23). Initial lesions resolve leaving residual allopathic
areas (Figs. 5.24, 5.25, 5.26, 5.27, and 5.28). This compromise can affect any
hair area and be associated with cutaneous lichen planus as well as non-scarring
axillary and pubic hair alopecia receiving the name of Graham-Little-Piccardi-
Lassueur syndrome. Frontal fibrosing alopecia presents as a progressive alope-
cic scar band that begins in the hairline and often affects women of postmenopausal
Lichen Planopilaris 157
Fig. 5.22 Lichen

planopilaris: In the scalp,
follicular keratotic papules
are observed that leave a
residual alopecic area
Fig. 5.23 Lichen

cicatricial area in the
vertex; note the presence
of peripheral desquamation
and trichostasis in some
follicular ostia
Fig. 5.24 Lichen

planopilaris: In the frontal
region, there is a residual
alopecic area in a patient
with a history of lichen
planopilaris
Fig. 5.25 Lichen

band area in the temporo-
occipital region with some
posterior parietal alopecic
areas due to the
progressive involvement of
lichen planopilaris
Fig. 5.26 Lichen

planopilaris: Diffuse
cicatricial alopecia in a
lichen planopilaris
age [19] (Figs. 5.27 and 5.28). The classic presentation of lichen planopilaris can
compromise any part of the scalp, the eyebrows (Fig. 5.29), and the beard area
(Fig. 5.30). Similarly, involvement of non-hairy skin has been documented, such
as that of the face and trunk.
• Diagnosis: The diagnosis is often clinical and confirmed with histopathological
findings. In the initial stages on a histological level, an interface of folliculitis
with lymphocytic infiltrate, dyskeratotic keratinocytes, and cytoid bodies is
Lichen Planopilaris 159
Fig. 5.27 Lichen

planopilaris (frontal
fibrosing alopecia type): In
the frontal and parietal
regions, an alopecic band
of some preserved hair
shafts is observed. In the
eyebrows, some alopecic
areas compatible with
lichen planopilaris are
observed
Fig. 5.28 Lichen

planopilaris (frontal
fibrosing alopecia type): In
the frontal and biparietal
regions, an alopecic band
is observed with a scalp
biopsy confirming lichen
planopilaris
observed. Perifollicular inflammation is denser around the infundibulum with

extension to the isthmus and lower segment. Classically, the interfollicular
epidermis is preserved. In the late stages, peripheral fibrosis and polytrichia are
observed [20] (Figs. 5.31, 5.32, and 5.33).
Fig. 5.29 Lichen

planopilaris: Residual
alopecic areas in eyebrows
in a patient with lichen
planopilaris
Fig. 5.30 Lichen

planopilaris: Alopecic area
with some follicular
euchromatic papules in the
surrounding area is
observed on the left
mandibular border
Discoid Lupus 161
Fig. 5.31 Lichen planopilaris: H&E-stained skin biopsy at 20× with presence of concentric scar
fibrosis and a mild peripheral inflammatory infiltrate
• Differential diagnosis: Follicular lichen planus should be distinguished accord-

ing to the findings at the histopathology of keratosis pilaris, Darier’s disease,
follicular mucinosis, lichen scrofulosorum, and lupus erythematosus [21].
Discoid Lupus
• Definition: Discoid lupus represents a variant of cutaneous lupus which affects

the scalp in 30–50% of patients [22].
• Pathogenesis: Discoid lupus is the result of an interaction between genetic, envi-
ronmental, and host factors. In patients with a genetic predisposition, exposure to
UV rays induces apoptosis of keratinocytes and immunosuppression that results
in an autoreactive inflammatory response with subsequent epithelial destruc-
tion [21].
• Clinical presentation: Initially, a coin-shaped erythematous plaque (discoid)
with centrifugal expansion is observed, which is covered by scales and adhered
to by corneal plugs. As lesions evolve, they leave scarring and atrophy with loss
Fig. 5.32 Lichen planopilaris: Skin biopsy in H&E stain with presence of mild peribulbar lym-
phocytic infiltrate, interfollicular mucin, and peripheral cicatricial fibrosis and an absence of seba-
ceous glands
Fig. 5.33 Lichen

planopilaris: H&E-stained
skin biopsy at higher
magnification with
evidence of mild peripheral
inflammatory infiltrate
Discoid Lupus 163
of follicular ostium, erythema, telangiectasias, and hyperkeratosis in the periph-

ery [22] (Figs. 5.34 and 5.35).
• Diagnosis: On a histopathological level in the inflammatory phase, vacuolization
of the basal follicular layer is observed with dyskeratotic keratinocytes that is
accompanied by a perivascular and periadnexal lymphocytic infiltrate. In the
interfollicular epithelium, one can observe orthokeratotic hyperkeratosis with
corneal plugs, epidermal atrophy, basal vacuolization with cytoid bodies, and
thickening of the basal membrane. The latter can show deposits of IgG and IgM
and complement by direct immunofluorescence in 70% of cases [22].
• Differential diagnosis: Residual lesions due to discoid lupus can clinically
resemble pseudopelade of Brocq. Other causes of scarring alopecia include
lichen planopilaris, folliculitis decalvans, and advanced traction alopecia among
others which should be ruled out [22].
Fig. 5.34 Discoid lupus:

In the left parietal region,
alopecic scar areas are
observed in a patient with a
history of discoid lupus
Fig. 5.35 Discoid lupus:

In the left parietal region,
there is a large achromic
scar area with irregular
borders in a patient with a
history of discoid lupus
Acne Keloidalis Nuchae
• Definition: A chronic inflammatory dermatosis that affects young adults of

African descent [23].
• Pathogenesis: Although its etiology is unknown, it is suggested that the lesions
are due to mechanical trauma and the use of aggressive chemicals for hair and
seborrhea [22].
• Clinical presentation: Acne keloidalis nuchae presents as a chronic scarring fol-
liculitis where follicular papules-pustules and euchromatic nodules are observed
that leave hyperpigmentation or residual keloid plaques on the neck and occiput
(Figs. 5.36, 5.37, and 5.38). Additionally, findings include abscesses and suppu-
rative fistulas [22].
• Diagnosis: The diagnosis is clinical and is supported by histopathology findings
according to the stage of the lesion. Histopathological findings include acute
inflammation with lymphocytic or neutrophilic infiltrate in the isthmus and the
lower portion of the infundibulum. The latter is dilated with similarity to the
Fig. 5.36 Acne keloidalis

nuchae: On the occipital
region, multiple hard
history of chronic
folliculitis

nuchae: In the occipital
region, there is a
eucrhomatic scar plate with
some hairy stems in a
plume in keeping with
acne keloidalis nuchae
Folliculitis Decalvans 165

nuchae: Multiple follicular
group together forming a
large scar plate in the
occipital region in patients
with chronic folliculitis
compatible with acne
keloidalis nuchae
initial stages of folliculitis decalvans and dissecting cellulitis. Subsequently, the

infiltrate becomes chronic and granulomatous around the lower portion of the
isthmus with hypertrophic scarring and destruction of sebaceous glands [24].
• Differential diagnosis: Folliculitis decalvans, dissecting cellulitis, keloid scars,
and keratosis follicularis spinulosa decalvans are included [22].
Folliculitis Decalvans
• Definition: Folliculitis decalvans forms a part of the group of scarring alopecias

with neutrophilic infiltrates on histopathology. The inflammatory process is
chronic, and it affects young and middle-aged patients of all races and both sexes
equally [22].
• Pathogenesis: The majority of patients are nasal carriers of staphylococci, and in
the lesions, growth of Staphylococcus aureus can be documented [22].
• Clinical presentation: Folliculitis decalvans is a rare entity that presents as fol-
licular pustules (Fig. 5.39) and painful nodules, leaving rounded alopecic areas
on the scalp or beard area (Fig. 5.40) [21–23].
• Diagnosis: On a histopathological level, it is possible to find keratin aggregates
in the infundibulum with intraluminal neutrophils as well as an intra-peripheral
and neutrophilic infiltrate. In the initial lesions, the sebaceous glands are
destroyed, and the infiltrate in the chronic lesions can consist of neutrophils,
lymphocytes, and plasma cells with extension into the dermis (Figs. 5.41 and
5.42). Frequently, granulomas are seen on the hair shaft with giant foreign body-
type cells. In the final stages, interstitial and follicular dermal fibrosis with
hypertrophic scarring is observed [23].
• Differential diagnosis: Folliculitis decalvans should be distinguished from dis-
secting cellulitis, keloid scars, keratosis follicularis spinulosa decalvans, and
acne keloidalis nuchae [22, 23].
Fig. 5.39 Folliculitis

decalvans: In the beard
area, papules and follicular
pustules are observed with
residual scarring alopecia
and trichostasis (plume
hairs)
Fig. 5.40 Folliculitis

decalvans: In the beard
area, there are papules and
scarce follicular pustules
with residual scarring
alopecia and residual
trichostasis (plume hairs)
Dissecting Folliculitis
• Definition: Dissecting folliculitis (also known as perifolliculitis capitis absce-

dens et suffodiens (PCAS)) is an inflammatory disease of the scalp that causes
scarring alopecia [22, 23].
• Pathogenesis: It is part of the tetrad follicular obstruction along with hidradenitis
suppurativa, acne conglobata, and pilonidal cyst. All the above diseases are the
result of follicular hyperkeratosis resulting in follicular obstruction with second-
ary bacterial infection and follicular rupture with granulomatous reaction to for-
eign body and scarring [22, 23].
Dissecting Folliculitis 167
Fig. 5.41 Folliculitis decalvans: H&E-stained skin biopsy with acute and chronic inflammatory
infiltrate with loss of the pilosebaceous unit
• Clinical presentation: Initial lesions are follicular pustules that affect the vertex
and occiput of the scalp. Lesions subsequently progress to form erythematous
nodules and abscesses with interconnected sinusoidal tracts. The nodules can
suppurate and leave atrophic or keloid scars [22, 23] (Fig. 5.43).
• Diagnosis: Trichoscopy is useful for addressing these patients in whom yellow
and red spots with empty follicular ostium and black spots are observed.
Histopathology shows an acneiform distension of the follicular infundibulum
with keratin plugs and peripheral and intrafollicular neutrophilic infiltrate
(Figs. 5.44 and 5.45). In chronic lesions, lymphocytic infiltrate, plasma cells, and
foreign body reaction can be observed. A diagnostic key to the disease is the
formation of sinusoidal tracts parallel to the stratified squamous epithelium
[22, 23].
• Differential diagnosis: The main differential diagnosis is folliculitis decalvans,
superficial folliculitis, and other forms of scarring alopecia such as acne keloida-
lis nuchae [22, 23].
Fig. 5.42 Folliculitis decalvans: H&E-stained skin biopsy with acute and chronic inflammatory
infiltrates with loss of pilosebaceous unit
Fig. 5.43 Dissecting

folliculitis: Young adult
atrophic areas of 0.5 cm in
places where there were
previously pustules
Dissecting Folliculitis 169
Fig. 5.44 Dissecting folliculitis: H&E-stained skin biopsy with evidence of acute and chronic
inflammatory infiltrate with abscess formation and loss of adnexal structuring
Fig. 5.45 Dissecting

folliculitis: H&E-stained
skin biopsy with evidence
of chronic inflammatory
infiltrate in the deep dermis
Hidradenitis Suppurativa
• Definition: Secondary inflammatory disease of the apocrine glands due to occlu-

sion of the pilosebaceous unit in intertriginous areas, especially the axillary, ano-
genital, and inframammary regions [25].
• Pathogenesis: It is proposed that hidradenitis suppurativa is an inflammatory dis-
ease of the hair follicle where the main pathogenic event is the obstruction of the
upper portion of the pilose follicle that leads to peripheral lympho-histiocytic
inflammation [26]. The rupture of the hair follicle with the subsequent extrusion
of keratin and bacteria into the dermis triggers an inflammatory cascade with the
formation of abscesses. There are clearly established genetic and environmental
factors [24].
• Clinical presentation: Inflammatory nodules and sterile abscesses are observed
in the armpits, genital area, or inframammary region. The lesions are usually
painful on palpation and can form sinusoidal tracts and hypertrophic scars [24].
The clinical severity of the disease can be graded according to the Hurley staging
system [26] which is composed of three stages. Stage I is characterized by the
presence of single or multiple abscesses without sinusoidal tract formation or
scarring (Fig. 5.46); in stage II, multiple abscesses with sinusoidal tracts or scar-
ring are observed, but the lesions can be separated by more than 10 cm (Figs. 5.47
and 5.48); and in stage III, multiple sinusoidal tracts with abscesses or diffuse
disease covering an affected area are observed [27] (Figs. 5.49 and 5.50).
Hidradenitis Suppurativa 171
Fig. 5.46 Hidradenitis

suppurativa, Hurley stage
l: Multiple suppurative
erythematous and painful
nodules on left armpit
palpation

II: On the right axillary
region, residual
hypertrophic scar is
Hurley stage II hidradenitis
suppurativa on treatment

II: Erythematoviolaceous
nodules that coalesce to
form suppurative tracts in
the right axillary region

III: Patient with a history
of hidradenitis suppurativa
on treatment who presents
nodules, some of which are
excoriated with scarring
without the presence of
active fistule tracts and
with post-inflammatory
hyperpigmentation
• Diagnosis: On a histopathological level, an inflammatory cellular infiltrate in the

middle dermis with extension to the subcutis is observed. Abscesses occur in
active cases whereby communication can be observed via sinusoidal tracts.
Granulomatous reactions with giant foreign body-type cells occur in 25% of
biopsies [24, 25] (Figs. 5.51 and 5.52).
Hidradenitis Suppurativa 173

III: In the anogenital
region with extension to
the buttocks and sacral
area, multiple suppurative
observed that are
connected to each other by
sinusoidal tracts that leave
residual hypertrophic and
atrophic scars
Fig. 5.51 Hidradenitis suppurativa: Skin biopsy in H&E stain with presence of acute and chronic
inflammatory infiltrates with abscess formation
Fig. 5.52 Hidradenitis suppurativa: Skin biopsy in H&E stain with the presence of acute and
chronic inflammatory infiltrates with suppurative granuloma formation without the presence of
bacterial structures and abscesses
• Differential diagnosis: The most important differential diagnosis is

Staphylococcus spp. furunculosis; however, Crohn’s disease, inguinal granu-
loma, mycetoma, and cutaneous tuberculosis may present with lesions similar to
suppurative hidradenitis [24, 25].
References
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Chapter 6
Inflammatory Diseases of the Sebaceous
and Apocrine Glands
The pilosebaceous unit is composed of the hair follicle, the sebaceous gland, and the
hair muscle. This section will address the inflammatory diseases that affect the seba-
ceous gland and specific components of the pilosebaceous unit. Within the most
frequent diseases, we find:
A. Acne
(a) Disease severity: mild, moderate, and severe
(b) Acne conglobata
(c) Acne fulminans
(d) Acne necroticans
(e) Pomade acne or cosmetic acne
(f) Steroid or medication-induced acne
(g) Hormonal acne
(h) Neonatal acne
(i) Childhood acne
(j) Acne excoriée des jeunes filles
(k) Occupational acne
(l) Radiation-induced acne
B. Rosacea
(a) Erythematotelangiectatic rosacea
(b) Papulopustular rosacea
(c) Phymatous rosacea
(d) Ocular rosacea
C. Perioral dermatitis

https://doi.org/10.1007/978-3-030-84107-2_6
178 6 Inflammatory Diseases of the Sebaceous and Apocrine Glands
Acne
• Definition: Acne represents an etiologically multifactorial inflammatory disorder

of the pilosebaceous unit that affects approximately 85% of the population
between 12 and 24 years old [1].
• Pathogenesis: The pathophysiological tetrad of acne is composed of seborrhea
(increased sebum secretion in the skin), comedogenesis (ductal hypercornifica-
tion), intrafollicular colonization by Cutibacterium acnes (C. acnes), and inflam-
mation. All of the above are the causes that lead to the formation of acne lesions
[2]. Similarly, the induction of the inflammatory cascade by C. acnes from Toll-
Like Receptor 2 has been documented [3].
• Clinical presentation: There are different clinical manifestations and subtypes of
the disease. Lesions usually develop on the face as well as the upper trunk where
there is higher expression of sebaceous glands. Acne patients also have non-
inflammatory lesions such as open comedones (donut-shaped papules with a
central dilated follicular opening and a black keratin plug secondary to the
deposit of melanin and lipid oxidation) and closed comedones which represent
small euchromatic papules without follicular openings [4] (Figs. 6.1 and 6.2).
Acne inflammatory lesions vary from small erythematous papules (Fig. 6.3) and
pustules (Fig. 6.4) to large, erythematous, and painful nodules that can converge
[5] (Fig. 6.5). Chronic lesions can leave atrophic and hypertrophic scars. Atrophic
scars are typically the most common and are subclassified according to their
morphology, including ice pick (Fig. 6.6), rolling, and boxcar [6] (Fig. 6.7).
Chronic nodular lesions can form hypertrophic and keloid scars [6] (Figs. 6.8
and 6.9).
Additionally, there are etiological and clinical classifications of acne within
which they are distinguished:
Fig. 6.1 Open comedones:

Follicular openings with
central keratin plugs,
corresponding to open
comedones with
perilesional erythema
Acne 179
Fig. 6.2 Closed

comedones: Adolescent
with multiple closed
comedones “whiteheads”
and open “blackheads” on
the forehead
Fig. 6.3 Acne papules:

Adolescent with acne
vulgaris who has
erythematous papules
isolated to the forehead,
accompanied by open and
closed comedones in the
same location
Fig. 6.4 Acne with

pustules and papules: On
the malar region, papules
and pustules are observed
on an erythematous
macular base. Note the
presence of erythematous
nodules in the right
mandibular angle
Fig. 6.5 Acne nodules and

pseudocysts: Patient with
severe nodular-cystic acne
multiple and erythematous
pseudocysts in the nasal
dorsum, malar region,
and chin
Fig. 6.6 Acne scars: On

the forehead, ice pick
atrophic scars are seen
with some associated
inflammatory lesions
–– Acne vulgaris: Characterized by the presence of seborrhea (oily skin) with

formation of open and closed comedones and erythematous papules and pus-
tules that in severe cases can occur with nodules and pseudocysts. The affected
population is between 12 and 16 years of age with resolution often happening
between 20 and 25 years of age [7]. The most affected area is the face fol-
lowed by the trunk. Depending on its severity, acne vulgaris can be classified
as mild, moderate, or severe acne:
• Mild acne: Comedones are the predominant lesions; hence, it is called
comedogenic acne. Comedones can be accompanied by papules and pus-
tules, but generally, there are less than ten [1] (Fig. 6.10).
• Moderate acne: Presents with a moderate number of papules and pustules
(between 40 and 100) and comedones (10 and 40). The trunk may be
affected [1] (Fig. 6.11).
• Severe acne: The number of inflammatory lesions (papules and pustules)
and non-inflammatory lesions (comedones) range from 40 to 100 with the
Acne 181
Fig. 6.7 Acne scars:

multiple atrophic boxcar
scars (well-defined vertical
edges with a broad
“U”-shaped base) and
rolling scars (wide base
with an “M” wavy
appearance) in the malar,
temporal, and mandibular
border region
Fig. 6.8 Acne scars:

Adolescent patient with a
history of severe nodular
acne, managed with
systemic retinoids with the
presence of multiple
hypertrophic scars and
keloids on his trunk
presence of inflamed and deep nodular lesions (more than 5) that affect the
face, chest, and back [1]. This form of acne is called severe nodular acne
[5] (Figs. 6.12, 6.13, 6.14, and 6.15).
–– Acne conglobata: Represents a form of severe nodular acne that most often
affects men. It presents as comedones, papules, pustules, nodules, abscesses,
and scars that affect the trunk, face, and buttocks. Non-inflammatory lesions
Fig. 6.9 Acne scars: Teen

erythematous nodules on
the upper trunk that leave
hypertrophic scars and
keloids
Fig. 6.10 Mild acne

vulgaris: Teen patient with
multiple open and closed
comedones on the
forehead. Note the absence
of papules
Fig. 6.11 Moderate acne

vulgaris: Teen with
pustules with some
erythematous nodules on
the back
Acne 183
Fig. 6.12 Severe nodular

acne: Adolescent patient
with multiple infiltrating
erythematous nodular cysts
that are painful to
palpation on the malar
region. Note the presence
of associated seborrhea
Fig. 6.13 Severe nodular-

cystic acne: In the malar
region involving the
mandibular angle,
preauricular region, and
neck, there are papules,
pustules, and some
erythematous nodules that
leave residual atrophic
scars
(comedones) have channels of communication in the deep dermis receiving

the name of “bridge comedones” (Fig. 6.16). The lesions resolve leaving atro-
phic and keloid scars [5] (Fig. 6.17).
–– Acne fulminans: Also called acute febrile ulcerative acne, it presents as ery-
thematous nodules and plaques which are both painful on palpation and sup-
purative and covered with hemorrhagic scabs (Fig. 6.18). These lesions
Fig. 6.14 Severe acne

vulgaris: On the malar
region, there are multiple
erythematous papules and
nodules with some isolated
closed comedones
Fig. 6.15 Severe acne

vulgaris: On the temporal
and malar region, papules
and erythematous nodules
are observed that leave
residual atrophic scars
mainly affect the back of male adolescents (Fig. 6.19). Unlike acne conglo-
bata, the number of comedones is scarce, and the presentation is acute,
accompanied by systemic symptoms and alterations in blood tests such as
leukocytosis [5] (Figs. 6.20 and 6.21).
–– Acne necroticans: Also called varioliform acne, it is an infrequently reported
variant of acne that is considered a chronic necrotizing folliculitis with two
clinical spectra: one superficial or miliary and another deep scar. Clinically,
acne necroticans manifests as follicular papulopustules on the scalp and face.
Acne 185
Fig. 6.16 Acne

conglobata: On the
anterior thorax, multiple
open bridging comedones
are observed
(interfollicular
communication)
Fig. 6.17 Acne

conglobata: Multiple open
comedones in pairs and
papulopustules that form
nodules that interconnect
with each other via
fistulous paths in patients
with acne conglobata
Fig. 6.18 Acne fulminans.

Pustules and erythematous
nodules that are ulcerated
and covered with central
hemorrhagic scabs are
observed that subsequently
leave residual atrophic
scars
Fig. 6.19 Acne fulminans:

Adolescent patient with an
acute presentation of
multiple papulopustules
and painful erythematous,
ulcerative nodules that are
covered with central
hemorrhagic crust and
associated with systemic
symptoms

On the anterior thorax and
malar region, multiple
observed with infiltrates
that converge to form
painful plaques, some of
which are eroded and
ulcerated with serous
exudate
The upper trunk is rarely affected, and lesions form a central necrosis and
depressed scars [8].
–– Pomade acne or cosmetic acne: Presents as a result of chronic exposure to
substances that occlude the follicle. Clinically, closed comedones are observed
on the face or elsewhere whereby the skin is exposed to cosmetics (cosmetic
acne), while the involvement of the forehead and temporal region is referred
to as pomade acne [4].
Acne 187

On the upper back, eroded
and ulcerated erythematous
plaques are observed with
serohematic scabs
Fig. 6.22 Steroid-induced

acne: On the trunk
involving the anterior
deltoid and anterior thorax,
history of oral steroid
exposure
–– Mechanical acne: Presented by the repetitive frictional and mechanical

obstruction of the ostium of the pilosebaceous unit. Mechanical acne is mainly
observed in violinists as a lichenified and hyperpigmented plate with come-
dones [4].
–– Steroid or medication-induced acne: Characterized by a monomorphic rash
consisting of erythematous papules or pustules that mainly affect the trunk,
shoulders, and arms with less involvement of the face (Figs. 6.22 and 6.23).
The main causative drugs are topical and oral corticosteroids, lithium, phe-
nytoin, isoniazid, high doses of B complex, halogenated compounds, and epi-
dermal growth factor inhibitors [5].
–– Hormonal acne: While the role of hormones as a causative agent of acne is
important, there are endocrinological conditions or abnormalities that favor
the presence of acne. The lesions can be erythematous papules or nodules that
typically affect the chin and jaw region and can extend to the neck (Fig. 6.24).
Patients are often women who concurrently present with menstrual altera-
tions, voice changes, increased libido, and hirsutism or children aged

acne: On the anterior
aspect of the right deltoid
and ipsilateral hemithorax,
follicular papules are
observed
Fig. 6.24 Hormonal acne:

Female patient with
multiple papules and some
nodules on the chin and
maxillary border with the
presence of mild
hypertrichosis (clinical
hyperandrogenism)
2–7 years [5]. There are clearly established syndromes that occur with hyper-
androgenism and acne such as polycystic ovary syndrome, HAIR-AN syn-
drome (hyperandrogenism, insulin resistance, and acanthosis nigricans), as
well as adrenal gland disorders [4, 5].
–– Neonatal acne: Occurs in up to 20% of healthy infants from 2 weeks of birth,
and self-resolution often results in the first 3 months. It is characterized by the
presence of erythematous papules on the nasal dorsum and cheeks (Figs. 6.25
and 6.26). It is suggested that neonatal acne is not a true variant of acne and
may simply be a variant of neonatal cephalic pustulosis. It is suggested that
Malassezia sympodialis or furfur may have a causal role in this variant. [5]
–– Childhood acne: This variant affects infants between 3 and 6 months of age
and is characterized by the presence of comedones, papules, pustules, and
nodules (Fig. 6.27). It is suggested that the cause is due to a transient elevation
of dehydroepiandrosterone (DHEA) levels by the immature adrenal gland.
The lesions resolve in the first to second year of life [5].
Acne 189
Fig. 6.25 Neonatal acne:

A 3-month-old patient with
multiple closed comedones
on the central facial region
–– Acne excoriée des jeunes filles: Also called excoriated acne of young women,
it mainly affects young women who have mild to moderate acne with neurotic
behavior that leads to the formation of excoriations. Clinically, it presents
with comedones and papules that leave erosions, scabs, and scars [5].
–– Occupational acne: Presents secondary to exposure to coal tar derivatives,
lubricating oils, and chlorinated hydrocarbons. The particular exposure to the
latter is called chloracne (Figs. 6.28 and 6.29). The lesions present as large
comedones, papules, pustules, large nodules, and true cysts in areas covered
by clothing that is impregnated with the causative agent [5].
–– Radiation-induced acne: Both ionizing and ultraviolet radiation can generate
acneiform lesions. It is suggested that ionizing radiation induces epithelial
metaplasia in the follicle with the consequent creation of a hyperkeratotic
plug in the pilosebaceous unit. Clinically, open comedones are observed that
may be accompanied by atrophic yellowish plaques in patients with chronic
Fig. 6.26 Neonatal acne:

A 2-month-old patient with
papulopustules on the
malar region
exposure to ultraviolet rays with involvement of the temporal and periorbital

region (Favre-Racouchot syndrome) [5] (Figs. 6.30 and 6.31).
• Diagnosis: The diagnosis is clinical, and the role of blood tests will depend on
the clinical subtype evaluated (e.g., such as in hormonal acne in the context of
hyperandrogenism) [4]. Although the skin biopsy is not indicative in most cases,
histopathological findings will depend on the clinical features. In closed come-
dones, a distended follicular infundibulum full of keratin and sebum with a
follicular epithelium attenuated with a narrow ostium is observed. These findings
are similar to those of open comedones, with the exception of in the case for open
comedones, the ostium is wider [5].
• Differential diagnosis: Rosacea is the main differential diagnoses of acne since
it presents with papules and pustules and, in some granulomatous forms, with
nodules and plaques. However, the absence of comedones is the main differential
characteristic in the case for rosacea. Perioral dermatitis, superficial Gram-
Rosacea 191
Fig. 6.27 Childhood acne:

A 2-year-old patient with
closed comedones on the
malar region
negative folliculitis, Malassezia sp. folliculitis, miliaria, milium cysts, maculo-

papular sarcoidosis, tinea barbae, and, rarely, dermatitis herpetiformis can
present with similar lesions to acne [9].
Rosacea
• Definition: Rosacea is an inflammatory disease of multifactorial etiology charac-

terized by the presence of different signs and symptoms [10].
• Pathogenesis: There are genetic predispositions and certain environmental fac-
tors that trigger the usual clinical symptoms and lesions of rosacea. It is proposed
that there is an induction of the innate immune system and stimulation of the
autonomic nervous system. This generates an alteration in the regulation of arte-
Fig. 6.28 Chloracne:

Young adult patient with a
history of hydrocarbon
exposure with multiple
open comedones with
some papules isolated on
the forehead, nasal dorsum,
and malar region
rioles and large venules responsible for the initial “flushing” that results in
chronic inflammation and fibrosis [9].
• Clinical presentation: The presence of persistent facial erythema, telangiecta-
sias, pustules, inflammatory papules, facial edema, eye inflammation, and phy-
matous changes in the nose but also in the ears, forehead, chin, and eyelids are
some of the clinical features of the disease [11]. According to the Committee of
Experts of the National Rosacea Society [12], there are four clinical subtypes of
the disease: erythematotelangiectatic rosacea, papulopustular rosacea, phyma-
tous rosacea, and ocular rosacea. Additionally, there is a rare variant called gran-
ulomatous rosacea.
–– Erythematotelangiectatic rosacea: Presents with persistent facial erythema
associated with telangiectasias and skin sensitivity, coupled with occasional
redness, also known as “flushing” [10] (Fig. 6.32).
Rosacea 193
Fig. 6.29 Occupational

acne: Young adult patient
with a history of
hydrocarbon exposure who
presents with multiple
open comedones on the
–– Papulopustular rosacea: Patients present with persistent central facial ery-

thema that is accompanied by papules, papulopustules, or pustules [10]
(Figs. 6.33, 6.34, 6.35, 6.36, 6.37, and 6.38).
–– Phymatous rosacea: Clinically, thickened skin with infiltrated nodular plaques
and increased pronunciation of normal skin porosity is observed (Fig. 6.39),
which can affect the nose (rhinophyma) (Figs. 6.40 and 6.41), the forehead
(metophyma), (Fig. 6.42), the chin (gnathophyma), the ears (otophyma)
(Fig. 6.43), and the eyelids (blepharophyma) [10].
–– Ocular rosacea: Patients present with blepharitis, conjunctivitis, chalazion,
foreign body sensation, and rarely keratitis, episcleritis, scleritis and iritis [10]
(Fig. 6.44).
–– Granulomatous rosacea: This rare variant of rosacea is defined according to
histopathological findings in which a granulomatous infiltrate can be observed
that can be nodular, peripheral, diffuse, or combined [13] (Fig. 6.45).
Fig. 6.30 Actinic or

ultraviolet radiation-
induced acne: Elderly
chronic exposure to
ultraviolet radiation who
presents with multiple
open comedones on the
right temporal and
zygomatic region
Fig. 6.31 Favre-

Racouchot syndrome:
Adult patient with multiple
open comedones in
bilateral periorbital region
Rosacea 195
Fig. 6.32 Erythemato

telangiectatic rosacea: On
the malar region, there is
persistent facial erythema
with some thin telangiectasias
in a patient with a clinical
flushing and sensitive skin
Fig. 6.33 Papulopustular

rosacea: Patient with
persistent malar and central
facial erythema with
isolated papules and
pustules on the chin

rosacea: Papules and
pustules with an
are observed on the malar
region, nasal dorsum,
and chin

rosacea: On the forehead
of an elderly patient,
papules-pustules are
observed

rosacea: Middle-aged
woman who presents with
multiple periorbital
papules and some
erythematous pustules on
her face, respecting the
nasogenian folds. On the
malar region, there are
erythematous macules with
some thick telangiectasias
Rosacea 197

rosacea: On the malar
region and chin,
history of rosacea

rosacea: Middle-aged
woman who on the
forehead has multiple
papules and some pustules
with an erythematous
macular base. Note the
absence of comedones
Fig. 6.39 Phymatous

rosacea: Patient with
plaques and accentuation
of normal skin porosity
Fig. 6.40 Rhinophyma:

Glandular hypertrophy
with prominent follicular
openings and soft tissue
distortion of the nose
Fig. 6.41 Rhinophyma:

Adult patient with a history
of several years of rosacea
with a multilobed skin
colored tumor with dilated
pores on the nasal tip,
dorsum, and nasal wings
compatible with severe
rhinophyma
Rosacea 199
Fig. 6.42 Metophyma: On

the forehead, there is a
large indurated
a porous appearance of
irregular edges compatible
with phymatous rosacea
Fig. 6.43 Otophyma:

Patient with a history of
phymatous rosacea with an
plaque with irregular
borders and a multilobular
surface with porous
accentuation in the left
earlobe
• Diagnosis: The diagnosis is clinical, and the biopsy is rarely indicated except for
granulomatous rosacea. Histopathological findings tend to correlate to the clini-
cal subtype and severity of the rosacea. In the erythematotelangiectatic rosacea,
it is possible to identify the histology of ectatic vessels and edema accompanied
by a perivascular and perifollicular lymphocytic infiltrate. Perifollicular inflam-
mation accompanied by lymphocytes, histiocytes, and neutrophils, ectatic ves-
sels, and Demodex folliculorum intrafollicular are typical findings of the
papular-pustular variant. Granulomatous rosacea yields a granulomatous periph-
Fig. 6.44 Ocular rosacea:

erythematotelangiectatic
rosacea with ocular
involvement due to chronic
conjunctivitis compatible
with ocular rosacea
Fig. 6.45 Granulomatous

rosacea: Male patient with
a clinical picture of several
years of evolution of
pustules, papules, and
nodules with
compatible with
granulomatous rosacea
eral inflammation. The findings for phymatous rosacea, especially rhinophyma,

are sebaceous gland hypertrophy accompanied by ectatic vessels and a lympho-
cytic infiltrate [14].
• Differential diagnosis: The main differential diagnoses are acne vulgaris, lupus
erythematosus, perioral dermatitis, seborrheic dermatitis, and nasal sarcoid-
osis [15].
Perioral Dermatitis
• Definition: Characterized by a papular or papulopustular rash that is distributed

in the perioral region (Fig. 6.46), the eyelids, or the periorbital skin (Fig. 6.47).
In the last two situations, it is called periocular dermatitis [16].
Perioral Dermatitis 201
Fig. 6.46 Perioral

dermatitis: Patient with
multiple small
erythematous papules in
the perioral region
Fig. 6.47 Periocular

erythematous papules on
the eyelids and periorbital
skin in a patient with a
history of atopy, managed
with topical corticosteroids
• Pathogenesis: There is no obvious causative infectious agent although it has

been suggested that infestations with Candida spp. and Demodex and fusiform
bacteria may have a causal role in perioral dermatitis. The highest incidence has
been documented in patients with atopy and those using topical corticosteroids,
the latter being the most related causative agent [15].
• Clinical presentation: Presents as an acute skin rash that begins in the nasolabial
folds with extension to the perioral area respecting the margin of the lips. The
lesions consist of monomorphic papules and pustules on an erythematous macu-
lar base and variable desquamation [15] (Figs. 6.48 and 6.49).
• Diagnosis: The diagnosis is based on the causal relationship in the vast majority
of cases with previous exposure to topical, inhaled, or oral corticosteroids pre-
ceding the onset of skin rash. In a few cases, a skin biopsy is useful in which a
perivascular and peripheral mononuclear cellular infiltrate with slight eczema-
tous changes can be observed [15].
• Differential diagnosis: The main differential diagnoses are rosacea, acne vul-
garis, disseminated facial lupus miliary, seborrheic dermatitis, and contact der-
matitis [15].
Fig. 6.48 Perioral

dermatitis: On the malar
region, nasal dorsum, chin,
and upper lip skin, multiple
converge forming
erythematous plaques in a
patient with chronic
exposure to topical
corticosteroids

dermatitis: A female with
papules on an
with scaly areas that are
observed with a history of
chronic betamethasone use
References 203
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Blackwell; 2010. p. 42.20–-26.
3. Orozco B, et al. Guías colombianas para el manejo del acné: una revisión basada en la evidencia
por el Grupo Colombiano de Estudio en Acné. Rev Asoc Colomb Dermatol. 2011;19:129–58.
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general medicine, vol. 2. 7th ed. New York: McGraw-Hill; 2010.
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Dermatol. 2013;21:328–36.
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N, Griffiths C, editors. Rook’s textbook of dermatology, vol. 2. 8th ed. Chichester: Wiley-
Blackwell; 2010. p. 42.17.
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9. Layton AM. Acne: Differential diagnosis. In: Burns T, Breathnach S, Cox N, Griffiths C,
editors. Rook’s textbook of dermatology, vol. 2. 8th ed. Wiley-Blackwell: Chichester; 2010.
p. 42.36–7.
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recent findings. J Am Acad Dermatol. 2013;69:S15–26.
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RP, editors. Dermatology, vol. 2. 3rd ed. London: Mosby; 2010. p. 561.
12. Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of National
Research Society Expert Committee on the classification and staging of Rosacea. J Am Acad
Dermatol. 2002;46:584–7.
13. Sarmiento-Laínez M, et al. Rosácea granulomatosa. Rev Med Hosp Gen Mex.
2008;71(4):204–8.
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Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of dermatology, vol. 2.
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titis. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook’s textbook of dermatology,
vol. 2. 8th ed. Chichester: Wiley-Blackwell; 2010. p. 43.11.
Chapter 7
Inflammatory Skin Diseases Induced
by Drugs
A number of skin diseases occur as a direct result of the activation of the immune
system secondary to exposure to medications. Within this group are:
A. Drug reactions
(a) Morbilliform drug eruption
(b) Erythema multiforme
(c) Stevens-Johnson syndrome (SJS)
(d) Toxic epidermal necrolysis (TEN)
(e) Drug reaction with eosinophilia and systemic symptoms (DRESS)
(f) Acute generalized exanthematous pustulosis (AGEP)
Morbilliform Drug Eruption
• Definition: Morbilliform drug eruption or also called drug rash represents the
most common adverse skin reaction [1].
• Pathogenesis: It is believed that the pathophysiological mechanism involves a
cell-mediated hypersensitivity response in which antigen presentation occurs
whereby dendritic cells present the drug haptens to T lymphocytes via the major
histocompatibility type II (MHC II) complex. This triggers a recruitment of
CD4+ and CD8+ cells with consequent epidermal necrosis. The rash typically
occurs in the first 7–14 days after drug exposure [1].
• Clinical presentation: The lesions initially present as palpable erythematous
macules with symmetrical distribution that affect the trunk and upper extremi-
ties. The lesions subsequently converge and may be polymorphic with some urti-
carial or purpuric lesions. The mucous membranes are generally spared from
disease activity [1] (Figs. 7.1 and 7.2).

https://doi.org/10.1007/978-3-030-84107-2_7
206 7 Inflammatory Skin Diseases Induced by Drugs
Fig. 7.1 Morbilliform

drug eruption: A
maculopapular rash is seen
on the trunk in a patient
with previous drug
exposure
Fig. 7.2 Morbilliform

drug eruption:
Erythematous macules
with irregular confluent
borders are observed in
patients with drug
exposure
• Diagnosis: The diagnosis is clinical since the histopathology findings are not
usually clinically significant. Histologically, a superficial interstitial and
perivascular lymphocytic infiltrate is observed that may be accompanied by
eosinophils in 30% of cases [1] (Fig. 7.3).
• Differential diagnosis: The most important differential diagnosis is a viral exan-
them which is often indistinguishable. Alternatively, other syndromes often pres-
ent secondary to drug administration and need to be ruled out such as
Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity
with eosinophilia and systemic symptoms (DRESS). Other differential diagno-
ses include scarlet fever, toxic shock syndrome, Kawasaki disease, and Still’s
disease [1].
Morbilliform Drug Eruption 207
Fig. 7.3 Morbilliform drug eruption: H&E-stained skin biopsy with superficial perivascular
inflammatory infiltrate and mild interstitial edema
Erythema Multiforme
• Definition: An acute, self-limited, and potentially recurrent disease that presents

with symmetrical fixed erythematous papules and the characteristic “target
lesions.” [2]
• Pathogenesis: It is currently proposed that erythema multiforme corresponds to
an immunological reaction that occurs in the context of infection in predisposed
patients. The most described causative agent is the herpes virus along with
Mycoplasma pneumoniae, Histoplasma capsulatum, and parapoxvirus.
• Clinical presentation: There are typical lesions relating to erythema multiforme
such as the “target lesions” in which three zones are distinguished, a darker
erythematous outer ring, a lighter erythematous inner ring, and the center, which
shows evidence of epidermal damage and blister formation (Figs. 7.4 and 7.5).
Other atypical lesions present in erythema multiforme which can be described as
erythematous or edematous papules or palpable plaques with poorly defined
edges where the zones mentioned above cannot be distinguished. There are two
clinical spectra of the disease: erythema multiforme minor, which is character-
ized by the presence of typical lesions that compromise the extremities and face
with minimal or absent involvement of the mucous membranes (Figs. 7.6 and
7.7), and erythema multiforme major, where there are typical and atypical lesions
of erythema multiforme with a more severe involvement of the mucous mem-
branes (Figs. 7.8, 7.9, 7.10, 7.11, 7.12, and 7.13).
• Diagnosis: The diagnosis is clinical and histopathological. In skin biopsies of
patients with erythema multiforme, individual apoptotic keratinocytes can be
found, which is subsequently accompanied by mild spongiosis and basal vacuo-
lar focal degeneration. Additionally, dermal edema and perivascular leukocyte
infiltration with exocytosis of the same toward the epidermis can be documented.
• Differential diagnosis: There are different entities that present with lesions simi-
lar to erythema multiforme such as giant urticaria, fixed erythema due to medica-
tions, subacute cutaneous lupus erythematosus, Kawasaki disease, erythema
annulare centrifugum, and some severe forms of vasculitis.
Fig. 7.4 Erythema

multiforme: Erythematous
plaques with a double halo,
of which the darker central
halo blisters and leaves
erosions, while the outer
paler halo results in
erythematosus to the
periphery
Stevens-Johnson Syndrome 209
Fig. 7.5 Erythema

multiforme: Adult patient
plaques with eroded center
and some dark red halos
compatible with erythema
multiforme
Stevens-Johnson Syndrome
• Definition: Like toxic epidermal necrolysis, Stevens-Johnson syndrome repre-

sents a severe drug reaction with extensive keratinocyte necrosis [3].
• Pathogenesis: Evidence suggests that Stevens-Johnson syndrome presents due to
an alteration in the ability to detoxify intermediate drug metabolites. This altera-
tion in addition to an underlying genetic susceptibility favors the activation of
cytotoxic T cells with subsequent release of pro-inflammatory cytokines
responsible for the systemic involvement of this entity. Lesions appear between
1 and 3 weeks after drug exposure, which causes a sensitization phase that plays
an important role in the pathogenesis of the disease [3].
• Clinical presentation: Lesions are preceded by a prodromal phase of fever, con-
junctivitis, and dysphagia. Subsequently, erythema and erosions appear in the
oral and genital mucosa in more than 90% of patients. Skin lesions present as
irregular, erythematous, and purpuric macules that converge with a dark center
Fig. 7.6 Erythema

multiforme: Patient with
plaques with violaceous
centers, some of which
possess eroded surfaces
which can show a positive Nikolsky sign (Figs. 7.14, 7.15, and 7.16). In the same
way, fragile blisters can be observed which expand centrifugally when pressure
is applied (Asboe-Hansen’s sign). Clinically, Stevens-Johnson syndrome is an
initial state of its most severe form, toxic epidermal necrolysis. The involvement
of 10% of the body surface is compatible with Stevens-Johnson syndrome, while
lesions covering between 10% and 30% of body surface is considered a state of
overlap between Stevens-Johnson syndrome and toxic epidermal necrolysis, and
lesions distributed in greater than 30% of total body surface are compatible with
toxic epidermal necrolysis [3].
• Diagnosis: The diagnosis is clinical and confirmed via histopathology whereby
epidermal necrosis associated with lymphocytic infiltrate mainly consisting of
CD8 cells that are accompanied by macrophages is observed [3].
• Differential diagnosis: The differential diagnosis should be made with other enti-
ties that present with erythema and subsequent blistering such as staphylococcal
Toxic Epidermal Necrolysis 211
Fig. 7.7 Erythema

multiforme: Erythematous
plaques with a violaceous
center and areas of erosion
are seen on the trunk
scalded skin syndrome, generalized fixed drug eruption, erythema multiforme,

paraneoplastic pemphigus, Kawasaki disease, drug-induced linear IgA dermato-
sis, and DRESS [3].
Toxic Epidermal Necrolysis
• Definition: Toxic epidermal necrolysis is an adverse drug reaction that affects the
skin and mucous membranes with systemic compromise and high mortality [4].
• Pathogenesis: Most cases result from a hypersensitivity reaction to medications;
however, it has also been associated with infections such as Mycoplasma pneu-
moniae, dengue virus, and cytomegalovirus as well as secondary to the adminis-
Fig. 7.8 Erythema

plaques with a lighter halo
of erythematosus and a
dark red center, some of
which are eroded and
covered with hemorrhagic
scabs. Note the presence of
oral mucosa involvement
Fig. 7.9 Erythema

multiforme: Erythema
multiforme involving the
oral cavity; note the
presence of ulcers covered
by scabs
Fig. 7.10 Erythema

plaques containing a center
covered with scabs,
involving the trunk
tration of contrast medium. Toxic epidermal necrolysis is a disease mediated by

T cells, especially CD8+, as the main mediator of keratinocyte apoptosis. Like
cell-mediated damage, epidermal necrosis is triggered by the Fas ligand, nitric
oxide, and tumor necrosis factor alpha [4].
• Clinical presentation: Initially, a morbilliform maculopapular rash is observed
with some macules presenting morphologically as atypical “target lesions”
which is subsequently accompanied by fragile blisters, erosions, painful skin
inflammation, and ulcers in the oral cavity (Figs. 7.17, 7.18, 7.19, and 7.20).
Lesions typically compromise more than 30% of body surface, distinguishing it
from Stevens-Johnson syndrome and the overlap Stevens-Johnson/toxic epider-
mal necrolysis syndrome. The above is also associated with ophthalmic, pulmo-
nary, cardiovascular, gastrointestinal, and renal involvement [4].
• Diagnosis: The diagnosis is made according to clinical and histological findings.
On a histological level, complete epidermal necrosis is observed with a
subepidermal bleb, a lymphocytic infiltrate in the dermoepidermal junction,
Fig. 7.11 Erythema

plaques, some with central
scabs
Fig. 7.12 Erythema

plaques, some of which
contain central
hemorrhagic crusting that
involve the suprascapular
region
Fig. 7.13 Erythema

with multiple mildly
plaques that converge with
some eroded areas covered
with hemorrhagic crust in
the posterior trunk
Fig. 7.14 Stevens-Johnson

syndrome: Erythematous
center with ocular and oral
involvement are observed
on the face, neck, and
thorax

syndrome: Erythematous
center are seen on the
left arm

syndrome: Multiple
violaceous centers are
observed on the arm
Fig. 7.17 Toxic epidermal

necrolysis: Erythematous
molecules with violet
centers and flaccid blisters

necrolysis: Observe the
presence of central fragile
blisters that erode
secondary to epidermal
necrosis

necrolysis: Multiple
macules with erosions that
compromise more than
30% of the total body
surface. Note the presence
of edema and erythema

necrolysis: Erythema with
multiple eroded areas and
over 90% involvement of
the total body surface area
is observed in the trunk
and limbs
CD4+ T cells in the dermis, and exocytosis of CD8+ T cells in the epidermis in
addition to endothelial apoptosis [5].
• Differential diagnosis: Differential diagnosis includes major and minor erythema
multiforme, staphylococcal scalded skin syndrome, linear IgA dermatosis, acute
generalized exanthematous pustulosis, and acute severe graft-versus-host dis-
ease [5].
Drug Reaction with Eosinophilia and Systemic Symptoms
• Definition: The drug reaction with eosinophilia and systemic symptoms (DRESS)
is an adverse drug reaction that has a cutaneous, hematological, and visceral
organ involvement [6].
• Pathogenesis: It is commonly related to anticonvulsants, allopurinol, minocy-
cline, sulfasalazine, and abacavir. It is suggested that there is a failure in the
detoxification pathways of these drugs, in which activated CD4+ and CD8+ T
lymphocytes promote the migration of eosinophils via the expression of interleu-
kin 5. However, the presentation of DRESS has also been related to reactivation
of herpes types VI and VII, Epstein-Barr virus, and cytomegalovirus. This typi-
cally occurs in genetically predisposed patients [6].
• Clinical presentation: Typically, patients present with fever, rash, lymphadenop-
athy, leukocytosis, and liver function test abnormalities that in some cases can be
interpreted as a systemic infection. Skin lesions are prominent and broad spec-
trum from urticariforme eruptions and morbilliform rashes to vesicular, blister-
ing, pustular, purpuric, and erythrodermic lesions in addition to “target lesions
and cheilitis.” One of the classic features is the presence of facial edema that in
some cases can be interpreted as angioedema [6] (Figs. 7.21, 7.22, 7.23, and 7.24).
• Diagnosis: The diagnosis is clinical and supported by blood tests. In recent
years, different diagnostic criteria have been proposed, the ones most commonly
described being those described by Bocquet, which include morbilliform rash
associated with hematological abnormalities (eosinophilia greater than 1500 or
presence of atypical lymphocytes) and systemic compromise (adenopathies
greater than 2 cm, hepatitis with elevation of transaminases twice above normal
range, interstitial nephritis, interstitial pneumonitis, and carditis). The diagnosis
according to Bocquet criteria is made with the inclusion of three or more of the
above aforementioned criteria. Histopathology findings typically yield a perivas-
cular lymphocytic infiltrate in the papillary dermis with eosinophils, atypical
lymphocytes, and spongiosis [7].
• Differential diagnosis: It should be distinguished from other forms of severe
toxidermias such as Stevens-Johnson syndrome, toxic epidermal necrolysis,
acute generalized exanthematous pustulosis, and erythroderma [8].
Acute Generalized Exanthematous Pustulosis 219
Fig. 7.21 Drug reaction

with eosinophilia and
systemic symptoms
(DRESS): Facial erythema
associated with eyelid
edema in a patient
following an adverse
reaction to a medication,
associated with
eosinophilia and systemic
symptoms
Acute Generalized Exanthematous Pustulosis
• Definition: Acute generalized exanthematous pustulosis (AGEP) or also called

pustular drug eruption or toxic pustuloderma is a drug eruption that presents as
multiple sterile non-follicular pustules over large areas of erythema and
edema [9].
• Pathogenesis: Ninety percent of AGEP cases are secondary to medications in
patients genetically predisposed with HLA polymorphisms [9].
• Clinical presentation: It is characterized by fever which is accompanied by mul-
tiple sterile non-follicular pustules that manifest in areas of erythema and edema
with involvement of the face and intertriginous areas. The lesions last 1–2 weeks
with subsequent resolution and residual desquamation [9] (Fig. 7.25).
Fig. 7.22 DRESS: Patient

maculopapular rash with
clinical and paraclinical
criteria compatible with
drug reaction with
eosinophilia and systemic
symptoms (DRESS)
Fig. 7.23 DRESS:

Involving the back and
arms, a maculopapular rash
is observed in a patient
with criteria for drug
reaction with eosinophilia
and systemic symptoms
(DRESS)
Acute Generalized Exanthematous Pustulosis 221
Fig. 7.24 DRESS: On the

back of the hand, multiple
seen that converge,
forming large plaques in a
patient satisfying DRESS
criteria
• Diagnosis: The diagnosis is clinical and confirmed via histopathology where

spongiform pustules are observed in the superficial layers of the epidermis and
subcorneas. Additionally, these findings are accompanied by edema of the papil-
lary dermis and a mixed perivascular infiltrate with neutrophils and some eosino-
phils [9].
• Differential diagnosis: The main differential diagnoses are acute pustular
psoriasis-type von Zumbusch as well as other drug reactions such as DRESS [9].
Fig. 7.25 Acute

generalized exanthematous
pustulosis: On the lower
limbs, multiple non-
follicular pustules are
observed on erythematous
skin. The desiccation of the
pustules leaves a thin
superficial peeling
References
1. Revuz J, Valeyrie-Allanore L. Drug reactions: exanthematous drug eruptions. In: Bologna JL,
2. French LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal
necrolysis: erythema multiforme. In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology,
vol. 2. 3rd ed. London: Mosby; 2010. p. 319–22.
3. French LE, Prins C. Erythema multiforme, Stevens-Johnson syndrome and toxic epider-
mal necrolysis: Stevens-Johnson syndrome. In: Bologna JL, Jorizzo JL, Rapini RP, editors.
4. Schwarts RA, McDonough PH, Lee BW. Toxic epidermal necrolysis. Part I. Introduction, his-
tory, classification, clinical features, systemic manifestations, etiology, and immunopathogen-
esis. J Am Acad Dermatol. 2013;69:e1–13.
5. Schwarts RA, McDonough PH, Lee BW. Toxic epidermal necrolysis. Part II. Prognosis,
sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol.
2013;69:e1–16.
6. Walsh SA, Creamer D. Drug reaction with eosinophilia and systemic symptoms (DRESS): a
clinical update and review of current thinking. Clin Exp Dermatol. 2011;36:6–11.
7. Husain Z, Reddy BY, Schwartz R. DRESS syndrome: part I. Clinical perspectives. J Am Acad
Dermatol. 2013;68:e1–14.
8. Husain Z, Reddy BY, Schwartz R. DRESS syndrome: part II. Management and therapeutics. J
Am Acad Dermatol. 2013;68:e1–9.
9. Revuz J, Valeyrie-Allanore L. Drug reactions: acute generalized exanthematous pustulosis. In:
Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2. 3rd ed. London: Mosby; 2010.
p. 342–3.
Chapter 8
Inflammatory Diseases of the Blood Vessels
with Cutaneous Compromise
This chapter documents inflammatory diseases that present as vasculitis. Vasculitis

is the direct inflammation of the blood vessels that compromises or destroys the
vascular wall, causing bleeding and ischemia of the affected tissue, which can mani-
fest as clinical findings in the skin [1]. These dermatological manifestations of vas-
culitis are diverse, and the etiological approach of each is carried out according to
the caliber of the compromised blood vessel. Within this group are:
A. Vasculitis
(a) Small vessel vasculitis
(i) Leukocytoclastic vasculitis
(ii) Henoch-Schonlein purpura*
(iii) Acute hemorrhagic edema of childhood
(iv) Erythema elevatum diutinum*
(b) Mixed vasculitis
(i) Cryoglobulinemia
(ii) ANCA antibodies associated
1. Microscopic polyangiitis*
2. Granulomatosis with polyangiitis (Wegener’s granulomatosis)
3. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss
syndrome)*
(iii) Secondary
1. Septic vasculopathy
2. Vasculitis associated with inflammatory disorders (disseminated
intravascular coagulation)*
*
Pathologis not documented in this atlas

https://doi.org/10.1007/978-3-030-84107-2_8
224 8 Inflammatory Diseases of the Blood Vessels with Cutaneous Compromise
(c) Medium vessel vasculitis

(i) Polyarteritis nodosa
(d) Vasculitis of large vessels
(i) Temporal arteritis*
(ii) Takayasu arteritis*
Leukocytoclastic Vasculitis
• Definition: It represents the most common form of vasculitis, also called hyper-
sensitivity vasculitis or cutaneous necrotizing vasculitis, with involvement of the
postcapillary venules [2].
• Pathogenesis: Different pathophysiological mechanisms of this entity are con-
sidered, including the formation of immune complexes by infectious agents such
as hepatitis B or C or HIV, direct endothelial damage caused by viruses such as
cytomegalovirus, complement activation by fungi such as Candida, or formation
of autoantibodies. Additionally, this type of entity can occur in the context of
different autoimmune diseases such as lupus erythematosus, rheumatoid arthri-
tis, Sjogren’s syndrome, or inflammatory bowel disease [1].
• Clinical presentation: Clinically, purpura or erythematous papules are observed,
occasionally along with vesicles, blisters, pustules, or annular plaques in the
lower extremities (Figs. 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, 8.10, 8.11, and
8.12). Skin lesions may be preceded by extracutaneous symptoms such as
arthralgia, fever, or anorexia [1].
Fig. 8.1 Leukocytoclastic

vasculitis: On the pretibial
area, multiple purpuric
macules and papules are
seen converging, forming
edges
Leukocytoclastic Vasculitis 225

vasculitis: On the lower
limbs, multiple purplish
and violaceous macules
edges are observed

vasculitis related to HIV
infection: On the lower
limbs, violaceous maculae,
purpura, and papules are
observed, some with
central blood scabs in a
patient with human
immunodeficiency virus
(HIV) infection

drug vasculitis: Patient
with multiple papules and
purpuric macules that
converge, forming plaques
on the legs after exposure
to a beta-lactam drug,
compatible with
leukocytoclastic vasculitis
on histology
• Diagnosis: The clinical diagnosis is confirmed via histopathology. The biopsies

of patients with leukocytoclastic vasculitis show compromise of the postcapil-
lary dermal venules with infiltration of polymorphonuclear cells into the vessel
wall and the presence of intra- and extravascular eosinophils [1]. Other findings
include leukocytoclasia (degranulation and fragmentation of neutrophils with
nuclear dust production), extravagant erythrocytes, and signs of endothelial cell
damage [3] (Figs. 8.13, 8.14, and 8.15).
• Differential diagnosis: Leukocytoclastic vasculitis should be distinguished from
other types of small vessel vasculitis such as Henoch-Schonlein purpura, pig-
mentary purpura, cryoglobulinemia, Lucio phenomenon, and vasculitic urticaria,
among others [2].
Granulomatosis with Polyangiitis 227

vasculitis associated with
Sjogren’s syndrome:
Sjogren’s syndrome with
presence of well-defined
regular purpuric macules,
compatible with
Granulomatosis with Polyangiitis
• Definition: Also called Wegener’s granulomatosis and recently reclassified as a

subtype of small vessel vasculitis associated with positive ANCA antibodies, it is
a granulomatous systemic vasculitis that compromises the respiratory and renal
tract [4].
• Pathogenesis: It is suggested that the formation of granulomas and the presence
of small and medium vessel vasculitis are secondary to environmental factors
(such as Staphylococcus aureus infection), the presence of anti-PR3-positive
antibodies, and genetic polymorphisms [3].

systemic lupus
erythematosus: On the left
leg, multiple purpuric
papules and macules are
seen that converge on the
distal third of the leg
• Clinical presentation: Mucocutaneous involvement occurs in 40% of patients.

The presence of palpable purpura (Fig. 8.16) and ulcers are the most commonly
found dermatological presentations (Figs. 8.17 and 8.18). Lower or upper respi-
ratory tract involvement is observed in 90% of patients, while nasal, sinus, tra-
chea, or ear mucosal involvement is present in 70% [3].
• Diagnosis: There are different clinical and paraclinical criteria compatible with
granulomatosis with polyangiitis such as the presence of sinus, nasal, or oral
inflammation, typical imaging characteristics of the disease, renal alterations,
presence of granulomatous inflammation in the biopsy, airway stenosis, and the
presence of positive ANCA antibodies [3]. Although skin biopsy in most cases is
nonspecific, when papulonecrotic lesions are sampled, it is possible to find a
palisaded neutrophilic dermatitis with areas of granulomatous inflammation with
foci of basophilic necrobiosis [3] (Fig. 8.19).
Polyarteritis Nodosa 229

systemic lupus
erythematosus: Patient
with multiple purpuric
macules and papules with
irregular borders that
converge forming more
extensive plaques and
maculae on the distal third
of the legs in a patient with
systemic lupus
• Differential diagnosis: The main differential diagnoses are the other types of
vasculitis associated with positive ANCA antibodies, in particular Churg-Strauss
syndrome (eosinophilic granulomatosis with polyangiitis) [3].
Polyarteritis Nodosa
• Definition: Polyarteritis nodosa or panarteritis nodosa is a mixed vasculitis of

small and medium vessels with systemic and cutaneous involvement [5].
• Pathogenesis: Its etiology is unknown; however, it is suggested that it is an
immune-mediated disease, as supported by the presence of deposits of C3 and
IgM in the wall of arterial vessels in direct immunofluorescence. It is proposed

viral respiratory infection:
On the malleolar region
and distal third of the leg,
papules and purpuric
regular edges are observed,
some of them coalescing
that the presence of anti-phosphatidylserine-prothrombin IgM complexes

induces an immune response that results in endothelial cell apoptosis [4].
• Clinical presentation: There are two clinical spectra of the disease:
1. Systemic or classical polyarteritis nodosa: characterized by cutaneous
involvement in 25% of patients, otherwise a multi-organ involvement with
constitutional symptoms such as weight loss and fever
2. Cutaneous polyarteritis nodosa: initially presents with a violaceous network
of maculae (livedo reticularis) associated with painful subcutaneous nodules
and punched-out ulcers [4] (Figs. 8.20, 8.21, and 8.22).
• Diagnosis: The diagnosis is confirmed via histopathology with evidence of a
segmental vasculitis of medium caliber arteries. Focal areas of compromise
result in weakness of the vessel wall and necrosis, which leads to dilatation,
aneurysm formation, and stenosis (Figs. 8.23 and 8.24). Direct immunofluores-
cence shows deposits of C3, IgM, and fibrin in or around the vessel wall [4].
• Differential diagnosis: The presence of limb nodules should be distinguished
from erythema nodosum, and vascular lesions of polyarteritis nodosa should be
ruled out from microscopic polyangiitis, Churg-Strauss syndrome (eosinophilic
granulomatosis with polyangiitis), Wegener’s granulomatosis (granulomatosis
with polyangiitis), livedoid vasculopathy, Bazin’s indurated erythema, and vas-
culitic urticaria via other paraclinical and histological findings [4].
Acute Hemorrhagic Edema of Childhood 231

viral respiratory infection:
Involving the distal third of
the right leg, multiple
papules and purpuric
regular edges are observed,
some of which coalesce
Acute Hemorrhagic Edema of Childhood
• Definition: It represents a rare form of small vessel vasculitis that affects children
between 4 and 24 months of age with a self-resolving benign course [6].
• Pathogenesis: Although its cause is unknown, it has been linked to infections,
medications, or immunization in 75% of cases. An infectious prodrome has been
evidenced in two thirds of patients, usually from a respiratory, gastrointestinal, or
urinary origin. It is suggested that this form of vasculitis is secondary to the
deposition of immune complexes in response to an antigenic trigger [6].
• Clinical presentation: Clinically, acute hemorrhagic edema of childhood appears
as large erythematous urticarial plaques that evolve to form purpuric plaques
resembling annular, medallion, or polycyclic target lesions, which, when
resolved, can leave atrophic scars [6] (Fig. 8.25).

vasculitis: Male patient
with multiple purpuric
macules and plaques with a
deeper violaceous center
and some central
hemorrhagic vesicles
compatible with
histological

lupus erythematosus:
systemic lupus with
multiple purpuric plaques
and hemorrhagic blisters
on the surface
Acute Hemorrhagic Edema of Childhood 233

systemic lupus
erythematosus: On the
lateral aspect of the arm,
purpuric plaques with
hemorrhagic blisters in the
center are observed in a
systemic lupus
• Diagnosis: The diagnosis requires a clinical-pathological correlation. The histo-

pathological findings usually show evidence of a leukocytoclastic vasculitis with
or without fibrinoid necrosis (Fig. 8.5) to less specific findings (i.e., lymphohis-
tiocytic perivascular infiltrate with extravasation of erythrocytes) [7].
Immunofluorescence shows deposits of IgA with a vascular pattern in a third to
a quarter of patients [6, 7].
• Differential diagnosis: Multiform urticarias such as Henoch-Schonlein purpura,
erythema multiforme, Kawasaki disease, Sweet syndrome, and vasculitic urti-
caria should be ruled out [6].
Fig. 8.13 Small vessel vasculitis: Skin biopsy with H&E stain at 20× magnification shows a nor-
mal epidermis with a perivascular infiltrate that compromises the vessel wall associated with intra-
luminal fibrosis and karyorrhexis compatible with small vessel vasculitis-type leukocytoclastic
vasculitis
Septic Vasculopathy
• Definition: It is one of the most frequent manifestations of an acute inflammatory

response syndrome due to an infection with a global mortality of between 10%
and 90% [8].
• Pathogenesis: Septic vasculitis is one of the pathophysiological mechanisms of
sepsis. Other mechanisms such as disseminated intravascular coagulation, direct
vessel wall invasion by the microorganism, and immune-mediated vasculitis
have been described. Septic vasculitis manifests as a small vessel neutrophilic
vasculitis caused by a type III hypersensitivity reaction due to the formation of
immune complexes that deposit on the vascular wall [8].
• Clinical presentation: Clinically, there are hemorrhagic lesions such as pete-
chiae, palpable purpura, pustules, and vesicles with symmetrical compromise of
the lower limbs (Figs. 8.26 and 8.27). In numerous cases, it is indistinguishable
from leukocytoclastic vasculitis [8].
Cryoglobulinemia 235
Fig. 8.14 Leukocytoclastic vasculitis: At histopathology with H&E staining at 40× magnification,
complete neutrophilic infiltration of the blood vessel with leukocytoclasia and fibrinoid necrosis of
the blood vessel is observed
• Diagnosis: The clinical diagnosis requires histopathological confirmation with

the identification of the causative agent. The histopathological findings include a
small vessel neutrophilic vasculitis with leukocytoclasia and fibrinoid necrosis.
This process affects the entire epidermis with formation of thrombi rich in neu-
trophils, bacteria, and fibrin, with the presence of extracellular microab-
scesses [8].
• Differential diagnosis: Differential diagnoses to be considered are other causes
of leukocytoclastic vasculitis and causes of secondary vasculitis such as blood
dyscrasias, among others.
Cryoglobulinemia
• Definition: Also called cryoglobulinemic vasculitis, it is caused by the precipita-

tion (clumping together) of cryoglobulins, which are monoclonal or polyclonal
immunoglobulins that typically precipitate in colder temperatures in blood ves-
sels [9].
Fig. 8.15 Small vessel vasculitis: High-power magnification (40×) skin biopsy showing a vascular
lumen compromised by a mixed infiltrate with associated necrosis of the vessel wall
• Pathogenesis: It is considered a systemic vasculitis with inflammation of the

blood vessel induced by the deposition of IgM-IgG immune complexes and
subsequent complement activation. There are three presentations of the disease
with different etiologies:
1. Type I cryoglobulinemia, due to the presence of monoclonal IgM and associ-
ated with malignant hematological disorders such as multiple myeloma and
Waldenstrom macroglobulinemia
2. Type II, characterized by monoclonal IgM directed against IgG
3. Type III, with polyclonal IgM against IgG
• These last two variants are considered mixed macroglobulinemia associated with
hepatitis C virus infections, HIV, autoimmune connective tissue diseases, and
some lymphoproliferative disorders [7].
• Clinical presentation: Cryoglobulinemia presents with purpura, arthralgia or
arthritis, and weakness. A typical cutaneous finding is the presence of palpable
purpura on the extremities which may be associated with ecchymosis, erythema-
tous papules, nodules, cutaneous necrosis, urticaria, livedo reticularis, bullous
lesions, and ulcers, the latter being rare. The chronic evolution of the lesions
Fig. 8.16 Granulomatosis

with polyangiitis: On the
anterior part of the thigh
and leg, multiple purpuric
macules and papules are
granulomatous necrotizing
vasculitis, presented as
palpable purpura
leads to the development of acral necrosis (Figs. 8.28, 8.29, 8.30, 8.31, 8.32,
8.33, and 8.34). Disease involvement of the head and mucous membranes as well
as the evolution of livedoid vasculitis, Raynaud’s phenomenon, and cold-induced
acrocyanosis in the helices of the ears occurs in patients with type I cryoglobuli-
nemia [7].
• Diagnosis: The clinical diagnosis usually requires correlation with laboratory
findings. Histologically, it is possible to find leukocytoclastic vasculitis in papu-
lar lesions, while necrotic or ulcerated lesions reveal medium vessel vasculitis
(Figs. 8.35, 8.36, and 8.37). In the direct immunofluorescence study, granular
deposition of IgM and C3 in a vascular pattern is observed in the papillary der-
mis. Moreover, serological findings are helpful in establishing the diagnosis,
such as the presence of cryoglobulins, anti-HCV antibodies, and hypocomple-
mentemia, being the most frequent findings in 90% of patients [7].
• Differential diagnosis: Other types of small and medium vessel vasculitis such as
those associated with positive ANCA antibodies should be ruled out, as well as
autoimmune connective tissue diseases with cutaneous involvement [7].

with polyangiitis: On the
lateral aspect of the right
leg, an ulcer with regular
violaceous edges is
observed

with polyangiitis: An
infiltrated ulcer with
regular borders and a
serous secretion is
witnessed on the leg
Fig. 8.19 Granulomatosis with polyangiitis: Skin biopsy stained with H&E at 40× magnification
showing medium caliber vasculitis as evidenced by a granulomatous infiltrate in the vessel wall
and lumen
Fig. 8.20 Polyarteritis

nodosa: Patient with
multiple painful nodules
on the pretibial region and
punching ulcers on the
dorsum of the left foot,
compatible with cutaneous
polyarteritis nodosa

nodosa: Multiple reticular
violaceous macules, some
converging to form a
network, while others are
discontinuous, compatible
with livedo racemosa in a
patient with polyarteritis
nodosa

nodosa: On the bilateral
lower limbs, multiple
violaceous macules are
seen that coalesce to form
a reticulated network
pattern, compatible with
livedo racemosa in a
patient with polyarteritis
nodosa

nodosa: In the medium-
deep dermis, medium-sized
vasculitis is observed with
the presence of
neutrophilic debris, fibrin,
and red blood cells in the
arteriolar wall
Fig. 8.24 Medium vessel

vasculitis: H&E-stained
skin biopsy at 40× with
evidence of a perivascular
and intraluminal infiltrate
with fibrin in the middle
vessel wall, located in the
dermo-hypodermic
junction
Fig. 8.25 Acute

hemorrhagic edema of
childhood: An infant with
the presence of infiltrated,
edematous, and
erythematous plaques on
the face and trunk,
compatible with small
vessel vasculitis
Fig. 8.26 Septic

vasculopathy: On the
dorsum of the left foot,
acrocyanosis with
hemorrhagic vesicles and
purpura is observed.
Histopathologically, there
is evidence of a small
vessel neutrophilic
vasculitis with bacteria
Fig. 8.27 Septic

vasculopathy: Patient with
digital gangrene secondary
to bacterial sepsis with
evidence of vasculitis
secondary to septic emboli
Fig. 8.28
Cryoglobulinemia: Patient
with ulcers covered with
necrotic scabs with
borders and infiltrates
compatible with
cryoglobulinemic vasculitis
Fig. 8.29
Cryoglobulinemia: On the
posterior aspect of the leg,
retinal purpura is observed
with some well-defined
irregularly shaped purpuric
plaques compatible with
Fig. 8.30
posterior aspect of the right
arm, a purpuric plaque
with a well-defined and
regular retiform border is
seen, compatible with
Fig. 8.31
auricular area, necrosis
secondary to
is observed
Fig. 8.32
Cryoglobulinemia:
Compromising the distal
phalanx of the second digit
of the right hand, digital
necrosis secondary to
vasculitis caused by the
precipitation of
cryoglobulins is observed
Fig. 8.33
Cryoglobulinemia:
Necrotic plaques
secondary to vasculitis due
to cryoglobulin
precipitation are observed
on the pulp of the fourth
and fifth digits of the foot
Fig. 8.34
Cryoglobulinemia: A
splinter dermatoscopy
shows splinter
hemorrhages secondary to
vasculitis
Fig. 8.35 Cryoglobulinemia: H&E-stained biopsy at 20× reveals a normal epidermis with dilated
small and medium vessels in the reticular dermis and dermo-hypodermic junction
Fig. 8.36 Cryoglobulinemia: H&E-stained skin biopsy with evidence of medium caliber vessels
with evidence of an intraluminal thrombus in the reticular dermis
Fig. 8.37 Cryoglobulinemia: H&E-stained skin biopsy at 40× with evidence of an intraluminal
thrombus with a perivascular infiltrate and hyaline wall necrosis in a patient with type II
cryoglobulinemia
References
1. Carlson JA. The histological assessment of cutaneous vasculitis. Histopathology. 2010;56:3–23.

2. Pulido-Pérez A, Avilés-Izquierdo JA, Suárez-Fernández R. Cutaneous vasculitis. Actas
3. Shinkai K, Fox LP. Cutaneous vasculitis: cutaneous leukocytoclastic vasculitis. In: Bologna JL,
4. Shinkai K, Fox LP. Cutaneous vasculitis: Wegener’s granulomatosis. In: Bologna JL, Jorizzo
JL, Rapini RP, editors. Dermatology, vol. 2. 3rd ed. London: Mosby; 2010. p. 403–4.
5. Morgan AR, Schwartz RA. Cutaneous polyarteritis nodosa: a comprehensive review. Int J
Dermatol. 2010;49:750–6.
6. Shinkai K, Fox LP. Cutaneous vasculitis: acute hemorrhagic edema of infancy. In: Bologna JL,
7. Legrain V, Lejean S, Taïeb A, Guillard JM, Battin J, Maleville J. Infantile acute hemorrhagic
edema of the skin: study of ten cases. J Am Acad Dermatol. 1991;24(1):17–22.
8. Delgado-Jiménez Y, Fraga J, Fernández-Herrera J, García-Diez A. Vasculopatía séptica. Actas
9. Fiorentino DF. Cutaneous vasculitis. J Am Acad Dermatol. 2003;48:311–40.
Chapter 9
Inflammatory Diseases Affecting
Melanocytes
The inflammatory diseases that affect the melanocyte are classified into two groups:
those that destroy the melanocyte via an autoimmune response, presenting as hypo-
chromic or depigmented macules, and, conversely, those that activate melanin pro-
duction within the melanocyte as a consequence of an inflammatory process that
results in hyperpigmented macules. The pigmentary disorders of inflammatory ori-
gin are grouped as follows:
A. Inflammatory diseases that occur with hyperpigmentation
(a) Post-inflammatory hyperpigmentation
(b) Erythema dyschromicum perstans (see chapter on lichen and lichenoid
reactions)
(c) Lichen planus pigmentosus (see chapter on lichen and lichenoid reactions)
(d) Melasma
(e) Flagellate erythema*
(f) Confluent and reticulated papillomatosis of Gougerot and Carteaud
(g) Erythema ab igne
B. Inflammatory diseases that occur with hypopigmentation
(a) Vitiligo
(b) Post-inflammatory hypopigmentation
(c) Lichen sclerosus et atrophicus (see chapter on lichen and lichenoid
reactions)
(d) Lichen striatus (see chapter on lichen and lichenoid reactions)
*
Pathologies not documented in this atlas

https://doi.org/10.1007/978-3-030-84107-2_9
254 9 Inflammatory Diseases Affecting Melanocytes
(e) Pityriasis alba
Post-inflammatory Hyperpigmentation
• Definition: Represents pigmentation acquired in response to exaggerated mela-

nin production following inflammation or trauma to the skin [1].
• Pathogenesis: In epidermal post-inflammatory hyperpigmentation, there is an
increase in melanin production and subsequent transfer of melanin to the kerati-
nocytes, caused by inflammatory mediators such as prostaglandins E2 and D2. In
dermal hyperpigmentation, melanin pigment is deposited in the dermis where it
is phagocytosed by macrophages, persisting for (up to) several years [1].
• Clinical presentation: It appears as brown hyperpigmented macules (epidermal
component) or gray-blue macules (dermal component). The macules appear in
Fig. 9.1 Post-

inflammatory
hyperpigmentation: llinear
hyperpigmented macules at
sites of previous trauma
(scratch) on the anterior
aspect of the right thigh
Melasma 255
Fig. 9.2 Post-

inflammatory
hyperpigmentation: brown
and hyperpigmented
irregular edges on the
pretibial region secondary
to sunburn
body sites exposed to the external mediator, which triggers the inflammatory
process, and for this reason, it may have the same dimensions corresponding to
the initial dermatosis (Figs. 9.1 and 9.2). This condition is exacerbated by ultra-
violet radiation, inflammation, and trauma [1].
• Diagnosis: The diagnosis is clinical, and a skin biopsy is reserved to rule out
other conditions such as lichen planus pigmentosus, lichenoid reaction, or fixed
drug eruption. On histopathological examination, an increase in melanin in the
epidermis or melanophages in the dermis can be observed depending on the
component of hyperpigmentation (epidermal or dermal) [1].
• Differential diagnosis: Entities such as erythema dyschromicum perstans,
melasma, pityriasis versicolor, and idiopathic atrophoderma of Pasini and Pierini
should be ruled out [1].
Melasma
• Definition: Melasma or chloasma is an acquired disease that appears as sym-

metrical hyperpigmented macules situated mainly on the face [2].
• Pathogenesis: Although it is not a proper inflammatory disease, it is suggested
that there is an underlying genetic and racial predisposition that is exacerbated
by ultraviolet radiation and the intake of oral contraceptives. Ultraviolet radia-

tion induces the proliferation and migration of melanocytes and melanogenesis.
Similarly, UV radiation can trigger the production of multiple cytokines (IL-1,
endothelin 1, the alpha-melanocyte-stimulating hormone, and adrenocorticotropic
hormone) by the keratinocyte, which favors the production and proliferation of
melanocytes [2].
Fig. 9.3 Malar melasma:

hyperpigmented and
reticulated macules with
irregular edges are
observed on the cheeks
Fig. 9.4 Melasma: a

patient who presents with
with irregular edges in the
malar region
Erythema Ab Igne 257
Fig. 9.5 Melasma:

with irregular edges are
observed in the zygomatic
and malar regions, with
some hypopigmented
macules in their center
Fig. 9.6 Melasma:

with irregular edges are
observed in the zygomatic
and right malar regions,
with some hypopigmented
macules in their center
• Clinical presentation: There are different clinical patterns of the disease, all of
which are characterized by the presence of brown or hyperpigmented macules
that are usually distributed on the central facial region, the forehead, the cheeks,
the chin, the nose, and the skin of the upper lip. The malar pattern comprises the
cheeks and nasal dorsum (Figs. 9.3, 9.4, 9.5, and 9.6). The mandibular melasma
pattern is distributed by the mandibular trigeminal branch and, in some cases,
may be accompanied by Civatte’s poikiloderma (telangiectasias, atrophy and
dyschromia due to photoaging) [2].
• Diagnosis: The diagnosis is clinical, and the skin biopsy is reserved only for
those cases in which there is a clinical suspicion for specific histopathological
findings such as Ramírez disease or lichenoid reactions. Wood’s light lamp is
useful in differentiating the depth of pigmented lesions, enhancing epidermal
pigment to a higher degree compared with dermal pigment [2].
• Differential diagnosis: Conditions that can be confused with melasma are post-
inflammatory hyperpigmentation, solar lentigines, ephelides, exogenous pig-
mentation, friction melanosis, blue nevus, Hori nevus, and Ota nevus [2].
Erythema Ab Igne
• Definition: Represents an acquired heat-induced dermatosis that presents clini-

cally with reticulated erythema, hyperpigmentation, epidermal atrophy, and tel-
angiectasias [3].
• Pathogenesis: It occurs due to repeated and prolonged exposure to infrared radia-
tion or temperatures higher than 45 °C, with consequent damage to the superfi-
cial vascular plexus of the dermis with hemosiderin deposition. Related physical
agents are hot water bottles, ultrasound, and laptops [3].
• Clinical presentation: Hyperpigmented reticulated macules are observed in
patients with repeated and prolonged exposure to physical agents that radiate
infrared light or heat (Figs. 9.7 and 9.8). Malignant transformation to squamous
cell carcinomas has been reported in some cases [4].
• Diagnosis: Ascertained usually via corresponding the clinical presentation with
the previous history of heat exposure. Histology shows epidermal atrophy with
loss of the dermoepidermal junction with vacuolar alteration of the basal layer
Fig. 9.7 Erythema ab

igne: reticulated
are seen on the back in a
low back pain and frequent
exposure to hot water
compresses
Fig. 9.8 Erythema ab

igne: male patient with
reticulated hyperpigmented
macules on the inner thighs
Confluent and Reticulated Papillomatosis of Gougerot and Carteaud 259
and fragmentation of collagen along with melanin and hemosiderin deposition.

Similarly, polymorphonuclear lymphocytic and histiocytic infiltrates can be
observed [3].
• Differential diagnosis: It should be distinguished from reticular livedo, livedoid
dermatitis such as livedoid vasculopathy, panarteritis nodosa, and livedo race-
mosa [3].
onfluent and Reticulated Papillomatosis of Gougerot

C
and Carteaud
• Definition: It is part of the group of dermatoses that occur due to an alteration in

keratinization secondary to an abnormal hypersensitivity response of the host to
a pathogen [5].
• Pathogenesis: There is an abnormal host response to fungal (Pityrosporum orbi-
culare) or bacterial (Actinomyces sp, Dietzia sp) antigens. Similarly, it is accepted
Fig. 9.9 Confluent and

reticulated papillomatosis
of Gougerot and Carteaud:
on the back of the neck,
macules and brown patches
of reticulated pattern are
observed

on the back of the neck,
multiple brown papules are
observed that converge,
forming a large reticulated
plaque

on the trunk, brown
reticulated macules are
observed that, on histology,
confirm a diagnosis of
confluent and reticulated
papillomatosis of Gougerot
and Carteaud

compromising the trunk
and abdomen, brown and
and plaques with
articulated and defined
edges are observed
Vitiligo 261

at the periumbilical level,
slightly scaly brown
papules and plaques are
observed, some in a linear
and reticular pattern
that there is a keratinization disorder of genetic or acquired origin that predis-

poses the host’s abnormal response to pathogens [5].
• Clinical presentation: It appears as brown or hyperpigmented macules or pap-
ules that involve the neck, the interscapular region, and the intermammary region
(Figs. 9.9 and 9.10). Lesions can become chronic and verrucous, forming a retic-
ulated appearance with mild flaking (Figs. 9.11, 9.12, and 9.13).
• Diagnosis: Different diagnostic criteria have been proposed, among which are:
1. The presence of scaly and brown macules and plaques that can be cross-
linked, compromising the superior part of the trunk and neck
2. Presence of a negative fungal culture and/or poor response to antifun-
gal therapy
3. Good response to minocycline
Histopathology shows acanthosis, hyperkeratosis, and atrophy of the granular
layer with irregular papillomatosis and hyperpigmentation of the basal layer. A
slight perivascular mononuclear infiltrate associated with edema is found in the
dermis [5].
• Differential diagnosis: The most common differential diagnosis is acanthosis
nigricans followed by seborrheic dermatitis, flat warts, verruciform
epidermodysplasia, Darier’s disease, Dowling-Degos disease, cutaneous amyloi-
dosis, and parapsoriasis [5].
Vitiligo
• Definition: Vitiligo is an acquired inflammatory disease of autoimmune origin

characterized by achromic macules secondary to selective destruction of the
melanocyte [6].
• Pathogenesis: Although its etiology is unknown, it has been related to autoim-

mune diseases and certain HLA polymorphisms (such as HLA-A*02, HLA-
A*33, and HLA-Aw31). The autoimmune theory is that which has documented
the most evidence as the etiology of vitiligo given the concomitant presentation
with other autoimmune entities such as thyroiditis, type I diabetes mellitus, ele-
vated levels of nuclear autoantibodies, and the response of vitiligo to immuno-
suppressive therapies [7].
• Clinical presentation: Vitiligo appears as achromic or hypopigmented macules
at the normally pigmented sites that may be accompanied by hairy depigmenta-
tion (leukotrichia). There are three presentations of the disease: the localized
type, the generalized type, and the universal type. The localized variant can be
subdivided into focal (Figs. 9.14, 9.15, 9.16, and 9.17), segmental (follows a
dermatome or a Blaschko line) (Fig. 9.18), and mucosal (Figs. 9.19 and 9.20).
The generalized variant is the most common form with a vulgar subtype that is
located in the fingers, wrists, armpits, groin, perioral region, genitalia, and peri-
Fig. 9.14 Focal vitiligo:

on the base and skin of the
penis, an achromic macula
edges is observed
Fig. 9.15 Focal vitiligo:

on the suprapubic region,
an achromic macula with
borders is observed
Vitiligo 263
Fig. 9.16 Focal vitiligo: in

the lumbar region, an
achromic macula with
borders is observed
Fig. 9.17 Focal vitiligo: a

hypopigmented macule
with poorly defined
irregular borders is seen on
the lateral aspect of
the neck
Fig. 9.18 Segmental

vitiligo: compromising two
dermatomes of the right
upper limb, achromic
irregular edges are
observed
ocular region (Figs. 9.21, 9.22, 9.23, 9.24, and 9.25). The universal variant affects
more than 80% of the body surface [7] (Figs. 9.26, 9.27, 9.28, 9.29, and 9.30).
• Diagnosis: The diagnosis is clinical, and the biopsy is reserved for atypical
cases. Wood’s light examination elucidates the extension and activity of the
disease (Fig. 9.31). Histopathological examination of the borders of the initial
skin lesions shows a lymphocytic infiltrate with absence of melanocytes in the
Fig. 9.19 Mucosal

vitiligo: in the perianal
region, an achromic
macula is observed with
extension to the anal
mucosa
Fig. 9.20 Vitiligo

vulgaris: achromic macules
edges are observed in the
labia majora and perianal
region. Note the presence
of linearly distributed,
slightly erythematous
papules on the inner side
of the left thigh that
corresponds to an
associated lichen striatus
achromic center, confirmed with immunohistochemistry (Melan A or HMB-45

markers). Additionally, a decrease in pigment confirmed with Fontana-Masson
staining can be observed [8].
• Differential diagnosis: The differential diagnoses are broad since it can be rela-
tively indistinguishable from leukoderma or diseases that occur with pigmentary
alteration such as pityriasis versicolor, treponematosis, genetic syndromes (e.g.,
piebaldism, tuberous sclerosis, and Vogt-Koyanagi-Harada syndrome), pityriasis
alba, post-inflammatory hypopigmentation, amelanotic melanoma, mycosis fun-
goides, and hypopigmented nevus [6].
Pityriasis Alba 265
Fig. 9.21 Vitiligo vulgaris: on the dorsum of the hands compromising the distal phalanges, achro-
mic macules with well-defined irregular edges are observed
Post-inflammatory Hypopigmentation
• Definition: Represents a frequent hypochromia in patients with darker photo-

types secondary to a basal inflammatory disease under treatment or self-
resolution [9].
• Pathogenesis: Skin inflammation alters the biogenesis of the melanosome, the
production of melanin, the transport of melanin, and especially the transfer of
melanosomes to the keratinocyte. Local severe inflammation leads to functional
loss of melanocytes and even cell death [9].
• Clinical presentation: Lesions present as hypopigmented macules that follow the
pattern of previous inflammatory lesions. The macules can be located or spread
with decreased pigment (Fig. 9.32). Total depigmentation is observed in the con-
text of severe atopic dermatitis (Fig. 9.33), discoid lupus erythematosus, or
severe bullous diseases [9] (Fig. 9.34).
• Diagnosis: The diagnosis is clinical, but other conditions appear similar to post-
inflammatory hypopigmentation that, on histopathology, demonstrate the pres-
ence of sarcoid changes and even mycosis fungoides [9].
• Differential diagnosis: Among them are achromic nevi, depigmented nevi, vitil-
igo, lichen sclerosus et atrophicus, hypopigmented macules of tuberous sclero-
sis, hypopigmented mycosis fungoides, and sarcoidosis [9].
Fig. 9.22 Acral vitiligo:

on the back of the hand
and foot, there are
achromic macules with
edges
Pityriasis Alba
• Definition: It is a common self-resolving pigmentary disorder that affects chil-

dren and adolescents with darker phototypes and lower socioeconomic sta-
tus [10].
• Pathogenesis: Its etiology is unknown; however, it has been related to hygro-
scopic skin defects as well as inflammatory processes in the epidermis that lead
to hypermetabolism by keratinocytes that decrease their ability to receive mela-
nin granules. The factor mainly related to the exacerbation of the disease is ultra-
violet radiation [10].
• Clinical presentation: The skin lesions present as round or oval hypopigmented
macules with well-defined edges that involve the face, the upper extremities, and,
rarely, the trunk and lower extremities. The lesions present in three stages:
Pityriasis Alba 267
Fig. 9.23 Vitiligo

vulgaris: on the anterior
aspect of the metatarsals
and ankles, there are
edges with some areas of
repigmentation
Fig. 9.24 Acral vitiligo: on the posterior aspect of the distal phalanges, achromic macules with
well-defined irregular edges are observed. Note the sharp white line of demarcation of disease
involvement on the posterior aspect of the right hand

vitiligo: compromising the
trunk, the periumbilical
region, the extremities, and
the neck, multiple
achromic and
hypopigmented macules
with irregular borders are
observed
Fig. 9.26 Universal

vitiligo: male patient with
involvement of more than
80% of total body surface
by achromic macules
Pityriasis Alba 269
Fig. 9.27 Universal

vitiligo: patient with
involvement of more than
by achromic macules
Fig. 9.28 Universal

vitiligo: female patient
with involvement of the
lower limbs by large
achromic macules
Fig. 9.29 Universal

vitiligo: multiple large
some islands of residual
pigmentation are observed
on the trunk and upper
limbs
Fig. 9.30 Universal

vitiligo: female patient
with extensive achromic
macules with some
residual islands of
pigmentation on her face
Pityriasis Alba 271
Fig. 9.31 Wood’s light

lamp examination in
vitiligo: a bright
fluorescent macula with
right side of the neck
Fig. 9.32 Post-

inflammatory
hypopigmentation: on the
proximal third of the right
leg, two hypopigmented
Pityriasis Alba 273
Fig. 9.33 Post-

inflammatory
hypopigmentation:
adolescent patient with a
history of severe atopic
dermatitis with secondary
multiple hypopigmented
edges at previous sites of
active eczema on the back
Fig. 9.34 Post-

inflammatory
hypopigmentation: child
with hypopigmented
macules secondary to
linear IgA dermatosis
under treatment
Pityriasis Alba 275
Fig. 9.35 Pityriasis alba:

preadolescent patient with
multiple hypopigmented
edges on the malar region,
chin, and forehead

adolescent patient with
hypopigmented patches on
the lateral aspect of the
right arm

school patient with
hypochromic patches with
borders on the malar
region
References 277
1. Initially, an erythematous or pink plaque is observed, sometimes associated

with pruritus.
2. The erythema subsequently disappears, and the plaque flattens with associ-
ated fine superficial scale.
3. Finally, a residual hypopigmented macula is observed that can last several
months to years [10] (Figs. 9.35, 9.36, and 9.37).
• Diagnosis: The diagnosis is clinical given that the findings on histopathology are
nonspecific. Histology shows hyperkeratosis and focal parakeratosis, acanthosis,
spongiosis, and decreased melanocytes and melanosomes in the basal layer with
atrophy of sebaceous glands [10].
• Differential diagnosis: Pityriasis alba should be distinguished from atopic der-
matitis, psoriasis, post-inflammatory hypopigmentation, pityriasis versicolor,
and hypopigmented mycosis fungoides [10].
References
1. Wu CM. Disorders of hyperpigmentation: postinflammatory hyperpigmentation. In: Bologna

2. Sheth VM, Pandya AG. Melasma: a comprehensive update. J Am Acad Dermatol.
2011;65:689–97.
3. Weber MB, et al. Erythema ab igne: a case report. An Bras Dermatol. 2005;80:187–8.
4. Arrington JH, Lockman DS. Thermal keratoses and squamous cell carcinoma in situ associ-
ated with erythema ab igne. Arch Dermatol. 1979;115:1226–8.
5. Fasano ME, et al. Papilomatosis confluente y reticulada: a propósito de dos casos y revisión
bibliográfica. Arch Argent Dermatol. 2011;61:233–8.
6. Alikhan A, et al. Vitiligo: a comprehensive overview. J Am Acad Dermatol. 2011;65:473–91.
7. Ianella G, et al. Vitiligo: pathogenesis, clinical variants and treatment approaches. Autoimmun
Rev. 2015;15:335–43.
8. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;4(386):74–84.
9. Ortone JP, Passeron T. Vitiligo and other disorders of hypopigmentation: postinflammatory
hypomelanosis. In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2. London:
Mosby; 2010. p. 1038–9.
10. Moreno-Cruz B, Castanedo-Cázares JP, Torres-Álvarez B y col. Pityriasis alba. Dermatol Rev
Mex 2010;54(2):67–71.
Chapter 10
Vesiculobullous Inflammatory Diseases
Within this group are all the diseases that clinically occur with vesicles and blisters
that, when broken, leave eroded areas and, on rare occasions, ulcers. The patho-
physiological mechanism of these entities involves an abnormal immune response
to different components of the epidermis or dermoepidermal junction. The most
representative diseases are thus grouped:
A. Pemphigus
(a) Pemphigus vulgaris
(i) Mucocutaneous
(ii) Vegetans
(b) Pemphigus foliaceus
(i) Seborrheic or classic
(ii) Type fogo selvagem
(iii) Senear-Usher syndrome*
(c) Paraneoplastic pemphigus*
B. Dermatitis herpetiformis
C. Linear IgA dermatosis
D. Bullous pemphigoid
E. Cicatricial pemphigoid*
F. Pemphigoid gestationis*
G. Acquired epidermolysis bullosa*
*
Pathologis not documented in this atlas

https://doi.org/10.1007/978-3-030-84107-2_10
280 10 Vesiculobullous Inflammatory Diseases
Pemphigus Vulgaris
• Definition: Pemphigus vulgaris, like other forms of pemphigus, belongs to the

group of vesiculobullous diseases of autoimmune etiology [1].
• Pathogenesis: Specific antibodies have been identified against intracellular bind-
ing proteins (e.g., desmogleins 1 and 3), which are widely distributed in the
stratified epithelium of the skin and mucosa.
• Clinical presentation: This is characterized by the presence of flaccid vesicles
and blisters that affect normal skin and mucosa. There are two clinical forms of
the disease: pemphigus vulgaris predominantly in the mucosa and pemphigus
vulgaris mucocutaneous. The blisters and vesicles leave eroded areas which
compromise any part of the body surface (Figs. 10.1, 10.2, 10.3, 10.4, 10.5, 10.6,
10.7, 10.8, and 10.9). The erosions are irregular and painful in some cases, while
blisters have a generally clear content that can become hemorrhagic, cloudy, or
sero-purulent [1]. Different clinical variants of pemphigus can be distinguished
such as:
–– Pemphigus vegetans: This represents a rare variant of pemphigus vulgaris that
occurs as vegetations and erosions that affect the flexor areas. Two variants of
pemphigus vegetans are recognized: the Neumann type, which commences as
vesicles and erosions that progress to vegetative plaques (Fig. 10.10), and,
another less common variant, the Hallopeau type with pustular lesions and a
benign course [2].
• Diagnosis: It is confirmed with histopathological findings in which intercellular
edema with loss of intercellular junctions and formation of suprabasal clefts and
blisters is initially observed. The basal epithelium remains attached to the der-
moepidermal junction with cells separated from each other giving a row-like
appearance of “headstones” on the floor of the blister. Blistering is preceded by
Fig. 10.1 Pemphigus

vulgaris: Eroded flaccid
blisters plus erosions with
irregular edges are seen in
the right gluteal region in a
patient with pemphigus
vulgaris
Pemphigus Vulgaris 281
Fig. 10.2 Pemphigus

vulgaris: Adult patient
with multiple erosions on
the trunk and upper limbs
with irregular edges,
covered with haemoserous
crust
Fig. 10.3 Pemphigus

vulgaris: Multiple
hemorrhagic erosions are
observed on the lower
back, some covered with a
serohematic crust
eosinophilic spongiosis in some cases. The superficial dermis shows a mixed

inflammatory infiltrate with some eosinophils. The diagnosis is confirmed with
direct immunofluorescence where IgG deposits (IgG autoantibodies directed
against desmoglein 3) are evident on the surface of the keratinocytes of the per-
ilesional skin [3].
• Differential diagnosis: A broad range of other bullous diseases may be mistaken
for pemphigus vulgaris. Mucosal lesions should be distinguished from stomatitis
secondary to herpes simplex, aphthous ulcers, lichen planus, paraneoplastic
pemphigus, or autoimmune diseases such as dermatitis herpetiformis and lupus
erythematosus. Cutaneous lesions should be differentiated from autoimmune
bullous diseases such as pemphigus foliaceus, pemphigus vegetans, IgA pemphi-
gus, paraneoplastic pemphigus, bullous pemphigoid, linear IgA dermatosis,
erythema multiforme, Grover’s disease, and benign familial pemphigus (Hailey-
Hailey disease) [4].
Fig. 10.4 Pemphigus

edges, covered with
serohematic crusts and
involving the trunk, upper
extremities, and face
Fig. 10.5 Severe

pemphigus vulgaris: Large
eroded erythematous
plaques are seen on the
trunk, upper extremities,
and face in a patient with
severe pemphigus vulgaris
Pemphigus Vulgaris 283
Fig. 10.6 Pemphigus

with multiple eroded
plaques covered with
irregular-edged
serohematic crusts
Fig. 10.7 Pemphigus

covered with hematic
crusts on the trunk and
upper extremities
Fig. 10.8 Pemphigus

covered with serohematic
crusts on the trunk
Pemphigus Foliaceus
• Definition: Pemphigus foliaceus belongs to the group of vesicular bullous dis-

eases of autoimmune etiology characterized by the presence of intraepidermal
blisters and IgG4-type autoantibodies against desmoglein 1 [5].
• Pathogenesis: The presence of autoantibodies directed against the amino-
terminal domain of desmoglein 1 generates the detachment of the desmosome in
the stratum corneum in its uppermost portion. Desmoglein expression is higher
in the upper torso compared to the lower torso and scalp. The weak expression of
desmoglein 1 makes this entity respect the mucosa [3].
• Clinical presentation: Clinically, it presents with scaly plaques on an erythema-
tous base with distribution in seborrheic areas of the face, scalp, and upper trunk.
On rare occasions, it is possible to observe fragile blisters that dissect leaving a
residual scab (Figs. 10.11 and 10.12). Lesions can be limited to seborrheic areas,
being the classic presentation or rapidly evolving to erythroderma [6]. There are
two infrequent clinical variants of pemphigus foliaceus:
–– Pemphigus foliaceus-type fogo selvagem: This variant has a particular epide-
miological and geographical profile that affects people living in countries of the
Amazonian tropics such as Colombia, Ecuador, Peru, Brazil, and Venezuela [6].
Pemphigus Foliaceus 285
Fig. 10.9 Pemphigus

vulgaris: Eroded
irregular edges can be seen
involving the back and
buttocks
The population group mainly affected is children or young adults under 25 years
of age in rural areas with poor sanitary conditions [7]. Clinically, it is indistin-
guishable from classic pemphigus foliaceus (Figs. 10.13 and 10.14).
–– Pemphigus erythematosus or Senear-Usher syndrome: It is part of a localized
form of pemphigus foliaceus with lesions distributed on the malar area of the
face and other seborrheic areas associated with positive antinuclear antibody
markers [6].
• Diagnosis: The diagnosis is made based on clinical findings, histopathology, and
direct immunofluorescence. Skin biopsies from pemphigus foliaceus in its initial
stages typically show vacuoles in the intercellular spaces with formation of
subcorneal, intergranular, or supraepidermal clefts. The presence of eosinophilic
spongiosis is rare. Direct immunofluorescence shows immune complexes pres-
ent in the upper epidermal portion but low or absent in the mucosa [6].
• Differential diagnosis: It should be differentiated from impetigo, impetiginized
eczema, erythema multiforme, and Stevens-Johnson syndrome along with other
autoimmune bullous diseases like pemphigus vulgaris and bullous pemphigoid [6].
Fig. 10.10 Pemphigus

vegetans: Some vegetating
eroded areas covered with
observed on the scalp
Dermatitis Herpetiformis
• Definition: Represents a chronic, pruritic papulovesicular rash with symmetrical

distribution in extensor areas associated with gluten-sensitive enteropathy [8].
• Pathogenesis: IgA autoantibodies are directed against tissue transglutaminase
present in the epidermis, often in the context of gluten-sensitive enteropathy in
60–75% of cases. The mechanism by which autoantibody deposition occurs is
unknown [8].
• Clinical presentation: Clinically, it appears as erythematous papules or urticarial
plaques with central vesicles or hemorrhagic crusts that group together giving
the herpetic appearance. Lesions can leave hyperpigmentation or hypopigmenta-
tion. Frequently affected areas include the elbows, knees, buttocks, shoulders,
and sacral areas in a symmetrical distribution. The hairline is also a common site
for lesions and less so on the palms and soles [8] (Figs. 10.15, 10.16, 10.17,
and 10.18).
• Diagnosis: Initially, clinical suspicion is based on clinical findings which are
then confirmed via immunofluorescence studies. Granular immunoglobulin A
deposition in normal skin is evident in this manner and associated with the pres-
ence of grouped neutrophils in the papillary dermis (microabscesses) [8].
• Differential diagnosis: Eczema, atopic dermatitis, and papular urticaria should
be considered as differential diagnoses along with neurotic excoriations, bullous
pemphigoid, pemphigoid gestationis, linear IgA dermatosis, and scabies [8].
Linear Iga Bullous Dermatosis 287

foliaceus: Multiple
are seen on the face and
trunk in a patient with
compatible with
pemphigus foliaceus
Linear Iga Bullous Dermatosis
• Definition: Chronic autoimmune blistering disease characterized by the linear

deposit of immunoglobulin IgA at the subepidermal level [9].
• Pathogenesis: It is characterized by the presence of IgA-type antibodies directed
against the dermoepidermal junction protein BP180/collagen XVII. Different
clearly recognized triggers have been identified, among which include drugs
such as vancomycin, nonsteroidal anti-inflammatory drugs, burns, vaccines,
lymphoproliferative disorders, and kidney and bladder cancer [9].
Fig. 10.12 Foliaceous

pemphigus: Multiple
covered with serohematic
crusts are observed on the
superior third of the
posterior trunk

foliaceus-type fogo
selvagem: A 9-year-old
male patient from Puerto
Inirida, Colombia, with
multiple eroded
erythematous plaques that
compromise more than

foliaceus-type fogo
selvagem: Erythematous
plaques with superficial
observed involving the
face, scalp, and trunk. Note
the sparing of oral mucosa
Fig. 10.15 Dermatitis

herpetiformis:
Erythematous papules and
plaques with central
serohematic crusts in a
patient with dermatitis
herpetiformis

herpetiformis:
Compromising the
posterior aspect of the
arms, elbows, forearms,
and sacral area, multiple
central serohematic crusts
are observed

herpetiformis: Involving
the posterior aspect of the
upper and lower limbs,
buttocks, and trunk,
papules and plaques
covered with central
serohematic crust are
observed

herpetiformis: Multiple
papules with central
serohematic crust are seen
on the back of the arm
• Clinical presentation: The clinical presentation will depend on the affected age
group. In children, it presents as urticarial, annular, or polycyclic plaques with
subsequent blistering of the same, causing the appearance of a raised pearly bor-
der affecting the face and perineal area. In adults, linear IgA bullous dermatosis
presents with plaques and papules with vesicles and blisters that mainly affect
the trunk, face, scalp, and extremities. Involvement of the oral mucosa is frequent
due to ulcers and erosions [9] (Figs. 10.19, 10.20, 10.21, 10.22, 10.23, 10.24,
and 10.25).
• Diagnosis: Histopathological findings combined with direct immunofluores-
cence yield the diagnosis. Skin biopsies from patients with linear IgA bullous
dermatosis show a subepidermal blister with a variable cell infiltrate, which in
some cases can be accompanied by eosinophils reminiscent of bullous pemphi-
goid. Direct immunofluorescence studies of non-affected skin show mainly lin-
ear deposits of IgA and other immune depositions such as those consisting of
IgG, IgG, and C3 [9].
Fig. 10.19 Linear IgA

bullous dermatosis:
Multiple erythematous
plaques are seen with a
pearly vesicular border and
a centrally eroded blister

bullous dermatosis: On the
sacral and gluteal area, a
large erythematous plaque
with a bullous rim and
central hemorrhagic crusts
is observed with some
polycyclic perilesional
plaques with the same
characteristics
• Differential diagnosis: Linear IgA bullous dermatosis must be differentiated

from other clinically similar bullous diseases such as bullous pemphigoid. Less
commonly, it can appear similar to atypical erythema multiforme, nodular pru-
rigo with excoriations, dermatitis herpetiformis, impetigo bullosa, papular urti-
caria bullosa, and epidermolysis bullosa [9].
Bullous Pemphigoid
• Definition: Bullous pemphigoid is an autoimmune vesiculobullous disease in

which IgG-type autoantibodies are directed against proteins of the dermoepider-
mal junction [10].
• Pathogenesis: It is based on two components: one autoimmune and the other
inflammatory. Cellular activation of IgG-type antibodies against the hemidesmo-
some proteins BP180 and BP320 via the Fc portion of the said antibodies leads
to the release of proteolytic enzymes which damages the dermoepidermal junc-
tion. There are different etiologies of this entity including drugs, phototherapy,
Bullous Pemphigoid 293

bullous dermatosis:
Affecting the trunk,
polycyclic plaques with
vesicular borders and
crusted centers are
observed with associated
tense blisters at the
periumbilical level
radiotherapy, vaccines, and viral infections that in patients with genetic predispo-
sition trigger the disease [10].
• Clinical presentation: It is characterized by urticarial plaques or eczematous
lesions with subsequent presence of vesicles and tense blisters with clear or hem-
orrhagic contents. Lesions typically develop on the trunk and flexor surface of
the extremities with rare involvement of the head or neck [10] (Figs. 10.26,
10.27, 10.28, and 10.29).
• Diagnosis: Clinical, histological, and immunological findings all play an
important role in ascertaining the diagnosis. Skin biopsies from patients with
bullous pemphigoid show a subepidermal blister with a mixed superficial peri-
vascular inflammatory infiltrate with abundant eosinophils (Fig. 10.30). Direct
immunofluorescence of healthy skin shows linear deposits of IgG and C3 on
the basement membrane with a predominance of C3 intensity. Indirect immu-
nofluorescence and saline lysis test are adjunctive tools in specific cases to
support the diagnosis [10].

bullous dermatosis:
Compromising the sacral
area, buttocks, and
lower limbs, numerous
plaques with crusty
vesicular borders and clear
centers are observed
• Differential diagnosis: The main differential diagnoses are subepidermal bullous

diseases such as dermatitis herpetiformis, epidermolysis bullosa acquisita, linear
IgA bullous dermatosis, and mucous membrane pemphigoid. Initially, the lesions
should be differentiated from urticaria, eczema, vasculitic urticaria, erythema
multiforme, drug reactions, scabies, and different viral exanthemas [10].

bullous dermatosis:
Multiple tense blisters on
an erythematous base with
superficial hemorrhagic
crusting are observed on
the lower extremities

bullous dermatosis: Tense
blisters are observed on the
knees, leaving eroded areas
covered with hemorrhagic
crusts

bullous dermatosis:
Erythematous plaques with
are observed on the
buttocks and thighs with
overlying tense blisters.
Some of the plaques are
eroded and covered by
hemorrhagic crusts
Fig. 10.26 Bullous

pemphigoid: Involving the
left arm, tense blisters with
regular edges and
containing haemoserous
fluid are observed
Fig. 10.27 Bullous

pemphigoid: Tense blisters
containing haemoserous
fluid in a patient with
bullous pemphigoid
Fig. 10.28 Bullous

pemphigoid: Strained
blisters that leave erosions
Fig. 10.29 Bullous

pemphigoid: Involving the
lower extremities, tense
blisters are observed, some
of which leave erosions
that are covered with
hemorrhagic crusts
References 299
Fig. 10.30 Pemphigoid bullous: H&E-stained skin biopsy with evidence of eosinophils within
subepidermal blisters
References
1. Amagai M. Pemphigus. In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2.
London: Mosby; 2010. p. 461–73.
2. The vesiculobullous reaction pattern: pemphigus vegetans. p. 152.
3. Wojnarowska F, Venning VA. Immunobullous diseases. In: Burns T, Breathnach S, Cox N,
Griffiths C, editors. Rook’s textbook of dermatology, vol. 2. 8th ed. Wiley-Blackwell; 2010.
p. 40-7–.8.
4. Venugopal SS, Murrell DF. Diagnosis and clinical features of pemphigus vulgaris. Immunol
Allergy Clin N Am. 2012;32(2):233–43.
5. Abreu AM. Pénfigo foliáceo endémico situación en Colombia. Acta Médica Colombiana.
1996;21:1.
6. Velásquez MM, et al. Pénfigo vulgar y pénfigo foliáceo. In: Velásquez MM, Hoyos JG,
Castro LA, editors. Enfermedades Ampollosas Autoinmunitarias. Asociación Colombiana de
Dermatología; 2012. p. 52–63.
7. Aoki V, Rivitti E, Díaz L. Update on fogo selvagem, an endemic form of pemphigus foliaceus.
J Dermatol. 2015;42:18–26.
8. Hall RP, Katz SI. Dermatitis herpetiformis. In: Wolff K, Goldsmith L, Katz S, Gilchrest B,
Hill; 2010. p. 500–4.
9. Venning VA. Linear IgA disease: clinical presentation, diagnosis, and pathogenesis. Immunol
Allergy Clin N Am. 2012;32:245–53.
10. Fuertes de Vega I, Iranzo-Fernández P, Mascaró-Galy JM. Penfigoide ampolloso: guía de
manejo práctico. Actas Dermosifiliogr. 2014;105:328–46.
Chapter 11
Inflammatory Skin Diseases Presenting
with Erythema, Urticaria, and Purpura
This section documents inflammatory skin diseases that occur with erythema,
erythematous-edematous wheals (urticaria), and purpura. The pathophysiological
mechanisms often differ, despite sharing comparable clinical presentations with
similar lesional distributions and morphology. Within this group are:
A. Urticaria
(a) Allergic urticaria
(b) Physical urticaria
(c) Cold and heat urticaria
(d) Cholinergic urticaria
(e) Urticarial vasculitis
B. Figurate erythemas
(a) Erythema annulare centrifugum
(b) Erythema gyratum repens
(c) Necrolytic migratory erythema*
(d) Erythema marginatum
C. Purpura
(a) Pigmented purpura
(i) Progressive pigmentary dermatosis of Schamberg
(ii) Purpura annularis telangiectodes of Majocchi*
(iii) Pigmented purpuric lichenoid dermatitis of Gougerot-Blum*
(iv) Lichen aureus*
(v) Eczematid-like purpura of Doucas and Kapetanakis*
*
Pathologies not documentated in this atlas

https://doi.org/10.1007/978-3-030-84107-2_11
302 11 Inflammatory Skin Diseases Presenting with Erythema, Urticaria, and Purpura
Urticaria
• Definition: Urticaria is an inflammatory disease characterized by the presence of

transient swelling of the skin or mucous membranes (angioedema) due to plasma
leakage into the interstitial space [1].
• Pathogenesis: The main cell involved in the pathogenesis of urticaria is the mast
cell. This cell contains granules of tryptase, histamine, and different proteases in
its interior that, when released, allow vasodilation and consequent extrusion of
plasma into the interstitial space. Mast cell activation can be due to three etiolo-
gies: idiopathic, immune, and non-immune. In idiopathic mast cell activation,
the causative agent is unknown, and this mechanism represents the majority of
cases that lead to urticaria. In immune mast cell activation, there are autoantibod-
ies against the high affinity IgE receptor, which act as allergens that activate the
production of immunoglobulin E (allergic urticaria). The presence of immune
complexes with the consequent activation of the mast cell is seen in vasculitic
urticaria. Non-immune causes of mast cell degranulation include vasoactive
stimuli (e.g., stinging nettle) and medications (e.g., opiates, acetylsalicylic acid,
and angiotensin-converting enzyme inhibitors) [1].
• Clinical presentation: It presents as swollen erythematous or pink edematous
plaques with singular or multiple irregular borders that last less than 24 hours.
Vasculitic urticaria is the exception to the rule where lesions last more than
24 hours with evidence of leukocytoclastic vasculitis on histopathology [1].
• Spontaneous urticaria: Also called common urticaria, it is characterized by fluc-
tuating hives that may be accompanied by angioedema. Two presentations can be
distinguished according to the duration: acute urticaria, with a duration of symp-
toms and signs of less than 6 weeks (Figs. 11.1, 11.2, and 11.3), and chronic
urticaria in which the disease duration exceeds 6 weeks. Acute urticaria is com-
mon in patients with atopic dermatitis, while the chronic variant peaks in the
fourth decade of life [1].
• Physical urticaria: They represent a different subgroup of wheals that are induc-
ible by an exogenous physical stimulus. The main triggers are mechanical stim-
uli (e.g., simple and symptomatic dermographism (Figs. 11.4, 11.5, 11.6, and
11.7), pressure urticaria, and vibratory angioedema) (Fig. 11.8), temperature
changes (e.g., heat or cold urticaria), and diaphoresis or emotional stress (e.g.,
cholinergic, adrenergic, or exercise-induced urticaria), solar urticaria, and water
urticaria [1].
• Vasculitic urticaria: It is a clinicopathological entity compromising wheals that
last more than 24 hours and histopathology findings consistent with leukocyto-
clastic vasculitis (Fig. 11.9). Urticarial lesions are accompanied by a painful or
burning sensation as well as itching that leaves residual purpura [1].
• Diagnosis: The diagnosis is made from a detailed medical history in order to
classify wheals clinically. In many cases in an inpatient or outpatient setting, the
diagnostic approach is straightforward. The use of bedside tests such as dermog-
Urticaria 303
Fig. 11.1 Acute urticaria:

an erythematous and
edematous plaque with a
pale center and well-
defined irregular edges is
observed on the posterior
side of the right shoulder
raphism makes it possible to determine if there is a physical agent that can be

linked to the wheals. Skin biopsies are often less useful but can serve especially
when there is a suspicion of urticarial vasculitis. Histopathology findings of
wheals typically include edema that compromises the superficial portion of the
dermis, whereas in angioedema, there is edema of the deep dermis with exten-
sion to the subcutaneous tissue. In both entities, dilatation of the venules may be
observed. The presence of necrotizing venulitis is compatible with urticarial vas-
culitis [2].

erythematous and
edematous plaques with
borders are observed on
the anterior aspect of the
left thigh
• Differential diagnosis: It should be distinguished from all dermatological disor-

ders with an urticarial component such as reactions to insect bites (papular urti-
caria), acute febrile neutrophilic dermatitis (Sweet syndrome), bullous
pemphigoid in the urticarial phase, acute contact dermatitis, urticarial reactions
to drugs, and urticaria pigmentosa [2].
Erythema Annulare Centrifugum
• Definition: Erythema annulare centrifugum manifests as erythematous annular

lesions that migrate centrifugally with trunk and limb involvement lasting days
to a few months [3].
• Pathogenesis: Erythema annulare centrifugum represents a pattern of hypersen-
sitivity associated with infectious agents, especially dermatophytes, but has also
been associated with other fungi such as Candida or Penicillium, viruses, para-
sites, and ectoparasites. Additionally, it has been related to drugs, pregnancy,
specific foods, autoimmune endocrinopathies, hypereosinophilic syndrome, and,
occasionally, neoplasms [3].
Erythema Annulare Centrifugum 305

on the posterior aspect of
the arm and forearm,
erythematous and
edematous plaques with
and a pale center are
observed
Fig. 11.4 Dermographism:

a patient with physical
urticaria and the presence
of urticariforme lesions
after touch
Fig. 11.5 Dermographism:

urticarial lesions are
triggered after a
mechanical stimulus such
as when the back of a
pencil is applied to
the back
Fig. 11.6 Physical

urticaria: urticarial lesions
are triggered by a
mechanical stimulus such
as when touched
(dermographism)
Fig. 11.7 Physical

urticaria: on the back,
erythematous and
edematous plaques in a
linear manner are observed
subsequent to physical
stimulation with a pencil
(dermographism)
Fig. 11.8 Angioedema:

elderly patient with a
history of angioedema with
the presence of erythema
and upper lip edema
• Clinical presentation: There are two clinical presentations: the superficial and
the deep type. In the first, the lesions are not elevated and begin as erythematous
or pinkish papules, with poorly defined edges that expand in a centrifugal m anner.
Lesions typically involve the trunk, limbs, buttocks, and thighs and may present
with a peripheral scaling halo. The deep lesions have a widely infiltrated and
defined external edge of 3–10 mm, with a non-scaly urticariforme appearance [4]
(Figs. 11.10, 11.11, 11.12, and 11.13).
• Diagnosis: The diagnosis is clinical given that the histopathology findings are
nonspecific, and these will depend on the site of the biopsy. On microscopic
examination, the center of the lesions shows a moderate perivascular infiltrate
composed of lymphocytes and sometimes histiocytes arranged in cuffs. At the
scaly edge, focal spongiosis and parakeratosis areas in the epidermis are
observed. In the deep subtype, there are no epidermal changes with findings usu-
ally consistent with only a perivascular lymphohistiocytic infiltrate with sleeve
arrangement, which is moderately dense and distributed in superficial and deep
plexuses [4] (Figs. 11.14, 11.15, and 11.16).
• Differential diagnosis: It must be distinguished from other forms of figurate ery-
thema and dermatoses such as pityriasis rosea, seborrheic dermatitis, syphilis,
mycosis fungoides, annular granuloma, tinea corporis, and urticaria, among
others [4].
Fig. 11.9 Urticarial

vasculitis: on legs, multiple
residual brown maculae are
history of vasculitic
urticaria
Fig. 11.10 Erythema

annulare centrifugum:
arciform erythematous
plaque bordered by a
darker semicircular
scaly halo
Fig. 11.11 Erythema

annulare centrifugum: on
the lateral side of the left
foot, there is an annular
plaque with peripheral
desquamation
Fig. 11.12 Erythema

annular erythematous
plaques with desquamating
arciform centers
Fig. 11.13 Erythema

annulare centrifugum: An
annular plaque with a
scaling edge in its center
Fig. 11.14 Erythema

H&E-stained skin biopsy
with evidence of a dense
superficial perivascular
inflammatory infiltrate
with foci of parakeratosis
in the epidermis
(representation of the
scaling edge)
Erythema Gyratum Repens
• Definition: It represents a rare variant of figurate erythemas present in paraneo-

plastic syndromes and is associated with lung, esophageal, and breast neo-
plasms [5].
• Pathogenesis: Although its etiology is not entirely clear, different immunological
mechanisms are raised in the pathogenesis of this entity. It is believed that the
Erythema Gyratum Repens 311
Fig. 11.15 Erythema

at higher magnification
with evidence of
parakeratosis in the
epidermis with an
inflammatory infiltrate of
lymphocyte predominance
at the perivascular and
interstitial level of the
superficial dermis
tumor induces the formation of antibodies that cross-react with the components
of the dermoepidermal junction (molecular mimicry). Similarly, it has been doc-
umented that peptides produced by the tumor interact with skin antigens, causing
subsequent formation of antigen-antibody complexes that generate a reactive
dermatitis with immunoglobulin deposits on immunofluorescence noted [5].
• Clinical presentation: Classically, it appears as erythematous arciform plaques
or rings with a scaly edge (train line) that expand rapidly in a centrifugal fashion
(1 cm per day). Lesions compromise large areas of the body and respect the face,
hands, and feet [ 5] (Figs. 11.17, 11.18, 11.19, and 11.20).
• Diagnosis: The diagnosis is clinical since histopathology findings are nonspe-
cific, usually displaying acanthosis, mild hyperkeratosis, and focal parakeratosis
with spongiosis in the epidermis. In the dermis, it is possible to find a mononu-
clear, lymphocytic, or histiocytic infiltrate that extends to the superficial plexus.
IgG, C3, or C4 deposits in the basement membrane can be appreciated in immu-
nofluorescence studies [5].
• Differential diagnosis: It must be differentiated from other causes of figurate
erythema such as necrolytic migratory erythema, erythema annulare centrifu-
gum, and migratory erythema [5].
Fig. 11.16 Erythema

annulare centrifugum: skin
biopsy in H&E stain with
evidence of parakeratosis
and spongiosis in the
epidermis (scaling edge).
Note the presence of dense
perivascular lymphocyte
infiltrate in the superficial
dermis
Fig. 11.17 Erythema

gyratum repens: arciform
plaques with a scaly edge
that give the appearance of
tree bark
Erythema Marginatum 313
Fig. 11.18 Erythema

gyratum repens: on the
anterior aspect of the left
thigh, arciform
scaly edges are observed
Erythema Marginatum
• Definition: It is a type of figurate erythema present in patients with rheumatic

fever and is one of the diagnostic criteria proposed by Jones in 1992 [6].
• Pathogenesis: The pathogenesis is unknown; however, the existence of an altered
autoimmune response to one or more antigens associated with group A beta-
hemolytic Streptococcus (Streptococcus pyogenes) is presumed [6].
• Clinical presentation: Erythematous-pink, flat, or slightly raised macules or pap-
ules that expand centrifugally with a clear or pale center are typical of erythema
marginatum. In some cases, it may occur with complete or incomplete arciform
erythematous plaques. The lesions compromise the trunk, armpits, and proximal
extremities. The migration of these lesions is usually rapid [6] (Figs. 11.21,
11.22, and 11.23).
Fig. 11.19 Erythema

upper and lower
extremities, arciform
a scaly edge are observed
that give a tree bark
appearance
• Diagnosis: The diagnosis is clinical and is related to the other symptoms and
signs of rheumatic fever. On histology, it is possible to document an interstitial
and perivascular infiltrate consisting predominantly of neutrophils [ 6].
• Differential diagnosis: It should be distinguished from other figurate erythemas
such as urticarias, granuloma annulare, erythema multiforme, and allergic
rashes [6].
Pigmented Purpura
• Definition: It represents a group of entities that are characterized by extravasa-

tion of red blood cells and hemosiderin deposition, associated with inflammation
of capillaries without vasculitis [7].
Pigmented Purpura 315
Fig. 11.20 Erythema

lower extremities, arciform
a scaly edge are observed
• Pathogenesis: Its etiology is unknown; however, it has been linked to venous

hypertension, exercise, capillary fragility, infections, and chemical agents. It has
been suggested that there may be a cell-mediated reaction, supported by the
presence of a perivascular infiltrate of CD1+ dendritic cells and CD3+ and CD4+
T cells. These findings occur along with deposits of immunoglobulins and the C1
and C1q complement components around the dermal vessels [5].
• Clinical presentation: There are different variants of pigmented purpura with
isolated clinical characteristics. Within this group of pigmentary dermatosis,
we find:
–– Progressive pigmentary dermatosis of Schamberg: Clinically, it manifests as
punctiform macules that resemble peppercorns that later converge forming
orange or brown plaques on the extremities or any skin site, occurring second-
ary to hemosiderin deposition [5] (Figs. 11.24, 11.25, 11.26, and 11.27).
Fig. 11.21 Erythema

marginatum: on the inner
thighs, erythematous
plaques with regular
borders are observed
Fig. 11.22 Erythema

marginatum: on the
anterior surface of the
forearm, annular plaques
are seen that converge with
a pale center
Fig. 11.23 Erythema

marginatum: on the trunk,
annular erythematous
plaques are observed in a
patient with rheumatic
fever
Fig. 11.24 Pigmented

purpura: multiple brown
macules are observed,
some brown (secondary to
the hemosiderin deposit)
edges on a body site with
venous insufficiency
Fig. 11.25 Progressive

pigmentary dermatosis of
Schamberg: on the right
foot, involving the dorsum
and distal third of the
ipsilateral leg, brown and
purpuric macules are
are reticulated in a patient
with Schamberg disease

Schamberg: on the right
leg on an underlying area
of field of venous
insufficiency, multiple
pointed brown macules are
observed, some giving the
appearance of peppercorns

Schamberg: on the dorsum
of the left foot, multiple
brown macules with
are confluent and resulting
from the dermal
hemosiderin deposition
–– Purpura annularis telangiectodes of Majocchi: It appears as erythematous-

violaceous annular macules with a pale center that extend peripherally, giving
the annular configuration. Lesions occur in the lower extremities with subse-
quent involvement of the upper extremities [5].
–– Pigmented purpuric lichenoid dermatitis of Gougerot-Blum: It manifests as
erythematous-orange or violaceous lichenoid papules or plaques that are
associated with erythema, pruritus, and desquamation. Lesions are grouped in
plaques and may resemble lesions similar to Kaposi’s sarcoma [8].
–– Eczematid-like purpura of Doucas and Kapetanakis: Associated with purpu-
ric and eczematous changes in the skin along with significant pruritus. It has
been related to allergic reactions to clothing [6].
–– Lichen aureus: This presentation is the localized, persistent, and pruritic form
that presents as lichenoid papules associated with gold-brown purpuric lesions
on the lower extremities and less so on the trunk and face [5].
• Diagnosis: The diagnosis is clinical and confirmed in histopathology. The
microscopy findings are the presence of lymphocytic infiltrate and neutrophils at
the perivascular level with endothelial edema and lumen obstruction. The pres-
ence of vasculitis is not usual, and extravasation of red blood cells with
hemosiderin deposition in macrophages is frequent [5]. The presence of epider-
mal spongiosis with lymphocyte exocytosis may be present in all variants except
lichen aureus where an infiltrate is observed in a band with a very narrow grenz
zone [6] (Figs. 11.28, 11.29, 11.30, and 11.31).
• Differential diagnosis: Differential diagnosis will depend on the age of presenta-
tion: in adults, it should be distinguished from cutaneous T-cell lymphoma, stasis
pigmentation, leukocytoclastic vasculitis, lichen nitidus, drug hypersensitivity,
polycythemia, Hodgkin’s disease, fungal mycosis, purpura, and Kaposi’s sar-
coma. In childhood, it should be differentiated with thrombocytopenias, trau-
matic purpura, acute benign purpura of childhood, Cushing’s syndrome,
vasculitis, and fungal infections [6].
Fig. 11.28 Pigmented purpuric dermatosis: H&E-stained skin biopsy with a superficial and deep
perivascular inflammatory infiltrate with mild endothelial edema
Fig. 11.29 Pigmented

purpuric dermatosis:
at high magnification with
an inflammatory interstitial
infiltrate in the superficial
dermis and some foci of
spongiosis in the
dermoepidermal junction
Fig. 11.30 Pigmented lichenoid purpura: H&E-stained skin biopsy with a lichenoid-type inflam-
matory infiltrate in the superficial dermis with extension to the deep perivascular level
Fig. 11.31 Pigmented lichenoid purpura: H&E-stained skin biopsy with an inflammatory lichen-
oid infiltrate in the superficial dermis. Note the deeper perivascular involvement of this infiltrate as
well as the absence of involvement of the dermoepidermal junction
References
1. Grattan CEH. Urticaria y angioedema. In: Bologna JL, Jorizzo JL, Rapini RP, editors.
2. Kaplan AP. Urticaria and angioedema. Fitzpatrick’s dermatology in general medicine.
New York: McGraw-Hill, 338-340.
3. Figurate EA. Erythemas. In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 1.
London: Mosby; 2010. p. 307.
4. Kaminsky A. Eritemas figurados: eritema anular centrifugo. Acctas Dermosifiliogr.
2009;100:88–109.
5. Core M, Winters ME. Erythema gyratum repens. A rare paraneoplastic rash. West J Emerg
Med. 2011;12:556–8.
6. Kaminsky A. Eritemas figurados. Eritema marginado o reumático. Acctas Dermosifiliogr.
2009;100:88–109.
7. Sardana K, Sarkar R, Sehgal VN. Pigmented purpuric dermatoses: an overview. Int J Dermatol.
2004 Jul;43:482–8.
8. Allevato M. Dermatosis purpúricas pigmentarias (Capilaritis). Act Terap Dermatol.
2007;30:222.
Chapter 12
Inflammatory Connective Tissue Diseases
Also called “connective tissue diseases” are a group of autoimmune diseases that
share some clinical similarities such as arthritis and inflammation of the arteries in
the tissues. Most of these diseases have clinically distinctive findings in dermatol-
ogy. Among the most frequent of the inflammatory connective tissue diseases are:
A. Cutaneous lupus
(a) Acute lupus erythematosus
(b) Subacute lupus erythematosus
(i) Annular-polycyclic
1. Neonatal lupus
(ii) Papulosquamous
(c) Chronic lupus cutaneous
(i) Chronic discoid lupus erythematosus
1. Localized
2. Disseminated
3. Hypertrophic
(ii) Lupus panniculitis
(iii) Chilblain lupus erythematosus
(iv) Lupus erythematosus tumidus
(v) Bullous systemic lupus erythematosus
(d) Other variants
(i) Rowell syndrome
B. Dermatomyositis
C. Scleroderma

https://doi.org/10.1007/978-3-030-84107-2_12
324 12 Inflammatory Connective Tissue Diseases
D. Morphea
E. Recurrent polychondritis
F. Graft-versus-host disease
Cutaneous Lupus Erythematosus
• Definition: Lupus erythematosus is an autoimmune disease with multisystem

involvement which often includes the skin. It possesses significant morbidity and
mortality [1].
• Pathogenesis: Cutaneous lupus erythematosus (CLE) occurs as a result of a com-
plex interaction between environmental and genetic factors. The main related
etiopathogenic factor linked to CLE has been ultraviolet radiation followed by
medications and possibly viral infections. Exposure to ultraviolet radiation gen-
erates apoptosis of keratinocytes with subsequent release of intracellular and
nuclear antigens. In genetically predisposed patients who have altered clearance
of apoptotic debris and immunoreactivity, antibodies directed against these indi-
vidual fragments are expressed. This triggers an inflammatory cascade with the
production of cytokines and chemokines with the subsequent establishment of a
lichenoid tissue reaction in the basement membrane [1].
• Clinical presentation: The clinical presentation of cutaneous lupus erythemato-
sus is highly variable. Several categories of CLE have been defined and derived
from the specific clinical, histopathological, and laboratory findings pertaining to
each respective category of CLE [2]. These include:
–– Acute cutaneous lupus erythematosus: Commonly presents as the classic
malar erythema or “butterfly” rash that temporarily affects the skin for weeks
to months before subsequent systemic involvement. The lesions present as
small symmetrical discrete erythematous macules or papules on the central
portion of the face that is sometimes associated with desquamation (Figs. 12.1
and 12.2). These lesions may be associated with ulcerations of the oral or
nasal mucosa [2].
–– Subacute cutaneous lupus erythematosus: Lesions appear as macules or pap-
ules that evolve into annular polycyclic plaques (annular form) (Figs. 12.3
and 12.4) or papulosquamous plaques (papulosquamous form) (Figs. 12.5
and 12.6). The distribution is normally symmetrical. Around 50% of cases of
subacute cutaneous lupus erythematosus meet criteria for systemic lupus ery-
thematosus [1].
–– Neonatal lupus: It occurs due to the transplacental passage of anti-Ro anti-
bodies by the mother. Clinically, the cutaneous presentation includes ery-
thematous, edematous, scaly, and annular plaques on the face in a periocular
distribution (resembling a mask) with onset in the first weeks of life
(Figs. 12.7 and 12.8). Heart block is the second most frequent clinical pre-
sentation [3].
Cutaneous Lupus Erythematosus 325
Fig. 12.1 Acute cutaneous

young adult female patient
with erythematous macules
and plaques in the malar
region and nasal dorsum in
the “butterfly” distribution
Fig. 12.2 Acute cutaneous

afro-descendant patient
with erythematous plaques
edges that compromise the
bilateral malar region
Fig. 12.3 Annular

subacute cutaneous lupus
erythematosus: an annular
a raised border and
atrophic center is observed
on the dorsum of the
left hand
Fig. 12.4 Polycyclic

annular subacute lupus
erythematosus: multiple
erythematous annular
plaques with scaly borders
and pale centers are
observed on the upper limb
Fig. 12.5 Papulosquamous

erythematosus:
papules with thick
superficial scaling are seen
on the left retroauricular
region, converging to form
plaques
–– Chronic cutaneous lupus erythematosus: Within this group, different forms of

the disease are distinguished.
–– Discoid lupus erythematosus: It is the most frequent clinical subtype of
chronic cutaneous lupus erythematosus. Localized discoid lupus presents
in 80% of patients as nummular regular-edged and erythematous plaques
with follicular hyperkeratosis that are (Figs. 12.9 and 12.10) limited to the
face (Figs. 12.11, 12.12, and 12.13), scalp (Fig. 12.14), and neck. When
the adhering scale is removed from the surface of the lesions, follicle-sized
Fig. 12.6 Papulosquamous

erythematosus: multiple
desquamating
compatible with subacute
cutaneous lupus are seen
on the back of an adult
patient
keratotic plugs are observed, giving the appearance of a “carpet tack.” Five
percent of patients with a localized form are at risk of developing systemic
lupus erythematosus. Twenty percent of discoid lupus patients present with
the disseminated form, characterized by squamous purple macules or pap-
ules that gradually expand to form nummular or discoid lesions that leave
a hypopigmented atrophic center and a scaly and hyperpigmented border
(Fig. 12.13). Twenty percent of patients with the disseminated form are at
risk of developing systemic lupus erythematosus. Disseminated discoid
lupus lesions involve the trunk and upper extremities. In some cases, the
palms and soles can be affected [2].
–– Hypertrophic chronic discoid lupus: This rare variant of discoid lupus
presents as thickened plaques that affect the extensor surfaces of the
extremities and face, sometimes bearing resemblance to lesions second-
ary to hypertrophic lichen planus or keratoacanthomas [4].
Fig. 12.7 Neonatal lupus:

infant with an
erythematous-edematous
plaque with poorly defined
irregular edges on the left
temporal region with
consistent with lupus
–– Lupus panniculitis: It is characterized by erythematous subcutaneous nod-

ules that resolve, leaving lipoatrophic areas that involve the proximal
extremities, particularly the lateral aspects of the arms and shoulders [5]. It
can also affect the buttocks, trunk (Fig. 12.15), chest, face (Fig. 12.16),
scalp, and limbs [6] (Fig. 12.17).
–– Lupus erythematosus tumidus: Clinically, urticarial erythematous plaques
are observed, while on histopathology, there is minimal epidermal change
without follicular plugs with mucin-rich deposits [3]. Lupus erythemato-
sus tumidus is the most photosensitive subtype of cutaneous lupus erythe-
matosus frequently affecting the face or trunk [1].
–– Chilblain lupus erythematosus: It presents as purplish papules or plaques
that affect the fingers or toes (Figs. 12.18 and 12.19), face, and ears. Skin
lesions are exacerbated by cold temperatures, moisture, and environmental
exposure (winter). Twenty percent of these patients will develop systemic
symptoms/develop systemic lupus erythematosus [3].
Fig. 12.8 Neonatal lupus:

infant with multiple
papules and erythematous-
edematous plaques, some
of which conform to an
annular configuration with
central erosions that are
noted, with
compatible with lupus
Fig. 12.9 Discoid lupus

erythematosus: an
coin-shaped plaque with a
keratotic surface and
is observed on the nose of
an older adult woman

erythematosus: on the right
malar region, an
and thick pigmented scale
in its center is observed

erythematosus: on the
anterior aspect of the nose,
plaque with irregular edges
and atrophic areas is noted
which are
histopathologically
compatible with discoid
lupus
–– Bullous systemic lupus erythematosus: This form of lupus occurs as a

result of severe damage to the basement membrane in patients with acute
or subacute cutaneous lupus erythematosus and less commonly so with
discoid lupus erythematosus. On rare occasions, the disease onset is sud-
den and rapid, conferring a clinical impression of toxic epidermal necroly-
sis or erythema multiforme major [1] (Figs. 12.20, 12.21, and 12.22). In
these cases, the presence of autoantibodies directed against collagen VII
has been reported [7].
• There are other rare variants of cutaneous lupus erythematosus, among which are:
–– Rowell syndrome: Characterized by the existence of systemic or subacute
lupus erythematosus associated with multiforme-like erythema with or with-
out mucosal involvement and the presence of positive antinuclear antibodies
with a mottled pattern [8].
• Diagnosis: The goal in diagnosis is to adequately identify and classify skin
lesions for subsequent laboratory confirmation and explore for systemic disease.
The cornerstone of the diagnosis of cutaneous lupus erythematosus is the skin
biopsy. The histopathological findings vary according to the clinical subtype, but

erythematosus:
thick adherent scaling is
observed on the apex of the
nose, which leaves
follicular openings when
removed
in general, the lesions share specific findings where a hydropic or vacuolar

change of the basal layer associated with a lymphocyte infiltrate stands out
(Figs. 12.23, 12.24, 12.25, 12.26, 12.27, and 12.28). Direct immunofluorescence
is a useful tool in patients with inconclusive histology. The lupus band test may
be performed via immunofluorescence and detects immunoglobulin and comple-
ment depositions from the skin biopsy, for which positive findings are classic for
cutaneous lupus (whereas in SLE, the depositions are found both in involved and
uninvolved skin) [9]. Systemic involvement in patients with cutaneous lupus
should be ruled out by evaluating clinical features of lupus in other organs and
complementary extension studies as necessary.
• Differential diagnosis: The differential diagnosis will depend on the clinical sub-
type of cutaneous lupus erythematosus. The main differential diagnoses of acute
cutaneous lupus erythematosus include rosacea, seborrheic dermatitis, sunburn,
drug-induced photosensitivity, dermatomyositis, erysipelas, pemphigus erythe-
matosus, and atopic or photocontact dermatitis. Subacute cutaneous lupus

erythematosus:
erythematous keratotic
edges and hypochromic
and atrophic centers are
seen on the left eyebrow
tail, nasal dorsum, nasal
apex, and submental region
in a patient with discoid
lupus

erythematosus: two
erythematous keratotic
plaques with thick,
strongly adherent scaling
and well-defined regular
edges are observed on the
vertex region of the scalp
Fig. 12.15 Lupus

panniculitis: indurated and
painful violaceous nodules
to palpation in the right
infrascapular and right
lumbar regions in a patient
with lupus panniculitis
Fig. 12.16 Lupus

panniculitis associated
with discoid lupus:
middle-aged woman with
keratotic erythematous
plaques that leave atrophic
and hypochromic scars on
the back and nasal bridge
compatible with discoid
lupus. In the right malar
region, she presents
achromic scars with
lipoatrophy, histologically
compatible with lupus
panniculitis
Fig. 12.17 Lupus

panniculitis: erythematous
irregular edges that leave
residual hypochromic
atrophic areas are seen
lesions should be differentiated from psoriasis, dermatophytosis (unknown

tinea), photo-lichenoid drug eruption, granuloma annulare, erythema figurate,
contact dermatitis, and pemphigus foliaceus. Discoid lupus lesions should be
differentiated from facial discoid dermatitis such as tinea, lichen planus, lichen
planopilaris, polymorphic light eruption, sarcoidosis, lymphoma cutis, facial
granuloma, and lupus vulgaris, among others [1].
Dermatomyositis
• Definition: Dermatomyositis is an idiopathic inflammatory myopathy of autoim-

mune origin characterized by the presence of proximal extensor inflammatory
myopathy associated with specific skin lesions [10].
Dermatomyositis 335
Fig. 12.18 Chilblain lupus erythematosus: multiple erythematous-violaceous papules are

observed on the dorsum of the hands, coalescing to form irregularly edged plates
Fig. 12.19 Chilblain lupus erythematosus: in the palmar region with involvement of the distal
third of the phalanges, slightly scaly and infiltrated erythematous plaques are observed in a patient
with Chilblain lupus erythematosus
Fig. 12.20 Bullous

systemic lupus
erythematosus: patient
with systemic lupus
erythematosus who
currently presents with
plaques with tensile
blisters on their surfaces
Fig. 12.21 Bullous

systemic lupus
erythematosus: patient
with a history of systemic
lupus erythematosus with
plaques with tensile
blisters on their surfaces
that leave residual
hypopigmented scars
• Pathogenesis: It is presented as the result of an immunological process triggered

by external agents such as tumors, drugs, or infectious agents in genetically pre-
disposed patients [10].
• Clinical presentation: Dermatomyositis is the only inflammatory myopathy with
associated cutaneous manifestations, distinguishing it from other types of myop-
athies. Skin lesions occur in 30–40% of adults and 95% of children [11]. The
pathognomonic lesions of dermatomyositis are:
–– Gottron’s papules, which are violaceous papules on the dorsum of the meta-
carpophalangeal, interphalangeal, elbow, and knee joints [11] (Figs. 12.29,
12.30, 12.31, and 12.32).
–– Gottron’s sign appears as erythematous macules or plaques with linear exten-
sion in the same distribution as Gottron’s papules [11] (Figs. 12.33, 12.34,
and 12.35).
–– Heliotrope erythema manifests as an erythematous-violaceous erythema at
the periorbital level with involvement of the eyelids that is accompanied by
eyelid or facial edema present in 30–60% of patients [11] (Figs. 12.36, 12.37,
12.38, and 12.39).
Dermatomyositis 337
Fig. 12.22 Acute lupus erythematosus: 20x H&E-stained skin biopsy with vacuolar degeneration
of the basal membrane cells and a perivascular lymphocytic infiltrate in the papillary dermis
–– Photosensitivity presents clinically with different signs: the V sign character-

ized by a violaceous erythema with involvement of the neck and upper chest;
the shawl sign [erythema involving the nape, upper back, and back of the
shoulders] (Figs. 12.40, 12.41, and 12.42); and the Holster sign, presenting
with erythema that compromises the lateral surface of the buttocks and hips
[11] (Figs. 12.43, 12.44 and 12.45).
–– Vascular atrophic poikiloderma clinically presents as violaceous erythema
associated with telangiectasias, hypopigmentation, and superficial atrophy.
The most affected sites are the shoulders, the back, the buttocks, and the ante-
rior area of the V of the neck and trunk [11] (Figs. 12.45 and 12.46).
–– Mechanic’s hands present as lichenified plaques with flaking and fissuring
affecting the lateral and palmar sides of the fingers. This condition occurs in
the context of the anti-synthetase syndrome (presence of anti-Jo1 antibodies,
Fig. 12.23 Acute lupus erythematosus: 40x H&E-stained skin biopsy with evidence of interface
dermatitis with vacuolar degeneration of the basal membrane cells and a perivascular lymphocytic
infiltrate
arthritis, interstitial lung disease, Raynaud’s phenomenon, and mechanic’s

hands) [11].
–– Periungual disorders are common in patients with dermatomyositis and are
characterized by periungual telangiectasias with cuticle hypertrophy and
associated with hemorrhagic infarcts [11] (Figs. 12.47 and 12.48).
–– Calcinosis cutis frequently affects children in up to 40% of cases and presents
as dystrophic calcinosis with a variable clinical presentation. Small superfi-
cial plaques, nodules, or calcium deposits can be observed subcutaneously or
in the muscle fascia [11] (Figs. 12.49, 12.50, 12.51, 12.52, and 12.53).
Other less common clinical manifestations are erosions, ulcerations, vesicular
bullous lesions, and flagellate erythema (Figs. 12.54 and 12.55).
• Diagnosis: The diagnosis is ascertained via both clinical and laboratory findings
(evidence of elevation of muscle enzymes in the context of dermatomyositis with
myositis). The histopathology findings are very subtle and include epidermal
atrophy with vacuolar degeneration of the basement membrane, while in the der-
Scleroderma 339
Fig. 12.24 Lupus panniculitis. H&E-stained skin biopsy revealing a lobular lymphocytic inflam-
matory infiltrate with mucin deposits in the septa and some scant eosinophils
mis, there is deposition of interstitial mucin and a dispersed lymphocytic infil-

trate (Figs. 12.56 and 12.57). When a muscle biopsy is taken, it is possible to find
atrophy of type II muscle fibers, necrosis, regeneration, and hypertrophy with
centralized sarcolemmal nuclei plus perifascicular and perivascular lymphocytic
infiltrates [10].
• Differential diagnosis: The most important differential diagnosis is systemic
lupus erythematosus or acute or subacute cutaneous lupus erythematosus.
Likewise, seborrheic dermatitis, contact dermatitis, lichen planus, psoriasis,
polymorphic light eruption, atopic dermatitis, or dermatomyositis-like changes
induced by hydroxyurea or statins should be ruled out [12].
Scleroderma
• Definition: Scleroderma is an autoimmune connective tissue disease of unknown

etiology that affects the skin, blood vessels, and internal organs [13].
• Pathogenesis: The etiology is unknown, although it is suggested that there is
vascular dysfunction in the skin and internal organs with autoantibody-producing
Fig. 12.25 Chilblain lupus erythematosus: acral skin biopsy in H&E stain with evidence of dense
superficial and deep lymphocytic infiltrates
immunoreactivity which leads to tissue fibrosis. This triggers deposition of col-

lagen and other proteins into the extracellular matrix [13].
• Clinical presentation: The clinical presentation of scleroderma is heterogeneous,
with certain clinical features almost always present, such as Raynaud’s phenom-
enon and skin fibrosis [14]. There are two clinical spectra of the disease:
–– Diffuse systemic sclerosis, where there is thickening of the skin that involves
the proximal extremities or the trunk and is associated with heart, lung, or
kidney damage, and limited systemic sclerosis, where dermal fibrosis is usu-
ally limited to the phalanges, hands, and face (including CREST syn-
drome) [14].
–– CREST syndrome refers to the acronym for calcinosis (Figs. 12.58 and 12.68),
Raynaud’s phenomenon, esophageal involvement, sclerodactyly (Figs. 12.59
and 12.60), and telangiectasias [14].
The thickening of the skin begins in the fingers (sclerodactyly) with proximal
extension to the metacarpophalangeal joints (Figs. 12.61, 12.62, and 12.63).
Scleroderma 341
Fig. 12.26 Chilblain lupus erythematosus: acral skin biopsy in H&E stain with evidence of a
predominantly lymphocytic inflammatory infiltrate at the superficial and perivascular dermis level
Sclerosis affects the extremities, the back, and the face. Fibrosis limits the oral
opening and makes the face expressionless [14] (Fig. 12.64). Other clinical findings
other than fibrosis are the presence of hypo- and hyperpigmented areas at sites of
previous fibrosis and photo-exposed areas. The depigmented or leukoderma areas of
scleroderma spare the perifollicular pigmentation, giving a particular clinical char-
acteristic called “salt and pepper” as quoted by some authors [13] (Figs. 12.65
and 12.66).
• Diagnosis: The diagnosis is clinical and is supported by different laboratory find-
ings. In 2013, the American College of Rheumatology together with the European
League Against Rheumatism determined different criteria with a sensitivity and
specificity of 91% and 92%, respectively, for the diagnosis of systemic sclero-
derma. When 9 points are obtained, the diagnosis is given. The criteria and
respective allocation of points per criterion include the following:
–– Skin thickening of the fingers or hands with extension to the metacarpopha-
langeal joints followed by sclerodactyly (thickening of the distal portion of
the fingers)—4 points
Fig. 12.27 Bullous systemic lupus erythematosus: 40x H&E-stained skin biopsy with evidence of
a subepidermal blister with a dense predominantly neutrophilic inflammatory infiltrate in the
superficial dermis
Fig. 12.28 Bullous systemic lupus erythematosus: H&E-stained skin biopsy at high magnification
with evidence of a dense subdermal inflammatory infiltrate with a predominance of neutrophils
Scleroderma 343
Fig. 12.29 Gottron’s

papules: on the dorsum of
the metacarpophalangeal
and interphalangeal joints,
multiple erythematous-
violaceous papules with
are observed
Fig. 12.30 Gottron’s

papules: compromising the
dorsal surface of the
interphalangeal joints,
converge forming plaques
are observed
Fig. 12.31 Gottron’s papules: erythematous-violaceous papules that converge forming plaques on
the interphalangeal and metacarpophalangeal joints are seen
Fig. 12.32 Gottron’s papules: on the back of the interphalangeal joints, violaceous papules are
observed that converge, forming plaques
Scleroderma 345
Fig. 12.33 Gottron’s sign:

on the dorsum of the
metacarpophalangeal
joints, erythematous
papules are observed,
which converge forming a
plaque with linear
extension to the dorsum of
the phalanges
Fig. 12.34 Gottron’s sign:

on the dorsum of the right
hand and compromising
the phalanges and articular
surface, erythematous-
violet papules are observed
that converge forming
linearly distributed plaques
–– Raynaud’s phenomenon—3 points

–– Scleroderma-related autoantibodies such as anti-centromere, anti-
topoisomerase (anti-Scl-70), and anti-RNA polymerase—1 point each
–– Sausage fingers, digital ulcers (Fig. 12.67), pinpoint scars on the fingertips,
pulmonary arterial hypertension or interstitial lung disease, alteration in capil-
laroscopy, and the presence of telangiectasias—2 points each [14]
Other documented cutaneous findings are limb ulcerations (40%) (Fig. 12.67),
telangiectasia (75%), hyperpigmentation (30%), and cutaneous calcifications (25%)
[14] (Fig. 12.68). Dermatoscopy has recently been used as a tool for the analysis of
periungual skin in order to identify patterns similar to those described with capilla-
roscopy and include dilated capillaries with hemorrhages from the ungular bed,
microbleeds, and avascular areas with loss of capillaries in the ungular bed with
sensitivity and specificity similar to capillaroscopy [15] (Figs. 12.69 and 12.70).
Fig. 12.35 Gottron’s sign.

erythematous
desquamative plaque that
compromises the extensor
surface of the elbows
The histopathology of the lesions indurated by scleroderma shows hyalinized

collagen with atrophy of the eccrine and pilosebaceous glands that may be accom-
panied by loss of subcutaneous tissue and a lymphocytic infiltrate dispersed within
the dermis and subcutis [13] (Fig. 12.71).
• Differential diagnosis: Other disorders within the spectrum of systemic sclero-
derma with a different prognosis are morphea or cutaneous scleroderma. Other
differential diagnoses include other causes of acral vasospasm such as primary or
secondary Raynaud’s phenomenon associated with other collagenopathies such
as lupus, rheumatoid arthritis, or dermatomyositis. Furthermore, diseases such as
cryoglobulinemia, systemic vasculitis, Buerger’s disease (thromboangiitis oblit-
erans), and macrovascular disease should be excluded. Diseases with cutaneous
sclerosis that must be differentiated from systemic sclerosis are amyloidosis,
scleromyxedema, scleredema, lichen sclerosus et atrophicus, porphyria cutanea,
acromegaly, eosinophilic fasciitis, and graft-versus-host disease [16].
Morphea 347
Fig. 12.36 Erythema in

heliotrope: macular rash
associated with eyelid
edema in a patient with
dermatomyositis
Morphea
• Definition: Morphea, also called cutaneous scleroderma, is a fibrosing condition

localized to the skin, the subcutaneous tissue, the underlying bone, and, rarely,
the central nervous system when it involves the face and head [17]. This condi-
tion does not present with vascular alterations or Raynaud’s phenomenon.
• Pathogenesis: The cause is unknown. However, different precipitating environ-
mental factors trigger the disease in genetically predisposed patients including
trauma, medications, silicone-derived fillers, and infections. Host factors such as
autoimmunity and microchimerism are proposed to play an important role in the
pathophysiology of the disease [17].
• Clinical presentation: Morphea lesions have different clinical phases throughout
the disease, including the inflammatory or active phase (Fig. 12.72), which then
subsequently passes into a sclerosing phase that resolves, leaving residual atro-
phy [18]. In the inflammatory phase, morphea lesions appear as erythematous to
violaceous plaques that resolve, leaving an anhidrotic, alopecic, and sclerotic
plaque with varying degrees of pigmentation (Figs. 12.73 and 12.74). The most

heliotrope: compromising
periorbital area with
extension to the cheeks,
forehead, and chin,
macules are observed in a
patient with
dermatomyositis. Note the
extension to the scalp

heliotrope: in the
periorbital region,
forehead, chin, and neck,
erythematous macules with
dermatomyositis
Morphea 349

heliotrope: erythema and
eyelid edema in a patient
with dermatomyositis.
Note the involvement of
photo-exposed areas
Fig. 12.40 Shawl sign:

large erythematous plaque
with poorly defined
irregular edges on the
suprascapular region
and neck
common clinical presentations are plaque morphea (Fig. 12.75), linear morphea
(Fig. 12.76), generalized morphea (Fig. 12.77), and panclerotic morphea
(Fig. 12.78). Linear morphea is the most common presentation in children and
associated with increased morbidity. Within the linear forms, there are two par-
ticular variants that affect the head, namely, linear morphea en coup de sabre,
which appears as a linear indurated plaque that involves the dermis of the face
and the scalp (Fig. 12.76), and Parry-Romberg syndrome, where there is a loss of
the dermis, subcutaneous tissue, and muscle and bone tissue with unilateral
involvement of the face [16] (Fig. 12.79).
Fig. 12.41 Shawl sign: on

the back, there is a large
scaly erythematous plaque
with poorly defined
irregular edges in a patient
diagnosed with
dermatomyositis
Fig. 12.42 Shawl sign: on

the back and posterior
aspect of the deltoids,
respecting the bra area,
there are scaly
macules with poorly
defined irregular edges
• Diagnosis: The initial histopathological findings of morphea are indistinguish-

able from systemic scleroderma, revealing a perivascular lymphocytic infiltrate
with extension into the reticular dermis and edema of the endothelial cells. When
the lesions progress, thickening of the collagen bands is observed throughout the
dermis with extension into the subcutaneous tissue, enveloping the eccrine
glands, follicular units, and blood vessels [17] (Figs. 12.80 and 12.81).
• Differential diagnosis: The most important differential diagnosis is systemic
scleroderma, which differs from morphea by the presence of Raynaud’s syn-
drome, sclerodactyly, and systemic compromise. Eosinophilic fasciitis, lichen
sclerosus et atrophicus, lupus panniculitis, connective tissue nevi, morpheaform
basal cell carcinoma, graft-versus-host disease, and lipodermatosclerosis are
other differential diagnoses to rule out [19].
Relapsing Polychondritis 351
Fig. 12.43 “Holster” sign:

on the lateral aspect of the
thigh
Relapsing Polychondritis
• Definition: Represents a systemic inflammatory disease characterized by inflam-

mation in cartilage tissues [20].
• Pathogenesis: It is stated that the etiopathogenesis is of autoimmune-auto-
inflammatory origin against type II collagen. The presence of autoantibodies
against type II collagen has been documented in 33–67% of patients. It has also
been related to autoimmune diseases such as Sjogren’s syndrome, rheumatoid
arthritis, and lupus erythematosus, among others.
• Clinical presentation: The most frequent manifestation, found in 85–90% of
cases, is auricular chondritis. This presents as edema, erythema, and pain with
involvement of bilateral pinna of the ears in their cartilaginous portion
(Figs. 12.82, 12.83, and 12.84). The cartilaginous inflammatory process may be
self-resolving or may progress to a chronic state, resulting in cartilage destruc-
tion and deformation of the pinna, forming the “cauliflower ear” deformity.
Similarly, it can present with arthritis, nasal chondritis (Fig. 12.85), and chondri-
tis of the respiratory tract.
Fig. 12.44 “Holster” sign:

thigh with extension to the
lumbar region,
papules are observed that
coalesce to form a large
plaque
Fig. 12.45 Vascular

atrophic poikiloderma:
erythematous macules
cross-linked with fine
telangiectasias as well as
hypopigmented and
atrophic macules in a
patient with
dermatomyositis
Fig. 12.46 Vascular

atrophic poikiloderma:
compromising the “V”
region of the superior trunk
and inferior neck,
papules are observed on a
macular base with some
telangiectasias and
atrophic areas in a patient
with dermatomyositis
Fig. 12.47 Periungular

disorders: multiple thick
telangiectasias are
observed at the
eponychium level in a
patient with
dermatomyositis. These are
non-exclusive findings of
this entity
• Diagnosis: The diagnosis is usually suspected clinically and confirmed by histol-

ogy in which a perichondral lymphocytic inflammatory infiltrate can be docu-
mented. Chronic lesions show a decrease in the number of chondrocytes with
loss of cell contour and pyknotic nuclei. McAdam et al. proposed clinical criteria
for the diagnosis of relapsing polychondritis, including bilateral atrial chondritis,
non-erosive and seronegative polyarthritis, nasal chondritis, eye inflammation,
respiratory chondritis, or vestibular injury.
• Differential diagnosis: In the initial phases, erythema and pain can be confused
with erysipelas or cellulitis, but in these cases, the involvement is bilateral and
respects the auricular lobes. Equally, infectious chondritis, traumatic chondritis,
Wegener’s granulomatosis, and congenital syphilis should be ruled out [21].
Fig. 12.48 Periungular

disorders: cuticular
hypertrophy in a patient
with dermatomyositis
Fig. 12.49 Calcinosis

cutis: compromising the
proximal third of the thigh,
multiple skin-colored or
erythematous and firm
nodules are found, one of
which is ulcerated and
indurated. These findings
are compatible with
dystrophic calcinosis cutis
secondary to
dermatomyositis

cutis: ulcerated plaques
and erythematous nodules
covered with hematic
crusts and extrusion of
calcium material on its
surface are observed on the
anterior aspect of the knee
in a patient diagnosed with
dermatomyositis

cutis: hard infiltrated
firm-whitish cysts on the
anterior aspect of the knee
are observed which are
compatible with dystrophic
calcinosis due to
dermatomyositis

cutis: two hard papules
with a calcified center are
seen on the posterior
aspect of the elbow

cutis: multiple firm-whitish
nodules adhering to deep
planes with well-defined
the elbow
Graft-Versus-Host Disease
• Definition: Graft-versus-host disease (GVHD) is one of the most frequent com-

plications of hematopoietic stem cell transplantation [22].
• Pathogenesis: Graft-versus-host disease results from the recognition of host tis-
sues as foreign by immunocompetent donor cells. There are two clinical presen-
tations of the disease with different pathogenic theories. In the acute phase of the
disease, it is suggested that tissue damage in the receptor occurs secondary to
toxicity caused by concurrent chemotherapy or radiotherapy that favors the
secretion of inflammatory cytokines by the receptor. Later, in the chronic phase,
mature donor lymphocytes begin to play a role pro-inflammatory generating
clonal expansion and activation of lymphocytes and antigen-presenting cells.
This in turn provokes the production of autoreactive T cells that induce tissue
damage and the release of inflammatory cytokines [22].
• Clinical presentation: The acute presentation of the disease consists of a triad of
skin rash and liver and gastrointestinal involvement. At the cutaneous level, a
maculopapular rash or rash is often reported that can partially or completely
compromise the total body surface. In the chronic presentation of the disease,
Graft-Versus-Host Disease 357
Fig. 12.54
Dermatomyositis: a plaque
macular border in the form
of flagella, compatible with
flagellate erythema, is
identified in a patient with
dermatomyositis
many cases do not require a biopsy for diagnosis since the clinical cutaneous
findings are characteristic of the disease, including poikiloderma, lichen planus
eruptions, lichen sclerosus-type lesions, morphea-type sclerosis, and fasciitis or
sclerosis of the skin (Figs. 12.86 and 12.87). Furthermore, there are clinical man-
ifestations of the chronic presentation of the disease that can range from vitiligo-
like lesions (Fig. 12.88) to simple keratosis pilaris-like lesions [22]. Likewise,
vascular proliferations that appear as erythematous-violaceous tumors have been
documented in patients with graft-versus-host disease of the sclerosing type, also
called angiomatosis associated with GVHD [23] (Fig. 12.89).
• Diagnosis: In the initial stages of the disease, clinical suspicion when combined
with histopathological findings secures the diagnosis of the disease.
Histopathological findings in the acute phase of the disease include a vacuolar or
diffuse alteration of the basement membrane that may be accompanied by dys-
keratotic squamous cells in the epidermis or hair follicle which may or may not
be associated with the formation of subepidermal vesicles. Microscopic findings
of chronic graft-versus-host disease include an interface dermatitis with lympho-
cyte satellites and vacuolar changes of the basement membrane [24].
Fig. 12.55
Dermatomyositis:
erythematous-violet
macules with some
atrophic and
hypopigmented areas that
comprise the lateral aspect
of the right arm
• Differential diagnosis: Differential diagnoses should be excluded in acute pre-

sentations such as morbilliform drug eruptions, viral exanthems, Stevens-
Johnson syndrome, erythema multiforme, and bullous fixed drug eruption,
among others. The chronic presentation of the disease must be differentiated
from scleroderma, disseminated lichen planus, morphea, and lichen sclerosus et
atrophicus, among others [22, 23].
Fig. 12.56 Dermatomyositis: H&E-stained skin biopsy of a patient with dermatomyositis with
evidence of epidermal acanthosis and hyperkeratosis with a superficial perivascular lymphocytic
infiltrate
Fig. 12.57 Dermatomyositis: PAS-stained skin biopsy with evidence of thickening of the basal
lamina and interstitial edema in the dermis

cutis: skin-colored plaques
the left forearm in a patient
with systemic scleroderma
Fig. 12.59 Sclerodactyly: systemic scleroderma patient with diffuse skin thickening of the fingers
with involvement of the interphalangeal joints
Fig. 12.60 Sclerodactyly: diffuse thickening of distal phalanges with extension to the interphalan-
geal joints in a patient with systemic scleroderma
Fig. 12.61 Sclerodactyly:

phalangeal edema with
flexion contracture
secondary to restricted
joint mobility with
associated erythematous
scaly plaques afflicting the
metacarpophalangeal joints
with linear extension to the
phalanges (Gottron’s sign)
in a patient with overlap
syndrome of systemic
dermatomyositis-
scleroderma
Fig. 12.62 Sclerodactyly:

finger edema with
associated “sausage finger”
appearance and necrosis of
the distal phalanges in a
patient with systemic
scleroderma
Fig. 12.63 Sclerodactyly: severe sclerodactyly with necrosis of distal phalanges in a patient with
systemic scleroderma
Fig. 12.64 Systemic

scleroderma: decreased
oral opening associated in
a patient with systemic
scleroderma
Fig. 12.65 Systemic

scleroderma: “salt-and-
pepper” pigmentation
changes and brown
macules with achromic
areas on
sclerodermiform skin
Fig. 12.66 Scleroderma:

“salt-and-pepper”
pigmentation changes on
the gluteal region with a
large associated
hypochromic
sclerodermiform plaque
with multiple perilesional
pinpoint plates are
Fig. 12.67 Digital ulcers:

on the distal phalanx of the
fourth finger of the right
hand, an ulcer covered
with necrotic crust is

cutis: an infiltrated
irregular edges and
ulcerated areas with serous
crusting is observed,
compatible with ulcerated
dystrophic calcinosis in a
patient with systemic
scleroderma
Fig. 12.69 Dermoscopy of

the periungual skin of a
patient with scleroderma:
dermatoscopic evidence of
hemorrhage in the cuticle
Fig. 12.70 Dermoscopy of

the periungual skin of a
patient with scleroderma:
dermoscopy showing a
decrease and absence of
capillaries in the proximal
periungual skin
Fig. 12.71 Scleroderma:

showing evidence of
dermal sclerosis
Fig. 12.72 Plaque

morphea: a young adult
patient with a
sclerodermiform plaque
with some erythematous
nodules in its center and a
silver-gray macular border
in a patient with active
morphea in the
inflammatory phase
Fig. 12.73 Plaque

morphea: on the lateral
aspect of the left arm, a
brown sclerodermiform
plaque with a hypochromic
center and irregular edges
is observed
Fig. 12.74 Plaque

morphea: on the temporal
region, a sclerotic and
atrophic plaque is observed
with loss of follicular units,
central hypochromia, and a
brown border with
irregular edges
Fig. 12.75 Plaque

morphea: middle-aged
woman with a brown
infiltrated plaque with
irregular edges and an
atrophic center in the
lumbar region
Fig. 12.76 Linear

scleroderma en coup de
sabre: on the mid-forehead
region and with extension
to the nasal dorsum, a
scleroatrophic plaque with
a silver-gray macular
border is observed

morphea: hypochromic
sclerodermiform plaques
with irregular brown
borders are observed on
the anterior trunk in a
patient with generalized
morphea
Fig. 12.78 Deep or

panclerotic morphea: in the
pretibial region, an
infiltrated sclerodermiform
plaque is observed with an
atrophic center and
irregular edges
Fig. 12.79 Parry-Romberg

syndrome: on the right
hemi-facial region, there is
a lipoatrophic area with
irregular edges that
compromises bone tissue
as confirmed via computed
tomography in a patient
with linear morphea
Fig. 12.80 Morphea: 20x H&E-stained skin biopsy with evidence of atrophic epidermis and
thickening of collagen bands in the dermis with loss of adnexa and fatty infiltration
Fig. 12.81 Morphea: at higher magnification, thickened collagen fibers with some lymphocytes
are observed
Fig. 12.82 Relapsing

polychondritis: erythema
and edema of the cartilage
are observed on the left ear

polychondritis: erythema
and edema involving the
left auricular cartilage

polychondritis: erythema,
heat, and edematous
edges are observed on the
right ear

polychondritis: patient
with edema affecting the
nasal cartilage
Fig. 12.86 Chronic

graft-versus-host disease:
on the back of the hand
and forearm,
sclerodermiform plates
some achromic macules
are observed. Note the
absence of sclerodactyly, a
differential clinical finding
of systemic scleroderma
Fig. 12.87 Chronic

young adult patient with a
history of allogeneic bone
marrow transplantation
with long-term
and achromic macules with
irregular and
hyperpigmented edges that
compromise the trunk and
upper extremities
Fig. 12.88 Chronic

young adult patient with
multiple achromic macules
on the trunk and upper
limbs with associated
Fig. 12.89 Angiomatosis

associated with graft-
versus-host disease: patient
with a history of chronic
graft-versus-host disease
with evidence of multiple
violaceous tumorous
plaques, some ulcerated
with hemorrhagic crusts
References
1. Lee LA, Werth VP. Lupus erythematosus. In: Bologna JL, Jorizzo JL, Rapini RP, editors.
2. Kuhn A, Landmann A. The classification and diagnosis of cutaneous lupus erythematosus. J
Autoimmun. 2014;48–49:14e19.
3. Rodríguez Nevado IM, et al. Lupus eritematoso neonatal. Med Cutan Iber Lat Am.
2008;36:27–9.
4. Wailling HW, Sontheimer RD. Cutaneous lupus erythematosus. Am J Clin Dermatol.
2009;10:365–81.
5. Fraga J, García-Díez A. Lupus erythematosus panniculitis. Dermatol Clin. 2008;26:453–63.
6. De la Moneda HC, Conde Zurita JM, Guerra Tapia A, et al. El lupus paniculitis: una paniculitis
mixta. Actas Dermosifiliogr. 1987;78:229–38.
7. González-Naranjo LA, Vásquez-Duque GM, Restrepo-Escobar M. Enfermedad cutánea
ampolloso en lupus eritematoso sistémico. Iatreia. 2012;25:229–39.
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8. Tirado SA. Síndrome de Rowell. Reumatol Clin. 2006;2:155–7.

9. Okon LG, Werth VP. Cutaneous lupus erythematosus: diagnosis and treatment. Best Pract Res
Clin Rheumatol. 2013;27:391–404.
10. Jorizzo JL, Vleugels RN. Dermatomyositis. In: Bologna JL, Jorizzo JL, Rapini RP, editors.
11. Restrepo JP, Medina LF, Molina MP. Manifestaciones cutáneas de la dermatomiositis. Rev
Asoc Colomb Dermatol. 2010;18:18–24.
12. Sontheimer RD, Costner MI. Dermatomyositis. In: Wolff K, Goldsmith L, Katz S, Gilchrest B,
Hill; 2010. p. 1547–8.
13. Cannolly MK. Systemic sclerosis (scleroderma) and related disorders. In: Bologna JL, Jorizzo
JL, Rapini RP, editors. Dermatology, vol. 1. London: Mosby; 2010. p. 643–9.
14. Desbois AC, Cacoub P. Systemic sclerosis: an update in 2016. Autoimmun Rev.
2016;15:417–26.
15. Ohtsuka T. Dermoscopic detection of nail fold capillary abnormality in patients with systemic
sclerosis. J Dermatol. 2012;39:331–5.
16. Denton CP, Black CM. Scleroderma (systemic sclerosis). In: Wolff K, Goldsmith L, Katz S,
Gilchrest B, Paller A, Leffell D, editors. Fitzpatrick’s dermatology in general medicine. 7th ed.
McGraw-Hill; 2010. p. 1557.
17. Fett N, Werth VP. Update on morphea: part I. Epidemiology, clinical presentation, and patho-
genesis. J Am Acad Dermatol. 2011;64:218–28.
18. Gaviria CM, Jiménez SB, Gutiérrez J. Morfea o esclerodermia localizada. Rev Asoc Colomb
Dermatol. 2014;22:126–40.
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2010. p. 545.
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21. Clarke JT. Other rheumatologic diseases: relapsing polychondritis. In: Bologna JL, Jorizzo JL,
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Chapter 13
Granulomatous Inflammatory Diseases
This chapter explores inflammatory skin diseases in which the pathophysiological

mechanism involves the generation of a granulomatous response, while on histol-
ogy, there is the formation of granulomas. Non-infectious illnesses will be high-
lighted in this chapter, while the infectious etiologies of granulomatous inflammatory
disease are excluded:
A. Sarcoidosis
B. Granuloma annulare
C. Necrobiosis lipoidica
D. Annular elastolytic giant cell granuloma*
E. Cutaneous Crohn’s disease*
F. Melkersson-Rosenthal syndrome
Sarcoidosis
• Definition: Sarcoidosis is a multisystemic inflammatory disease characterized by

the presence of noncaseified granulomas (centrally organized collections of mac-
rophages and epithelial cells surrounded by lymphocytes), mainly involving the
lungs (in 90–95% of cases), the lymph nodes, and, in 20% of cases, the skin [1, 2].
• Pathogenesis: The etiology of sarcoidosis is unknown; however, genetic suscep-
tibility and environmental and infectious factors contribute to the development of
the disease [2]. Among the causal factors related to sarcoidosis are infections
caused by Mycobacterium and Cutibacterium acnes, Epstein-Barr virus, and her-
pes virus [3].
*

https://doi.org/10.1007/978-3-030-84107-2_13
384 13 Granulomatous Inflammatory Diseases
Fig. 13.1 Sarcoidosis with

lymph node involvement:
right cervical
lymphadenopathy
approximately 2x3 cm in
diameter with sarcoid
infiltration
• Clinical presentation: The most frequent manifestations of sarcoidosis are per-

sistent cough, cutaneous and ocular findings typical of the disease, peripheral
lymphadenopathy (Fig. 13.1), fatigue, and radiological features compatible with
sarcoidosis [2]. Cutaneous findings are divided into specific and nonspecific.
Specific findings develop in 9–15% of patients with cutaneous sarcoidosis and
include papular sarcoidosis (Figs. 13.2 and 13.3), plaque sarcoidosis (Fig. 13.4),
annular or circinate sarcoidosis (Fig. 13.5), maculopapular sarcoidosis
(Fig. 13.6), lupus pernio, and subcutaneous sarcoidosis. Erythema nodosum is
the most common nonspecific manifestation, presenting in 17% of cases as sub-
cutaneous, erythematous, and painful nodules on the pretibial region [1, 3].
Likewise, within the ocular manifestations are anterior uveitis in 66–70% of
cases, followed by posterior uveitis in 14–28% of cases, granulomas in the pal-
pebral border (Fig. 13.2) and the orbit in 26% of cases, and optic neuropathy
with a representation of 1–7% of cases [1].
Sarcoidosis 385
Fig. 13.2 Sarcoidosis:

with multiple bright
skin-colored and
violaceous papules that
converge, forming a plaque
on the back of the neck

skin-colored and slightly
infiltrated brown papules
are observed on the upper
eyelid

with skin-colored and
infiltrated, regular, and
papular edges with
atrophic center

female patient with an
annular, erythematous,
central depression on the
dorsum of the wrist

irregular achromic macules
and papules on the back
and lumbosacral region in
a patient with systemic
sarcoidosis with cutaneous
involvement
• Diagnosis: The diagnosis is usually ascertained from a combination of positive

clinical findings, radiological features, and histopathological evidence. The latter
usually shows noncaseating granulomas and the exclusion of another entity.
However, there are clinical manifestations of sarcoidosis that do not require
histological confirmation such as Löfgren’s syndrome (erythema nodosum, pul-
monary lymphadenopathy, arthralgia, and fever), Heerfordt syndrome (uveitis,
swelling of the parotid gland, facial nerve palsy, and fever), or asymptomatic
bilateral hilar adenopathy [4].
• Differential diagnosis: Like syphilis, sarcoidosis is a condition that simulates
different diseases. Differential diagnoses to consider are granulomatous mycosis
Granuloma Annulare 387
fungoides, Hodgkin’s disease, granulomatous rosacea, cutaneous Crohn’s dis-

ease, Blau syndrome, granulomatous cheilitis, and sarcoid reaction secondary to
lymphoma [5, 6].
Granuloma Annulare
• Definition: Represents a granulomatous inflammatory dermatosis that appears as

infiltrated papules that group to form a ring [7].
• Pathogenesis: Its etiology is unknown although different precipitating agents
have been connected to the disease such as trauma, insect sting, tuberculin test,
sun exposure, psoralen phototherapy, and viral infections. Granuloma annulare is
Fig. 13.7 Granuloma

annulare: on the leg, brown
annular plaques with
infiltrated edges are
observed
Fig. 13.8 Granuloma

annulare: erythematous
annular plaque with raised
edges and depressed center
is observed in the palmar
region
Fig. 13.9 Perforating

granuloma annulare: pink
papules with well-defined
regular edges, some with
central umbilication, are
observed on
metacarpophalangeal joints
proposed to represent a delayed hypersensitivity reaction to an unknown antigen.

The inflammatory reaction is Th1 type in which interferon-γ produces lympho-
cytes that mediate the degradation of the extracellular matrix [7].
• Clinical presentation: Granuloma annulare is a benign, self-limiting condition
that classically presents as annular to arcuate plaques on the extremities of young
adults [7] (Figs. 13.7 and 13.8). There are different clinical forms of the disease:
–– Generalized granuloma annulare: It occurs in a low percentage of patients as
multiple skin-colored or erythematous papules that cluster in annular plaques
that compromise the trunk and extremities [7] (Fig. 13.7).
–– Perforating granuloma annulare: It appears as small papules with a central
umbilication covered with a serohematic crust that affects the back of the
hands and fingers [7] (Fig. 13.9).
–– Subcutaneous or deep annular granuloma: It presents as large, painless skin-
colored nodules reminiscent of rheumatoid nodules and affecting the palms,
hands, and anterior surface of the tibia and feet, as well as the buttocks and
scalp [7].
Necrobiosis Lipoidica 389
–– Patchy granuloma annulare: Present as erythematous patches on the extremi-

ties and trunk [7].
• Diagnosis: The diagnosis is usually suspected via the clinical findings and sub-
sequently confirmed by histopathology, where granulomatous dermatitis with
focal degeneration of collagen and elastic fibers associated with mucin d eposition
and perivascular and interstitial lymphohistiocytic infiltrates in the superficial
and middle dermis is observed [7].
• Differential diagnosis: Differential diagnosis should include other annular-
presenting dermatoses such as annular sarcoidosis and annular elastolytic giant
cell granuloma, annulare mycosis fungoides, and borderline leprosy. Additionally,
flat warts, secondary syphilis, rheumatoid nodules, eruptive xanthomas, non-
Langerhans cell histiocytosis, rheumatic fever nodules, and deep granulomatous
infections, among others, should be ruled out [7].
Necrobiosis Lipoidica
• Definition: Represents a palisade granulomatous dermatitis that is related to dia-

betes mellitus in 15–65% [8].
• Pathogenesis: Its etiology is unknown; however, it is suggested that it is an
immunologically mediated vascular disease initially and then followed by the
alteration of collagen. It has been postulated that in cases associated with
diabetes, there is a microangiopathy that contributes to collagen degeneration
and dermal inflammation [8].
• Clinical presentation: It presents as yellowish-brown plaques with an atrophic
center and with telangiectasias with elevated violaceous edges that compromise
the pretibial region (Figs. 13.10, 13.11, 13.12, and 13.13). Ulceration occurs in
approximately one third of patients [8].
• Diagnosis: The diagnosis is clinical and confirmed by histology, where an inter-
stitial granulomatous dermatitis and a diffuse palisade are observed. The epider-
mis is normal or atrophic, and a predominantly lymphocytic perivascular infiltrate
Fig. 13.10 Necrobiosis

lipoidica: on the pretibial
region, a brown plaque
with infiltrated regular
edges, a hypochromic
atrophic center, and
telangiectasias is observed

lipoidica: on the pretibial
region, two brown plaques
with regular infiltrated
edges with a
hypopigmented atrophic
center with telangiectasias
are observed

lipoidica: brown plaque
edges and infiltrates and a
yellowish-brown center
with areas of atrophy and
fine superficial
desquamation
can be seen in the superficial and deep dermis with occasional eosinophils. Focal
loss of elastic tissue may be observed in areas of connective tissue sclerosis [8].
• Differential diagnosis: Within the differential diagnoses are granuloma annulare,
necrobiotic xanthogranuloma, sarcoidosis, diabetic dermopathy, and lipoderma-
tosclerosis. Other entities that can simulate a necrobiosis lipoidica are infectious
granulomatous diseases (leprosy, syphilis, dimorphic fungal infections), mor-
phea, lichen sclerosus, and sclerosing lipogranuloma [8].
Melkersson-Rosenthal Syndrome
• Definition: It is a rare granulomatous disease that presents with a triad of recur-

rent orofacial edema, development of folds and furrows in the tongue, and
peripheral facial paralysis [9].
• Pathogenesis: Although its etiology is unknown, it has been linked to factors
such as infections, genetics, allergic reactions, and benign lymphogranulomato-
sis. Smeets et al. have reported that Melkersson-Rosenthal syndrome is an auto-
somal dominant disease located on chromosome 9p11 [10].
Melkersson-Rosenthal Syndrome 391

lipoidica: a brownish-
yellowish plaque with
edges and atrophic center
with some telangiectasias
is observed on the
proximal third of the leg
Fig. 13.14 Melkersson-

Rosenthal syndrome:
edema of the lips
associated with episodes of
peripheral facial paralysis
granulomatous cheilitis in
histology

Rosenthal syndrome:
tongue edema associated
with fissures on the ventral
side of the tongue in a
patient with episodes of
peripheral facial paralysis
with a granulomatous
reaction on histology

Rosenthal syndrome:
chronic lip edema with
histopathology showing
benign lymph granulomas
• Clinical presentation: It is characterized by a triad of lip or face edema with

recurrent acute peripheral facial paralysis and tongue fissuring [11] (Figs. 13.14,
13.15, and 13.16).
• Diagnosis: There are no clear diagnostic criteria for the disease when presenting
in oligosymptomatic or monosymptomatic forms. However, for some authors, a
skin biopsy is important where a tuberculoid or sarcoidal granulomatous reaction
is observed, which may or may not be accompanied by a plasma lymph node
infiltrate [11].
References 393
References
1. Haimovic A, Sanchez M, Judson MA, Prystowsky S. Sarcoidosis. A comprehensive

review and update for the dermatologist. Part I: cutaneous disease. J Am Acad Dermatol.
2012;66:699.e1–18.
2. Sehgal VN, et al. Sarcoidosis as a systemic disease. Clin Dermatol. 2014;32:351–63.
3. Valeyre D, et al. Sarcoidosis. Lancet. 2014;383:1155–67.
4. Wolff K, Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D. Sarcoidosis. In: Fitzpatrick’s
dermatology in general medicine. 7th ed. New York: McGraw-Hill; 2008. p. 1484–92.
5. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society
(ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders
(WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee,
February 1999. Am J Respir Crit Care Med. 1999;160:736–55.
6. Reisenauer A, White KP, Korcheva V, White CR. Non-infectious granulomas: sarcoidosis.
In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2. London: Mosby; 2010.
p. 1562.
7. Reisenauer A, White KP, Korcheva V, White CR. Non-infectious granulomas: granuloma
annulare. In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2. London: Mosby;
2010. p. 1563–6.
8. Reisenauer A, White KP, Korcheva V, White CR. Non-infectious granulomas: necrobiosis
lipoidica. In: Bologna JL, Jorizzo JL, Rapini RP, editors. Dermatology, vol. 2. London: Mosby;
2010. p. 1566–8.
9. Feng S, Yin J, Li J, Song Z, Zhao G. Melkersson-Rosenthal syndrome: a retrospective study of
44 patients. Acta Otolaryngol. 2014;134:977–81.
10. Smeets E, Fryns JP, Van den Berghe H. Melkersson-Rosenthal syndrome and de novo autoso-
mal t(9;21)(p11;p11) translocation. Clin Genet. 1994;45:323–4.
11. Bordino L, et al. Melkersson Rosenthal syndrome. Report of two pediatric cases. Arch Argent
Pediatr. 2016;1(114):e224–7.
Chapter 14
Inflammatory Diseases Induced
by Ultraviolet Radiation
Photodermatoses are skin diseases induced or exacerbated by ultraviolet radiation

in which differing pathophysiological mechanisms are involved. Although the ultra-
violet radiation exposure in these diseases usually leads to direct or indirect activa-
tion of the immune system, in some cases, they can be mediated by phototoxic
agents or genetic defects that produce photoallergic substances or abnormalities in
DNA repair [1]. There are five groups in which the most frequent photodermatoses
are grouped according to the respectively involved pathophysiological mechanism:
A. Immunologically mediated dermatoses
(a) Polymorphic light eruption
(b) Actinic prurigo
(c) Chronic actinic dermatitis
(d) Solar urticaria**
(e) Hydroa vacciniforme**
B. Photodermatosis secondary to exogenous agents
(a) Photocontact dermatitis
(i) Phototoxic and photoallergic dermatitis
C. Photodermatosis secondary to endogenous agents*
(a) Congenital erythropoietic porphyria
(b) Erythropoietic protoporphyria
(c) Porphyria cutanea tarda
(d) Pseudoporphyria**
(e) Hepatoerythropoietic porphyria**
*
Pathologies not documentated in this atlas

https://doi.org/10.1007/978-3-030-84107-2_14
396 14 Inflammatory Diseases Induced by Ultraviolet Radiation
D. Diseases caused by defects in DNA repair

(a) Xeroderma pigmentosum**
(b) Trichothiodystrophy**
E. Photo-aggravated disorders (present in each respective section)
(a) Lupus erythematosus
(b) Dermatomyositis
(c) Rosacea
(d) Atopic dermatitis
(e) Seborrheic dermatitis
**Pathologies with a determined genetic component that are included in the
atlas of inflammatory diseases as an example of rare photodermatosis
Polymorphic Light Eruption
• Definition: Represents the most frequent photodermatosis, usually manifesting

within minutes to hours or, rarely, days after exposure to ultraviolet radiation.
The distribution is worldwide [2].
• Pathogenesis: It has been linked to exposure to ultraviolet radiation (sometimes
visible light) and other light devices such as tanning beds. The polymorphous
light rash presents as a delayed hypersensitivity response secondary to an endog-
enous and photoinduced skin antigen. This antigen is a form of heat shock pro-
tein. This is supported by the migration of CD4+ and CD8+ T lymphocytes in
association with an increase in the number of antigen-presenting cells in the
dermis and epidermis [2].
• Clinical presentation: Lesions appear within minutes to hours after sun exposure
on photodistributed areas such as the face, neck, lateral aspect of the arms, and
dorsum of the hands. Skin-colored or itchy erythematous papules evolve which
coalesce together to form symmetrically distributed plaques. The presence of
Fig. 14.1 Polymorphic

light eruption:
erythematous papules with
on the face and neck, some
of which converge to form
plaques without
compromising areas not
exposed to the sun
Polymorphic Light Eruption 397

light eruption:
observed involving the face
and neck, converging to
form plaques without
compromising the
submandibular area and
thorax

light eruption:
erythematous plaques are
observed on the dorsum of
bilateral hands, some of
which contain hemorrhagic
crusts and excoriations on
their surface
vesicles, blisters, as well as papulovesicular and edematous plaques can also be

found, especially on the face [2] (Figs. 14.1, 14.2, and 14.3).
• Diagnosis: The diagnosis is made according to the clinical presentation and sup-
ported by findings on histopathology and sometimes with photo-patch tests.
Epidermal spongiosis with a superficial, deep, periadnexal, and perivascular
lymphohistiocytic infiltrate can be found with some eosinophils and neutrophils
in the pathology of patients with polymorphic light eruption [2] (Figs. 14.4, 14.5,
and 14.6).
• Differential diagnosis: Differential diagnosis includes lupus erythematosus,
photo-aggravated dermatoses (seborrheic dermatitis, atopic dermatitis), solar
urticaria, and sometimes erythropoietic protoporphyria [2].
Fig. 14.4 Polymorphic light eruption: H&E-stained skin biopsy with evidence of a dense perivas-
cular inflammatory infiltrate predominantly of lymphocytic origin
Fig. 14.5 Polymorphic light eruption: H&E-stained skin biopsy at higher magnification with a
dense inflammatory infiltrate of predominantly lymphocytic origin
Actinic Prurigo 399

light eruption: H&E-
stained skin biopsy with an
inflammatory lymphocytic
infiltrate in the dermis and
spongiosis in the epidermis
Actinic Prurigo
• Definition: Actinic prurigo is an immunologically mediated photodermatosis

present in North and South American patients with genetic predisposition con-
ferred by polymorphisms in the human leukocyte antigen HLA-DR4 [3].
• Pathogenesis: Actinic prurigo arises as a delayed hypersensitivity reaction to a
yet-to-be-identified ultraviolet radiation-induced autoantigen. This is supported
by the presence of lymphocytes reactive against keratinocytes that are irradiated
by ultraviolet radiation, coupled with a high proliferation of autoantigens against
the skin and associated with intense inflammatory response in genetically predis-
posed patients [3].
• Clinical presentation: It appears as flat, polygonal, and shiny papules on the
face, neck, and hands sometimes covered with hemorrhagic crust on the extensor
areas of the forearms. The lesions are typically highly pruritic and manifest in
photodistributed areas. The presence of cheilitis is reported in between 33% and
85% of cases and ocular involvement in 62% of cases [3] (Figs. 14.7, 14.8, 14.9,
and 14.10).
Fig. 14.7 Actinic prurigo:

observed on the malar
region and nasal dorsum
which converge forming
excoriated plaques with
overlying hemorrhagic
crusts

on the malar region and
nasal dorsum, scaly and
plaques are observed in a
patient with actinic prurigo
• Diagnosis: The diagnosis is clinical since the histopathological findings are rela-
tively nonspecific. Nonetheless, skin biopsies from patients with actinic prurigo
show hyperkeratosis with orthokeratosis or parakeratosis that is accompanied by
regular acanthosis and focal or multifocal spongiosis with thickening of the base-
ment membrane. A superficial and mid-depth lymphocytic infiltrate is observed
in the dermis. The presence of eosinophils and melanophages and extravasation
of red blood cells may also be identified. Lip biopsies may report follicular
cheilitis, which report a sensitivity of 74.3% and specificity of 36.4% as predic-
tors of actinic prurigo [3].
• Differential diagnosis: Lupus erythematosus, cutaneous porphyrias, arthropod
assault, and nodular prurigo should be ruled out [2].
Chronic Actinic Dermatitis 401

actinic prurigo, currently
treated with thalidomide.
Note the presence of
secondary chronic
conjunctivitis
Chronic Actinic Dermatitis
• Definition: Represents a chronic eczematous rash in photo-exposed areas that

affects adults over 50 years of age secondary to a photoinduced endogenous
antigen [4].
• Pathogenesis: The main etiological agents are UVA, UVB, and visible light
ultraviolet rays. Clinically, the lesions are eczematous, and on histology, they
show a CD8+ lymphocytic infiltrate similar to allergic contact dermatitis second-
ary to an endogenous, photoinduced, or cutaneous agent [4].
• Clinical presentation: Chronic actinic dermatitis affects older adults of any race.
Lesions develop on healthy skin or in a patient with a previous history of
dermatitis (allergic or irritant contact dermatitis or polymorphic light eruption).
The lesions commence as scaly erythematous plaques, some of which are exuda-
tive or lichenified. Lesions occur in photo-exposed areas with margins that
respect the folds of clothing [4] (Figs. 14.11 and 14.12).
Fig. 14.10 Actinic

prurigo: on the malar
region, nasal dorsum, and
chin, excoriated violaceous
plaques are observed that
leave hyperpigmented
macules. Associated actinic
conjunctivitis is observed
Fig. 14.11 Chronic actinic

dermatitis: young adult
patient with brownish-
violet papules that
converge forming
“V”-shaped plaque on the
superoanterior trunk
• Diagnosis: The diagnosis is clinical since the histopathological findings are sim-
ilar to eczema. Histology can show epidermal spongiosis, acanthosis, and lym-
phocytic exocytosis that is accompanied by superficial and deep perivascular
lymphohistiocytic infiltrates that may be accompanied by eosinophils and plas-
mocytes [4].
Photocontact Dermatitis 403
Fig. 14.12 Chronic actinic

dermatitis: elderly patient
with infiltrated
erythematous plaques on
the face and “V” section of
the superior trunk in
photo-exposed areas. Note
the absence of affected
skin in areas covered by
clothing and hat
• Differential diagnosis: Contact eczemas and photo-aggravated dermatoses such

as cutaneous lupus erythematosus, actinic prurigo, polymorphic light eruption,
and solar urticaria, among others, should be ruled out [4].
Photocontact Dermatitis
• Definition: This type of dermatitis belongs to the group of diseases induced by

ultraviolet radiation whereby two photosensitivity mechanisms are distinguished:
phototoxic and photoallergic [5].
• Pathogenesis: Photosensitivity can be triggered by endogenous or exogenous
agents that absorb ultraviolet radiation [1]. There are two pathophysiological
mechanisms: phototoxic and photoallergic reactions. Phototoxic reactions are
due to an exogenous agent that is activated by ultraviolet radiation and mediates
phototoxic damage via an excited chemical state. Meanwhile, in photoallergic
reactions, ultraviolet radiation causes light activation of the culpable agent,

inducing the formation of an antigen to which a cell-mediated immune response
occurs via activation of the immune system [5].
• Clinical presentation: Phototoxic reactions manifest signs and symptoms within
minutes to hours after exposure to ultraviolet radiation and can clinically bear
resemblance to an exaggerated sunburn, displaying burning erythema, edema,
vesicles, and blisters associated with residual post-inflammatory hyperpigmenta-
tion. Unlike phototoxic reactions, photoallergic manifestations require a photo-
allergen sensitization phase of 24–48 hours prior and present as erythematous
plaques with or without scaling and with associated pruritus in photo-exposed
areas [1] (Fig. 14.13).
• Diagnosis: Confirmed with a detailed medical history where the photosensitive
agent can be associated. However, there are photo-patch tests or phototests avail-
able that allow the identification of a large number of photo-allergens [5].
• Differential diagnosis: It should be differentiated from allergic and irritative con-
tact dermatitis, contact dermatitis due to airborne substances, and other idio-
pathic photodermatoses such as actinic prurigo, polymorphic light eruption, and
chronic actinic dermatitis [5].
Fig. 14.13 Photocontact

dermatitis: older adult
patient who, on the face
and “V” of the neckline
and upper torso, has some
fissured, erythematous, and
scaly plaques. Note the
distribution of lesions is
limited to photo-exposed
areas
Congenital Erythropoietic Porphyria 405
Congenital Erythropoietic Porphyria
• Definition: Congenital erythropoietic porphyria (CEP) is a rare hereditary auto-

somal recessive disease caused by the homozygous defect in the enzyme known
as uroporphyrinogen III synthase (UROS) [6].
• Pathogenesis: The UROS gene, located on the long arm of chromosome 10, is
known to contain more than 35 identifiable mutations, with the missense type
mutation being the most frequent [7, 8]. This metabolic defect increases the lev-
els of the uroporphyrinogen and coproporphyrinogen porphyrins of the type I
isoform [7]. Uroporphyrin and other metabolites are thus deposited on the skin
secondary to accumulation, generating oxygen-dependent phototoxic damage
characterized by subepidermal blisters with severe inflammation [6, 7].
• Clinical presentation: CEP represents one of the most mutilating porphyrias due
to the delayed healing and repair processes in these patients [6, 7]. This is evi-
denced by the loss of acral tissue in the earlobes, nose, and fingers along with
facial mutilation [9] (Figs. 14.14, 14.15, 14.16, 14.17, and 14.18). Additionally,
hirsutism can be evidenced in photo-exposed areas (Fig. 14.19) and scarring alo-
pecia on the scalp [7, 9]. Other findings within the disease course include ocular
changes such as photophobia, keratoconjunctivitis (Figs. 14.20 and 14.21),
ectropion, corneal ulcers, as well as hyper- and irregular hypopigmentation of
Fig. 14.14 Congenital erythropoietic porphyria: mutilation of the distal phalanx of the second
finger associated with areas of residual scarring
Fig. 14.15 Congenital

erythropoietic porphyria:
multiple eroded plaques on
the nasal dorsum that leave
hypertrophic and atrophic
scars on the face. Note the
presence of eyelash
trichomegaly present in
patients with this variant of
porphyria

multiple atrophic and
hypertrophic scars on the
dorsum of the left hand
with amputation of distal
phalanges

amputation of distal
phalanges accompanying
erosions covered with
hemorrhagic crusts and
multiple residual atrophic
scars
Fig. 14.18 Congenital erythropoietic porphyria: defective healing leading to amputation of distal
phalanges in the context of bone resorption and secondary to a porphyrin-mediated phototoxicity
reaction

facial hypertrichosis in a
patient with porphyria

adult patient with multiple
atrophic scars in photo-
exposed areas
the skin [10] (Fig. 14.22). Erythrodontia (Figs. 14.23 and 14.24), osteodystro-
phy, and hypercellular bone marrow are other findings that present in almost all
patients [11].
• Diagnosis: The diagnosis is usually suspected clinically and later confirmed by
measuring porphyrin levels in the serum and urine [7]. Histopathology findings
tend to be nonspecific, but subepidermal blistering may be seen in the acute
phase (Figs. 14.25 and 14.26)[7, 9, 10].
• Differential diagnosis: The differential diagnoses are other forms of porphyrias
such as delayed cutaneous porphyria, erythropoietic protoporphyria, pseudopor-
phyria and photocontact dermatitis, and cutaneous lupus erythematosus,
among others.

adult male with severe
keratitis

multiple hypo- and
on the face with associated
hypertrichosis and dental
purple discoloration
(erythrodontia)

patient with erythrodontia
secondary to porphyrin
deposition in the dentin

fluorescent erythrodontia
in Wood’s lamp
examination
Porphyria Cutanea Tarda
• Definition: Porphyria cutanea tarda occurs due to partial or total deficiency of

uroporphyrinogen decarboxylase in an acquired or inherited form [12].
• Pathogenesis: Deficiency of uroporphyrinogen decarboxylase leads to accumula-
tion of uroporphyrin and 7-carboxy porphyrinogen. These proteins are deposited
in the skin and interact with different compounds such as reactive oxygen species,
mast cells, and complement and metalloproteinases to subsequently absorb light
energy and generate porphyrins in excited states that mediate tissue damage [12].
• Clinical presentation: Vesicles and blisters initially appear, followed by erosions
and crusts on areas exposed to the sun and trauma such as the face, back, and
dorsum of the hands. Additionally, patients present skin fragility along with
tense hemorrhagic blisters without perilesional inflammation that resolve, leav-
ing hypo- and hyperpigmented scars with milia cysts [12] (Figs. 14.27 and 14.28).
• Diagnosis: The diagnosis of porphyria cutanea tarda is made clinically, histo-
logically, and according to the analysis of porphyrins in urine, blood, and feces.
Erythropoietic Protoporphyria 411

red staining of urine with
ultraviolet light in a patient
with CEP
At the histological level, a subepidermal blister is observed with extension of the

dermal papilla to the interior of the blister. This phenomenon is called scalloping,
which is explained by the rigidity of the superficial dermis induced by the eosin-
ophilic material in the vessel wall [12].
• Differential diagnosis: It should be differentiated from hereditary copropor-
phyria, variegate porphyria, hepatoerythropoietic porphyria, congenital erythro-
poietic porphyria, pseudoporphyria, acquired epidermolysis bullosa, and
scleroderma [12].
Erythropoietic Protoporphyria
• Definition: Represents a hereditary disease due to the defect of ferrochela-

tase [13].
• Pathogenesis: Ferrochelatase is the enzyme catalyzing the final step in the
heme synthesis pathway in which iron is inserted into the protoporphyrin IX
ring. A defect in the gene coding for this enzyme causes the accumulation of
a b
Fig. 14.26 Congenital erythropoietic porphyria: (a) Reddish-colored urine in a patient with por-
phyria secondary to the excretion of porphyrins. (b) Wood’s lamp examination showing porphyrins
in urine
Fig. 14.27 Porphyria cutanea tarda: multiple hypo- and hyperpigmented macules with hemor-
rhagic crusting are seen on the dorsum of the hands
Erythropoietic Protoporphyria 413
Fig. 14.28 Porphyria

cutanea tarda: hemorrhagic
crusting with multiple
residual varioliform scars
is observed on the right
shoulder
Fig. 14.29 Erythropoietic

protoporphyria: multiple
varioliform scars are seen
on the dorsum of the hands
in a patient with
erythropoietic
protoporphyria
protoporphyrin IX in the erythrocytes, plasma, skin, and liver, which is respon-

sible for the clinical picture [13].
• Clinical presentation: Unlike other forms of porphyrias, erythropoietic protopor-
phyria presents acutely with photosensitivity, edema, and pain on the skin similar
to a sunburn. Chronic lesions present as facial punctiform and “varioliform”
scars, as well as a “waxy” thickening of the skin in the perioral region and dor-
sum of the hands (Figs. 14.29 and 14.30) [13].
• Diagnosis: The diagnosis is based on both clinical and laboratory findings.
Typically recognizable biochemical alterations include elevated levels of proto-
porphyrin IX in plasma and feces since it is not eliminated by the renal route [13].
• Differential diagnosis: It must be differentiated from other forms of porphyria
such as congenital erythropoietic porphyria, porphyria cutanea tarda, and pseu-
doporphyria [13].
Fig. 14.30 Erythropoietic

protoporphyria: adolescent
varioliform scars with
residual hyperpigmented
macules on the nasal
dorsum and malar region
in a patient with a history
of erythropoietic
protoporphyria
References
1. Mariaca CJ, Nuñez R. Fotodermatosis mediadas inmunológicamente. Rev Asoc Colomb

Dermatol. 2016;24:29–44.
2. Lim HW, Hawk JLM. Photodermatologic disorders: PMLE. In: Bologna JL, Jorizzo JL, Rapini
RP, editors. Dermatology, vol. 2. 3rd ed. London: Mosby; 2010. p. 1467–77.
3. Valbuena MC, Muvdi S, Lim HW. Actinic prurigo. Dermatol Clin. 2014;32:335–44.
4. Lim HW, Hawk JLM. Photodermatologic disorders: chronic actinic dermatitis. In: Bologna
5. Lim HW. Abnormal responses to ultraviolet radiation: photosensitivity induced by exog-
enous agents. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, edi-
tors. Fitzpatrick’s dermatology in general medicine. 7th ed. New York: McGraw-Hill; 2008.
p. 828–34.
6. Fritsch C, Bolsen K, Ruzicka T, Goerz G. Congenital erythropoietic porphyria. J Am Acad
Dermatol. 1997;36:594–610.
7. Darwich E, Herrero C. New developments in erythropoietic porphyrias. Actas Dermosifiliogr.
2013;104:212–9.
8. Phillips JD, Steensma DP, Pulsipher MA, Spangrude GJ, Kushner JP. Congenital erythropoi-
etic porphyria due to a mutation in GATA1: The first trans-acting mutation causative for a
human porphyria. Blood. 2007;109:2618–21.
9. Wolff K, Goldsmith L, Katz S, Gilchrest B, Paller A, Leffell D. The porphyrias. In: Fitzpatrick’s
dermatology in general medicine. 7th ed. New York: McGraw-Hill; 2008. p. 1247–50.
10. González LF, Motta A. Porfiria eritropoyética congénita. Rev Asoc Colomb Dermatol.
2014;22:246–9.
11. Puy H, Gouya L, Deybach JC. Porphyrias. Lancet. 2010;375:924–37.
12. Vieira FMJ, Martins JEC. Porphyria cutánea tarda. An Bras Dermato. 2006;81:569–80.
13. Darwich E, Herrero C. Novedades en las porfirias eritropoyéticas. Actas Dermosifiliogr.
2013;104:212–9.
Chapter 15
Neutrophilic and Eosinophilic
Inflammatory Diseases
This chapter documents inflammatory diseases that have a predominantly neutro-

philic or eosinophilic infiltrate on histopathology. The clinical presentation of these
dermatoses is diverse and can be classified into two large groups:
A. Neutrophilic dermatoses
(a) Acute febrile neutrophilic dermatosis (Sweet syndrome)
(b) Pyoderma gangrenosum
(c) Subcorneal pustular dermatosis (Sneddon-Wilkinson disease)*
(d) Behcet’s disease
(e) Neutrophilic dermatosis of the hands*
(f) Eccrine neutrophilic hidradenitis*
(g) Rheumatoid neutrophilic dermatitis*
B. Eosinophilic dermatosis
(a) Facial granuloma *
(b) Eosinophilic pustular folliculitis
(c) Eosinophilic cellulitis*
(d) Eosinophilic fasciitis*
Sweet Syndrome
• Definition: Also called acute febrile neutrophilic dermatosis, it represents an

inflammatory dermatosis characterized by fever, neutrophilia, skin lesions with
neutrophilic infiltrate, and resolution of the condition after administration of cor-
ticosteroids [1].
*

https://doi.org/10.1007/978-3-030-84107-2_15
416 15 Neutrophilic and Eosinophilic Inflammatory Diseases
• Pathogenesis: Its etiology is unknown; however, it is suggested that it represents

a dermatosis secondary to a hypersensitivity reaction. It is believed that there is
a local or systemic alteration in the secretion of cytokines such as interleukin 1
(IL-1), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage
colony-stimulating factor (GM-CSF), and interferon gamma [2].
• Clinical presentation: Sweet syndrome can be classified into the classic presenta-
tion, associated with malignancy or induced by medications. The classic form pres-
ents as edematous erythematous papules or plaques and painful infiltrates on
palpation with the presence of a dermal neutrophilic infiltrate without vasculitis
(Figs. 15.1, 15.2, 15.3, 15.4, 15.5, 15.6, 15.7, and 15.8). Patients presenting in this
manner have a prodromal phase consisting of fever, general malaise, and conjunc-
tivitis. The form associated with malignancy appears as vesiculobullous skin
lesions with subsequent ulceration which may be reminiscent of gangrenous pyo-
derma, mainly affecting the extremities. The drug-associated form may present as
the classic form subsequent to the administration of the related causative agent [1, 2].
• Diagnosis: There are already established diagnostic criteria for this condition,
including the identification of both of two major criteria (abrupt onset of the typi-
cal lesions of Sweet syndrome along with histopathological findings compatible
Fig. 15.1 Sweet

syndrome: patient with
multiple erythematous,
edematous, and infiltrated
plaques on the palmar
surface of the left hand
associated with a feverish
state
Sweet Syndrome 417
Fig. 15.2 Sweet

syndrome: a slightly
infiltrated erythematous to
irregular edges is observed
on the anterior aspect of
the knee
with the disease) and four minor criteria of which two must be identified in order
to form a diagnosis (prodromal phase associated with an infectious agent or vac-
cine, presence of malignancy, inflammatory disease, exposure to medications or
pregnancy, constitutional symptoms, fever, leukocytosis, and an excellent
response to systemic steroids) [2]. Histopathology findings include the presence
of a diffuse perivascular and nodular neutrophilic infiltrate without vasculitis,
although in some cases, it may be associated with leukocytoclastic vasculitis [1,
2] (Figs. 15.9 and 15.10).
• Differential diagnosis: The differential diagnosis is wide, ranging from inflam-
matory dermatoses such as gangrenous pyoderma, eccrine neutrophilic hidrade-
nitis, rheumatoid neutrophilic dermatitis, and neutrophilic dermatosis of the
hands, among others. Infectious dermatoses such as cellulitis, pyoderma, furun-
culosis, and erythema migrans can also be mistaken for Sweet syndrome [2].
Fig. 15.3 Sweet syndrome: on the posterior aspect of the metacarpophalangeal joints, slightly
infiltrated erythematous plaques with irregular edges are observed
Fig. 15.4 Sweet

syndrome: on the dorsum
of the hand, involving the
forearm and phalanges,
pustules are observed on a
slightly infiltrated
erythematous base,
histologically compatible
with Sweet syndrome
Pyoderma Gangrenosum
• Definition: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of

unknown etiology that affects adults and rarely children [3].
• Pathogenesis: Although its etiology is unknown, it is suggested that there is an
alteration in the neutrophil chemotaxis associated with different benign inflam-
matory conditions and malignant processes [3, 4].
• Clinical presentation: There are five distinct clinical variants that are recognized,
which include classic, bullous, vegetative, pustular, and peristomal PG. [4] One
Pyoderma Gangrenosum 419
Fig. 15.5 Sweet

syndrome: adult man with
multiple infiltrated
some of which are
ulcerated in their center
Fig. 15.6 Sweet

syndrome: male patient
with erythematous plaques
and infiltrates on the malar
region and nasal dorsum,
compatible with Sweet
syndrome
Fig. 15.7 Annular Sweet

syndrome: on the distal
third of the left anterior leg
and dorsum of the foot,
annular and infiltrated
erythematous plaques are
observed
Fig. 15.8 Sweet

syndrome: on the left
malar region, multiple
erythematous-edematous
plaques with poorly
defined edges associated
with ipsilateral
conjunctivitis are observed
Fig. 15.9 Sweet syndrome: H&E-stained skin biopsy with foci of neutrophilic infiltration in the
superficial dermis without epidermal change
of the clinical characteristics of pyoderma gangrenosum is the presence of the

pathergy phenomenon which is defined as the development of skin lesions sec-
ondary to skin injury [3].
–– Classic or ulcerative PG: Clinically, lesions present as a painful small ery-
thematous or violaceous papule or pustule (the “malignant pustule”), which
evolve into violaceous ulcers or necrotic plaques [3, 4]. One of the hallmark
features of classic PG is the presence of an undermined or raised border with
a characteristic gun metal gray or violaceous to blue color [4] (Figs. 15.11,
15.12, 15.13, 15.14, 15.15, 15.16, 15.17, 15.18, 15.19, and 15.20).
–– Bullous or vesiculobullous PG: Fluid-filled vesicles or bullae are seen affect-
ing the face and arms, particularly the dorsal hands. The lesions clinically
resemble superficial bullous variants of Sweet syndrome. These rarely ulcer-
ate and are related with malignant dyscrasias [4].
Fig. 15.10 Sweet syndrome: H&E-stained skin biopsy with polymorphonuclear (neutrophilic)
infiltrates in the superficial and deep dermis with vessel permeation
–– Vegetative PG: It is a very rare variant that presents as single or multiple

superficial, asymptomatic lesions that heal without scarring [4]. Vegetative
PG affects the trunk and rarely is associated with underlying systemic dis-
ease [5].
–– Pustular PG: This is the variant most associated with other PG forms and
related with IBD [4, 5]. The pustules commonly ulcerate affecting the limbs
and trunk [4, 5]. There are some clinical reports of pustules on the scalp and
penis [6].
–– Peristomal PG: Occurs around a stoma, frequently observed in patients with
a colostomy and represents approximately 15% of cases of PG. [4]
Fig. 15.11 Pyoderma

gangrenosum: on the distal
third of the leg, there is an
ulcer with well-defined and
irregular erythematous-
violaceous edges with a
fibrinoid center
Fig. 15.12 Pyoderma

third of the left leg, an
ulcer with regular
erythematous and
violaceous edges with a
fibrinoid center is observed
• Diagnosis: The diagnosis is clinical and histopathological. There are major and
minor criteria for diagnosis, among which are a rapidly growing painful ulcer
with poorly defined and irregular edges in a patient in whom other causes of
ulcers have been ruled out, together with the history of pathergy, cribriform scar-
ring, systemic diseases associated with pyoderma gangrenosum, presence of
histological findings of the disease, and rapid response to systemic glucocorti-
coids [3]. The histopathology of pyoderma gangrenosum is not very specific,
where, in the vast majority of cases, ulceration with abscess formation is
observed. The underlying dermis tends to show acute and chronic inflammation
[7] (Figs. 15.21, 15.22, 15.23, 15.24, and 15.25).
Fig. 15.13 Pyoderma

third of the leg, an ulcer
with well-defined
erythematous and
violaceous regular edges is
observed with granulation
tissue in the center
Fig. 15.14 Pyoderma

gangrenosum:
erythematous, violaceous,
and irregularly edged ulcer
with granulation and
fibrinoid tissue in its center
Behcet’s Disease 425
Fig. 15.15 Pyoderma

gangrenosum: ulcer with
well-defined erythematous
and infiltrated regular
edges with a fibrinoid
center in the first
interdigital space of
the foot
Fig. 15.16 Pyoderma

gangrenosum: ulcer with
violaceous angled edges
and infiltrates with
edges and a necrotic center
with areas of granulation
• Differential diagnosis: The diagnosis of gangrenous pyoderma is of exclusion;

therefore, other causes of ulcers such as vasculitis, squamous cell carcinomas,
venous or arterial ulcers, infections such as tuberculosis, leishmaniasis, sporotri-
chosis, or factitious ulcer must be ruled out in some cases [3].
Behcet’s Disease
• Definition: It is an inflammatory disease characterized by recurrent oral ulcers

and systemic compromise [8].
• Pathogenesis: Behcet’s disease has been reported to present as an aberrant
immune response precipitated by exposure to primarily infectious antigens in
Fig. 15.17 Pyoderma

gangrenosum: an ulcer
with erythematous,
well-defined, infiltrated,
and regular edges with
granulation in the center
Fig. 15.18 Pyoderma

third of the right leg, there
is an ulcer with irregular
edges with areas of
necrosis and granulation
tissue in its center
Behcet’s Disease 427
Fig. 15.19 Pyoderma

gangrenosum: multiple
violaceous-edged ulcers
with fibrinoid centers
secondary to local trauma
(pathergy phenomenon)

suppurativa associated with
pyoderma gangrenosum:
nodules that communicate
with fistulous tracts that
ulcerate, compromising the
inguinal and anogenital
region
genetically predisposed patients. Infectious antigens have cross-reactivity with

human peptides as well as heat shock proteins capable of activating T lympho-
cytes, fuelling the inflammatory process [5].
• Clinical presentation: Behcet’s disease is an inflammatory dermatosis with sys-
temic involvement with dermatological, ophthalmological, musculoskeletal, and
central nervous system manifestations. At the cutaneous level, the disease begins
with recurrent oral ulcers in 97–100% of patients (the vast majority start with
aphthous ulcers of less than 1 cm in diameter) (Fig. 15.26) associated with geni-
tal ulcers in 85% of cases (Fig. 15.27), acneiform papulopustular lesions, ery-
thema nodosum, and superficial thrombophlebitis. Like pyoderma gangrenosum,
Behcet’s disease presents with a positive pathergy test (development of the dis-
ease after local injury) [5].
• Diagnosis: The International Study Group for Behcet’s Disease proposed differ-
ent criteria for diagnosis, including recurrent aphthous ulcers plus two of the
following: recurrent genital ulcers, eye pathologies (anterior or posterior uveitis,
retinal vasculitis), skin lesions (papulopustular lesions, erythema nodosum,
heavy folliculitis), and a positive pathergy test [5].
Fig. 15.21 Pyoderma gangrenosum: H&E-stained skin biopsy with evidence of acute and chronic
inflammatory infiltrates with a predominance of polymorphonuclear cells that involve the superfi-
cial and deep dermis with some remnants of infundibular epithelium
• Differential diagnosis: The differential diagnoses are broad and include recur-
rent oral thrush, pyoderma gangrenosum, acne fulminans, and inflammatory
bowel disease with skin involvement, among others [5].
Eosinophilic Pustular Folliculitis
• Definition: Also called Ofuji disease, it is an inflammatory disease of unknown

etiology characterized by a folliculotropic non-infectious eosinophilic infil-
trate [9].
• Pathogenesis: It has been proposed that eosinophilic pustular folliculitis presents
as a hypersensitivity reaction secondary to various infections as well as drugs.
The presence of different receptors in the hair unit that are able to promote the
Eosinophilic Pustular Folliculitis 429
Fig. 15.22 Pyoderma gangrenosum: H&E-stained skin biopsy at higher magnification with the
presence of multiple polymorphonuclear cells and some plasmocytes
migration of lymphocytes and eosinophils has been documented. When related

to HIV infection, this condition is characterized by an imbalance in T lympho-
cyte populations, with favoring of a TH2 predominance in the follicular epithe-
lium [6].
• Clinical presentation: There are three clinical presentations of the disease: clas-
sic type eosinophilic pustular folliculitis (Fig. 15.28) or Ofuji disease, infantile
eosinophilic pustular folliculitis, and immunosuppression-associated eosino-
philic pustular folliculitis (mainly advanced HIV infection). In the classic form,
there are agminated follicular papules or pustules arranged in plaques or annular
arrangements with more common involvement of the face (Fig. 15.29). The
infantile form presents as follicular erythematous papules, rarely forming plaques
Fig. 15.23 Pyoderma gangrenosum: H&E-stained skin biopsy with evidence of acute and chronic
inflammatory infiltrates with invasion of the subcutaneous tissue
that compromise the scalp with subsequent extension to the limbs.

Immunosuppression-associated eosinophilic pustular folliculitis presents as iso-
lated pruritic follicular papules, rarely pustules, and almost never plaques [6].
• Diagnosis: Diagnosis requires a clinical-pathological correlation. Microscopy of
skin biopsies shows spongiosis and pustulosis of the infundibular region of the
hair follicle with extension of the infiltrate at the perivascular and periadnexal
level [6].
• Differential diagnosis: It should be differentiated from infections and inflamma-
tory diseases such as bacterial folliculitis, scabies, acne, rosacea, tinea faciei,
cutaneous lupus, Demodex infestation, insect bite, subcorneal pustular dermato-
sis, acute generalized exanthematous pustulosis, and follicular mucinosis [6].
Fig. 15.24 Pyoderma gangrenosum: H&E-stained skin biopsy with evidence of a polymorpho-
nuclear inflammatory infiltrate in the deep dermis and subcutaneous tissue
Fig. 15.25 Pyoderma gangrenosum: H&E-stained skin biopsy with evidence of polymorphonu-
clear cells permeating the pilosebaceous unit
Fig. 15.26 Behcet’s

disease: patient with
multiple recurrent oral
ulcers on the jugal mucosa
and hard palate compatible
with Behcet’s disease
Fig. 15.27 Behcet’s

disease: recurrent genital
ulcers in a patient with
Behcet’s disease
Fig. 15.28 Eosinophilic

pustular folliculitis:
multiple isolated follicular
papules are observed on
the face and neck, some of
which are excoriated,
while histopathology
findings yield an
eosinophilic inflammatory
infiltrate compatible with
eosinophilic folliculitis
References 435
Fig. 15.29 Adult

eosinophilic folliculitis: a
65-year-old man with
skin-colored follicular
papules on the nasal
dorsum, right infraorbital
region, and forehead
References
1. Cohen PR, Kurzrock R. Sweet’s syndrome revisited: a review of disease concepts. Int J
Dermatol. 2003;42:761–78.
2. Rochet NM, et al. Sweet syndrome: clinical presentation, associations, and response to treat-
ment in 77 patients. J Am Acad Dermatol. 2013;69:557–64.
3. Callen JP, Jackson JM. Pyoderma gangrenosum: an update. Rheum Dis Clin N Am.
2007;33:787–802.
4. Ahn C, Negus D, Huang W. Pyoderma gangrenosum: a review of pathogenesis and treatment.
Expert Rev Clin Immunol. 2018;14:225–33.
5. Kim RH, Lewin J, Hale CS, et al. Vegetative pyoderma gangrenosum. Dermatol Online J
2014;16(20):1–3
6. Sakiyama M, Kobayashi T, Nagata Y, et al. Bullous pyoderma gangrenosum: a case report and
review of the published work. J Dermatol. 2012;39:1010–5.
7. Calonje E, Brenn T, Lazar A. Neutrophilic and eosinophilic dermatoses: pyoderma gan-
grenosum. In: McKee PH, editor. McKee's pathology of the skin: with clinical correlations.
Edinburgh: Elsevier/Saunders; 2012. p. 634.
8. Sánchez PM, Valenzuela-Ahumada F. Enfermedad de Behcet. Piel. 2015;30:358–64.
9. Cordo MV, et al. Foliculitis pustular eosinofílica clásica o enfermedad de Ofuji. Arch Argent
Dermatol. 2015;65:203–6.
Chapter 16
Inflammatory Diseases
of the Subcutaneous Adipose Tissue
This chapter describes and illustrates the inflammatory conditions that affect the
anatomical components of the subcutaneous tissue. Adipocytes, which are found in
this layer, undergo inflammatory changes of the lobules, the septa, or both.
Inflammation of the subcutaneous adipose tissue is called panniculitis and can be
classified as below:
A. Lobular and mixed panniculitis
(a) Erythema induratum of Bazin or nodular vasculitis*
(b) Pancreatic panniculitis*
(c) Sclerema neonatorum*
(d) Subcutaneous fat necrosis of the newborn*
(e) Post-steroid panniculitis*
(f) Lupus panniculitis
(g) Panniculitis associated with dermatomyositis*
(h) Lipoatrophic panniculitis*
(i) Cold panniculitis*
(j) Sclerosing lipogranuloma*
(k) Panniculitis from injected substances*
(l) Lipodermatosclerosis
B. Septal panniculitis
(a) Erythema nodosum
(b) Scleroderma and morphea panniculitis*
(c) Panniculitis due to alpha-1 antitrypsin deficiency*
*

https://doi.org/10.1007/978-3-030-84107-2_16
438 16 Inflammatory Diseases of the Subcutaneous Adipose Tissue
Erythema Nodosum
• Definition: Erythema nodosum is the most frequent form of panniculitis and the
variant of septal panniculitis that may be associated with systemic disorders [1].
• Pathogenesis: A delayed hypersensitivity response to different antigenic stimuli
including bacteria, viruses, and chemical agents that has been considered with
contribution from Th1 lymphocytes, different adhesion molecules, and neutro-
phils has been identified. The clinical response observed from administration of
anti-neutrophilic medications such as colchicine supports the role of neutrophils
in the pathogenesis of erythema nodosum. Likewise, the role of tumor necrosis
factor alpha (TNF-alpha) in the pathogenesis of chronic erythema nodosum has
been documented [1].
• Clinical presentation: It classically presents as erythematous, painful, and bilat-
eral nodules that predominantly affect the anterior aspects of the legs and, less
commonly, affect the thighs and forearms (Figs. 16.1, 16.2, and 16.3). Ulceration
Fig. 16.1 Erythema

nodosum: young adult
woman with multiple
erythematous and painful
nodules with well-defined
irregular borders on the
pretibial region
Erythema Nodosum 439
Fig. 16.2 Erythema

nodosum: painful
erythematous nodules with
borders that involve the
medial pretibial region
Fig. 16.3 Erythema

nodosum: on the pretibial
region, well-defined
irregular erythematous
nodules are observed
is not a typical clinical feature of erythema nodosum; thus, when it is observed,

the clinician should consider a broader differential diagnosis. The presentation is
acute and may be accompanied by systemic symptoms such as fever, arthralgia,
and malaise with a self-limited duration lasting a few days to a few weeks [1].
• Diagnosis: The diagnosis is suspected clinically and confirmed on histopathol-
ogy, which typically shows evidence of septal panniculitis with a neutrophilic
infiltrate in early lesions. The presence of vasculitis is not a classic finding of this
entity; however, secondary vasculitis has been documented in some cases with a
dense infiltrate rich in neutrophils (Figs. 16.4, 16.5, 16.6, and 16.7). Miescher
microgranulomas (small collections of macrophages in the septa) can be observed
in early lesions [1] (Fig. 16.8).
• Differential diagnosis: Other forms of panniculitis such as erythema induratum
of Bazin or nodular vasculitis, pancreatic panniculitis, and panniculitis induced
by infectious agents should be ruled out [1].
Fig. 16.4 Septal panniculitis: skin biopsy stained in H&E with evidence of infiltration in the sep-
tum of the adipose panicle
Lupus Panniculitis 441
Fig. 16.5 Erythema nodosum: biopsy of the skin and subcutaneous tissue in H&E stain at 40×
with evidence of lymphocyte infiltration and some neutrophils with septum augmentation
Lupus Panniculitis
• Definition: Lupus panniculitis (LP), also known as lupus profundus, is a rare

subtype of chronic cutaneous lupus erythematosus that may develop in patients
with systemic lupus erythematosus or discoid lupus erythematosus but can also
occur in isolation [2].
• Pathogenesis: It has been hypothesized that the recruitment of T lymphocytes in
lupus panniculitis is related to T lymphocyte recruitment in cutaneous lupus ery-
thematosus [7]. It is proposed that this recruitment is mediated by the expression
of type I interferons in the skin, which induce the production of antiviral proteins
Fig. 16.6 Septal panniculitis: biopsy of subcutaneous cellular tissue in H&E stain at 40× with
evidence of a mild perivascular inflammatory infiltrate and erythrocyte extravasation without evi-
dence of vasculitis
Fig. 16.7 Erythema nodosum: biopsy of subcutaneous adipose tissue in H&E stain with evidence
of septal thickening and a mixed inflammatory infiltrate
such as MxA and IFI27, as well as chemokines such as CXCL9 and CXCL10,
which are ligands for the CXCR3 receiver [3]. This translates into a recruitment
of positive CXCR3 lymphocytes and dendritic cells that mediate the local inflam-
matory process.
• Clinical presentation: LP is characterized by the presence of erythematous sub-
cutaneous nodules that resolve, leaving lipoatrophic areas. It mainly involves the
proximal extremities, in particular the lateral aspects of the arms and shoulders,
and less frequently the buttocks, trunk, face, and scalp [1] (Figs. 16.9 and 16.10).
• Diagnosis: The diagnosis is clinical and confirmed via histopathology. Peters
and Su [4] propose some histopathological criteria for the diagnosis of LP, con-
sisting of two groups: major criteria (important for diagnosis) and minor criteria
(not necessary for diagnosis). The major criteria include:
–– Hyaline fat necrosis with lymphocytic infiltration
–– Lymphoid follicle formation
–– Lobular or paraseptal lymphocytic panniculitis and calcification (less
frequent)
Fig. 16.8 Erythema nodosum: biopsy of subcutaneous adipose tissue in H&E stain at 40× show-
ing evidence of a thickened septum with a lymphocytic infiltrate and formation of some Miescher
microgranulomas (arrow)
Fig. 16.9 Lupus

panniculitis: young adult
patient with residual
lipoatrophic areas
secondary to lupus
panniculitis
Fig. 16.10 Lupus

panniculitis: on the
bilateral malar region,
residual lipoatrophic areas
are observed on a patient
with lupus panniculitis
The minor criteria include:

–– Histopathological changes of cutaneous lupus erythematosus such as vacuo-
lar degeneration of the basement membrane and a superficial and deep peri-
vascular lymphoid infiltrate with peripheral extension [5] (Figs. 16.11, 16.12,
16.13, 16.14, and 16.15).
–– Perivascular lymphocytic inflammation
–– Hyalinization of the subepidermal area
–– Mucin deposits
–– Presence of histiocytes
–– Small granulomas and infiltrates of plasma and eosinophil cells
• Differential diagnosis: Other subtypes of lobular panniculitis for which a differ-
ential diagnosis should be made are erythema induratum of Bazin (nodular vas-
culitis), pancreatic panniculitis, and subcutaneous panniculitis-like T-cell
lymphoma [1].
Fig. 16.11 Lupus panniculitis. Biopsy of the skin and subcutaneous adipose tissue in H&E stain
at 20× in which a lobular lymphocytic panniculitis without vasculitis stands out
Lipodermatosclerosis
• Definition: It represents a frequent panniculitis associated with chronic venous

disease and sometimes triggered by microtrauma mainly on the lower limbs [6].
• Pathogenesis: Although there are different theories surrounding the pathogenesis
of the disease, the main cause is venous insufficiency. Venous hypertension
favors the deposition of fibrin in the endothelial walls which translates to an
Lipodermatosclerosis 447
Fig. 16.12 Lupus panniculitis. Biopsy of the skin and subcutaneous adipose tissue in H&E stain-
ing at 40× with areas of fibrinoid necrosis surrounding lobules of subcutaneous adipose tissue with
a lymphoid infiltrate
alteration in oxygen exchange and macromolecule diffusion. This process results

in the recruitment of inflammatory cells and the release of cytokines that per-
petuate the inflammatory process. Similarly, alterations in proteins C and S have
been documented that favor the presentation of microthrombi that lead to endo-
thelial thickening and dermal fibrosis [6].
• Clinical presentation: There are two clinical phases of the disease: the acute
phase, which is characterized by the presence of indurated, infiltrated, and ery-
thematous plaques that involve the limbs, and the chronic phase, which is char-
acterized by fibrosis of the dermis, induration, and narrowing of the distal
lower limb, forming an “inverted champagne bottle” appearance [6] (Figs. 16.16
and 16.17).
• Diagnosis: The diagnosis is clinical, and the skin biopsy is reserved for those
cases in which it is necessary to rule out pathologies such as morphea, sclero-
myxedema, erythema nodosum, or infectious etiologies. In most cases, it is man-
datory to study the venous and arterial systems with ultrasonography.
Histopathology identifies a lobular panniculitis with fibrosis and focal infiltration
with macrophages around small lobules [7] (Figs. 16.18, 16.19, and 16.20).
• Differential diagnosis: Differential diagnoses include infectious processes such
as cellulitis, erysipelas, and necrotizing fasciitis or inflammatory processes such
as eosinophilic fasciitis, morphea, scleromyxedema, and erythema nodosum,
among others [7].
Fig. 16.13 Lupus panniculitis: biopsy of the subcutaneous adipose tissue stained with H&E show-
ing evidence of a mixed perilobular and septal inflammatory infiltrate without vasculitis
Fig. 16.14 Lupus panniculitis: biopsy of subcutaneous adipose tissue in H&E staining illustrating
an inflammatory septal infiltrate and low perilobular infiltrate
Fig. 16.15 Lupus panniculitis: major perilobular inflammatory infiltrate

Fig. 16.16 Lipodermatosclerosis: on the lower limbs, there are indurated brownish plates that give
the appearance of an inverted champagne bottle
Fig. 16.17 Lipodermatosclerosis: an indurated and fibrous plaque with well-defined irregular
edges involving the distal third of the right leg
Fig. 16.18 Lipodermatosclerosis: skin biopsy stained in 10× H&E showing thickened collagen
fibers and fibrosis in the reticular dermis with subcutaneous adipose tissue involvement with an
inflammatory septal and lobular infiltrate
Fig. 16.19 Lipodermatosclerosis: H&E-stained skin biopsy with fragments of subcutaneous adi-
pose tissue coated with septal fibrosis and a mild lobular inflammatory infiltrate
References 455
Fig. 16.20 Lipodermatosclerosis: biopsy of the skin and subcutaneous adipose tissue stained in
H&E at 40× showing evidence of sclerosis of the reticular dermis and inflammatory lobular, septal,
and perivascular infiltrates
References
1. Petterson JW. Panniculitis: erythema nodosum. In: Bologna JL, Jorizzo JL, Rapini RP, editors.
Dermatology, vol. 2. 3rd ed. London: Mosby; 2010. p. p1642–3.
2. Fraga J, García-Díez A. Lupus erythematosus panniculitis. Dermatol Clin. 2008;26:453–63.
3. Wenzel J, Tüting T. Identification of type I interferon-associated inflammation in the pathogen-
esis of cutaneous lupus erythematosus opens up options for novel therapeutic approaches. Exp
Dermatol. 2007;16:454–63.
4. Peters MS, Su WP. Lupus erythematosus panniculitis. Med Clin North Am. 1989;73:1113–25.
5. Patterson JW. Panniculitis. In: Weedon D, Geoffrey S, Adam IR, editors. Weedon’s skin pathol-
ogy. Edinburgh: Churchill Livingstone/Elsevier; 2010. p. 542–3.
6. Gómez LV, Belatti AL, Valdivia DC, Capellato N, Rodríguez MF, Galimberti
RL. Lipodermatoesclerosis aguda. Las celulitis que nunca fueron. Dermatología
CMQ. 2016;14:7–11.
7. Gouveiaa C, Soares Almeida LM. Paniculitis lipomembranosa: correlación clínico-patológica
de 8 casos. Actas Dermosifiliogr. 2006;97:379–84.
Part II
Infectious Skin Diseases
Chapter 17
Bacterial Infections
Staphylococcal and Streptococcal Infections of the Skin
Impetigo
• Definition: A common and contagious superficial skin infection. It can be crusty

(not blistering) and less often blistering [1, 2].
• Etiopathogenesis: Staphylococcus aureus is the main causal agent. Non-bullous
or crusty impetigo is less commonly caused by Streptococcus pyogenes. The
contagion occurs person to person in places with alteration of the cutaneous bar-
rier (sting, excoriations, and atopic dermatitis). S. aureus produces exfoliative
toxins A and B that destroy desmosomes, causing acantholysis and bullous
lesions [1–4].
• Clinical presentation: It affects children, especially those under six years of age;
when it occurs in the neonatal period, bullous impetigo is more common. It
rarely affects adults. It mainly involves the face and extremities. Generally, there
are no systemic symptoms; fever and regional lymphadenopathy can rarely
occur. It is self-limited and resolves without scarring [2, 3].
–– Bullous impetigo: It is characterized by small vesicles that expand up to
1–2 cm, with transparent or yellowish content. When they break, they leave
slight peripheral scaling and erythema, without the formation of thick crusts
[1–3] (Fig. 17.1).
–– Crusted impetigo (not bullous): It is characterized by rounded erythematous
macules of 2–4 mm with subsequent formation of a flaccid vesicle or pustule
that rapidly ruptures, leaving a superficial erosion covered by a yellow myelite
crust. Classically, they give a cigarette burn appearance due to the rounded
shape of the lesions [1–3] (Fig. 17.2).
• Diagnosis: The diagnosis is clinical. The Gram stain of the contents of a vesicle
can be of diagnostic utility and the culture of microorganisms when it is n ecessary

https://doi.org/10.1007/978-3-030-84107-2_17
460 17 Bacterial Infections
Fig. 17.1 Bullous

impetigo: Small vesicles
with yellowish content and
erythematous borders
involving the chin and
perioral region
to determine the sensitivity to antibiotics. Histopathology shows a neutrophil and

lymphocyte infiltrate in the superficial dermis. Additionally, in crusted impetigo,
neutrophilic vesicles and pustules are seen in the epidermis, with spongiosis. In
bullous impetigo, there is acantholysis of the granular layer with the formation of
vesicles with little inflammatory infiltrate [1–3].
• Differential diagnosis: Differential diagnoses are insect bites with vesicle forma-
tion, eczematous dermatoses, and herpes simplex infection and burns [2, 3].
Erysipelas
• Definition: Erysipelas is a specific form of superficial cellulitis, with prominent

involvement of the lymphatic vessels [1, 2].
• Etiopathogenesis: The main causative agent is group A beta-hemolytic strepto-
coccus and less frequently group G. Streptococci from group B, C, and D have
also been described; S. aureus, Klebsiella pneumoniae, Yersinia enterocolitica,
Staphylococcal and streptococcal infections of the skin 461
Fig. 17.2 Crusted

impetigo: Multiple
ruptured vesicles, rounded
shaped, superficial erosions
covered by a yellow
myelite crust with a moist
erythematous base,
involving the nose, chin,
mouth, perioral region, and
part of the cheeks
and Haemophilus influenzae type B. The identified risk factors are: the extremes
of life, chronic diseases, lymphedema, a history of lymph node dissection,
venous insufficiency, obesity, and chronic ulcers [1–3].
• Clinical presentation: It is more common in women in adulthood and in men in
pediatric age. The lower limbs are the main site of compromise, although erysip-
elas were classically described on the face [1, 2]. It is characterized by an
intensely erythematous plaque, with a well-demarcated border that separates the
infected area from healthy skin and progressively advances. Additionally, it pres-
ents heat, intense pain, and non-pitting edema with an orange-peel appearance
(Fig. 17.3). Pustules, vesicles, bullae, and areas of necrosis can be seen. It is usu-
ally accompanied by regional lymphadenopathy and systemic symptoms, with
general malaise, chills, fever, and leukocytosis. When the infection resolves,
there is a slight superficial peeling and post-inflammatory pigmentary changes
[1–3]. Lymphatic involvement can lead to obstruction and damage to the lym-
phatic vascular system, predisposing to recurrent episodes, which can occur over
weeks, months, or years [2].
• Diagnosis: The diagnosis is clinical. The blood count shows leukocytosis with
neutrophilia. Blood cultures are negative in most cases. When identification of
the causative agent is required, tissue culture is recommended [1–3].
Histopathology shows a neutrophilic inflammatory infiltrate with dermal edema.
It may present dilated lymphatic vessels with foci of suppurative necrosis and
formation of subepidermal bullae [1, 2].
• Differential diagnosis: The differential diagnosis of erysipelas includes eczema,
fixed pigmented erythema, and other soft tissue infections [1, 2].
Fig. 17.3 Erysipelas: On

the cheeks, intensely
irregular and well-defined
edges, with some vesicles
on the surface
Cellulitis
• Definition: Cellulitis is an infection of the deep dermis and subcutaneous cellular

tissue [1, 2].
• Etiopathogenesis: Streptococci, particularly Streptococcus pyogenes and
Staphylococcus aureus, are the most common causative agents. The latter is the
most frequent in the pediatric population, in which Haemophilus influenzae was
an important pathogen before the introduction of the H. influenzae type b vac-
cine. In cellulite originating from diabetic or decubitus ulcers, gram-negative and
anaerobic aerobes have been implicated. Bacteria typically enter the skin through
a break in the skin barrier in immunocompetent patients. In immunocompro-
mised patients, hematogenous spread is common [2–4].
• Several risk factors have been identified, including: lymphedema, chronic ulcers,
interdigital mycosis of the feet, traumatic wounds, alcoholism, diabetes, periph-
eral vascular disease, and intravenous drug use [1–4].
• Clinical presentation: It is characterized by the typical signs of inflammation
that are: erythema or redness, heat, pain, and edema or swelling in the affected
area. The edges are poorly defined and not palpable (Figs. 17.4 and 17.5). In
severe infections, vesicles, blisters, or necrotic tissue may be seen. There may be
regional lymphadenopathy. It is frequently accompanied by systemic involve-
ment such as malaise, fever, chills, and leukocytosis. The lower limbs are the
most commonly affected sites in adults and in children the head and neck, but
any area can be compromised [1–4].
• Diagnosis: In most cases the diagnosis is clinical. The blood count may be nor-
mal or with mild to moderate leukocytosis. Blood cultures are almost always
negative in immunocompetent patients. In patients who require isolation of the
causative agent, tissue culture is recommended [2, 4].
–– The pathology shows a moderate inflammatory dermal infiltrate with a pre-
dominance of lymphocytes and neutrophils, which extends to the hypodermis,
with dilation of lymphatic vessels and varying degrees of dermal edema that
can lead to subepidermal blistering. With Gram stain, the presence of micro-
organisms can be identified [1, 2, 4].
• Differential diagnosis: The main differential diagnoses to take into account in
lower limb involvement are: deep vein thrombosis, stasis dermatitis, thrombo-
phlebitis and panniculitis, mainly lipodermatosclerosis. In other locations, it is
important to take eczema into account [2, 4].
Fig. 17.4 Cellulitis: On

the lateral aspect of the left
leg, multiple erythematous
plaques associated with
edema and fine scaling on
the surface
Fig. 17.5 Cellulitis.

Erythematous nodule in
proximal third of leg,
perilesional edema
Necrozing Fascitis
• Definition: Necrotizing fasciitis is a rapidly progressive and potentially fatal

infection of the subcutaneous fat and fascia [1–3].
• Etiopathogenesis: It can occur after open or closed trauma, or without a history
of trauma. Risk factors include: diabetes mellitus, immunosuppression, cardiac
or peripheral vascular disease, kidney failure, IV drug use, recent surgery, and
ischemic or pressure ulcers. However, it can occur in young, previously healthy
people [1, 2] According to the nature of the infection, necrotizing fasciitis is clas-
sified as follows: type I or polymicrobial; type II, usually streptococci, mainly
group A and occasionally S. aureus; type III, by gram-negative agents such as
Escherichia coli, Bacteroides, Clostridium spp., Aeromonas hydrophila, and
Pseudomonas aeruginosa [1–3].
• Clinical presentation: It manifests with a rapid progression of an initially ery-
thematous, hot, edematous area, with a shiny and taut surface, with a very intense
Staphylococcal and streptococcal infections of the skin0 465
Fig. 17.6 Necrotizing

fasciitis: Right lower limb,
posterior face, vesicles,
and blisters are evidenced
that confirm a large
erythematous and
areas of erosions
pain, disproportionate to the cutaneous findings (Fig. 17.6). There is no response

to antibiotic treatment, and the skin takes on a blue-gray color, with poorly
defined purplish patches with the development of hemorrhagic blisters and areas
of necrosis. Subcutaneous emphysema is characteristic and a foul-smelling
watery discharge, the result of necrosis of the subcutaneous fascia. Later, the
affected area becomes hard, stony, and anesthetic, due to the involvement of the
cutaneous nerves. The extremities are the most frequently affected in adults and
the trunk in children. Necrotizing fasciitis involving the genitalia and the peri-
neal region is known as Fournier’s gangrene [1–3].
–– The systemic compromise is severe, with general malaise, signs of a systemic
inflammatory response with severe leukocytosis and progression to multi-
organ failure and shock. Mortality is high and increases with age, extent of
infection, late diagnosis with delay of the first debridement, degree of multi-
organ involvement, and Streptococcus pyogenes infection [1–3].
• Diagnosis: Diagnosis is based on clinical features and is difficult in the early
stages of the disease. MRI can determine the depth of involvement.
Complementary studies (hemogram, cultures, blood chemistry, and among oth-
ers) are used to determine the degree of systemic involvement [1–3].
• Differential diagnosis: The main differential diagnoses are trauma with bruising
and phlebitis [1–3].
Folliculitis, Forunculum, Carbunculum
• Definition:
–– Folliculitis: superficial or deep infection of the hair follicle.
–– Boils: Infection of the entire hair follicle and surrounding tissue.
–– Abscesses and carbuncles: Nonencapsulated collections of pus. Carbuncles
involve hairy areas and are formed by the grouping and interconnection of
boils, while an abscess can occur in any location.
• Etiopathogenesis: Staphylococcus aureus is the most common causal agent of

folliculitis. Occasionally, it can be caused by gram negative bacteria, mainly in
patients with chronic antibiotic treatments, or by anaerobes in perianal lesions.
Risk factors include occlusion: shaving, waxing, poor hygiene; use of topical
corticosteroids; hot and humid climates; atopic dermatitis; obesity; diabetes mel-
litus; and immunosuppression. The use of bathtubs has also been associated with
Pseudomonas spp. folliculitis.
• Clinical presentation: Hair follicle infections more frequently affect adolescents
and young adults. It mainly affects the face, scalp, anterior chest, back, armpits,
groin, buttocks, and intergluteal region (Fig. 17.7). When it affects the beard
area, it is known as Sycosis barbae. The clinical features depend on the depth of
the involvement, including itching or pain that increases with the depth of the
infection and occasionally regional lymphadenopathy may occur.
–– Superficial folliculitis presents with small 1–4 mm pustules with an erythem-
atous base or papules covered by scabs and present with a fine peripheral or
collarette scaling. Lesions are generally grouped and heal without scarring.
–– Deep folliculitis presents as larger, erythematous papules with a central pus-
tule or scabs, which can coalesce and form large plaques covered by pustules
and scabs.
–– Boils are seen as hot, red, painful, erythematous nodules involving a hair fol-
licle, occasionally with purulent discharge and can progress and coalesce and
interconnect by sinuous tracts to form carbuncles that can extend to the sub-
cutaneous tissue and surface show multiple drainage points.
• Diagnosis: The diagnosis is clinical. Gram stain and microorganism cultures can
be helpful in identifying the causative agent, especially in recurrent or refrac-
tory cases.
• Differential diagnosis: The differential diagnoses are acne, rosacea, pseudofol-
liculitis of the beard, and keratosis pilaris. The main differential diagnosis of
Sycosis barbae is ringworm of the beard.
Fig. 17.7 Folliculitis and

boils: Erythematous
nodules with central
whitish area and against
hematica on the surface are
evidenced in the limb.
Likewise, few follicular
pustules
Botriomycosis
• Definition: Botryomycosis is a rare, chronic, granulomatous, and suppurative

bacterial infection [1, 2]. Etiopathogenesis: It is produced by nonfilamentous
granule-forming bacteria. Staphylococcus aureus is the causative agent in most
cases, although Pseudomonas aeruginosa, coagulase-negative staphylococci,
Streptococcus spp., Escherichia coli, Proteus spp., Moraxella spp., Serratia spp.,
and Corymebacteria spp. It has not been associated with immunosuppression,
although there are cases reported in patients with immunodeficiencies, particu-
larly HIV/AIDS. It usually involves the head, neck, extremities, and groin region.
There is often a history of trauma or a foreign body [1–4].
• Clinical presentation: It is characterized by the presence of indurated, suppura-
tive, confluent papules, nodules, and pseudotumors, forming plaques with the
formation of sinuous tracts, with the presence of white or yellow bacterial gran-
ules of 0.2–1.5 mm in the lesion (Fig. 17.8). Extension to adjacent subcutaneous
Fig. 17.8 Botriomycosis:

Over the back of the right
foot and the ankle, there
are multiple indurated and
confluent violaceous
erosions and ulcers over its
surface
tissue, muscle, and bone may occur. A rare visceral form has also been identified,
most commonly involving the lung [1–4].
• Diagnosis: The diagnosis is made with the clinical, histopathological, and cul-
ture findings. The biopsy shows a chronic inflammatory reaction with fibrosis
and foreign body-type giant cells, with the presence of bacterial granules, usu-
ally basophilic, which stain with PAS, Gram and Giemsa stains, and which are
surrounded by an eosinophilic hyaline material secondary to the deposit of anti-
bodies, known as the Splendore-Hoeppli phenomenon, which is also seen in
other granule-forming infections [1–4].
• Differential diagnosis: The main differential diagnoses are other infectious dis-
eases with granule formation, such as mycetomas (eumycetoma and actinomyce-
toma) and actinomycosis. Furthermore, it is necessary to rule out granulomatous
diseases with clinical similarity such as sclofuroderma [1–4].
Staphylococcal and Streptococcal Toxin Syndromes
Staphylococcal Scald Skin Syndrome
• Definition: Generalized disorder produced by exfoliative toxins of Staphylococcus

aureus [1–3].
• Etiopathogenesis: It is produced by the hematogenous dissemination of exfolia-
tive toxins A and B produced by S. aureus, from a localized focus, usulamenere
nasopharynx, conjunctiva, perinanal region, or pyogenic collections in the skin.
These toxins, also known as epidermolytic, adhere to desmoglein 1 of the des-
mosomes of the epidermis, causing acantholysis in the superficial layers of the
epidermis (granulosa) with the formation of flaccid blisters [1–3].
• Clinical presentation: It is more frequent in men than in women. It occurs in
neonates, infants, and young children who have a decreased renal clearance of
toxins, especially neonates, or with a lack of production of toxin-neutralizing
antibodies. Occasionally, it can be seen in adults with chronic kidney failure or
immunosuppressed [1, 2].
–– Generally, starts with general malaise, fever, irritability, and skin sensitivity.
Later, erythema develops that begins on the head, occasionally with facial
edema, and in the intertriginous areas and becomes generalized in 1–2 days.
The skin develops a wrinkled appearance as a reflection of the formation of
very superficial blisters.
–– Nicolsky’s sign, which is the detachment of the epidermis with pressure with
the fingertips, is positive. The blisters break quickly leaving eroded areas with
peeling and yellowish crusting (Figs. 17.9,17.10, and 17.11). In the perioral or
periocular region, they present a characteristic radial configuration [1–3]
(Fig. 17.12). There is no blistering on the mucosa. Lesions resolve without
scarring with residual scaling that persists for 1–2 weeks [1, 2].
Fig. 17.9 Staphylococcal

scald skin syndrome: In the
back eroded areas with
peeling and erythema

back of the ear eroded
areas with peeling and
erythema
–– The most frequent complications are sepsis and pneumonia [2, 3].
• Diagnosis: The diagnosis is clinical. Gram stain, micro-organism cultures from
blisters, and blood cultures are negative; however, they may be positive at pri-
mary sites of infection. Blood cultures can be positive in adults. The skin biopsy
shows acantholysis in the stratum granulosa, with minimal or no inflammatory
infiltrate in the cleavage area and upper dermis [1–3].

perioral region, a
characteristic radial
configuration with peeling
and yellowish crusting

perioral region, a
characteristic radial
configuration with peeling
and yellowish crusting
• Differential diagnosis: Differential diagnoses include viral exanthemas, drug

reactions (toxic epidermal necrolysis), Kawasaki disease, sunburn, and pemphi-
gus foliaceus [1–3].
Erysipeloid
• Definition: Erysipeloid is a rare skin infection caused by traumatic inoculation of

Erysipelothrix rhusiopathiae. It occurs mainly in people in contact with animals
(breeders, veterinarians, slaughterhouse workers, butchers, fishermen, house-
wives, and cooks) [1–3].
• Etiopathogenesis: Erysipelothrix rhusiopathiae is a gram-positive, facultative
aerobic bacillus. It can be found in soil, food residues, and water contaminated
by infected animals, mainly pigs. The bacteria penetrate the skin through small
wounds, with an incubation period of 2–7 days [1, 3].
• Clinical presentation: Classically, it appears on the back of the hands or fingers,
unilateral, with respect for the palms, forearms, face, and legs. It is characterized
by an intensely erythematous, edematous plaque with well-defined, raised edges.
It expands centrifugally (Fig. 17.13). Annular cases and bullous lesions have
been described. The lesion is usually asymptomatic or has mild itching. It is not
accompanied by systemic symptoms and improves rapidly with proper treat-
ment [1–3].
• Diagnosis: The diagnosis is clinical. Leukocytosis and increased acute phase
reactants may occur. The skin biopsy shows nonspecific findings, with edema of
the upper and middle dermis, vascular dilation;, neutrophilic and lymphocytic
inflammatory infiltrate, and few eosinophils. Microbiological isolation is diffi-
cult [1, 3].
• Differential diagnosis: The main differential diagnoses are erysipelas and con-
tact dermatitis [1].
Fig. 17.13 Erysipeloid:

On the back left hand,
erythematous arcuate
and raised edges
Erythrasma
• Definition: Erythrasma is a superficial skin infection caused by Corynebacterium

minutissimum [1–3].
• Etiopathogenesis: Corynebacteria are gram-positive rods that correspond to 50%
of the normal flora of the skin. Unlike fungal infections, there is no evidence of
exogenous contamination, only local environmental changes that favor bacterial
overgrowth. The risk factors described include hot and humid climates,
overweight, advanced age, diabetes, immunosuppression, hyperhidrosis, and
poor hygiene [1–3].
• Clinical presentation: It is characterized by well-defined, erythematous-brown
patches with a thinned surface and slight scaling (Fig. 17.14). The lesions are
chronic and usually asymptomatic; occasionally, they may have mild itching. It
generally involves the skin folds (inguinal, intergluteal, axillary, submammary,
and the navel). When it affects the interdigital spaces, it presents as erythema,
maceration, and fissures [1–3].
• Diagnosis: The diagnosis is clinical. Wood’s light reveals a brilliant coral-red
color, the result of the presence of porphyrins produced by corynebacteria. Direct
examination is used to rule out dermatophyte infection. Histopathology shows
normal skin with hematoxylin–eosin. Small coccobacilli in the superficial part of
the stratum corneum are visible with periodic acid Schiff (PAS), methenamine
silver, or Gram stains [1–3].
• Differential diagnosis: The main differential diagnosis is superficial mycoses.
Other pathologies to consider are inverted psoriasis and contact eczema [1–3].
Keratolysis Punctata
• Definition: Punctate keratolysis is a superficial cutaneous infection of the skin of

the palms and soles [1, 2].
Fig. 17.14 Erythrasma: In

the left inguinal fold, a
well-defined erythematous
brown patch, irregular in
shape, with a thinned
surface and slight scaling,
and some smaller satellite
lesions
Gram-Negative Infections 473
• Etiopathogenesis: It is caused by bacteria such as Dermophilus congolensis,

Kyctococcus sedentarius, and other Corynebacterium spp. The risk factors
described include hot and humid climates, occlusive footwear, hyperhidrosis,
maceration, and poor hygiene. Being more frequent in farmers, military, and
some athletes. The bacterial production of serine proteases degrades the stratum
corneum producing the characteristic depressions. The sulfur components are
responsible for the bad smell [1–3].
• Clinical presentation: It occurs more frequently in young men. It is characterized
by well-defined crateriform depressions that can coalesce and form large holes;
they are accentuated after bathing and are commonly accompanied by a bad
smell. They involve the soles and less frequently the palms, with a predilection
for pressure zones (Fig. 17.15). The lesions are chronic and usually asymptom-
atic, although pain, and burning sensations have been described [1–3].
• Diagnosis: The diagnosis is clinical. Histopathology shows well-defined depres-
sions of approximately 2/3 of the stratum corneum; bacteria can be seen on crater
walls and bottoms with periodic acid Schiff (PAS), methenamine silver, or Gram
stains. Inflammation is not usually seen [1, 2].
• Differential diagnosis: Differential diagnoses include viral warts, ringworm, and
disease [1, 2].
Gram-Negative Infections
Gangrenous Ecthyma
• Definition: Ecthyma gangrenosum is a relatively rare disease characterized by

necrotic ulcers [1, 2].
• Etiopathogenesis: Classically, it is a pathognomonic disease of systemic infec-
tion by Pseudomonas aeruginosa, usually seen in immunosuppressed patients
and hematological malignancies. However, it is currently considered that
Fig. 17.15 Keratolysis

punctata: Well-defined
crateriform depressions
that can coalesce and form
large holes in the sole of
the food
ecthyma gangrenosum can occur in immunocompetent patients and be caused by

a variety of agents such as: Escherichia coli, Citrobacter freundii, Klebsiella
pneumonia, Morganella morganii, and other Pseudomonas species. Some fungi
(Candida albicans, Fusarium) have also been described as causative agents.
Invasion of the venules results in secondary thrombosis, tissue edema, and epi-
dermal necrosis [1, 2].
• Clinical presentation: It begins as papules or hemorrhagic vesicles and rapidly
progresses to necrotic ulcers that may have an erythematous halo (Figs. 17.16
and 17.17). It occurs mainly in the extremities, buttocks, and perineal region,
although it can be seen in any location. Lesions can be single or multiple.
Ecthyma gangrenosum affects patients of any age; associated sepsis is more
common at the extremes of life [1, 2].
• Diagnosis: The diagnosis is clinical, and in some cases, a skin biopsy is required
for tissue culture; in case of systemic compromise, it is necessary to do blood
cultures [1, 2].
• Differential diagnosis: In most cases the clinical picture is typical. The main dif-
ferential diagnoses include warfarin- or cocaine-induced necrosis, calciphylaxis,
septic embolism, livedoid vasculopathy, and vasculitis [1, 2].
Bacillary Angiomatosis
• Definition: Bacillary angiomatosis is a rare, systemic, infectious, vasculoprolif-

erative disease that can affect different organs [1, 2]. It occurs in people with
human immunodeficiency virus (HIV) infection, mainly with a CD4 + T lym-
phocyte count lower than 200 per microliter [2]; it has rarely been reported in
other immunodeficiencies, including post-organ transplantation and exceptional
cases in immunocompetent patients [1, 2].
• Pathogenesis: It is produced by the infection of species of the Bartonella genus,
mainly Bartonella henselae and B. quintana, which have the ability to produce
Fig. 17.16 Ecthyma

gangrenosum: In the
lumbar region, there was
an erythematous plaque, a
scaly halo, and a necrotic
crust on the surface
Gram-Negative Infections 475
Fig. 17.17 Ecthyma

gangrenosum: The
posterior trunk presents
multiple plaques with a
scaly erythematous halo in
its center with a necrotic
crust
angiogenic factors [1]. The reservoir of the former is domestic cats and is trans-
mitted by cat bites or scratches, with subsequent contamination with cat flea
feces (Ctenocephalides felis). The only reservoir for B. quintana is humans, and
the infection is transmitted through Pediculis humanus corporis (body lice) [2].
• Clinical presentation: The most common clinical form of cutaneous bacillary
angiomatosis is an erythematous-violaceous papule approximately 1 cm in
diameter that bleeds easily, with progressive growth, and the appearance of new
lesions; the lesions are painful and friable, which may ulcerate and become cov-
ered with thick crusts [1, 2] (Fig. 17.18).
–– Four skin patterns have been described:
Erythematous, angiomatous, globular papules or nodules, and reminiscent
of pyogenic granuloma [2].
Fig. 17.18 Bacillary

angiomatosis: Solitary
well-defined violaceous
tumoral plaque with an
ulcerated bright red center
located over the right wrist
crease
Violaceous nodules covered by a thin and adherent scale reminiscent of

Kaposi’s sarcoma [2].
Lichenoid violaceous plaques, typically on the extremities, often over
bone defects [2].
Papules or nodules erythematous-violaceous, exophytic, polypoid, friable
pedunculated more than 1 cm [2].
–– Subcutaneous lesions present as violaceous or erythematous nodules up to
10 cm in diameter, single or multiple, which may or may not ulcerate [2].
–– Although bacillary angiomatosis mainly affects the skin and subcutaneous
tissue, [2] it can affect any organ, most commonly the lymph nodes, respira-
tory tract, spleen, and liver [1]. Disseminated visceral involvement is known
as peliosis [2]. Symptoms that suggest systemic compromise include fever,
weight loss, night sweats, general malaise, anorexia, adenomegaly, nausea,
vomiting, diarrhea, and hepatosplenomegaly, among others, depending on the
affected organ [1, 2].
• Diagnosis: The diagnosis is clinical, but confirmation with biopsy is required, in
which three main characteristics are found, which are seen in both skin and vis-
ceral lesions [2]:
–– Lobular proliferations of blood vessels, composed of clusters of epithelioid
endothelial cells; these are found within a fibrotic and edematous stroma [1, 2].
–– Neutrophilic infiltrate, mostly perivascular [1, 2].
–– Interstitial aggregates of bacilli that appear as a granular amorphous material
reminiscent of fibrin, best seen with silver stains (Warthin-Starry, Groccot, or
methenamine silver) or electron microscopy [1, 2].
• Differential diagnosis: The main differential diagnoses are telangiectatic granu-
loma and Kaposi’s sarcoma, as well as other tumors with a vascular component
such as angiokeratoma. It must also be differentiated from other infectious dis-
eases such as the Peruvian wart and mycobacterial infections [1, 2].
References 477
References
1. Requena L, Requena C, Cockerel C, et al. Benign epidermal tumor and proliferations chapter,
Benign melanocytic neoplasms, neural and neuroendocrine neoplasms (Other than neurofibro-
matosis). In: Dermatology, vol. II. 202. Third ed; 2012. p. 1795–815.
2. Bernhard JD, Owen WR, Steinman HK, et al. Inflammatory linear epidermal nevus. Arch
Dermatol. 1984;120:214–5.
3. Atherton DJ. Naevi and other developmental defects. In: Champion RH, Burton JL, Ebling
FJ, editors. Textbook of dermatology. London: Blackwell Scientific Publications; 1992.
p. 445–526.
4. Goldsmith L, Katz S, et al. Benign epithelial tumors, hamartomas and hyperplasias. In:
Fitzpatrick’s dermatology in general medicine. 8th ed; 2012. p. 1319–36.
Chapter 18
Mycobacterial Infections
Leprosy (Hansen’s Disease)
• Definition: Leprosy or Hansen’s disease is a chronic infectious disease that

mainly affects the skin and nerves. It is a disfiguring and disabling disease; how-
ever, it has a low mortality rate. It represents a public health problem in develop-
ing countries, predominantly in tropical and subtropical regions of Asia, Africa,
and Central and South America [1–3].
• Etiopathogenesis: It is caused by the bacillus Mycobacterium leprae, which is
contracted by inhaling secretions from the upper respiratory tract (nose and
mouth) [1, 2], as its spread requires a contagious patient and a susceptible person
in close contact. M. leprae is a very small, acid-fast, intracellular obligate, non-
culturable bacillus, with a predilection for macrophages and Schwann cells.
Although leprosy mainly affects the skin and peripheral nerves, it can also affect
the mucous membranes, bones, and viscera such as the liver or testes. The bacil-
lus requires a temperature of approximately 35 °C to replicate, which is why it
has a preference for colder areas of the body such as the nose, testicles, and ear-
lobes [1–3]. There is a variability in susceptibility and resistance depending on
environmental and genetic factors, which is why most individuals do not develop
the disease [1]. Susceptibility and type of immune response correlate with spe-
cific HLA types. The tuberculoid form develops more in individuals with
HLA-DR2 and HLA-DR3, while the lepromatous form in individuals with
HLA-DQ1. Susceptibility loci shared with Parkinson’s disease (PARK2-PACRG)
and polymorphisms in different genes have also been identified, which code for
tumor necrosis factor-alpha (TNF-α) interleukin (IL) 10, lymphotoxin-α, hydro-
lase of leukotriene A4, vitamin D receptor, and toll-like receptor (TLR) 2 [1–3].
Depending on the degree and type of immunity, the disease may progress, limit
itself to spontaneous resolution. A predominant Th2 response leads to the release
of a series of cytokines (IL-4, IL-5, IL-10, and IL-13) that suppress the activity
of macrophages and is associated with the lepromatous form. The tuberculoid

https://doi.org/10.1007/978-3-030-84107-2_18
480 18 Mycobacterial Infections
form is associated with a predominance of the Th1 response, in which produces

cytokines (IL-2, INF-ϒ, and TNF-β) that stimulate macrophages and maintain
inflammation [1–3].
• Clinical presentation: Leprosy has a wide spectrum of clinical manifestations
that mainly involve the skin and the peripheral nervous system and depend on the
immune status of the patient. The lesions are hypo or anesthetic, with loss of the
sensation of temperature, pain, and touch [1]. Peripheral nerves undergo growth
and become palpable, with the most superficial ones being more commonly
affected (greater auricular, ulnar, radial, median, common perineum, and poste-
rior tibial nerves) [1, 2]. Secondary to nerve involvement, there are changes such
as muscular atrophy, flexion contractures, vasomotor alterations, and secretory
alterations (xerosis of the skin and mucosa). There are several classifications of
leprosy [1]:
–– Rabello’s classification (1983) divides leprosy into four types:
Lepromatous: It occurs in patients with decreased cellular immunity [1].
This form has the highest number of bacilli. It is initially characterized by
multiple, poorly defined, erythematous macules, papules, plaques, and
nodules, scattered and symmetrical. The face and earlobes, buttocks, and
lower limbs are more frequently involved. (Figs. 18.1, 18.2, 18.3, and
18.4). Other findings include madarosis (alopecia of the eyebrows), leo-
nine facies, saddle nose (Fig. 18.5), glove and stocking anesthesia with
Fig. 18.1 Lepromatous

leprosy (LL):
Erythematous plaques and
nodules, infiltrated on the
face, with symmetrical
distribution “leonine
fascies,” infiltration of
nasal cartilage, also
bilateral madarosis
Leprosy (Hansen’s Disease) 481

leprosy (LL):
infiltrated on the nasal
region
acquired ichthyosis of the extremities, and other neuropathic changes such

as lagophthalmos [1, 2].
Histiode leprosy: It is a clinical form of multibacillary leprosy that some
authors classify as a variant of lepromatous leprosy. It is characterized by
firm, erythematous brown papules, and nodules that resemble dermatofi-
bromas [1–3] (Fig. 18.4).
Tuberculoid: It occurs in patients with intact cellular immunity. It mani-
fests as erythematous, infiltrated plaques with well-defined edges, slightly
elevated, with central clearance giving it an annular appearance. There
may also be hypopigmented lesions, desquamation, hypohidrosis, alope-
cia, and hypo or anesthesia with unilateral neuropathic changes such as
resorption of the fingers [1, 2].
Dimorphic or unstable: It has intermediate characteristics between the two
extremes of the disease that, depending on the immune status, can evolve
to the lepromatous or tuberculoid form. Skin lesions are usually asymmet-
ric, and the severity of the involvement depends on whether the patient
leans to the tuberculoid or lepromatous pole [1, 2].
Indeterminate: It occurs at the beginning of the disease. They are the early
lesions before the commitment and the definitive immune response is
established. Hypopigmented macules or patches are seen with or without
sensory involvement, and bacilli are scarce or absent [1, 2].

leprosy (LL):
infiltrated on the nasal
region with septum
perforation
Fig. 18.4 Histioide

leprosy: Firm,
erythematous papules and
nodules on the leg
–– Classification of Ridley and Jopling (1966) divides leprosy into five types [1]:
Lepromatous (LL): Ill-defined nodules with symmetrical distribution are
the most common lesion. Diffuse infiltration of the face (leonine facies),
earlobes, and fusiform inflammation of the fingers can also be seen [1, 2].
(Figs. 18.1, 18.2, 18.3, 18.4, and 18.5).

leprosy (LL): Nodules
infiltrated with
symmetrical distribution
on the face “leonine
fascies,” also bilateral
madarosis
Borderline lepromatous (borderline) (LB): Presents multiple, poorly

defined plaques and nodules, with a tendency to symmetry [1, 2] (Fig. 18.6).
Borderline personnel (BB): Swiss cheese-like lesions are classic of this
type of leprosy. They look like multiple large plaques with islands of
healthy skin inside. Annular lesions with ill-defined borders can also be
seen [1, 2].
Borderline tuberculoid (TB): It is characterized by multiple lesions (more
than five lesions) and extensive, more than 10 cm in diameter [1, 2]
(Fig. 18.7).
Tuberculoid (TT): Usually has solitary or few lesions (up to five lesions) of
maximum 10 cm in diameter, annular configuration and well-defined
edges [1, 2].
–– Classification of the world health organization (1988) includes the five types
of Ridley’s classification plus the indeterminate form. This is the most used
classification [1].
–– Classification of the World Health Organization (1997):
Paucibacillary: Bacilli are not found on biopsy or direct examination [1].
• Single lesion paucibacillary
Fig. 18.6 Borderline

leprosy: Presents multiple
plaques and nodules, with
a tendency to symmetry on
the face
• Paucibacillary with two to five lesions
Multibacillary: Presence of one or more bacilli and/or more than five

lesions.
–– Leprotic reactions: Leprotic reactions are characterized by sudden inflamma-
tion, which are mainly related to the start of antimicrobial treatment, although
they can also be associated with other conditions such as: pregnancy, other
infections, or stress [1, 2].
Type 1 reactions can affect patients with any form of leprosy, with a predi-
lection for borderline forms. They correspond to a delayed hypersensitivity
reaction with an increase in Th1 cellular immunity. It manifests as: [1]
• Acute increase in inflammation of preexisting lesions.
• Sudden appearance of new lesions.
• Acute neural pain (neuritis) and loss of function.
• Acute neurological compromise (less than six months) or progressive in
the absence of neural pain.
Type 2 reactions occur most often at the lepromatous end. They correspond
to a small vessel vasculitis, with immune complex formation secondary to
Fig. 18.7 Borderline

tuberculoid: Annular
plaques, erythematous
edges with central
clearance, anesthetic on the
trunk and buttock
excessive Th2 humoral immunity. There are two types of type 2 leprotic
reactions [1, 2]:
• Erythema nodosum leprous: It manifests as deep erythematous, edema-
tous, hot, and painful nodules, affecting both the lower and upper
extremities [1–3].
• Pike phenomenon: It consists of erythematous macules that rapidly
evolve into necrotic eschar followed by atrophic scars [1–3].
• Diagnosis: The diagnosis is clinical and requires microbiological confirmation,
which is preferred to be carried out with biopsy and not with direct examination.
The latter requires trained personnel; however, it is used to obtain the bacillary
index (smear microscopy) as a follow-up. Microbiological confirmation can also
be obtained by isolating mycobacterium DNA with PCR. Changes to histopa-
thology depend on the type of leprosy [2–4]:
–– In lepromatous leprosy, dense perianexal and perineural infiltrates of histio-

cytes with a foamy cytoplasm known as Virchow cells are seen. A band of
healthy dermis (Unna band) separates the epidermis from the inflammatory
infiltrate. Isolated or grouped bacilli can be seen in the dermis, which are best
visualized with Gram, Ziehl-Neelsen, Fite, or Wade stains [2–4].
–– In tuberculoid leprosy, a granulomatous, lymphohistiocytic, nodular infiltrate
is seen, with perianexial and perineural involvement and with marked inflam-
mation and fragmentation of the nerves and adnexa [2–4].
–– In borderline leprosy, findings of the two forms of leprosy are shared [1].
• Differential diagnosis: Like clinical lesions, the differential diagnoses of leprosy
are broad. Hypopigmented lesions can mimic pityriasis alba, pityriasis versi-
color, or mycosis fungoides. Ring lesions may resemble tinea corporis or sar-
coidosis [1].
Cutaneous Tuberculosis
• Definition: Tuberculosis (TB) is a chronic granulomatous infection produced

mainly by infection of the acid-alcohol-resistant bacillus Mycobacterium tuber-
culosis, in rarer cases by M. bovis and the Calmette-Guérin bacillus. TB contin-
ues to be a public health problem worldwide. Cutaneous forms represent 10–15%
of all TB cases, the most frequent being pulmonary TB, which is the fifth house
of death worldwide [1–3].
• Etiopathogenesis: Cutaneous tuberculosis is acquired by direct inoculation or by
hematogenous spread or by contiguity of a previously acquired infectious focus
(by inhalation or ingestion of mycobacterium) [1–4]. The infection triggers a
delayed hypersensitivity reaction, which is completed after 2–10 weeks and is
responsible for the clinical and histological manifestations [1]. Mycobacterium
induces the release of target antigenic protein-6 (ESAT-6), which stimulates epi-
thelial cells to produce matrix metalloproteinase type 9 (MMP-9); the latter
increases the recruitment of macrophages, and in this way, the formation of gran-
ulomas is facilitated. The interaction of T lymphocytes and mycobacterial anti-
gens induce the release of interferons and other cytokines that promote the
activation and expression of the interleukin receptor (IL) -2 and major histocom-
patibility complex (MHC) class II molecules in presenting cells of antigens.
During this initial sensitization process, memory T lymphocytes are generated
that remain for decades in the lymphoid organs and circulation [1].
• Clinical presentation: The type of cutaneous tuberculosis that occurs will depend
on the route of infection, the patient’s immune status, previous exposure to the
bacillus and its immunogenicity [1–4]. There are several classifications of cuta-
neous tuberculosis that are based on the route of spread (direct inoculation,
infection by contiguity, or hematogenous spread) and on the bacterial load (mul-
tibacillary and paucibacillary).
–– Cutaneous multibacillary tuberculosis:

Tuberculous chancre (primary inoculation skin tuberculosis): It is pro-
duced by direct inoculation to the skin or mucosa in a patient without pre-
vious exposure to the bacillus, that is, without specific immunity and
affects health workers and children more frequently. It initially presents as
a small papule that progresses to a painless, granular, or hemorrhagic-
based ulcer that may be covered with necrotic tissue. A painless regional
lymphadenopathy may occur, generating a clinical picture analogous to the
Gohn complex of pulmonary tuberculosis. It involves more frequently on
the face, hands, and feet [2–4].
Scrofuloderma: It is produced by compromise by contiguity toward the
skin from a focus of tuberculosis (lung, pleura, ganglion, and bone). It
appears as firm subcutaneous nodules that ulcerate, draining a caseous, or
purulent material. Sinuous tracts develop and scar tissue forms on the
periphery of the lesion (Fig. 18.8). It usually affects children, young adults,
and older adults and primarily affects the neck, armpits, chest wall, and
groin [2–4].
Periorificial tuberculosis: It is produced by self-inoculation in the mucosa
or skin adjacent to a natural orifice, from an active internal tuberculosis
infection that can be pulmonary, gastrointestinal, or genitourinary tract. It
presents as a yellowish or reddish nodule that ulcerates, with well-defined
edges and a punched-out appearance. This clinical form is rare and most
often affects middle-aged men [2–4].
Acute miliary tuberculosis: It is caused by hematogenous spread from a
primary pulmonary focus in a patient with a decreased immune status. It
affects the whole body, especially the trunk. It begins as macular lesions
that progress to papules that can be erythematous or purpuric; occasionally
with vesicles, crusts, or central necrosis [2–4].
Gomatous tuberculosis: It is produced by acute hematogenous spread from
a primary focus during periods of bacteremia and low resistance. It presents
Fig. 18.8 Scrofuloderma:

Firm subcutaneous
ulcerated nodules draining
a purulent material.
Sinuous tracts and scar
tissue forms on the
periphery of the lesions
as subcutaneous nodules that soften and ooze, forming ulcers, and fistulas.
They can be single or multiple and most often affect the trunk and extremi-
ties [2–4].
–– Paucibacillary cutaneous tuberculosis:
Tuberculosis verrucous skin: It is produced by direct inoculation to skin or
mucosa in a previously exposed person with moderate immunity. It pres-
ents as a papule or pustule with an erythematous halo that grows progres-
sively. It has a hyperkeratotic surface, covered with thick scales that give it
a warty appearance. The injuries are usually unique and mainly affect the
Lupus vulgaris: It can be produced by direct external inoculation in a pre-
viously exposed patient or by autoinoculation or hematogenous or lym-
phatic dissemination from an internal tuberculosis focus. It appears on the
face or extremities as a brown-erythematous papule with a smooth surface,
which converge to form slow-growing plaques;, with a slightly elevated
infiltrated border and an atrophic center [2–4].
–– Tuberculides: Tuberculides are classically considered as skin eruptions sec-
ondary to immune phenomena generated by remote infection but not as true
infections. However, it is currently considered to correspond to the end of the
paucibacillary pole of the spectrum of cutaneous tuberculosis [2–4]. There are
three varieties:
Lichen scrofulosorum: It appears as multiple follicular or parafollicular
papules, erythematous-violaceous, and grouped. It occurs most frequently
in children or young adults, almost always on the trunk. In most cases, it is
associated with a focus of pulmonary, lymph node, or bone tuberculo-
sis [2–4].
Bazin’s indurated erythema: It is the most common tuberculosis. It repre-
sents a panniculitis associated with tuberculosis. Clinically, it presents as
erythematous nodules; they converge to form plaques that can ulcerate and
drain purulent material (Fig. 18.9). It typically affects women on the back
of the legs and is often associated with active lung disease [2–4].
Papulonecrotic tuberculosis: It is produced by hematogenous spread. It
most often affects children or young adults with an active focus of tuber-
culosis. It presents as multiple symmetric papules of 1–5 mm in diameter
with necrosis and central umbilication. They heal leaving varioliform
scars. They are located on the extensor surfaces of the trunk and extremi-
ties [2–4].
• Diagnosis: The diagnosis is based on a set of findings. The clinical characteris-
tics, the histological findings with special stains for the visualization of the bacil-
lus (Ziehl-Neelsen), the tuberculin test (PPD), and the microbiological
confirmation (with culture or PCR) must be taken into account. In addition to
tuberculin, interferon release tests (INF)-ϒ (QuantiFERON®, T-SPOT®) can be
used [1, 5].
Fig. 18.9 Bazin’s

indurated erythema: On
the back of the legs
edema and pain with the
physical exam
–– Multibacillary forms:
Tuberculous chancre: PPD is initially negative and becomes positive by
two to eight weeks. Histopathology shows a nonspecific inflammatory
infiltrate with the presence of bacilli. With the passing of days, a granulo-
matous inflammation with caseification, epithelioid cells, and Langhans-
type giant cells with disappearance of the bacilli develops [2, 3].
Scrofuloderma: PPD is strongly. Histopathology shows granulation tissue,
caseous necrosis in the upper dermis, and bacilli can be seen [2, 3].
Periorificial tuberculosis: PPD can be positive or negative. Nonspecific
inflammatory infiltrate with necrosis and some caseation granulomas in
the deep dermis [2, 3].
Acute miliary tuberculosis: PPD is usually negative. Histopathology shows
a nonspecific inflammatory infiltrate, surrounded by macrophages and
necrosis. Microabscesses sometimes form and bacilli are abundant [2, 3].
Gomatous tuberculosis: PPD can be positive or negative. Histopathology

shows a nonspecific inflammatory infiltrate with suppurative granulo-
mas [2, 3].
–– Paucibacillary forms
Tuberculosis verrucous skin. PPD is strongly positive. Histopathology
shows an acute inflammatory infiltrate, pseudo-epitheliomatous hyperpla-
sia, microabscesses in the upper dermis, foci of tuberculoid granulomas,
and bacilli occasionally present [2, 3].
Lupus vulgaris: PPD can be negative or positive. Histopathology revealed
multiple noncaseating granulomas, with a nonspecific inflammatory infil-
trate and few bacilli [2, 3].
–– Tuberculides:
Papulonecrotic: PPD is positive. On histopathology, palisade granulomas
are seen, with coagulation necrosis and follicular necrosis. Bacilli are
absent [2, 3].
Bazin indurated erythema: PPD strongly positive. Histopathology shows
septal panniculitis, fat necrosis, small or medium vessel vasculitis, and
granuloma formation. Bacilli are rarely found, which have been demon-
strated using PCR [2, 3].
Lichen scrofulosorum: PPD is strongly positive. On histopathology, peri-
pollicular epithelioid granulomas are seen, with occasional multinucleated
giant cells. Bacilli are rarely found [2, 3].
• Differential diagnosis: The differential diagnoses depend on the form of cutane-
ous tuberculosis: Tuberculous chancre: The main differential diagnoses are spo-
rotrichosis, cat scratch disease, and tularemia [2].
–– Scrofuloderma: The main differential diagnoses are actinomycosis, inguinal
granuloma, venereal lymphogranuloma, and hidradenitis suppurativa [2].
–– Periorificial tuberculosis: The main differential diagnosis is paracoccidiodo-
micosis [2]. Tuberculosis verrucous cutis: The main differential diagnoses
are: leishmaniasis, chromomycosis, sporotrichosis, and lobomycosis.
Hypertrophic lichen planus, rupioid psoriasis, and squamous cell carcinoma
should also be considered [2].
–– Indurated bazin erythema: The main differential diagnoses are panarteritis
nodosa and erythema nodosum [2].
–– Lichen scrofulosorum: The main differential diagnoses are lichen spinulosa,
lichen nitiidus, keratosis pilaris, pityriasis rubra pilar, and lichenoid sarcoid-
osis [2].
Non-tuberculosis Mycobacteria 491
Non-tuberculosis Mycobacteria
• Definition: Atypical mycobacteria are a group of mycobacteria other than

M. tuberculosis and M. leprae.
• Pathogenesis: This type of mycobacteria is found in water, moist soil, dust, dairy
products, cold-blooded animals, vegetation, and human feces, which are trans-
mitted by inhalation, ingestion, or percutaneous penetration, which can result in
lung, lymphatic, or skin disease. The type of disease depends on the mycobacte-
rial species, route, degree of exposure, and the immune status of the host [1]. Its
recognition was of importance in immunosuppressed patients, being one of the
most frequent systemic bacterial opportunistic infections [1]. Among them are
Mycobacterium ulcerans, Mycobacterium marinum, Mycobacterium kansasii,
Mycobacterium fortuitum, Mycobacterium chelonae, Mycobacterium abscessus,
Mycobacterium avium complex, Mycobacterium haemophilum, and
Mycobacterium scrofulaceum [1].
• Clinical presentation: Often skin lesions are not diagnosed because they are non-
specific lesions or are sometimes mild clinical presentations, especially in
patients who are immunosuppressed combined with inadequate biopsy technique
and cultures. These infections should be suspected in patients with indolent
ulcers, nodules, or plaques, especially in immunosuppression [1] (Fig. 18.10).
• Diagnosis: The histopathological characteristics, as in any type of mycobacterial
infection, present an acute and chronic inflammation of tuberculoid granulomas.
Fibrinoid changes and caseified necrosis can occur [1]; the recommended method
for staining samples of acid-fast bacilli (ABB), both for M. tuberculosis and for
nontuberculous Mycobacteria, is the fluorochrome technique, although the Ziehl
stain Neelsen, Kinyoun stains are acceptable but with lower sensitivity [2].
Fig. 18.10 Non-

tuberculosis mycobacteria:
Erythematous papules that
converge to form an
erythematous, scaly,
infiltrated plaque with
well-defined edges, in the
right perioareolar region
However, to perform diagnostic confirmation will require a culture for mycobac-

teria, which is positive in 70–80% of cases [1]. Laboratory samples can be taken
from any part of the body, but its risk of contamination is very high; if the sample
takes more than an hour to be taken to the laboratory, it must be kept refrigerated
at 4 °C [2].
• Differential diagnosis: The main differential diagnoses include: sporotrichosis,
lymphadenitis due to Epstein–Barr virus or cytomegalovirus, folliculitis, lepro-
matous leprosy, dimorphic fungal infections, panniculitis, and ulcers [1].
References
Dermatol. 1984;120:214–5.
p. 445–526.
Fitzpatrick’s dermatology in general medicine. 8th ed Vol 2; 2012. p. 1319–36.
5. Simonds RM, Segal RJ, Sharma A. Extramammary Paget’s disease: a review of the literature.
Int J Dermatol. 2019;58(8):871–9. https://doi.org/10.1111/ijd.14328. Epub 2018 Dec 19.
Chapter 19
Fungal Infections
Superficial Mycosis
Dermatophytosisor Ringworm
Tinea (Dermatophytosis)
• Definition: Ringworms are superficial infections of the stratum corneum by der-

matophyte fungi [1]
• Etiopathogenesis: Dermatophytes are the most common agents of superficial
fungal infections, with a global prevalence of 20–25%. Ringworms are superfi-
cial infections of the stratum corneum or keratinized appendages, such as nails
or hair, by dermatophyte fungi. The main causal agents are Trichophyton rubrum,
T. mentagrophytes, Epidermophyton floccosum, Mycrosporum canis, M. gyp-
seum, T. violaceum, and T. erinacei [1, 2].
–– Tinea incognita: When the clinical lesions have been modified by the use of
topical or systemic immunomodulators and immunosuppressants, it is known
as tinea incognita. These drugs decrease cellular immunity, which allows the
progression of the infection and the transformation of clinical lesions [2].
• Clinical presentation: They can affect patients of any sex and age, and all areas
of the body. They are classified according to the affected site as tinea capitis,
tinea faciei, tinea barbae, tinea corporis, tinea manus, tinea cruris (English), tinea
pedis, and tinea ungulars. Other clinical variants include tinea imbricata, tinea
pseudoimbricara, and Majocchi’s granuloma. They manifest clinically as ery-
thematous plaques, with a raised, scaly border and central clearance (Figs. 19.1,
19.2, 19.3, and 19.4). When there is involvement of hairy areas, follicular pap-
ules and pustules with alopecia can be seen [1, 2].

https://doi.org/10.1007/978-3-030-84107-2_19
494 19 Fungal Infections
Fig. 19.1 Tinea pedis:

Multiple papules that
converge to form a large
involvement throughout
the distal third of the foot
with a well-defined active
border
Fig. 19.2 Tinea faciei:

Multiple papules that
rounded erythematous
plaque with a plaque on
the round periphery with
an active well-defined
border
Fig. 19.3 Tinea pedis:

Erythematous papules
converging on a base with
yellowish hyperkeratosis
with defined border on the
sole of the right foot
–– Tinea incognita: In general, they tend to have a less elevated border and to be
less scaly than common dermatophytoses. They can present pustules, nod-
ules, be itchy, erythematous, and extensive [2].
• Diagnosis: The diagnosis is mainly clinical; however, sometimes confirmation is
required with the visualization of fungal structures by direct examination with
potassium hydroxide (KOH) in a c oncentration of 10%, in the histological with
PAS stain (periodic acid Schiff), or in the microbiological isolation in culture on
Sabouraud agar [1, 2].
Superficial Mycosis 495
Fig. 19.4 Tinea

interdigital: Interdigital
maceration with moisture
cracks on an
erythematous base
• Differential diagnosis: The main differential diagnoses include centrifugal annu-

lar erythema and contact dermatitis [1].
• Tinea incognita: Modified lesions can simulate other dermatoses such as: rosa-
cea (when it affects the face), pyodermatitis, seborrheic dermatitis, and more
frequently eczema (contact dermatitis, nummular eczema, and gravitational
eczema) [2].
Mucocutaneous Candidiasis
• Definition: Mucocutaneous candidiasis is caused by superficial infection of dif-

ferent Candida species. It has a wide spectrum of clinical presentation, it can
affect the skin, with a predominance of skin folds and mucous membranes [1, 2].
• Etiopathogenesis: In humans, the most common type of Candida is C. albicans,
which can exist as hyphae or yeast depending on the environment [1]. Other spe-
cies that have been identified are C. dublinensis, C. glabrata, C. krusei, C. ketyr,
C. parapsilosis, C. stellatoidea, and C. tropicalis [2–5]. The latter have also been
implicated, although less frequently, in oral candidiasis and intertrigo candidiasis
[2, 4, 5], while only in rare cases of vulvovaginal candidiasis has C. glabrata
been isolated [3]. Candida is present in the normal oral and skin flora of healthy
individuals. In the vaginal mucosa, colonization occurs by migration from the
gastrointestinal tract. A number of local or systemic factors can cause Candida
species to overgrow [1–3].
–– Systemic factors: Immunosuppression (infection by the human immunodefi-
ciency virus (HIV), leukemia, malnutrition, systemic chemotherapy, diabetes
mellitus, corticosteroids, or systemic immunomodulators), advanced age, and
broad-spectrum antibiotics [1–5]. Additionally, postmenopausal status, preg-
nancy, and the use of oral contraceptives have been associated with the devel-
opment of vulvovaginal candidiasis [3].
• Local factors, mainly those that favor humidity, depend on the type of
candidiasis.
–– Oral candidiasis: The factors associated with this type of candidiasis are
mainly the use of dental prostheses, inhaled corticosteroids, and xerostomia.
Smoking has been associated with certain forms of oral candidiasis such as
median rhomboid glossitis [2].
–– Candida balanitis: Non-circumcision, poor hygiene, and the use of occlusive
clothing are risk factors for this type of candida [4].
–– Intertrigo Candida: The risk factors identified for this type of candida are
hyperhidrosis, poor hygiene, hot and humid climates, and obesity (due to the
formation of large skin folds) [4, 5].
–– In chronic mucocutaneous candidiasis (CMC), patients have a deficiency of
cellular immunity mediated by T lymphocytes that prevents effective control
over Candida. This deficiency is not always detectable in vitro, it can be spe-
cific to Candida species and sometimes the immune response to other organ-
isms is also altered [1, 2, 6].
• Clinical presentation: There are several forms of candidiasis depending on the
affected anatomical site.
–– Oral candidiasis: Oral candidiasis can present as whitish or erythematous
lesions [2].
White oral candidiasis
• Pseudomembranous candidiasis: It is the classic and most common
presentation of oral candidiasis. It is characterized by whitish plaques,
which are easily removed, leaving an erythematous surface. It can
involve the tongue, cheeks, palate, and oropharynx. Patients are typi-
cally asymptomatic, although they may describe a burning sensation,
changes in taste, or easy bleeding. The lesions can be acute or chronic
[1, 2] (Fig. 19.5).
Fig. 19.5 Oral

candidiasis: Multiple
whitish and erythematous
plaques over the lower lip
and the gums
• Hypertrophic candidiasis: It presents as well-defined, slightly elevated,

adherent plaques that do not detach easily; lesions are initially small
and may progress to large plaques, with a mottled appearance that
simulates leukoplakia. The labial mucosa, the oral commissures, the
lateral aspects of the tongue, and the palate may be affected [1, 2].
Erythematous oral candidiasis

• Acute atrophic candidiasis: This form most commonly affects the pal-
ate, although the cheeks and the back of the tongue may also be involved.
It presents as erythematous patches that may be accompanied by a sen-
sation of pain or burning. It is seen more frequently in patients with
HIV infection or who have received broad-spectrum antibiotic ther-
apy [1, 2].
• Chronic oral candidiasis: This form occurs mainly in patients with den-
tal prostheses. It is seen as erythematous and edematous patches that
only compromise the areas of contact with the prostheses, which are
associated with pain or burning sensation. It can present with other
forms of candidiasis such as angular cheilitis [2].
• Middle rhomboid glossitis: It is a rare form of oral candidiasis charac-
terized by atrophy of the filiform papillae of the tongue. It presents as a
symmetrical, erythematous, diamond-shaped patch with a smooth,
shiny surface. It is located in the center of the dorsum of the tongue and
anterior to the circumvalate papillae, and it is frequently accompanied
by pain [2].
• Angular cheilitis: This form of candidiasis, also known as perleche,
presents as fissured, erythematous patches in the oral commissures. The
involvement is typically bilateral and is associated with pain and burn-
ing [1, 2].
• Gingival linear erythema or gingival band: It is a form of oral candidia-
sis that occurs in patients with HIV infection. It is characterized by a
discrete erythematous band on the gingival margin of one or more
teeth [2].
–– Genital candidiasis
Vulvovaginal candidiasis (CVV): Clinically presents with a whitish, odor-
less, lumpy vaginal discharge, accompanied by itching, irritation, pain, and
dyspareunia. The vulva may be erythematous, edematous, and fissured,
and occasionally may have whitish membranes. Recurrent CVV is referred
to when there are at least three symptomatic episodes in 12 months [1, 3].
Candida balanitis: Usually occurs within the first 3 months of a sexual
relationship with an infected woman. It presents as erythematous patches,
with small erythematous papules and pustules; there may also be cracks,
erosions, and flaking. It mainly affects the glans but can affect the shaft of
the penis and is accompanied by burning pain [4].
–– Intertrigo candidiasis: It appears as erythematous plaques, with well-defined

edges, with a macerated surface. It may present scaling at the edge, satellite
lesions, and pustules (Fig. 19.6). It mainly involves the skin folds and
interdigital spaces, where it can also present fissures. It is frequently accom-
panied by pruritus [4, 5].
–– Nappy candidiasis: Diaper rash is an inflammatory disease that affects 10%
of all infants, which occurs most frequently between 7 and 9 months. Although
Candida species are not the only causative agent of diaper rash, cultures of
erythematous lesions with satellite pustules are almost always positive for
Candida sp. Classically it presents as an erythematous plaque, with defined
edges, scaly, and occasionally elevated, with satellite pustules and sometimes
with punched-out superficial ulcers. A granulomatous form of diaper candi-
diasis that presents with paulae and erythematous nodules has also been
described and is known as infantile gluteal granuloma [4].
–– Chronic mucocutaneous candidiasis (CMC): It is a heterogeneous disease
that presents with chronic lesions on the skin, mucous membranes, and nails.
In the mucosa, it can include any of the forms of oral or genital candidiasis
described. Ungular lesions are characterized by chronic paronychia and ungu-
lar dystrophy with thickening of the nail plate, fragility, and shedding. The
cutaneous lesions are erythematous or whitish, crusty, and thick plaques;
They mainly affect periorificial or intertriginous areas and the scalp, where it
can generate scarring alopecia. It is characterized by a poor response to anti-
fungal drugs and has been associated with endocrine disorders such as diabe-
tes mellitus, hypoparathyroidism, and hypothyroidism [1, 2, 6]. A subgroup
of chronic mucocutaneous candidiasis has also been described in children and
adolescents, which are [6]:
Pure family CMC
Localized chronic candidiasis or candida granuloma
Fig. 19.6 Cutaneous and

intertrigo candidiasis:
Over the pubic region and
the inguinal folds, there are
multiple red to violaceous
plaques with an ill-defined
and irregular edge,
macerated surface, and
satellite papules
Ectodermal dystrophy-candidiasis-autoimmune polyendocrinopathy

syndrome
CMC associated with CARD9
Dectin-1 deficiency
CMC late start
Familial chronic ungular candidiasis CMC associated with keratitis
CMC associated with other immunodeficiencies
CMC associated with predominantly non-immunological conditions
• Diagnosis: The diagnosis is clinical. Confirmation of the diagnosis is made by
visualizing the pseudohyphae or budding yeasts in a direct examination with
potassium hydroxide (KOH) or in a biopsy. Special stains such as periodic acid
Schiff, Gram or methylene blue, among others, are required. The causative agent
can also be isolated by culture [1–4].
• Differential diagnosis: Differential diagnoses depend on the type of candidiasis.
–– Oral candidiasis:
The forms of white oral candidiasis must be differentiated from: oral leu-
koplakia, lichen planus, chronic lesions of bullous diseases, chemical
burns, and trauma [2].
The main differential diagnoses of erythematous oral candidiasis include:
lichen planus, pernicious anemia, trauma, and oral thrush associated with
systemic lupus erythematosus and erythema multiforme [2].
–– Intertrigo candidiasis: Eczema, inverse psoriasis, erythrasma, and dermato-
phytosis are the main differential diagnoses of this type of candidiasis [4, 5].
–– Diaper dermatitis: It must be differentiated mainly from psoriasis, seborrheic
dermatitis, Langerhans cell histiocytosis, acrodermatitis enteropathica, biotin
deficiency, and Kawasaki disease [4].
Onychomycosis
• Definition: Onychomycosis is defined as infection of the nail system caused by

dermatophyte fungi, yeasts, and non-dermatophyte molds [1, 2].
• Etiopathogenesis: Dermatophytes such as Trichophyton rubrum are the main
cause of onychomycosis representing 59%, followed by non-dermatophyte
molds with 20% and lastly yeasts with 20%. There are multiple established risk
factors such as tinea pedis, nail trauma, diabetes, peripheral vascular disease,
personal or family history of onychomycosis, advanced age, genetic susceptibil-
ity due to HLA polymorphisms, and immunosuppression. There is also a signifi-
cant association with inflammatory pathologies that affect the nail unit such as
psoriasis [1–3].
• Clinical presentation: Clinically, it can manifest with onycholysis or detachment
of the nail plate, subungular hyperkeratosis giving it an appearance that has been
described as “ruined,” thickening of the nail plate or pachyonychia, changes in

color that can present various patterns, from homogeneous discoloration with
opacity, in patches or in the form of striae whether they are transverse or longi-
tudinal, and that can appear in different shades, the most common being white,
yellow, orange, brown, and blackish [1, 2]. You can also see a grouping of fungal
arthrospores in the nail plate, with thickening of the cell wall and the presence of
spaces in the surrounding keratin, which can form a subungular mass composed
of keratin infiltrated with fungi, known as dermatophytoma, which has been
associated with resistance to treatment, may require excision, and is more com-
mon in certain types of onychomycosis such as distal and lateral subungular
(OSDL) [2, 3]. The original classification of onychomycosis proposes three
forms of invasion of the nail plate: distal and lateral subungular onychomycosis
(OSDL), superficial white onychomycosis (OBS), and proximal subungual ony-
chomycosis (OSP) [1]. The concept of total dystrophic onychomycosis was later
introduced. However, there are a number of modifications that have been intro-
duced to explain new findings such as endonyx onychomycosis, a revision of the
concept of OBS, where the nail plate is attacked from the distal end causing
greater penetration of the fungus [1, 2]. As new fungi have been identified as
causative agents of onychomycosis that can produce different alterations, the
development of new classifications has been necessary, and the most recent one
includes the subtypes of invasion of the nail plate. This revised classification
proposes seven types of onychomycosis: distal and lateral subungular (OSDL),
superficial (OS), endonyx (OE), proximal subungular (OSP), mixed pattern
(OPM), total dystrophic (ODT), and secondary [3].
–– Distal and lateral subungular onychomycosis (OSDL) is the most common
form of invasion of the nail plate. The main features are onycholysis with
hyperkeratosis and various forms of dyschromia, most commonly white or
yellowish, but other changes in color such as brown, blackish, or orange have
occasionally been seen (Fig. 19.7). It is also the subtype in which dermato-
phytomas are most frequently found and is the one associated with a larger
number of fungi, mainly dermatophytes (T. rubrum, T. mentagrophytes, and
E. floccosum), Candida albicans, Fusarium species, Scytalidium, and
Scopulariopsis brevicaulis [1–3].
–– Superficial onychomycosis (OS) can present with a wide range of dyschro-
mias depending on the organism involved, that is why the term “superficial
white onychomycosis” is restrictive, since superficial black onychomycosis
caused by Trichophyton rubrum and Scytalidium dimidiatum have been
described. Dyschromia may be patchy or transverse, may have a distal or
proximal origin, and may have deep penetration (Fig. 19.8). The most com-
monly associated causative agents are T. mentagrophytes and T. rubrum in the
patchy subtype and Fusarium, Acremonium, Scytalidium, T. rubrum in the
transverse subtype [1–3].
–– Onychomycosis endonyx (EO) is recognized by the combination of laminar
detachment of the nail, dyschromia, and the absence of invasion of the nail
Fig. 19.7 Distal and

lateral subungular
onychomycosis.
Onycholysis with mild
hyperkeratosis and
yellowish nail dyschromia
Fig. 19.8 Superficial

onychomycosis. White
superficial chromonychia
on the fifth finger nail plate
bed with internal involvement of the nail plate (Fig. 19.9). The route of inva-
sion is believed to be penetration of the hyphae directly from the distal end of
the nail plate. It was originally described as a T. soudanense infection, but it
has also been described by T. violaceum [3].
–– In proximal subungular onychomycosis (OPS), the infection classically origi-
nates at the proximal subungular end and extends distally. Some forms that
Fig. 19.9 Onychomycosis

endonyx. Nail plate
onycholysis, white-yellow
dyschromia affecting distal
segment of the nail
present with a transverse striated pattern have been associated with concur-
rent OS (Fig. 19.10). This subtype has been associated with immunosuppres-
sion, particularly HIV/AIDS and a wide variety of fungi, mainly T. rubrum,
Fusarium, C. albicans, and Aspergillus (2.3).
–– Mixed pattern onychomycosis (OM) corresponds to the presence of two of
those already described; some examples include OSDL plus OS frequently
associated with T rubrum, OS plus OPS associated with T. rubrum, and
Fusarium and OSDL plus OPS associated with T rubrum [3] (Fig. 19.11).
–– The concept of total dystrophic onychomycosis (ODT) represents a terminal
state of the different modes of invasion of the nail plate that compromises its
entirety [1–3] (Fig. 19.12).
–– Secondary onychomycosis refers to the coexistence of fungal infection of the
nail apparatus previously compromised by other non-fungal pathologies,
mainly nail psoriasis and traumatic nail dystrophy. In these secondary forms,
the diagnosis is particularly difficult [3].
• Diagnosis: Routinely for the diagnosis of onychomycosis, the presence of fungal
structures in diseased nails is required by means of a direct examination with
potassium hydroxide (KOH) in a concentration of 20–40% or microbiological
isolation in agar culture Sabouraud. Additionally, there are other diagnostic
methods that include isolation of the genetic material of the fungus by PCR
(polymerase chain reaction) and histological visualization with PAS (periodic
acid Schiff) stain. Recently, confocal scanning laser microscopy, optical coher-
ence tomography, and dermoscopy have been proposed as diagnostic tests for
onychomycosis [1–3].
• Differential diagnosis: The main differential diagnoses include psoriasis, lichen
planus, trauma, among others [1–3].
Fig. 19.10 Proximal

subungual onychomycosis.
Proximal segment white
and yellow dyschromia
affecting multiple toenails
in an immunosuppressed
patient
Fig. 19.11 Mixed pattern

onychomycosis. Superficial
white nail plate
discoloration, along with
yellow lateral and distal
chromonychia and
onycholysis
Fig. 19.12 Total

dystrophic onychomycosis.
Complete affectation of
distal and proximal
segments of the ungueal
plate in association with
white-yellow discoloration
and subungual
hyperkeratosis
Pityriasis Versicolor
• Definition: Pityriasis versicolor is a superficial skin infection caused by

Malassezia species [1–3]
• Etiopathogenesis: M. furfur, M. globosa, and M. restricta are the main Malassezia
species identified in pityriasis versicolor [1]. Other species such as M. pachyder-
matis, M. sympodialis, M. obtusa, and M. slooffiae have also been associated,
although less frequently [2]. The relationship between Malassezia species and
humans is saprophytic, with little or no inflammatory response of the skin [1].
Some triggering factors are responsible for the passage from the saprophytic
phase to the parasitic phase of the fungus. These factors include hot and humid
climates, hyperhidrosis, immunosuppression (corticosteroids or systemic immu-
nomodulators), and genetic factors that are not yet fully understood [1–3].
• Clinical presentation: Pityriasis versicolor is a frequent, benign, and recurrent
disease that affects both sexes, mainly young adults. It is characterized by conflu-
ent oval patches, slightly scaly, whose coloration varies from pink to brown [1–3]
Fig. 19.13 Pityriasis

versicolor. Multiple,
erythematous, papules, and
plaques with fine scale on
the trunk
(Fig. 19.13). Occasionally, a skin tightening (evoked peeling sign or Zireli’s

sign) or gentle scraping (fingernail sign) is required for peeling to be evident [1,
2]. Hypopigmented lesions may appear in exposed areas, and it is known as
pityriasis versicolor alba. The rubra and nigra forms, characterized by erythema-
tous and blackish lesions, respectively, have recently been described [1].
• It preferentially affects the upper part of the trunk (chest, back, and shoulders)
and can extend toward the neck, face, and arms [1–3]. The face is affected fre-
quently, especially in tropical climates. Other rarer locations are the eyelids,
armpits, penis, and perineum [1]. Patients are often asymptomatic, although they
may rarely itch [1–3].
• Diagnosis: The diagnosis is mainly clinical; Wood’s light can be useful, showing
a yellowish fluorescence of the lesions. It can be confirmed with a direct exami-
nation with potassium hydroxide with black Parker ink where yeast and pseudo-
hyphae are evidenced that generate a typical “spaghetti with meatballs” image.
Normal skin or mild parakeratosis is typically seen on biopsy of the lesions;
fungal structures can be observed with periodic acid Schiff or methenamine sil-
ver stains, and among others (Fig. 19.14). Culture is useful only when the impli-
cated Malassezia species is to be identified; however, it does not grow in classical
culture media (Sabouraud), with the exception of M. pachydermatis; special
media such as Dixon medium or Leeming and Notman medium are required [1–3].
• Differential diagnosis: The main differential diagnoses include pityriasis rosea,
confluent, and reticulated papillomatosis, in the hypopigmented variant, vitiligo,
and progressive macular hypomelanosis [1].
Tinea Nigra
• Definition: Tinea nigra is a superficial mycosis caused by Hortaea werneckii [1].

• Etiopathogenesis: H. werneckii is a dematiaceous, polymorphic fungus that
grows in aqueous media. The infection is seen most frequently in children and
Fig. 19.14 Pytiriasis versicolor. Presence of hyphal-shaped structures in the stratum corneum
Fig. 19.15 Tinea nigra: A

single brown patch with
fine blackish-brown scaling
in the palm of the hand
young adults in tropical and coastal regions [1]. Clinical presentation: It usually
involves the palms and soles, although it can affect the dorsal aspects of the
hands and feet and less frequently the legs, arms, trunk, and neck. It is
characterized by a single lesion, which may be a macula or a patch with fine
blackish-brown scaling [1] (Fig. 19.15).
• Diagnosis: The diagnosis can be made by visualizing the fungus with a direct
examination with potassium hydroxide (KOH) 10%. Dermoscopy is a useful
tool. The most frequent findings are a light brown amorphous macula on which
can be seen some pinpoint, fine, brown granular structures. The pigment does not
respect the dermatoglyphs or follow a specific pattern [2].
• Differential diagnosis: The main differential diagnoses are other viral exanthe-
mas and drug reactions [1, 2].
Deep Mycoses 507
Deep Mycoses
Sporotrichosis
• Definition: Sporotrichosis is a deep mycosis, prevalent mainly in tropical and

subtropical areas, with hot and humid climates [1, 2].
• Etiopathogenesis: It is produced mostly by Sporothrix schenckii, although other
species have recently been identified such as (S. inflate, S. brasiliensis, S. glo-
bosa, and S. mexicana) [1, 2] S. schenckii in a fungus dimorphic that can be
found in soil or decomposing material. The most common way of acquiring the
infection is by traumatic inoculation of the fungus. The incubation period varies
from days to months. S. schenckii binds specifically to fibronectin and activates
toll-like receptors (TLR), thereby activating inflammation and inducing a sup-
purative granulomatous reaction in the infected tissue. In the early phase of the
disease, a Th1 response predominates and the Th2 response is activated later [1].
–– The risk factors for acquiring the disease are individuals who work with
wood, plants, flowers, or animals (cats, dogs, horses, camels, monkeys, or
rats) [1, 2]. Immunosuppressed, alcoholic, and diabetic patients have a predis-
position to develop a disseminated disease [1].
• Clinical presentation: Sporotrichosis is slightly more prevalent in men than in
women. It can occur at any age, but it is most common in children and young
adults. The lesions are chronic and most commonly affect the face in children,
while in adults they involve the hands and forearms, although any part of the
body can be affected. Sporotrichosis is classified as [1, 2] follows:
–– Primary skin disease
Fixed sporotrichosis: It is characterized by a papule that rapidly evolves
into a nonpainful, infiltrated, erythematous, or violaceous plaque covered
by scales that give it a warty appearance and that can ulcerate [1, 2]
(Fig. 19.16).
Lymphangitic sporotrichosis: It begins with the inoculation chancre, which
presents as an erythematous nodule that can become necrotic. Subsequently,
new gummy lesions develop (ulcerated nodules) following a lymphatic
path. Lymphatic drainage may be compromised, generating lymphedema
[1, 2] (Fig. 19.17).
Disseminated sporotrichosis: Disseminated disease refers to extensive
skin involvement, with multiple lesions, without systemic involvement. It
is more frequent in immunosuppressed patients [1–3].
–– Extracutaneous disease
Osteoarticular: It can manifest as tenosynovitis, periostitis, or monoartic-
ular arthritis. In most cases, joint involvement is preceded by skin lesions
in immunocompromised patients [1, 4]
Fig. 19.16 Sporotricosis:

Plaques with violet edges,
irregular, well defined,
with a whitish surface with
a warty appearance with a
linear distribution on the
lower left limg
Fig. 19.17 Sporotricosis:

In the medial side of the
left upper limb, there is
presence of qrythematous
nodules and tubercles that
converge to form plaques,
some with central
ulceration and hematic
crusts on the surface with a
linear path
Systemic Mycoses 509
Mucosa: This form is rare. It is seen as warty, granulomatous, or ulcerated

lesions that can involve the palate, pharynx, trachea, or nose [1].
Pulmonary: It occurs in immunosuppressed patients, particularly with
human immunodeficiency syndrome (AIDS). It manifests as a cough with
or without hemoptysis, fever, and weight loss (1.4).
Systemic: These forms have only been reported in immunocompromised
patients. It can affect the central or peripheral nervous system [1, 4].
• Diagnosis: The diagnosis requires clinical suspicion due to the characteristics of
the lesions and the medical history. A direct examination of the lesion can be
performed to visualize yeast with periodic acid Schiff (PAS) or Gomori-Grocott
(GG) stains; however, it has a low sensitivity. Intradermal reactions can also be
used but are of little use. The gold standard for diagnosis is the isolation of the
fungus on Sabouraud agar, which is characterized by rapid growth [1, 2].
–– Histopathology shows epidermal hyperplasia with or without ulceration, for-
mation of suppurative granulomas in the dermis within which asteroid bodies
can be observed. The latter represent a resistance mechanism in yeast; it is
seen as a radiated matrix that is surrounded by an eosinophilic material, which
corresponds to immune complexes. This phenomenon is known as Splendore–
Hoeppli and can be seen in other deep mycoses. Fungal structures are rarely
found [1, 2].
• Differential diagnosis: The main differential diagnoses are the diseases that are
part of the tropical wart syndrome such as: tuberculosis, leishmaniasis, chromo-
mycosis, and among others [1].
Systemic Mycoses
Histoplasmosis
• Definition: Histoplasmosis is a systemic infection caused by Histoplasma capsu-

latum [1, 2].
• Etiopathogenesis: H. capsulatum is a dimorphic fungus that has two pathogenic
variants for humans; the H. capsulatum var. duboisii, found mainly in Africa and
H. capsulatum var capsulatum, found mainly in North and South America. The
fungus is found in the droppings of bats and birds and can remain in the environ-
ment for long periods of time [1]. H. capsulatum is found in the soils of hot and
humid climates, particularly in the Mississippi, Ohio, and St. Lawrence River
valleys in the United States and Canada. Between 80% and 90% of people in
endemic areas may test positive for histoplasmin [2]. The infection is acquired
by inhalation in the form of mycelia and mainly affects the lungs. Spontaneous
resolution occurs in 95% of patients, and the infection induces immune memory.
The pathogenic process after inhalation of conidia is initially localized as pneu-

monitis, followed by hematogeneous spread after 2 weeks, and the cell-mediated
immune response after 3 weeks. In patients with human immunodeficiency syn-
drome (AIDS), the infection can progress, spread, and involve the skin [1].
• Clinical presentation: Symptoms of acute pulmonary histoplasmosis include
fever, malaise, weight loss, cough, and chest pain; it is an infection that can
develop a rapid course with compromise of the reticuloendothelial system, where
in these cases it can be fatal. Central nervous system involvement may be pri-
mary or associated with disseminated disease (5–10% of cases). Manifestations
include meningitis, encephalitis, and vascular syndrome. Half of the patients
have disseminated forms that compromise adrenal function; however, only 7%
have adrenal insufficiency [1]. Primary skin lesions are uncommon. Skin involve-
ment occurs in association with disseminated histoplasmosis in 70–80% of cases
[1]. Skin manifestations are seen mainly in adults and more frequently in South
America, where the strains are thought to be more virulent. Skin lesions are non-
specific and varied, which can range from erythematous or brownish-
erythematous papules to hyperkeratotic plaques. Two-thirds of patients
experience mucosal involvement, particularly in the oropharyngeal region and
ulcers at the level of the palate, as well as scaly lesions mainly on the face and
disseminated violaceous non-pruritic maculopapular lesions [1].
• Diagnosis: The diagnosis is based on clinical suspicion, due to skin lesions in an
immunosuppressed patient. Confirmation with a skin biopsy is required.
Histology shows mycotic structures, with special stains such as periodic acid
Schiff (PAS), Giemsa, and Gomori-Grocott, forming intracellular buds with a
clearance ring. Additionally, histiocytes and giant cells can be observed [2].
Laboratories that use histoplasmosis diagnostic support include anemia, leuko-
penia, thrombocytopenia, abnormal liver enzymes, elevated lactic dehydroge-
nase, and ferritin [1]. Samples of bone marrow, sputum, or material obtained by
bronchoscopy to search for the fungus can also be obtained. The intradermal
reaction is not very useful in patients with HIV [1]. Laboratory techniques such
as polymerase chain reaction (PCR), immunodiffusion, and complement fixation
can be used to identify antibodies. These tests are positive in 90% of patients
with acute pulmonary histoplasmosis without immunosuppression; however,
they are frequently negative in patients with HIV [1].
Differential diagnosis The main differential diagnoses include secondary syphilis,
cryptococcosis, contagious molluscs, and among others [1].
Paracoccidioidomycosis
• Definition: Paracoccidioidomycosis is a systemic fungal infection caused by

Paracoccidioides brasiliensis. It is an endemic disease in South and Central
America (Mexico, Venezuela, Colombia, Ecuador, Brazil, and Argentina) [1–3].
Systemic Mycoses 511
• Ethiopathogenesis: P. brasiliensis is a dimorphic fungus that is found in the envi-

ronment, mainly in the soil, as a mold [2]. In most cases, infection occurs by
inhalation of conidia; once in the alveoli, the fungus assumes the form of yeast
[1, 2]. Later the infection can spread, either by reinoculation or by hematogenous
spread, to the skin, mucous membranes, gastrointestinal tract, spleen, adrenal
glands, and lymph nodes [1, 2]. Classically affects men, being extremely rare in
women, probably related to an inhibitory effect of estrogens on the transition of
the fungus from its mold to yeast state [2].
• Clinical presentation: The initial exposure generally occurs at an early age,
which in most cases is self-limited without causing disease; in 10% of cases, an
acute or subacute form is present. Later in life, a reactivation of the latent infec-
tion occurs, presenting the classically known picture of chronic paracoccidioido-
mycosis that represents 90% of cases [2, 3].
–– Acute-subacute (juvenile) paracoccidioidomycosis: Typically affects those
under 30 years of age or immunosuppressed. It mainly involves the reticulo-
endothelial system (liver, spleen, lymph nodes, and bone marrow) [2].
–– Chronic paracoccidioidomycosis (adult): It occurs in adults over 50 years of
age. It is a slowly progressive form that is characterized by pulmonary
involvement.
On the skin, it classically presents as an ulcer with infiltrated edges, peri-
orificial location, predominantly perioral, with lip involvement, and peri-
nasal [2, 3]. Papular, nodular, or plaque lesions and other locations (perianal
region, scalp, and lower limbs, mainly the feet) have also been described
[3] (Fig. 19.18).
The oral mucosa is usually affected, with diffuse infiltration of the gums,
giving it a moriform erythematous-violaceous appearance; ulcers on the
gums or tongue and perforation of the palate may also occur. Dysphonia is
Fig. 19.18 Chronic

paracoccidioidomycosis.
On the left aspect of the
chin, there is an infiltrated
ulcer with well-defined
erythematous edges and
clean bottom
Fig. 19.19 Mucous

paracoccidioidomycosis.
“Moriform gums,” defined
as erythematous gum
diffuse infiltration, along
with periodontal disease
a common sign that suggests laryngeal involvement. The ocular or genital

mucosa is rarely affected [2, 3] (Fig. 19.19).
In more than 90% of the autopsies of patients with paracioccidiodomico-
sis, involvement of the adrenal gland has been reported, but only half of the
patients have adrenal insufficiency [2].
The sequelae of the disease are usually chronic obstructive pulmonary dis-
ease, dysphonia, and laryngeal scarring [3].
• Diagnosis: The gold standard for diagnosis is based on the visualization of the
causative agent, either with a direct examination with potassium hydroxide
(KOH) or in biopsy samples, with stains such as methenamine silver or periodic
acid Schiff. P. brasiliensis appears as thick-walled yeasts with multiple small,
attached daughter yeasts, giving it a ship’s rudder appearance. The culture has
low sensitivity. Agar gel double immunodiffusion serological tests have a sensi-
tivity and specificity of more than 80% and 90%, respectively [2, 3].
Histopathology shows epidermal hyperplasia with suppurative granulomas.
Yeasts can be found outside and inside giant cells [1].
• Differential diagnosis: The main differential diagnoses include: leishmaniasis,
granulomatosis with polyangiitis (Wegener’s), NK cell lymphoma, and other
deep mycoses [1].
References
Benign melanocytic neoplasms, Neural and neuroendocrine neoplasms (Other than neurofibro-
Dermatol. 1984;120:214–5.
References 513
p. 445–526.
Fitzpatrick’s dermatology in general medicine. 8th ed; 2012. Vol 2 p. 1319–36.
5. García-Gavín J, Gonzáles-Vilas D, Montero I, Rodriguez-Pazos L, Pereiro MM, Toribio
J. Disseminated eruptive clear cell acanthoma with spontaneous regression: further evidence of
an inflammatory origin. Am J Dermatopathol. 2011;33:599–602.
6. Fukushiro S, Takei Y, Ackerman A. Pale-cell acanthosis: a distinctive histologic pattern of epi-
dermal epithelium. Am J Dermatopathol. 1985;7:515–27.
Chapter 20
Virus Infections
Herpesvirus
Herpes Simplex Type 1 (HHV1) and Type 2 (HHV2)
• Definition: They are frequent infections around the world, caused by ubiquitous
pathogens that mainly cause orolabial and genital herpes infections [1, 2].
• Pathogenesis: HHV1 and HHV2 are members of the herpesviridae family, a
group of lipid-enveloped double-stranded DNA viruses. Both HHS serotypes are
members of the alpha virus subfamily herpesviridae, which infect multiple cell
types in culture, with rapid and efficient growth, thereby destroying host cells
[2]. Transmission of herpes simplex virus can occur during asymptomatic peri-
ods of the virus. HHV-1 spreads mainly through direct contact with contami-
nated saliva or other infected areas, whereas HHV-2 spreads mainly through
sexual contact [1]. Infection in the natural host is characterized by lesions in the
epidermis that frequently compromises the mucosal surface [2]; the virus repli-
cates at the mucocutaneous site of infection and then travels via retrograde axo-
nal flow to the dorsal sheath ganglion, where latency is established until
reactivation [1]. HHV -1 can accumulate CD1d molecules intracellularly in
antigen-presenting cells, which provides a possible explanation for how the virus
evades detection and establishes latency. Normally, CD1d molecules are trans-
ported to surface cells, where they present lipids and stimulate natural killer
cells, promoting the immune response. The mechanisms of HHV that evade the
immune system also include downregulation of various immune cells and cyto-
kines [1]. Toll-like receptors play an important role in the innate immune
response against simple HHV and their functions include CD8 T cells, which are
selectively activated and retain latent infection in the sensory ganglion, control-
ling infections and preventing symptomatic recurrences [1]. HHV can be sponta-
neously reactivated when exposed to emotional stress, ultraviolet light, fever,
tissue damage local, or immunosuppression [1].

https://doi.org/10.1007/978-3-030-84107-2_20
516 20 Virus Infections
• Clinical presentation: Primary infection, symptoms typically occur 3–7 days

after exposure. A prodrome of lymphadenopathy, chills, anorexia, and fever fre-
quently occur before the onset of mucocutaneous lesions, which may be pre-
ceded by localized pain, burning, or stinging. A conglomerate of painful vesicles
that appear on an erythematous base and can be umbilicated followed by pro-
gression to pustules, erosions, and/or ulcerations with a characteristic scalloped
edge (Figs. 20.1, 20.2, and 20.3). Scab formation and resolution of lesions occur
within 2 to 6 weeks. A similar prodrome may precede recurrent lesions, but these
are often few in number, with a decrease in severity and duration compared with
a primary infection [1]. Most orolabial infections are asymptomatic. Symptomatic
infections frequently present as gingivostomatitis in children or as pharyngitis
and mononucleosis-like syndrome in young adults. The mouth and lips are the
most frequently involved sites. Genital lesions can be very painful with erosive
balanitis, vulvitis, or vaginitis. In women, the lesions frequently involve the cer-
vix, buttocks, and perineum and are associated with inguinal adenopathy and
dysuria. Gneital lesions in men typically occur on the glans penis, and the but-
Fig. 20.1 Herpes simplex:

In the upper lip are
evidenced vesicles that
converge in a cluster of
grapes on an erythematous
background

On the fifth finger in the
middle and distal phalanx,
multiple vesicles are
evidenced in an
erythematous background
Herpesvirus 517

In an older adult patient,
multiple vesicles converge
to form ulcers and
associated erosions are
evident
tocks are occasionally affected. Extragenital lesions such as urinary retention

and aseptic meningitis occur in 20% [1].
• Diagnosis: The diagnosis is mainly clinical. There are multiple laboratory tests
available for the diagnosis of HHV including culture, fluorescent antibodies,
molecular techniques such as PCR, serology, and additionally the Tzanck [1].
Culture usually requires two to five days to obtain a positive result: PCR is a
specific, sensitive, and rapid method for detecting HHV in skin or other organs
[1]. Western blot represents the gold standard for assay serological. It is 99%
sensitive and specific for HHV antibodies and can be distinguished between
HHV 1 and HHV 2 [1]. Tzanck is useful for early lesions, which reveals multi-
nucleated giant cells. this is observed in most HHV, but HHV1 does not differ
from HHV2 [1]. Histopathology herpes simplex, chickenpox and herpes zoster
are very similar, the changes involve the nucleus of epidermal cells with develop-
ment of a peripheral chromatin conglomerate and appearance of homogeneous
ground glass, combined with ballooning of the core. Vacuolization is the earliest
cytoplasmic alteration (Fig. 20.4). These changes start focally in the basal layer
but involve the entire epidermis. Types of degenerative change: degenerative bal-
looning and reticular degeneration. The edema of the cells and the loss of their
cellular union separate them forming secondary acantholysis. The cytoplasm of
these cells becomes homogeneous and intensely eosinophilic, and some are mul-
tinucleated (Tzanck Biopsied lesions generally present an intraepidermal vesi-
cle). This result forms two cells). At the same time, the basal layer of the
epidermis is also destroyed, leading to the formation of a subepidermal vesicle.
These changes are known as a reticular degeneration that is characterized by a
progressive hydropic edema of the epidermal cells [3].
• Differential diagnosis: The main differential diagnoses of orolabial herpes are
aphthous ulcers, syphilis, herpangina, erythema multiforme, Stevens-Johnson
syndrome, and mucositis-induced chemotherapy [1, 2]. In genital herpes, it
Fig. 20.4 Herpes simplex: Balloonization is evident, ballooned keratinocytes with a ground glass
appearance. And some multinucleated cells. Lymphocytic infiltrate
should be taken into account: chancroid, syphilis, venerial lymphogranuloma,

inguinal granuloma [2].
VHH 3 Congenital Varicela Syndrome
• Definition: Congenital varicella syndrome (CVS) is an entity with high morbid-

ity, caused by the herpes zoster virus (HHV3), but with a fortunately low fre-
quency [1]. The clinical picture varies between being asymptomatic and severe
fetus disease with low birth weight, ocular involvement, central nervous system,
skeletal muscle, genitourinary, gastrointestinal and cardiac, the most frequent
manifestation being the skin (70–76%) [2, 3].
• Epidemiology: An incidence of 2% is reported, when the pregnant woman is
infected by the varicella zoster virus between week 13 and 20 [1]. There are
around 110 reported cases of CVS [4, 5] and in one low percentage is acquired
before the 13th week of gestation [1].
• Clinical presentation: Clinically described cases of CVS present with neurologi-
cal involvement in 60% (cortical atrophy, spinal atrophy, lower limb paresis,
microcephaly, Horner's syndrome, encephalitis, dysphagia, and seizures), ocular
Herpesvirus 519
in 51% (microphthalmia, enophthalmia, chorioretinitis, cataract, nystagmus,

anisocoria, and optic atrophy), limb hypoplasia, and other musculoskeletal
abnormalities in 49%, intrauterine growth restriction in 22%, muscle hypoplasia
in 21%, gastrointestinal abnormalities in 15%, genitourinary abnormalities in
12%, cardiovascular defects 8%, and defects in other organs 7%; the skin showed
an erythematous-violet scar with a central depression in the appearance of a zig-
zag, generally on the extremities [2] (Fig. 20.5).
• Diagnosis: Given the antecedent of a mother who has developed varicella infec-
tion during pregnancy, a thorough physical examination is required for the prod-
uct of that pregnancy and studies to rule out systemic involvement. The pertinent
follow-up should be carried out by pediatrics given all the short- and long-term
risks that newborns with low birth weight have, in addition to IgM and IgG for
varicella virus for the mother [2].
• Differential diagnosis: Congenital infections are caused by Coxsackie B, herpes
virus type 2, rubella, cytomegalovirus, toxoplasma gondii, and MIDAS syn-
drome (microphthalmia, cutaneous aplasia and sclerocornea) [2].
VHH 3 Varicela and Herpes Zoster
• Definition: Chickenpox and herpes zoster are different clinical entities caused by
a single family of herpes viruses, herpes viruses 3, or varicella zoster viruses [1].
Chickenpox is usually symptomatic, and herpes zoster represents latent reactiva-
tion of infection by varicella zoster virus and develops in approximately 20% of
adults and 50% of those who are immunosuppressed [2].
• Pathogenesis: Chickenpox: Flushing droplets in the air are the route of transmis-
sion of chickenpox; however, direct contact with gallbladder fluid is another
mode of spread. The incubation period is 11–20 days [2]. It is extremely conta-

varicella syndrome: In a
newborn patient in the
thigh region, an atrophic
area of approximately 2 cm
× 2 cm erythematous
violacea is evidenced
gious, and 80–90% of household contacts are susceptible and develop an obvious
clinical infection [2]. The affected individual is infectious 1–2 days earlier skin
lesions appear until all vesicles are crusted. During chickenpox infection, pri-
mary viremia occurs after viral replication in regional lymph nodes begins
2–4 days [2]. A cycle of viral replication in the liver, spleen, and other organs is
followed by a secondary viremia, which is inoculated throughout the body 14–16
days after exposure. During this period, the virus travels to the epidermis by
capillary invasion of endothelial cells. The varicella zoster virus subsequently
travels from mucocutaneous lesions to the cells of the dorsal root ganglia, where
it is latent until reactivation some time later [2]. Herpes zoster appears after the
reactivation of the varicella zoster virus, which occurs spontaneously, or it can be
induced by stress, fever, radiation, local trauma, or immunosuppression. During
a herpes zoster outbreak, the virus continues to replicate in the dorsal sheath
ganglion, causing painful ganglionitis. Neural inflammation and necrosis can
result in severe neuralgia that intensifies as the virus spreads through the sensory
nerve. The fluid from the vesicles can transmit the varicella zoster virus to sero-
negative individuals, generating chickenpox but not herpes zoster since this is the
reactivation of the latent varicella zoster virus from a primary infection. The
transmission rate is about 15% susceptible to contacts for zoster compared with
>70% for chickenpox [2].
• Clinical presentation: Chickenpox can begin in adults rather than in children
with a prodrome of mild fever, chills, and myalgia. This is followed by an itchy
rash, erythematous macules, and papules beginning on the scalp, face, and
spreading to the trunk and extremities. The lesions rapidly evolve in 12–14 hours
into clear 1–3 mm vesicles with surrounding red halos (rose petal). The number
of vesicles varies from one to many and frequently involves the oral mucosa.
Extension of the distal area of the lower extremities is common. Old lesions
evolve into pustules and scabs and heal in 7–10 days. The presence of lesions in
all stages is characteristic of varicella (Figs. 20.6 and 20.7). In immunocompro-
mised patients, varicella can have significant morbidity and mortality. These
patients frequently have a greater extent and an atypical skin rash with bleeding
or purpuric lesions. The lungs, liver, and central nervous system are frequently
involved [2]. Reactivation of the herpes zoster virus can develop at any time after
chickenpox. Herpes zoster begins with a prodrome of pruritus, paresthesia,
hyperesthesia, and severe pain (which can mimic a myocardial infarction, surgi-
cal abdominal pain, or tooth pain) in more than 90% of patients. These symp-
toms occasionally occur without subsequent lesions on the skin, a phenomenon
referred to as “zoster without herpes.” However, many of the patients develop a
pain in the eruption of vesicles grouped on an erythematous base in the distribu-
tion of a dermatome. Lesions can involve more than one dermatome and can
occasionally cross the midline. Edematous papules and plaques may precede
vesicles and progress to pustules or bullae (Figs. 20.8 and 20.9). Any site can be
affected; however, the trunk is the most frequent location, followed by the
face [2].
Herpesvirus 521
Fig. 20.6 Chickenpox:

Erythematous macules and
papules on the scalp, face,
ears, and neck spreading to
the trunk. Vesicles with
surrounding red halos (rose
petal) are also observed,
and few pustules in the
same patient.
• Diagnosis: The diagnosis is usually made by medical history (including previous

chickenpox or administration of the vaccine) and physical examination. Tzanc
quickly helps to confirm the diagnosis [1]. Herpes simplex, chickenpox, and her-
pes zoster are very similar in histopathology, the changes involving the nucleus
of epidermal cells with the development of a peripheral chromatin conglomerate
and a glass appearance homogeneous grinding, combined with ballooning of the
core. Vacuolization is the earliest cytoplasmic alteration. These changes start
focally in the basal layer but involve the entire epidermis. Biopsied lesions gen-
erally present an intraepidermal vesicle. This result forms two types of degenera-
tive changes: degenerative ballooning and reticular degeneration. The edema of
the cells and the loss of their cellular union separate them forming secondary
acantholysis. The cytoplasm of these cells becomes homogeneous and intensely
eosinophilic, and some are multinucleated (Tzanck cells). At the same time, the
basal layer of the epidermis is also destroyed, leading to the formation of a sub-
epidermal vesicle. These changes are known as a reticular degeneration that is
characterized by a progressive hydropic edema of the epidermal cells [3]. Other
diagnostic tools include viral cultura, detection of IgM or IgG antibodies and
PCR. Viral culture is a very specific test; however, it is not very sensitive, and it
is not available for more than one week. Serological techniques are only useful
in retrospect. PCR is a fast and highly sensitive technique [1].
• Differential diagnosis: For chickenpox: viral rashes, (Coxsackie and echovirus),
impetigo, contact dermatitis, and ricketsiosis [1]. Pityriasis lichenoides, PLEVA,
drug eruptions, and scabies [2]. For Herpes zoster: herpes simplex zosteriform,
contact dermatitis, insect bite, and burns [1].
Fig. 20.7 Chickenpox:

multiple vesicles with
surrounding red halos of
different sizes ranging
between 1 and 4mm, some
of them with an umbilicus
center.
VHH 4 (Epstein–Barr) Leucoplasia Vellosa
• Definition: Hairy leukoplakia is an asymptomatic, nonremovable, whitish plaque.

It is typically localized on the lateral aspects of the tongue and is caused by infec-
tion with the Ebstein–Barr virus (EBV) [1].
• Pathogenesis: EBV, which resides in B lymphocytes and in the tissue of the sali-
vary gland [2]. It infects the epithelium of the tongue and replicates in the same
cell lysis generated. Oral hairy leukoplakia is a common manifestation in patients
with human immunodeficiency virus (HIV) infection [1, 2]; however, in rare
cases, it can occur in other forms of immunosuppression (e.g., organ transplanta-
tion) [1, 2].
• Clinical presentation: Asymptomatic hyperplastic whitish plaques on the lateral
aspect of the tongue unilaterally or bilaterally. The lesions are typically asym-
metric and have undulations that accentuate the normal ridges of the tongue
(Figs. 20.10 and 20.11). There is no clear association with malignant transforma-
tion [1].
Herpesvirus 523
Fig. 20.8 Herpes zoster:

Eruption of vesicles
grouped on an
erythematous base in the
distribution of a
dermatome
Fig. 20.9 Herpes zoster:

Eruption of vesicles and
bullae grouped on an
erythematous base in the
distribution of a
dermatome
• Diagnoses: The diagnosis is clinical [1]. Foot biopsy with epidermal herplasia
with the absence of inflammatory infiltrate.
• Differential diagnosis: The main differential diagnosis is oral candidiasis [2].
VHH 4 (Epstein–Barr): Lipschutz Ulcers
• Definition: Lipschutz ulcers or acute genital ulcer (ulcus vulvae acutum) are
painful, sudden-onset ulcers on the vulva of girls and adolescents [1, 2].
Fig. 20.10 Hairy

leukoplakia: Whitish and
nonremovable plaque on a
lateral aspect of the tongue
Fig. 20.11 Hairy

leukoplakia: Whitish and
nonremovable plaque
localized on the lateral
aspects of the tongue
• Epidemiology/Pathogenesis: Lipschutz ulcers or acute genital ulcers, the inci-

dence is low with few cases reported in the literature [3]. They occur in girls or
adolescents without an active sexual life [4]. It is believed that the ulcers may
represent a nonspecific inflammatory response mainly to the Epstein–Barr virus
(EBV), and in a lower frequency, it is related to herpes simplex virus type 1
(HSV-1) [4].
• Clinical presentation: These are sudden, painful, single, or multiple ulcers, typi-
cally with a mirror arrangement (Fig. 20.12). They are located in the medial part
of the labia majora, minora, and perineum [1, 4]. Sometimes it manifests as gen-
Herpesvirus 525
Fig. 20.12 Lipschutz

ulcers: Multiple ulcers
with a gray-yellowish crust
located in labia majora,
minora, and perineum
eral malaise, fever, asthenia, myalgia, headache, pharyngitis, and lymphadenop-

athy [1, 4].
–– There are three clinical presentations:
Gangrenous vulvar ulcers are the most common form and are painful
ulcers with a gray-yellowish crust [4].
The chronic form is persistent undercut ulcers with significant edema [4].
Miliary ulcers are purulent, fibrin-filled, the size of the head of a pin with
inflammatory margins [4].
–– Ulcers tend to resolve spontaneously in 2–6 weeks [1].
• Diagnosis: For its diagnosis, a complete medical history must be made, includ-
ing questions about the patient's sexual life and even sexual abuse. The skin
biopsy may show superficial edema, hypergranulosis, with neutrophilic infiltra-
tion and ulceration with necroinflammatory tissue; however, it is not conclusive
(Fig. 20.13). Polymerase chain reaction (PCR) can be performed in the tissue to
identify viral genetic material from either EBV or HSV virus [1, 4].
• Differential diagnosis: Due to the few cases reported in the literature, it is a diag-
nosis of exclusion of multiple etiologies such as: sexually transmitted infections,
including syphilis; herpes simplex virus type 1 infection; noninfectious causes,
such as autoimmune, traumatic, and neoplastic [3–5].
Fig. 20.13 Lipschutz ulcers: Superficial edema, hypergranulosis with neutrophilic infiltration and
ulceration with necroinflammatory tissue (not conclusive)
VHH 5 Cytomegalovirus
• Definition: It is endemic in all parts of the world and is the most common cause
of intrauterine infections in humans. In immunocompetent hosts, 95% of infec-
tions are asymptomatic or subclinical. Neonates and immunocompromised indi-
viduals especially with AIDS, hematopoietic stem cell transplants, and patients
who received alemtuzumab are at risk of severe clinical manifestations from
CMV [1].
• Pathogenesis: CMV transmission is by body fluids including saliva, blood, urine,
semen, breast milk, and cervical and vaginal secretions. It also spreads indirectly
to contaminated fomites such as toys. Transplacental transmission of CMV to the
fetus is more likely in the setting of a primary infection in the mother, with 40%
of fetuses infected, compared with <1% in recurrent cases. CMV has an incuba-
tion period of 4–8 weeks [1].
• Clinical presentation: Although most are subclinical (>90%), a mononucleosis-
like syndrome similar to that of the Epstein–Barr virus has more presentation in
Herpesvirus 527
immunocompetent people. This syndrome has been described after blood trans-
fusion. Infected patients develop exudate sore throat, fever, chills, myalgia,
lymphadenopathy, and hepatosplenomegaly. May have atypical lymphocytes
and elevated liver enzymes. The skin presents a morbilliform, urticarial, pete-
chiae, or purple rash in a small percentage of patients. Generally self-limited,
there are rarely complications including hemolytic anemia, thrombocytopenia,
granulomatous hepatitis, Guillain-Barre, meningoencephalitis, myocarditis,
interstitial pneumonia, arthritis, and gastrointestinal and genitourinary manifes-
tations [1]. Congenital CMV causes mental retardation. Five to ten percent of
infected neonates have symptoms at birth such as hepatosplenomegaly, intrauter-
ine growth retardation, thrombocytopenia, chorioretinitis, seizures, and/or intra-
cranial calcifications. Cutaneous manifestations include purpuric papules and
hematopoiesis nodules that refer to bluberry muffin lesions such as petechiae,
purples, and vesicles [1] (Figs. 20.14 and 20.15). In AIDS patients, CMV can
cause chronic perineal or leg ulcers, chorioretinitis, esophagitis, colitis, and
pneumonitis, as well as endocrine, bone marrow, CNS, and kidney abnormali-
ties. The cutaneous manifestations are usually vesicles to nodules to verrucous
plaques [1].
• Diagnoses: The diagnosis is based on clinical suspicion but requires microbio-
logical confirmation. Culture for CMV is the gold standard, but it takes many
days. Specific antigens for CMV, DNA for CMV by PCR. Suspicious skin lesions
are due to biopsies Histopathology reveals spongiosis, a perivascular lympho-
cytic infiltrate in the upper dermis, with minimal epidermal changes; the charac-
teristic finding is the infection of endothelial cells that have an owl's eye is
pathognomonic [1] (Fig. 20.16).
• Differential diagnosis: The main differential diagnoses include Epstein–Barr
virus mononucleosis, toxoplasmosis, hepatitis, DRESS, and lymphoma [1].
Fig. 20.14 Cytomegalovi-

rus. Erythematous
ulcerated plaques at the
corners of the lips
Fig. 20.15 Cytomegalovi-

rus. Erythematous ulcers
on the labia majora of the
vagina
Fig. 20.16 Cytomegalovirus histology. A perivascular lymphocytic infiltrate in the upper dermis,
with minimal epidermal changes; the characteristic finding is the infection of endothelial cells that
have an owl's eye is pathognomonic
Herpesvirus 529
VHH7 Herpes Virus Type 7 Pytiriasis Rosea
• Definition: Pityriasis rosea (RP) is an acute, self-limited skin rash that typically
begins with a single scaly oval lesion on the trunk “herald plaque” and is asymp-
tomatic [2].
• Pathogenesis: PR has been associated with infection by human herpes virus
(HHV) 7 and in rare cases by HHV 6. HHV is a ubiquitous lymphotropic virus.
This virus mainly occurs in the first five years of life with a peak at 1–2 years of
age [1]. Its transmission via the salivary route is the most frequent and is only
replicated in the salivary glands of humans. Its pathogenesis is poorly understood
except when the CD4 molecule is used as a receptor. HHV-7 regulates the expres-
sion of CD4 molecules on lymphocytes and can regulate HIV infectivity; how-
ever, both viruses compete for the same receptor [1].
• Clinical presentation: RP is characterized by a single, larger initial lesion on the
skin on the trunk, called herald plaque, which is followed in a few days or weeks
by numerous smaller lesions on the trunk (Figs. 20.17, 20.18, and 20.19).
Typically, the lesions are oval or rounded, salmon-pink in color and in rare cases
hyperpigmented, especially in tall phototypes. In the periphery, it presents a fine
collarette desquamation that generally does not reach the outer edge of the
lesions. It is usually located on the trunk or on areas covered by clothing but is
sometimes on the neck or proximal extremities in a “Christmas tree” distribu-
tion. The lesions are usually asymptomatic although itching may occur, which is
severe in 25% of cases. Flu-like symptoms including chills, headache, nausea,
loss of appetite, fever, and arthralgias have been reported in a minority of
patients [2].
• Diagnoses: The diagnosis is clinical. There are methods to detect HHV-7 includ-
ing serological tests, PCR, viral culture, and immunohistochemical staining.
• Differential diagnosis: The main differential diagnoses include viral exanthe-
mas, syphilitic roseola, drug reactions and psoriasis drops, among others.
Fig. 20.17 Pytiriasis

rosea. Multiple oval scaly
salmon-pink plaques, in
the abdominal region

salmon-pink plaques, in
the trunk area
VHH 8 Sarcoma of Kaposi
• Definition: Kaposi's sarcoma is a multifocal tumor originating from endothelial

cells, associated with infection by human herpes virus (HHV) type 8 [1].
• Etiopathogenesis: HHV-8 is a member of the herpesviridae subfamily of the
genus Rhadinovirus [2], whose genetic material is homologous to the human
genes that regulate apoptosis, proliferation, and angiogenesis [2]. This virus can
infect both vascular and lymphatic endothelial cells and induce transcriptional
reprogramming, which leads to an expression of lymphoangiogenic molecules
and infection of blood vascular endothelial cells [1]. The endothelial nature of
the tumor is now accepted, but whether the phenotype is vascular, lymphatic, or
mixed remains controversial. Most of the cells that form a SK plaque or nodule
are clearly spindle cells, unlike normal endothelial cells; however, they express
pan-endothelial markers CD31. These spindle cells also coexpress markers of
Herpesvirus 531

salmon-pink plaques and
papules, in the back
blood vascular differentiation (CD34) and lymphatic differentiation (VEGFR-2,

podoplanin, and LYVE-1) [1, 2].
• Clinical presentation: The lesions typically start as erythematous-violaceous or
bluish macules, which converge, progressively infiltrate to form plaques and
later tumors. During tumor progression, the color may change to brown and
become more hyperkeratotic. It can compromise any part of the skin and mucosa
(Fig. 20.20, 20.21, 20.22, 20.23, 20.24, 20.25, 20.26, and 20.27), including the
oral mucosa (Fig. 20.28) and the gastrointestinal tract. It has a predilection for
acral areas. In more rare cases, it can affect the lymph nodes and lungs. There are
four clinical subtypes of Kaposi sarcoma (KS) [1, 2].
–– Classic SK: It is typical in Caucasian men over 60 years of age. This subtype
usually affects the lower limbs, with a chronic but benign course with slow
progression [2]. In rare cases, lesions may occur in the palate or gastrointesti-
nal tract that are usually asymptomatic [1].
Fig. 20.20 Sarcoma of Kaposi. Multiple nodules and tumors violaceous in facial region and trunk
–– Endemic African KS: It is an endemic subtype in Central Africa, independent

of infection by the human immunodeficiency virus (HIV). It is more common
in men and is seen in adults between the ages of 35 and 39 [2]. It has four
clinical forms that are nodular, florid, infiltrative, and lymphadenopathic [1].
–– KS associated with immunosuppression: It occurs in patients with prolonged
immunosuppression by drugs, mainly in those who have received an organ
transplant, mostly kidney. It can resolve completely by withdrawing immuno-
suppressive therapy. Depending on the degree of immunosuppression, the
commitment can be extensive.
–– KS associated with HIV: It is in advanced stages of infection by the human
immunodeficiency virus (HIV), usually in patients with CD4 T lymphocyte
counts less than 500 cells/mL. Depending on the degree of immunosprusion,
patients may present single lesions or generalized and systemic involvement
in severe cases [1].
• Diagnosis: The diagnosis is clinical, but histopathological confirmation is
required. In histology, there is no difference between the different clinical sub-
types, these vary with the stage of the lesion. The patch stage presents lesions
that show a slight increase in the number of dermal vessels outlined by slightly
irregular endothelial cells, and there is superficial dermal proliferation of the
Herpesvirus 533
Fig. 20.21 Sarcoma of

Kaposi. Multiple nodules
and macules erythematous,
some of them converge in
the trunk
small, angled vessels. Bordered by poorly visible endothelial cells, suggesting

lymphatic involvement. In the surrounding dermis, focal deposits of hemosiderin
and extravasated erythrocytes can be found, as well as a moderate inflammatory
infiltrate [2]. Plaque stage: The pathology is more characteristic and reveals
extensive vascular proliferation at all levels of the dermis with multiple dilated
and angled vascular spaces degrading collagen and leaving a spongy network of
collagen tissue [2] (Fig. 20.29). A characteristic sign of KS papules is the pres-
ence of solid cords and fascicles of spindle cells with dilated irregular vascular
canals surrounding a preexisting vessel (promontory sign) [3] (Figs. 20.30
and 20.31).
• Differential diagnosis: The main differential diagnoses are: bacillary angiomato-
sis, well-differentiated angiosarcoma, capillary malformations, microvenular
hemangioma, spindle cell hemangioma, skin metastases, leukemia, lymphoma
cutis, lymphatic, and venous malformations [1].

Kaposi. Violaceous
nodules that converge to
form large tumors in the
lower extremities
Papillomavirus
Viral Warts and Flat Warts
• Definition: Viral warts are a common infectious skin disease caused by the
human papillomavirus (HPV).
• Etiopathogenesis: HPV is a ubiquitous DNA virus that belongs to the
Papillomaviridae family.
–– The HPV genome contains three functional regions [1–3]:
Early genes (E1, E2, E4, E5, E6, and E7): These genes are in charge of
controlling replication, transcription, and nuclear proliferation. They are
generally expressed shortly after infection [1, 3].
Late genes (L1 and L2): These genes encode the structural proteins of the
capsid and are expressed in later stages of infection [1, 3].
Long control region: This region contains the regulatory sequences that
coordinate the replication and transcription of early and late genes [1, 3].
Papillomavirus 535

Kaposi. Multiple macules
and nodules erythematous,
in the face
–– Infection begins in the basal cell layer, where the viral genome is incorporated
into the nucleus, maintaining a stable copy number of viral genomes. As basal
cells migrate and differentiate in the superficial layers of the epithelium, com-
plete vegetative replication of viral DNA and expression of structural proteins
occurs; with assembly of infectious virions in the most superficial layer of the
epithelium, where they are released with normal desquamation [1, 3]. This
causes benign cell growth in low-risk and cutaneous types; and aberrant with
persistent infection by several high-risk HPV types, mainly 16 and 18 [1, 2].
–– HPV infection is spread mainly by direct contact (skin-to-skin) from an
infected lesion. In plantar warts, fomites on damp surfaces (gym floor, swim-
ming pool) are a potentially important source of infection. Infections move to
new locations by autoinoculation [1, 2]. HPV infection and its manifestations
are more common in immunocompromised patients [2]. HPV completes its
life cycle only in differentiated epithelial cells [1].
–– There are around 150–200 types of HPV, more than 40 of which infect the
skin and genital mucosa [1–3] and are associated with specific clinical mani-
festations [1–3]:

Kaposi. Violaceous
nodules, some of them
hyperkeratotic on the
left leg
Common warts: They are more frequently associated with HPV subtypes
2, 27, and 57 and less frequently with subtypes 1, 3, and 4 [2].
Plantar warts: The HPV subtypes of vulgar warts are the same as those
involved in plantar warts; however, they have a predominance of subtypes
1 and 2 that are associated with the mirmecia and mosaic forms, respec-
tively [2].
The development of plantar warts is favored by factors such as plantar
hyperhidrosis, acrocyanosis, local trauma, fissures, and skeletal or ortho-
pedic malformations [2].
Flat warts: They are produced predominantly by HPV subtypes 3 and 10,
but subtypes 10, 28, 38, 42, 49, 75, and 76 may also be involved [1, 2].
Butcher's warts: HPV type 7 is the most common. Recurrent trauma and
maceration are predisposing factors [2].
Filiform warts: They are generally associated with HPV type 3 [2].
Papillomavirus 537

Kaposi. Hyperkeratosic,
violaceous nodules, on the
lower extremities

Kaposi. Multiple macules
and nodules erythematous-
brown, in the arm

Kaposi. Dark brown-brown
macules and plaques on
lower limbs

Kaposi. On the palate,
there are multiple lobulated
violaceous erythematous
tumors with a shiny
smooth surface
Papillomavirus 539
Fig. 20.29 Sarcoma of Kaposi. Histology. Extensive vascular proliferation at all levels of the
dermis with multiple dilated and angled vascular spaces, degrading collagen and leaving a spongy
network of collagen tissue
Fig. 20.30 Sarcoma of Kaposi. Histology. HHV-7 immunohistochemical staining

Fig. 20.31 Sarcoma of Kaposi. Histology. Solid cords and fascicles of spindle cells with dilated
irregular vascular canals surrounding a preexisting vessel
Clinical presentation: The clinical manifestations appear at any age but are more
frequent between 10 and 16 years; vary according to anatomical location and
viral type [2, 3]:
–– Vulgar warts (common): They are the most common type. They are character-
ized by exophytic papules with a well-defined border; with an irregular hyper-
keratotic surface. They vary from 1 to several millimeters in diameter and can
be euchromic or brown. A common finding is thrombosed capillaries, which
give them a stippled appearance and a blackish color. They are most often
seen on the hands (Fig. 20.32), but any part of the body may be affected,
including the genital skin [1–3].
–– Plantar warts: They appear as hyperkeratotic, endophytic, and often very
painful papules or plaques. Thrombosed capillaries often give these warts a
stippled appearance, with blackish hyperkeratosis, a finding that helps differ-
entiate it from a tylosis. They are usually asymptomatic, but due to endo-
phytic growth in the pressure areas, they can become very painful. There are
two clinical forms of plantar warts [1, 2]:
Mirmecia: Generally, it is a single lesion, well circumscribed; with a
hyperkeratotic ring that partially covers the surface and microbleeds [2].
Papillomavirus 541
Fig. 20.32 Vulgar warts:

On the dorsal side of the
hand, multiple
hyperkeratosic papules,
with thrombosed vessels
Fig. 20.33 Mosaic warts:

On the sole of the foot,
multiple papules that
converge to form
hyperkeratic plaques
Mosaic warts: They are formed by the coalescence of multiple lesions,

usually superficial; generating an extensive plaque with a hyperkeratotic
surface (Fig. 20.33). Although they are more frequently located on plants,
they can also be seen on the hands and the periungular region [2].
–– Flat warts: They are characterized by small papules, with a smooth surface,
brownish erythematous or euchromic. They usually affect the face, forearms,
the back of the hands, and the legs [2, 3].
–– Periungular or subungular warts: They appear in the contour of the nails and
often converge forming extensive plates with nail deformity; they can be pain-
ful when they compromise the bed (Fig. 20.34). They are difficult to treat
since this can lead to alteration of the nail matrix and permanent dystro-
phy [2, 3].
–– Butcher's warts: This type of wart is characterized by extensive profuse warts
on the hands, which particularly affect workers who have contact with raw
meats [2, 3].
–– Filiform warts: They are characterized by elongated, erythematous, or euk-
romic exophytic lesions, which at the end present keratotic projections
(Fig. 20.35). They are mainly found in the cephalic, perioral and shaving
areas [2, 3].
Fig. 20.34 Periungular or subungular warts: In the periungular area, there are multiple hieprke-
ratic papules that converge to form plaques
Fig. 20.35 Filiform warts:

the upper right eyelid
shows a filiform papula of
2 mm × 2 mm
Papillomavirus 543
Fig. 20.36 Viral warts: Parakeratosis, koilocytes with prominent vacuolated cytoplasm and small
pignotic nucleus are evidenced in the upper layers of the epidermis
• Diagnosis: The diagnosis is clinical. Skin biopsy is not done routinely.

Histopathology shows epidermal acanthosis, papillomatosis, hyperkeratosis,
parakeratosis, and parabasal cell hyperplasia. Koilocytes are a characteristic
finding of HPV infection; it refers to the presence of atypical keratinocytes, with
irregular hyperchromatic nuclei surrounded by a perinuclear halo [1, 2]
(Fig. 20.36).
• Differential diagnosis: The main differential diagnoses include seborrheic kera-
toses, hypertrophic actinic keratoses, nevi, irritated skin tags, squamous cell car-
cinoma. Plantar tylosis sometimes causes diagnostic difficulty with plantar
warts. In periungular warts, it is important to bear in mind that in the event of a
recalcitrant lesion with a doubtful clinical appearance (flat, erythematous, highly
hyperkeratotic, ulcerated, or with spontaneous bleeding), a biopsy should be per-
formed to rule out squamous cell carcinoma [1, 2].
Condylomas and Bowenoid Papulosis
• Definition: Condylomas are the clinical manifestation of infection of the mucous

membranes (genital and oral) by the human papillomavirus (HPV).
• Etiopathogenesis: HPV is a ubiquitous DNA virus that belongs to the
Papillomaviridae family.
–– The HPV genome contains three functional regions [1–3]:
Early genes (E1, E2, E4, E5, E6, and E7): These genes are in charge of
controlling replication, transcription, and nuclear proliferation. They are
generally expressed shortly after infection [1, 3].
Late genes (L1 and L2): These genes encode the structural proteins of the
capsid and are expressed in later stages of infection [1, 3].
Long control region: This region contains the regulatory sequences that
coordinate the replication and transcription of early and late genes [1, 3].
–– Infection begins in the basal cell layer, where the viral genome is incorporated
into the nucleus, maintaining a stable copy number of viral genomes. As the
basal cells migrate and differentiate in the superficial layers of the epithelium,
a complete vegetative replication of viral DNA and the expression of struc-
tural proteins occurs, with assembly of infectious virions in the most superfi-
cial layer of the epithelium, where they are released with normal desquamation
[1, 3]. This causes benign cell growth in low-risk and cutaneous types; persis-
tent infection with several high-risk genital HPV types, mainly 16 and 18, is
firmly established as the cause of squamous cell carcinoma of the mucosa and
cervix [1, 2].
–– HPV infection is transmitted mainly by direct contact from an infected lesion.
Genital infection is usually contracted during sexual intercourse [1, 2].
Additionally, genital HPV infection can be transmitted to the mouth and
upper respiratory tract perinatally, from mothers to newborns [2]. Infections
pass to new locations by autoinoculation [1]. HPV infection and its manifesta-
tions are more common in immunocompromised patients. Infection of the
anal and genital mucosa by HPV is very common and occurs from the first
sexual intercourse [1–3].
–– The main risk factors for infection are young age of initiation of sexual inter-
course, greater number of recent or lifetime sexual partners, predisposition
(lack of circumcision in men), and lack of preventive measures (non-use of
condoms or lack of vaccination) [2].
–– HPV completes its life cycle only in differentiated epithelial cells. There are
about 150–200 types of HPV, more than 40 of which infect the skin and oral
and genital mucosa [1–3].
Genital warts are caused mostly by HPV subtypes 6 and 11, although other
types can be detected, such as 16 and 81 [2, 3].
Papillomavirus 545
Bowenoid papulosis is almost always due to HPV 16. Although there is

still controversy, it is generally accepted that this entity corresponds to a
low-risk intraepithelial squamous cell carcinoma, in which the basaloid
appearance, low differentiation and, generally, the presence of vulvar der-
matosclerosis, an effect cytopathic changes of HPV, are markers of viral
origin [2, 3].
• Clinical presentation:
–– Anus-genital warts or condylomas: They are characterized by echromic or
brown erythematous papules, which can become very pigmented; its surface
is rough, papillomatous [1, 3]. The degree of keratinization of the lesions is
proportional to that of the epithelium in which it is found, whether it is
mucous, semi-mucous (anal margin, labia minora, and glans) or cutaneous
[2]. They are generally multiple lesions that can be isolated or grouped [1].
They mainly involve the external genitalia, the groin, the gluteal fold, the
perineum, and the anal canal; but they can be located in the entire area between
the navel and the upper part of the gluteal fold [2, 3]. The size varies from a
few millimeters to several centimeters, reaching lesions that obstruct the anal
canal in immunocompromised patients, mainly those infected by the human
immunodeficiency virus (HIV) [1, 2].
Condylomata acuminata: When the lesions are very large, with a rough
surface with a cockscomb or cauliflower appearance, they are known as
condylomata acuminata [2] (Figs. 20.38 and 20.40).
Perianal condylomas: They occur more frequently in patients with a his-
tory of anal intercourse, and involvement of the anal canal is not uncom-
mon. Due to the location, patients consult when the lesions have reached a
considerable size and usually perceive a “lump.” They can occasionally
cause itching or pain. They can become superinfected and necrotic [2, 3]
(Fig. 20.37).
–– Bowenoid papulosis: It occurs classically in young adults, mainly men. It is
characterized by brown, flattened, smooth-surfaced papules. Although they
can be single or isolated, in most cases, they are multiple and confluent
(Figs. 20.39 and 20.41). They involve the same sites as anogenital warts.
Bowenoid papulosis is included in the classifications of level 3 intraepithelial
neoplasms: CIN III in the vulva or PIN III in the penis and AIN III in the anal
margin; however, it is considered a good prognosis since its evolution to inva-
sive carcinoma is relatively rare. However, it is a marker of high-risk HPV
infection and constitutes a potential source of contamination of couples;
therefore, dysplastic neck lesions should be treated and detected in women
with BP or in affected male partners [2, 3].
• Diagnosis: The diagnosis is mainly clinical. There are some diagnostic aids.
–– Acetic acid test: Subclinical HPV infections can be more easily visualized
with the application of 3–5% acetic acid, which produces a whitening of the
Fig. 20.37 Perianal

condylomas. In the
perianal region, it presents
violaceous plaques, and
verruciform surface
lesions in 3–5 minutes. However, this test can also be positive in some inflam-
matory dermatoses such as psoriasis or lichen planus [1, 2].
–– Skin biopsy: Skin biopsy is not performed routinely in condylomata but
should always be performed when Bowenoid papulosis is suspected.
Histopathology shows epidermal acanthosis, papillomatosis, hyperkeratosis,
parakeratosis, and parabasal cell hyperplasia (Fig. 20.42). Koilocytes are a
characteristic finding of HPV infection, refers to the presence of atypical
keratinocytes, with irregular hyperchromatic nuclei surrounded by a
perinuclear halo. Intraepithelial lesions additionally present increased mitotic
figures in the upper half of the epidermis [3].
–– In all patients with external condylomata, lesions in the urethral meatus and
lesions of the anal canal should be looked for. While anoscopy should be sys-
tematic in patients who have perianal and marginal condylomas, urethroscopy
is only indicated in patients with signs of urinary obstruction [2].
• Differential diagnosis: The main differential diagnoses of anogenital warts
include condylomata planes of secondary syphilis and molluscum contagiosum.
Poxvirus 547
Fig. 20.38 Condylomata

acuminata. In the perianal
region, multiple greyish-
brown tumors, cauliflower
surface, and mummies
Biopsy is indicated in all patients with atypical, recalcitrant, or indicative ana-

tomical locations of possible malignant transformation [2].
Poxvirus
Molluscum Contagiosum
• Definition: Molluscum contagiosum is a viral disease caused by the molluscum

contagiosum virus of the poxvirus family and is characterized by pearly lesions
on the skin [1–4].
• Etiopathogenesis: Molluscum contagiosum is a double-stranded DNA virus that
is particularly adapted to human skin, both in terms of growth and evasion of the
immune system [1]. It mainly affects the skin and in rare cases the mucous mem-
Fig. 20.39 Bowenoid

papulosis. In the foreskin,
multiple flat pale brown
papules, smooth surface,
and some converge to form
plaques
branes; the initial inoculation of the virus generally occurs through a wound in
the skin [1, 2, 4]. The virus attaches itself to the cells of the epidermis, introduces
its DNA into the cytoplasm, becomes incorporated into the DNA of the host cell,
and assumes control of its genetic machinery. The viral DNA replicates and is
released into the cytoplasmic space of the host cell, which increases in size and
eventually dies, releasing new viral particles that infect new epidermal cells [1].
The infection is confined to the epidermis, bypassing the basement membrane,
which protects it from the immune system; however, it eventually induces a local
response that leads to spontaneous resolution of the lesions and seroconversion
[1, 2]. Molluscum contagiosum lesions are highly contagious. The main form of
transmission is direct contact. In children, it occurs during periods of play, while
in adults it frequently occurs during sexual contact. Therefore, the appearance of
lesions in the genital or pubic area should alert us to the possible presence of
other sexually transmitted diseases [1–4].
Poxvirus 549
Fig. 20.40 Condylomata

acuminata. Solitarie and
coalescing brown papules
that have a verruciform
appearance in the vulvar
region
Fig. 20.41 Bowenoid

papulosis. In the
balanopreputial sulcus and
dorsum of the penis,
grayish-brown plaques,
smooth surface, and
well-defined
• Clinical presentation: Classically, it presents as euchromic, cupuliform papules,

with a smooth surface and with a characteristic central umbilication [1–4]
(Fig. 20.43). They usually measure between 1 and 5 mm in diameter and the
number of lesions in immunocompetent patients is generally less than 20; how-
ever, it can be higher [2]. A localized contact dermatitis around the lesion can
often be seen, corresponding to an immune response of the host against the virus
[1, 4]. When the lesions are traumatized or “squeezed” a grayish-white material
is released [2].
Fig. 20.42 Condylomata acuminata. Epidermal hyperplasia, parakeratosis, koilocytosis, and

papillomatosis
Fig. 20.43 Molluscum

contagiosum. Multiple
euchromic, cupuliform
papules with a central
umbilication located in
abdomen
Poxvirus 551
–– Most patients are children or young adults, but it can present at any age. It is
highly prevalent in individuals with atopic dermatitis, probably due to the
alteration of the skin barrier and immunological changes [2, 3].
–– It more frequently involves the skin folds, trunk, buttocks, and thighs [4]. In
rare cases, it can affect the palms, soles, and the mucous membranes of the
lips and conjunctivae [2]; in adults, they are commonly seen in the pubic and
genital area from sexual contact, and the infection is spread by scratching or
shaving [2].
–– Individual lesions persist for 6–12 weeks and eventually resolve spontane-
ously, leaving a scab or small depressed scar. The resolution of the entire
outbreak can take between 12 and 18 months [1–3].
–– In immunocompromised patients, whether due to HIV virus infection or other
causes, the clinical presentation is more severe, persistent, with atypical loca-
tions and larger and more numerous lesions [1, 2] (Fig. 20.44).
• Diagnosis: The diagnosis is clinical.
–– Dermoscopy is useful, with a radial, crown or punctate vascular pattern.
–– Skin biopsy is not done routinely. Histopathology shows large intracytoplas-
mic inclusion bodies, within epidermal keratinocytes, known as mollusk bod-
ies or Henderson-Patterson bodies [2, 4] (Fig. 20.45).
• Differential diagnosis: The main differential diagnoses are flat viral warts, basal
cell carcinomas, intradermal melanocytic nevi, and in immunocompromised
patients, it must be differentiated from cryptococcosis [2, 4].
Fig. 20.44 Facial

molluscum contagiosum.
Multiple euchromic, cup
uliform papules with a
central umbilication
located in upper and lower
eyelids of an
immunosuppressed patient
Fig. 20.45 Molluscum

contagiosum histology.
Henderson-Paterson bodies
on epidermal keratinocytes
Other Virus Diseases
HTLV Infective Dermatitis
• Definition: Infective dermatitis is a rare and severe chronic type of eczema asso-
ciated with human T-cell lymphotropic virus type 1 (HTLV-1) infection [1].
• Etiopathogenesis: HTLV-1 infection is worldwide [2]. It is a disease considered
rare [2]; however, due to the introduction of better diagnostic methods, its inci-
dence has been increasing [1]. Certain regions of Japan, sub-Saharan Africa, and
Central America are endemic areas. In South America, there have been cases in
Colombia, Bolivia, Ecuador, Brazil, and Peru [1].
Other Virus Diseases 553
–– HTLV-1 transmission occurs mainly vertically (in the birth canal or through
breast milk) in children and through sexual contact or contaminated blood
products in adults [1, 2].
–– HTLV-1 is an oncovirus, which has regulatory proteins encoded in the TAX
region, which generate immune dysregulation, cell lymphoproliferation, and
the production of pro-inflammatory lymphokines and immunoglobulin G
with demyelinating effects. Infective dermatitis is a risk factor for developing
tropical spastic paraparesis in children and young adults, and T-cell lym-
phoma and leukemia in adulthood [2].
• Clinical presentation: It most frequently affects female children, with an average
age of onset at two years of life [1]. It manifests as erythematous papules and
vesicles, confluent forming extensive plaques, crusty, exudative, excoriated, and
pruritic (Figs. 20.46 and 20.47). It more frequently involves the scalp, the retro-
auricular region, and the skin folds (armpits, inguinal area, and neck), in adults
the face. It can be associated with watery rhinorrhea and blepharoconjunctivitis.
In severe cases, it can become generalized and present lymphadenopathy. It is
common for the lesions to become superinfected, in most cases by Staphylococcus
aureus or Streptococcus pyogenes [1, 2].
Fig. 20.46 HTLV infective

confluent, that form
extensive plaques with
crust on the surface,
whitish and serohematic in
some areas, involving the
scalp, outer ear, and face,
mainly the paranasal skin
and eyelid margin. Notice
the bilateral
blepharoconjunctivitis.
Fig. 20.47 HTLV infective

confluent that form
extensive plaques with
crust on the surface,
serohematic in the earlobe,
and presence of
excoriations, involving the
scalp, neck, the
retroauricular region, outer
ear, and face
• Diagnosis: For the diagnosis, a minimum of four of Lois la Grenade's diagnostic

criteria must be met, of which 1, 2, and 5 [1, 2] are mandatory.
–– The criteria are:
1. Eczema of the scalp, armpits, groin, outer ear, retroauricular area, eyelid
margin, paranasal skin, and neck. (There must be at least two affected
areas for it to be appositive.)
2. Chronic watery rhinorrhea without other signs of rhinitis or desquamation
of the nostrils.
3. Recurrent chronic dermatitis with prompt response to appropriate antibi-
otic treatment, but with prompt recurrence upon abandonment of it.
4. Usual onset in early childhood.
5. Seropositivity for HTLV-1.
Other Virus Diseases 555
Fig. 20.48 “Slap”

erythema. Bilateral
erythematous irregular
macules over cheeks
–– Confirmation of infection with the detection of antibodies against different

viral antigens can be done by ELISA and confirmed with Western Blot, immu-
nofluorescence or radioimmunoprecipitation techniques. Polymerase chain
reaction (PCR) can also be used to detect viral DNA in peripheral blood
mononuclear cells and tissue samples, which also allows determining the
viral load [1, 2].
–– The blood count may show anemia and lymphocytosis with atypical lympho-
cytes. ESR is usually elevated. Peripheral blood immunoglobulins, CD4 and
CD8 lymphocytes, and their ratio (CD4/CD8) are usually increased [1, 2].
–– Histopathology shows hyperkeratosis, parakeratosis, and psoriasiform acan-
thosis; Mild spongiosis and Munro's microabscesses. There may also be vacu-
olar degeneration of the basalis. In rarer cases, epidermotropism and Pautrier's
microabscesses can be found. A superficial perivascular or lichenoid lympho-
cytic infiltrate can also be seen, with a predominance of lymphocytes, without
mitosis or atypia, in the dermis [1, 2].
• Differential diagnosis: The main differential diagnoses are atopic dermatitis and
seborrheic dermatitis. Psoriasis, intertrigo, and mycosis fungoides [1].
Fig. 20.49 Maculopapular

rash. Geographical
macules affecting trunk
and extremities
Parbovirus B19 Infectious Erythema
• Definition: Fifth disease or fifth disease is a childhood viral rash that is caused by
infection with parvovirus B19 [1].
• Etiopathogenesis: Parvovirus B19 is a DNA virus, whose incubation period is
6–14 days. The infection is transmitted through respiratory secretions [1].
• Clinical presentation: It mainly involves children between 5 and 10 years old.
Has peak seasons [1].
–– It is characterized by nonspecific and mild general symptoms such as fever,
headache, upper respiratory, and gastrointestinal symptoms, lasting two to
five days [2]. Subsequently, the skin lesions that develop in three phases are
presented [1, 2]:
References 557
Erythema “slap”: It is characteristic of the disease. It manifests as a bilat-

eral and symmetrical erythema on the cheeks, with respect to the perioral
region [1, 2] (Fig. 20.48).
Maculopapular erythema: It occurs 24–48 hours after the previous one. It
mainly affects the lower limbs and buttocks but later becomes generalized,
acquiring a figurative appearance such as lace, garland, or geographical
map and can last between one and three weeks [1, 2] (Fig. 20.49).
Fluctuating rash: This phase of the disease is fickle. It is characterized by
a variable eruption depending on the light or the temperature, sometimes
even from emotions. It can remain for months and be recurrent [1].
–– Parvovirus B19 can also be responsible for other clinical pictures such as
purpura in gloves and stockings. It has also been associated with complica-
tions such as arthralgia and acute anemia crisis in patients with chronic hemo-
lytic anemia [1].
• Diagnosis: The diagnosis is mainly clinical. It can be confirmed by specific viral
serology (presence of IgM) or by detection of the virus by PCR [1, 2].
• Differential diagnosis: The main differential diagnoses are other viral exanthe-
mas and drug reactions [1, 2].
References
matosis). In: Dermatology, vol. II. 202. Third ed; Elsevier Saunders. 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
4. Goldsmith, L. Katz, S., et al. Benign epithelial tumors, hamartomas and hyperplasias.
Fitzpatrick’s dermatology in general medicine, 8th. McGraw Hill. New York. 1319–1336. 2012
Chapter 21
Sexually Transmitted Diseases
Syphilis
• Definition: Syphilis is a sexually transmitted disease caused by the spirochete

Treponema pallidum. It is spread by direct contact with syphilitic lesions or ver-
tical route during pregnancy [1–3].
• Clinical presentation: Syphilis is categorized into different stages.
–– Primary syphilis: The incubation time is 21 days, but it can go from 10 to
90 days. It typically presents with a painless papule or ulcer (syphilitic chan-
cre) at the site of infection, usually genitalia. It can occur 1–3 weeks before
serological tests are positive, last for weeks, and heal spontaneously without
treatment [1–3].
–– Secondary syphilis: Starts 6–8 weeks after the initial injury, although they
may overlap. It is known as the great mimic because it can present a wide
variety of manifestations, from a skin rash to systemic compromise that
includes: low-grade fever, general malaise, headache, osteomyalgia, lymph-
adenopathy, photophobia, polyarthralgia, anemia, leukocytosis, kidney
involvement, and hepatitis. At this stage, serology is usually positive [1–3].
The skin lesions are asymptomatic, more evident on the trunk, with a ten-
dency to cluster; generalize characteristically involving the palms and soles,
genitalia, and intertriginous areas.
Initially they are pink macules, and it is known as syphilitic roseola; later
they become pigmented and show superficial desquamation, reminiscent
of pityriasis rosea, and guttate psoriasis [1–3] (Figs. 21.1 and 21.2).
Over time, they become more infiltrated, with a psoriasiform appearance
and may show ring configurations; occasionally, they may present circum-
scribed areas of anetoderma [3]. When it affects the hairline and the lateral
aspects of the neck, it is known as the crown and collar of the venus [3].

https://doi.org/10.1007/978-3-030-84107-2_21
560 21 Sexually Transmitted Diseases
Fig. 21.1 Syphilis.

Macules and plaques, pink
color with scaly in the
trunk
Fig. 21.2 Syphilis. Papules and plaques, erythematous with scaly in the palms
Condylomata latos are produced by the erosion of the papules in intertrigi-

nous areas, mainly perianal and in the groin. (Fig. 21.3). These are usually
humid with a high content of treponemes, therefore highly infectious [1].
Eroded patches with a slightly whitish halo are seen on the mucous mem-
branes, mainly the tongue, lips, and soft palate [1, 3].
Alopecia is common as part of the skin compromise, with areas of irregu-
lar depopulation that give it a moth-eaten appearance, or as telogen efflu-
vium secondary to systemic compromise [3] (Fig. 21.4).
Syphilis 561
Fig. 21.3 Syphilis.

Condyloma latos, caused
by erosion of papules in
the perianal area
Fig. 21.4 Syphilis.

Alopecia in the scalp with
areas of irregular
depopulation that give it a
moth-eaten appearance
Lúes maligna is a rare presentation of nodular lesions that can occur in

association with HIV [1, 2].
–– Latent syphilis: If the patient is left without treatment, it can be cured with a
variety of sequelae. There may be a relapse in the first 2 years of mucocutane-
ous lesions, particularly affecting genitalia, palms, and soles. This stage con-
tinues to be infections. After 2 years, it passes to an asymptomatic phase with
a negative serology, in this phase a spontaneous cure can occur [1–3].
–– Tertiary syphilis: One-third of untreated patients progress to this phase, which
occurs 3–7 years after infection. It is characterized by the presence of gums,
chronic granulomatous lesions that develop several years after the primary
inoculation and are not infectious; they soften, ooze, and leave punched ulcers
with a yellowish base. There may also be firm, solitary, or scant papules or
nodules;, confluent in an annular, asymmetric pattern, which may present a
superficial scaling reminiscent of psoriasis. Skin lesions in this phase heal,
leaving scars and occur mainly on the upper third of the legs, chest, face, and
scalp. Gums can occur on the mucosa, with a diffuse infiltration of the tongue,
with whitish plaques, erosions, and fissures [1–3]. Systemic involvement
includes neurosyphilis that can result in dorsal tabs (diplopia, paresthesias,
loss of sphincter control, visceral crisis, Argyll-Robertson pupils, and demen-
tia) and cardiovascular syphilis [1, 3].
–– Congenital syphilis: In early pregnancy, abortions or stillbirths covered in
blisters occur. Later in pregnancy, the neonate may present with a rash similar
to secondary syphilis, hepatomegaly, and lung and bone involvement. Late
congenital syphilis presents in childhood with features similar to tertiary
syphilis, including perforation of the palate and nasal septum as a result of
gums, tibia sable from periostitis, and Hutchinson’s triad (abnormal teeth,
interstitial keratitis, and deafness) [1–3].
• Diagnosis: Since the culture of T. pallidum is not possible and PCR is of low
sensitivity, the diagnosis is based on serology or direct visualization of the patho-
gen either by direct dark-field microscopy of the exudate of the lesions, or in
histopathology with silver stains. Traditionally, a non-treponemal test (RPR or
VDRL) is performed, if it is positive, a confirmatory treponemal test is per-
formed (FTA-ABS, TP-PA, EIAs, or CIA). Non-treponemal tests are subse-
quently used as a control during management, as they become nonreactive with
successful treatment; unlike treponemal tests, they remain detectable for life
despite successful treatment. However, a reverse algorithm sequence has recently
been used, in which a treponemal test is performed first; if it is positive, a non-
treponemal test is performed to monitor the treatment; if it is negative, a second
treponemal test is performed to evaluate concordance. Patients with signs and
symptoms of neurosyphilis require cerebrospinal fluid analysis. There are also
rapid screening tests in development [1–3].
• Differential diagnosis: The differential diagnosis of primary syphilis is mainly
that of genital ulcers, since it is the most common site of inoculation. The most
frequent are chancroid, lymphogranuloma venereum, genital herpes, and trauma.
Lymphogranuloma Venereum 563
The differential diagnosis of secondary and tertiary syphilis is broad and includes
papulo-scaly lesions, such as pityriasis rosea and psoriasis [1–3].
Lymphogranuloma Venereum
• Definition: Lymphogranuloma venereum (LGV) is a sexually transmitted dis-

ease [1].
• Etiopathogenesis: It is produced by infection with Chlamydia trachomatis. It is
spread primarily through sexual contact with people who have asymptomatic
urethritis, cervicitis, and proctitis. The incubation period varies from 3 days to
3 weeks, with an average of 12 days [1].
• Clinical presentation: LGV manifests itself in three stages.
–– The primary phase in women is more frequently located on the external geni-
talia, the back of the vagina, the cervix, and the vulva. In men, in the coronal
sulcus, the frenulum, the foreskin, the penis, the posterior urethra, and the
scrotum. It usually heals spontaneously in several days, and, after a latency
period, the patient progresses to the secondary phase [1]. You can start in
four ways:
A non-indurated papule on the external genitalia [1].
A small, painless herpetiform vesicle [1].
A skin ulcer 4–6 mm in diameter, with an indurated base and raised
edges [1].
A nonspecific urethritis [1].
–– The secondary phase or inguinal syndrome is characterized by suppurative
regional lymphadenopathy, usually inguinal, and severe constitutional symp-
toms, LGV. The iliac and obturator lymph nodes may be involved if the pri-
mary infection occurs in the anorectal region. Lymphadenopathy develops
2–6 weeks after exposure; it is most often unilateral, although it can be bilat-
eral. It is a painful lesion, initially mobile, which later becomes fixed and is
accompanied by erythema, heat, suppuration, and ulceration [1] (Fig. 21.5).
–– The tertiary phase or anorectal syndrome characterized by protocolitis, peri-
rectal abscess formation, and anal fissures [1].
• Diagnosis: The diagnosis is based on clinical suspicion.
–– There are several techniques to diagnose infections caused by C. trachomatis
including: isolation in cell cultures, direct immunofluorescence (DFI),
enzyme-linked immunosorbent assays (EIA), antigen determination by
ELISA, and confirmation of specific DNA using PCR [1].
–– The histopathology of a primary lesion shows a superficial ulcer with a plas-
macytic infiltrate, with lymphocytes and histiocytes. Lymph nodes show
highly vascular fibrotic nodules with periadenitis. The characteristic sign is
Fig. 21.5 Lymphogranu-

loma venereum: In the left
inguinal region, there is an
ulcer with well-defined
edges, with a granuloma-
tous surface, associated
with perilesional edema
and erythema, swelling of
the inguinal lymph nodes
the stellar abscess. With routine stains, microorganisms are not detected, for
which electron microscopy is required [1].
• Differential diagnosis: The differential diagnosis in the primary stage should be
made with genital herpes, primary syphilis, and chancroid. In early inguinal
syndrome, an incarcerated inguinal hernia and inguinal infadenitis due to septic
foci in the lower extremities should be ruled out [1].
References 565
References
matosis). In: Dermatology, vol. II. 202. 3rd ed; Elsevier Saunders. 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
Chapter 22
Infections by Parasites
Protozoa
Leishmaniasis
• Definition: Leishmaniasis is a zoonosis that can affect the skin, mucous mem-
branes, or the viscera. It is the result of infection by a protozoan of the genus
Leishmania, which is transmitted by the bite of a sandfly insect [1].
• Etiopathogenesis: Infection in man can occur from parasites from an animal
reservoir (zoonotic cycle) or from another human host (anthroponotic cycle).
The vectors of leishmaniasis in Colombia correspond to the genus Lutzomyia
popularly known as capotillo, grit or pringador, of which 133 species have been
described. The geographical distribution of the Lutzomyia ranges from sea level
to 3500 masl; however the transmission cycle does not remain at altitudes above
1750 masl [1]. When the vector bites the host, it regurgitates promastigotes of
Leishmania sp. in the skin, which are phagocytosed by macrophages. Within the
macrophage phagolysosome, promastigotes evolve into amastigotes (obligate
intracellular form) and replicate, infecting other macrophages either locally or
remotely. When the vector bites an infected host, it ingests the amastigostes,
which in the intestine of the insect are transformed back into promastigostes;
these migrate to the proboscis, thus completing the life cycle of Leishmania [1, 2].
–– Leishmaniasis has been divided according to the geographical distribution of
the causal species, in [2, 3]:
Old World Leishmaniasis: This is found primarily in the Middle East, Asia,
Africa, and southern Europe. Cutaneous leishmaniasis is caused mostly by
L. major and L. aethiopica species, the latter with mucosal tropism, also
causing mucocutaneous leishmaniasis. Other species involved in the cuta-
neous form are L. tropica, L. infantum, the latter, also responsible for the
visceral form along with L. donovani [1–3].

https://doi.org/10.1007/978-3-030-84107-2_22
568 22 Infections by Parasites
New World Leishmaniasis: It is the form that occurs in Central and South
America. The species L. mexicana and L. brasiliensis are the main causes
of cutaneous leishmaniasis; however, L. brasiliensis is also involved in the
development of mucocutaneous leishmaniasis. Other species associated
with skin disease are L. amazonensis, L. panamensis, L. peruviana, and
L. guyanensis, while visceral leishmaniasis is caused by L. chagasi and
L. infantum [1–3].
–– The vector that transmits the disease, which is determined by the ecological
conditions of each region, determines the infecting species. Cutaneous leish-
maniasis is also classified according to the foci of transmission, whether
maintained by reservoirs of jungle habitat (jungle transmission); o Yes, trans-
mission occurs at a rural level due to the adaptation of the vectors to home or
peridomiciliary environments (peridomestic transmission) [1]:
• Zoonotic cutaneous leishmaniasis of jungle transmission: It occurs predomi-
nantly in middle-aged men, who due to their work activities must penetrate into
jungle areas. The reservoirs of this type of transmission in Colombia are:
Choloepus hoffmanni (two-toed sloth), Bradypus griseus (three-toed sloth), pos-
sibly rodents of the genus Proechimys sp. (spiny rat), and canids of the genus
Procyon sp. (raccoon or mangrove fox) [1].
• Zoonotic and/or anthroponotic cutaneous leishmaniasis of peridomestic trans-
mission: The vector inhabits and reproduces in crops and animal farms near
houses, facilitating its interaction with any member of the family nucleus, which
produces cases more frequently in women and children. Melanomys caliginosus
(wild mouse), Microryzomys minutus (dwarf mouse), Rattus rattus (rat),
Sylvilagus brasiliensis (moor rabbit), Didelphis marsupialis (mutt, fara, and run-
cho), Micoureus demerarae (ashy weasel, Canis familiaris) (dog), and man
could act as reservoirs [1].
• Clinical presentation: The clinical presentations of the disease vary according to
the Leishmania species, the response of the host, and the evolutionary stage of
the disease. The clinical forms of leishmaniasis are the cutaneous, mucosal or
mucocutaneous, and the visceral form. The incubation period is variable. Lesions
typically appear within a few weeks of the bite [1].
–– Cutaneous leishmaniasis: The clinical lesions vary from papules, nodules,
and plaques, which can be warty in appearance to ulcerated forms; they can
be single or multiple (Figs. 22.1 and 22.2). In Colombia, the most frequent
presentation is a painless, slow-growing ulcer with lymphangitic involve-
ment, and regional adenopathy. They can be painful when there is superinfec-
tion. Typically, the ulcer is rounded, with raised edges, erythematous,
cordoned, with a clean granulomatous center, and an infiltrated base. The
lesion tends to become chronic with evolution to a warty plaque with raised
edges and a bottom covered with scales and/or crusts [1–3].
Diffuse cutaneous leishmaniasis: This form occurs in immunosuppressed
patients. It begins as a nonspecific brown erythematous nodule, which
Protozoa 569
Fig. 22.1 Cutaneous

leishmaniasis: Rounded
ulcer with raised, purplish
erythematous, cordoned
edges, with a clean
granulomatous center and
an infiltrated base,
involving the upper outer
corner of the right gluteus
Fig. 22.2 Cutaneous

leishmaniasis: Rounded
ulcer with raised, slightly
erythematous, edges with a
clean granulomatous
center, involving the
forearm
increases in size progressively, with the appearance of new lesions that

spread without ulceration. Lesions resemble keloid scars or lepromatous
leprosy nodules. It can compromise the entire body surface and responds
poorly to treatment [2, 3].
–– Mucous or mucocutaneous leishmaniasis: It is a form of leishmaniasis that
occurs as a result of the lymphohaematogenous spread of the parasite. It can
occur simultaneously with skin lesions or 2–3 years, even 10 years, after skin
lesions. It affects the mucous membranes of the upper areas (nose, pharynx,
mouth, palate, larynx, and trachea), with a predilection for the nasal septum.
An old scar is found in 90% of cases of mucosal leishmaniasis. Symptoms
include nasal hyperemia, nodulations, ulceration; congestion, pruritus, epi-
staxis, and serohematic rhinorrhea. The skin overlying the nose, upper lip, and
malar region may present diffuse infiltration, with erythema, edema, and an
orange-peel appearance. Rhinoscopy reveals erythema, edema, ulcerations,
perforation, and destruction of the septum and soft tissues [1–3].
–– Visceral leishmaniasis (kala azar): It is a disease of the reticule-endothelial
system, of slow progression. It is characterized by fever, splenomegaly, and/
or hepatomegaly, polyadenopathies, anemia, leukopenia, thrombocytopenia,
and progressive weakness. Once the clinical picture is installed, its progres-
sion is fatal if treatment is not received [1, 2].
• Diagnosis: Diagnosis requires confirmation of infection, for which there are sev-
eral methods.
–– Direct examination (smear): The direct examination is a quick, inexpensive
and easy to perform method. However, its sensitivity varies according to the
time of evolution of the lesion (the shorter the evolution time, the greater the
sensitivity), the technique of taking and staining the sample and the training
of the personnel who perform the reading. It is recommended to take at least
three samples, both from the active edge and from the center of the ulcer, to
increase sensitivity [1].
–– Biopsy: The biopsy is a useful procedure to visualize the amastigotes.
Histology shows areas of ulceration, pseudoepitheliomatous hyperplasia a
mixed inflammatory infiltrate composed of histiocytes, lymphocytes, neutro-
phils, and plasma cells. Granuloma formation with multinucleated giant cells
and macrophages containing amastigotes can also be seen. In endemic areas
such as Colombia, it is recommended to perform a skin biopsy when at least
three smears have been negative; instead, in all cases of mucosal leishmania-
sis, a biopsy should be performed [2].
–– Serological tests: Serological tests for the detection of circulating antibodies
by different methods, such as indirect immunofluorescence (IFI) and ELISA,
have limited sensitivity but are useful as a confirmatory test [1].
–– Montenegro test or intradermoreaction: It is a complementary test, but it is
not a diagnostic test; in patients from areas with high transmission of leish-
maniasis, it may be positive without necessarily implying that they present the
disease. In suspected cases of mucosal leishmaniasis, a positive result can
guide the diagnosis and indicate a biopsy [1].
–– Visceral leishmaniasis: In the visceral leishmaniasis approach, it is necessary
to do a complete paraclinical study, in which hematological alterations con-
sisting of anemia, leukopenia, and thrombocytopenia can be found, as well as
alterations in liver function [1]. Diagnostic confirmation should be made by
Helminths 571
observing the amastigotes, either in a bone marrow aspirate or by a puncture

biopsy of the spleen. The Montenegro reaction is always negative during the
active phase of the disease and generally becomes positive between 3 and
6 months after the end of treatment, so its usefulness is limited to patient fol-
low-up [1].
• Differential diagnosis: The differential diagnosis depends on the type of
leishmaniasis:
–– Cutaneous leishmaniasis: the following conditions should be considered:
traumatic or vascular ulcers; sporotrichosis, paracoccidioidomycosis, chro-
momycosis, and cutaneous tuberculosis; atypical mycobacterial ulcers; pyo-
derma gangrenosum: and ulcerated malignant tumors, mainly squamous cell
carcinoma [1, 2].
–– Mucosal leishmaniasis: the main differential diagnoses include traumatic
ulceration, lesions secondary to the use of vasoconstrictors, chronic cocaine
aspiration, lepromatous leprosy, paracoccidioidomycosis, late lúes, orificial
tuberculosis histoplasmosis, angiocentric lymphoma of the midline, and rhi-
noscleroma and granulomatosis Wegener) [1, 2].
–– Visceral leishmaniasis: differential diagnoses of all prolonged febrile syn-
drome with splenomegaly should be considered. The entities to consider
include malaria, disseminated tuberculosis, Chagas disease, brucellosis, sal-
monellosis, systemic histoplasmosis, lymphomas, leukemias, and sarcoid-
osis [1, 2].
Helminths
Larva Migrans Cutaneous
• Definition: Cutaneous larva migrans (LM) is a sergynous eruption caused by

helminth nematodes that circulate through the epidermis [1].
• Ethiopathogenesis: The following are the main etiological agents:
–– The nematodes Ancylostoma caninum and Ancylostoma braziliense [2] in
adult form colonize in the digestive tract of dogs and cats where they produce
eggs that will be eliminated in the feces [1]. Once on the ground, if they find
favorable circumstances, they hatch until they reach the filariform (infective)
stage. Upon reaching this phase, they can enter through the skin, infesting a
new animal and thus complete their life cycle, or they can enter the skin of
humans [1–3]. On penetrating the skin, the larvae produce a small, erythema-
tous, itchy papule, or vesicle; it advances through the epidermis at a rate of
1–3 cm per day [1, 2]. As the larvae work their way through the epidermis, the
distal end of the lesion becomes dry and crusty. The larvae migrate through
the epidermis for an indeterminate time until they die without being able to
complete their life cycle, since they lack collagenase, so they cannot penetrate
the epidermal basement membrane [1, 3].
–– Gnathostoma spp. larvae, which are housed in different definitive hosts
depending on the species of the parasite, not only can cause a clinical picture
identical to cutaneous larva migrans but also can have visceral or systemic
involvement [2].
–– Strongyloides stercoralis and Necator americanus can cause a similar picture;
when it comes to the former, it is known as larva currens [2].
–– Much less frequently, Ancylostoma tubaeforme, Hookworm stenocephala,
Hookworm ceylanicum, Baylisascaris procyonis, and Bunostomum phleboto-
mum can produce a clinical syndrome of cutaneous larva migrans [2].
• Clinical presentation: Cutaneous larva migrans is characterized by a pruritic
rash with a serpeginous path [1, 2]. It mainly involves exposed areas of the skin
such as feet, knees, legs, thighs, buttocks, perineal area and genitals, hands, and
chest that come into contact with the ground when walking or during beach
activities [2, 3]. Initially, a small erythematous papule appears at the site of pen-
etration of the larva, from where a serpentine, erythematous and slightly raised
path is formed (Fig. 22.3). These paths are accompanied by erythema and a pap-
ulovesicular eruption [2]. The condition resolves spontaneously in the majority
of cases (80%) [2], with the death of the larvae after 2–8 weeks (although occa-
sionally it can last for months to 2 years) [1–3].
• Diagnosis: The diagnosis is mainly clinical. Skin biopsy is not necessary. If per-
formed, it should be known that the larva is 1 or 2 cm in front of the forward end
of the serpeginous lesion, so it is unlikely to find parasitic structures in the
biopsy [1–3].
• Differential diagnosis: The differential diagnosis includes myiasis, scabies, der-
matophytosis, and the erythema of Lyme disease [1–3].
Fig. 22.3 Larva migrans

cutaneous: A serpentine,
erythematous, and slightly
raised path involving the
plantar region of a foot
Infestations 573
Infestations
Scabies
• Definition: Scabies definition is a common skin infestatio caused by Sarcoptes

scabiei, variety hominis [1, 2].
• Etiopathogenesis: The incubation period for scabies is 4–6 weeks, although it
may be less if the initial parasite load is high [2]; subsequently, the host’s immune
system is sensitized resulting in pruritus and characteristic skin lesions, so the
severity of clinical lesions is not always related to the parasite load [1]. In the
case of reinfection, the clinical manifestations appear faster (between 24 and
48 hours) [1]. The life cycle of the parasite is 30 days, which occurs completely
within the epidermis. Each day the female produces three eggs, which require
approximately 3 days to mature [1–3].
–– The most common risk factors are overcrowding, poor hygiene, and malnutri-
tion [4]. It is a highly infectious disease so affected individuals quickly
become a source of infection for cohabitants [1].
• Clinical presentation: Scabies can affect all genders, races, and ages. The cardi-
nal symptom is intense itching, which worsens at night; however, several types
of scabies have been described based on clinical lesions [1, 2]:
–– Typical or classic scabies: It is the most frequent type, it mainly involves the
arms, armpits, wrists, hands, elbows, feet and ankles, genital area, and but-
tocks. Typical clinical lesions are erythematous papules with a central crust or
excoriation and may be comatose in shape (Fig. 22.4). The tunnels, which can
measure a few millimeters to several centimeters in rare cases and are irregu-
lar in shape; although less obvious, they are pathognomonic lesions of sca-
bies. At the end of the tunnel, you can find a female of the parasite, since they
Fig. 22.4 Scabiosis:

Erythematous papules with
surface abrasions that
converge to form plaques
with fine desquamation on
the surface. In the right
chest, there is evidence of
grayish plaque with poorly
defined irregular edges
with fine superficial scaling
with areas of
lichenification
excavate them when they deposit their eggs. Lesions can cluster together and
create an eczematous appearance [1, 2]. In infants and young children, typical
lesions include nodules, vesicles, and pustules, which are asymmetrically dis-
tributed and most commonly involve the hands, feet, and skin folds. In older
adults, the inflammatory response is less severe so it can be confused with
senile itching due to the absence of typical lesions [1].
–– Nodular scabies: This form of scabies is characterized by a delayed hypersen-
sitivity response to infection. It manifests as round nodules, with a smooth
surface, 5–8 mm in diameter, erythematous or brownish erythematous. It
mainly affects areas of thinned skin such as the genitals or skin folds [1].
–– Norwegian scabies o Crusted scabies: It is a rare variant of scabies that occurs
due to infestation with a high load of parasites; therefore, it is very contagious
[1, 5]. It occurs in immunocompromised patients in most cases, including
patients with connective tissue diseases and chronic immunosuppression with
systemic or immunomodulatory corticosteroids [1] and patients with mental
or physical disabilities, chronic illnesses, or the elderly [1, 5]. It is character-
ized by a proliferative response, associated with increased levels of IL-4,
manifested by the formation of thick scales (one). Clinically, polymorphic,
hyperkeratotic, and eczematous papulovesicular lesions are seen; there may
be occasional pustules. Typical tunnels are usually not seen [1, 2, 5]. Secondary
superinfection, particularly with Staphylococcus aureus or Streptococcus
pyogenes, is common and can progress to sepsis [1, 2]. The lesions are usually
generalized, with a predilection for skin folds and acral areas, where it can
cause keratoderma and compromise the subungular area with extensive hyper-
keratosis and secondary dystrophy [5].
–– Bullous scabies: It is a rare and debated variety of scabies, which occurs more
frequently in older adults. It can resemble bullous pemphigoid both clinically
and histologically, even on immunofluorescence findings. The formation of
blisters is associated with the prolonged presence of the parasite in the epider-
mis, which activates an immune response with activation of Th 2 lympho-
cytes, increased levels of interleukin (IL) 5, and recruitment of eosinophils,
with production of proteolytic enzymes and blistering [1, 4].
• Diagnosis: The diagnosis is mainly clinical. There are several basic methods that
can help:
–– Ink test: It consists of applying ink to the skin to be examined and then gently
cleaning it with a gauze or alcohol swab. The ink will remain in the depth of
the tunnels, which makes it easier to identify them, as irregular tracts.
However, you have up to a 30% chance of false negatives [1].
–– Direct examination: The diagnostic confirmation is made with the visualiza-
tion of the parasite, for which the direct examination is useful. The sample can
be obtained by scraping the lesions with a scalpel blade or a curette, or using
transparent adhesive tape [1, 2].
–– Skin biopsy: Skin biopsy is not performed routinely and is of low sensitivity.
Histopathology reveals a diffuse infiltrate with eosinophils, lymphocytes, and
Infestations 575
histiocytes in the reticular dermis. Sarcoptes can be seen sectioned as spiral

eosinophilic (“pigtail”) structures in the superficial epidermis [5].
–– Dermoscopy: In vivo visualization of the parasite or eggs can also be per-
formed using the dermatoscope [1].
• Differential diagnosis: The main differential diagnoses include atopic dermatitis,
contact dermatitis, insect bites, dermatitis herpetiformes, and impetigo [1, 2].
Pediculosis
• Definition: Pediculosis is the infestation of the human being by hematophagous

parasites of the order Phthiraptera, suborder Anoplura, which can affect the
head, body, and pubic region, each area by a specific species of louse [1].
• Etiopathogenesis: The different varieties of human lice, although morphologi-
cally similar, are considered different species since they do not interbreed and
prefer exclusive anatomical niches [1, 2]. Pediculosis is classified, according to
the variety of lice involved, in:
–– Pediculosis capitis: Pediculosis of the scalp is caused by Pediculus humanus
var. capitis. They are usually transmitted through direct body contact or by
sharing headwear among infested individuals [1, 2].
–– Pediculosis corporis: Pediculosis of the body is caused by P. humanus var.
corporis. They are transmitted by direct body contact or, less frequently, by
indirect contact through fomites, such as bedding, clothing, and towels.
Unlike scalp and pubic lice, body lice (P. humanus var. corporis) can transmit
various diseases caused by bacteria such as Borrelia recurrentis, Bartonella
quintana, and Rickettsia prowazekii. Indigent, immunosuppressed, and over-
crowded populations are at increased risk for pediculosis corporis infestations
and epidemics of lice-borne bacterial diseases [1, 2].
–– Lice on the scalp and on the body leave their respective niches in the hair shaft
and the seams of clothing, to feed on blood on the skin. The pubic louse
remains relatively immobile, anchored to the bases of the hair shafts while
feeding on blood, unless they are mating or laying eggs [1].
–– Pediculosis pubis: Pediculosis of the pubic region is caused by Phthirus
pubis, which, despite having a predilection for the pubic and inguinal region,
can travel through the body and infest the perianal region, the abdomen, the
thorax, the armpits, and even the mustache, beard, eyebrows, and eyelashes.
Pubic lice are transmitted more frequently during sexual contact, rather than
through fomites, and often coexist with sexually transmitted diseases [1, 2].
• Clinical presentation: The main clinical manifestations include intense itching,
pinpoint erythematous papules, excoriations, and scabs in the compromised
areas; secondary impetiginization is common (Fig. 22.5). In pediculosis capitis
and pubis, the eggs are strongly attached to the hair shafts, being brown in color
Fig. 22.5 Pediculosis.

Presence of erythematous
papules and excoriations in
the ear region and retro
auricular skin, in addition
to nits on the scalp
when they are viable and white when they have already been hatched. Lice can
sometimes be seen. Some characteristics are specific to each type of pediculo-
sis [1–3]:
–– Pediculosis capitis is the most common type. It is usual to find lesions in the
skin of the retro auricular and posterior cervical region [1, 2].
–– In pubic pediculosis, blue-gray macules can be seen, known as macula ceru-
lea, which corresponds to the sites of louse bites [1, 3].
–– In the case of pediculosis corporis, lice are rarely observed since they inhabit
and reproduce on clothing [1, 2].
–– Diagnosis: Diagnosis is clinical, given by clinical lesions and direct visualiza-
tion of live lice and viable or hatched eggs (nits). Dermoscopy has recently
been used to immediately distinguish viable from empty eggs [1–3].
–– Differential diagnosis: The differential diagnoses to take into account depend
on the type of pediculosis.
Infestations 577
–– Pediculosis capitis: The main differential diagnoses of scalp pediculosis are

seborrheic dermatitis, trichorrhexis nodosa, and white or black stone.
Seborrheic dermatitis is a frequently seen disease of the scalp and can cause
itching; however, the scales are easy to detach from the hair shaft, unlike nits,
which are strongly attached [1, 2].
–– Pediculosis pubis: Pediculosis pubis must be differentiated from white or
black stone and trichomycosis [2].
–– Pediculosis corporis: Due to the absence of lice in the body, pediculosis of the
body is often confused with other causes of generalized itching such as kid-
ney or liver disease, drug reactions, atopic dermatitis, or other infestations
such as scabies [1, 2].
Cutaneous Myasis
• Definition: Myiasis is an infestation of living vertebrates, both animals and

humans [1], with a larva (worm) of flies of the order Diptera. Many organs may
be involved, but the skin is the most common site [2].
• Etiopathogenesis: The route of infection and the species of larvae determine the
type of cutaneous myiasis, which is classified as furuncular, wound, and
migratory.
–– Furuncular myiasis: In this type of cutaneous myiasis, the transmission routes
of the fly larvae to humans depend on the species [1]. The flies that most com-
monly cause infestation in humans are Dermatobia hominis (human blowfly)
and Cordylobia anthropophaga (tumbu fly). The first one deposits the eggs in
mosquitoes, which are later inoculated in warm-blooded vertebrates;
C. anthropophaga lays its eggs on wet clothing, dirty sheets, and in sand [1,
3]. The larva can live up to 15 days without food; once it penetrates the skin,
maturation begins, a period that lasts from 1 to 12 weeks [1]. Subsequently,
the larva looks for the skin surface, falls to the ground where it reaches the
form of a fly, thus completing its life cycle [3].
–– Wound myiasis: The main cause of this type of myiasis in the Americas is
Cochliomyia hominivorax, a screwworm; while in Africa, Australia and Asia,
it is associated with Chrysomya bezziana. Typically, an open wound attracts
the fly, which lays the eggs.
–– Migratory cutaneous myiasis: This form of myiasis is associated with expo-
sure to infected cattle or horses; it is mainly caused by Hypoderma bovis in
the first case and Gasterophilus intestinalis in the second.
• Clinical presentation: Cutaneous myiasis is a self-limited disease in most cases,
with minimal morbidity. In rare cases of infestation by C. hominivorax in the
periorificial areas of the face, the larvae can migrate to brain tissue [1, 3].
Symptoms develop 1–2 days after infestation [3]. It is mainly divided into furun-
cular myiasis, wound myiasis, and migratory myiasis [1, 3].
–– Furuncular cutaneous myiasis: It is the most common form of cutaneous

myiasis [3] and is characterized by seasonal peaks, with most cases reported
between August and September [2]. The infections caused by blowflies more
frequently involve exposed areas (face, scalp, forearms, and legs), while those
caused by the tumbu fly affect more the covered areas (trunk, thighs, and but-
tocks) [1]. The lesions begin as erythematous, pruritic papules with progres-
sive growth and edema, reaching 1–3 cm in diameter [1, 3]. It generally has a
small central hole through which the larva pops its head out to breathe about
once a minute (Fig. 22.6). Occasionally, the respiratory movement of the lar-
vae can be observed [2, 3]. The lesions are painful and can become crusty and
drain serosanguineous material [1], rarely purulent [3]. Patients may report
feeling of movement and anxiety. Lesions can be single or multiple and can
be accompanied by regional lymphadenopathy [3].
–– Wound myiasis: The larvae are deposited in suppurative open wounds or with
decomposing tissue. Any part of the body can be involved [1, 3]. Symptoms
are nonspecific with increased edema, pain, and discharge from the lesions.
The larvae can be evident or localized in deep tissue, making diagnosis diffi-
cult [1].
–– Cutaneous migratory myiasis: This form is reminiscent of cutaneous larva
migrans, with the formation of erythematous-edematous sinuous tracts
(Fig. 22.7); however, the larvae of the fly migrate more slowly and persist for
longer periods, even months and are larger than the larvae of the helminths.
Fig. 22.6 Cutaneous

myasis: On the scalp, there
is an ulcer, with well-
defined edges, bottom with
bloody discharge, with
perilesional erythema
Fig. 22.7 Cutaneous

myasis: Erythematous-
edematous sinus tracts on
left forearm
References 579
• Diagnosis: The diagnosis is mainly clinical. It is obvious when the larvae are
visible [1]. Ultrasound can help establish the size of the larvae [1–3]. The biopsy
is not done routinely; histology shows an inflammatory response with lympho-
cytes, giant cells, neutrophils, eosinophils, mast cells, and plasma cells. The
larva can be seen in section [1]. Dermoscopy may be useful to observe parts of
the larva within the central opening [2].
• Differential diagnosis: The main differential diagnoses are a ruptured epider-
moid cyst, abscesses, furunculosis, foreign body reaction, tungiasis, and an exag-
gerated sting reaction.
References
matosis). In: Dermatology, vol. II. 202. 3rd ed; 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
Fitzpatrick’s dermatology in general medicine. 8th ed; 2012. p. 1319–36.
Part III
Neoplastic Skin Diseases
Chapter 23
Benign Neoplasms
Benign Epidermal Tumors
Seborrheic Keratosis
• Definition: It is the most common benign skin lesion that is almost always pres-
ent in older individuals. They only occur on hairy skin. They can develop on the
face, neck, and trunk (especially the upper back), as well as the extremities [1, 2].
• Epidemiology/pathogenesis: It has an age of presentation around the fourth
decade of life, with a predilection for Caucasian populations and an equal inci-
dence between men and women. Although its etiology is not yet clear, it has been
associated with an increase in the proliferation of keratinocytes and suppression
of the apoptotic process [2]. Likewise, somatic mutations of genes that encode
factors have been identified in more than 80% of the lesions. Epidermal growth
factor receptor was further investigated in growing and quiescent seborrheic
keratoses; Among these oncogenes, the most common is FGFR3, a receptor tyro-
sine kinase, involved in growth, differentiation, cell migration, and angiogenesis
processes [3]. Other types of oncogenes such as PIK3CA, KRAS, and EGFR
have been described [3]. The degree of pigmentation of the lesions has been
associated with the secretion of melanocyte-stimulating cytokines, such as endo-
thelin-1, which induce the melanization process and lead to hyperpigmentation
of the lesions in question [1].
• Clinical presentation: Often manifests as multiple macules, papules or pig-
mented, brown plaques with well-defined edges, and a velvety, unctuous surface,
accompanied or not by hyperkeratosis (Fig. 23.1, 23.3, and 23.4). The unique
lesions, less frequent, can vary in size, usually from 1 to 5 cm [1]. They are gen-
erally asymptomatic lesions; however, in some cases they are accompanied by
inflammation (associated with rupture of small pseudocysts, trauma, or infection
by microorganisms) and may be accompanied by pain, itching, erythema, crust-
ing, or pustule formation [1]. In some cases, the eruption of multiple seborrheic

https://doi.org/10.1007/978-3-030-84107-2_23
584 23 Benign Neoplasms

keratoses: multiple
pigmented, brown plaques
with well-defined edges
and a velvety, unctuous
surface, with little
hyperkeratosis [1]
Fig. 23.2 Leser-Trélat

sign: A sudden eruption of
multiple seborrheic
keratoses [1].
keratoses has been reported, of sudden, progressive appearance and with

extensive involvement, associated with neoplastic processes (gastrointestinal,
hepatic, lymphoproliferative, among others), for which its presentation has been
attributed to the manifestation of a paraneoplastic syndrome, known as the Leser-
Trélat sign (Fig. 23.2) [5–8].
• Diagnosis: The diagnosis of QS is mainly clinical; however, in some cases in
which there is diagnostic doubt, the biopsy with histopathological study is very
useful [1]. Within the histological findings, hyperkeratosis, acanthosis, and pap-
illomatosis can be observed. In some cases, corneal pseudocysts occur, the prod-
uct of epidermal invaginations, although they are very characteristic findings of
these lesions. In case of intercellular edema, intercellular bridges can be seen.
Keratinocytes with mild atypia and mitotic figures, if present, are associated with
an inflammatory process [1]. There are at least six histological subtypes, among
which are acanthotic, hyperkeratotic, reticulated, irritated, clonal, and desmo-
plastic QS [1, 2].
Benign Epidermal Tumors and Proliferations 585

keratoses: A pigmented,
exophytic dark brown
edges and a velvety,
unctuous surface, with
little hyperkeratosis [1]

keratoses: a pigmented,
flattened brown plaque
with well-defined edges
and a unctuous surface,
with little
hyperkeratosis [1]
–– Acanthotic QS: It is the most frequent variant and acanthosis, and corneal
pseudocysts predominate in it (Fig. 23.5) [1, 7].
–– Hyperkeratotic or papillomatous QS: Marked papillomatosis and hyperkera-
tosis and a preponderance of squamous cells in relation to the basal cells are
observed. Likewise, epidermal projections characteristic of this presentation
have been described (Fig. 23.6) [1, 7].
–– Reticulated CS: Epithelial projections of hyperpigmented basaloid cells are
seen extending from the dermis in a reticular pattern. It may be accompanied
by lymphocytic infiltrate in the dermis, spongiosis, and necrotic keratino-
cytes [1, 7].
–– Irritated QS: It is characterized by a poorly defined base [1] [7].
–– Clonal QS: Presents packed keratinocyte conglomerates (Fig. 23.7) [1, 7].
–– Desmoplastic QS: Irregular squamous nests and strands of cells that extend
into a desmoplastic stroma. Trapped cells can mimic squamous cell carci-
noma [7].
• Differential diagnosis: Among the differential diagnoses of this entity, benign
pathologies are identified, such as lentigo solaris, skin tags, common wart, con-
Fig. 23.5 Acanthotic QS: basaloid cell population and multiple pseudohorn cyst [1]
dyloma acuminata, acrokeratosis verruciform, and eccrine poroma, to patholo-

gies of malignant course such as CEC and melanoma [1, 8].
Stucco Keratosis
• Definition: Also known as keratosis alba, it corresponds to a benign dermatosis,

which presents as asymptomatic white-grayish keratotic papules, distributed
symmetrically in the extremities [1].
• Epidemiology/pathogenesis: Stucco keratosis is an uncommon entity, with a
prevalence of 7–20%, generally occurring around 40 years of age, with a male/
female ratio of 4:1 [1]. It is common in patients with clear phototypes and in cold
climates. Its course is benign, with a tendency to spontaneous involution [1].
Although the etiology of this entity remains unknown, some studies have sug-
gested a form of acquired focal abnormal keratinization, in which the role of
exposure to UV radiation and HPV infection as implicated factors [1].
• Clinical presentation: It is characterized by the presence of multiple small,
hyperkeratotic, grayish-white papules and plaques, with an approximate diame-
ter of 1–4 mm, and focal accumulations of keratotic material (Figs. 23.8 and
23.9) [1]. They are symmetrically distributed in the lower limbs, below the knees,
Fig. 23.6 Papillomatous QS: very marked papillomatosis and conspicuous pseudohorn cyst [1]
mainly in the dorsal and lateral repairs of the feet and ankles, and rarely involve
upper limbs [1].
• Diagnosis: For its diagnosis, a correct anamnesis and physical examination are
required, taking into account that its age of presentation, morphology, and pre-
sentation are key to be able to establish a differential diagnosis with other pathol-
ogies. In case of diagnostic doubt, a biopsy and histopathological study can be
used, in which histological changes similar to those of a hyperkeratotic sebor-
rheic keratosis such as orthokeratosis, hyperkeratosis, and mild acanthosis are
evidenced. It is also possible to observe epidermal papillomatosis similar to
church towers (with a “saw” appearance) [2].
• Differential diagnosis: Seborrheic keratosis, Hopf verruciform acrokeratosis,
verruciform epidermodysplasia, Darier’s disease, verrucous epidermal nevus,
disseminated superficial actinic porokeratosis, and flat warts are mentioned in
the literature as differential diagnoses [3].
Fig. 23.7 Clonal QS: presents packed keratinocyte conglomerates [1]
Fig. 23.8 Single

well-delimited keratotic
and unctuous papule, light
brown, flattened, with
quadrilateral shape,
without ulceration and
measures approximately 3
× 4 mm [1]
Fig. 23.9 Stucco

keratosis: single well-
delimited unctuous papule,
brown, flattened, with
round shape, without
ulceration and measuring
12 mm in diameter [1]
Porokeratosis
• Definition: Porokeratosis is a group of hereditary and acquired dermatoses, the

product of an alteration in keratinization of probable clonal origin [1].
• Epidemiology/pathogenesis: These are rare lesions; the exact incidence of which
is unknown. At least five types of porokeratosis have been identified, which have
been reported and can coexist in more than one type in the same patient. Among
these are mentioned:
–– The classic or Mibelli form (PQM).
–– Disseminated superficial actinic porokeratosis (DSAP).
–– Linear porokeratosis (PQL).
–– Palmoplantar punctate porokeratosis (PQPP).
–– Disseminated palmoplantar porokeratosis (PQPPD).
• Among those that predominates in frequency is the first (PQM) [1, 2]. Of the
morphological variants, some, such as PQPPD and PQL, have been associated
with an autosomal dominant hereditary pattern; others, on the contrary, appear
spontaneously [2]. The predilection for age group differs according to each sub-
type: The classical or Mibelli forms (PQM) and the linear (PQL) appear during
childhood and are predominantly in males, while palmoplantar dotted forms
(PQPP) and disseminated actinic forms (PASD) are observed more frequently in
adolescent males and adult females, respectively [2]. There is no clear ethnic
predominance; however, some forms of presentation, such as PQA, have been
related to the high degree of sun exposure and light phototypes [2].
• Clinical Presentation.
–– PQM manifests itself during childhood, with multiple small, brown papules
that can converge to form large plaques (up to 20 cm), well-defined, whose
contour is high, and its center is hyperkeratotic and, in some cases, atrophic
(Figs. 23.10, 23.11, 23.12, 23.13, 23.14, and 23.15). They are located espe-
cially in the extremities (Fig. 23.14), but cases of facial, palmoplantar, genital,
Fig. 23.10 Porokeratosis:

brown papules that
converge to form plaques,
well defined with center
hyperkeratotic in the
thumb of the left hand [1]

plaques, well defined with
center hyperkeratotic in the
second finger of the left
hand [1]
and mucosal involvement have been reported, with a predominantly unilateral

distribution pattern. In general, they are asymptomatic lesions but may pres-
ent with itching in skin folds [1].
–– Patients with PASD, on the other hand, present multiple keratotic papules,
2–7 mm in diameter, that vary in color from pink to red and are characterized
by an atrophic center and raised margins as they expand (Fig. 23.12). The
location of the lesions is exclusive of photo-exposed areas, such as the extrem-
ities, shoulders, back, and face, which tend to be aggravated with sun expo-
sure. However, there is a disseminated superficial variant (PSD) whose
distribution is symmetric and bilateral and involves both photo-exposed and
covered areas, such as the trunk, genitalia, and palmoplantar areas [1, 2].
–– In PQL, one or multiple linear, unilateral hyperkeratotic plaques are evident,
which follow Blaschko’s lines and extend along the extremities and, in some
cases, the face and trunk. They may have fingernail or finger involvement
(bone thinning) [1, 2].

on the right cheek multiple
macules and keratotic
plaques with cornoid
lamella, 2–10 mm in
diameter, color from pink
to red and are characterized
by an atrophic center and
raised margins as they
expand [1]

on the right cheek keratotic
plaque with cornoid
lamella, of 10 mm in
diameter, color pink with
atrophic center [1]

two plaques, of 2.5 and
3 cm in diameter, color
pink with atrophic center
and elevated margins
located in the left leg [1]
–– PQPP manifests with multiple papules of 1–2 mm in diameter, predominantly

palmoplantar [1, 2].
–– Lastly, in PQPPD multiple reddish-brown keratotic papules are observed,
1–2 mm in diameter, which begin in the palmoplantar region and subsequently
spread, including mucous membranes [1, 2]. The association of these lesions,
with the exception of the punctate variant, with the development of SCC,
mainly those present in older adults, of long duration and linear variants, has
been reported. In these cases, growth of a papule or plaque adjacent to the
porokeratosis is evidenced, giving the latter an asymmetrical appearance [1].
• Diagnosis: The clinical course and the morphological description of the lesion
are the basis of the diagnosis, taking into account the possible differential diag-

multiple small, brown
papules that converge to
form plaques in the right
arm [1]
noses. Diagnostic confirmation, through biopsy and histopathology, is based on

the identification of the “cornoid lamella,” which correspond to columns of para-
keratotic corneocytes, which underlie a depression of the epidermis, sometimes
corresponding to a follicular or sweat pore and whose vertex it is related to the
interior of the plaque [1]. At the dermis level, capillary dilation and perivascular
lymphocytic infiltrate and the presence of colloid bodies can be observed. Other
rare findings are the presence of colloid bodies and eosinophilic spongiosis. Mild
hyperkeratosis and an atrophic mucosal body are seen in the center of the lesions
[9]. Using electron microscopy, cornoid lamellae can be identified, containing
pyknotic nuclei, degraded organelles, and lipid droplets, as well as keratinocytes
with vacuolar degeneration (Fig. 23.16) [9].
• Differential diagnosis: According to the clinical presentation, the following
should be established as the differential diagnosis: seborrheic, actinic and stucco
keratosis, lichen planus and sclerosus, pityriasis rubra pilaris, and linear psoriasis
[1]. Within the palmoplantar presentations, one must distinguish of nevi, Darier’s
disease, and hereditary keratoderma punctata [9]. Regarding the histological
Fig. 23.16 Porokeratosis: column of parakeratosis arising from a focus of epidermal dysmatura-
tion associated with invagination of the epidermis. Deficient granular cell layer at the base of
lamella [1]
findings, cornoid lamella can also be found in actinic keratoses; however, the
latter is usually associated with epidermal cytological atypia, unlike porokera-
tosis [1].
Dermatosis Papulosa Nigra
• Definition: Dermatosis papulosa nigra (PND) is a benign skin condition, which

commonly occurs in dark phototypes, characterized by the appearance of multi-
ple sessile and filiform hyperpigmented papules, 1–5 cm [1].
• Epidemiology/pathogenesis: According to selective studies carried out in some
populations, its incidence ranges from 10% to 75%, with a male/female ratio of
1:2. Despite being a predilection for dark phototypes, cases of DPN have been
Fig. 23.17 Dermatosis

papulosa nigra: at the neck
region, there are multiple
euchromatic and light-
brown papules with
well-defined, regular
edges. Diameters are
measured from 1 to
5 mm [1]
reported in Mexicans and Asians [2]. Its etiology is unknown; however, given the
high family association, a genetic correlation has been proposed. On the other
hand, a correlation with seborrheic keratosis has been discussed, given the simi-
larity in the histological findings of both entities [3]. Likewise, in the analysis of
samples from patients with DPN and stucco keratosis, the presence of FGFR3
and PIK3CA mutations, the same genes involved in the pathogenesis of sebor-
rheic keratosis, has been evidenced [1].
• Clinical presentation: It manifests with multiple hyperpigmented, dark, sessile,
and filiform papules, with a smooth surface, with a diameter of 1–5 cm
(Fig. 23.17), located in the facial region, neck, and thorax [1]. Typically, the
lesions appear in middle-aged adults, starting at the facial level, and show pro-
gressive growth and distribution over the years, toward photo-exposed areas [1].
• Diagnosis: PND shares histopathological findings with Seborrheic Keratosis,
including acanthosis, papillomatosis and sometimes a cystic pattern similar to
that of seborrheic keratosis characterized by the presence of horn cysts and pseu-
docysts can be seen [1].
• Differential diagnosis: It is necessary to rule out entities such as multiple sebor-
rheic keratosis, skin tags, melanocytic nevus, warts, trichoepitheliomas, follicu-
lar hamartoma, and syringomas [1].
Skin Horn
• Definition: Cutaneous horn is a clinical term for a white to yellowish, conical

keratotic plaque or papules, which can measure few to many centimeters [1].
• Epidemiology/pathogenesis: The cutaneous horn is a relatively uncommon
lesion, of which data on its incidence and prevalence are unknown [1]. Its pro-
portion is higher in men than in women, presenting around the fifth decade of life
and is frequent in populations with light phototypes [9]. Although its etiology
has not been identified, a relationship with sun exposure has been established as
a possible triggering factor, due to the high number of cases that manifest in
photo-exposed skin areas. Another hypothesis that has been suggested is the pos-
sible relationship with HPV, mainly the HPV 2 serotype [1]. A variety of benign
and malignant skin pathologies associated with this lesion have been reported.
The latter are more frequent in adults over 60 years of age and correspond to
39–44% of cases, among which up to 20% are related to squamous cell carci-
noma in situ or invasive [1]. In other cases, it has been observed the appearance
of these lesions on skin scars due to burns [1].
• Pathogenesis: It is the result of an exaggerated accumulation of keratin. With an
abnormal overlap of the underlying horny layer [1].
• Clinical presentation: It is characterized by a hyperkeratotic and circumscribed
papule or plaque lesion of variable size, conical, pedunculated, straight, curved
or twisted, yellowish-white in color, on a flat, nodular, or crateriform base
(Fig. 23.18) [1]. Its distribution extends to the entire skin surface; however, it is
frequent that it occurs in photo-exposed areas up to 70%, of which up to 30%
compromise the scalp and face [3]. Within the skin pathologies that have been
related to this type of injury, stand out:
–– Benign such as angiokeratoma, benign lichenoid keratosis, cutaneous leish-
maniasis, dermatofibroma, discoid lupus, sebaceous adenoma, vulgar wart [4].
–– Premalignant: actinic keratosis and arsenical keratosis [4].
–– Malignant: sebaceous carcinoma, Bowen’s disease, Kaposi’s sarcoma, basal
cell carcinoma, and squamous cell carcinoma. The latter represents 16–20%
of the cases of malignant skin pathologies associated with this type of
injury [4].
• Diagnosis: Its diagnosis is purely clinical and can be found associated with or in
response to a variety of benign, pre-malignant or malignant skin diseases, which
require a histopathological study for their differentiation, so it is recommended
to submit a biopsy to study the base of injury [1]. Histologically, the lesion is
Fig. 23.18 Skin horn: at

the nasal bridge, there is a
6 mm yellowish-white,
conical, hyperkeratotic
exophytic tumor with
projection to the right axis
seen as a zone of hyperkeratosis and parakeratosis, associated with acanthosis

and atypical keratinocytes [1].
• Differential diagnosis: Within the differential diagnoses, hypertrophic actinic
keratosis, squamous cell carcinoma, keratoacanthoma, and viral wart are estab-
lished [1].
Clear Cell Acanthoma
• Definition: Also called acanthoma of Degos. It is a benign epidermal tumor, usu-

ally asymptomatic, presenting as a solitary erythematous papule or plaque, often
located on the lower extremities [3].
• Epidemiology/pathogenesis: Described by Degos in 1962, it was initially associ-
ated with an epithelial tumor of benign origin, in which its origin was confirmed
by identifying the expression of involucrin, as well as the presence of antigens
against the epithelial membrane [4]. Although its etiology is still unknown, it has
been related to certain inflammatory dermatoses, due to the cytokeratin staining
pattern that occurs, similar to that found in some inflammatory dermatoses such
as lichen planus, discoid lupus, and psoriasis. Likewise, an alteration in the mat-
uration of keratinocytes has been identified, a component that it shares with pso-
riasis [1, 2].
• Clinical presentation: It manifests as an erythematous papule or plaque, which
pales on acupressure and with the presence of a scaly collarette on its periphery
(Figs. 23.19 and 23.20) [1, 4]. In most cases, it is singular and asymptomatic. It
involves the lower limbs, and on rare occasions, it may appear on the face, fore-
arms, trunk, or inguinal region. There are few cases in the literature in which a
multiple and disseminated presentation has been reported, which has been cate-
gorized as discrete or eruptive according to the number of lesions [1]. It often
occurs concurrently with other dermatoses such as stucco keratosis and ichthyo-
sis or develops in areas of pre-existing dermatoses such as epidermal nevi [1].
Fig. 23.19 Clear cell

acanthoma: epidermal
tumor
Fig. 23.20 Clear cell

acanthoma: epidermal
tumor
The clear cell acanthoma usually presents a slow growth, in a period of

2–10 years, during which it can reach an average diameter of 0.3–2 cm, being
reported some cases of giant clear cell acanthomas that reach a diameter of up to
6 cm [1, 4].
• Diagnosis: The diagnosis of this type of lesion is purely histological. Among the
histopathological findings, a well-defined area of epidermal
thickening is evi-
denced, with regular psoriasiform hyperplasia, composed of a conglomerate of
pale keratinocytes. It is possible to find an eroded epidermis and the presence of
neutrophils that extend from the papillary dermis to the stratum spinosum, with
a decrease in the thickness of the granular layer [1, 4]. In PAS staining, a reddish
coloration of the cytoplasm of keratinocytes is present, confirming the presence
of glycogen sensitive to diastase [1]. On the other hand, electron microscopy can
verify the presence of abundant glycogen within the cytoplasm of keratinocytes
and the presence of elongated epidermal ridges; at the level of the dermis, edema
can be observed in the papillary dermis, dilation of the blood vessels, and dis-
seminated perivascular lymphocytes [1].
• Differential diagnosis: It is necessary to rule out some pathologies with which
these lesions can often be confused with, among which are pyogenic granulo-
mas, traumatic hemangiomas, dermatofibroma, warts, basal cell carcinoma,
squamous cell carcinoma, amelanotic melanoma, inflammatory stucco keratosis,
or psoriasis. Due to their appearance given by the presence of clear cells, it is
necessary to consider, within the histopathological differential diagnosis, clear
cell hidradenoma, clear cell syringoma, and simple hidroacanthoma, such as
trichilemoma and sebaceous neoplasms [4–6].
Epidermal Nevus
• Definition: It is a type of benign cutaneous neoplasm that occurs in childhood

and is characterized by the presence of linear psoriasiform papules or plaques,
usually involving a limb and persisting over the years [1, 7].
• Epidemiology/pathogenesis: Verrucous epidermal nevus (NEV) represents a rare
variant of epidermal nevus, of which, three main types have been proposed: epi-
dermolytic NEV, whose histological distinction is due to epidermolytic hyper-
keratosis; non-epidermolytic NEV, which lacks this histological characteristic;
and linear inflammatory NEV, which is clinically differentiated by lesions
arranged along the lines of Blaschko. It is an early-onset clinical entity, which
occurs in up to 75% during the first 5 years of life, of chronic course and with
little therapeutic response [1]. Its male/female ratio is 1:4, finding a predilection
for the female gender. The etiology of this lesion is unknown. Some authors
consider it to be due to the overexpression of involucrin, a component of the
squamous epithelium that is also elevated in psoriasis. Others, on the other hand,
associate its development to a clonal dysregulation in the growth of keratino-
cytes [1, 7].
• Clinical presentation: Clinically it presents as multiple erythematous papules
with a warty appearance, which coalesce to form plaques with fine scaling, with
a warty or psoriasiform appearance (Fig. 23.21). Sometimes they can be symp-
tomatic and accompanied by intense itching [1]. Generally, the involvement is at
the level of the limbs, with the lower left limb being the limb most frequently
involved. Occasionally, it may have a distribution at the level of the trunk, and in
some cases, mucosal involvement has been reported [1]. Occasionally, it is asso-
ciated with congenital abnormalities of the musculoskeletal apparatus, the cen-
tral nervous system, the ocular system, among others, categorizing within the
epidermal nevus syndrome [2]. Cases of association with other neoplasms such
as basal cell carcinoma, sebaceous nevus, and papilliform syringocystadenoma
have been reported [8].
Fig. 23.21 Epidermal

nevus. Multiple brown and
erythematous papules with
a warty appearance,
coalescing to form plaques
involving the neck, thorax,
and upper left arm in
segmentary distribution [1]
• Diagnosis: Within the histological findings, the presence of elongated epidermal

ridges and large areas of parakeratosis, with areas of orthokeratosis and hyper-
granulosis, can be observed. It is also common to identify lymphocytic and neu-
trophilic exocytosis in the spongiotic epidermis, as well as, occasionally, Munro
microabscesses [1].
• Differential diagnosis: The differential diagnosis is mainly made up of other
variants of epidermal nevus such as lichenoid epidermal nevus, psoriasis super-
imposed on an epidermal nevus and CHILD syndrome (congenital hemidyspla-
sia with ichthyosiform nevus and limb defects [1].
Verrucous Epidermal Nevus
• Definition: It constitutes a type of benign cutaneous neoplasm, which occurs in

childhood and is characterized by the presence of linear psoriasiform papules or
plaques, usually involving a limb and persisting over the years [1].
• Epidemiology/pathogenesis: Warty epidermal nevus (NEV) represents a rare
variant of epidermal nevus, of which three main types have been proposed: epi-
dermolytic NEV, whose histological distinction is due to epidermolytic hyper-
keratosis; non-epidermolytic NEV, which lacks this histological characteristic;
and linear inflammatory NEV, which is differentiated clinically by lesions
arranged along Blaschko’s lines. It is an early-onset clinical entity, which occurs
in up to 75% during the first 5 years of life, of chronic course and with little
therapeutic response [1]. Its male/female ratio is 1:4, finding a predilection by
the female gender. The etiology of this lesion is unknown. Some authors consider
that it is due to the overexpression of involucrin, a component of the squamous
epithelium that is also elevated in psoriasis. Others, on the other hand, associate
its development to a clonal dysregulation in the growth of keratinocytes [1].
• Clinical presentation: Clinically it presents as multiple erythematous papules
with a warty appearance, which coalesce to form plaques with fine scaling, with
a warty or psoriasiform appearance (Figs. 23.22, 23.23, 23.24, and 23.25).
Sometimes they can be symptomatic and accompanied by intense itching [1].
Generally, the involvement is at the level of the limbs, with the lower left limb
being the limb most frequently involved. Sometimes, it can have a distribution at
the level of the trunk, and in some cases mucosal involvement has been reported
[1]. Occasionally, it is associated with congenital anomalies of the musculoskel-
etal apparatus, the central nervous system, and the ocular system, among others,
being categorized within the epidermal nevus syndrome [8]. Cases of association
with other neoplasms such as basal cell carcinoma, sebaceous nevus, and papil-
liform syringocystadenoma have been reported [9].
• Diagnosis: Within the histological findings, the presence of elongated epidermal
ridges and large areas of parakeratosis, with areas of orthokeratosis and hyper-
granulosis, can be observed. It is also common to identify lymphocytic and neu-
Fig. 23.22 Verrucous

epidermal nevus. Multiple
brown and erythematous
papules with a warty
appearance, which
coalesce to form exophytic
plaque located in left
zygomatic and temporal
region [1]

brown and erythematous
papules with a warty
appearance located in
upper chest [1]

brown papules with a
warty appearance, which
coalesce to form linear
distribution plaques in
hypogastrium and right
hypochondrium [1]

epidermal nevus. multiple
light-brown and
euchromatic papules
coalesce to form linear
plaques in the inner aspect
of right arm [1]
trophilic exocytosis in the spongiotic epidermis, as well as occasionally Munro

microabscesses [1].
• Differential diagnosis: The differential diagnosis is mainly made up of other
variants of epidermal nevus such as lichenoid epidermal nevus, psoriasis super-
imposed on an epidermal nevus, and CHILD syndrome (congenital hemidyspla-
sia with ichthyosiform nevus and defects in the extremities) [1].
Comedonal Nevus
• Definition: It is a rare epidermal nevus, of the folliculosebaceous unit, the result

of numerous dilated keratin-filled comedones [1]. Usually has a predilection for
the face and neck area [10].
• Epidemiology/pathogenesis: Approximately 20–50% of comedonal nevi are evi-
dent at birth or appear during childhood, usually before age 10 years [1, 2]. Adult
onset is rare in them; it has been associated with irritation or trauma. There is no
predilection for race or sex. However, many cases appear sporadically and a fam-
ily history has also been reported [1]. Comedonal nevi represent growth dysregu-
lation affecting the mesoderm portion of the pilosebaceous unit. Epithelial
invaginations form terminal hairs and sebaceous glands, accumulating horny
products that result in a comedo-like plug [1]. In 1998, the FGFR1 mutation was
Fig. 23.26 Comedonal

nevus. Multiple follicular
dilatations with corneal
plugs that resemble acne
“blackheads” are observed
in the posterior region of
the thighs [1]
Fig. 23.27 Comedonal

nevus. on the left aspect of
the face, multiple follicular
dilations with linear
distribution are observed
along with atrophic
scars [1]
detected in comedogenic nevi [1]. It occurs in 1 in 45,000 to 1 in 100,000 with

no preference for gender or race [10].
• Clinical presentation: It is usually asymptomatic and frequently affects the face
and neck, with the exception of other anatomical regions that include the genital
area, palms, and soles. Clinically, it presents as a group of dilated follicular plug-
ging in a honeycomb pattern, and these follicular ostia are filled with lamellar
keratinized material. Giving an appearance of blackheads, but this material can-
not be easily removed mechanically compared to acne comedones (Figs. 23.26
and 23.27) [2]. Comedonal nevi have several patterns of distribution: unilateral,
bilateral, linear, interrupted, segmental, or blaschkoid. Two types of comedonal
nevi have been identified; the first and the second types are characterized by the
formation of cysts, papules, pustules, and abscesses at various stages of develop-
ment [10, 11].
• Diagnosis: It is clinical, however, on histopathology, comedonal nevi consist of
a group of undeveloped hair follicles that present dilated invaginations filled with
cornified detritus devoid of hair shafts. Epidermolytic hyperkeratosis can occur,
sometimes, in the follicular epithelium [1, 11].
• Differential diagnosis: Childhood acne, chloracne, Winer’s enlarged pore [1, 10].
Acanthosis Nigricans
• Definition: Acanthosis nigricans (AN) is a dermatological condition recognized

for more than 100 years [12, 13]. It is defined as cutaneous thickening and
grayish-brown hyperpigmentation in the form of generally symmetrical plates
and with preference for the folds and flexion faces of the extremities [1, 12, 13].
• Epidemiology/pathogenesis: In adults it is considered associated with malig-
nancy, but recently it has been primarily considered a marker of insulin resis-
tance. Some studies show that in adolescents it has been associated with obesity
[12]. The exact pathogenesis associated with obesity is complicated and not yet
clearly established. The main proposed mechanism is the direct and indirect acti-
vation of the insulin growth factor receptor by hyperinsulinemia, which focuses
on the proliferation of epidermal keratinocytes and dermal fibroblasts. The pref-
erential location of the AN suggests friction and may play a role in pathogenesis.
It has rarely been reported in patients receiving insulin [12].
• Clinical presentation: It is characterized by symmetrical thickening and darken-
ing of the skin, from brown to black depending on the patient’s phototype.
Accentuation of skin lines is observed, giving a rough appearance and texture:
the lesions can progress to papillomatous or warty plaques (Figs. 23.28, 23.29,
23.30, 23.31, 23.32, 23.33, 23.34, 23.35, 23.36, and 23.37). AN is frequently
asymptomatic; however, it can occasionally cause itching. Its onset is insidious
and is often not noticeable or the patient and family perceive a dirty appearance
[12]. It can affect any part of the skin, but the most common sites are the neck,
armpit, inguinal region, and anogenital area. In contrast, sites in the face, the
Acanthosis Nigricans 605
Fig. 23.28 Acanthosis

nigricans: grayish-brown
over the lower back [1]

over the right underarm [1]

over the left underarm [1]

over the right and left
underarms [1]

nigricans: cutaneous
thickening and grayish-
brown hyperpigmentation
in the chest and the upper
abdominal wall [1]
Acanthosis Nigricans 607

in the neck [1]

over the nape [1]

in the finger [1]

in the back of the hand [1]

over the nape [1]
Cysts 609
eyelids, the antecubital fossae and popliteus, the umbilical region, the palmar
region, the plantar region, the area of the nipples, and the areolas are less fre-
quent. Mucosal involvement is more associated with malignancy than obe-
sity [12].
• Diagnosis: clinical and histopathological. Typical histopathology shows epider-
mal hyperkeratosis and papillomatosis. Areas of minimal to mild acanthosis that
may alternate with points of apparent atrophy in the epidermis. Pigmentation is
usually epidermal hyperkeratosis; however, increased melanin can be found in
the stratum corneum. Inflammatory dermal infiltrate is usually absent.
Papillomatosis, hyperkeratosis, and acanthosis are usually rare [12].
• Differential diagnosis: It is not clinically different; however, it is important to
distinguish the malignant form and the hereditary form and that associated with
obesity. It can be confused histopathologically with a Kaposi’s sarcoma, skin
tags, epidermal nevi, or confluent reticulated papillomatosis [1, 12].
Cysts
• Definition: It is a circumscribed, spherical lesion that may or may not be ele-

vated, of fluctuating or remitting consistency with a non-visible liquid or semi-
solid content. Its consistency orients toward a non-solid content, and occasionally
an operculum or drainage point can be observed [1].
• Pathogenesis: They are formed at the expense of embryonic remains, epithelial
inclusions, or glandular elements [1].
• Clinical presentation: A great variety of cysts within them are found [1]:
Fig. 23.38 Epidermoid

cyst: a well-defined
erythematous and
exophytic tumoral cyst on
the scalp [1]
Fig. 23.39 Millium cyst:

on the eyelid a dome-
shaped white-yellow
papule, 1–2 mm, not
painful, with a smooth and
shiny surface [1]
Epidermoid Cyst
They derive from the follicular infundibulum; the cysts are well-defined achromic
or yellow dermal or subcutaneous nodules of variable size from mm to cm, with a
central operculum; they are usually asymptomatic and have a content with a “ran-
cid” odor due to the “keratin.” They are located on the face and upper part of the
trunk (Fig. 23.38) [1, 2].
Milium Cysts
They are dome-shaped papules, 1–2 mm white-yellow, not painful, with a smooth
and shiny surface, and frequently located on the cheeks and eyelids of adults. In
children, it is common on the face and mucous membranes. On the palate, they are
called Epstein pearls. Eruptive milia have been reported in rare cases (Fig. 23.39) [1, 2].
Trichilemmal Cyst
Derived from the follicular isthmus, they are round, mobile, firm cysts, slow grow-
ing, asymptomatic, and rubbery in consistency and strongly adhered to the skin; the
size can vary from millimeters to 3 or 4 cm. Ninety percent is found on the scalp.
They can be single or multiple (synchronously or metachronically) [1, 2].
Cysts 611
Proliferating Trichilemmal Cyst
Clinically indistinguishable from trichilemmal cysts, they are larger up to 25 cm; it

occurs in 84% of elderly women; it is more common to have a benign course, but in
rare cases spindle cell carcinoma develops, and 30 cases of distant metastasis have
been reported [1, 2].
Eruptive Villous Cyst
Multiple small dome-shaped papules or cysts that can be asymptomatic achromic or

dark brown, located more on the trunk and less frequently on the extremities [1, 2].
Steatocystoma
They are circumscribed achromic-yellow cysts of variable size with oily content
and asymptomatic, frequently located in the thorax, armpits, and groin [1].
Dermoid Cyst
It is a circumscribed solitary cyst of variable size that generally does not exceed
2 cm located on the face [1].
Preauricular Cyst
It is a congenital preauricular fistula. Cyst or achromic invagination in the unilateral

preauricular region, mainly on the right side, occurs due to the defect in embryo-
logical fusion with entrapment of the epithelium. It occurs in 0.5–1% of the general
population. In these cases, it is advisable to evaluate hearing [1].
Pilonidal Cyst
Painful cyst with erythema on the surface that is located in the superior gluteal cleft
or sacrococcygeal area, with a higher frequency in men with a male/female ratio of
4:1 [1].
Hidrocystoma
They are translucent achromic or light blue cysts with a facial location, which can
be single or multiple. Those with an apocrine component are solitary and represent
adenomas of the apocrine sweat glands (HIDROCYSTADENOMA). Those with an
eccrine component are single or multiple and develop by dilation in the ducts due to
retention of secretion [1].
Single Bronchogenic Cyst
It is a single cyst with variability in color and size whose most frequent location is
the sternal fork, neck, or beard [1].
Thyroglossal Duct Cyst
It is a cyst located in the midline of the anterior neck in children or young adults that
arises from remains of the thyroglossal duct [1].
Ciliated Cyst of the Vulva
Rare cysts that are located on the vulva and lower extremities in young women; they
are variable in size from 1 to 3 cm, and with the rupture they drain a clear fluid that
originates in the Müllerian ducts [1].
Transparent Solitary Cyst
They have a shiny smooth surface of variable size from mm to cm that are located
on the ventral aspect of the penis of young men [1].
Omphalomesenteric Duct Cyst
It is caused by a developmental defect in the closure of the omphalomesenteric

duct [1].
Mucocele
Shiny translucent cyst with a smooth surface that varies in size that arises due to
interruption of the ducts of the minor salivary glands and develops in the lower
labial mucosa (floor of the mouth, buccal mucosa, and tongue) [1].
Cysts 613
Fig. 23.40 Myxoid cyst:

on the dorsal surface of the
distal phalanx of the finger
an erythematous cyst, with
a smooth, transparent
surface [1]
Myxoid Cyst
The most frequent digital mucous cyst in the hands, located on the dorsal surface
of the distal phalanx of the finger. They are achromic cysts, with a smooth, trans-
parent surface that drain a clear gelatinous material and ungual dystrophy (Fig.
23.40) [1, 2].
• Diagnosis:
–– Epidermoid cyst: cystic cavity lined by stratified squamous epithelium, its
rupture can generate an inflammatory or granulomatous response [1].
However, it has recently been suggested that the diagnosis can be exclusively
clinical; at the time of making the incision to extract the cyst, a characteristic
odoriferous material similar to toothpaste comes out, and, in this way, signifi-
cant costs would be saved by avoiding the histopathological study [3].
–– Trichilemmal cyst: The wall is covered by stratified squamous epithelium with
keratinization analogous to that of the root sheath of hair in catagen. The con-
tents show a homogeneous mixture of keratin aligned in concentric sheets and
lipids and frequently show calcification foci [1].
–– Proliferating trichilemmal cyst: proliferating epithelium with abrupt keratini-
zation and dense keratin formation [1].
–– Eruptive villous cysts: Stratified squamous epithelium wall, with epidermal
keratinization, its content presents loose keratin and numerous hairs in the
lumen [1].
–– Steatocystomas: The wall is made up of stratified squamous epithelium with-
out granular layer and surrounded by a thin irregular eosinophilic cuticle [1].
–– Dermoid cyst: Stratified squamous epithelium with a variety of attached struc-
tures that may be present on the cyst wall. Smooth muscle, pilosebaceous
unit, apocrine or eccrine glands, or goblet cells may be present in the wall.
This cyst contains keratin and hair follicles [2].
–– Unique bronchogenic cyst: sequestered respiratory epithelium is observed

during embryological development, which is lined with ciliated columnar epi-
thelium [1].
–– Thyroglossal duct cyst: cyst lined by squamous columnar stratified cubic epi-
thelium [1].
–– Ciliated cyst of the vulva: lined with simple columnar ciliated epithelium [1].
–– Solitary transparent cyst: lined by stratified columnar epithelium [1, 2].
–– Omphalomesenteric duct cyst: It is lined by intestinal mucous epithelium [1].
–– Mucocele: there are spaces within the connective tissue filled with mucinous
material but without lining epithelium [1].
–– Myxoid cyst: there are fissures in the dermis without epithelial lining [1].
• Differential diagnostics:
–– Epidermoid cyst: Steatocystoma, pilar cyst, lipoma, and dermoid cyst [2].
–– Trichilemmal cyst: Epidermoid cyst [2].
–– Eruptive villous cysts: Steatocystoma [2].
–– Steatocystomas: Epidermal inclusion cysts, eruptive villous cysts [2].
–– Dermoid cyst: Gliomas, encephaloceles, hemangiomas, soft tissue sarcoma,
and other epidermal cysts such as branchial sheath cysts and thyroglossal duct
cysts [2].
–– The rest of cysts do not present a differential diagnosis [1–3].
Winer’s Dilated Pore
• Definition: It is a benign adnexal tumor, derived from the infundibulum, and

represents an ectasia of the immediate intraepidermal and subepidermal portion
of the hair follicle [14, 15].
• Epidemiology/pathogenesis: Often affects white individuals, young adults,
males, and those over 40 years of age. The lesion is unique and involves the skin
of the face or neck, although it sometimes develops on the trunk; A plug is devel-
Fig. 23.41 Winer’s dilated

pore: skin-colored pore,
with white discharge on
manipulation, of 2 mm in
size, in the left cheek [14]
References 615
Fig. 23.42 Winer’s dilated pore: follicular cystic dilatation, pore cavity contains keratinous mate-
rial [14]
oped which, when removed, allows a cheesy, whitish, and moist material to
escape [14].
• Clinical presentation: It is a unique dermatosis, made up of a giant comedo in the
seborrheic areas of the face or on the back, although a case of dilated Winer’s
pore in the external ear has been documented [1]. The keratin plugs: the central
pore may be white or black, and the skin surrounding the tumor is unchanged,
inflamed, or indurated (Fig. 23.41) [14, 15].
• Diagnosis: Clinical with histopathological confirmation showing an infundibular
dilation with extension to the deep dermis, with a cavity filled with keratotic
material arranged in a laminar pattern, and epithelial covering. At the ostium
level, the lining is atrophic, while in the deep dermis, there is hypertrophy and
acanthosis. Deeper areas can be seen atrophic follicles and sebaceous structures
(Fig. 23.42) [14, 15].
• Differential diagnosis: basal cell carcinoma and trichoblastoma [14, 15].
References
1. Requena L, Requena C, Cockerel C et al. Benign epidermal tumor and proliferations chapter.
Benign melanocytic neoplasms, Neural and Neuroendocrine Neoplasms (Other than neurofi-
bromatosis) Dermatology. 3rd edn. Vol II. 202 Pag 1795- 1815-2012
Dermatol. 1984;120:214–5.
p. 445–526.
4. Goldsmith, L. Katz, S., et al. Benign Epithelial tumors, hamartomas and hyperplasias.
Fitzpatrick´s dermatology in general medicine. 8th edn. p. 1319–36. 2012.
J. Disseminated eruptive clear cell acanthoma with spontaneous regression: further evidence
of an inflammatory origin. Am J Dermatopathol. 2011;33:599–602.
6. Fukushiro S, Takei Y, Ackerman A. Pale-cell acanthosis: a distinctive histologic pattern of
epidermal epithelium. Am J Dermatopathol. 1985;7:515–27.
7. Weedon D. Lentigines, nevi and melanomas chapter 32. Weedons skin pathology. 3rd edn.
2010. p. 712–56.
8. Sardana K, Chakravarty P, Goel K. Optimal management of common acquired melanocytic
nevi (moles): current perspectives. Clin Cosmet Investig Dermatol. 2014;7:89–103.
9. Leite A, Gontijo B, Vásques F. Giant congenital nevus. An Bras Dermatol. 2013;88(6):863–78.
10. Poroqueratosis. Kanitakis. J. Dermatología. 2013;47(1):1–6, Copyright © 2013 Elsevier
Masson SAS.
11. Tchernev G, Ananiev J, Semkova K. Nevus comedonicus: an updated review. Dermatol Ther
(Heidelb). 2013;3:33–40.
12. Yung H. Acanthosis nigricans in obese adolescents: prevalence, impact, and management chal-
lenges. Adolesc Health Med Ther. 2016;8:1.
13. Schwarzenberger K, Callen J. Dermatology: L. Bolognia 2-Volume “Dermatologic
Manifestation in Patients with systemic disease” chapter 53. Vol II. 3rd edn. p 762. 2012.
14. Chang P, Rosales D, Calderón G, Gallardo C. Dilated pore of Winer. Dermatology
CMQ. 2013;11(4):261–3.
15. Stone M. Cyst. chapter 110. Vol II, 3rd edn. p. 1818. 2012.
Chapter 24
Skin Adnexal Neoplasms
Nevus Sebaceous of Jadassohn
• Definition: Originally known as an organoid nevus. The sebaceous nevus is a

non-neoplastic congenital malformation that manifests itself during childhood,
in which there is benign hyperplasia of the sebaceous glands, accompanied by
alterations of other elements of the skin of the glandular, follicular, or mesenchy-
mal type [1].
• .Epidemiology/pathogenesis: It is a benign congenital lesion, whose incidence is
estimated between 0.0002% and 0.2% of dermatological consultations. Although
its prevalence is currently unknown, it is considered a common entity in child-
hood [2]. It manifests from an early age, gradually increasing in size with growth,
during the first years of life [3]. Regarding their predilection for gender, there are
no differences. At the moment, the cause that determines its appearance is
unknown. However, it has been associated with defects in embryonic develop-
ment at the ectoderm and mesoderm, secondary to a somatic mutation or genetic
mosaicism, among which the PTCH gene has been postulated [2]. A risk of
30–50% malignant degeneration, which may appear after the age of 30, justify-
ing its surgical resection [2].
• .Clinical presentation: It is described as an alopecic plaque, with oval or linear
morphology, circumscribed, usually solitary, with a yellowish-white color and a
velvety surface, with a diameter of 1–10 cm, which is generally located on the
scalp (Fig. 24.1) (72%) and may eventually affect the face (23%), trunk, or
extremities [1, 3]. During the first years of life, it presents a progressive growth
simultaneous to that of the skin and may exhibit hyperkeratotic changes, acquir-
ing a brown color and a warty appearance, or secondary changes (20–30%) with
the appearance of papules, nodules, cysts, or papillomatous lesions inside [2, 3].
It can be part of the epidermal nevus syndrome, including abnormalities in the
central nervous system and ocular system. Additionally, it has been associated
with concomitant neoplastic lesions, both during childhood and adulthood,

https://doi.org/10.1007/978-3-030-84107-2_24
618 24 Skin Adnexal Neoplasms
Fig. 24.1 Jadassohn

sebaceous nevus: on the
scalp, there is an irregular,
yellowish, and
mammillated plaque 2.5
for 10 cm [1]
including syringocystadenoma papilliferum, trichoblastoma, keratoacanthoma,

nodular hydroadenoma, trichilemoma, sebaceous, and apocrine tumors [4].
• .Diagnosis: Although the diagnosis is mainly clinical, the histopathological
study allows the identification of microscopic changes that vary depending on
the age of the patient [5]. Thus, in the newborn, a flattened or slightly thickened
epidermis can be observed in the first months of life. The sebaceous glands are
small in size and located in the upper part of the dermis, exhibiting slight growth
around 3 months of age (due to the influence of maternal androgens) and adopt-
ing a pyriform morphology, with a wide base and narrow surface, connected to
the epidermis or infundibular follicular epithelium through the sebaceous duct
(Fig. 24.2) [5]. At puberty, a hyperplastic, hyperkeratosic, and papillomatous
epidermis is evidenced, accompanied by acanthosis, fibrovascular proliferation
of the superficial dermis, and marked hypertrophy of sebaceous glands, consti-
tuting the main finding of this entity [5, 6]. Finally, in adulthood, the epidermis
presents the maximum degree of hyperplasia, a verrucous appearance and promi-
nent sebaceous glands, with little development of hair follicles [2].
• .Differential diagnosis: It is necessary to differentiate clinically in young patients,
from juvenile xanthogranuloma, Spitz nevus; in adolescent and adult patients, it
can be confused with adnexal tumors, xanthomas, and malignant neoplasms [7].
In the event of a verrucous appearance, it must be differentiated from verrucous
epidermal nevus, verrucous vulgaris, and lichen simplex chronicus [7]. Other, no
less important, differential diagnoses are sebaceous hamartoma and sebaceous
hyperplasia [2].
.Trichoepitheliomas
• Definition: They are benign neoplasms with germinal follicular differentia-

tion [1].
• .Epidemiology: More frequent in women in the third decade of life [8, 9], or
genetic syndrome such as rhombus syndrome, Brooke-Spiegler syndrome, and
Rasmussen syndrome are associated [1].
Jadassohn Sebaceous Nevus 619
Fig. 24.2 Jadassohn

sebaceous nevus:
verrucous epidermal
hyperplasia,
papillomatosis, multiple
sebaceous glands
superficially located [1]
Fig. 24.3 Trichoepithelio-

mas: multiple papules of
4 mm and 5 mm erythema-
tous and erythematous in
the midface region [1]
• .Clinical presentation: Usually presents as a papule or nodule on the face or

upper trunk (Figs. 24.3 and 24.4). The lesions have a predilection for the nose,
and there are three clinical variants:
–– Solitary: It occurs on the nose, upper lip, and cheeks.
–– Multiple: Brooke’s disease: it occurs in 1/4 of the cases; it is of autosomal
dominant inheritance, beginning in childhood with multiple papules in the
central facial area.
Fig. 24.4 Trichoepithelio-

mas: erythematous papule
with some serous crusts is
evidenced in the left
nostril [1]
–– Desmoplastic variant: They are asymptomatic lesions that are generally soli-
tary, formed as a small annular papular lesion, with a yellowish-white color,
indurated, of firm consistency, with a raised border and a depressed center. It
is located mainly on the face, predominantly on the cheeks, near the corner of
the mouth, and exceptionally it can appear on the scalp, neck, and upper trunk.
There are also multiple cases described, and some cases are familiar [1, 8].
• .Diagnosis.
–– Trichoepitheliomas: dermal tumor with islands of basaloid cells, linear cor-
neal cysts, with squamous epithelium; in the hair follicle, it presents papillary
mesenchymal bodies, and some Merkel cells are observed. In addition, there
are fissures between the stroma and the dermis, with positive immunohisto-
chemistry for Ber-EP4, bcl-2, CK20, and CD34 positive with negative
CK7 [9].
–– .In desmoplastic trichoepithelioma: a symmetrical lesion is observed, limited,
and well circumscribed to the superficial and middle dermis, rarely extending
to subcutaneous cellular tissue. This lesion is constituted by cords and nests
of basaloid cells, they can connect with the epidermis and with the pre-exist-
ing infundibular cyst, they can intermingle with small infundibular cysts,
which contain orthokeratotic keratin. With numerous keratin cysts, foreign
body granulomas, and eosinophilic collagen. In addition to some Merkel cells
[1, 8]. Diagnostic support can be performed with immunohistochemistry
marking positive for Ber-EP4, Bcl2, CD34, CK20, and involucrin and nega-
tive for stromelysin-3 and carcinoembryonic antigen. This supports its pillar
origin. It can also express cytokeratins associated with the outer root sheath,
such as CK-15, which is used as a differential marker with basal cell carci-
noma [9].
• .Differential diagnosis: Basal cell carcinoma, sebaceous hyperplasias, sebaceous
adenomas [9], morpheiform basal cell carcinoma, sebaceous hyperplasia, soli-
tary trichoepithelioma, granuloma annulare, or scleroderma [1]. (Fig. 24.5).
Pilomatrixoma 621
Fig. 24.5 Trichoepitheliomas: juxtalobular connective tissue condensations. Keratocyst are com-
mon in this lesion [1]
Pilomatrixoma
• Definition: Malherbe’s calcified epithelioma or pilomatrixoma is a benign lesion

with differentiation of the follicles of the hair matrix. It occurs in children,
mainly on the face, neck, and extremities [8].
• .Epidemiology/pathogenesis: A mutation has been found in the activity of Beta-
catenin in 75% of cases and in the CTNNB-1 gene; with a role in the develop-
ment of the hair follicle, the gene that codes for B-catenin is a key component for
signaling that influences cell differentiation and proliferation [8, 10].
• .Clinical presentation: It presents as a solitary multilobular papule, with a stone
consistency, achromic to a bluish color (Fig. 24.6). With the sign of the positive
camping tent, which is that when stretching the skin, it shows multiple angles
and facets. In addition, calcium may leak from eroded areas [1]. Multiple lesions
are associated with myotonic dystrophy, sarcoidosis, trisomy 18, Turner syn-
drome, and Gardner and Rubinstein-Taybi syndrome [8, 10].
• .Diagnosis: A well-circumscribed nodule is seen in the reticular dermis similar
to a cyst. There are two types of cells: basophilic cells at the periphery and ghost
cells or eosinophilic shadows with a palisade that instead of nuclei have an empty
Fig. 24.6 Pilomatrixoma:

Firm 1 × 1 cm nodule,
grayish color, with central
hematic crust [10]
space. It also presents keratinocyte debris, calcifications (2/3 of cases), ossified

stroma (13%), and foreign body giant cells with a mixed inflammatory infiltrate
(Fig. 24.7) [8].
• .Differential diagnosis: Pilomatrical carcinoma, epidermoid cyst, lipoma [8, 10].
.Sebaceous Hyperplasia
• Definition: Represents an enlargement of the sebaceous gland [1].

• .Clinical presentation: It presents as one or multiple telangiectatic papules, in the
central or upper region of the face and sometimes in the upper trunk. They pres-
ent a central umbilication that corresponds to the ostium of the follicular infun-
dibulum [8]. It is associated with sun exposure and the use of cyclosporine
(Figs. 24.8 and 24.9) [10].
• .Diagnosis: It is clinical and histopathological. Histopathology shows large
mature sebaceous glands with a dilated center (it can be full of debris, bacteria,
or hair follicles), frequently present with solar elastosis (Fig. 24.10) [8, 10].
• .Differential diagnosis: Molluscum contagiosum, basal cell carcinoma [1].
.Sebaceous Carcinoma
• Definition: Sebaceous carcinoma (CS) is a rare adnexal tumor with aggressive

behavior. CS can occur in any area that contains sebaceous glands [11].
Sebaceous Carcinoma 623
Fig. 24.7 Pilomatrixoma: basophilic cell tumor with prominent nucleus, surrounded by fibrous
tissue [3]
Fig. 24.8 Sebaceous

hyperplasia: multiple
telangiectatic papules, over
the face [8]
Fig. 24.9 Sebaceous

hyperplasia: multiple
telangiectatic papules, in
the central region of the
face, they present a central
umbilication [8]
Fig. 24.10 Sebaceous hyperplasia: unchanged epidermis, proliferation of sebaceous glands, with-
out atypia. HE, 10× [8]
• .Epidemiology/pathogenesis: Represents 0.7% of skin cancer [12] [13], with an

incidence rate of 0.11 per 100,000 inhabitants per year [9], a mortality rate and
metastasis to lymph nodes and organs at a distance of 25% [12, 13]. The risk
factors for CS that have been reported in the literature are advanced age (mean
72 years) and female sex (73%) [12], although recent studies have found a slight
predominance in men [12], ethnicity (Caucasians, Asians, and Indians) [12, 13],
irradiation, genetic factors with pre-existing sebaceous lesions (Muir-Torre
Sebaceous Carcinoma 625
syndrome, Lynch syndrome), immunosuppression (kidney transplantation or

HIV), the use of diuretics, and chalazion [12].
• .Clinical presentation: The vast majority of CS occurred in the periocular region
[14], but the distribution has recently changed to 38.7% in the periorbital region,
40.8% in the extraorbital skin of the head and neck, and 19.9% in other sites such
as the trunk, extremities, or genitalia (Fig. 24.11) [12]. The clinical presentation
is a painless pink-yellowish nodule, but this clinical presentation can vary from
red papules, plaques, or nodules that are easily confused with benign skin tumors
[12]; the behavior, management, and prognosis of CS are similar regardless of
the place of origin [13].
• .Diagnosis: Histopathology shows unencapsulated lobular collections of undif-
ferentiated sebaceous cells, lipid granules present in the cytoplasm that result in
“frothy” appearance characteristics with special staining for oil red and Sudan IV
[12]. Characteristics of tumor cells consist of nuclear pleomorphism, mitotic fig-
ures, and nuclear hyperchromatism (Fig. 24.12) [12]. Adicionally, immunohisto-
chemistry plays a key role in making the differential diagnosis, and a panel of
appropriate antibodies may be useful [13]; as the antigen of epithelial membrane
(EMA), the cocktail of cytokeratins AE1 and AE3, p53, cytokeratin 7, the andro-
gen receptor, BRST-1, Cam 5.2, HMFG-1 and -2, BCA-225, and Ki67 are posi-
tive for CS [14, 15]; adipophilin and periphilin have recently shown high
sensitivity and specificity [12]; Ber-EP4 in all cases is negative for CS [14, 15].
• .Differential diagnosis: Extraocular sebaceous carcinomas should be performed
with differential diagnosis with basal cell carcinoma, squamous cell carcinoma,
amelanotic melanoma, Merkel cell carcinoma, cutaneous lymphomas, metasta-
ses, sebaceous nevus, xanthomas, and sarcoidosis [12]. Sebaceous carcinomas in
the periorbital region should make a differential diagnosis with chalazion, bleph-
aritis, conjunctivitis, keratoconjunctivitis, basal cell carcinoma, squamous cell
carcinoma, sebaceous nevi, metastasis, and xanthelasma [12].
Fig. 24.11 Adenosqua-

mous carcinoma: In the
perianal region, there is
evidence of a tumor of
approximately 4 cm, with
an erythematous friable
verrucous surface with
serous crusts [12]
Fig. 24.12 Adenosquamous carcinoma: In a histological approach, it can be evidential nuclear

pleomorphism, mitotic figures, and nuclear hyperchromatism [22]
.Syringomas
• Definition: Represents a benign adnexal tumor with much ducal differentiation

(syrinx). It can be used to describe neoplasms of either apocrine or eccrine lin-
eage [1].
• .Epidemiology/pathogenesis: Neoplasia of both apocrine and eccrine lineage.
These lesions are removed more frequently by women than by men. However, it
is not clear that it represents a true gender predilection. There is an increase in the
incidence in the Asian population as in association with Down syndrome [1] and
Nicolau-Balus syndrome (eruptive syringomas, milia, and atrophoderma ver-
miculata) [8]. Clear cell syringomas are associated with diabetes mellitus [1].
• .Clinical presentation: They appear as achromic, yellowish, small papules of
firm consistency. They are often multiple and can be eruptive (Figs. 24.13 and
24.14). Syringomas can occur anywhere on the body; it can occur in the perior-
bital area, especially the eyelids [1]. Sometimes the lesions include the upper
trunk; other sites such as the scalp, armpit, abdomen, forehead, penis, and vulva
can be compromised [9]. Although acral syringomas are rare, they have the most
eccrine lineage [1]. There are four clinical variants: (1) the localized form, (2) the
one associated with Down syndrome, (3) the generalized eruptive form, and (4)
an autosomal dominant familial form [9].
Eccrine Poroma 627
Fig. 24.13 Syringomas:

multiple light brown
papules with shiny surface
and small diameter on the
face [1].
• .Diagnosis: It is clinical and histopathological. Histopathology shows symmetri-

cal collections of fibrotic stroma, with multiple irregular islands and central cysts
in the form of “witch mirrors” or “tadpole-shaped.” [8] These structures are lined
by a single or double layer of epithelial cells, monomorphic, cuboidal [9].
• .Differential diagnosis: Microcystic adnexal carcinoma, desmoplastic trichoepi-
thelioma, sclerosing basal cell carcinoma [8].
.Eccrine Poroma
• Definition: Eccrine poroma or simple hydroacanthoma is a rare, benign neo-

plasm that originates in the eccrine sweat glands, composed of cells that differ-
entiate toward the intraepidermal portion of the eccrine sweat duct [16].
Fig. 24.14 Syringomas:

multiple skin color and
yellowish papules with
shiny and smooth surface
on the periocular area [1]
Fig. 24.15 Eccrine

poroma: solitary red
nodule, with a verrucous
surface on the right second
toe [16]
• .Epidemiology: Its incidence ranges between 0.001% and 0.008% [8]. It can
occur at any age, although it is more frequent in patients over 40 years of age. No
racial or gender predilection has been found. The pathogenesis of eccrine poroma
is unclear, but its appearance after trauma, burn, or radiation exposure has been
documented [16].
• .Clinical presentation: It presents as an exophytic lesion, pinkish or skin-colored
that usually occurs solitary; it is not more than 3 cm and can be lobed (Figs. 24.15
and 24.16) [16]. Although cases of pigmented lesions have been reported [17],
most are found on the soles or lateral faces of the feet and on the palms, where
there is a high concentration of eccrine sweat glands [16, 17]. They have also
been described in non-hairy areas of the extremities, chest, back, head, and
neck [16].
Eccrine Poroma 629
Fig. 24.16 Eccrine

poroma: Tumor plaque of
2 cm, violet color, with
hyperkeratosis, is observed
on the left sole [16]
• .Diagnosis: Histology is characterized by being a tumor composed of masses of

cubic monomorphic epithelial cells that originate in the epidermis and extend
toward the dermis. Occasionally, it is located entirely in the epidermis (known as
a simple hydroacanthoma) or in the dermis (dermal duct tumor).
Immunoperoxidase staining demonstrates epithelial membrane antigen on poroid
cells and carcinoembryonic antigen on the peripheral border of cuticle cells [16].
• .Differential diagnosis: Amelanotic melanoma, telangiectatic granuloma,
adnexal tumor [16, 17].
.Hidradenoma
• Definition: It is an infrequent benign tumor of the distal portion of the sweat

glands, asymptomatic with slow growth; it is also called clear cell hydroade-
noma, eccrine acrospiroma, solid cystic hydroadenoma, clear cell acrospiroma,
clear cell myoepithelioma, and eccrine adenoma of the sweat gland [8, 18].
• Epidemiology/pathogenesis: Hidradenoma is a rare tumor that represents 1.61%
of adnexal tumors and arises from the distal portion of the acrosyringium duct
[18]. The average age of presentation is 37.2 years, but it can occur at any age,
being more common in women, with a ratio of 1:1.7. Hydroadenomas can have
eccrine or apocrine origin [18, 19]. Most are benign in 94%; only 5.8% have a
risk of malignancy. It rarely occurs in children; there are few cases reported in
childhood and they resolve spontaneously [18]. An attempt has been made to
classify hydroadenomas into two groups: those of eccrine differentiation, called
poroid hydroadenomas, and those of apocrine differentiation, called clear cell
hydroadenomas or nodular hydroadenomas [19]. Nodular clear cell hidradenoma
is the most common subtype, 95% [20]. It usually presents as a single lesion, of
different sizes ranging between 0.5 and 2 cm in diameter, round or oval in shape,
pedunculated or with a cystic appearance; they tend to ulcerate, although this is
exceptional. The presence of pigment in sweat gland tumors is uncommon. In the
present case, the presence of color could correspond to dilated, congestive vas-
cular channels, full of erythrocytes. It is frequently located on the scalp, face,
chest, and extremities, but it has also been described in the armpits, breasts,
shoulders, abdomen, palms, inguinal region, and vulva [20].
• .Clinical presentation: The clinical manifestation of nodular hidradenoma is
confused with nodular or cystic lesions of the skin and has classic characteristics
of other skin tumors (Figs. 24.17 and 24.18) [21]. Therefore, histopathology and
immunohistochemistry are key to the diagnosis [18].
• .Diagnosis: Histopathology is characterized by a well-circumscribed nodular
proliferation in the dermis, whose nodules show a solid and cystic configuration
(Fig. 24.19) [18]. The cysts can be of considerable size and are surrounded by
tumor cells that contain homogeneous eosinophilic material. Cystic spaces are
formed as a result of a degeneration of tumor cells [19]. It is composed of a mix-
ture of polyhedral and spindle cells with eosinophilic cytoplasm and other clear
ones rich in glycogen [19]. Likewise, elongated grooves have been described in
the nucleus of polyhedral cells in 88% of cases [20]. This tumor presents a clear
formation of ductal structures, and it is common to find squamous metaplasia.
Their stroma is hyaline [18]. They have tubule or cuticle duct formation with
apocrine, eccrine, or squamous differentiation [14]. They may also have horn-
plugged cornified cells arising around the lumen with a well-defined eosinophilic
cuticle that resembles an intraepidermal portion of the eccrine duct [14]. PAS is
Hidradenoma 631
Fig. 24.17 Nodular

hidradenoma: red tumor,
round in shape, cystic
surface [18]
Fig. 24.18 Nodular

hidradenoma: red tumor,
round in shape, cystic
surface over right
frontoparietal region [18]
Fig. 24.19 Nodular

hidradenoma: Well-
circumscribed nodular
proliferation in the dermis,
whose nodules show a
solid and cystic
configuration. It is
composed of a mixture of
polyhedral and spindle
cells with eosinophilic
cytoplasm. HE, 4× [19]
positive, due to the accumulation of glycogen; the tumor has reactivity to keratin,
epithelial membrane antigen, carcinoembryonic antigen, S-100 protein, and
vimentin, with expression of cytokeratins 6/18, 7, 8/18 in squamous cells, tubu-
lar lining cells, and cystic spaces. 10/17/18 cytokeratins are expressed in squa-
mous cell aggregates [19, 22].
• Differential diagnosis: Clinical differential diagnoses may include metastatic
tumors, leiomyomas, and other adnexal tumors, such as poromas, hemangiomas,
glomus tumor, cutaneous lymphomas, dermatofibrosarcoma protuberans, follic-
ular, and trichilemmal cyst [19–22]. (Fig. 24.20).
Syringocystadenoma papilliferum
• Definition: Syringocystadenoma papilliferum (SCAP) is an adnexal tumor of the

sweat glands whose nature, eccrine or apocrine, is yet to be determined [1, 8].
• .Epidemiology/clinical presentation: It appears as a usually solitary plaque pap-
ule or nodule, preferentially located on the head and neck, generally having a
crusty surface, associated in up to 50% of cases with an organoid nevus
(Fig. 24.21). Although it can occur at any age, the diagnosis is frequently made
Syringocist Papillary Adenoma 633
Fig. 24.20 Nodular

hidradenoma: Well-
circumscribed nodular
proliferation in the dermis,
whose nodules show a
solid and cystic
configuration. HE,
10× [19]
Fig. 24.21 Syringocist

papillary adenoma: tumor
plaque on the scalp
yellowish with irregular
edges, well defined, with a
verrucous surface with
some eroded areas [1]
during adolescence, since it often increases in size during puberty. Local bleed-
ing is often seen after minor trauma, and clear fluid drainage is not uncom-
mon [1, 8].
• .Diagnosis: It is characterized by a crateriform formation that in the upper area
is lined by a surface of infundibular squamous epithelium and in the lower area
by a bilayer of cells, cuboidal basaloids, and columnar apocrine cells with secre-
tion by decapitation in the inner layer (Fig. 24.22). This cellular bilayer coats
papillary formations that project into the cavity and contain central connective
axes with an infiltrate typically rich in plasma cells. Apocrine glands enlarged in
Fig. 24.22 Syringocist

papillary adenoma:
papillary structures
covered by a double layer
of epithelium, in the inner
side: decapitation
secretion. Stroma with
lymphocytes and large
numbers of plasma
cells [1]
number and size are frequent in the vicinity. A plasma cell infiltrate is frequently
accompanied by apocrine lineage neoplasms and the presence of plasma
cells [1, 8].
• .Differential diagnosis: With other adnexal tumors [1].
.Spiradenoma
• Definition: Benign neoplasm of sweat glands [1, 8].

• .Pathogenesis: Classically, spiradenoma has been considered an eccrine neopla-
sia. Some authors consider that it is a lesion with apocrine differentiation mainly
due to its association with follicular lesions [1].
• .Clinical presentation: It is generally a solitary lesion [1], but there are multiple
segmental cases [8] that appear as a deep or subcutaneous dermal nodule that is
Syringocist Papillary Adenoma 635
Fig. 24.23 Spiradenoma:

posterior internal view of
the right leg, on distal third
shows a single nodular
lesion, pink-gray, raised,
with a central
ulceration [1]
located preferentially on the trunk and proximal portion of the extremities, with-
out predilection for sex or by any age group (Figs. 24.23 and 24.24). It usually
presents as a hemispheric lesion with a firm touch, bluish-red in color, and a
diameter between 0.3 and 5 cm. They can be asymptomatic tumors, but they are
usually painful. The presence of pain is a sign of suspicion of the diagnosis of
spiradenoma before a tumor lesion of this type [1].
• .Diagnosis: The clinic has two diagnostic keys that are deep dermal or subcuta-
neous tumors on the trunk and are painful. Its correct diagnosis requires a com-
plete histopathology study [8], where tumor nodules are observed at low
magnification, well-defined, rounded, and hypercellular, located in the deep der-
mis or the adipose panicle, which are separated from each other (Fig. 24.25) [9].
In others, there is a very prominent loose and vascular stroma around and inside
the nodules, giving rise to an angiomatoid image [1]. Each of the tumor nodules
are composed of two types of cells: dark basaloid cells that are in the periphery
Fig. 24.24 Spiradenoma:

single nodular lesion,
pink-gray, raised, showing
a central ulceration
and lighter cells that tend to occupy the central area. Occasionally, there are
images of ductal differentiation [9]. No nuclear atypia or mitosis is observed [1, 9].
• .Differential diagnosis: Clinically, a differential diagnosis should be made with
other painful skin tumors such as those encompassed under the acronym
ENGLAND: spiradenoma (E), neurofibroma (N), glomangioma (G), leiomyoma
(L), Angioleiomyoma (A), neurilemoma (N) and dermatofibroma (D) [1].
Histologically, only highly cellular glomus tumors with few vascular images can
pose a differential diagnosis. In case of doubt, immunohistochemistry is diag-
nostic. Cutaneous cylindroma: preferential clinical location on the scalp and
head. They are practically never painful. Histologically, they are composed of
large irregular masses, are more superficial than spiradenomas, and show the
presence of a large amount of basement membrane-like material surrounding the
tumor nests and in the form of PAS-positive eosinophilic globules within the
tumor nodules [1].
.Cylindroma 637
Fig. 24.25 Spiradenoma (histopathology). a well-circumscribed lesion composed of round-oval

and eosinophilic cell nests in dermis, also shows ductal structures and cystic degeneration
.Cylindroma
• Definition: A form of benign adnexal tumor that is closely related to spirade-

noma [1, 8].
• .Epidemiology/pathogenesis: It is more frequent in women, with a predominance
in the head and neck. It is related to Brooke-Spiegler syndrome, or multiple cyl-
indromatosis (both are autosomal dominant conditions) [1, 8], where there is a
mutation in the CYLD gene that increases the transcription factor NF-KB given
by cylindromas, multiple trichoepitheliomas, and spiradenomas [1].
• Clinical presentation: Presented as a red, smooth, solitary nodule, or multiple
tumors, which are clinically indistinguishable [8]. Solitary lesions frequently
involve the head and neck, with a predilection for the scalp (Figs. 24.26 and
24.27) [1, 8]. When multiple cylindromas coalesce and form a giant plaque on
the scalp, it is called a turban tumor [1, 8].
• .Diagnosis: It is clinical and histopathological, showing islands of basaloid cells
in puzzle form in the dermis. Surrounding the hyaline material contains sweat
ducts and contains type IV collagen which are PAS (+) [1].
• .Differential diagnosis: Spiradenoma, milia [1].
Fig. 24.26 Cylindroma:

an erythematous solitary
tumor with a smooth
surface, without hair shafts
and well-defined edges, on
the scalp of a woman [1]
Fig. 24.27 Cylindroma:

skin color tumor on the
scalp of a woman, with a
smooth surface and
well-circumscribed
edges [1]
References
1. Requena L, Requena C, Cockerel C et al. Benign epidermal tumor and proliferations chapter,
bromatosis) Dermatology. 3rd edn. Vol II. 202 Pag 1795- 1815-2012
Dermatol. 1984;120:214–5.
p. 445–526.
4. Schwarzenberger K, Callen J. Dermatologic Manifestation in Patients with systemic disease
chapter 53. Vol II. 3rd edn. p 762. 2012.
5. Stone M. Cyst.chapter 110.Vol II, Third Edition.p1818 2012
6. Valdivia L, Escalante E, et al. Características clínicas e histopatológicas del nevus sebáceo de
Jadassohn en el Hospital Central de Aeronáutica. Dermatol PERU. 2012;22(1):10.
7. Rtihbciri H. Organoid nevus (nevus sebaceous). In: Demis J, editor. Clinical dermatology, vol.
4. Philadelphia: Lippincott Company; 1994. p. 23–4.
8. Brinster N, Liu N, et al. Nevus sebaceus of Jadassohn. Dermatopathology: high-yield pathol-
ogy. 2011. p. 407–8.
References 639
9. Llancapi P, Paiva O. Nevo sebáceo de Jadassohn. Rev Chil Pediatr. 1996;67(2):84–6.

10. Johnston R. Tumors of cutaneous appendages Chapter 33. Weedons skin pathology essentials:
expert consult: dic. 2011
11. McCalmont T. Adnexal neoplasms. Bolognia dermatology. Vol II. 3rd edn. p. 1829–1849. 20
12. Kyllo RL, Brady KL, Hurst EA. Sebaceous carcinoma: review of the literature. J Dermatol
Surg. 2014;41:1.
13. Buitrago W, Joseph AK. Sebaceous carcinoma: the great masquerader Emerging concepts in
diagnosis and treatment. Dermatol Ther. 2008;21:459–66.
14. Chang AY, Miller CJ, Elenitsas R, et al. Management considerations in extraocular sebaceous
carcinoma. Dermatol Surg. 2016;42 Suppl 1:S57.
15. Mulay K, White VA, Shah SJ, Honavar SG. Sebaceous carcinoma: clinicopathologic fea-
tures and diagnostic role of immunohistochemistry (including androgen receptor) Originally
received Jan. 8, 2014. Final revision Mar. 18, 2014
16. Vélez N, Calle J, Velásquez C, et al. Poroma ecrino. Rev Asoc Colomb Dermatol.
2009;17:233–5.
17. Cardenas M, Diaz C, Rueda R. Pigmented eccrine poroma in abdominal region. a rare presen-
tation. Colombia medica de Cali. 2013;44(2):115.
18. Claudia Marcela Arenas, Yuly Andrea Garcías María Claudia Carrillo Hidroadenoma Rev
Asoc Cohmb Dermatol. 2013;21:4 (Oct-Dic), 364-3
19. Maiti T, Somanna S, Devi BI. Malignant nodular hidradenoma of scalp. J Neurosci Rural
Pract. 2014;5(4):423.
20. Lee YB, Song EJ, Park SM, et al. Nodular hidradenoma of the wrist with spontaneous regres-
sion in a 7-month-old infantInternational. J Dermatol. 2014;53:e578–96.
ogy. p. 407–408. 2011.
22. Cortes E, Dominguez L, Vega E. Hidradenoma nodular de células claras. Dermatol Rev Mex.
2013;57:336–41.
Chapter 25
Muscle, Adipose Tissue, and Cartilaginous
Neoplasms
Lipoma
• Definition: The most frequent benign tumor composed of mature adipocytes [1].
• Epidemiology/pathogenesis: Represents the most common mesenchymal neopla-
sia. Lipomas are usually solitary, but in 5–10% they can be multiple and associ-
ated with lipomatosis or less frequently a multisystemic syndrome. Lipomas
develop at any age, but usually appear between the fourth and sixth decades of
life. Their pathogenesis is unknown since most of the time they represent an inci-
dental finding [1, 2]. The incidence of lipomas increases in two-thirds of the cases
who are overweight and diabetic and in those with chromosomal aberrations. This
abnormality is heterogeneous and frequently consists of translocations between
12q13-15 and other chromosomes. This 12q13-15 region contains HMGA2 genes
that encode a transcriptional regulatory factor and indicator of high morbidity [1].
• Clinical presentation: Classically, lipomas present as solitary, mobile, asymp-
tomatic, and soft nodules (Fig. 25.1). They are usually oval in shape and can feel
multilobular. Many of the lipomas are a few centimeters in diameter, but occa-
sionally they can reach up to 10 cm in diameter. However, lipomas can develop
from any fatty tissue, the most frequent sites are the neck, proximal extremities,
forearms, and buttocks. Lipomas also occur on the trunk but are rarer. The inci-
dence of lipomas is slightly higher in men than in women [1, 2]. Lipomas usually
have a slow growth phase then remain stable in size and do not tend to regress.
The growth rate can accelerate during periods of weight gain, but losing the
weight does not affect your size. Losing weight makes lipomas more clinically
apparent. Multiple lipomas can be seen in patients with lipomatosis or in multi-
systemic syndromes such as Proteus syndrome, diffuse or infiltrated lipomatosis
which is characterized by infiltration of the subcutaneous cell tissue, muscle,
skin, and sometimes fascia and bone. This entity usually occurs before the age of
30 and is rarely congenital. Diffuse lipomatosis has been described associated
with tuberous sclerosis and paralytic poliomyelitis, familial multiple lipomato-

https://doi.org/10.1007/978-3-030-84107-2_25
642 25 Muscle, Adipose Tissue, and Cartilaginous Neoplasms
sis, Proteus syndrome, hemihyperplasia– multiple lipomatosis syndrome,

CLOVE syndrome, benign symmetric lipomatosis, painful adiposis, Gardner
syndrome, Bannayan–Riley–Ruvalcaba syndrome [1].
• Diagnosis: Soft tissue ultrasound is clinical and useful for diagnosis [2]. However,
the confirmatory test will always be the histopathological study [1]. Lipomas are
composed of a population of uniform mature fat cells with an eccentric nucleus.
Fat cells start in the lobes with scattered capillaries in the lesion. With absence of
mitosis (Fig. 25.2) [1].
Fig. 25.1 Lipoma: a soft,

round, movable,
euchromatic solitary
nodule, located in the
thigh [1]
Fig. 25.2 Lipoma: mature adipocytes with a conspicuous fibrous tissue component [1]
References 643
• Differential diagnosis: Other variants of bening fatty tumors: Hibernomas,

angiolipoma, myolipoma, chondroid lipoma, lipoblastoma, and spindle-cell/
pleomorphic lipoma [1].
References
1. Requena L, Requena C, Cockerel C, et al. Benign epidermal tumor and proliferations chapter
bromatosis). Dermatology. 3rd edn. Vol II. 202 Pag 1795- 1815-2012.
Dermatol. 1984;120:214–5.
Chapter 26
Vascular Malformations
Capillary Malformations
• Port-wine stain: They are present at birth as well-demarcated macules and red
patches (Fig. 26.1). The port-wine stain is not the correct term for congenital
capillary lesions of the middle of the face (forehead, glabella, nasal tip, and fil-
ter), eyelids, or occipital region. These lesions are known as simple nevus or
salmon spot. It is also known as the “kiss of the angel” on the forehead or the
“peck of the stork” on the neck. Many spontaneously fade between 1 and 3 years
of age, the facial ones more often than those in the nape area [1]. The growth of
the port-wine stain is proportional to the growth of the child. This may be local-
ized or have a segmental pattern, but they do not follow Blaschko’s lines. Some
are multifocal and generalized. The facial port-wine spots are frequently distrib-
uted according to what have classically been considered sensitive dermatomes of
the trigeminal nerve, with three recognized areas: V1 (ophthalmic region: fore-
head and upper eyelid), V2 (maxillary region), and V3 mandibular region [1].
Ocular involvement is more frequent when it affects both the V2 and V1 regions.
Glaucoma may become apparent only in late childhood; therefore, regular evalu-
ation of visual function and eye pressure should be routine throughout your life.
Neurological symptoms are due to cerebral hemiatrophy and calcifications that
can develop in association with leptomeningeal vascular malformation.
Neurological consequences can include seizures, either affecting the side of the
body opposite the vascular abnormality or generalized. Additionally, they may
have contralateral hemiparesis or hemiplegia, developmental delay (e.g., in
motor and cognitive skills), emotional and behavioral problems, attention deficit,
and migraine headaches. Doing early neuroimaging studies can identify and
delimit the extension of the central nervous system, as well as endocrine dys-
function; it can occur due to the effects of Sturge-Weber syndrome in the
hypothalamic-pituitary axis [1].

https://doi.org/10.1007/978-3-030-84107-2_26
646 26 Vascular Malformations
Fig. 26.1 Port-wine stain:

male patient presents a
macula or erythematous
spot with well-defined
irregular borders that
compromises the
interciliary region, right
upper and lower eyelid,
nasal dorsum, right malar
and zygomatic arch area,
and upper lip with an
increase in size [1]
• Phakomatosis pigmentovascularis can be associated with Sturge-Weber syn-

drome: phakomatosis pigmentovascularis Ia/b occurs in less than 5% with an
epidermal nevus + Sturge-Weber syndrome; IIa / b phakomatosis cesio flammea
occurs in 75% of the cases of dermal melanocytosis (aberrant Mongolian
spot) + Sturge-Weber syndrome; other lesions that may occur include an anemic
nevus, hypotrichosis, lipohypoplasia, and hypoplastic nails. Phakomatosis spilo-
rosea IIIa / b occurs in 10% with nevus spilus + Sturge-Weber syndrome such as
anemic nevus, lymphedema, and hypotrichosis. Unclassified phakomatosis pig-
mentovascularis Iva / b occurs in 10% with variable characteristics of type II + III
or II + V: anemic, hyper or hypopigmentation nevus, and sebaceous nevus. Va /
b phakomatosis cesiomarmorata occurs in less than 5% of cases as a dermal
melanocytosis + congenital telangiectatic marmorata cutis [1, 2].
• Klippel-Trenaunay syndrome: It is defined as a capillary malformation associ-
ated with progressive overgrowth of the affected limb. Additional findings may
include extension of trunk skin vascular malformation, lipomatosis, lymph-
edema, and vascular lesions of the gastrointestinal and urinary tract. The skin
Arterial 647
lesions appear as a pink to bright red macula in distribution when roasting on the
affected limb or a well-defined, geographic, red to purple patch that tends to
affect the lateral aspect of the thigh, knee, and leg, often having a lymphatic
component and overlapping purple or light-colored vesicles. They have compli-
cations such as limb overgrowth and cellulite [1]. It can also be associated with
chronic intravascular coagulopathy with high levels of D-dimer and low levels of
fibrinogen, and patients are at risk of deep vein thrombosis, chronic thromboem-
bolism, pulmonary hypertension, or even life-threatening embolism [1].
Arterial
Angiohistiocytoma
• Definition: It is a reactive tumor process of vascular origin, of slow evolution and

benign course [1].
• Epidemiology/clinical presentation: Angiohistiocytoma is an entity with a higher
prevalence in women of 40 years, characterized by slowly growing erythematous
or violaceous papules, generally grouped on the extremities: on the calves,
thighs, and back of the hands (Figs. 26.2 and 26.3). Cases have also been
described in the face, chest, and generalized forms. It is not clear whether it is a
reactive process or a neoplasm, as it may resemble Kaposi’s sarcoma, but it is not
associated with herpes virus 8 [2].
• Diagnosis: It is clinical and histopathological with a proliferation of capillaries
and venules in the dermis, accompanied by a lymphohistiocytic infiltrate, with
multinucleated giant cells, with a palisade nucleus, and with eosinophilic cyto-
plasm that expresses vimentin and positive factor XIIIa (Fig. 26.4) [2, 3].
• Differential diagnosis: Dermatofibroma, angiofibroma, lymphocytoma, lichen
planus, angiolymphoid hyperplasia with eosinophilia and Kaposi’s sarcoma [2].
Telangiectasias There is dilation of the capillaries. It presents as punctiform, stel-
late, or linear red lesions that are distributed in a localized, segmental, or general-
ized way [1].
Cutis marmorata telangiectatica congenita It is characterized by a reticulated

pattern interspersed with telangiectasias and prominent veins. It frequently affects
one or more extremities and quadrants of the trunk. There may be atrophy in the
network pattern especially over the joints and may result in ulceration and scar for-
mation. It resolves after the year of life, but some remain a residual purplish net-
work. Up to 50% of patients have associated abnormalities such as hypoplasia of the
affected limb and additional vascular malformations. Skeletal defects (syndactyly),
ocular involvement (glaucoma), and neurological defects are occasionally observed,
especially in patients with generalized telangiectatic cutis marmorata. Adams-Oliver
Fig. 26.2 Angiohistiocy-

toma: multiple erythema-
tous papules that coalesce
to form annular plaques
located in the left lower
extremity [1]
syndrome combines distal defects of the transverse limbs, scalp skin, and skull
defects (aplasia cutis congenita) and variable heart malformations with congenital
telangiectatic cutis marmorata or a reticulated skin marmorata. Recently, a telangi-
ectatic pseudo cutis marmorata has been described in infants with neonatal lupus
erythematosus [1].
• Angiokeratomas: They are well-circumscribed vascular lesions consisting of
superficial vascular ectasia and hyperkeratosis (Figs. 26.6 and 26.8) [1]. They
result from ectatic dilation of pre-existing vessels in the papillary dermis. Of
which five variants have been reported [1].
• Mibelli variant angiokeratoma: It predominates in women in childhood and ado-
lescents, as warty lesions on the bony prominences of the hands, feet, elbows, or
knees (Fig. 26.5) [1].
• Fordyce angiokeratomas: More frequently in older men (can develop in their 20s
and 30s). They present as red-black papules along the superficial vessels of the
scrotum but also on the vulva (Fig. 26.7) [1].
Arterial 649

toma: multiple erythema-
tous papules that coalesce
to form plaques with an
active border, located in
the right lower
extremity [1]
• Solitary or multiple angiokeratomas: They appear as small warty black papules

on the lower extremities or in any part of the body, resulting secondary to trauma
or chronic irritation of the wall of the venule vessel in the papillary dermis [1].
• Circumscribed angiokeratoma: It presents in children, as a unilateral plaque with
small discrete or hyperkeratotic papules and nodules that frequently converge
(Figs. 26.9 and 26.10). They occur on the trunk, limbs, or legs, with a predomi-
nance in women [1, 2].
In the plantar region, violaceous papules of 1 mm with well-defined regular
edges are evident.
• Angiokeratoma corporis diffusum: It has a swimsuit-trunk distribution, as multiple
papules, frequently conglomerated (Fig. 26.11), associated with Anderson-Fabry
disease (alpha galactosidase deficiency, caused by accumulation of lysosomes;
recessive X-linked disorder), fucosidosis, and other enzyme disorders [2].

toma: thin-walled vessels
and lines by bland
endothelial cells. Note the
angulated multinucleate
cell with prominent
nucleoli. Mast cells and
spindled cells are also
apparent [2]
Fig. 26.5 Mibelli variant

angiokeratoma: lateral
aspect of the second finger
on the right hand, presence
of erythematous papules
with violaceous areas
2 mm in diameter with
borders [1]
• Diagnosis: In most capillary malformations, it is clinical; however, in angiokera-

tomas, histopathology shows dilation of the vessels of the papillary dermis,
forming large cavernous canals, with irregular acanthosis of the epidermis and
elongation of the epidermal ridges; they look like a small papule on the epider-
mis [2]. They are PAS and Sudan positive. The vessels of angiokeratomas do not
express positive CD34 [2].
• Differential diagnosis: Differentiate from other vascular lesions, and due to its
dark or thrombosed color, it can resemble a melanoma [1].
Arterial 651
Fig. 26.6 Angiokerato-

mas: left hand, palmar
region, presence of
erythematous papules of
1–2 mm with violaceous
areas inside, some of
which converge to form a
plaque [1]
Fig. 26.7 Fordyce

angiokeratomas: Violet
papules 1 mm in diameter
in the scrotum [1]
Fig. 26.8 Angiokerato-

mas: abdomen at the level
of the midline, there are
violaceous papules with a
smooth and shiny surface
edges with a linear
distribution [1]
Fig. 26.9 Circumscribed

angiokeratoma: Lower
limb, presence of
converge forming plates
edges with a verrucous
surface with yellowish
hyperkeratotic areas
Arterial 653
Fig. 26.10 Circumscribed

angiokeratoma: Lower
limb, presence of
converge forming plates
edges with a verrucous
surface with yellowish
hyperkeratotic areas [1]
Fig. 26.11 Angiokeratoma

corporis diffusum: The left
hemithorax shows
erythematous and
violaceous non-follicular
papules of 2–3 mm in
diameter on an
erythematous background,
some papules converge to
form a plaque with
edges [1]
Venous Malformations
• Cephalic venous malformation: They are recognized for being blue and soft and
with a tendency to fill. It can occur focally or segmental. These injuries lead to
aesthetic and functional problems. It can affect the lips, the oral mucosa, and
deeper structures such as the muscles, the infratemporal fossa, and the orbit. It
can be expanded to the head depending on the position. Patients with
parapharyngeal and laryngeal malformation should be monitored for sleep apnea
due to the risk of death during sleep. Twenty percent of patients with cephalic
venous malformation have skeletal defects. The development of this venous
anomaly can cause headache but does not confer a risk of cerebral hemor-
rhage [1].
• Glomuvenous malformation Previously known as glomangioma, this represents
a variant of venous malformation of glomus cells around distorted venous chan-
nels. They occur as small solitary lesions, nodules, or large segmental blue-
purpuric plaques with hyperkeratosis and a cobblestone appearance [1]. It tends
to be tender on palpation or when partially compressed. It does not affect the
viscera or the joints. Occasionally, there is compromise of the mucosa (deep
intraoral lesions) or superficial invasion of the muscles. Only 1% have a family
history of similar injuries [1].
• Diagnosis: It is clinical [1].
• Differential diagnosis: They are usually confused with deep infantile hemangi-
omas [1].
Lymphatic Malformations
• Hemangiolymphangioma: These are angiomatous lesions in which blood and

lymphatic vessels are combined. Currently, it is thought that its origin is a pro-
cess of altered angiogenesis, caused by an excess of fibroblast growth factor
(FCF), a peptide with the ability to stimulate the differentiation of mesenchymal
cells into cells of vascular lineage, which induces the proliferation of an angio-
blastic embryonic tissue. They are usually congenital or appear in the first years
of life. Growth is progressive and painless. Their prognosis is good since they
generally, but not always, follow a benign course [3].
• Diagnosis: It can be clinical, by magnetic resonance or by computerized axial
tomography when they are deep, but the definitive diagnosis will always be given
by histopathology. When there is a mixture of blood and lymphatic vessels, in
order to distinguish one from the other, immunohistochemical techniques are
sometimes used. These techniques make it possible to detect the vascular endo-
thelial growth factor receptor, which is present in a higher proportion in lym-
phatic vessels, by means of antibodies. When they appear in adults, there are
Other Vascular Disorders 655
authors who speak of a confluence of predisposing factors (areas with abnormal

lymphatic vessels) and precipitating factors (repeated traumas in the area) [3].
Arteriovenous Malformations
• Arteriovenous malformations are fast-flow vascular malformations composed of

a complex vessel network directly connecting feeding arteries to draining vein,
creating anarteriovenous nest. They are rare and constitute the most dangerous
group of vascular abnormalities. Schobinger s taging was adopted by the ISSVA
in order to classify arteriovenous malformations according to their severity [1].
• It presents four stages:
–– 1. Resting/inactive stage – macular or slightly infiltrated, red lesions simulat-
ing a Sturge-Weber syndrome [1]
–– 2. Expansion phase of the hot mass with a blow [1]
–– 3. Destruction phase – necrosis, hemorrhage, ulceration, and osteolytic lesions [1]
–– 4. Decompensation phase [1]
–– In 40% of patients [1], arteriovenous malformations are visible at birth; the
rest appear later. Its most common location is cephalic (~ 70% of patients).
Puberty (75% of patients), pregnancy (25% of women), and trauma can lead
to a worsening. The syndromes associated with these arteriovenous malfor-
mations are Cobb syndrome, Bonnet-Dechaume-Blanc syndrome, Parkes
Weber syndrome, and hamartoma-PTEN tumor syndrome [1].
Other Vascular Disorders
• Venous lake: Small, slightly raised, dark-blue lesions that predominate on the
lips, ears, or face of older adults (Fig. 26.12) [4].
• Diagnosis: Clinical to histopathology represents telangiectasias in the dermis,
like a dilated venule or many interconnected spaces that contain erythrocytes.
Thrombosis is sometimes present [4].
• The anemic nevus: It is a congenital pale area of the skin, which is most com-
monly found in the upper part to the middle of the trunk. These patches have an
irregular border and an average diameter of 5–10 cm. Within the lesion, local
blood vessels are highly sensitive to endogenous catecholamines and perma-
nently vasoconstrict (Figs. 26.13 and 26.14). The limits of the lesion are rendered
imperceptible under pressure (or diascopy) to produce whitening of the sur-
rounding skin. In contrast, the application of local heat or ice often accentuates
the injury. The limits become hyperemic during warm-up, while the lesion wid-
ens pale. There are no histological changes reported [4].
• Diagnosis: Clinical [4].
Fig. 26.12 Venous lake:

Red-bluish papule of 4 mm
glossy surface, well-
defined regular edges on
the lower lip [3]
Fig. 26.13 Anemic nevus:

a hypopigmented macula is
evident in the posterior
thorax
Cherry or Cherry Angioma
• Definition: It is the most common acquired cutaneous vascular proliferation [1].

• Pathogenesis: It occurs equally in both sexes. Occasionally, it can develop during
adolescence and in the third decade of life and increases with the passing of the
years. Many patients have more than one injury after age 60, with an increase in
the number of angiomas after pregnancy and can regress with postpartum.
Therefore, it is suggested that a hormonal factor may be important in the patho-
genesis [1], observing an increase in prolactin levels [2] and inflammatory medi-
ators such as chemokines (IL-8 / CXCL8, RANTES / CCL5, MCP- 1 / CCL2
and fractalkine / CX3CL1) [2].
• Clinical presentation: They are dome-shaped, round or oval papules of bright red
color that vary from a few to many millimeters in diameter. Lesions can be pol-
ypoid. The most frequent site is the trunk and hind limbs; it is rarely found on the
hands, feet, and face (Fig. 26.15) [1].
• Diagnosis: It is clinical and histopathological; ectatic capillaries and postcapil-
lary venules are observed between the papillary dermis and the superficial reticu-
Telangiectatic Granuloma 657
Fig. 26.14 Anemic nevus:

hypopigmented macula is
evidenced in the posterior
thorax with a well-defined
approach of irregular
borders
lar dermis (Figs. 26.16 and 26.17). Early lesions are characterized by a small
lumen and endothelial cells [1].
• Differential diagnosis: glomeruloid or petechiae hemangiomas [1], eruptive
hemangiomas, like in patients with multiple myeloma [3].
Telangiectatic Granuloma
• Definition: Idiopathic vascular neoplasm, presenting abruptly that tends to grow

rapidly and bleed easily. There is no evidence that it is an infectious process [6].
• Epidemiology/pathogenesis: With a slight predominance in men but without
racial or family predisposition. Gingival lesions are relatively common during
pregnancy. Pyogenic or telangiectatic granuloma exhibits a number of clinical
features that suggest reactive neovascularization, including a common associa-
Fig. 26.15 Cherry

angioma: Red shine
papules [3]
Fig. 26.16 Cherry angioma: Ectatic capillaries and postcapillary venules are observed [3]
tion with a pre-existing lesion or irritation, with limited growth capacity, and
multiple eruptions can be localized or disseminated. The occasional eruption of
pyogenic granulomas with other pre-existing malformations such as the vino-
porto vascular malformation suggests that blood flow abnormalities may be ety-
mologically important [6]. There are also pyogenic satellite granulomas, and one
theory of these would be the release of an angiogenic substance by the primary
tumor [6, 7].
Telangiectatic Granuloma 659
Fig. 26.17 Cherry angioma: between the papillary dermis and the superficial reticular dermis,
ectatic capillaries [3]
• Clinical presentation: It presents as a solitary red papule or polyp that grows

rapidly over a course of weeks to months, stabilizes, and then may decrease in
size. The actual size is seldom greater than 1 cm and can persist indefinitely if not
removed. About a third develop followed by minimal trauma, are extremely fri-
able, frequently ulcerate, and can bleed profusely with minimal trauma
(Figs. 26.18, 26.19, and 26.20) [6]. Multiple satellite lesions occasionally
develop near the primary pyogenic granuloma usually after destruction of the
lesion [6] and are a rare phenomenon. Multiple satellite lesions usually appear on
the trunk; unlike the single lesions of pyogenic granuloma, they are more fre-
quent on the face and scalp. These differences in locations may be because the
skin on the trunk is poor in capillary anastomoses, so the destruction of a single
arterial vessel leads to the formation of eruptive satellite angiomas [7]. Pyogenic
granulomas have been reported in association with systemic retinoids, indinavir,
and EGFR inhibitors; this may represent excessive granulation tissue [6].
• Diagnosis: The lesion is well-circumscribed, exophytic, sometimes peduncu-
lated, with proliferation of small capillaries, often arranged in a globular pattern.
The injured capillaries are lined by endothelial cells, surrounded by pericytes
and by an edematous fibromyxoid interstitial stoma, with little infiltrate of lym-
Fig. 26.18 Telangiectasic

granuloma: Red exophytic
tumor, pedunculated on the
left malar region, with
proliferation of small
capillaries [6]

granuloma: red, exophytic
tumor, round shape,
irregular surface on the
lower lip [6]

granuloma: red, exophytic
tumor, smooth surface,
round shape on the
finger [6]
Infantile Hemangioma 661
Fig. 26.21 Telangiectasic granuloma: polypoid lesion, covered by epidermis, and stromal vascu-
lar proliferation without atypia. HE, 4X [6]
phocytes, plasma cells, and mast cells. Branching, ectasia, intravascular throm-
botic foci, and papillary endothelial hyperplasia may be present (Fig. 26.21) [6].
• Differential diagnosis: Amelanotic melanoma, Kaposi’s sarcoma, bacillary angi-
omatosis, hemangiomas, irritated melanocytic nevus, and viral warts [6–8].
Infantile Hemangioma
• Definition: They are benign proliferations of the endothelial tissue, characterized

by rapid growth in the first months of life, followed by spontaneous involution in
the following years [1, 9].
• Epidemiology/pathogenesis: It is the most frequent tumor in childhood, espe-
cially in the neonatal stage, since most appear during the first year of life; it
occurs in 3–10% of infants [9]. It occurs more in Caucasian children than in
other racial groups. This vascular tumor is more common in girls than in boys,
with a girl-to-boy ratio of 2–5:1 and approximately 7:1 for more complicated
lesions. Infantile hemangiomas develop more frequently in premature infants,
affecting 23–30% of infants weighing less than 1000 g and 15% of those weigh-
ing 1000–1500 g. Infantile hemangiomas represent localized or regional areas of

abnormal vascular development and proliferation [1].
• There are several hypotheses of the control of multiple genes, additionally local
effects that play a role in the development of growth and involution of heman-
giomas [1].
–– As the origin derived from endothelial progenitor cells or pluripotent
stem cells
–– The placental hypothesis where hemangioma cells originate from the placenta
by embolization
–– The expression of glucose transporter protein-1 (GLUT-1) has also been
detected in all stages of hemangioma, which is not found in other vascular
tumors; hypoxia is among the other hypotheses, since it has been reported that
prematurity and low weight cause placental insufficiency, therefore a greater
risk of hemangiomas [1, 9].
• There are also other extrinsic factors such as:
–– Expression of proliferation markers, for example, proliferation nuclear cell
antigen (PCRNA)
–– The increase in proangiogenic molecules such as endothelial growth factor
(VEGF) and fibroblast growth factor (bFGF) [1, 9]
• During the transition phase from proliferative to involutional, there is a decrease
in pro-angiogenic factors that are not yet understood. Already in the involutional
stage, an increase in the expression of angiogenesis and apoptosis promoters is
observed [1, 5]
• Clinical presentation: Lesions usually appear during the first weeks of life; how-
ever, only 15 to 60% are congenital hemangiomas (Figs. 26.22, 26.23, 26.24, and
26.25) [1]. Lesions usually develop at birth and are generally diagnosed during
the first 4–6 months of life with a maximum growth in the first 5 months. The
evolutionary characteristics of infantile hemangiomas present a proliferation
phase, a plateau phase, and slow spontaneous involution [9].
• There are several subgroups of hemangiomas:
–– 1. Precursor lesions of hemangioma.
–– 2. Typical infantile hemangiomas that are well formed at birth and subse-
quently demonstrate a natural history (variable proliferation and then slow
involution) similar to those that arise later [1].
–– 3. A rare subgroup of congenital hemangiomas that demonstrate intrauterine
proliferation with little or no postnatal growth and then exhibit rapid early
involution in postnatal life or absent involution. In this third group are the
rapidly involuting congenital hemangioma (RICH) and the non-involuting
congenital hemangioma (NICH) which are considered as separate entities
from infantile hemangiomas [1, 9].
–– The precursor lesions of hemangiomas: They manifest as telangiectasias sur-
rounded by a vasoconstrictor halo, with areas of paleness, pink, blue macules,
Fig. 26.22 Infantile

hemangioma: Bright red
plaque on the oral mucosa
and lower lip [9]

hemangioma: Well-
delineated red plaque
overlying a larger, poorly
circumscribed light blue
nodule over posterior
thorax [9]

hemangioma: Well-
delineated wine red tumor
over the upper
extremity [9]

hemangioma: Well-
delineated bright red tumor
over the posterior
thorax [9]
and bruise-like patches; rarely, ulceration can be a precursor lesion.

Hemangiomas can occur anywhere on the skin and mucosal surfaces, with
approximately 50% of infants being located on the head and neck. The clini-
cal appearance of a hemangioma is determined by its location within the skin
and subcutaneous tissues. Superficial hemangiomas are located in the super-
ficial dermis and are bright red during their proliferation phase. The surface is
finally lobed, and the term “strawberry hemangioma” has been used to
describe them. Most superficial hemangiomas are focal lesions [1]. Deep
hemangiomas are found in the deep dermis and/or subcutaneous tissue. At
birth they are not usually evident; it becomes evident after a few weeks of age.
They present as ill-defined, hot blue-purple masses with little or no change in
the overlying skin. The presence of dilated veins or telangiectasias lining a
deep hemangioma provides an indication that the lesion is of vascular ori-
gin [1, 9].
–– Mixed hemangiomas: They have both superficial and deep components, often
present during the vascular proliferative phase as a well-delineated red plaque
overlying a larger, poorly circumscribed light-blue nodule [1].
–– Superficial hemangiomas: They are the most frequent subtype, approximately
50–60% of infantile hemangiomas. Additionally, 25–35% of hemangiomas
are mixed, and 15% are deep. Approximately 25% of patients have multiple
lesions and are occasionally associated with visceral hemangiomatosis [1].
Pattern subtypes include:
–– 1. Focal lesions that appear to arise localized from a single nest and
–– 2. Segmental lesions covering an area or unit of development (the terms
“plaque-like” or “diffuse” are also used to describe this group). Lesions that
are difficult to classify and designated as indeterminate are segmental heman-
giomas that are more likely to be associated with regional extracutaneous
abnormalities, including PHACE (S), consisting of P for posterior fossa and
another malformation of brain structure, H for hemangioma, A for arterial
anomalies of the cervical and cerebral vessels, C for heart defects (especially
coarctation of the aorta), E for ocular anomalies (eyes), and S for sternal
defects (sternal) and supraumbilical raphe, and LUMBAR syndrome, consist-
ing of L for lumbosacral hemangioma/lower body and lipomas or other skin
abnormalities, e.g., lax fibromas, U for urogenital anomalies and ulceration,
M for myelopathy (spinal dysraphism), B for bony deformities (bony), A for
anorectal and arterial anomalies, and R for renal abnormalities [1, 9].
–– The distribution patterns of segmental hemangiomas on the face correlate
little with classic embryonic facial prominences, which differ more on the
upper face. Researchers have identified four main segments for facial
hemangiomas, S1 through S4. The involvement of these segments may be
incomplete, and some hemangiomas may encompass more than one seg-
ment [1].
–– Studies have documented the typical growth pattern of infantile hemangio-
mas. Stages include early proliferation (rapid increase in size), late prolifera-
tion (continued growth at a slower rate), plateau, and involution [1].
–– Hemangiomas tend to “mark their territory” early on and subsequently
undergo volumetric growth rather than centrifugal growth. During the prolif-
erative phase, hemangiomas often become firmer in texture, and the surface of
superficial hemangiomas may appear taut. Mixed and deep hemangiomas in
the proliferative phase often feel firmer with crying or activity. Deep heman-
giomas tend to proliferate for about a month longer than superficial heman-
giomas, and the depth component of mixed lesions often continues to grow
even after the superficial component has stagnated [1]. Natural history studies
of untreated hemangiomas show that 30% of lesions will fully regress at
3 years of age, 50% at 5 years, 70% at 7 years, and more than 90% in 9 years.
Some hemangiomas completely regress, while others can leave residual atro-
phy, fibrosis, or telangiectasia [1]. Predicting whether the residual injury will
be of cosmetic significance is one of the most challenging aspects of manag-
ing hemangiomas [1].
• Differential diagnosis: Precursor lesions can be confused with capillary malfor-

mations or telangiectasias [1]. Deep hemangiomas can be mistaken for venous,
lymphatic, or mixed-type vascular malformations and a kaposiform hemangio-
endothelioma [1]. Superficial hemangiomas can mimic a pyogenic granu-
loma [1, 9].
References
Dermatol. 1984;120:214–5.
p. 445–526.
Fitzpatrick’s dermatology in general medicine. 8th ed. New York: McGraw-Hill; 2012.
p. 1319–36.
5. Cortes E, Dominguez L, Vega E. Hidradenoma nodular de células claras. Dermatol Rev Mex.
2013;57:336–41.
6. Sarwal P. Kamolyut lapumnuaypol pyogenic granuloma (lobular capillary hemangioma).
Treasure Island: StatPearls Publishing; 2020.
7. Zaballos P, Llambrich A, Cuellar F, et al. Dermoscopic findings in pyogenic granuloma. Br J
Dermatol. 2006;154:1108–11.
8. Supriya S, Shaleen CH, Shalini G, Saurabh S. Heterogeneous conceptualization of etiopatho-
genesis: oral pyogenic granuloma 2019 National Journal of Maxillofacial Surgery (sarcoma:
dermoscopic clues for the differential diagnosis). Turk J Med Sci. 2019;49:1471–8.
9. Vivar KL, Mancini AJ. Infantile hemangiomas: an update on pathogenesis, associations, and
management. Indian J Paediatr Dermatol. 2018:293–303.
Chapter 27
Fibrous and Fibrohistiocytic Proliferations
of Skin and Tendons
Dermatofibroma
• Definition: It is the second most common fibrohistiocytic tumor of the skin (after
lax fibromas) [1].
• Etiology/pathogenesis: Sometimes it can start at sites of trauma or arthropod
bites, and its precise etiology is unknown. When eruptive dermatofibromas
occur, they have been observed in patients with autoimmune disorders, such as
lupus erythematosus, atopic dermatitis, and immunodeficiencies. It is seen
mainly in adults in the extremities [1].
• Clinical presentation: They are dome-shaped, minimally raised, firm papules
that measure a few to many millimeters of 1 cm in diameter but occasionally can
measure up to 2 cm (Fig. 27.1). These lesions are generally hyperpigmented, but
in patients with white skin, they may appear pink. On palpation it may present
the sign of the lozenge [2].
• Diagnosis: It is characterized by a nodular dermal proliferation, non-encapsulated
bundles of fibroblasts in the form of spindle cells oriented in parallel [2] and have
a keloid appearance. The dermis contains small “muscle band” structures.
Fibroblasts and myofibroblasts have an oval nucleus with a small nucleolus, and
mitosis may also be present (Figs. 27.2 and 27.3) [1].
• Differential diagnosis: It can be confused with cyst or melanocytic nevi, espe-
cially with fibrosis. In these cases, large lesions should be ruled out as a derma-
tofibrosarcoma protuberans. Monocoque or multinucleated histiocytes with
vacuolated cytoplasm (xanthomatous) with keloid bands of collagen with a
refractory polarized light [1]. An increase in the number of perivascular blood
vessels with infiltrated lymphocytes and plasma cells can be. Findings of hemo-
siderin may be observed. The epidermis is usually hyperplastic with converging
plasma ridges and hyperpigmentation of the base layer (dirty fingers). The
attached structures are usually absent in the center of the lesion [1].

https://doi.org/10.1007/978-3-030-84107-2_27
668 27 Fibrous and Fibrohistiocytic Proliferations of Skin and Tendons
Fig. 27.1 Dermatofibroma:

at the right inframammary
region, an 8 mm cupuliform
papule of firm consistency is
observed; it has a red-
yellowish color and regular,
well-defined edges [2]
Fig. 27.2 Dermatofibroma (histology): it is observed hyperkeratosis and acanthosis of the overly-
ing epidermis. There is basal melanosis and a mild lymphocytic infiltrate over superficial dermis.
The tumor involves up to the superficial dermis [1, 2]
Angiofibromas 669
Fig. 27.3 Dermatofibroma (histology): in a collagenous stroma, there are multiple and uniform
interlacing spindle cells [1, 2]
Angiofibromas
• Definition: They are solitary fibrous dome-shaped papules [3].

• Epidemiology/clinical presentation: Angiofibromas are shiny, skin-colored to
reddish papules, dome-shaped, located on the face of adults, mainly on the nose
(Fig. 27.4) [3]. Multiple facial angiofibromas are seen in tuberous sclerosis, mul-
tiple endocrine neoplasia type 1, and Birt-Hogg-Dubé syndrome. They are usu-
ally distributed on the cheeks, nasolabial folds, nose, and chin. Angiofibromas in
tuberous sclerosis usually appear during early childhood; 75% of individuals
eventually develop these lesions. Patients with tuberous sclerosis generally have
periungual angiofibromas; although rare in children, they can be seen in adult-
hood. Both facial and periungual angiofibromas represent a major criterion for
tuberous sclerosis [3, 4].
Fig. 27.4 Angiofibroma:

red papule over nose [3, 4]
• Diagnosis: It is clinical and histopathological. Hematoxylin shows a dermal pro-

liferation of fibroblasts and a collagen stroma that is organized in a concentric
manner around the hair follicle. There may be onion skin around the follicles and
common vessels [4]. Elastic fibers are diminished in number, and fibroblasts are
star-shaped and multinucleated [3]. Immunohistochemistry is positive for factor
XIIIa and CD31 and [4] negative for S100 [3]. Overlying epidermis is sometimes
slightly atrophic [3].
Lax Fibroids (Skin Tags)
• Definition: It is the most common fibrous tumor of the skin. Also called skin
tags [1].
Lax Fibroids (Skin Tags) 671
• Epidemiology/pathogenesis: It is considered a slight predominance in women,

but there is no gender difference; they are located in the neck, armpit, inguinal
region, thorax, and upper extremities [1, 2]. Nanney et al. determined that the
growth of skin tags correlates with the increase in epidermal growth factor recep-
tors (EGF-R); Mathur and Bhargavc proposed R-EFG overexpression caused by
an increase in unstratified fatty acids due to hyperinsulinemic states; [5] how-
ever, a study by Kahana et al. of 216 patients found no correlation between size,
location, age, color, and number of lesions with the presence of glucose intoler-
ance [5]. Sari et al. found 113 patients with lax fibromas who presented arterial
hypertension 30.1%, dyslipidemia 59.3%, metabolic syndrome 39.8%, and resis-
tance to insulin by 21.2% [5]. However, Norris et al. found more hyperinsulin-
emic states than diabetes [5], so these associations are highly debated. There are
few studies on the relationship between skin tags and liver enzymes, but recently
the possibility of conducting new studies to observe the association between skin
tags and elevated liver enzymes is being considered [5]. An association with
genodermatosis such as Birt-Hogg-Dubé syndrome has also been found [1, 2].
• Clinical presentation: It presents as achromic or slightly hyperpigmented pedun-
culated papules, which can be single or multiple and vary from 1 to 2 mm on the
eyelids or even polyps of 1 to 2 cm on the trunk; they are usually asymptomatic
and can become secondary, painful to irritation or necrosis (Figs. 27.5 and 27.6)
[1]. They are also divided into three clinical variants: (1) grooved papule shape,
(2) filiform lesion, or (3) a large bag-like lump [2].
• Diagnosis: Histopathology varies according to the clinical variant; it can present
itself as the polypoid with loss of the fibrous stroma and absence of the adnexal
structures, or the fibrovascular center can be replaced by adipose tissue
(Fig. 27.7) [1].
• Differential diagnosis: Nevus, fibrolipoma, neurofibroma [1].
Fig. 27.5 Lax fibroid: on

the upper eyelid, in the
central region, appears a
pedunculated papule,
slightly hyperpigmented,
grayish-brown in color,
with a rough surface and
3 mm in diameter [1, 2]
Fig. 27.6 Lax fibroid:

Lateral view of the neck
shows multiple
pedunculated papules,
brown, pink, or
euchromatic in color, with
a rough surface, with sizes
between 1 and 5 mm in
diameter [1, 2]
Fig. 27.7 Lax fibroid

(histopathology):
Fibrovascular cores
covered by squamous
epithelium with a flattened
epidermis [1]
Superficial Fibromatosis-Plantar Fibromatosis
• Definition: It is a disorder of the proliferation of fibrous tissue, characterized by

the replacement of the plantar aponeurosis with abnormal fibrous tissue which
slowly invades the skin and deep structures [1].
• Epidemiology/pathogenesis: It most often affects adult patients with an average
age of 40 years; (1) the incidence increases with age, (2) but cases have also been
seen in children [1]. Some reports show a higher incidence in men, especially in
Superficial Fibromatosis-Plantar Fibromatosis 673
Caucasians. It is characterized by nodular lesions that begin as asymptomatic,

single or multiple, unilateral or bilateral, which then slowly spread, becoming
painful. The etiology of this disease is unknown; multiple precipitating factors
such as trauma, impaired healing, diabetes, liver disease secondary to alcohol-
ism, smoking, neuropathy, and genetic factors have been proposed [2].
• Clinical presentation: It presents as single or multiple nodules of 0.5–3 cm, flat,
poorly defined, of fibrous consistency and variable size; they are more frequently
located in the anteromedial part of the heel (Figs. 27.8 and 27.9) [1].
• Diagnosis: The diagnosis is clinically based, and the main histological findings
are large amounts of mature and relatively acellular collagen with occasional
mature fibrocytes. Other important auxiliary methods are imaging, such as radi-
ography that reveals a non-specific mass, without precise delineation of the
extent. Ultrasound shows a solid hypoechoic mass which can help us to know the
extent of the lesion and as a guide for biopsy in case of deep lesion. Magnetic
resonance imaging allows the evaluation of multiple planes of the lesion [1].
• Differential diagnosis: Dermatofibroma [1].
Fig. 27.8 Plantar

fibromatosis: on the lateral
side of the right sole, close
to the heel, a single
rounded nodule measuring
12 mm in diameter, raised,
pink, euchromatic, with a
smooth surface, with a
scaly collar [1]
Fig. 27.9 Plantar

fibromatosis: On the lateral
side of the right foot
border, close to the heel, a
single rounded nodule
measuring 12 mm in
diameter, raised, pink,
euchromatic, with a
smooth surface, with a
scaly collar [1]
Atypical Fibroxanthoma
• Definition: It is a rare mesenchymal tumor [6].

• Epidemiology/pathogenesis: It is rare and has an incidence of all skin tumors of
1–4%, occurring in individuals between the seventh and eighth decades of life.
In the transplanted population, it reaches 78 new cases per 100,000 inhabitants
[7]. Actinic damage induced by ultraviolet radiation is considered to be the main
causative factor, other possible risk factors include immunosuppression, trauma,
and other underlying skin disorders such as xeroderma pigmentosum. Its most
frequent location is the head and neck [7].
• Clinical presentation: It is a large, immobile and firm nodule that frequently
ulcerates and rarely exceeds 3 cm in diameter and typically appears in less than
1 year, around which age, it may present photodamage changes such as actinic
keratoses; metastases are exceptional; however, there are reports of metastases in
the lymph nodes, lung, and peritoneum (Figs. 27.10 and 27.11) [7].
• Diagnosis: It is a spindle cell tumor that erodes the epidermis, with atypical cells
and some histiocytic cells with high pleomorphic grade. The tumor is predomi-
nantly composed of pleomorphic spindle cells, arranged in a vaguely storiform
Fig. 27.10 Atypical

fibroxanthoma: large,
immobile, firm tumor,
ulcerates over left parietal
region [7]
Dermatofibrosarcoma Protuberans 675
Fig. 27.11 Atypical

fibroxanthoma: large,
immobile, firm tumor,
ulcerates over left parietal
region [7]
pattern. Mitosis is frequently observed. Immunohistochemistry is positive for

CD99, CD68, CD10, smooth muscle actin, and vimentin; occasionally, it is posi-
tive for HMB 45, Melan-A, P63, and CD31; generally, it is negative for S100 and
demines [6, 7].
• Differential diagnosis: Malignant fibrous histiocytoma, basal cell carcinoma, or
any malignant tumor located in the head and neck [6].
Dermatofibrosarcoma Protuberans
• Definition: It is a sarcoma of local aggressiveness of intermediate malignancy

that favors middle-aged adults [8].
• Epidemiology/pathogenesis: Corresponds to less than 0.1% of skin neoplasms
and 1% of all soft tissue sarcomas. It is a rare tumor with an incidence of
0.8–5/100,000 inhabitants. It affects men and women equally, with a predilection
for the black race, between 30 and 50 years of age [2]. Injuries at birth or during
childhood have also been reported [8]. Fifty to sixty percent are located on the
trunk (especially in the shoulder girdle and back), 20–30% in the extremities
(proximal), and 10–15% in the head and neck [8]. Ten to twenty percent have a
history of trauma that could trigger the tumor or be a coincidence (cases in areas
of burns, radiotherapy, scar, vaccination, arteriovenous fistulas) [8]. A 17:22
translocation has been identified by cytogenetics and molecular biology (PCR
and FISH – fluorescence in situ hybridization); this translocation involves the
genes COL1A1 on chromosome 17 and PDGFB on chromosome 22 (collagen I
alpha 1 and growth factor beta derived from platelets), giving rise to an activation
of the PGFGB receptor by means of an autocrine and paracrine production of a
functional ligand that translates into a chronic mitogenic signal, capable of
inducing neoplastic transformation [9].
• Clinical presentation: Initially it presents as a slow-growing, asymptomatic,
achromic indurated plaque [8]. As the tumor grows, it infiltrates deeply and
extensively and develops nodules on the surface of a purplish to erythematous
brown color, many centimeters wide in diameter [8, 9]. The time to go from
plaque phase to tumor phase ranges from 1 month to 50 years. The size of the
tumor depends on the time of evolution from 1–5 to 20 cm. It is usually located
in the dermis and subcutaneous cellular tissue, so it is generally mobile and not
attached to deep planes, although it can invade fascia, muscle, periosteum, and
bone in advanced stages [9]. In the initial or plaque stage, it can adopt three
aspects:
–– Morphea type: achromic, whitish, or grayish indurated plaque.
–– Atrophoderma type: soft, depressed, atrophic-looking, achromic plaque.
–– Angioma type: less frequent and resembles vascular lesions as flat angioma. It
can occur in children, and some of these are congenital. They are difficult to
diagnose [10].
• Diagnosis: It requires a clinical, histopathological, and immunohistochemical
study to confirm the diagnosis. At histopathology, it is formed by a dense and
uniform proliferation of spindle cells in the lower dermis, and the epidermis
appears normal. Cell density is much higher in the central part of the tumor than
in the periphery, where finger-like protections are emitted, in the form of few
cellular fibrous tracts that infiltrate the subcutaneous cell tissue, muscle fascia,
muscle, and even the bone [10]. Immunohistochemical markers are CD34 posi-
tive in 92–100% of cases; vimentin and nestin are 94% positive in DFSP and
only 13% in DF (useful to differentiate them), factor XIIIa is positive in 10–15%
of cases, and it serves to differentiate from dermatofibroma, in which it is posi-
tive in 90–95%. P53 is positive when there is fibrosarcomatous transformation:
(more aggressive evolution) high degree of cellularity, cytological atypia, high
mitotic activity, p53 mutation [10].
• Differential diagnosis: Keloids, large dermatofibroma, and morphea. Congenital
or childhood dermatofibrosarcoma protuberans have an atrophic appearance and
or reddish-blue hypopigmentation that can be confused with a vascular malfor-
mation [8].
Low Differentiation Fibromyxoid Sarcoma
• Definition: Low-grade fibromyxoid sarcoma (SFBG) is a rare, soft-tissue sar-

coma originating from subcutaneous or muscle tissue predominantly in the lower
• Epidemiology/pathogenesis: It is a rare neoplasm, but probably underdiagnosed
because it often arises in association with other entities. According to the World
Classification of the Health Organization of tumors, 150 cases have been docu-
mented up to the year 2000 with local recurrence, metastasis, and death [12, 14].
Subsequently, several reports and case series have been published and 180 more
cases were added [14]. It is seen in both men and women [11], but there is a
slight predominance in young male adults with an average age of 34 years, but it
Low Differentiation Fibromyxoid Sarcoma 677
Fig. 27.12 Low

differentiation fibromyxoid
sarcoma: on the inside of
the right leg, a large friable
exophytic tumor with
fibrinoid areas and a
necrotic base is
observed [11]
can appear in any age group [12]. The most frequent locations are the proximal
extremity of the lower limbs, the shoulder, and the inguinal region [12]. There
are cases reported in the chest wall, armpit, buttocks, and neck [13]. Fusion of
the FUS/CREB3L2 genes that express translocation (7; 16) (q33; p11) being a
useful tool for differential diagnosis [12–14].
• Diagnosis: Histologically, SFBG is characterized by the presence of spindle cells
with a vertical pattern that alternates myxoid areas with fibrous sarcoma and low
to moderate cellularity; neoplastic cells are fibroblastic cells with minimal
nuclear pleomorphism. Nucleoli are absent or indistinguishable. The tumor,
although macroscopically well-circumscribed, usually shows a microscopic
infiltration into the surrounding soft tissues [12, 14]. The SFBG vasculature con-
sists of arches of small vessels and arterioles with perivascular sclerosis. Mitoses
are usually absent or rare [2]. Immunohistochemical analysis may be helpful.
The spindle cells are positive for vimentin and negative for enolase, epithelial
membrane antigen, cytokeratin, desmin, CD34, CD68, ALK1, S-100, and
CD99 [12].
• Differential diagnosis: Dermatofibrosarcoma protuberans, spindle cell

tumors [11].
Low Differentiation Fibromyxoid Sarcoma characteristic features include
fibrous and myxoid areas, a swirling whorled growth pattern, low to moderate cel-
lularity, and bland cells with minimal nuclear pleomorphism (Fig. 27.12).
References
Benign melanocytic neoplasms, neural and neuroendocrine neoplasms (other than neurofibro-
Dermatol. 1984;120:214–5.
3. Weedon D. Lentigines, nevi and melanomas chapter 32. In: Weedons skin pathology. Third ed;
2010. p. 712–56.
4. Johnston R. Weedon Fibrous tumors and tumor-like proliferations chapter 34. In: Skin pathol-
ogy essentials; 2011. p. 708.
p. 445–526.
6. Calonje E, Brenn T, Lazar A, et al. Mckee’s pathology of the skin with clinical correlation. 4th
ed. p. 1658–62.
7. Mahalingam S, et al. Atypical fibroxanthoma: a case series and review of literature. Auris
Nasus Larynx. 2015;42:469–71.
8. Kamino H, Reddy VB, Pui J. Fibrous and fibrohistiocytic proliferations capítulo 116 J. In:
Dermatology. 3rd ed; 2012. p. 1973–4.
9. Serra Guillen C, et al. Dermatofibrosarcoma protuberans.Actas Dermo-Sifiliográficas.
2012;103(9):762–77.
10. Calonje E, et al. Mckee pathology of the skin: with clinical correlations. 4th ed. Elsevier/
Saunders; 2012. angiofibromas
11. Kamino H, Reddy V, Pui J. Fibrous and fibrohisticocytic proliferation of the skin and ten-
dons. In: Bolognia J, Jorizzo J, Schaffer J, eds. Dermatology. 3rd ed. Philadelphia: Saunders,
2012:1961–63.
12. Johnston R. Weedon Fibrous tumors and tumor-like proliferations chapter 34. In: Weedon’s
Skin Pathology Essentials; 2011. p. 61.
13. Folpe AL, Lane KL, Paull G, Weiss SW. Low-grade fibromyxoid sarcoma and hyalinizing
spindle cell tumor with giant rosettes: a clinicopathologic study of 73 cases supporting their
identity and assessing the impact of high-grade areas. Am J Surg Pathol. 2000;24(10):1353–60.
14. Mustafa M, Cyril F, Khin T. Low-grade fibromyxoid sarcoma: clinical, morphologic and
genetic features. Ann Diagn Pathol. 2017;28:60–7.
Chapter 28
Congenital and Acquired Melanocytic
Nevus
1. Congenital melanocytic nevus. It occurs at birth in 1% of newbornsCongenital

melanocytic nevus, on the trunk. It presents as a macula, papule, or brown patch
with an increase in hair follicles on the lesion; in 63% they are 1–4 cm in size.
They are associated with Carney’s syndrome, epidermal nevus syndrome, and
type 1 neurofibromatosis [1, 5]. They are classified according to their size as
small under 1.5 cm, medium from 1.5 to 19.9 cm, and giant over 20 cm [5]. The
incidence of giant melanocytic nevus is <1:20,000 in live births [5]. It is rare, but
this lesion is important because it can be associated with severe complications
such as malignant melanoma (with a risk of 5%) and involvement of the system
central nervous system, (neurocutaneous melanosis) and have a greater psycho-
social impact on the patient and their family due to their unpleasant appearance.
Giant congenital melanocytic nevus generally presents as a brown, flat, or mam-
millated surface lesion with well-demarcated edges and hypertrichosis [5], usu-
ally in a bathing suit area (Figs. 28.1, 28.2, and 28.3).
Congenital Melanocytic Nevus, Acquired Nevus and Others
• Definition: Nevi are benign proliferations of melanocytes [1].

• Epidemiology/pathogenesis: The prevalence of melanocytic nevi is related to
age, race, and genetic and environmental factors. It occurs in childhood, but their
number may increase. The period where it develops the fastest is during puberty.
Caucasians have more nevi than dark-skinned ones. Nevi on palms, soles, nail
bed, and conjunctiva are related to race; nevi in these areas are of dark and Asian
races more than in whites [1]. Genetic factors such as the presence of somatic
BRAF mutations that induce senescence and in the minority of cases an NRAS
mutation may be present. Environmental factors such as sun exposure, which
influence its development, are also involved [1]. Melanocytic nevi originate from

https://doi.org/10.1007/978-3-030-84107-2_28
680 28 Congenital and Acquired Melanocytic Nevus
Fig. 28.1 Small

congenital melanocytic
nevus: on the right eye’s
lower eyelid, there is a
dark-brown papule.
Classified as a small
congenital nevus [5]
Fig. 28.2 Medium

congenital melanocytic
nevus: over the left gluteal
region, there is a large
light-brown patch with
well-demarcated edges and
slight hypertrichosis.
Classified as a medium
size nevus [6]
Congenital Melanocytic Nevus, Acquired Nevus and Others 681
Fig. 28.3 Giant congenital

melanocytic nevus: on the
left upper leg and lower
back, there is a large
dark-brown macule with
hypertrichosis with a
gluteal tumoral growth
with hyperpigmented and
hypopigmented spots.
Classified as a giant
nevus [6]
neural crest stem cells that migrate to the epidermis. His hypothesis results from
the slightly altered proliferation of melanocytes [1].
–– In junctional nevi, the “nevic cells” are found between the epidermis.
–– In compound nevi, nevic cells migrate to the dermis generating com-
pound nevi.
–– In dermal nevi, there are no residual nevic cells in the epidermis [1].
• Clinical Presentation
–– Acquired melanocytic nevi: Melanocytic nevi are well-circumscribed, round
to ovoid in shape, generally measuring 2–6 mm in diameter. However, many
nevi play a slight asymmetry of the edges which are usually regular and well-
defined [1].
–– Junctional nevus: It is a macular lesion, characterized by a uniform dark-
brown color [1] (Fig. 28.4).
–– Compound nevus: Shows varying degrees of elevation, with slightly lighter
brown tones [1] (Fig. 28.5).
Fig. 28.4 Junctional

nevus: on the left popliteal
region, a well-defined
macule with light- and
dark-brown pigment is
observed [1, 5]
Fig. 28.5 Compound

nevus: Light- and
dark-brown macule with
poorly defined and
irregular edges with a
central brown papule is
observed [1]
–– Intradermal nevus: Usually, it is more raised; it shows lighter brown or achro-

mic tones [1] (Fig. 28.6).
2. Melanocyte nevi of the nail matrix: Usually present as a longitudinal band with
a uniform brown to dark-brown pigment [1]. Nevi, especially those acquired,
contain thick and dark hair follicles compared to the hair follicles of the sur-
rounding skin [1] (Fig. 28.7).
3. Spilus nevus: It is a nevus that appears during childhood. It presents as a brown-
to-brown macula with hyperpigmented spots. It is sometimes associated with
subtypes of phakomatosis pigmentovascularis (pigment abnormalities with con-
genital syndromes or vascular abnormalities such as capillary malformations,
Mongolian spots) [5] (Fig. 28.8).
4. Miescher’s nevus: Melanocytic nevus with a long evolution time that adopts a
papular, hemispherical, slightly hyperpigmented lesion morphology or the color
Fig. 28.6 Intradermal

nevus: A light-brown small
papule is observed on the
upper lip of this patient
[1, 5]
of normal skin, smooth surface and that sits, preferably, on the face of elderly
people, with slightly more often in women than in men and sometimes contains
thick hair follicles [1, 5] (Fig. 28.9).
5. Spitz nevus: It is the least frequent of the melanocytic nevi. It is a lesion that
occurs mainly in children, as a hemispherical papule, slightly larger than other
melanocytic nevi, with a pink to erythematous color with a hyperkeratotic or
papillomatous surface. The most common location is on the face, and it is often
mistaken for a small angioma or a common wart. The importance of this Spitz
nevus is that, although it is an absolutely benign lesion, it is sometimes very dif-
ficult to differentiate histopathologically from melanoma [1].
6. Meyerson nevus: Nevus around an eczematous halo, occurs in young adults [1].
An eczematous halo around an erythematous and pruritic desquamation, can be
an intradermal, compound, or junctional nevus, does not return spontaneously
unlike the halo nevus [5].
Fig. 28.7 Melanocyte nevi

of the nail matrix: A
uniform dark-brown
coloration without
Hutchinson’s sign is
observed on the left foot
hallux toenail [1, 5]
Fig. 28.8 Spilus nevus:

On the right neck side,
there is a light brown
macula with multiple
hyperpigmented spots [5]
Fig. 28.9 Miescher’s

nevus. On the right
nasolabial fold, there is an
euchromatic papule with a
slight central
hyperpigmentation and
smooth surface [1, 5]
7. Halo nevus or Sutton’s nevus: It occurs mainly in adolescents, in the trunk and
can involve one or more nevus [5]. It consists of a melanocytic nevus, and around
it presents an achromic halo of depigmentation, which frequently precedes the
destruction of melanocytes and consists of a regression phenomenon [5].
8. Becker nevus: It is derived from the ectoderm and the mesoderm; with an increase
in androgen receptors, it has been described in all races, it can be acquired or
congenital. It presents as a unilateral patch or plaque, slightly raised,
hyperpigmented, and frequently with hypertrichosis, usually occurring on the
shoulder of male patients [1] (Fig. 28.10).
9. Dysplastic or Clark’s nevus: It occurs in children to young adults, mainly on the
scalp and trunk. It looks like a macula, papule, or plaque with pigmentation
and/or irregular borders [5].
Fig. 28.10 Becker nevus:

In the left scapular region,
there is a light-brown
patch, slightly raised with
hypertrichosis [5]
Fig. 28.11 Common blue

nevus: In the glabellar
region of a male patient
there can be observed a
dark blue papule [5]
10. Blue nevus: Appears after infancy, with a predominance in women and limbs,
represents retention of the migration of melanocytes [5]. There are two main
variants:
• Common blue nevus (dendritic): Light- or dark-blue macula or papule [5].
• Cellular blue nevus (50% on the buttocks and sacrococcygeal area): It is
observed as a large nodule like the blue nevus, with a greater number of
retained melanocytes [5] (Fig. 28.11).
11. Diagnosis: Contain dermal or intraepidermal collections of nevic cells or both.
(a) Junctional nevi: Discrete nests of melanocytes only at the dermoepidermal
junction, with elongated epithelial ridges, without mitosis or rarely
mitosis [5].
(b) Compound nevi: Presents nests of melanocytes at the dermoepidermal and
intradermal junction. The epidermis may be flat similar to a seborrheic-like
keratosis with corneal cysts [5] (Fig. 28.12).
(c) Intradermal nevus: Nests and cords limited to the dermis only; the deep
parts may have the form of a spindle-shaped neural nevus and structures
like Meissner-like body [5] (Fig. 28.13).
Fig. 28.12 Compound nevi: Nests of melanocytes at the dermoepidermal and intradermal
junction [5]
Fig. 28.13 Intradermal nevus: nests and cords limited to the dermis
(d) Congenital melanocytic nevi: It can be of the junctional, compound, or

intradermal type, where the melanocytes in congenital nevi are usually
deep in 2/3 of the dermis, between the collagen; the arrector pili muscle is
observed, and the glands are compromised eccrines [5].
(e) Spilus nevus: It is totally clinical; however, if a biopsy is taken, it will have
an appearance of a simple lentigo (the background area) and a hyperpig-
mentation reminiscent of a lentiginous nevus with areas that progress to a
junctional nevus or composite (dotted area) [1].
(f) Miesher’s nevus: Exo-endophytic or completely endophytic lesion, pre-
dominantly intradermal or with little juncture component, with a V-shape
open upward and extending to the deep reticular dermis or even the hypo-
dermis [1] (Fig. 28.14).
Fig. 28.14 Miesher’s nevus: Exo-endophytic nevus, predominantly intradermal extending to the
deep reticular dermis and hypodermis with occasional hair follicles [5]
Solar Lentigo 689
• Meyerson nevus: There is spongiosis plus a nevus, with eosinophils and exocy-
tosis [5].
(g) Halo nevus or Sutton’s nevus: Usually it is a compound nevus with a dense
infiltrated lichenoid lymphocyte (CD8 +); few melanocytes survive; with a
depigmented halo showing the absence of melanin and basal melano-
cytes [2].
(h) Becker’s nevus: Variable papillomatosis, acanthosis, and hyperkeratosis,
with regular elongation of the epidermal ridges and hyperplasia of the pilo-
sebaceous unit. The melanin contained in the keratinocytes is increased,
where the number of melanocytes is normal or slightly increased, without
nests [5].
(i) Dysplastic or Clark’s nevus: It has four main characteristics: (1) intraepi-
dermal lentiginous hyperplasia of melanocytes, (2) solitary proliferation of
melanocytes, (3) elongation of the ridges, and (4) poor circumscribed nests.
With an architectural atypia called the “shoulder phenomenon” with
peripheral extension of the junctional component beyond the dermal com-
ponent. With interconnection between the ridges and concentric fibroplasia
around the ridge [5].
(j) Blue Nevus
(i) Common blue nevus: Presents fusiform elongated dendritic melano-
cytes with slight extensions in the middle and upper dermis, with some
melanophages and a normal epidemic.
(ii) Cellular blue nevus: Presents a bell shape with growth along the
attached structures, with dendritic and palisade cells, and also have
normal epidermis and melanophages [5].
• Differential diagnosis: Seborrheic keratoses, dermatofibromas, neurofibromas,
fibroepithelial polyps, and solar lentigo [1, 5, 6].
Solar Lentigo
• Definition: It consists of a benign melanocytic neoplasm, derived from melano-

cytes that occurs particularly in clear phototypes manifesting as hyperpigmented
macules that develop in areas of the skin that have been exposed to ultraviolet
radiation [1, 2].
• Epidemiology/pathogenesis: They can develop at any age and disappear with the
passage of time or after the cessation of sun exposure; however, most persist
indefinitely. It has been identified in up to 90% of the Caucasian population,
around the sixth decade of life; however, in a small proportion (20%), it can be
observed in young individuals under 30 years of age. Regarding the gender rela-
tionship, they are more common in men than in women [1, 2]. Solar lentigos are
the result of an epidermal hyperplasia, with proliferation of basal melanocytes
and a subsequent increase in melanogenesis, in response to chronic exposure to
ultraviolet radiation [1]. As in the ephelides, the presence of mutations in the
gene encoding the melanocortin-1 receptor has been identified [1]. Among the
genetic mutations that have been identified in patients who develop this type of
lesion, there are FGFR3 and PIK3CA, which have been involved in the patho-
genesis of this entity [3]. There is a variant known as PUVA lentigo (psoralen +
ultraviolet A), which has been associated with up to 50% of patients who receive
long-term chemotherapy around 5–7 years of treatment. In contrast to solar len-
tigos, PUVA lentigos occur on skin protected from the sun and can persist for
years after discontinuation of PUVA therapy. Clinical monitoring is important in
these patients due to their high risk of developing melanoma [1]. On the other
hand, in some cases in which it presents with a disseminated presentation, its
association with multiple systemic disorders has been established, among which
is Peutz-Jeghers syndrome, LEOPARD syndrome, and LAMB syndrome [4].
• Clinical presentation: It is characterized by the presence of single or multiple
hyperpigmented macules, light- to dark-brown in color, well-circumscribed and
with regular borders, which vary between 1 and 3 cm in diameter and tend to
converge between them. They are located in photoexposed areas, mainly on the
face, neck, V area of the neckline, and back and back of the hands [1, 3].
Dermoscopy can identify a light-brown area, well defined or with irregular bor-
ders and a pattern reticular with lines that occasionally break [1]. A hypermela-
nocytic variant, called an “ink spot,” has been described, characterized by its
jet-black color, a starry outline [1]. In the case of the PUVA variant, it is evi-
denced as a hyperpigmented macula, darker than the solar lentigo, well-defined,
sometimes presenting a star shape [1] (Figs. 28.15 and 28.16).
• Diagnosis: The diagnosis of this pathology is usually clinical; however, its histo-
logical confirmation allows clarifying the diagnosis in cases of doubt. Among the
histopathological findings of the lesions, elongation of the interpapillary ridges
Fig. 28.15 Solar lentigo:

single hyperpigmented
macule, dark-brown in
color, well-circumscribed,
with regular borders
located in nasal tip [1, 3]
Solar Lentigo 691
Fig. 28.16 Solar lentigo:

single oval hyperpigmented
macule, light-brown in
color, well-circumscribed,
located in nasal dorsum [1]
Fig. 28.17 Solar lentigo: there is elongation of the rete ridges, hyperpigmentation, and increased
numbers of solitary melanocytes are present [1]
can be observed, with an appearance similar to a “hockey stick,” giving rise to

keratinocytic finger-like projections, whose fusion can adopt a histological appear-
ance similar to the reticulated type of seborrheic keratoses. There is also an
increase in the pigmentation of the basal layer, especially in the basaloid cells of
the epithelial ridges. In some cases, enlarged melanocytes occur. At the level of the
superficial dermis, a lymphocytic perivascular infiltrate and some melanophages
are observed [1]. The PUVA variant is characterized histologically by lentiginous
hyperplasia of large melanocytes, which often exhibit mild cytological atypia [1].
In electron microscopy studies, abundant melanosome complexes have been iden-
tified in keratinocytes, which appear to be larger than healthy tissue [1] (Fig. 28.17).
• Differential diagnosis: As differential diagnoses, the presence of seborrheic kera-
tosis, lentigo maligna, ephelides, pigmented actinic keratosis, melanocytic nevus,
and large cell acanthoma should be considered [1].
References
Dermatol. 1984;120:214–5.
p. 445–526.
p. 1319–36.
5. Weedon D. Lentigines, nevi and melanomas chapter 32. In: Weedons skin pathology. 3rd ed.
Edinburgh: Churchill Livingstone/Elsevier; 2010. p. 712–56.
6. Kusumi T, Nishikawa S, Tanaka M, Ogawa T, Jin H, Sato F, et al. Low-grade fibromyxoid
sarcoma arising in the big toe. Pathol Int. 2005;55(12):802–6.
Chapter 29
Neural and Neuroendocrine Neoplasms
Neurofibroma
• Definition: Proliferation of neuromesenchymal tissue (Schwann cells, perineural

cells, fibroblasts, and mast cells) with residual nerve fibers (axons). Cutaneous
neurofibromas are common, especially as solitary lesions. The presence of mul-
tiple neurofibromas is associated as part of neurofibromatosis [1].
• Epidemiology/pathogenesis: It is generated by the proliferation of the entire neu-
romesenchymal tissue that includes Schwann cells, endoneural fibroblasts, peri-
neural cells, and mast cells. Studies in patients with neurofibromatosis indicate
that its mutation leads to inactivation of one copy of the NF1 gene (haploinsuf-
ficiency) [1]. Solitary cutaneous neurofibromas are common, especially in adults,
without gender preference [1].
• Clinical Presentation: Solitary neurofibromas are papules, nodules, or peduncu-
lated tumors, achromic, of smooth consistency that range from 2 to 20 mm in
diameter, which grow slowly and are asymptomatic [1], with a predilection for
the upper part of the trunk. Rarely, it has a fuzzy pattern. They present invagina-
tions when pressing (the buttonhole sign). In some cases, subungual lesions
have been reported, compromising the toes [5] (Figs. 29.1, 29.2, 29.3, 29.4
and 29.5).
• Diagnosis: Cutaneous neurofibromas are tumors that are centered in the dermis
and are not encapsulated. It can spread to the subcutaneous cellular tissue, with
a diffuse infiltrative pattern [1]. Sometimes the lesion is separated by a grenz
zone on the lower surface of the epidermis. A typical finding is thin spindle cells
with a “wavy” and a spindle-shaped nucleus [1]. When a neurofibroma is associ-
ated with type I neurofibromatosis, multinucleated giant cells may present with
a nuclear pleomorphism, but mitoses are rare [2]. Solitary neurofibromas are
sometimes more compact than neurofibromatosis. Blood vessels are increased in
number, in the stroma [1]. Bodian stain demonstrates axonal material, but not in

https://doi.org/10.1007/978-3-030-84107-2_29
694 29 Neural and Neuroendocrine Neoplasms
Fig. 29.1 Neurofibroma:

cervical region and anterior
thorax present multiple
light-brown nodules, some
pedunculated, contiguous,
smooth surface with
light-brown macules [1, 5]

On the trunk, upper limb,
and left axilla, multiple
light-brown nodules,
smooth surface,
contiguous, and multiple
light-brown macules [1, 5]
Neurotechoma 695

On the face and neck, it
has multiple euchromatic
nodules and light-brown,

On the posterior trunk,
multiple contiguous
nodules, light-brown,
the 1:1 ratio with Schwann cells as occurs in neuromas. Protein S100 and factor
XIIIa may be present [5].
• Differential diagnosis: Solitary neurofibromas are similar to a dermal melano-
cytic nevus, schwannoma, fibroma, and fibrolipoma [1, 5].
Neurotechoma
• Definition: Neurotechoma is a benign tumor that originates in the endoneurium

of the peripheral nerves. It was first described in 1969 by Harkin and Reed who
gave it the name “myxoma of the nerve sheath” [6, 7].
Fig. 29.5 Neurofibroma (histopathology): Well-defined lesion, made up of cell proliferation,

fusions of elongated, wavy nuclei, and clear cytoplasm. HE 10 × (2) [1, 5]
• Epidemiology/pathogenesis: Two hundred ninety-two cases have been reported

in the literature, including patients between 15 months and 84 years of age, with
a peak in incidence in the second decade. Of these statistics, 82 cases occurred in
pediatric age (under 18 years). Its etiology is unknown, and it has been observed
more frequently in women with a 2:1 ratio compared to men [8, 9]. Neurotechomas
are uncommon benign tumors in pediatric age. In the literature, 35 cases are
described in children under 10 years of age [9, 10].
• Clinical presentation: It is characterized by being a solitary, slow-growing lesion,
generally asymptomatic; most are small in size and generally starting as a papule
or nodule. The most frequently described locations are the head and neck fol-
lowed by the trunk. The size of the lesion in 90% of cases is less than 2 cm [8, 9]
(Fig. 29.6).
Schwannoma 697
Fig. 29.6 Neurotechoma:

An exophytic erythematous
tumor with a smooth
surface with multiple
telangiectasias is observed
on the medial aspect of the
right arm [8]
• Diagnosis: Three histological variants are described, classic, cellular, and mixed,
which are based not only on microscopic findings but also on immunohistochem-
ical studies. The cell type is characterized by being S100 (−), CD 68 (−), enolase
(+), vimentin (+), and smooth muscle actin (+); the classic one presents a pattern,
S-100 (+), CD 68 (+), collagen IV (+), enolase (−), while the mixed one shares
immunohistochemical characteristics of the previous two [9, 10] (Fig. 29.7).
• Differential diagnosis: It must be established with fibrous, histiocytic, melano-
cytic, and lymphoid tumors [9–11].
Schwannoma
• Definition: Tumor derived from periaxonal or endoneural proliferation of

Schwann cells [1].
• Epidemiology/pathogenesis: Tumor originating from Schwann cells. Ninety per-
cent are solitary and are not associated with any specific syndrome. It occurs
frequently in the lower extremities of adults. When multiple lesions appear, they
can be associated with von Recklinghausen’s neurofibromas, or neurofibromato-
sis type 1, where there are somatic mutations of the NF1 gene, a tumor suppres-
sor gene located in the pericentromeric region of chromosome 17 [2], as well as
it can be associated with neurofibromatosis type 2 due to mutations in NF2
(22q12.2) and mutations in the INI1 gene, also known as SMARCB1: a local
tumor suppressor gene or in the vicinity of the NF2 gene, which has been impli-
cated as responsible for multiple schwannomas [1].
• Clinical presentation: It presents as a papule or nodule, with a smooth surface in
the dermis or subcutaneous cellular tissue, with an achromic to yellowish-pink
color, 0.5 and 3.0 cm in diameter. Sometimes they can have cystic changes par-
Fig. 29.7 Neurotechoma (histopathology): proliferation of spindle and/or epithelioid cells involv-
ing reticular dermis, arranged in fascicles and nests surrounded by sclerotic collagen [10, 11]
ticularly in deep tumors [1]. It is mainly found in the flexor areas of the extremi-
ties, along the nervous trunk and followed by the head and neck. They are
asymptomatic and occasionally painful when a nerve is involved [1].
Schwannomas have been reported in the head and neck regions within the parotid
or in the nasal cavity where they are generally asymptomatic; however, their
slow growth can be painful and may present a spasm or facial paralysis, due to
compromise of cranial nerves [2]. Intraoral schwannomas occur less frequently
(<1%) [3] (Fig. 29.8).
• Diagnosis: It is composed of two types of cells called “Antoni A” with Schwann
cells that have a fusiform shape, and these have indistinguishable cytoplasmic
borders. Verocay bodies are cells with nuclei that are fused together with eosino-
philic masses. A variant has been described, where the verocay body is found in
75–100% of the tumor [1]. There are also Antoni B cells that consist of a gelati-
nous mesh tissue and a microcystic tissue separated with Schwann cells; macro-
phages with lipids, dilated blood vessels, and calcified hyaline areas are also
observed [1]. The immunohistochemistry is positive for S100, vimentin, SOX10,
and myelin basic protein [1].
Merkel Cell Carcinoma 699
Fig. 29.8 Schwannoma:

skin color tumor, with
smooth surface, soft
consistency, and well-
circumscribed borders, on
one right toe [1]
• Differential diagnosis: Neurofibromas, lipomas, angiolipomas, intradermal

melanocytic nevi, and adnexal tumors [1].
Merkel Cell Carcinoma
• Definition: Merkel cell carcinoma (MCC), known as neuroendocrine tumor,

(however not every neuroendocrine tumor is synonymous with Merkel cell car-
cinoma), other terms used for this tumor is trabecular cell carcinoma, anaplastic
cancer skin, and primary small cell tumor [1].
• Epidemiology/pathogenesis: The Merkel cell is part of the epidermis and the
hair follicle and is recognized as a neuroendocrine cell, due to its dense neuro-
secretory granules, in addition to expressing intermediate keratin filaments,
desmosomes, and desmosomal proteins. It migrates toward the epidermis fol-
lowing the path of the peripheral nerves [2]. Of unknown etiology, its appear-
ance is mainly on photoexposed skin of older adults, particularly on the head
and neck (50%) and extremities [3]. Cases have been reported at the perianal
and eyelids level. The incidence in the United States in 2001 has been estimated
at 0.44 cases per 100,000 [4]. There are associations with chronic lymphocytic
leukemia, chronic exposure to arsenic, HIV infection, postmastectomy lymph-
edema, sarcoidosis, paraneoplastic syndrome, therapeutic immunosuppression,
ectodermal dysplasia [3, 4], and B cell neoplasms [1]. It tends to present local
recurrence and regional lymph node metastases. A high incidence of a second
neoplasm has been described in patients with Merkel cell carcinoma [3, 4]. In
2008, an association with the polyomavirus detected was reported in 80% of
the cases, concluding that the virus may be a factor that contributes to this
tumor [4].
• Clinical presentation: The tumor is clinically indistinguishable from other skin

tumors; it presents as an erythematous plaque or nodule with an appearance
sometimes reminiscent of a painless and fast-growing angiosarcoma [1, 4]. With
an average diameter of 2 cm; however, giant and small variants have been
reported. The acronym “A, E, I, O, U” (asymptomatic, expanding rapidly, immu-
nosuppression, older than age 50, and UV-exposed) has been proposed to easily
remember the clinic [4]. Local recurrences occur in about 1/3 of cases. The
tumor spreads to the lymph nodes in over 75% of cases and distant metastasis
with death in 1/3. Metastases start in the lymph nodes followed by the skin, liver,
lung, bone, and brain (Figs. 29.9, 29.10, and 29.11).
• Diagnosis: It must be made by means of a histopathological examination and
generally requires immunohistochemistry, due to its great clinical similarity to
other cutaneous neoplasms [3]. The tumor is composed of small oval to round
cells, of uniform size with a vesicular nucleus and multiple small nucleoli. It
presents mitosis, and apoptotic bodies are usually numerous [4]. The cytoplasm
is sparse and anophilic, and the borders are vaguely defined. Tumor cells may be
larger in recurrences after radiation therapy. An early large cell variant also
occurs. The cells are presented as solid sheets and nests that infiltrate the entire
dermis and sometimes extend to the subcutaneous cellular tissue [4]. Stromal
desmoplasia is rare [4].
• Differential diagnosis: Clinically Merkel cell carcinoma is indistinguishable
from other skin tumors, it can be similar to an angiosarcoma, or to an amelanotic
melanoma. And histopathologically similar to basal cell carcinoma, squamous
cell carcinoma, and neuroendocrine tumors, so immunohistochemistry will be of
great help for an accurate diagnosis [1].
Fig. 29.9 Merkel cell

carcinoma: In the forearm,
there are two contiguous
tumors approximately 2 cm
* 1 cm and 3 cm * 2 cm
with poorly defined
irregular borders, with a
hyperkeratotic surface with
an erythematous base,
infiltrated [1, 4]
Merkel Cell Carcinoma 701

carcinoma: the tumor cell
express CK20 typically
with perinuclear
accentuation [4]

carcinoma: the tumor cell
express CK20 typically
with perinuclear
accentuation [4]
References
Benign melanocytic neoplasms, Neural and neuroendocrine neoplasms (Other than neurofi-
bromatosis). In: Dermatology, vol. II. 202. 3rd ed; 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
p. 1319–36.
5. Weedon D. Lentigines, nevi and melanomas chapter 32. In: Weedons skin pathology. 3rd ed.
Edinburgh: Churchill Livingstone/Elsevier; 2010. p. 712–56.
nevi (moles): current perspectives. Clin Cosmet Investig Dermatol. 2014;7:89–103. Leite A,
Gontijo B, Vásques F. Giant congenital nevus An Bras Dermatol. 2013;88(6):863–78.
7. Papadopoulos EJ, Cohen PR, Hebert A. Neurothekoma: report of a case in an infant and review
of the literatura. Journal American Academic of Dermatology. 2004;50:129–34.
8. Santamaría IB, Estévez IZ, López AS, Murga II, de Miguel Herrán E, Martínez JAÁ, et al.
Cellular neurothekeoma. Report of two cases. Rev Esp Patol. 2009;42(1):52–8.
9. Hornick JL, Fletcher CDM, Path FRC. Cellular Neurothekeoma: detailed caharacterization in
a series of 133 cases. Am J Surg Pathol. 2007;31(3):329–40.
10. Sage RJ, Lopiccolo MC, Laungani AG, Kouba DJ. “Mohs micrographic surgery for the treat-
ment of cellular neurothekeoma and review of its use in surgical management of benign
tumors” 2010 by the American Society for Dermatologic Surgery, Inc. Published by Wiley
Periodicals. Dermatol Surg. 2010;36:1214–12183.
11. Tothill R, Estall V, Rischin D. Merkel cell carcinoma: emerging biology, current approaches,
and future directions. Am Soc Clin Oncol Educ Book. 2015;(35):e519. (PMID 25993218).
Chapter 30
Disorders of Cells of Langerhans
and Macrophages
Non-Langerhans Cell Histiocytosis
• Definition: They make up a more heterogeneous group of less frequent and worse
studied diseases. The classification of benign forms has always been discussed
and is based on clinical criteria, evolution, histopathology, and phenotypes [1].
• Epidemiology/clinical presentation:
–– Benign cephalic histiocytosis: It is a self-limited histiocytic proliferative dis-
order. There are few cases reported in the literature; the age of presentation is
in children under 1 year of age; it manifests as reddish-brown macules and
papules of 2–5 mm in diameter on the face and necks. It presents spontaneous
resolution from months to years [1].
–– Generalized eruptive histiocytoma: It is characterized by recurrent outbreaks
of small papules, distributed axially, that heal with hyperpigmented macules.
It occurs in adults between the ages of 30 and 60 and in children under 4 years
of age. Physical examination shows reddish-brown papules smaller than 1 cm
on the trunk, proximal extremities, and face with a symmetrical pattern with
compromised mucosa; in children the lesions are more xanthomatic and less
symmetrical [2].
–– Juvenile xanthogranuloma: It is the most common histiocytosis; it occurs in
children with a male:female ratio of 1.5:1, in Caucasians. Seventy-five per-
cent of the cases present during the first year, 15% from birth. In adults it is
rare, 20–30 years, solitary lesions. Usually in infants and children with
involvement of the head, neck, and upper body (Figs. 30.1 and 30.2). Large
and small nodular lesions that turn yellow with maturity. With a rare associa-
tion with NF-1 and juvenile myelomonocytic leukemia, as a “triple associa-
tion” [2].
–– Necrobiotic xanthogranuloma: It is a progressive multisystemic histiocytic
disease, characterized by destructive skin and subcutaneous lesions. It begins
in the sixth decade of life. It presents with cutaneous lesions,

https://doi.org/10.1007/978-3-030-84107-2_30
704 30 Disorders of Cells of Langerhans and Macrophages
Fig. 30.1 Non-Langerhans

cell histiocytosis – juvenile
xanthogranuloma: multiple
large and small yellow-
orange nodules located in
the abdomen, lower
extremities, and genital
area [2]
Fig. 30.2 Non-Langerhans

cell histiocytosis – juvenile
xanthogranuloma: multiple
large and small yellow-
orange and erythematous
nodules located in the
genital area [2]
h epatosplenomegaly, and ocular alterations. The cutaneous lesions are usu-

ally multiple, asymptomatic, such as indurated papules, nodules, or yellow-
colored plaques with telangiectasias, atrophy, ulceration of the lesions, and
scars. The most frequent site is the priority region; it can also be located on
the trunk, face, and proximal extremities. Presents ocular manifestations in
50% of cases such as orbital masses, ectropion, ptosis, conjunctival lesions,
keratitis, scleritis, episcleritis, anterior uveitis, and proptosis. Eighty percent
presents with monoclonal IgG gammopathy, either due to plasma cell
Non-Langerhans Cell Histiocytosis 705
d yscrasias or lymphoproliferative disorders. The synthetic manifestations are

paraproteinemia, hepatomegaly, splenomegaly, increased sedimentation rate
(ESR), leukopenia, hypocomplementemia, plasma cell dyscrasias (myeloma),
cryoglobulinemia, and/or lymphoproliferative disorders [2].
–– Reticulohistiocytosis: They appear as skin lesions of a few millimeters to
2 cm, they are achromic, pink, reddish-brown, or yellow in color. Acral distri-
bution (head, hands, fingers, ears, and limb joints). It presents as small pap-
ules lined up along the periungual “coral bead” region. Fifty percent of the
lesions are in the oral, pharyngeal, and nasal mucosa. “Leonine facies” sec-
ondary to severe facial involvement, periarticular nodules similar to rheuma-
toids, initial photodistribution, and nail changes. Multi-joint, erosive,
symmetric arthritis is common; in 45% of cases, they progress to mutilating
arthritis of the fingers, hands, wrists, and knees. Also, from the cartilaginous
destruction of the nose and ears. Rarely, there is compromise of the heart,
eyes, lung, thyroid, liver, kidney, muscle, salivary glands, and bone marrow.
Although it remits spontaneously at 5–10 years, patients are left with signifi-
cant disability [2].
–– Rosai-Dorfman disease: It is a rare, characterized, proliferative histiocytic dis-
order with variable symptoms, in which lymph node growths and skin changes
are characteristic. Nodes may appear frequently in various organs, frequently
in the head and neck, in superficial and deep locations, present with fever,
anemia, elevated ESR, neutrophilia, and polyclonal hypergammaglobu-
linemia. Children and young adults are the most common, the systemic form
is more common in men, and the skin-limited form is more common in women.
It was previously thought to be limited to the lymph nodes, but it has now been
documented to affect many organs and systems of extranodal involvement;
skin involvement is the most frequent in 16%; it can manifest itself in various
ways such as (a) papulonodular (the most common), (b) indurated plaque, (c)
the form of a tumor, (d) pustular or acneiform lesions, and (e) erythematous
rash [3]. They are xanthomatous or red-brownish [2]. It is found in 15% asso-
ciated with non-Hodgkin’s lymphomas and with immune disorders [2].
–– Disseminated xanthoma: It is a proliferative, normolipemic, histiocytic disor-
der that presents a triad made up of (1) cutaneous xanthomas, (2) xanthomas
in mucous membranes, and (3) diabetes insipidus. Few cases were reported in
the literature, with a higher frequency in men between 8 months and 85 years;
60% are under 25 years of age. It has a symmetric distribution with flexural
and intertriginous involvement. It presents a rare association with monoclonal
gammopathies (blood dyscrasias and thyroid disorders). Primary xanthoma-
tous lesion is a yellow, red, or brown papule that begins with a symmetric
papillomatous eruption, on the face, trunk, and proximal extremities; the
lesions are grouped forming plaques. Mucosal and upper airway lesions occur
in 40–60%. Corneal and conjunctival lesions and diabetes insipidus present in
40% of cases. It has three clinical presentations of the disease: (1) self-healing
form, spontaneous resolution of the lesions which is rare; (2) persistent form,
lesions can never resolve, and it is the most common; and (3) progressive
form, with organ dysfunction and CNS involvement which is rare [2].
• Diagnosis
–– Benign cephalic histiocytosis: It presents three histological patterns:
1. Dermal papilla: It is the most common and occurs as a well-defined infil-
trate similar to the epidermis with pleomorphic histiocytes.
2. Diffuse: Pleomorphic histiocytes are rare; they are round and regular with
little cytoplasm.
3. Lichenoid: Small regular histiocytes, occasional perivascular lympho-
cytes, and superficial dermis [2].
–– Generalized eruptive histiocytoma — They are prominent dense cytoplasmic
bodies, occasional worm-shaped bodies, and laminated concentric bodies
with positive immunohistochemistry for lysozyme, 1-antitrypsin, CD11b,
CD14b, CD68, and factor XIIIa [2].
–– Juvenile xanthogranuloma: Touton giant cells have a crown-shaped arrange-
ment of nuclei within the cell; in some cases, the histiocytes are spindle-
shaped [2].
–– Necrobiotic xanthogranuloma: Presents granulomas with areas of necrobio-
sis, presence of Touton giant cells and giant cells of foreign bodies with posi-
tive immunohistochemistry for lysozyme+, CD68+, CD11b+ [2].
–– Reticulohistiocytosis: Histiocytes are mono- and multinuclear, with abundant
eosinophilic, homogeneous, and granular cytoplasm that gives a ground-glass
appearance, positive immunohistochemistry for lysozyme, alpha-1-
antitrypsia, CD11b, CD14b, CD68, Factor XIIIa, and HAM56 [2].
–– Rosai-Dorfman disease: It presents emperipolesis, which is the uptake of
lymphocytes and intact plasma cells by histiocytes both in the lymph nodes
and in the skin. By immunohistochemistry, they are S100, CD11c, CD14,
CD68, laminin 5, and lysozyme [2].
–– Disseminated xanthoma: In the early stages, there is a dense dermal infiltrate
of histiocytes with foam cells or other inflammatory cells. Plasma cells and
Touton cells are observed. Immunohistochemistry labels for Lysozyme, alpha
1 antitrypsin, and they also express CD69, CD11b, CD14, CD11c, and factor
XIIIa [2].
• Differential diagnosis
–– Generalized eruptive histiocytosis: Pigmented urticaria, eruptive syringomas,
papular granuloma annulare, juvenile xanthogranuloma, and other histiocy-
toses [2]
–– Juvenile xanthogranuloma: Molluscum contagiosum, Spitz nevus [2]
–– Necrobiotic xanthogranuloma: lipoid necrobiosis, flat xanthomas, xanthe-
lasma, other histiocytoses, foreign body granulomas, and sarcoidosis [2]
–– Reticulohistiocytosis: rheumatoid arthritis, dermatomyositis, and other histio-
cytosis [2]
–– Rosai-Dorfman disease: Other histiocytosis, sarcoidosis, infectious pro-
cesses, and other infiltrative disorders [2]
Xanthomas 707
–– Disseminated xanthomas: Juvenile xanthogranuloma, eruptive xanthoma,

generalized eruptive histiocytoma, papular xanthoma, reticulohistiocytosis [2]
Xanthomas
• Definition: Cutaneous xanthomas develop as a result of intracellular and dermal

deposition of lipids. One of the main distinctive clinical features of xanthoma-
tous tissue is a characteristic yellow of orange hue. Xanthomas can present a
variety of morphologies, from macules and papules or plaques and nodules.
They can be generated by primary or secondary disorders of lipid metabolism [1].
• Epidemiology/pathogenesis: Hyperlipidemia is common in the general popula-
tion. In North America, an estimated 100 million people currently have elevated
cholesterol levels >200 mg/dl. Despite the large number of people suffering from
hyperlipidemia, only a minority develops skin xanthomas. It is not always pos-
sible to predict the development of xanthomas since the exact pathophysiological
mechanism is still not totally clear [1]. Skin lesions are caused by lipid deposits
located in the dermis. These lesions are generally caused by high levels of plasma
lipoproteins that through capillaries are phagocytosed by macrophages in the
dermis, forming cells loaded with lipids known as foam cells [1, 2].
• Clinical presentation
–– Eruptive xanthomas: They appear as erythematous to yellow papules, approxi-
mately 1–5 mm in diameter. They are generally distributed on the extensor sur-
faces of the extremities, hands, and buttocks. May present Koebner phenomenon.
They can be secondary to primary or secondary hypertriglyceridemia that often
present triglyceride levels greater than 3000–4000 mg/dl [1]. Recent articles
show that these lesions may indicate the onset of a serious complication.
Recognition of this clinical manifestation can alert us and prevent the develop-
ment of fatal medical conditions such as coronary artery disease and pancreati-
tis [2, 3]. With lipid-lowering treatment, lesions decrease considerably [2].
–– Tuberous and tuberoeruptive xanthomas: They are clinically and pathologi-
cally related. They appear as pinkish-yellowish papules or nodules on the
extensor surfaces, especially on the elbows and knees. Tuberous lesions are
large and can exceed up to 3 cm in diameter (Fig. 30.1). Hypercholesterolemia
can be found as dysbetalipoproteinemia and familial hypercholesterolemia.
When treating dyslipidemia, they may self-resolve but very slowly [1].
–– Tendon xanthomas: They are smooth, firm nodular lipid deposits that affect the
Achilles tendon or the extensor tendons of the hands, elbows, or knees. The
surface of the skin appears normal. Ultrasound can aid in the diagnosis of these
Achilles tendon injuries by demonstrating hypoechoic nodules or an increase
in the anteroposterior diameter of the tendon. The presence of at least one
tendon xanthoma is key to looking for a lipid metabolism disorder. It has been
associated with familial hypercholesterolemia, dysbetalipoproteinemia, and
hypothyroidism [1, 3]. They rarely resolve so dyslipidemia is corrected [1].
–– Flat xanthomas or xanthelasma: they look like yellow-orange macules, pap-

ules, patches, and plaques (Fig. 30.2). They can be well circumscribed or dif-
fuse. Their location can vary from place to place, and they are often key to a
particular disease, for example, intertriginous flat xanthomas which can occur
in the antecubital fossa or the space between the fingers where it is pathogno-
monic of homozygous familial hypercholesterolemia. Flat xanthomas of the
palmar folds or palmar xanthomas are diagnostic of dysbetalipoproteinemia,
especially when accompanied by tuberous xanthomas [1].
–– Xanthelasmas or palpebral xanthelasmas: they are frequently observed in flat
xanthomas of the eyelids (Fig. 30.3). However, the presence of xanthelasma
warns that it presents some hyperlipidemia, which occurs in only half of the
patients who have these lesions. Young patients with xanthelasmas or with a
family history of hyperlipidemia and xanthelasma have more lipid disorders
and should have appropriate screening. Flat xanthomas can occur in normo-
lipid patients, but they can have monoclonal gammopathy, usually due to
plasma cell dyscrasia, but occasionally secondary to lymphoproliferative
disorders such as B-cell lymphoma or Castleman disease. This type of xan-
thoma can also be seen in patients with chronic myelomonocytic leukemia [1].
–– Verruciform xanthomas: asymptomatic flat or warty plaques 1–2 cm in diam-
eter. They occur mainly in the mouth but sometimes in the anogenital region
or periorificial sites. There is usually no associated hyperlipidemia [1]
(Figs. 30.4, 30.5, and 30.6).
Fig. 30.3 Non-Langerhans cell histiocytosis (histopathology): the infiltrate consists of nonxan-
thomatized histiocytes. Lymphocytes as seen in this field are generally present [2]
Xanthomas 709
Fig. 30.4 Tuberous and

tuberoeruptive xanthomas:
Multiple erythematous
papules on the knee over
patella [1, 3]
Fig. 30.5 Flat xanthomas

or xanthelasma: multiple
papules that converge to
form plates with well-
defined irregular edges,
yellowish and brown in the
armpit [1]
Fig. 30.6 Xanthelasmas or

palpebral xanthelasmas:
multiple papules that
converge to form tumor
plaques, well-defined
irregular edges, yellowish
and brown, periocular, and
perioral [1]
• Diagnosis: It is clinical, and histopathology is characterized by foam cells which

consist of macrophages that contain lipids within their cytoplasm. All xanthomas
contain dermal lipid infiltrates, but these can vary in their degree of lipid content,
the inflammatory infiltrate, its location, the amount, and the presence of extracel-
lular lipid [1].
Differential Diagnosis
• Eruptive xanthomas: Non-Langerhans cell histiocytosis, disseminated xan-

thoma, papular xanthoma, Rosai-Dorfman histiocytosis
• Tuberous xanthomas: Erythema elevatum diutinum, multicentric
reticulohistiocytosis
References 711
• Tendon xanthomas: Giant cell tumor of the tendon sheath, rheumatoid nodule,
subcutaneous granuloma annulare
• Xanthelasma: Syringomas, necrobiotic xanthogranuloma, sebaceous hyperpla-
sia, palpebral sarcoidosis [1]
References
matosis). In: Dermatology Bolognia, vol. II. 202. 3rd ed; 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
Chapter 31
Malignant Neoplasms
Actinic Keratoses
• Definition: A frequent premalignant skin lesion associated with chronic exposure

to ultraviolet radiation and which is currently considered the earliest clinically
recognizable manifestation of a squamous cell carcinoma since it has the ability
to transform into squamous cell carcinoma in situ or invasive squamous cell car-
cinoma [1].
• Epidemiology/pathogenesis: Actinic keratoses are the second most frequently
seen diagnosis by dermatologists in the United States with a prevalence of 5.2
million visits per year. Cumulative exposure to ultraviolet light, immunosuppres-
sion, and age increase the risk of developing actinic keratoses. In addition, molec-
ular alterations such as mutations in p53, MYC, and the epidermal growth factor
receptor are recognized in its development, with a genetic profile similar to that
of squamous cell carcinoma. The risk of developing squamous cell carcinoma
from actinic keratoses is 1% per year; however, this progression depends on the
number of lesions, and this percentage is maintained up to 5 lesions; the risk
increases to 20% in those patients with more than 20 lesions. Therefore, actinic
keratoses are considered to be a biomarker of squamous cell carcinoma [1, 2].
• Clinical presentation: Actinic keratoses appear as slow-growing papules or
plaques less than 1 cm in diameter, rough, erythematous, or pigmented with tel-
angiectasias, mostly covered with adherent yellow or brown scale with little or
no infiltration. They are located in photoexposed areas (face, neck, neckline,
shoulders, back of forearms, back of hands, and scalp). The level of infiltration,
hyperkeratosis, pigmentation, and secondary ulceration can be variable. The per-
ilesional areas may show obvious signs of chronic diffuse sun damage due to
telangiectasias, elastosis, pigmentary alteration, and scars [1]. Actinic keratoses
located on the back of the hands and forearms are generally thicker and more
keratotic, with some lesions cutaneous horn-like [1, 2] (Figs. 31.1, 31.2,
and 31.3).

https://doi.org/10.1007/978-3-030-84107-2_31
714 31 Malignant Neoplasms
Fig. 31.1 Actinic

keratoses: in the
cheekbone, an
erythematous and brown
plaque, rough, covered
with adherent yellow and
brown scale with little
infiltration [1, 2]
Fig. 31.2 Multiple actinic

keratoses: in the forehead
skin, multiple
erythematous and brown
plaques, rugous, without
infiltration [1, 2]
Fig. 31.3 Multiple actinic

keratoses: in the forehead
skin, multiple
rugous, with little
infiltration [1, 2]
• Diagnosis: The diagnosis of actinic keratoses is based on the clinical presenta-

tion; however, they are sometimes indistinguishable from squamous cell carci-
noma, for which the histopathological study is used as a useful tool for their
diagnosis [1]. Histologically, actinic keratoses are characterized by the presence
Basal Cell Carcinoma 715
of atypical keratinocytes in the epidermis and an increase in the number of mito-

ses with disorganized structure; these keratinocytes also show loss of polariza-
tion with pleomorphic nuclei, increased size and hyperchromatism, pale
eosinophilic cytoplasm, and vacuolization. There is usually solar elastosis and
perivascular or lichenoid lymphocytic infiltrate of varying intensity in the dermis.
On histopathological examination, actinic keratoses can be divided into six types:
hypertrophic, atrophic, bowenoid, acantholytic, lichenoid, and pigmented [2].
• Differential diagnoses: Clinically, the differential diagnosis of erythematous
actinic keratosis should be established with seborrheic keratosis, common wart,
porokeratosis, psoriasis, discoid lupus, and squamous cell carcinoma. The hyper-
trophic variant must be distinguished from the cutaneous horn secondary to viral
wart, seborrheic keratosis, and squamous cell carcinoma. The lichenoid form of
basal cell carcinoma and the pigmented form of lentigo solar and lentigo
maligna [1, 2].
Basal Cell Carcinoma
• Definition: A malignant epithelial tumor originating from the pluripotent cells of

the epithelium with a slow growth rate; however, it is locally invasive with
destruction of compromised tissues, but with a low metastatic potential [1].
• Epidemiology/pathogenesis: Its etiology seems to be induced by intermittent
solar radiation, ionizing radiation, and ultraviolet radiation such as tanning
chambers or phototherapy chambers for medical use [2, 3]. Exposure to arsenic
and genetic syndromes such as xeroderma pigmentosum, Rombo syndrome,
Bazex-Dupré-Christol syndrome, Gorlin-Goltz syndrome, as well as immuno-
suppression and transplants [2]. Where there is regulation of the cell cycle, the
Hedgehog signaling pathway and mutations in the p53 gene are altered [2]. By
2020, approximately 102 new cases per 100,000 population could be expected
[4]. The incidence of basal cell carcinoma has increased in the last four decades;
this increase has been reported in countries in Europe, Canada, Australia and the
United States. Australia is the country in the world that reports the highest inci-
dence rate (884 per 100,000 people per year) [1] and the Arizona and New
Mexico regions of the United States report rates similar to those in Australia [1].
In Europe and Canada, incidence rates range from 100 to 150 per 100,000 inhab-
itants [1]. The incidence of skin cancer in Colombia went from 23 to 41 new
cases per 100,000 inhabitants, during the years 2003–2007 [1]. At the National
Cancer Institute, 340 new cases are treated each year [3]. Also, 80% and 90% of
the cases are located in the head and neck. In the black race, the incidence is very
low (3.5 per 100,000 inhabitants) [3].
• Risk factors are given by residence in a rural area after age 30, no use of hats in
childhood, outdoor sports throughout life, family history of skin cancer, history
of more than 10 sunburns throughout life, a history of actinic keratoses, actinic
conjunctivitis, and phototype I–III [3].
• Clinical presentation: The lesion is characterized by being located in photoex-

posed areas given by achromic or pigmented papules of 1–10 mm in diameter
with a pearly, shiny, and smooth surface with telangiectasias [4]. There are seven
clinical subtypes that are superficial, nodular, scar plane, morpheiform, ulcus
rodens, terebrant, and fibroepithelioma of pinkus. Eighty-five percent of basal
cell carcinomas belong to the nodular and superficial subtypes [4].
–– Nodular basal cell carcinoma: It is the most frequent clinical form; it is
located mainly on the head, neck, and shoulders, as a papule or nodule of vari-
able size, well-defined edges, with a shiny smooth surface, with telangiecta-
sias, and occasionally, it may present a central ulceration [2, 4].
–– Superficial basal cell carcinoma: It can occur at an average age of 57 years in
the trunk and extremities as a well-defined, scaly, round, or oval plaque or
erythematous patch and crusting, with a raised pigmented border, which can
sometimes regress leaving a hypopigmented atrophic plaque [2]. It may or
may not have a pearly border and is found predominantly on the trunk [1].
–– Morpheiform basal cell carcinoma: It is a less frequent clinical variety, with
aggressive behavior that is observed as a poorly defined plaque, indurated,
light-pink to whitish in color, with a smooth surface, with telangiectasias,
eroded or ulcerated, and an edge that is not pearly [2].
–– Pinkus fibroepithelioma: It is a rare tumor described by Hermann Pinkus in
1953, who called it “premalignant fibroepithelial tumor,” then defined as a
proliferation that gives rise to multiple small basal cell carcinomas in each
lesion [2]. It is a nodule of rubbery consistency, erythematous, and peduncu-
lated, located on the back [3].
–– Ulcus rodens: Its initial presentation is as an ulcer, with indurated edges, of
superficial extension [2].
–– Terebrant: It is an infiltrating, destructive tumor, with invasion of anatomical
structures such as the cartilage, bone, and eyeball. Rapidly evolving and more
aggressive [2].
–– Scar plane: It is a plate with a central scar, of variable size, with a papular
edge [2] (Figs. 31.4, 31.5, 31.6, 31.7, 31.8, 31.9, 31.10, 31.11, 31.12, 31.13,
31.14, 31.15, 31.16, 31.17, and 31.18).
• Association of basal cell carcinoma with other pathologies:
–– Gorlin-Goltz syndrome: It is an autosomal-dominant genodermatosis, the
product of a mutation in the PTCH1 gene, characterized by the development
of defects that include horizontalization of the ribs, palmar cavities, and pre-
disposition to multiple tumors such as basal cell carcinoma (BCC),
medulloblastoma, ovarioma, fibromas, and odontogenic keratocysts, also

with facial dysmorphism (macrocephaly, cleft lip and palate, and serious eye
abnormalities) and intellectual deficit in 5% of cases [6].
–– Xeroderma pigmentosum: It is an autosomal recessive genodermatosis with
extreme sensitivity to UV-induced changes in the skin and eyes, with multiple
skin cancers. There are mutations in 8 genes involved in DNA repair. Seven of
Fig. 31.4 Nodular basal

cell carcinoma: on the left
aspect of the nose can be
observed an erythematous
nodule with well-defined
edges, a shiny smooth
surface, and multiple
telangiectasias [2, 4]

and violaceous well-
defined nodule with a
shiny smooth surface and
central ulceration [2]

well-defined shiny papule
with smooth surface and
multiple telangiectasias [4]
Fig. 31.7 Superficial basal

cell carcinoma. There can
be observed an oval
a raised pigmented border,
mild hypopigmented
atrophic center and
superficial crust [2]
Fig. 31.8 Superficial basal

cell carcinoma: over the
mastoid region there can
be observed a round
a raised pigmented border
and mild hypopigmented
atrophic center [2]
Fig. 31.9 Morpheiform

basal cell carcinoma: Over
the left zygomatic region,
there can be observed a
poorly defined light-pink
plaque, with a smooth
surface and mild
telangiectasias [2]

basal cell carcinoma: over
dorsum nasi region, there
can be observed a poorly
defined light-pink to
whitish plaque, with a
smooth surface and mild
ulcerated upper edge [4]

basal cell carcinoma: over
the tip of the nose, there
can be observed a poorly
defined light-pink atrophic
area, with a smooth
surface [4]
Fig. 31.12 Pinkus

fibroepithelioma: rubbery
light pink nodule partially
pedunculated [3]
Fig. 31.13 Pinkus

fibroepithelioma: multiple
erythematous and yellow
papules confluence in a
well-defined plaque with
mild erosion [3]
Fig. 31.14 Ulcus rodens:

over the right medial malar
process, there can be
ulcer with indurated edges
with multiple
telangiectasia [2]
Fig. 31.15 Ulcus rodens:

on the frontal region, there
is an erythematous and
violaceous ulcer with
indurated edges with
hematic crust surface [2]
Fig. 31.16 Terebrant

carcinoma: over the left
ocular and malar regions,
there is an infiltrating,
erythematous, poorly
defined, destructive tumor,
with invasion of
anatomical structures
including the eyeball [2, 4]
Fig. 31.17 Terebrant

carcinoma: over the nose
and right malar region,
there is an infiltrating,
poorly defined, destructive,
and friable tumor, with
invasion and distortion of
anatomical structures [2, 4]
these genes, XPA to XPG (ERCC5), are involved in nucleotide excision

repair, which code for DNA polymerase, necessary for DNA replication with
UV-induced damage. They may have ocular disorders such as keratitis, pho-
tophobia, squamous cell carcinoma, and ocular melanoma. Neurological
abnormalities include microcephaly, decreased or absent deep reflexes, hear-
ing loss, spasticity, ataxia, seizures, and progressive cognitive decline [5].
–– Bazex-Dupré-Christol syndrome: It is a rare genodermatosis of autosomal
dominant inheritance linked to the X chromosome that predisposes to the early
appearance of carcinoma. Such as the onset in the neonatal period or during
childhood. The UBE2A gene found on the long arm of the X chromosome, in
position Xq24-q27.1, which codes for a protein involved in the repair of dam-
age caused by ultraviolet rays. Clinically, follicular atrophoderma is observed
on the back of the hands and feet, on the extensor aspect of the shoulders and
knees, and on the face. In addition to hypotrichosis of the scalp and sometimes
eyebrows, hypohidrosis and milium cysts. Also, basal cell carcinoma occurs in
40% of patients in the second or third decade of life. Other features present are
basal cell hamartomas, trichoepitheliomas, and, exceptionally, atopy, keratosis
Fig. 31.18 Scar plane

carcinoma: over the left
frontal region, there is a
poorly defined plaque with
a central scar and a
gray-violet papular
edge [2]
pilaris, ichthyosis, arachnodactyly with joint hypermobility, osteochondritis,

deafness, and learning difficulties [5] (Figs. 31.19 and 31.20).
• Diagnosis: Basal cell carcinomas are made up of islands or nests of basaloid
cells, with a palisade of cells at the periphery and a disorderly arrangement of
cells in the center of the islands. Tumor cells have a hyperchromatic nucleus with
relatively little cytoplasm. Intercellular bridges are invisible under the routine
light microscope. There are numerous atypical mitotic figures at times and a high
number of apoptotic tumor cells [7].
–– Nodular basal cell carcinoma: Presents well-circumscribed tumoral lobes or
nodules of various sizes, located in the dermis, made up of basaloid neoplastic
cells with peripheral palisade and stroma cleft. The nests take on a more baso-
philic color than the normal epidermis or the epithelium of the hair follicle
[8]. Occasionally, an inflammatory reaction is seen in the periphery of the
tumor and the adjacent dermis. Necrotic cells can also be seen in masses in
tumor nests [1].
Fig. 31.19 Gorlin-Goltz syndrome: multiple face, scalp and dorsal basal cell carcinomas, palmar
cavities, and odontogenic keratocysts [6]
–– Superficial basal cell carcinoma: It occurs as multiple tumor nests of basaloid

cells, which detach from the basal layer of the epidermis and only extend to
the papillary dermis. Peripheral palisade and stromal cleft are occasionally
seen [8]. Tumoral islands may be scattered in surrounding tissue or separated
by large portions of normal skin [1].
Fig. 31.20 Xeroderma

pigmentosum: a young
adult with severe UV
damage, ocular
compromise, and right
malar squamous cell
carcinoma [6]
–– Micronodular basal cell carcinoma: There are small tumor nests (less than
15 μm), uniform, rounded and with peripheral palisade. This pattern usually
does not have a stromal cleft. This historical type can be circumscribed or
scattered; the dispersion of micronodules can be associated with a large sub-
clinical extension [1, 8].
–– Morpheiform basal cell carcinoma: Small elongated, sharp tumor islands are
observed immersed in a dense, fibrous, sclerous and scar-like stroma. The
tumor islands are poorly delimited and do not show a peripheral palisade. It is
dispersed and with an infiltrative advance front, reaching up to the deep der-
mis [1, 8].
–– Trabecular basal cell carcinoma: Presents tumor islands with a band pattern,
elongated, forming trabeculae with pointed or serrated edges. In this histo-
logical pattern, no peripheral palisade is observed, since the tumor islands are
not rounded. Stromal fibrosis is not observed, it is diffuse, infiltrative, and
presents an advance front with ill-defined limits [8]. It is called in the Anglo-
Saxon literature as infiltrative basal cell carcinoma, but this term can be con-
fused with morpheiform basal cell carcinoma, because it is also present an
infiltrative pattern [1] (Figs. 31.21, 31.22, 31.23, and 31.24).
• The risk factors for recurrence for basal cell carcinoma are fundamental and are
divided into two groups: clinical factors for recurrence and histological factors
for recurrence.
–– Clinical factors of recurrence: Age under 30 years old, long evolution time,
tumor located in a high-risk area (H zone), size >1 cm located in a high-risk
area or >2 cm in a low-risk area, poor clinical borders delimited and recurrent
tumors [3].
–– Histological factors of recurrence: scattered micronodular, trabecular, mor-
pheaform pattern, basosquamous carcinoma due to diffuse infiltration (for-
ward front), dispersion, depth of infiltration, and perineural invasion [3].
Fig. 31.21 Nodular basal cell carcinoma: well-circumscribed tumor nodules of multiple sizes,
made up of basaloid neoplastic cells with peripheral palisade and stroma cleft located in epidermis
and dermis. Focal micronodular basal cell carcinoma [1, 8]
Fig. 31.22 Superficial basal cell carcinoma: tumor nests of basaloid cells that extend to the papil-
lary dermis being separated by large portions of normal skin [1, 8]
Fig. 31.23 Morpheiform basal cell carcinoma: small tumor islands are observed immersed in a
dense, fibrous, sclerous stroma. Being dispersed and reaching up to the deep dermis [1, 8]
• Differential diagnosis: It is usually performed with benign lesions such as sebor-

rheic keratosis, neurofibroma, intradermal melanocytic nevus, and skin tag [5].
With malignant lesions such as sebaceous carcinoma, basosquamous carcinoma.
Histopathology can be confused with adenoid cystic carcinoma, ameloblastoma,
basaloid follicular hamartoma, cloacogenic carcinoma, dermatofibroma, eccrine
carcinoma, folliculocentric basaloid proliferation, metastasis of breast cancer,
microcystic adnexal carcinoma, tricyclic carcinoma, and trichoepithelioma seba-
ceous carcinoma, and trichoepithelioma [5].
Basosquamous Carcinoma
• Definition: A tumor with mixed morphology between basal cell carcinoma

(BCC) and squamous cell carcinoma (SCC) has been considered [1].
Basosquamous carcinoma is defined histologically as a tumor that contains areas
Basosquamous Carcinoma 727
Fig. 31.24 Trabecular basal cell carcinoma: diffuse and infiltrative tumor islands that are elon-
gated, forming trabeculae with pointed or serrated edges with ill-defined limits [1, 8]
of BCC and SCC: with a transition zone between them. The most widely accepted
histological definition is that carcinoma comprises two elements:
–– Basaloid cells with infiltrative growth with a scant cytoplasm and a long, uni-
form nucleus [1].
–– Squamous cell aggregates containing abundant eosinophilic cytoplasm either
found near the center or dispersed throughout the lesion [1].
• Epidemiology/pathophysiology: Basosquamous carcinoma has an estimated
incidence of 1.2–2.7% of all skin cancers; most are found in areas of sun
exposure, head, and neck with a frequency of 82–97%. It predominates in the
central facial and perinasal area. They rarely occur on the trunk and extremities.
This distribution is similar to that of BCC and CEC [1, 2]. Basosquamous carci-
noma occurs mainly in white-skinned, elderly, male individuals, which has
reported having a more aggressive behavior. A rare feature of basal squamous
cell carcinoma and metastatic BCC is the presence of a long-standing lesion [1].
However, basosquamous carcinoma is relatively rare. It has an aggressive local
behavior, with an increase in recurrence and metastasis. This aggressive clinical
behavior differs significantly from basal cell carcinoma. Despite this, studies are
limited by small cohorts, and their histology is debated [1]. Many studies have
shown a trend toward a worse prognosis and higher incidence of recurrence and
metastasis compared to BCC [1]. Some authors have equated the behavior of
basosquamous carcinoma with CPB. The local recurrence rate of basosquamous
carcinoma can be above 45% after surgical excision [1].
• In a study of 28 patients, Martin and colleagues reported significant predictors of

basosquamous carcinoma recurrence, including male gender, positive surgical
resection margins, lymphatic invasion, and perineural invasion [1]. The most
common pattern of recurrence was local, followed by local recurrence plus
lymph node involvement and less frequent lung and lymph node involvement [1].
The CBC metastasis rate has been estimated to be less than 0.1%; however, it
increases by approximately 2% when the tumor is larger than 3 cm. Compared
with basosquamous carcinoma, the rate of metastasis ranges from 5% to 8.4%
with respect to CPB. The 5-year survival rate is 54%. These numbers suggest an
intermediate prognosis between CBC and CEC [1].
• Clinical presentation: The clinical characteristics are difficult to elucidate,
because they have semiological features of basal cell and squamous cell carci-
noma [2] (Figs. 31.25 and 31.26).
1. Diagnosis: It is important to exclude a collision tumor where the areas are sepa-
rated from CBC and CEC, but there is no transition zone other than one of the
two. This diagnosis must be distinguished from a form of keratinizing BCC,
Fig. 31.25 Basosquamous

carcinoma: tumor in the
right temporal region and
external canthus of the
right eye measuring 3 cm *
3 cm infiltrated and
indurated [2]
Fig. 31.26 Basosquamous

carcinoma: infiltrated and
indurated erythematous left
infrapalpebral tumor with
hematic crusts [2]
Keratoacanthoma 729
which contains abrupt keratinization usually of the center of the BCC tumor
nodule but lacks areas of squamous cells [1]. Immunohistochemistry can be
helpful in the diagnosis of basosquamous carcinoma. Most CBCs show strongly
positive staining for Ber-EP4, and CEC tends to show staining for EMA
(Epithelial Membrane Antigen). Basosquamous carcinoma plays a mixed immu-
nohistochemical pattern with Ber-EP4 and EMA [1]. Immunohistochemistry in
areas with CBC has been shown to be positive for Ber-EP4, cytokeratin 1 (AE1),
and cytokeratin 3 (AE3) and in the CEC areas have positive AE1, AE2, and
CAM 5 with variable EMA staining. In the transition zone, there is a gradual loss
of cellular markers [1].
2. Differential diagnosis: A differential diagnosis should be made between basal
cell carcinoma and squamous cell carcinoma. In addition, it is important to
exclude a collision tumor where the areas are separated from CBC and SCC, but
there is no transition zone other than one of the two. It must also be differentiated
from a form of keratinizing CBC that contains abrupt keratinization usually of
the center of the tumor nodule, but it lacks squamous cell areas [1].
Keratoacanthoma
• Definition: It is an epidermal tumor [1], with a history of rapid growth of

4–5 weeks and resolution after 6 months [1, 2]; however, this remains highly
controversial [1].
• Epidemiology/pathogenesis: Keratoacanthoma has a peak incidence at
50–69 years, although they have been reported in all ages, it is unusual to find it
in those under 20 years; the incidence ranges between 22–150 per 100,000
inhabitants [1]; the same predilection has been found in both men and women but
with a slight predominance in men [2]. Its etiology is unknown; however, it is
assumed that the lesion is derived from the hair follicles, due to the keratin analy-
sis, which suggests that it has characteristics of follicular differentiation and
squamous cell carcinoma [1]. The location in photoexposed areas and the
increase in its incidence in the summer make ultraviolet rays increase the risk of
onset keratoacanthoma [1]. Other etiological factors have been implicated. They
can be classified as chemical, mineral oil, cigarette, trauma (peels, CO2 laser,
megavoltage radiation therapy, cryosurgery) and immunosuppression [1]. The
expression of the protein bcl-2 / BAK has been implicated in the pathogenesis of
keratoacanthoma and squamous cell carcinoma. Low bcl-2 expression in con-
junction with high BAK expression has been found in self-resolving keratoacan-
thomas [1].
• Clinical presentation: It presents itself as a solitary or multiple lesion with a firm,
pink nodular shape of 1–2 cm, with shiny epidermis and a central keratin plug,
generally, located on areas exposed to the sun, on the face and extremities [1]. It
can appear sporadically or associated with a syndrome (Muir-Torre syndrome) or
inflammatory diseases [2]. It has three stages: the first stage is a phase prolifera-
tive, where the tumor increases in size 10–25 mm in diameter in 6–8 weeks [1].
Some keratoacanthomas can metastasize, so the relationship of squamous cell
carcinoma and the classification as a benign or malignant keratoacanthoma is
debated. Association with sebaceous nevi and inflammatory disorders has been
reported. They recur in 3–5% of cases [1]. The lesion begins as a small pink
macula that transforms into a papule and then assumes a volcano-like shape with
a central crater filled with keratin [1]. The second stage is the maturation of the
keratoacanthoma, where the lesion stops its growth, maintains the shape of a
crater, and appears as a dome; the structure contains a hair, a central keratin plug,
and signs of fragmentation. Finally, in the involution stage, 50% of keratoacan-
thomas resolve spontaneously in 4–6 weeks, with expulsion of the keratin plug,
and the tumor mass is reabsorbed, leaving a hypopigmented and atrophic scar.
Some lesions are persistent for a year or more; however, the entire process from
their origin to spontaneous resolution usually takes about 4–9 months [1]
(Figs. 31.27, 31.28, and 31.29).
• Diagnosis: Clinical and histopathological criteria have been diagnosis of kerato-
acanthoma. Typical keratoacanthoma features include an exophytic-endophytic
architecture with a central keratotic plug, protruding epithelial lips, surrounded
by a polymorphonuclear infiltrate with intracytoplasmic glycogen and intraepi-
thelial elastic fibers. Mitoses and atypical keratinocytes are generally not
prominent. The tumor in most cases does not spread to the dermis or eccrine
glands nor does it present perineural invasion. Keratoacanthoma regression
shows a flatter base of the tumor epithelium with surrounding fibrosis [2, 3].
• Differential diagnosis: Squamous cell carcinoma, hypertrophic actinic keratosis,
viral wart [3].
• Definition: In current practice, Bowen’s disease is considered a synonym for
squamous cell carcinoma (SCC) in situ for non-genital lesions [1].
• Epidemiology/pathogenesis: Bowen’s disease occurs in both sexes of all ages but
is more common in Caucasian men [1]. With a peak incidence in the seventh
Fig. 31.27 Keratoacanthoma:

on top of the left hand, a firm,
pink tumoral nodule of 3 cm,
with shiny epidermis and a
central keratin plug [1, 2]
Keratoacanthoma 731

on the lateral side of the right
forearm, a firm, pink
exophytic tumoral nodule of
2 cm, with a central keratin
plug [1, 2]

on the right cheek, a pink
tumoral plaque of 3 cm, with
a central keratin plug [1, 2]
decade of life and a slight predominance in women, the majority of in situ reports
of CEC occur at sun exposure sites. In England, an annual incidence of
15 × 100,000 inhabitants has been suggested [2]. A higher incidence has been
reflected in areas of sun exposure [2]. The most frequently affected area is the
neck in 29–54% [3]. In women it is more frequent in the lower extremities.
Palmar, periungual, subungual, and genital involvement are less common, and
the risk of progressing to invasive squamous cell carcinoma has been found to be
about 3–5%. Also, those that affect the perianal region have a higher risk of inva-
sion and recurrence [3]. The etiological factors for in situ SCC include: irradia-
tion, ultraviolet radiation (solar, iatrogenic, and tanning beds) and radiotherapy;
carcinogens, arsenic (lesions may arise in areas protected from the sun); and
immunosuppression, in particular viral therapy. There is an association between
the human papillomavirus (HPV), especially HPV16, and the development of
anogenital SCC in situ, but this is not of any condition for its development. HPV
DNA has demonstrated in situ extragenital CPB in varying amounts of 4.8–60%.
HPV 16 from in situ SCC of the hands and feet has been implicated in 60% of
palmoplantar and periungual lesions, chronic lesions, or dermatoses (such as
lupus vulgaris or chronic lupus erythematosus) [2].
• Clinical presentation: It frequently appears as a solitary lesion on areas of

exposed skin or skin not exposed to the sun; there are generally other concomi-
tant lesions that indicate chronic sun damage such as actinic keratoses, solar
lentigines, poikilothermia, and even basal cell carcinomas. It presents clinically
as a discrete irregular erythematous plaque, with slow evolution and centrifugal
growth. Progression to invasive CPB only occurs in 5–10% of patients [1]
(Figs. 31.30, 31.31, 31.32, 31.33, 31.34, 31.35, 31.36, 31.37, and 31.38).
• Diagnosis: Squamous cell carcinoma in situ is a histological diagnosis. It is rep-
resented by an atypia of transepidermal or transepithelial keratinocytes with
numerous mitotic figures, dyskeratotic cells, and hyperchromasia [3].
• Differential diagnosis: Superficial basal cell carcinoma, extramammary Paget
disease [1].
Erythroplasia of Queyrat
• Definition: It is a squamous cell carcinoma in situ of the glans penis [1]

• Epidemiology/pathogenesis: Contains a high risk of human papillomavirus
(HPV) serotypes, mainly HPV-16, which may represent a precursor to vulgar,
penile, or perianal cancer [2]. It usually occurs in uncircumcised men; others risk
factors are poor hygiene, herpes virus infection, and preparation with HPV type
8, 16, 39, and 51 serotypes [1]. It occurs in men between the ages of 20 and
80 years [2].
• Clinical presentation: Well-demarcated velvety erythematous plaque located in
the transitional epithelium of the penis over the glans, the foreskin, or the less
frequent urethra, involving the vulva [2, 3]. Between 10% and 40% of these
squamous cell carcinomas in situ evolve to invasive squamous cell carcinomas,
and of these, 20% metastasize [3] (Fig. 31.39).

plaque on the right temple,
irregular margins and
infiltrates and scaling on
the surface [1, 2]
Squamous Cell Carcinoma 733
Fig. 31.31 Proximal third

of the left leg,
fine scaling on the surface
[1, 2]
• Diagnosis: Histologically it is detected as a high-grade intraepithelial neo-

plasia [2].
• Differential diagnosis: Erosive lichen planus, zoom balanitis, psoriasis, candidi-
asis, lymphogranuloma venereum, and syphilis [1, 2].
Squamous Cell Carcinoma
• Definition: Squamous cell carcinoma (SCC) corresponds to a malignant tumor of

epithelial origin made up of atypical squamous cells that originate in the epider-
mis and that can spread to the dermis with different degrees of maturation and
keratin formation [1]. Ranking second in frequency among skin cancers [1, 2]. It
has a very aggressive biological behavior and causes local recurrence; unlike
basal cell carcinoma, squamous cell carcinoma has the capacity to cause great
local destruction, metastasis, and death [1, 2].
Fig. 31.32 Hyperkeratotic

tumor, yellowish brown
with an infiltrated base
[1, 2]
Fig. 31.33 Irregular

plaque with areas of
hyperkeratosis, its lower
pole an erythematous
tumor with areas of
ulceration [1, 2]

plaque, hyperkeratotic
surface, with hematic
crusts on the surface [1, 2]
Fig. 31.35 In the right

mandibular branch,
irregular borders; in its
lower pole, it presents a
yellowish-brown
hyperkeratotic papula
[1, 2]

plaque in the right external
malleolar region, in its
lower pole a brownish
hyperkeratotic tumor with
a hematic crust [1, 2]
Fig. 31.37 On the medial

aspect of the fifth finger of
the right hand, there was
an infiltrated erythematous
brown hyperkeratotic
tumor [1, 2]
Fig. 31.38 Epidermis with irregular acanthosis caused by the proliferation of dysplastic keratino-
cytes that focally compromise its entire thickness [3]
• Epidemiology/pathogenesis: 100,000–200,000 cases are diagnosed each year in

the United States. The National Cancer Institute treats 150 new cases each year
[1]. The development of SCC has been associated with various environmental
factors, as well as intrinsic or constitutional factors. Among the intrinsic factors,
the most important are patients with light skin and eyes, phototypes I and
II. Patients with certain genodermatoses (albinism or xeroderma pigmentosum,
verruciform epidermodysplasia, porokeratosis, dystrophic epidermolysis
bullosa) [1, 2] are more susceptible to keratinocyte damage from ultraviolet radi-
ation [2].
Fig. 31.39 Erythroplasia

of Queyrat: inferior view
of the area of glans penis
shows a plaque on the
ventral surface of foreskin
and frenulum, which
appears raised and
erythematous, with poorly
defined borders and
measures approximately
3 × 3 cm [2, 3]
• Chronic exposure to ultraviolet (UV) radiation, mainly UVB, is the main risk
factor for developing SCC, and to a lesser degree UVA [2]. Other sources of
ultraviolet radiation such as tanning rooms or sun rooms. Phototherapy for medi-
cal use can also generate this tumor [1]. Ultraviolet radiation, X-rays, occupa-
tional exposure to arsenic and polycyclic aromatic hydrocarbons, and chronic
exposure to heat produce mutations in the DNA within them, the formation of
pyrimidine dimers in the tumor suppressor gene p53 that prevents apoptosis by
inducing proliferation of tumor cells [2]. Other frequent genetic aberrations are
the following:
–– The silent mutation of the CDKN2A locus.
–– Mutations activated in the Ras oncogene (10–50%).
–– The loss of function of the mutation in NOTCH1 or NOTCH2 (75%). These
genes encode cellular receptors in signaling pathways, interacting with the
Wnt/B-catenin pathway [3].
–– Amplification of the c-Myc oncogene has been reported in over 50% of SCC
in immunosuppressed patients [3].
• Clinical Presentation
–– Squamous cell carcinoma originating from damaged actinic skin: It is located
exclusively in photoexposed areas; it is usually preceded by actinic keratosis.
It presents as a hyperkeratotic erythematous papule or nodule with progres-
sive growth, ulceration, and bleeding [2].
–– Squamous cell carcinoma “de novo”: It predominates in Caucasians; the
symptoms are similar to the previous one; however, it originates in skin not
exposed to the sun and without a triggering factor. It has an increased poten-
tial for metastatic disease [2].
–– Squamous cell carcinoma originating from chronic lesions: SCCs develop
with some frequency from chronically diseased skin, such as chronic ulcers,
fistulous tracts, scars secondary to burns, osteomyelitis, previously irradiated
skin, and skin affected by chronic inflammatory dermatoses (discoid lupus
erythematosus, lichen sclerosus and atrophicus, lichen planus, dystrophic epi-

dermolysis bullosa, and lupus vulgaris). Being more aggressive, with a higher
percentage of invasion, recurrence, and metastatic potential [2].
–– Verrucous carcinoma: It is an infrequent variant of invasive CPB; at the clinic
an indolent verrucous tumor in the shape of cauliflower is observed that is
characterized by its local aggressiveness and low metastatic potential. There
are four clinical variants according to anatomical location [2]:
• Oral florid papillomatosis: This occurs in 2–12% of oral carcinomas, in
white men, in the oral and gingival mucosa (larynx) when chewing tobacco,
secondary to the human papillomavirus (HPV) [10–12], lichen or chronic
candidiasis [4].
• Buschke-Lowenstein tumor: It occurs in middle-aged men, circumcised,
located in the glans and foreskin, occurs in 5–24% of all penile carcinomas
and is associated with HPV 6 and 11, followed by HPV 16 and 18 [3].
• Epithelioma cuniculatum: It occurs in middle-aged white men, on the soles
of the feet (53%), on the toes (21%), and on the heel (16%). Initially it
looks like a plantar wart, secondary to trauma and secondary to HPV 6
and 11 [3].
• Periungual squamous cell carcinoma [2]
–– SCC of the mucosa: More than 90% of tumors in the oral cavity and pharynx
are SCC [4]. Ninety percent occur in people over 40 years of age and more
than 50% are over 65 years of age [5]. Risks for a mucosal SCC are the
following:
• Genetics
• Immunodeficiency
• Tobacco
• Alcohol
• Oral lichen planus
• Malnutrition
• Oral hygiene
• Related to HPV 16 [4].
–– It has a 5-year survival rate of 55–60% [4]. Fifty percent metastasize at the
time of diagnosis. The involvement of the tongue is 46%, of the lips 18%, the
floor of the mouth in 12%, the salivary glands 10%, the oral mucosa in 5%,
the gums 5%, and the palate 4% [5] (Figs. 31.40, 31.41, 31.42, and 31.43).
• Diagnosis: The clinic and histopathology are useful for the diagnosis.
Histopathology shows nests of squamous epithelial cells that start in the epider-
mis and extend to the dermis. Cells have abundant eosinophilic cytoplasm and a
large vesicular nucleus. There is a variable formation of central keratinization
and horn plugs, depending on the differentiation of the tumor. Keratinized cells
are usually present. The degree of anaplasia in tumor nests has been used in high-
grade SCC [6]. Histopathology should include the degree of differentiation
(good, moderate, or poorly differentiated), the thickness of the CEC in millime-

ters (the equivalent of the Breslow), the depth level infiltrated by the CEC (the
equivalent of Clark), the growth pattern (cohesive, circumscribed tumor that
grows expansively or, on the contrary, diffuse tumor that grows infiltratively),
and the presence or absence of perineural invasion [6].
–– Well-differentiated ECC generally begins at sites of epidermal change consist-
ing of actinic keratoses. There is a proliferation of lobes and aggregates of
shiny eosinophilic keratinocytes that contain nuclei with some degree of pleo-
morphism and mitosis. The nucleolus may be prominent. Intercellular bridges
(desmosomes) are frequently observed, with keratin beads and apoptotic
cells. Cos degrees of nuclear atypia and cell differentiation and pink cyto-
plasm with abundant keratin. As a rule, atypical keratinocyte aggregates are
present at different levels of the dermis [3].
–– Poorly differentiated SCC is a highly infiltrative keratinized tumor and some-
times has a fusiform morphology. Perineural and desmoplastic infiltration or
sclerotic stroma is the most frequent change in this form [3] (Fig. 31.44).
The use of the TNM-2010 classification, American Joint Committee on Cancer
(AJCC) 7th version, is recommended for staging patients with squamous cell carci-
noma of the skin. To evaluate the primary tumor (T), the following groups and risk
factors must be considered [6]. The classification groups are the following:
• TX: Non-evaluable tumor
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ
• T1: Tumor <2 cm with less than two
• risk factors
• T2: Tumor >2 cm size or tumor of any size with two or more risk factors
• T3: Tumor with invasion of the maxilla, mandible, orbit, or temporal bone
• T4: Tumor with invasion of the axial or appendicular skeleton or perineural inva-
sion of the skull base [6]
Fig. 31.40 Squamous cell

carcinoma: friable
erythematous tumor with
regular borders in the left
periorbital region [2]

carcinoma: in oral mucosa:
euchromatic warty tumor
mass [2]

carcinoma: in perianal
region, warty,
papillomatous tumor
mass [2]

carcinoma: plantar region,
tumor plaque with
ill-defined borders,
yellowish erythematous
[2, 3]
Fig. 31.44 Squamous cell carcinoma: note the presence of groups of irregularly shaped atypical
squamous cells infiltrating the dermis [3]
After the TNM classification, it is recommended to apply the 2013 Jambusari

classification for patients with skin SCC:
• T1: No risk factors
–– T2a: presence of 1 risk factors
–– T2b: presence of 2–3 risk factors
–– T3: presence of 4 risk factors [6]
The risk factors that must be taken into account in these cases are the following:
• Tumor diameter >2 cm
• Poor histopathological differentiation
• Perineural invasion
• Invasion beyond subcutaneous fat (not including bone) [6]
–– Differential diagnosis: actinic keratosis, basal cell carcinoma, vulgar warts,
seborrheic keratosis, amelanotic malignant melanoma, Merkel’s tumor, pseu-
doepitheliomatous hyperplasia, fibrosarcoma, and atypical fibroxanthoma [3].
Sebaceous Carcinoma
• Definition: Sebaceous carcinoma (CS) is a rare adnexal tumor with aggressive

behavior. CS can occur in any area that contains sebaceous glands [1].
• Epidemiology/pathogenesis: Represents 0.7% of skin cancer [1, 2], with an inci-
dence rate of 0.11 per 100,000 inhabitants per year [3], a mortality rate and
metastasis to lymph nodes and organs at a distance of 25% [1, 2]. The risk factors
for CS that have been reported in the literature are advanced age (mean 72 years)
and female sex (73%) [2], although recent studies have found a slight predomi-
nance in men [1], ethnicity (Caucasians, Asians, and Indians) [1, 2], irradiation,
genetic factors with pre-existing sebaceous lesions (Muir-Torre syndrome, Lynch
syndrome), immunosuppression (kidney transplantation or HIV), the use of
diuretics, and chalazion [2].
• Clinical presentation: The vast majority of CS occurred in the periocular region
[4], but the distribution has been recently changed to 38.7% in the periorbital
region, 40.8% in the extraorbital skin of the head and neck, and 19.9% in other
sites such as the trunk, extremities, or genitalia [1]. The clinical presentation is a
painless pink-yellowish nodule, but this clinic can vary from red papules,
plaques, or nodules that are easily confused with benign skin tumors [1]. The
behavior, management, and prognosis of CS are similar regardless of the place of
origin [2] (Fig. 31.45).
• Diagnosis: Histopathology shows unencapsulated lobular collections of undif-
ferentiated sebaceous cells, lipid granules present in the cytoplasm that result in
“frothy” appearance characteristics with special staining for oil red and Sudan IV
[1, 4]. Characteristics of tumor cells consist of nuclear pleomorphism, mitotic
figures, and nuclear hyperchromatism [1]. In addition, immunohistochemistry
plays a key role in making the differential diagnosis, and a panel of appropriate
antibodies may be useful [4], as the antigen of epithelial membrane (EMA), the
cocktail of cytokeratins AE1 and AE3, p53, cytokeratin 7, the androgen receptor,
Fig. 31.45 Sebaceous

carcinoma: in the right
temporal region, there is
evidence of a tumor
measuring 1.5 * 1.5 cm
with a friable erythematous
surface [1]
Mastocytosis 743
BRST-1, Cam 5.2, HMFG-1 and -2, BCA-225, and Ki67, which are positive for
CS [4, 5]; adipophilin, periphilin, has recently shown high sensitivity and speci-
ficity [1]; Ber-EP4 in all cases is negative for CS [4, 5].
• Differential diagnosis: Extraocular sebaceous carcinomas should be made dif-
ferential diagnosis with basal cell carcinoma, squamous cell carcinoma,
amelanotic melanoma, Merkel cell carcinoma, cutaneous lymphomas, metasta-
ses, sebaceous nevus, xanthomas, and sarcoidosis [1]. Sebaceous carcinomas in
the periorbital region should make a differential diagnosis with chalazion, bleph-
aritis, conjunctivitis, keratoconjunctivitis, basal cell carcinoma, squamous cell
carcinoma, sebaceous nevi, metastasis, and xanthelasma [1].
Mastocytosis
• Definition: It is a mast cell disorder which derives from CD34+ pluripotent pre-
cursor cells in the bone marrow that circulate in the peripheral blood as agranular
monocytic cells [1]. Patients with this disorder were initially thought to have
only skin disease, but it was later discovered that patients with mastocytosis
could have multiple organ involvement [1, 2].
• Epidemiology/pathogenesis: Agranular monocytic cells. After migrating into the
tissues, these immature mast cells assume their typical granular morphology.
These circulating precursor mast cells express CD34, kit tyrosine kinase (CD117)
receptors, and IgG receptors. The principally altered structure in the pathogene-
sis of many forms of mastocytosis is the KIT [1]. The KIT receptor is expressed
in different tissues: in mast cells, melanocytes, primitive hematopoietic stem
cells, primordial germ cells, and interstitial box cells [1]. Adult mastocytosis are
incurable diseases associated with c-KIT mutations, especially in exon 17
(D816V). In contrast, pediatric mastocytosis often regresses spontaneously and
is considered a reactive disease [1]. However, despite the fact that pediatric mas-
tocytosis can reverse spontaneously, it is a clonal disease most commonly associ-
ated with the activation of mutations in c-KIT [1].
• Clinical presentation: The clinical features of mastocytosis include flushing,
pruritus, abdominal pain, diarrhea, hypotension, syncope, and musculoskeletal
pain. These features are primarily the result of mast cell mediators and infiltra-
tion of the skin, gastrointestinal tract, spleen, lymph nodes, and bone marrow.
The skin is one of the most frequent sites with compromise. Cutaneous manifes-
tations include urticaria pigmentosa, diffuse cutaneous mastocytosis, mastocy-
toma, and eruptive telangiectasia macularis perstans [1]. The presence of mast
cell hyperplasia in the skin of patients with mastocytosis can be confirmed clini-
cally by firmly rubbing a characteristic lesion. The formation of an urticarial
papule (Darier’s sign) at the site of injury is indicative of the release of mast cell
mediators [1]. Darier’s sign is readily demonstrated in childhood mastocytomas
and lesions such as urticaria pigmentosa, while it may be less apparent in adult
mastocytosis lesions and is rarely detected in eruptive telangiectasia macularis

perstans [1]. This can be explained from mast cell quantification studies in the
skin of children and adults. Mast cell concentrations in childhood mastocytosis
and urticaria pigmentosa have been reported to be 150–40 times higher than
normal skin, while the mast cell content of injured skin in adult patients was only
8 times higher than normal skin [1]. The regression of the lesions does not always
indicate improvement of the disease. Studies in adults have reported regression
of lesions that is occasionally associated with increased serum tryptase levels
and worsening of the disease [1].
• Urticaria pigmentosa: It occurs in 65% of mastocytosis in children; they develop
during early childhood. It has a variable number of macules or brown papules.
The typical appearance of urticaria pigmentosa is yellowish brown macules or
papules, mainly on the trunk and legs with less commitment in the areas of expo-
sure to the sun, classically avoiding the central face, scalp, palms, and soles.
Urticaria pigmentosa is the most common in both adults and children, but in
children the size and number are variable and more uniform than in adults [2].
• Mastocytoma: It presents as a solitary yellow to brown plaque or nodule. Mast
cell tumors may be present at birth or may appear during infancy, favoring the
distal extremities. It is estimated that 10–35% of patients with childhood onset
mastocytosis have mastocytomas [1]. In solitary mastocytoma, there is a dense
aggregation of mast cells in the dermis, sometimes extending deep even into the
cellular tissue subcutaneous. Cells with a bilobed or multilobed nucleus are
observed. Eosinophils may be present in small numbers, and massive infiltration
rarely occurs. Localized necrobiosis and stromal fibrosis have been reported [1].
• Diffuse cutaneous mastocytosis: The skin of patients with this form of mastocy-
tosis has numerous erythematous to yellow-brown papules and plaques with
areas of confluence. Some babies and children can develop non-scarring vesicles
or blisters. Bullous lesions of mastocytosis are generally resolved by 3–5 years
of age and are believed to be the result of the release of serine proteases by mast
cells [1].
• Urticaria pigmentosa in adults: They differ significantly from those of children
due to the fact that they are reddish-brown macules and papules that are 1 cm or
less in diameter in patients with phototype I, which are pink to red in color. These
lesions are more numerous on the trunk and proximal extremities and appear less
frequently on the face, distal extremities, or palms and soles. Individual injuries
may resolve, but the total number generally increases over time. Close inspection
reveals variable hyperpigmentation and fine telangiectasias [1].
• Persistent eruptive macular telangiectasia (PMTT): It is an uncommon type of
cutaneous mastocytosis characterized by erythematous macules with fine telan-
giectasias, distributed mainly on the trunk and extremities. This dermatosis gen-
erally has a benign course, although some cases with systemic involvement or
malignant transformation have also been described. Darier’s sign is slightly posi-
tive or may be absent [1].
• Adult diffuse cutaneous mastocytosis: The skin of these patients has a pasty con-
sistency and the presence of numerous confluent yellowish papules, which have
Mastocytosis 745
led to the termination of xanthelasma mastocytosis. In more advanced stages,

much thicker skin folds are seen, distorting facial features. In diffuse cutaneous
mastocytosis, there is a loss of mast cells throughout the dermis. Fibrosis is
sometimes present. Mast cells are deeper in the dermis in a xanthomatous
manner [1].
• Nodular mastocytosis: Another rare variant, nodular mastocytosis, has recently
been described in an adult who had red-purple nodules in the armpits and ingui-
nal region; the mast cells had the c-KIT V560G mutation [1] (Figs. 31.46, 31.47,
31.48, 31.49, 31.50, and 31.51).
• Diagnosis: Mastocytoses occur in both children and adults. In 2007, in an addi-
tional diagnostic proposal for the WHO nomenclature, the term cutaneous mas-
tocytosis (MIS) was introduced; it proposes to evaluate the state of the disease on
the cutaneous findings, before performing a bone marrow biopsy. The criteria for
mastocytosis are major criteria, typical mastocytosis rash, and minor criteria, a
conglomerate of abnormal mast cells >15, spread >20 per field, or detection of
the KIT mutation in codon 816. To make the diagnosis of mastocytosis, the skin
must have a major criterion with 1 or 2 minor criteria [3].
• Histopathology
• In urticaria pigmentosa, it can vary in a scant or abundant infiltrate of mast cells
at the perivascular level. Perivascular mast cells can be cuboidal or fusiform;
most of the time, it tends to be cuboidal, usually scattered eosinophils can be
found with immunohistochemistry ckit C117 (+). Superficial edema in rubbing
lesions. In toluidine blue, basal hyperpigmentation is a useful clue to the diagno-
sis of urticaria pigmentosa and some other types of mastocytosis [1].
• Mastocytoma: There is a dense aggregation of mast cells in the dermis, some-
times extending deep even into the subcutaneous cellular tissue. Cells with a
bilobed or multilobed nucleus and eosinophils are observed, which may be pres-
ent in small numbers. Massive infiltration rarely occurs. Localized necrobiosis
and stromal fibrosis have been reported [1].
Fig. 31.46 Mastocytosis:

male patient, trunk and
extremities present
light-brown macules with
edematous papula in the
center [1, 2]

on the face, light-brown
spots with well-defined
borders with a residual
appearance [1, 2]

edematous with well-
defined borders in anterior
chest [1, 2]
Mastocytosis 747

wrist, there is an orange
erythematous nodule [1, 2]

erythematous brownish
plaque on left cheek [1, 2]

brown plaques and
macules [1, 2]
• Diffuse cutaneous mastocytosis: mononuclear dense infiltrate, with some eosino-

phils in the dermis with expression of CD117 in 80% of cases [1, 2].
• Eruptive macular telangiectasia perstans: May have a subtle number of mast
cells. Cells tend to be spindle-shaped and arranged around dilated vessels in the
superficial plexus. Eosinophils are usually absent [1] (Figs. 31.52 and 31.53).
• Differential diagnostics:
–– Urticaria pigmentosa: Histiocytosis, papular sarcoidosis, or initial pigmental
incontinence lesions; these have a negative Darier’s sign. Other bullous infant
eruptions such as bullous pemphigoid, epidermolysis bullosa, and dermatitis
herpetiformis [1].
Fig. 31.52 The dermis is occupied by a population of small- to medium-sized cells, with a central
nucleus, dense chromatin, and scant clear cytoplasm. They are highlighted with the immunohisto-
chemical marker CD117 and the Alcian blue stain [1]
Melanoma 749
Fig. 31.53 Increase in the number of normal-appearing mast cells in the dermis. The mast cells
are identified by their fusiform structure [1]
–– Solitary mastocytoma: bullous impetigo, juvenile xanthogranuloma, nevus,

insect bites, and bullous urticaria [1].
–– Eruptive telangiectasia macularis perstans: hereditary hemorrhagic telangi-
ectatic [1].
Melanoma
• Definition: It is a malignant tumor that arises from melanocytes and commonly

presents cutaneous. It can occur in mucosa (oral, conjunctival, vaginal), uveal
tract, and leptomeninges [1]. It has high mortality due to its metastatic
capacity [2].
• Epidemiology: Melanoma ranks third in frequency among skin cancers and is

responsible for the highest number of deaths [2]. In recent decades, there has
been an increase in its incidence, the highest being reported in Australia and New
Zealand, with 40–60 cases per 100,000 inhabitants. Stabilization of mortality
rates was observed in 1990 [3]. In Colombia, although there are not many data,
a report from 1978–1982 showed that the prevalence in women is 3 per 100,000
inhabitants and in men it is 3.3 per 100,000 inhabitants. In 2000, there were 22
deaths from cutaneous melanoma, corresponding to 2% of deaths from cancer in
the National Institute of Cancerology. Acral lentiginous melanoma being the
most frequent in 46% of cases [4]. The main etiological factor is ultraviolet radi-
ation from the sun in phototype I and II light-skinned individuals, that is, it burns
easily with the sun. Other sources of ultraviolet radiation, such as tanning cham-
bers or phototherapy chambers, can cause malignant melanoma [2]. Sun expo-
sure in childhood is a very important etiological factor; for this reason, it should
always be questioned about the history of three or more sunburns with blisters in
childhood. Acute and intermittent sun exposure is the most important [2]. In
countries with high incidence, the most common clinical type of melanoma is
superficial spreading melanoma, which is associated with chronic sun exposure.
However, in Colombia the most frequent clinical subtype is acral lentiginous
melanoma, and this has not been associated with chronic sun exposure [2].
• Pathogenesis:
–– The MAP Kinase (MAPK) pathway regulates cell proliferation, growth, and
migration. This pathway contains the RAS, RAF, MEK, and ERK proteins
[5], where the most documented mutations are at the RAS and RAF level.
However, there may be mutations at any level of the pathway that theoreti-
cally activate it and play a role in oncogenesis [1]. It consists of a transmem-
brane tyrosine kinase receptor such as the KIT receptor, which, when
autophosphorylated, creates binding sites for proteins, adapters that are GRB2
and SOS, from which a cascade of signals is triggered that involves GTPASA
activity of NRAS and kinase activity of RAF, MEK and ERK. ERK is the one
that will reach the nucleus and activates cyclin D1, forming a CDK4/6-cyclin
D1 complex. This complex phosphorylates retinoblastoma (RB) (tumor sup-
pressor protein), resulting in the release of E2F. E2F represents a family of
transcription factors that have an important role in regulating cell cycle
progression. P16 is a tumor suppressor that, when binding to CDK4/6, pre-
vents binding to cyclin D1 and thus RB activation and E2F release [1].
–– The KIT gene encodes a tyrosine kinase membrane receptor that stimulates
the MAPK pathway and the phosphatidylinositol triphosphate pathway
(PI3K). This gene is involved in the development of the melanocyte, and stud-
ies have found melanocytes with chromosomal mutations on chromosome 4q
in acral melanomas. This location includes the KIT gene [1]. Eleven percent
of KIT mutations are acral melanomas, 21% in mucosa, and 17% in skin with
chronic photodamage [1].
Melanoma 751
–– There may also be inherited mutations that are related to familial melanomas,
or acquired mutations, such as the mutation in the CDKN2A gene [1].
• Clinical presentation: The clinicopathological classification of malignant mela-
noma involves six groups which are the following:
–– Lentigo maligna melanoma 10–40%
–– Superficial spreading melanoma 30–60%
–– Nodular melanoma 15–35%
–– Acral lentiginous melanoma 5–10%
–– Desmoplastic and neurotropic melanomas which are rare
–– Rare miscellaneous group [5]
• The clinical characteristics of melanoma are easily remembered through the fol-
lowing mnemonics: The ABCDE which consist of:
–– A for asymmetry
–– B for ragged edges
–– C for variety in color
–– D diameter greater than 6 mm
–– E for evolution
–– Some authors implement the F for family history
–– Feeling of foreboding by the dermatologist that it is a melanoma [5]
–– Lentigo maligna (LM): It is a variant of melanoma in situ (radial growth
phase), which can evolve to lentigo maligna melanoma (LMM) when there is
dermal invasion (vertical growth phase) [6, 7]. It occurs as a macula with
irregular edges, poorly defined, slow growing, variable pigmentation, and
asymmetric distribution [7]. It is located on the head and neck, with a predi-
lection for the cheeks [6].
–– Superficial spreading melanoma: It can develop anywhere on the body at any
age. It is common in the trunk in men and lower extremities in women. This
has a shorter radial growth phase than lentigo maligna melanoma and usually
has less superficial invasion at the time it presents. An amelanotic variety has
also been reported; it can rarely be simulated as a vitiligo patch. Regression
area is not as frequent [5].
–– Nodular melanoma: No antecedent of radial growth phase. It presents as a
polypoid or occasionally pedunculated dark-brown or bluish-black nodule
that occurs anywhere on the body. They can occasionally be amelanotic.
Ulceration may be present, and giant lesions of up to 12 cm have been
reported [5].
–– Acral lentiginous melanoma: It develops on the palmar, plantar, and subun-
gual skin. This is particularly more common in Black, Japanese, and Taiwanese
people and has been found as plaques or nodules that frequently ulcerate.
Subungual melanomas can present as longitudinal melanonychia that slowly
envelop the nail. Atypical presentations such as intertriginous and amelanotic
have been reported. This entity is often in advanced stages when the diagnosis
is made. The most common site of lesions is in the thick artery [5].
–– Mucosal melanoma (lentiginous): Melanomas of the oral cavity and other
mucosal surfaces such as the vagina have a low prognosis with a 5-year sur-
vival of 37–47% [5].
–– Desmoplastic melanoma: It is a rare variant; it occurs in 4% of all melanomas.
Usually found on the head and neck as an extensive indurated plaque with
firm swelling. It predominates in men with a male/female ratio of 2:1. The
lesions are usually unpigmented; however, they may overlap with a lentigo
maligna or be on the periphery. Its diagnosis is challenging due to its broad
spectrum as it resembles a scar, a dermatofibroma, a neurofibroma, or malig-
nant lesions such as basal cell carcinoma, squamous cell carcinoma, and
amelanotic melanoma [5, 8].
–– Neurotropic melanoma: It is within desmoplastic melanoma and can corre-
spond up to 30–40%, with an average age of 65.5 years, and a male/female
ratio of 2.7:1 and whose most frequent location is the head and neck (51%).
This subtype has deeper Clark levels (IV and V) and greater mitotic activity
compared to desmoplastic. Because most of them occur in the head and neck,
it can cause neuropathies of the facial nerve [7] (Figs. 31.54, 31.55, 31.56,
31.57, 31.58, 31.59, 31.60, 31.61, and 31.62).
• Diagnosis: It is based on the clinical history, physical examination, and diagnos-
tic confirmation by histopathology. Histopathology is varied according to the
previously mentioned classification [5].
–– Lentigo maligna melanoma: A proliferation of atypical melanocytes located
along the dermoepidermal junction is observed. The cells are often perpen-
dicular to the surface and involve the perianexal epithelium [6].
–– Superficial spreading melanoma: It is characterized by a proliferation of atyp-
ical melanocytes and nests throughout the epidermis with a pagetoid spread.
The superficial epithelium of the adnexa can be compromised. There is thin-
Fig. 31.54 Violaceous

brown tumor, asymmetric,
with three tones of
pigment [5]
Melanoma 753
Fig. 31.55 In left hallux

ulcerated tumor that has
destroyed the nail plate [5]

tumor on the left cheek,
asymmetric, with crusts on
the surface [5, 7]
Fig. 31.57 Scalp purplish

brown tumor,
pedunculated, well-
demarcated, with a crust
on the surface [5, 7]

malar region, light brown
macula with irregular
borders, asymmetric in its
center, irregular dark-
brown plaque and
hypopigmented area [5]
Melanoma 755

malar region, asymmetric
gray-brown macula, with
areas of hypopigmentation,
in its lower pole a
dark-brown tumor [5]
ning of the epidermis with attenuation of the basal and suprabasal layer and
loss of the ridges adjacent to the collection of melanocytes [5].
–– Nodular melanoma: It does not have an adjacent intraepidermal component of
atypical melanocytes; however, there is a usual epidermal invasion by malig-
nant cells directly into the dermis. The dermal component is usually com-
posed of oval epithelioid cells. Mast cells are present as in other types of
melanoma [5].
–– Acral lentiginous melanoma: It has a radial growth phase characterized by a
lentiginous pattern of atypical melanocytes with some nests. Melanocytes can
become swollen with a clear halo around them, giving a lacunar appearance
or have a pigmented dendritic process. Approximately, 15% of cases are
amelanotic [5].
–– Desmoplastic melanoma: It is composed of bands of elongated spindle cells.
It has two variants: one pure and one mixed.
Fig. 31.60 Right heel,

erythematous and blackish
tumor, asymmetric,
irregular borders, moist
surface, in its center an
area of
hypopigmentation [5]

preauricular region,
dark-brown plaque,
asymmetric, irregular
borders [7]
Melanoma 757
Fig. 31.62 On the left

nasal wing, it is light
brown macula with
globules of dark brown
pigment, asymmetric,
hypopigmentation
center [5]
• Pure: when the lesion is histologically entirely desmoplastic [9].

• Mixed: when you have desmoplastic melanoma combined with conven-
tional melanoma. The cells resemble fibroblasts, but the cells have a
bizarre, hyperchromatic nucleus. Multinucleated cells are present with
small foci of neural transformation, and neurotropism have been seen [9].
• When in doubt about the diagnosis, the use of immunohistochemistry is also use-
ful, finding that melanomas are positive for Melan A, HMB 45, MITF (microph-
thalmia transcription factor), and S100 positive. In addition, it has been found
that Ki67 levels can predict early metastases of melanomas [8].
• Differential diagnosis
–– Melanocytic lesions that simulate clinical melanoma: Acral nevus, dysplastic
nevus, hypermelanocytic nevus, blue nevus, congenital nevus, halo nevus,
longitudinal melanonychia, melanosis of the mucous membranes, nevus and
lentigos in the genital region, nevus in patients with epidermolysis bullosa,
and Spitz nevus [1].
–– Non-melanocytic lesions simulating superficial spreading melanoma:
Seborrheic keratosis, thrombosed hemangioma, angiokeratomas, pigmented
basal cell carcinoma, pigmented actinic keratosis, extramammary Paget dis-
ease, pigmented variant Bowen’s disease [1].
–– Non-melanocytic lesions simulating nodular melanoma: Seborrheic kerato-
sis, pyogenic granuloma, dermatofibroma, thrombosed hemangioma, angio-
keratoma, pigmented basal cell carcinoma, pigmented pilomatricoma,
pigmented dermatofibrosarcoma protuberans [1].
–– Non-melanocytic lesions simulating a lentigo maligna melanoma: Seborrheic
keratosis, pigmented variant actinic keratoses, pigmented basal cell carci-
noma [1].
–– Non-melanocytic lesions simulating acral lentiginous melanoma on palms
and soles: Plantar warts, plantar tylosis, tinea nigra [1]. A subungual hema-
toma, Bowen’s disease, viral wart, paronychia, drug-induced pigmenta-
tion [1].
–– Non-melanocytic lesions mimicking amelanotic melanoma: Basal cell carci-

noma, Bowen’s disease, benign lichenoid keratosis, patchy psoriasis [1].
Cutaneous Metastases
• Definition: They are the result of skin infiltration by a malignant cutaneous or

extracutaneous neoplastic process, located at a distance from where the meta-
static process appears [1].
• Epidemiology: It occurs in 1–10% of patients with metastatic disease [2]. Its
recognition is important because it can be the first sign of extranodal metastasis
and have prognostic implications. The proportion of patients with metastatic dis-
ease depends on the malignancy, e.g., the high incidence of individuals with
metastatic melanoma is above 45% of patients and can develop skin metastases.
The gender will depend on the type of cancer. In women, skin metastases of
breast carcinoma are 70%, and melanoma of 12% are the most frequent, fol-
lowed by ovarian, head, and neck cancer (mainly squamous cell carcinoma) lung
[1] and by adenocarcinoma of the pancreas [2]. In men, skin metastases are due
to melanoma 32%, in head and neck cancer 65%, lung 12%, and colon in 11%.
Skin metastases on average develop in 36 months (range of to 177 months) after
the initial diagnosis of the primary tumor [1].
• Clinical presentation: It presents as a rapidly growing erythematous nodule or a
multiple eruption of nodules; however, those with progressive slow growth can
mimic other entities such as lipomas or dermatitis to erysipelas and ulcers [1, 2].
On occasion, skin metastases can be a presenting sign of a primary tumor of
unknown origin. The location can be a key to the diagnosis of skin metastases.
For example, in patients with cutaneous melanoma, satellite and metastases in
transit have a clear relationship with the primary site and its lymphatic drainage.
Papules range in color from pink to blue to black and may initially require palpa-
tion for detection. Certain malignant diseases favor particular anatomical sites,
for example, the periumbilical region for gastrointestinal cancers [1]. Although
some case reports show the propensity of a particular malignant tumor to metas-
tasize to the skin, the prevalence of specific carcinoma in population, gender, and
age all play an important role in determining which malignant tumors are most
likely to metastasize to the skin. Additionally, certain metastases may have a
more unique clinical appearance, for example, both Paget’s disease and extrama-
mmary Paget disease may resemble dermatitis, and metastases from renal carci-
noma may have the appearance of bright red vascular tumors and/or bleed easily.
However, they do not always have the classic presentation, from time to time,
cutaneous metastases, including those of renal origin, may have a zosteriform
distribution pattern. Of all the carcinomas metastatic to the skin, breast cancer
may be the one with the widest range of clinical presentations [1]. Due to its high
prevalence in the population and its propensity to produce skin metastases (lym-
phatic, hematogenous, and direct extension), breast cancer accounts for 70% of
Cutaneous Metastases 759
skin metastases in women [2]. Presentations vary from papulonodules to ery-

thematous macules that mimic erysipelas or indurated plaques marked with an
orange-peel appearance that are called “in cuirass” due to its resemblance to the
armor of a cavalry soldier. In addition, intralymphatic metastases can give rise to
appearing vascular papules that can be confused clinically with the vascular pro-
liferations (including angiosarcoma) that can result from breast cancer irradia-
tion. Differentiating between metastasis of squamous cell carcinoma of the skin
and primary cutaneous squamous cell carcinoma can be challenging, especially
in patients with SCC of the oropharynx or larynx [1, 3] (Figs. 31.63, 31.64,
31.65, and 31.66).
• Diagnosis: From a histopathological point of view, there are four patterns in the
cutaneous metastases of visceral carcinomas. Most commonly, skin metastasis
shows a solid nodular pattern, in which large aggregates of neoplastic cells infil-
trate the entire thickness of the dermis and can spread to the subcutaneous cel-
lular tissue [1]. Another histopathological pattern observed in visceral
Fig. 31.63 Cutaneous

metastases. The left
cervical region and the
base of the neck show
violet nodules that
asymmetric tumor, some
ulcerated on the surface
[1, 3]
Fig. 31.64 Scalp

erythematous brown tumor,
circumscribed, with
hematic crust on the
surface [1, 2]
Fig. 31.65 Asymmetric

tumor in the proximal third
of the left leg, some
telangiectasias on the
surface [3]
Cutaneous Metastases 761

areola, there is an
asymmetric tumor that
protrudes and deforms the
anatomical area in its
center, a blackish-brown
nodule [1–3]
adenocarcinoma metastases consists of the presence of glandular structures lined

by an atypical epithelium and that do not correspond to any skin adnexal struc-
ture [1]. A third pattern, especially common in breast carcinoma metastases, but
which can also be seen in metastases from other carcinomas, is the presence of
very atypical neoplastic strands or rows of cells, sometimes only one or two rows
of cells, arranged interstitially between the collagen bundles of the dermis.
Finally, a fourth histopathological pattern consists of the presence of tumor cell
emboli within the lumen of vascular structures, especially within the lymphatic
vessels. However, the histopathological study does not always allow to identify
the origin of the primitive tumor, since visceral carcinomas of very different
origin can show the same histopathological pattern when they spread to the skin.
In the best of cases, in the study of the skin biopsy we observe a series of findings
that allow us to guide the search for the primitive tumor [1]. There are very spe-
cific cases in which the histopathological image is diagnostic of the origin of the
primitive tumor (such as the presence of colloid material in the cutaneous
metastases of thyroid carcinomas or the observation of cytotrophoblast and syn-
cytiotrophoblast in the cutaneous metastases of choriocarcinomas), but these are
the exceptions [1]. Sometimes the immunohistochemical study is very helpful,
since it allows us to identify in the skin biopsy the production of certain sub-
stances by the tumor cells that indicate the origin of the primitive tumor (thyro-
globulin in thyroid carcinomas, chorionic gonadotropin in choriocarcinomas,
prostate-specific antigen in prostate carcinomas) [1]. However, in most cases, the
histopathological study only allows the diagnosis of cutaneous metastasis to be
established, and the origin of the primitive tumor can only be determined by
subsequent analytical study and exploration with different imaging techniques.
In any case, even with the most exhaustive examinations, in all the series of skin
metastases described, there is a percentage of cases in which the origin of the
original tumor is not identified, and the patient dies as a consequence of the dis-
semination of the metastatic process, without being able to pinpoint exactly
where it originated [1] (Fig. 31.67).
Fig. 31.67 Necrosis, vascular invasion [1]
• Differential diagnosis: Due to the highly variable symptoms of cutaneous metas-

tases, which can simulate both inflammatory processes or skin infections (eczem-
atous, erysipeloid lesions, similar to panniculitis, etc.), as well as other primitively
cutaneous tumors, the diagnosis of skin metastases is always histopatholog-
ical [1].
Breast and Extramammary Paget Disease
• Definition: Paget disease of the breast is almost always associated with carci-
noma of the breast in situ or invasive.
• Extramammary Paget disease is a tumor found in areas of higher density of apo-
crine glands [1].
• Epidemiology/pathophysiology: The pathophysiology continues to be specu-
lated. It has been hypothesized that Paget disease originates from mammary car-
cinoma, migrating via the lactiferous ducts to the surface of the epithelium of the
nipple and areola, with an incidence of breast cancer of 15%. In contrast, extra-
mammary Paget disease has been hypothesized that pluripotent germ cells of the
epidermis and adnexa are precursors of the disease. Toker cells have been identi-
Breast and Extramammary Paget Disease 763
fied in the vulvar epidermis, more precisely as mammary-like glands of the

vulva, present in the interlabial sulcus between the labia majora and the labia
minora. The vulvar-like mammary glands have histological features that resem-
ble sweat glands and the mammary gland. It is also suggested that it may be the
result of a proliferation of adnexal stem cells that reside in the sebaceous infun-
dibulum unit and the adnexal structures, since Paget cells for cytokeratin 15 and
19 are considered markers of follicular stem cells located in the pons of the hair
follicle. Twenty percent of cases are associated with adnexal tumors, and 10%
are associated with anorectal, prostate, bladder, skin, and vulvar cancer [1, 2].
• Paget disease has a low prevalence of 3–5%, and extramammary Paget disease
occurs in 6.5% of cases of breast Paget [1]. Paget disease occurs more frequently
in women in the fifth and sixth decade of life, while extramammary Paget disease
occurs equally in men and women from the sixth to the eighth decade of life. The
vulva is the most commonly affected site in extramammary Paget disease, repre-
senting 65% of cases, followed by the perianal region. Other less frequent sites
are the penis, scrotum, armpits, navel, eyelids, and external auditory canal and
others extremely rare as in the face, scalp, knees, abdomen, anterior thorax, and
esophagus [2].
• Clinical presentation: Breast Paget disease · The onset of the disease is insidious.
Itching is often an important symptom and can precede the appearance of lesions.
The lesions are sometimes painful and erythematous and present as erythema-
tous plaques, well demarcated on their own or multicentric that can be ulcerated,
scaly, or eczematous in appearance [1]. A characteristic finding is that Paget
disease will always compromise the nipple from the initial stages compared to
eczema of the nipple. In late stages, infiltration and tumor nodules may be evi-
dent [1]. Extramammary Paget disease presenting with a pattern of “underwear”
erythema usually has an uncertain prognosis. This clinical appearance is due to
lymphatic invasion and is often associated with regional lymph node involve-
ment and distant metastases. On rare occasions, extramammary Paget disease
has hypopigmented macules or may clinically mimic lichen sclerosus.
Papillomatous epidermal hyperplasia has been described in extramammary Paget
disease and may resemble a condylomata acuminata [1] (Fig. 31.68).
• Diagnosis: Both mammary and extramammary Paget disease show an acanthotic
epidermis with hyperkeratosis, parakeratosis, or ulceration. There is an infiltra-
tion with a variable number of abundant large, clear cells or sometimes eosino-
philic cytoplasm that contains a prominent vesicular nucleus. The mythical
figures can occasionally be identified. The cells are present singly or in conglom-
erates and usually dispersed throughout the layer of the epidermis. Occasionally,
glandular or acinar differentiation is observed, and signet ring cells with intracy-
toplasmic mucin are identified [2]. In rare cases, tumor cells may mark cytologic
atypia where it has been described as an anaplastic variant of Paget disease.
Distinguishing it from Bowen’s disease can be difficult without the use of special
stains and immunohistochemistry. However, it should be remembered that
Bowen’s disease of the nipple is exceptional. Pigmentation can be seen in both
Fig. 31.68 Extramammary

Paget disease: at the
perianal region, there is an
8 × 10 cm, erythematous
tumoral plaque with poorly
defined, irregular borders.
It has excoriated areas and
an ulcer in the upper pole
of the lesion [1]
and may be mistaken for melanoma. Tumor cells can be pigmented or colonized
by non-neoplastic dendritic melanocytes. Biopsies from patients with anogenital
Paget disease frequently show associated epidermal lesions and have been
divided into three types:
–– Squamous hyperplasia
–– Papillomatous hyperplasia
–– Pinkus-like fibroepithelioma [2]
• Pinkus-like fibroepithelioma being more frequent in perianal Paget disease.
Cells frequently stain positively for periodic acid Schiff and mucicarmine,
indicating the presence of neutral mucopolysaccharides. Much less frequent, it is
reactive for Alcian blue. However, immunohistochemistry is a more reliable
method to confirm the diagnosis. Immunohistochemistry is usually positive for
low molecular weight cytokeratins such as CK7, CAM 5.2, AE1/AE3, and epi-
thelial membrane antigen. Cystic disease fluid protein 15 (GCDFP-15) is posi-
tive in 50% of cases and is typically positive in primary extramammary Paget
disease and negative in secondary extramammary Paget disease. CK7 staining is
specific for extramammary Paget disease. An extramammary primary Paget
tends to be positive for CK7 but negative for CK20, and if it is secondary it is
positive for both CK7 and CK20; however, staining for CK20 is not totally spe-
cific [1].
• Differential diagnosis: In most cases, the diagnosis of cutaneous Paget’s disease
presents little difficulty. Occasionally, however, it can be mistaken for a superfi-
cial spreading melanoma (especially pigmented cases). Pagetoid Bowen’s dis-
ease can be differentiated with a useful marker such as p63 where in Bowen’s
disease it is positive, while in Paget disease it is not. Mammary Toker cells are
negative for p63 [1].
Adult Langerhans cell histiocytosis may mimic Paget disease of the breast, but
epidermotropic lesion cells are strongly positive for CD1a and negative for Paget
disease [1].
Lymphoproliferative Disorders Cd30 765
Pagetoid dyskeratosis is a distinct histological change representing an incidental

finding on biopsy taken at various sites including the uterus, lips, and hemor-
rhoids. It develops as an abnormal proliferative keratinocyte response to fric-
tion [2].
Lymphoproliferative Disorders Cd30
Lymphomatoid Papulosis
• Definition: CD30-positive T-cell lymphoma whose benign vs. malignant entity is

controversial [1]. Defined as a recurrent self-resolving papulonecrotic or papulo-
nodular skin disease [2]. However, most experts consider it to be indolent cutane-
ous lymphoma [1].
• Epidemiology: It has a peak incidence in the fifth decade of life with an excel-
lent prognosis given by a 10-year survival of 100%. Some cases are associ-
ated with genetic rearrangement of T-cell receptors, and it is associated with
other lymphomas in 20% of cases, such as anaplastic T-cell lymphoma, myco-
sis fungoides, Hodgkin’s lymphoma, and other lymphomas [1]. Its pathogen-
esis is unknown; many authors have suggested a viral etiology. However,
studies have found an etiological role for HTLV-1, Epstein-Barr virus, and
other herpes viruses, including herpes simplex virus type 1, and type 2 and
type 6 have been considered negative. The mechanism that compromises the
spontaneous disappearance of skin lesions or tumor progression observed in
some patients has not been identified. Interplay between CD30 and ligand
(CD30), which may contribute to apoptosis of neoplastic T cells and subse-
quent regression of skin lesions, has been suggested, but the exact mechanism
is unknown [2].
• Clinical presentation: Erythematous to brown erythematous papules (in different
stages of development) and nodules that can develop central hemorrhage, necro-
sis, and scab are seen. Its most frequent location is in the trunk or proximal
extremities with a spontaneous healing of 3–8 weeks [1, 2]. The papulonodular
lesions can leave transient hypopigmented or hyperpigmented macules and occa-
sionally superficial atrophic scars (varioliform), or they can disappear without
leaving ulceration or sequelae [2] (Fig. 31.69).
• Diagnosis: Histopathology shows cells with an outstanding cytoplasm and a
prominent nucleolus; there is a population of lymphocytes and neutrophils, with
an epidermotropic infiltrate of B lymphocytes of small to medium vessel.
Histology can vary with a predominance of CD4+ or CD8+ T cells and catego-
rized into five different subtypes; however, a single patient can exhibit many
histological patterns. The most frequent subtype is type A which resembles a
wedge-shaped conglomerate of CD30+ large atypical lymphocytes interspersed
Fig. 31.69 Lymphomatoid

papulosis: at the internal
aspect of the right knee,
there are multiple
red-brown papules with
well-defined, regular
edges. A scattered pattern
is observed [2]
between a mixture of inflammatory infiltrate of neutrophils, histiocytes, eosino-

phils, and small lymphocytes; epidermotropism is generally absent [1].
• Differential diagnosis: Pityriasis lichenoides, mycosis fungoides, anaplastic
large cell lymphoma [1].
T-Cell Leukemia-Lymphoma
• Definition: It is a type of T-cell neoplasia associated with HTLV1 [1]. Skin

lesions are general manifestations of systemic compromise. However, progres-
sion is slow, and sometimes only skin lesions have been described [1].
• Epidemiology/pathogenesis: It occurs in endemic areas with a high prevalence of
HTLV-1. As in the population of southeastern Japan [2], in China [3], Caribbean
Islands, and parts of central Africa [1]. It occurs in adults and men are more
affected than women. Vertical transmission is common [1].
• Clinical presentation: They are characterized by the presence of leukemia,
lymphadenopathy, organomegaly, (hepatomegaly, splenomegaly), lymphade-
nopathy, hypercalcemia [1, 3], and frequently skin lesions which have a bad
prognosis. Hepatitis B virus coinfection should be ruled out since high rates of
54.5% have been detected [3] (Fig. 31.70).
• Diagnosis: The skin lesions show a superficial or diffuse infiltration of pleomor-
phic T cells of small to medium size, which frequently plays a marked epider-
motropism. Histopathology may be indistinguishable from a mycosis fungoides.
Immunohistochemistry is positive for CD3+, CD4+, CD8–, and CD25+ [1]. In
addition, diagnostic confirmation of HTVL-1 detected by PCR can also be per-
formed [3]. There may be frequent elevation of LDH [3].
• Differential diagnosis: Mycosis fungoides [1].
Fig. 31.70 T-cell

leukemia-lymphoma:
rounded hypochromic
plaque with marked folds
on skin surface and mild
skin atrophy [3]
Mycosis Fungoid
• Definition: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma [1].

• Epidemiology/pathogenesis: Represents the most common type of cutaneous
lymphoma, approximately 50% of all cutaneous lymphomas [2]. Its pathogene-
sis is unknown. Genetic, environmental, and immunological factors have been
considered [2]. At the genetic level, activation of STAT3 and inactivation or loss
of CDKN2A, PTEN, and p53 are found [2]. Within the environmental factors,
persistent antigenic stimulation has been demonstrated, but the histopathological
exact agent has not yet been established [2]. Recent studies suggest that immu-
nological factors such as CD8+ cytotoxic T lymphocytes play a crucial role in
the antitumor response in MF [2].
• Clinical presentation: Classic MF lesions are described as patches, plaques, or
tumors. The patches are flat but may be scaly or have a change in texture [1].
Plaques are defined as slightly raised lesions and may be smooth, scaly, crusty,
or ulcerated. A tumor is defined as a lesion of at least 1 cm in diameter that has
vertical or deep growth. Most of these subtypes are erythematous but may be
hyperpigmented. When you have plaques or patches with diffuse or confluent
scaling that cover 80% of the body surface area, it meets the criteria for the term
of erythroderma [3] (Figs. 31.71, 31.72, 31.73, 31.74, and 31.75).
• MF patches: It is an asymptomatic and transitory MF given by patches located in
the buttocks, mammary region, and flexor areas with spontaneous disappearance.
It can last for months to years before progressing to advanced stages. Less than
10% progress to advanced stages [3]
• MF in plaques: It has a presentation form of infiltrated, scaly brown erythema-
tous, ring-shaped actuate or serpiginous plaques [3].
• TUMOR MF: They are exophytic tumors of exaggerated vertical growth of
brown-erythematous or violet erythematous color, with a smooth surface that
Fig. 31.71 Multiple

brown-violet plaques on
the posterior trunk, some
of an annular configuration
[1, 3]
Fig. 31.72 On the

posterior trunk, multiple
hypopigmented macules
with irregular edges [1, 3]

thigh with involvement of
the knee, multiple
erythematous plaques of
polycyclic configuration,
with fine scaling on the
surface [1, 3]
occurs on the face and skin folds (armpits, antecubital fossa, neck, and inframa-
mmary areas). Tumors can ulcerate and this is an indicator of poor prognosis [3].
• Folliculotropic MF: They are erythematous, indurated plaques, or tumors; their
typical characteristic is to present acneiform lesions, lesional or perilesional
comedo-like papules: They are follicular papules around the head and neck that
leave alopecia and area accompanied by severe itching. They have a worse prog-
nosis than classic MF [3].
• Pagetoid reticulosis (Woringer-Kolopp disease): It is a localized variant of MF. It
is observed as a scaly erythematous patch or plaque on the distal part of the
extremities or acral skin. It is a slow grown lesion without extracutaneous
spread [3].
• Granulomatous lose skin syndrome: It predominates in young women, as ery-
thematous plaques with hanging skin in flexor and intertriginous areas: associ-
ated with a second lymphoid neoplasm such as Hodgkin’s lymphomas [3].
Fig. 31.74 In the posterior

region of the lower
extremities, multiple
irregular borders, scaling
on the surface [1, 3]
• Diagnosis: The diagnosis of MF or SS requires a clinicopathological correlation

that begins with a skin biopsy suggestive of MF, because the type of lesion can
affect both hematoxylin and eosin, the results of immunophenotyping, the find-
ings of a receptor clone of T cells, and gene rearrangement, so the choice for
biopsy is critical. The area with induration of the skin biopsied is critical. The
most indurated lesion should be biopsied, and if multiple types of lesions are
present, a biopsy should be taken from each type of lesion: this is important to
help identify prognostic, clinical, and histological factors as well as to help dif-
ferentiate between the types of cutaneous T-cell lymphomas [4].
Histopathology Will Depend on the MF Subtype
–– Patchy MF: A mild band infiltrate is observed in the superficial dermis, with
atypical lymphocytes [4].
–– MF Plaques: There is a band infiltrate with atypical small to intermediate lym-
phocytes. Atypical lymphocytes are hyperchromatic with a cerebriform nucleus
and clear cytoplasm. It also presents epidermotropism with Pautrier’s microab-
Fig. 31.75 In the posterior

trunk and upper
extremities, multiple
plaques of polycyclic
configuration [1, 3]
scesses (pathognomonic for MF, but they are present only in 25% of cases). The
confusion with inflammatory entities occurs because at the beginning the MF:
there are reactive lymphocytes with absence of cytological atypia [4].
–– Folliculotropic MF: It has an atypical folliculotropic lymphoid infiltrate, which
consists of mucin deposit, within the follicular epithelium [4].
–– Pagetoid reticulosis (Woringer-Kolopp disease): Hyperkeratosis, parakeratosis,
prominent pagetoid epidermotropism with atypical cerebriform lymphocytes
with halo, hyperchromatic nucleus, and clear cytoplasm [3].
–– Lax granulomatous skin syndrome: diffuse infiltrate of lymphocytes with multi-
nucleated giant cells and phagocytosis of elastic fibers, sarcoid-like granulomas,
and small lymphocytes with atypical nuclei [3].
• Differential diagnosis: Initial patch or plaque lesions can be eczematous, lichen-
oid, or psoriasiform. Therefore, in these phases, the differential diagnosis of
mycosis fungoides is very broad and requires ruling out many inflammatory der-
matoses [4]. In addition, benign conditions with histological characteristics are
highly suggestive of MF; examples of this are lymphomatoid contact dermatitis
and lymphomatoid drug reactions [2].
B-Cell Lymphoma
B-Cell Lymphoma of the Primary Cutaneous Marginal Area
• Definition: It has been recognized as a low-grade variant of B-cell lymphoma

in the classification of the World Health Organization (WHO) and the
European Organization for the Treatment of Cutaneous Lymphoma Cancer
(EORTC) [1].
• Epidemiology/pathogenesis: B-cell lymphomas represent 22.5% of all cutaneous
lymphomas and marginal zone B-cell lymphoma accounts for 42% of B lympho-
mas [1]. It occurs more frequently in adults without predilection for gender.
However, it rarely occurs in the pediatric population; it can also be observed with
a predominance in males [2]. The pathogenesis is unknown; however they have
been related to genetic alterations. Some clinicopathological features have been
observed in B-cell lymphomas that start in the gastric mucosa (the so-called
MALTs associated with lymphoid tissue), which leads to the hypothesis that it is
caused by long-standing antigenic stimulation; possibly due to chronic infection
with specific microorganisms in Europe, an association with Borrelia has been
found [1].
• Diagnosis: Histologically, it shows a patch with a diffuse or nodular infiltrate
that involves the dermis and subcutaneous cell tissue. It has a characteristic
pattern that can be observed and magnified, with a nodular infiltrate (some-
times containing reactive germinal centers) which are surrounded by a popula-
tion of small to medium cells with discrete nucleoli and abundant pale
cytoplasm; it is described as a marginal zone, with centrocyte-like cells or
monocytoid cells. Additionally, it has plasma cells (around the infiltrate) and
lymphoplasmacytoid cells, and occasionally blast cells are also seen.
Eosinophils are also common. A granulomatous reaction with giant epithelioid
cells is also found in some patients. It also presents PAS-positive intranuclear
inclusions (Dutcher bodies) that are key in the diagnosis. Immunohistochemistry
shows CD20, CD79a, and Bcl-2 positive and CD5, CD10, and Bcl-6 nega-
tive [1, 3].
• Clinical presentation: It presents as recurrent pink to brown erythematous pap-
ules, plaques, or nodules located mainly on the extremities (more on the upper
than the lower) or on the trunk. Lesions can also be generalized in a small num-
ber of patients. Ulceration rarely occurs, and these lesions are usually asymp-
tomatic. B symptoms such as fever, night sweats, weight loss, or general malaise
are not present. Serum LDH levels are within normal limits. On some occasions,
the resolution of the lesions may be accompanied by secondary anetoderma due
to the loss of elastic fibers in the areas where the tumor infiltrated. It can begin in
areas with chronic atrophic acrodermatitis and may be related to Borrelia infec-
tions [1] (Fig. 31.76).
• Differential diagnosis: Pseudolymphomas [1].
References 773
Fig. 31.76 B- cell

lymphoma of the primary
cutaneous marginal area:
two contiguous
smooth surface, multiple
telangiectasias, and few
thin hair shafts on top, on
an alopecic area of the
scalp [1]
References
Benign melanocytic neoplasms, Neural and neuroendocrine neoplasms (Other than neurofi-
bromatosis). In: Dermatology, Bolognia vol. II. 202. 3rd ed; 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
p. 1319–36.
J. Disseminated eruptive clear cell acanthoma with spontaneous regression: further evidence
of an inflammatory origin. Am J Dermatopathol. 2011;33:599–602.
6. Fukushiro S, Takei Y, Ackerman A. Pale-cell acanthosis: a distinctive histologic pattern of
epidermal epithelium. Am J Dermatopathol. 1985;7:515–27.
7. Weedon D. Lentigines, nevi and melanomas chapter 32. In: Weedons skin pathology. 3rd ed;
2010. p. 712–56.
nevi (moles): current perspectives. Clin Cosmet Investig Dermatol. 2014;7:89–103.
9. Leite A, Gontijo B, Vásques F. Giant congenital nevus. An Bras Dermatol. 2013;88(6):863–78.
10. Valdivia L, Escalante E, et al. Características clínicas e histopatológicas del nevus sebáceo de
Jadassohn en el Hospital Central de Aeronáutica. Dermatol Peru. 2012;22(1)
11. Rtihbciri H. Organoid nevus (nevus sebaceous). In: Demis J, editor. Clinical dermatology, vol.
4. Philadelphia: Lippincott Company; 1994. p. 23–4.
ogy, 407–408.
Chapter 32
Other Lymphoproliferative Disorders
Plasmacytoid Dendritic Cell Neoplasia
• Definition: It is a disease of adults, with an average age of presentation of 50

years and a male/female ratio of 3:1. Pediatric cases have rarely been reported. It
begins at the level of the interfollicular zones of the peripheral lymphoid tissue,
an area that plays a crucial role in the first response to various pathogens.
Furthermore, plasmacytoid dendritic cells produce large amounts of interferon
(INF), especially INFalpha, and express many Toll-like receptors (TLR7, TLR9).
Being critical in the defense against viruses and other pathogens [1].
• Clinical presentation: Patients are usually asymptomatic and have solitary or
multiple erythematous or violaceous papules, plaques, or nodules with variable
pruritus [1, 2]. Fifty percent of patients have skin involvement [1]. However,
extracutaneous disease is seen in most patients at diagnosis, so it frequently
involves subclinical lymph nodes, peripheral blood, and bone marrow [1, 2]. In
some cases, it is seen with chronic myelomonocytic leukemia [3].
• Diagnosis: Histopathology shows a diffuse dermal infiltrate of mononuclear
cells of the medium vessel. These cells have fine blast chromatin, with an indis-
tinguishable nucleolus and an agranular eosinophilic cytoplasm. There are
numerous mitoses, without necrosis or angioinvasion. In early lesions, there is a
dense perivascular and perianexal infiltrate. Grenz zone is frequently present,
and the infiltrate can extend to the subcutaneous cellular tissue [1].
Immunohistochemistry is positive for CD4+, CD56+, CD123+, TCL1, and
BDCA2 [1].
• Differential diagnosis: Acute myeloid leukemia and other cutaneous lym-
phomas [1].

https://doi.org/10.1007/978-3-030-84107-2_32
776 32 Other Lymphoproliferative Disorders
References
bromatosis). In: Dermatology, vol. II. 202. 3rd ed; 2012. p. 1795–815.
Dermatol. 1984;120:214–5.
p. 445–526.
Index
A severe acne vulgaris, 184

Acanthoma of Degos, see Clear cell acantoma severe nodular-cystic acne, 183
Acanthosis nigricans (AN), 140 steroid-induced acne, 187, 188
clinical presentation, 604–608 systemic retinoids, 181
definition, 604 Acne conglobata, 181, 185
diagnosis, 604 Acne excoriée des jeunes filles, 189
differential diagnosis, 609 Acne fulminans, 183, 185–187, 428
epidemiology/pathogenesis, 604 Acne inflammatory lesions, 178, 180, 183,
Acne 184, 186–189
acne papules, 179 Acne keloidalis nuchae, 164, 165
actinic/ultraviolet radiation-induced Acne necroticans, 184
acne, 194 Acne papules, 179
atrophic boxcar scars, 181 Acne scars, 180, 181
atrophic scars, 180 Acne vulgaris, 180
childhood acne, 191 Acquired melanocytic nevus, 679, 681–683
chloracne, 192 Acral lentiginous melanoma, 751
clinical presentation, 178 Acral vitiligo, 266, 267
closed comedones, 179 Acrodermatitis continua of hallopeau (ACH),
conglobata, 185 58, 65, 66, 78, 79
definition, 178 Actinic keratosis
diagnosis, 190 definition, 713
differential diagnosis, 190 epidemiology/pathogenesis, 713
Favre-Racouchot syndrome, 194 Actinic lichen planus, 86, 89, 90
fulminans, 185–187 Actinic prurigo, 400–402
hormonal acne, 188 clinical presentation, 399
multiple erythematous nodules, 182 definition, 399
multiple infiltrating erythematous nodular diagnosis, 400
cysts, 183 differential diagnosis, 400
multiple papules and pustules, 182 pathogenesis, 399
neonatal acne, 189, 190 Actinic/ultraviolet radiation-induced acne, 194
nodules and pseudocysts, 180 Acute atrophic candidiasis, 497
occupational acne, 193 Acute contact dermatitis, 6, 7
open comedones, 178 Acute cutaneous lupus erythematosus,
pathogenesis, 178 325, 331
pustules and erythematous nodules, 185 Acute exanthematous lichen
pustules and papules, 179 planus, 86, 91, 92

https://doi.org/10.1007/978-3-030-84107-2
778 Index
Acute generalized exanthematous pustulosis solitary/multiple angiokeratomas, 649

(AGEP), 218, 219, 221, 222 telangiectasias, 647
Acute hemorrhagic edema epidemiology/clinical
childhood, 243 presentation, 647–649
clinical presentation, 231 Angular cheilitis, 497
definition, 231 Annular lichen planus, 95–97
diagnosis, 233 Annular psoriasis, 58, 64, 65
differential diagnosis, 233 Anus-genital warts/condylomas, 545
pathogenesis, 231 Ashy dermatosis, 112
Acute lupus erythematosus, 337, 338 Asteatotic dermatitis
Acute miliary tuberculosis, 487, 489 clinical presentation, 16, 19
Acute-subacute (juvenile) definition, 15
paracoccidioidomycosis, 511 diagnosis, 16
Acute urticaria, 303–305 differential diagnosis, 16
Acute varioliform, 132 pathogenesis, 15
Allergic contact dermatitis, 4, 5, 7, 8 Atopic dermatitis
Alopecia areata, 148 clinical presentation, 12–14
clinical presentation, 144, 145 adult, 12, 16
definition, 144 Besnier prurigo, 13, 18
diagnosis, 145 childhood, 12, 14, 15
differential diagnosis, 146 erythroderma, 12, 17, 18
patches, 145–147 infants, 12
pathogenesis, 144 definition, 12
therapeutic response, 144 diagnosis, 13
totalis, 147 differential diagnosis, 13
universal alopecia areata, 148 pathogenesis, 12
Alopecia areata totalis, 147 Atypical fibroxanthoma
Androgenetic alopecia clinical presentation, 674, 675
androgenetic alopecia female pattern, 152 definition, 674
androgenetic male alopecia, 150, 151 diagnosis, 675
clinical presentation, 149 differential diagnosis, 675
definition, 149 epidemiology/pathogenesis, 674
diagnosis, 150 Autosensitization dermatitis, 32–34
differential diagnosis, 152 Axillary granular parakeratosis, 140
hair shaft miniaturization, 150
pathogenesis, 149
Angioedema, 307 B
Angiofibroma Bacillary angiomatosis, 474, 476
definition, 669 Bacterial infections
diagnosis, 670 gram-negative infections
epidemiology/pathogenesis, 669, 670 bacillary angiomatosis, 474, 476
Angiohistiocytoma gangrenous ecthyma, 473–475
definition, 647 staphylococcal and streptococcal
diagnosis, 647, 650 infections
differential diagnosis, 647 botryomycosis, 467, 468
circumscribed angiokeratoma, 649, carbunculum, 465, 466
652, 653 cellulitis, 462, 463
cutis marmorata telangiectatic erysipelas, 460–462
congenita, 647, 648, 651, 652 folliculitis, 465, 466
diffuse corporis angiokeratoma, forunculum, 465, 466
649, 653 impetigo, 459–461
Fordyce angiokeratomas, 648, 651 necrotizing fasciitis, 464, 465
Index 779
staphylococcal and streptococcal toxin definition, 609

syndromes dermoid, 611, 613, 614
erysipeloid, 471 epidermoid, 609, 612, 613
erythrasma, 472 eruptive villous, 610, 613, 614
punctate keratolysis, 472, 473 hydrocystoma, 611
staphylococcal scald skin millium, 610
syndrome, 468–470 mucocele, 612, 613
Basal cell carcinoma myxoid, 612, 613
Bazex-Dupré-Christol syndrome, 721 omphalomecenteric duct cyst, 612, 613
clinical presentation pathogenesis, 609
morpheiform, 716, 718, 719 pilonidal, 611
nodular, 716, 717 preauricular, 611
superficial, 716, 718 single bronchogenic cyst, 611, 613
definition, 715 steatocystoma, 611, 613, 614
diagnosis, 722, 724–727 thyroglossal duct, 612, 613
differential diagnosis, 726 transparent solitary cyst, 612, 613
epidemiology/pathogenesis, 715 trichilemmal, 610, 613, 614
Gorlin-Goltz syndrome, 716, 723 Winer´s dilated pore, 614, 615
Pinkus fibroepithelioma, 716, 719, 720 epidermal nevus, 598, 599
risk factors, 715 NEV, 600–602
scar plane, 716, 722 PND, 594, 595
terebrant carcinoma, 716, 721 porokeratosis
ulcus rodens, 716, 720 clinical presentation
xeroderma pigmentosum, 716, 724 atrophic center and margins, 589, 591
Basosquamous carcinoma, 726–729 extremities, 589, 592
Bazex-Dupré-Christol syndrome, 721 fingernail/finger involvement, 590
Bazin indurated erythema, 488–490 hyperkeratotic, 589–593
B-cell lymphoma, 772, 773 definition, 587
Becker nevus, 685, 686, 689 diagnosis, 592–594
Behcet’s disease, 425, 427, 428, 433 differential diagnosis, 593
Benign neoplasm epidemiology/pathogenesis, 587, 589
acanthosis nigricans seborrheic keratoses
clinical presentation, 604–608 clinical presentation, 583–585
definition, 604 definition, 583
diagnosis, 604 diagnosis, 584–588
differential diagnosis, 609 differential diagnosis, 585
epidemiology/pathogenesis, 604 epidemiology, 583
clear cell acantoma stucokeratosis (see Stucokeratosis)
clinical presentation, 597, 598 skin horn
definition, 597 clinical presentation, 596
differential diagnosis, 598 diagnosis, 596
epidemiology/pathogenesis, 597 differential diagnosis, 596
comedonal nevus epidemiology, 595, 596
clinical presentation, 603 pathogenesis, 596
definition, 602 Besnier prurigo, 13, 18
diagnosis, 604 Blue nevus, 686, 689
differential diagnosis, 604 Body dysmorphic disorder, 154
epidemiology/pathogenesis, 602 Boils, 465, 466
cysts Borderline lepromatous leprosy, 483
ciliated cyst of vulva, 612, 613 Borderline leprosy, 486
clinical presentation, 609 Borderline personnel leprosy, 483
780 Index
Borderline tuberculoid leprosy, 483, 485 diagnosis, 598

Botryomycosis, 467, 468 differential diagnosis, 598
Bowen's disease, 140 epidemiology/pathogenesis, 597
diagnosis, 732 Closed comedones, 179
differential diagnosis, 732 Common warts, 536
hematic crust, 735 Compound nevus, 681, 682, 686, 687
hyperkeratosic surface, 735 Condyloma latos, 561
infiltrated erythematous brown Condylomas, 544, 545
hyperkeratosic tumor, 736 Condylomata acuminata, 545, 547, 549, 550
irregular acanthosis, 736 Confluent and reticulated papillomatosis, 140
irregular erythematous plaque, 732–734 brown papules and plaques, 261
ulceration, 734 brown reticulated macules, 260
yellowish-brown hyperkeratosic clinical presentation, 259
papula, 735 definition, 259
Bowenoid papulosis, 544, 545, 548, 549 diagnosis, 259
Bullous diseases, 281 differential diagnosis, 261
Bullous lichen planus/lichen planus hyperpigmented macules and plaques, 260
pemphigoides, 94 macules and brown patches, 259
Bullous pemphigoid, 292–294, 297–299 multiple brown papules, 259
Bullous systemic lupus erythematosus, 330, pathogenesis, 259
336, 342 Congenital erythropoietic porphyria
Butcher's warts, 536, 541 (CEP), 405–411
Congenital melanocytic nevus, 679–681, 688
Congenital varicella syndrome (CVS),
C 518, 519
Calcinosis cutis, 338, 354–356, 360, 365 Contact dermatitis, 403
Candida balanitis, 496, 497 clinical presentation, 4, 6–11
Cellulitis, 462, 463 definition, 4
Cherry angioma, 656–659 diagnosis, 4, 6, 11, 12
Chickenpox, 521, 522 differential diagnosis, 12
Chilblain lupus erythematosus, 328, 335, pathogenesis, 4–6
340, 341 Contact eczema, see Contact dermatitis
Childhood acne, 188, 191 Cosmetic acne, 186
Chloracne, 192 Cryoglobulinemia
Chronic actinic dermatitis, 402, 403 auricular area, 247
clinical presentation, 401 clinical presentation, 236
diagnosis, 402 diagnosis, 237
pathogenesis, 401 differential diagnosis, 237
Chronic allergic contact dermatitis, 10, 11 dilated small and medium vessels, 250
Chronic contact dermatitis, 9, 10 necrotic plaques, 248
Chronic graft-versus-host disease, 378–380 necrotic scabs, 245
Chronic mucocutaneous candidiasis (CMC), pathogenesis, 236
496, 498 purpuric plaque, 246
Chronic oral candidiasis, 497 retinal purpura, 246
Chronic paracoccidioidomycosis, 511 skin biopsy, 251
Chronic vesiculobullous, 31, 32 splinter dermatoscopy, 249
Churg-Strauss syndrome, 230 type II cryoglobulinemia, 252
Clark's nevus, 685, 689 Cutaneous and intertrigo candidiasis, 498
Clear cell acantoma Cutaneous larva migrans (LM)
clinical presentation, 597, 598 clinical presentation, 572
Index 781

differential diagnosis, 572 pathogenesis, 336
etiological agents, 571, 572 Dermatosis papulosa nigra (PND), 594, 595
Cutaneous lupus, 430 Dermographism, 305, 306
Cutaneous lupus erythematosus (CLE) Dermoid cyst, 611, 613, 614
clinical presentation, 324, 327, 328, 330 Desmoplastic melanoma, 752
definition, 324 Diaper dermatitis, 499
diagnosis, 331 Diffuse systemic sclerosis, 340
differential diagnosis, 331, 334 Digital ulcers, 365
pathogenesis, 324 Dimorphic/unstable leprosy, 481
Cutaneous tuberculosis Discoid eczema/microbial eczema, see
definition, 486 Nummular dermatitis
differential diagnosis, 490 Discoid lupus, 161, 163
etiopathogenesis, 486 Discoid lupus erythematosus, 329–332
multibacillary forms Dissecting folliculitis
clinical presentation, 487, 488 clinical presentation, 167
paucibacillary forms diagnosis, 167
diagnosis, 490 H&E-stained skin biopsy, 169, 170
tuberculides, 489 multiple atrophic areas, 168
clinical presentation, 488 pathogenesis, 166
diagnosis, 490 Disseminated eczema, 32–34
Cylindroma, 637, 638 Disseminated sporotrichosis, 507
Cytomegalovirus (CMV), 526–528 Distal and lateral subungular onychomycosis
(OSDL), 500
Drug reaction with eosinophilia and systemic
D symptoms (DRESS)
Darier’s disease, 35, 138 clinical presentation, 218
Deep mycoses, 508 definition, 218
definition, 507 diagnosis, 218
diagnosis, 509 differential diagnosis, 218
differential diagnosis, 509 eosinophilia and systemic
etiopathogenesis, 507 symptoms, 219
extracutaneous disease, 507 erythematous maculopapular rash, 220
primary skin disease, 507 maculopapular rash, 220
Demodex infestation, 430 multiple erythematous papules, 221
Dermatitis herpetiformis, 286, 289–291 pathogenesis, 218
Dermatofibroma Dysplastic nevus, 685, 689
clinical presentation, 667, 668
definition, 667
diagnosis, 667–669 E
differential diagnosis, 667 Eccrine poroma, 627–629
etiology/pathogenesis, 667 Ecthyma gangrenosum, 473–475
Dermatofibrosarcoma protuberans Eczema craquelé, see Asteatotic dermatitis
clinical presentation, 675, 676 Eosinophilic pustular folliculitis, 428–430,
definition, 675 434, 435
diagnosis, 676 Epidermoid cyst, 609, 612, 613
differential diagnosis, 676 Epstein pearls, 610
epidemiology/pathogenesis, 675 Eruptive villous cyst, 610, 613, 614
Dermatomyositis, 357–360 Erysipelas, 460, 461
clinical presentation, 336, 337 Erysipeloid, 471
782 Index
Erythema ab igne Filiform warts, 541, 542

clinical presentation, 258 Fixed pigmented erythema
definition, 257 clinical presentation, 107, 111–113
differential diagnosis, 258 diagnosis, 107, 114
patient with reticulated hyperpigmented pathogenesis, 104
macules, 258 Fixed sporotrichosis, 507
reticulated hyperpigmented macules, 258 Flat warts, 536, 541
Erythema annulare centrifugum, 304, 308–312 Focal vitiligo, 262, 263
clinical presentation, 307 Follicular lichen planus, 86
diagnosis, 307 Folliculitis, 465, 466
differential diagnosis, 307 Folliculitis decalvans
pathogenesis, 304 acute and chronic inflammatory
Erythema dyschromicum perstans infiltrate, 167
clinical presentation, 113, 122–127 clinical presentation, 165
diagnosis, 116 diagnosis, 165
pathogenesis, 112 H&E-stained skin biopsy, 168
Erythema gyratum repens, 310–314 papules and scarce follicular pustules, 166
Erythema, heliotrope, 347–349 pathogenesis, 165
Erythema marginatum, 313, 314, 316, 317 residual scarring alopecia and
Erythema multiforme, 233 trichostasis, 166
clinical presentation, 208 Frontal fibrosing alopecia, 156
definition, 208 Fungal infections
diagnosis, 208 deep mycosis, 507–509
differential diagnosis, 208 superficial mycosis (see Superficial
erythematous plaques, 211 mycosis)
multiple erythematous plaques, 209, systemic mycoses
210, 212–214 histoplasmosis, 509, 510
multiple mildly infiltrated erythematous paracoccidioidomycosis, 510–512
plaques, 215 diagnosis, 512
oral cavity, 212 differential diagnosis, 512
pathogenesis, 208
Erythema nodosum
clinical diagnosis, 440–444 G
clinical presentation, 438, 439 Gangrenosum, 428
definition, 438 Generalized eczema, 32–34
differential diagnosis, 440 Generalized morphea, 371
pathogenesis, 438 Generalized vitiligo, 268
Erythema nodosum leprous, 485 Generalized von zumbusch-type pustular
Erythematotelangiectatic rosacea, 192, 195 psoriasis, 57, 64
Erythematous oral candidiasis, 497 Genital candidiasis, 497
Erythrasma, 140, 472 Genital lichen planus, 94, 95
Erythroderma, 17, 18 Genital psoriasis, 69, 77
Erythropoietic protoporphyria, 411, 413, 414 Genital warts, 544
Gingival linear erythema/gingival band, 497
Glucose transporter protein-1 (GLUT-1), 662
F Gomatous tuberculosis, 487, 490
Facial molluscum contagiosum, 551 Gorlin-Goltz syndrome, 716, 723
Favre-Racouchot syndrome, 194 Gottron’s papules, 336, 343, 344
Fibrosing frontal alopecia, 83 Gottron’s sign, 336, 345, 346
Index 783
Graft-versus-host disease (GVHD), 356, 358 Herpetic eczema

Graham-Little-Piccardi-Lasseur syndrome, 83 clinical presentation, 34–36
Gram-negative infections definition, 34
bacillary angiomatosis, 474, 476 diagnosis, 34
gangrenous ecthyma, 473, 474 differential diagnosis, 35
Granulocyte colony stimulating factor pathogenesis, 34
(G-CSF), 416 Hidradenitis suppurativa
Granuloma annulare, 387–389 clinical presentation, 170
Granulomatosis with polyangiitis definition, 170
caliber vasculitis, 239 diagnosis, 172
definition, 227 Hurley stage l, 171
diagnosis, 228 Hurley stage II, 171, 172
differential diagnosis, 229 Hurley stage III, 172, 173
infiltrated ulcer, 238 pathogenesis, 170
multiple purpuric macules, 237 skin biopsy in H&E-stain, 173, 174
pathogenesis, 227 Histioide leprosy, 481, 482
ulcer with regular violaceous edges, 238 Histoplasmosis, 509, 510
Granulomatous rosacea, 193, 200 Holster sign, 351, 352
Gravitational dermatitis Hormonal acne, 187, 188
clinical presentation, 38–42 Human immunodeficiency virus (HIV), 22
definition, 37 Human T-cell lymphotropic virus type 1
diagnosis, 38 (HTLV-1) infection, 552–555
differential diagnosis, 38, 39 Hydrocystoma, 611
pathogenesis, 37 Hyperkeratotic dermatitis of the hand, 33
Guttate psoriasis, 56, 62, 71 Hypersensitivity with eosinophilia and
systemic symptoms (DRESS), 206
Hypertrophic candidiasis, 497
H Hypertrophic lichen planus, 94–96
Hairy leukoplakia, 524
Halo nevus, 685, 689
Heliotrope erythema, 336 I
Henoch-Schonlein purpura, 233 Ichthyosiform plaques, 16
Herpesvirus Impetigo, 35
Kaposi's sarcoma bullous impetigo, 459, 460
clinical presentation, 531–538 crusted impetigo, 459, 461
diagnosis, 532, 539, 540 diagnosis, 459
etiopathogenesis, 530, 531 etiopathogenesis, 459
VHH1 and VHH2 herpes Indeterminate leprosy, 481
simplex, 515–517 Infant atopic dermatitis, 12
VHH3 Infantile hemangioma
congenital varicella syndrome, clinical presentation, 662–665
518, 519 definition, 661
varicela and herpes zoster, 519–523 epidemiology/pathogenesis, 661, 662
VHH 4 (Epstein–Barr) Infective dermatitis, 36–38
leucoplasia vellosa, 522, 524 Interleukins, 54
Lipschutz ulcers/acute genital ulcer, Intertrigo candidiasis
523, 525, 526 clinical presentation, 498
VHH 5 cytomegalovirus, 526–528 differential diagnoses, 499
VHH 7 pityriasis rosea, 529–531 local factors, 496
Herpes zoster virus, 519–523 Intradermal nevus, 682, 683, 686, 687
784 Index
Inverse lichen planus, 93, 94 leprotic reactions, 484, 485

Inverse psoriasis, 56, 63 multibacillary, 484
Irritant contact dermatitis, 4, 6 paucibacillary, 483
tuberculoid leprosy, 483
Leser-Trélat sign, 584
J Leucoplasia vellosa, 522, 524
Jacquet’s syphilis, 6 Leukocytoclastic vasculitis
Junctional nevus, 681, 682, 686 clinical presentation, 224
Juvenile plantar dermatosis, 46, 47, 49, 50 definition, 224
diagnosis, 226
differential diagnosis, 226
K H&E-staining, 235
Kaposi's varicelliform rash, 34–36 histological leukocytoclastic vasculitis, 232
Kawasaki disease, 138, 211, 233 multiple papules and purpuric
Keratoacanthoma macules, 226
clinical presentation, 729–731 multiple papules and purpuric plaques, 231
definition, 729 multiple purplish and violaceous
diagnosis, 730 macules, 225
differential diagnosis, 730 multiple purpuric macules, 224
epidemiology/pathogenesis, 729 multiple purpuric plaques, 232
Keratolysis exfoliativa, 31 pathogenesis, 224
Keratolysis punctata, 472, 473 purpuric macules and papules, 229
Keratosis alba, see Stucokeratosis small vessel vasculitis, 234
Klippel - Trenaunay syndrome, 647 systemic lupus erythematosus, 228,
Koebner phenomenon, 54, 55 232, 233
vascular lumen, 236
violaceous maculae, 225
L viral respiratory infection, 230
Lax fibroid Leukomelanoderma lichenoid pityriasis, 132
clinical presentation, 671, 672 Lichen nitidus
definition, 670 clinical diagnosis, 109
diagnosis, 671, 672 clinical presentation, 108, 115–121
differential diagnosis, 671 definition, 108
epidemiology/pathogenesis, 671 differential diagnosis, 109
Leishmaniasis pathogenesis, 108
clinical presentation, 568–570 Lichen planopilaris, 82, 83, 85, 86
definition, 567 alopecic area, 160
diagnosis, 570, 571 clinical presentation, 156
differential diagnosis, 571 concentric scar fibrosis, 161
etiopathogenesis, 567, 568 definition, 156
Lentigo maligna melanoma (LMM), 751 diagnosis, 158
Lepromatous leprosy (LL), 480–483, 486 differential diagnosis, 161
Leprosy/Hansen's disease diffuse cicatricial alopecia, 158
borderline leprosy, 483, 485 fibrosing alopecia type, 159
definition, 479 frontal and biparietal regions, 159
diagnosis, 485 mild peripheral inflammatory infiltrate, 162
differential diagnosis, 486 multiple follicular erythematous
dimorphic/unstable leprosy, 481 papules, 156
histioide leprosy, 481, 482 pathogenesis, 156
indeterminate leprosy, 481 peripheral desquamation and
lepromatous leprosy, 480–483 trichostasis, 157
Index 785
residual alopecic areas, 160 definition, 131

scalp follicular keratotic papules, 157 diagnosis, 132
temporo-occipital region, 158 differential diagnosis, 133
V-peripheral cicatricial fibrosis, 162 pathogenesis, 131
Lichen planopilaris classic, 156 pityriasis lichenoides chronica, 133–137
Lichen planus, 339 Linear IgA bullous dermatosis, 287, 291–296
clinical diagnosis, 101, 103, 104 Linear lichen planus, 95, 97, 98
clinical presentation Lipodermatosclerosis
actinic lichen planus, 86, 89, 90 clinical diagnosis, 447, 453–455
acute exanthematous lichen planus, clinical presentation, 447, 451, 452
86, 91, 92 definition, 446
annulare, 95–97 differential diagnosis, 447
bullous lichen planus, 94 pathogenesis, 446
genital lichen planus, 94, 95 Lipoma
hypertrophic lichen planus, 94–96 clinical presentation, 641–642
inverse lichen planus, 93, 94 definition, 641
lichen planopilaris, 82, 83, 85, 86 diagnosis, 642
linear lichen planus, 95, 97, 98 differential diagnosis, 642
lupus overlap syndrome, 99, 101, 102 epidemiology/pathogenesis, 641
nail lichen planus, 95, 98, 99 Lipschutz ulcers/acute genital ulcer, 523,
oral lichen planus, 83, 87–89 525, 526
palmoplantar, 99, 100 Loose anagen hair syndrome, 146
pigmentosus, 86, 91 Low differentiation fibromyxoid sarcoma,
ulcerative lichen planus, 95 677, 678
violaceous papules, 82–84 Low-grade fibromyxoid sarcoma (SFBG)
Lichen sclerosus et atrophicus epidemiology/pathogenesis, 676
clinical diagnosis, 123 Lupus overlap syndrome, 99, 101, 102
clinical presentation, 117, 127, 128 Lupus panniculitis (LP), 328, 333, 334, 339
definition, 117 clinical diagnosis, 443, 445–450
differential diagnosis, 123 clinical presentation, 443–445
pathogenesis, 117 differential diagnosis, 441, 445
Lichen scrofulosorum, 488, 490 pathogenesis, 441, 443
Lichen simplex chronicus Lupus profundus, see Lupus panniculitis (LP)
clinical presentation, 40, 42, 43 Lupus vulgaris, 488, 490
definition, 39 Lymphangitic sporotrichosis, 507
diagnosis, 40, 43, 44 Lymphogranuloma venereum
pathogenesis, 39 (LGV), 563, 564
Lichen spinulosus, 138 Lymphomatoid papulosis
Lichen striatus, 109, 110, 122 clinical presentation, 765, 766
Lichenoid drug eruption definition, 765
clinical diagnosis, 103 diagnosis, 765
clinical presentation, 102, 104–110 differential diagnosis, 766
definition, 102 epidemiology, 765
pathogenesis, 102
Lichenoid pityriasis M
acute varioliform, 132 Malherbe's calcified epithelioma, see
clinical presentation, 131 Pilomatrixoma
786 Index
Malignant neoplasm lymphomatoid papulosis

actinic keratosis clinical presentation, 765, 766
clinical presentation, 713, 714 definition, 765
definition, 713 diagnosis, 765
diagnosis, 715 differential diagnosis, 766
differential diagnosis, 715 epidemiology, 765
epidemiology/pathogenesis, 713 mastocytosis
basal cell carcinoma clinical presentation, 743–747
Bazex-Dupré-Christol syndrome, 721 definition, 743
definition, 715 diagnosis, 745, 748, 749
diagnosis, 722, 724–727 differential diagnosis, 748
differential diagnosis, 726 epidemiology/pathogenesis, 743
epidemiology/pathogenesis, 715 melanoma
Gorlin-Goltz syndrome, 716, 723 clinical presentation, 751–757
morpheiform, 716, 718, 719 definition, 749
nodular, 716, 717 diagnosis, 752, 755, 757
Pinkus fibroepithelioma, 716, 719, 720 differential diagnosis, 757, 758
risk factors, 715 epidemiology, 750
scar plane, 716, 722 pathogenesis, 750, 751
superficial, 716, 718 mycosis fungoides
terebrant carcinoma, 716, 721 clinical presentation, 767–771
ulcus rodens, 716, 720 definition, 767
xeroderma pigmentosum, 716, 724 diagnosis, 770, 771
basosquamous carcinoma, 726–729 differential diagnosis, 771
B-cell lymphoma, 772, 773 epidemiology/pathogenesis, 767
Bowen's disease Paget's disease
definition, 730 clinical presentation, 763, 764
differential diagnosis, 732 diagnosis, 763, 764
epidemiology/pathogenesis, 730, 731 differential diagnosis, 764, 765
hematic crust, 735 epidemiology/pathogenesis, 762, 763
hyperkeratosic surface, 735 sebaceous carcinoma, 742, 743
infiltrated erythematous brown squamous cell carcinoma
hyperkeratotic tumor, 736 clinical presentation, 737–740
irregular acanthosis, 736 definition, 733
irregular erythematous plaque, 732–734 diagnosis, 738, 739, 741
ulceration, 734 differential diagnosis, 741
yellowish-brown hyperkeratosic epidemiology/pathogenesis, 736, 737
papula, 735 T-cell leukemia-lymphoma, 766, 767
cutaneous metastases MAP Kinase (MAPK) pathway, 750
clinical presentation, 758–761 Mastocytosis
definition, 758 clinical presentation, 743–747
diagnosis, 759, 761 definition, 743
differential diagnosis, 762 diagnosis, 745, 748, 749
epidemiology, 758 differential diagnosis, 748
erythroplasia of Queyrat, 732, 733, 737 epidemiology/pathogenesis, 743
keratoacanthoma Mechanical acne, 187
clinical presentation, 729–731 Melanoma
differential diagnosis, 730 diagnosis, 752, 755, 757
epidemiology/pathogenesis, 729 differential diagnosis, 757, 758
Index 787
epidemiology, 750 local factors, 496

pathogenesis, 750, 751 Mucosal melanoma (lentiginous), 752
Melasma Mucosal vitiligo, 264
clinical presentation, 256 Mucous paracoccidioidomycosis, 512
definition, 255 Mycobacterial infections
diagnosis, 257 cutaneous tuberculosis
hyperpigmented macules, 256, 257 differential diagnosis, 490
pathogenesis, 255 etiopathogenesis, 486
reticulated macules, 256 multibacillary forms, 489
Melkersson-Rosenthal syndrome, 390–392 paucibacillary forms, 487, 488, 490
Merkel cell carcinoma (MCC), 699–701 tuberculides, 488–490
Metophyma, 199 leprosy/Hansen's disease
Meyerson nevus, 683 borderline leprosy, 483, 485
Microscopic polyangiitis, 230 definition, 479
Middle rhomboid glossitis, 497 diagnosis, 485
Miescher microgranulomas, 440 differential diagnosis, 486
Miescher's nevus, 682, 685, 688 dimorphic/unstable, 481
Millium cyst, 610 histioide leprosy, 481, 482
Minor erythema multiforme, 208 indeterminate, 481
Mirmecia, 540 lepromatous leprosy, 480–483
Mixed pattern onychomycosis (OM), 502, 503 leprotic reactions, 484, 485
Molluscum contagiosum, 547, 548, 550, 551 multibacillary, 484
Morbilliform drug eruption paucibacillary, 483
clinical presentation, 205 tuberculoid leprosy, 481, 483
definition, 205 non-tuberculosis
diagnosis, 206 mycobacteria, 491, 492
differential diagnosis, 206 Mycosis fungoides (MF)
H&E-stained skin biopsy, 207 clinical presentation, 767–771
irregular confluent borders, 206 definition, 767
pathogenesis, 205 diagnosis, 770, 771
Morphea, 373 differential diagnosis, 771
clinical presentation, 347 epidemiology/pathogenesis, 767
definition, 347 Myiasis
diagnosis, 350 clinical presentation, 577, 578
pathogenesis, 347 diagnosis, 579
Mosaic warts, 541 differential diagnosis, 579
Mucha-Habermann disease, 131 etiopathogenesis, 577
Mucocutaneous candidiasis Myxoid cyst, 612, 613
cutaneous and intertrigo candidiasis, 498
definition, 495
diagnosis, 499 N
etiopathogenesis, 495 Nail lichen planus, 95, 98, 99
intertrigo candidiasis Nail matrix, 682, 684
clinical presentation, 498 Nail psoriasis, 59, 72, 73
differential diagnoses, 499 Nappy candidiasis, 498
local factors, 496 Necrobiosis lipoidica, 389–391
oral candidiasis, 496 Necrotic plaques, 248
clinical presentation, 496 Necrotizing fasciitis, 464, 465
diaper dermatitis, 499 Neonatal acne, 188–190
differential diagnoses, 499 Neonatal lupus, 328, 329
788 Index
Neuroendocrine tumor, 699–701 secondary onychomycosis, 502

Neurofibroma, 694–696 superficial, 500, 501
clinical presentation, 693 total dystrophic onychomycosis, 502, 504
definition, 693 Onychomycosis endonix (EO), 500
diagnosis, 693 Open comedones, 178
differential diagnosis, 695 Oral candidiasis, 496
epidemiology/pathogenesis, 693 clinical presentation, 496
Neurothecoma differential diagnoses, 499
clinical presentation, 696 local factors, 496
definition, 695 Oral lichen planus, 83, 87–89
diagnosis, 697 Organoid nevus, see Sebaceous nevus
differential diagnosis, 697, 698 Otophyma, 199
epidemiology/pathogenesis, 696
Neutrophilic dermatosis, 417
Neutropic melanoma, 752 P
Nicolsky's sign, 468 Paget's disease
Nodular hidradenoma, 630–633 clinical presentation, 763, 764
Nodular melanoma, 751 definition, 762
Nodular prurigo diagnosis, 763, 764
clinical presentation, 41, 44–46 differential diagnosis, 764, 765
definition, 41 epidemiology/pathogenesis, 762, 763
diagnosis, 45, 47, 48 Palmoplantar lichen planus, 99, 100
differential diagnosis, 41 Palmoplantar psoriasis, 58, 66–71
pathogenesis, 41 Palmoplantar vesicular dermatitis
Non-Langerhans cell histiocytosis clinical presentation, 27–29, 31–33
diagnosis, 706, 708 diagnosis, 29
differential diagnosis, 706 differential diagnosis, 29, 31
epidemiology/clinical pathogenesis, 27
presentation, 703–705 Panarteritis nodosa, 229
Non-tuberculosis mycobacteria, 491, 492 Panniculitis, see Subcutaneous adipose tissue
Nummular dermatitis Papillomavirus
clinical presentation, 19, 20 Bowenoid papulosis, 544, 545, 548, 549
definition, 18 condylomas, 544–547, 549
diagnosis, 19, 21–25 viral warts and flat warts
differential diagnosis, 19 clinical presentation, 540, 541
diagnosis, 543
O etiopathogenesis, 534, 535
Occupational acne, 189, 193 Papulonecrotic tuberculosis, 488, 490
Ocular rosacea, 193, 200 Papulopustular rosacea, 193, 195–197
Omphalomecenteric duct cyst, 612, 613 Papulosquamous subacute cutaneous lupus
Onychomycosis erythematosus, 326, 327
definition, 499 Paracoccidioidomycosis
diagnosis, 502 acute-subacute (juvenile)
differential diagnosis, 502 paracoccidioidomycosis, 511
distal and lateral subungular chronic paracoccidioidomycosis, 511
onychomycosis, 500 definition, 510
mixed pattern onychomycosis, 502, 503 diagnosis, 512
onychomycosis endonix, 500 differential diagnosis, 512
proximal subungual onychomycosis, ethiopathogenesis, 511
501, 503 mucous paracoccidioidomycosis, 512
Index 789
Parbovirus B19 infectious erythema, 556, 557 Pityriasis lichenoides and varioliformis acute
Parkinson’s disease, 22 (PLEVA), 131
Parry-Romberg syndrome, 372 Pityriasis lichenoides chronica, 132–137
Pediculosis Pityriasis rosea (RP), 529–531
clinical manifestation, 575, 576 Pityriasis rubra pilaris, 138
differential diagnosis, 576, 577 diagnosis, 138
etiopathogenesis, 575 differential diagnosis, 138
Pemphigus foliaceus, 284, 287–289 erythematous and scaly plaques, 139
clinical presentation, 284 irregular edges, 138
diagnosis, 285 pathogenesis, 136
differential diagnosis, 285 scaling and erythema, 139
pathogenesis, 284 scaly brownish-yellowish plaques, 138
Pemphigus vegetans, 280 Pityriasis simplex capillitii, 23
Pemphigus vulgaris, 280–285 Pityriasis versicolor, 504, 505
clinical presentation, 280 Pityrosporum ovale, 21
diagnosis, 280, 281 Plantar fibromatosis
differential diagnosis, 281 clinical presentation, 673
Perianal condylomas, 545, 546 diagnosis, 673
Periocular dermatitis, 201 differential diagnosis, 673
Perioral dermatitis, 200–203 epidemiology/pathogenesis, 673
Periorificial tuberculosis, 487, 489 Plantar warts, 536, 540
Periungular alterations, 353 Plaque morphea, 367–369
Periungular disorders, 354 Plaque psoriasis, 54–61, 71
Periungular/subungular warts, 541, 542 Plasmocytoid dendritic cell neoplasia
Phakomatosis pigmentovascularis, 646 clinical presentation, 775
Photocontact dermatitis, 403, 404 definition, 775
Photosensitivity, 337 diagnosis, 775
Phymatous rosacea, 193, 197 differential diagnosis, 775
Physical urticaria, 302, 306 Polyarteritis nodosa
Pigmented lichenoid purpura, 321, 322 bilateral lower limbs, 242
Pigmented purpura, 314, 315, 317–319 clinical presentation, 230
Pigmented purpuric dermatosis, 320, 321 cutaneous polyarteritis nodosa, 240
Pike phenomenon, 485 definition, 229
Pilomatrixoma dermo-hypodermic junction, 243
clinical presentation, 621, 622 diagnosis, 230
definition, 621 differential diagnosis, 230
diagnosis, 621, 623 medium-deep dermis, 242
differential diagnosis, 622 multiple reticular violaceous macules, 241
epidemiology/pathogenesis, 621 pathogenesis, 229
Pilonidal cyst, 611 Polycyclic annular subacute lupus
Pityriasis alba erythematosus, 326
clinical presentation, 265 Polymorphic light eruption, 396–399
hypochromic patches, 276 differential diagnosis, 397
hypopigmented patches, 276 pathogenesis, 396
multiple hypopigmented macules, 275 Pomade acne, 186
pathogenesis, 265 Pompholyx/dyshidrotic eczema, 27
790 Index
Porokeratosis palmoplantar psoriasis, 58, 66–71

clinical presentation types, 56, 64
atrophic center and margins, 589, 591 scalp psoriasis, 67, 75, 76
extremities, 589, 592 Psoriasis 1 (PSORS1), 54
fingernail/finger involvement, 590 Psoriasis erythroderma, 60, 66, 73, 74
hyperkeratotic, 589–593 Psoriatic arthropathy, 69
definition, 587 Psoriatic erythroderma, 60, 66
diagnosis, 592–594 Psoriatic onycholysis, 73
differential diagnosis, 593 Punctate keratolysis, 472, 473
epidemiology/pathogenesis, 587, 589 Pustular psoriasis, 74
Porphyria cutanea tarda, 410, 412, 413 ACH, 58, 65, 66
clinical presentation, 410 annular psoriasis, 58, 64, 65
diagnosis, 410, 411 generalized von zumbusch-type, 57, 64
differential diagnosis, 411 palmoplantar psoriasis, 58, 66–71
pathogenesis, 410 types, 56, 64
Post-inflammatory hyperpigmentation Pyoderma gangrenosum (PG), 418,
clinical presentation, 254 421, 423–432
definition, 254
diagnosis, 255
differential diagnosis, 255 R
hyperpigmented macules, 255 Radiation-induced acne, 189
linear hyperpigmented macules, 254 Relapsing polychondritis, 351, 353, 375–378
pathogenesis, 254 Rheumatoid neutrophilic dermatitis, 417
Post-inflammatory hypopigmentation Rhinophyma, 198
clinical presentation, 264 Rosacea
hypopigmented macules, 272 differential diagnosis, 200
linear IgA dermatosis, 274 erythematotelangiectatic rosacea, 195
pathogenesis, 264 granulomatous rosacea, 200
severe atopic dermatitis, 273 metophyma, 199
Poxvirus, 547, 548, 550, 551 ocular rosacea, 200
Preauricular cyst, 611 otophyma, 199
Proximal subungular onychomycosis (OPS), papulopustular rosacea, 195–197
501, 503 pathogenesis, 191
Pseudomembranous candidiasis, 496 phymatous rosacea, 197
Psoriasis rhinophyma, 198
definition, 54 Rowell syndrome, 330
diagnosis, 70, 78, 79
differential diagnosis, 71, 74
erythroderma, 73, 74 S
genital psoriasis, 69, 77 Sarcoidosis, 383–386
guttate psoriasis, 56, 62 clinical presentation, 384
inverse psoriasis, 56, 63 diagnosis, 384, 386
nail psoriasis, 59, 72, 73 differential diagnosis, 386
pathogenesis, 54, 55 pathogenesis, 383
plaque psoriasis, 54–61 Sarcoma of Kaposi
psoriatic arthropathy, 69 clinical presentation, 531–538
pustular psoriasis definition, 530
ACH, 58, 65, 66 diagnosis, 532, 539, 540
annular psoriasis, 58, 64, 65 differential diagnosis, 533
generalized von zumbusch-type, 57, 64 etiopathogenesis, 530, 531
Index 791
Scabies pathogenesis, 234

clinical presentation, 573, 574 Severe acne vulgaris, 184
definition, 573 Severe nodular acne, 183
diagnosis, 574, 575 Severe nodular-cystic acne, 183
differential diagnosis, 575 Sexually transmitted disease, 563, 564
etiopathogenesis, 573 See also Syphilis
Scalp psoriasis, 67, 75, 76 Shawl sign, 349, 350
Schwannoma, 697, 699 Skin tags, see Lax fibroid
Sclerodactyly, 361–363 Small vessel vasculitis, 234
Scleroderma, 364 Solar lentigo
clinical presentation, 340 clinical presentation, 690, 691
diagnosis, 341, 345, 346 diagnosis, 690–692
pathogenesis, 339 epidemiology/pathogenesis, 689, 690
Scrofuloderma, 487, 489 Spilus nevus, 682, 684, 688
Sebaceous carcinoma (SC), 742, 743 Spiradenoma, 634–637
clinical presentation, 625 Spitz nevus, 683
definition, 622 Spontaneous urticaria, 302
diagnosis, 625, 626 Sporotrichosis, 425, 508
epidemiology/pathogenesis, 624 diagnosis, 509
Sebaceous hyperplasia, 622–624 differential diagnosis, 509
Sebaceous nevus etiopathogenesis, 507
clinical presentation, 617, 618 extracutaneous disease, 507
definition, 617 primary skin disease, 507
diagnosis, 618, 619 Squamous cell carcinoma (SCC)
differential diagnosis, 618 clinical presentation, 737–740
epidemiology/pathogenesis, 617 definition, 733
Seborrheic dermatitis, 339 diagnosis, 738, 739, 741
clinical presentation differential diagnosis, 741
adult, 23, 30, 31 epidemiology/pathogenesis, 736, 737
infantile, 23, 26–29 Staphylococcal and streptococcal infections
definition, 21 abscesses and carbuncles, 465, 466
diagnosis, 24 boils, 465, 466
differential diagnosis, 24, 25 botryomycosis, 467, 468
pathogenesis, 21, 22, 25, 26 cellulitis, 462, 463
Seborrheic keratoses erysipelas, 460, 461
clinical presentation, 583–585 folliculitis, 465, 466
definition, 583 impetigo, 459–461
diagnosis, 584–588 necrotizing fasciitis, 464, 465
differential diagnosis, 585 toxin syndromes
epidemiology, 583 erysipeloid, 471
Segmental vitiligo, 263 erythrasma, 472
Septal panniculitis, 440, 442 keratolysis punctata, 473
Septic vasculopathy staphylococcal scald skin
acrocyanosis, 244 syndrome, 468–470
bacterial sepsis, 245 Staphylococcal scald skin syndrome,
clinical presentation, 234 210–211, 468–470
definition, 234 Stasis dermatitis, 37–42
diagnosis, 235 Steatocystoma, 611, 613, 614
differential diagnosis, 235 Steroid-induced acne, 187, 188
792 Index
Steroid-induced dermatitis, 202 secondary onychomycosis, 502

Steven-Johnson syndrome, 206, 218 superficial onychomycosis, 500, 501
clinical presentation, 209 total dystrophic onychomycosis,
definition, 209 502, 504
diagnosis, 210 pityriasis versicolor, 504, 505
differential diagnosis, 210 tinea nigra, 505, 506
erythematous plaques, 215, 216 tineas (dermatophytosis)
multiple erythematous plaques, 216 definition, 493
pathogenesis, 209 etiopathogenesis, 493–495
Stucokeratosis tinea faciei, 494
clinical presentation, 586, 588, 589 tinea interdigital, 495
definition, 586 tinea pedis, 494
diagnosis, 587 Superficial onychomycosis (OS), 500, 501
differential diagnosis, 587 Sutton's nevus, 685, 689
epidemiology/pathogenesis, 586 Sweet syndrome, 233, 416–422
Subcorneal pustular dermatosis, 430 clinical presentation, 416
Subcutaneous adipose tissue definition, 415
erythema nodosum diagnosis, 417
clinical diagnosis, 440–444 differential diagnosis, 417
clinical presentation, 438, 439 pathogenesis, 415
definition, 438 Syphilis
differential diagnosis, 440 congenital, 562
lipodermatosclerosis diagnosis, 562
clinical diagnosis, 447, 453–455 differential diagnosis, 562
clinical presentation, 447, 451, 452 latent, 562
definition, 446 primary, 559
differential diagnosis, 447 secondary, 559–562
pathogenesis, 446 tertiary, 562
lupus panniculitis Syringocystadenoma papilliferous
clinical diagnosis, 443, 445–450 (SCAP), 632–634
clinical presentation, 443–445 Syringoma, 626–628
differential diagnosis, 441, 445 Systemic lupus erythematosus, 233
pathogenesis, 441, 443 Systemic scleroderma, 363, 364
Superficial mycosis
mucocutaneous candidiasis
cutaneous and intertrigo T
candidiasis, 498 T-cell leukemia-lymphoma, 766, 767
definition, 495 Telangiectasic granuloma
diagnosis, 499 clinical presentation, 659, 660
diaper dermatitis, 499 definition, 657
etiopathogenesis, 495 diagnosis, 659, 661
intertrigo candidiasis, 496, 498, 499 differential diagnosis, 661
local factors, 496 epidemiology/pathogenesis, 657, 658
oral candidiasis, 496, 499 Telogen effluvium, 152–154
onychomycosis Temporal triangular alopecia, 146–149
definition, 499 Terebrant carcinoma, 716, 721
diagnosis, 502 Thyroglossal duct cyst, 612, 613
differential diagnosis, 502 Tinea faciei, 494
distal and lateral subungular Tinea incognita
onychomycosis, 500 clinical presentation, 494
mixed pattern onychomycosis, 502, 503 differential diagnosis, 495
onychomycosis endonix, 500 etiopathogenesis, 493
proximal subungual onychomycosis, Tinea interdigital, 495
501, 503 Tinea nigra, 505, 506
Index 793
Tinea pedis, 494 Vascular malformation

Tineas (dermatophytosis) anemic nevus, 655–657
definition, 493 angiohistiocytoma
etiopathogenesis, 493–495 definition, 647
tinea faciei, 494 diagnosis, 647, 650
tinea interdigital, 495 differential diagnosis, 647–653
tinea pedis, 494 epidemiology/clinical
Total dystrophic onychomycosis (ODT), presentation, 647–649
502, 504 capillary malformation, 645–647
Toxic epidermal necrolysis, 206, 217, 218 Cherry angioma, 656–659
clinical presentation, 213 infantile hemangioma
erythematous molecules, 216 epidemiology/pathogenesis, 661, 662
macules with erosions, 217 lymphatic malformation, 654, 655
multiple erythematous plaques, 217 telangiectasic granuloma
pathogenesis, 211 clinical presentation, 659, 660
secondary to epidermal necrosis, 217 definition, 657
Traction alopecia, 155, 156 diagnosis, 659, 661
Trichilemmal cyst, 610, 613, 614 differential diagnosis, 661
Trichoepitheliomas epidemiology/pathogenesis, 657, 658
clinical presentation, 619–621 venous lake, 655, 656
definition, 618 venous malformation, 654
diagnosis, 620 Vasculitic urticaria, 233, 302
epidemiology, 618 Verrucous epidermal nevus (NEV), 600–602
Trichotillomania, 154 Vitiligo
Tuberculoid leprosy, 481, 483, 486 acral vitiligo, 266, 267
Tuberculosis verrucous skin, 488, 490 clinical presentation, 261
Tuberculous chancre (primary inoculation skin definition, 261
tuberculosis), 487, 489 diagnosis, 262
focal vitiligo, 262, 263
U generalized vitiligo, 268
Ulcerative lichen planus, 95 mucosal vitiligo, 264
Universal alopecia areata, 148 pathogenesis, 261
Universal vitiligo, 268–270 segmental vitiligo, 263
Urticaria, 302 universal vtiligo, 268–270
clinical presentation, 302 vitiligo vulgaris, 264, 265, 267
diagnosis, 302 wood’s light lamp examination, 271
differential diagnosis, 304 Vitiligo lichenoid reaction, 110
pathogenesis, 302 Vitiligo vulgaris, 264, 265, 267
physical, 302 V-peripheral cicatricial fibrosis, 162
spontaneous urticaria, 302 Vulvovaginal candidiasis (CVV), 497
vasculitic, 302
Urticarial vasculitis, 308
W
Wegener’s granulomatosis, 227, 230
V White oral candidiasis, 496
Varicella zoster virus (VZV), 35, 517–521 Wickham striae, 82
Vascular atrophic poikiloderma, 352, 353 Wine-port stain, 645, 646
794 Index
X xanthelasmas/palpebral xanthelasmas,
Xanthomas 708, 710
clinical presentation definition, 707
eruptive xanthomas, 707 diagnosis, 710
flat xanthomas/xanthelasma, 708, 709 differential diagnosis, 710
tendon xanthomas, 707 epidemiology/pathogenesis, 707
tuberous and tuberoeruptive xanthomas, Xeroderma, 16
707, 709 Xeroderma pigmentosum, 716, 724
verruciform xanthomas, 708

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Atlas

Gonzalo García Jennifer Guzmán

Lorena Prada Hugo Herrera

ISBN 978-3-030-84106-5 ISBN 978-3-030-84107-2 (eBook)

© Springer Nature Switzerland AG 2022

Part I Inflammatory Skin Diseases

4 Other Papular, Erythematous, and Scaly Diseases ������������������������������ 131

9 Inflammatory Diseases Affecting Melanocytes ������������������������������������ 253

Photocontact Dermatitis�������������������������������������������������������������������������� 403

Part II Infectious Skin Diseases

19 Fungal Infections�������������������������������������������������������������������������������������� 493

Part III Neoplastic Skin Diseases

Lymphatic Malformations������������������������������������������������������������������������ 654

Breast and Extramammary Paget Disease ���������������������������������������������� 762

© Springer Nature Switzerland AG 2022 3

• Definition: Contact dermatitis (also known as contact eczema) represents the

Fig. 1.1 Allergic contact

Fig. 1.2 Allergic contact

Fig. 1.3 Allergic contact

Fig. 1.4 Erythematous

Fig. 1.5 Acute contact

Fig. 1.6 Acute contact

Fig. 1.7 Allergic contact

Fig. 1.8 Allergic contact

Fig. 1.9 Allergic contact

Fig. 1.10 Chronic contact

Fig. 1.11 Chronic contact

Fig. 1.12 Chronic contact

Fig. 1.13 Chronic contact

Fig. 1.14 Contact

Fig. 1.15 Chronic allergic

Fig. 1.16 Chronic allergic

variable infiltration of the epidermis by lymphocytes with an increase in epider-

• Definition: Atopic dermatitis is a chronic and inflammatory skin disease caused

Fig. 1.17 Atopic

Fig. 1.18 Atopic

Fig. 1.19 Childhood

Fig. 1.20 Childhood

• Definition: Asteatotic dermatitis or eczema craquelé is a special variant of irritant

Fig. 1.21 Adult atopic

• Clinical presentation: Xeroderma and ichthyosiform plaques present on the skin

Fig. 1.22 Erythroderma

Fig. 1.23 Erythroderma

Fig. 1.24 Erythroderma

Fig. 1.25 Besnier prurigo:

• Definition: Nummular dermatitis, also called discoid eczema or microbial

Fig. 1.26 Asteatotic

Fig. 1.27 Eczema

related in some cases to bacterial superinfection or contact sensitization.

Fig. 1.28 Nummular

Fig. 1.29 Nummular

• Definition: It is considered a chronic dermatitis that involves areas rich in seba-

azole or itraconazole. Similarly, it is believed that seborrhea (excess sebum)

presentation of the disease often varies according to the age of presentation.

• Diagnosis: It is normally a clinical diagnosis as per the clinical findings of the

Fig. 1.35 Seborrheic

Fig. 1.36 Seborrheic

Fig. 1.37 Infantile

Fig. 1.38 Infantile

Vesicular Palmoplantar Dermatitis

• Definition: Also called pompholyx or dyshidrotic eczema, it represents an acute

Fig. 1.39 Infantile

Fig. 1.40 Infantile

to a particular antigen created during the inflammatory process of the infec-

Part I Inflammatory Skin Diseases

4 Other Papular, Erythematous, and Scaly Diseases �� 131

9 Inflammatory Diseases Affecting Melanocytes �� 253

Photocontact Dermatitis�� 403

Part II Infectious Skin Diseases

19 Fungal Infections�� 493

Part III Neoplastic Skin Diseases

Lymphatic Malformations�� 654

Breast and Extramammary Paget Disease �� 762

Disseminated Eczema (Autosensitization Dermatitis)

Lichen Simplex Chronicus

Juvenile Plantar Dermatosis