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TABLE OF CONTENT DERMATOLOGICAL DISEASES Introduction of Skin Diseases Dr. K.K. LO Pruritus Dr. C.S. LEUNG Eczema Dr. Y.M. TANG, Dr. H.F. HO & Dr. K.H. YEUNG Psoriasis Dr. K.K. LO & Dr. L.Y. HO Acne Vulgaris and Other Acneiform Eruptions Dr. C.Y. LEUNG Urticaria Dr. C.Y. LEUNG Vitiligo Dr. R. SU Cutaneous Vasculitis Dr. R. SU Collagen-vascular Diseases Dr. R. SU & Dr. Y.M. TANG Blistering Diseases Dr. C.N. LOOK Alopecia Dr. C.N. LOOK Nail Diseases Dr. H.F. HO Cutaneous Malignancies Dr. H.F. HO Infection: Bacterial, Viral, Fungal Dr. W.K. FUNG Infestations Dr. T.S. AU Cutaneous Tuberculosis and Atypical Mycobacterial Infection Dr. L.Y. CHONG Leprosy (Hansen's Disease) Dr. N.R. HONEY & Dr. K.K. LO Practical Guidelines for Phototherapy Dr. L.Y. CHONG Health Nursing in Skin Clinics Ms. M. WONG, Mr. W. LEUNG, Mr. E. WAN & Subordinates Health Nursing in Special Skin Clinics Ms. M. WONG, Mr. W. LEUNG & Subordinates Cutaneous Laser Therapy Dr. L.Y. CHONG & Dr. H.H.L. CHAN Cutaneous Manifestation of Internal Disease Dr. H.H.L. CHAN & Dr. W.K. FUNG Cutaneous Drug Eruptions Dr. L.Y. CHONG
SEXUALLY TRANSMITTED DISEASES Introduction of STD Dr. L.Y. CHONG Syphilis Dr. L.Y. CHONG Gonorrhoea Dr. K.H. LAU & Dr. H.F. HO Non-Gonococcal Urethritis and Non-Specific Genital Infection Dr. K.T. CHAN Chancroid Dr. Y.M. TANG Lymphogranuloma Venereum Dr. N.M. LUK Genital Warts Dr. C.Y. LEUNG Genital Herpes Dr. C.N. LOOK HIV Infection Dr. L.Y. CHONG Molluscum Contagiosum Dr. S.Y. CHENG Candidiasis Dr. L.Y. CHAN Trichomoniasis Dr. C.S. LEUNG Pediculosis Pubis Dr. W.M. CHEUNG Balanitis, Bacterial Vaginosis and Other Genital Conditions Dr. T.S. AU & Dr. K.H. YEUNG STD in Pregnancy Dr. K.M. HO & Dr. W.S. LAM Health Nursing in Social Hygiene Clinics Mr. W. LEUNG, Mr. S. LEUNG, Mr. T. LAM & Subordinates TOPICAL PREPARATIONS FOR DERMATOLOGICAL & SEXUALLY TRANSMITTED DISEASES Basic Pharmacology and Terminology of Topical Preparations Dr. Y.M. TANG & Dr. R. SU Principles of Prescribing Topical Preparations and Topical Steriods Dr. Y.M. TANG & Dr. R. SU Government Formulary Dr. Y.M. TANG & Dr. R. SU Commercial Dermatological Preparations and Sunscreens Dr. K.M. HO, Dr. R. SU & Dr. Y.M. TANG APPENDIX Dermatology, Social Hygiene and Special Skin Clinics in Hong Kong Medical staff of Social Hygiene Service Publications from/Contributed by Social Hygiene Service Annual Incidence and Trends of Disease Suggested Books for Reading
Normal Laboratory Values INTRODUCTION OF SKIN DISEASES Dr. K.K. LO CHAPTER 1 The art of diagnosis in dermatology in the past was particularly emphasized by the visual experience of the skin and the skin lesions. The story of arriving a dermatological diagnosis even when the patient has not the time to sit down is less true nowadays for a careful dermatologist. It is a good way to impress the neophyte dermatologist but it is not the rule. It is true that some skin lesions can be diagnosed on sight with a high degree of confidence but even in such cases a systematic approach is indispensable for a good dermatologist not to miss other important skin lesions. When dermatology first evolved from general internal medicine in the nineteenth century, the principle of diagnosis in medicine still held valid till today even in the highly specialized specialty: dermatology. Hence, detailed systematic history with good physical examination, supplemented by appropriate investigations will be the golden rule for the correct approach in the diagnosis of skin conditions. The old days of when you can recognize the lesion and so the lesion can recognize you will only be true for some senior dermatologists but it will not be seen again in modern dermatology. 1. SKIN FUNCTION AND STRUCTURE OF SKIN 1.1. Skin Function Skin is actually the largest organ in the body. Its wet weight can be as heavy as 4 kg and covers an area of 1.4 to 2 sq metres. It also plays many important functions in the body as summarized in Table I. Table I: Function of the Skin Function Protection from harmful agents of external environment: biological germs, ultraviolet light & chemicals Preservation of a balanced internal environment Shock absorber Structure Epidermis
Epidermis Subcutaneous fat
Temperature regulation Insulation Sensation Lubrication Protection & grip Calorie reserve Vitamin D synthesis Body odour Psychosocial
Blood vessels & eccrine sweat glands Subcutaneous fat Nerve endings Sebaceous glands Nails Subcutaneous fat Epidermis Apocrine sweat glands Hair & Nails
1.2. Structure of Skin Epidermis: Thickness varies from 0.1 mm at the eyelids to nearly 1 mm on the palms and soles. The outermost is the horny layer (stratum corneum) which is made up of flattened dead keratinocytes. It acts as the major physical barrier in the epidermis. The granular layer, spinous layer or prickle cell layer are composed of the living keratinocytes and the basal layer which is the deepest, most active and single layer of the epidermis is the germinative layer for the epidermis. There is a gradual differentiation from basal layer to the horny layer. Skin appendages: Hair, nail, eccrine sweat glands, apocrine sweat glands, sebaceous glands. Dermo-epidermal junction: At the interface between the epidermis and dermis lies the basement membrane zone. Electron microscopy shows that it can further be divided to basal cell membrane, lamina lucida (20-40 nm), lamina densa (30-60 nm, Type IV collagen) and sublamina densa with anchoring fibrils (Type VII collagen), dermal microfibril bundles and Types I & III collagen fibres. The structures of the dermo-epidermal junction provide good mechanical support, adhesion and growth of the basal layer unless it is diseased. Dermis: It is thickest at the palms, soles and back (3 mm) least at the eyelids (0.3 mm) and penis. There are papillary dermis and deeper reticular dermis.
It contains many cells, fibres and amorphous ground substance. Fibroblast for synthesis of collagen, reticulin, elastin, glycosaminoglycans is the major cell in the dermis. The ground substance consists of two glycosaminoglycans: hyaluronic acid and dermatan sulphate. Other structures found in the dermis include: blood vessels, lymphatics, nerves, nerve endings and receptors, dartos muscles in scrotum, appendageal glands and their accessories e.g. arrector pili muscles. Subcutaneous fat: It is absent from the eyelids and the male genitalia. It has abundant blood and lymphatic supplies. 1.3. Cell Types Epidermis: Keratinocytes (85% of cells in epidermis), Langerhans cells (800 per sq mm), Melanocytes (from neural crest, wedged between basal keratinocyte in 1 to 10 ratio; 1 melanocyte supplies pigments to 36 keratinocyte), Merkel Cells. Dermis: Fibroblast, mononuclear phagocytes, lymphocyte, Langerhans cell, Mast cell. 1.4. Kinetics of Skin Epidermis: Cell cycles of keratinocytes: 300 hours (from G1, S, G2 to M phases); keratinocytes need 14 days to move from basal layer to horny layer and another 14 days to slough off from horny layer (i.e. from the basal layer to the environment requires 28 days). Skin appendages: Hair (scalp): growth rate: 0.37 mm/day, 80% in anagen at any one time; anagen phase: 3 years, catagen phase: 3 weeks, telogen phase: 3 months. Nail: fingernail growth rate: 1 cm/3 months (0.1 mm/day), toenail growth 1 cm/9 months 2. HISTORY TAKING IN DERMATOLOGY 2.1. General History Race, geographical factors (especially for immigrants), occupation, sports, hobbies, social background, ethnic tradition (dietary habits) Past medical history: allergy to medication, hay fever, asthma, past major illness or operation. Social & occupational history: travel abroad, hobbies and details of the type of work, substances in contact. 2.2. Special History (Dermatology) History of present illness: duration, date & site of onset, details of spread, evolution of rash & original morphology, symptoms such as itchiness, pain, burning sensation, numbness, precipitating and relieving factors such as climate, sunlight etc., treatment (topical & systemic medication) sought or applied.
Past history of skin disorders, history of sunburn. Family history of skin disorders (e.g. skin cancers) and atopic disorders. Drugs: include herbs, topical, systemic, patient initiated or physician prescribed. Patient's own perception on the cause of the problem. 3. PHYSICAL EXAMINATION 3.1. General Examination Good lighting, adequate privacy, light torch, spatula, magnifying glass and transparent glass slide for diascopy. General impression on the patient is very important especially for the general health, pallor, intellectual assessment, queer personality etc. will be picked up by an observant doctor when patient enters the consultation room. 3.2. Examination of Skin Distribution of the rash, arrangement and morphology of individual rash. Distribution of the lesion: symmetrical, asymmetrical, exposed area, sun exposed area, scalp region, hand, extensor aspect, flexor aspect. Arrangement and configuration of the lesion: grouped (as in insect bites, dermatitis herpetiformis, herpes simplex, common warts), annular or arciform (as in granuloma annulare, mycosis fungoides, tinea circinata, erythema annulare centrifugum), linear pattern (as in Koebner phenomenon, Psoriasis, lichen planus, plane wart, molluscum contagiosum; epidermal naevus, sporotrichosis, lichen striatus, lichen simplex, morphoea, lichen sclerosis, phytophotodermatitis). Morphology of lesion: Individual lesion described with the help of magnifying glass. To find out the early primary lesion and to inspect it closely. Note the shape(geometric shape, oval), colour(salmon-pink, erythematous, skin colour, yellow), size, margin (sharpness of edge, welldefined, ill-defined), the surface characteristics (dome-shaped, umbilicated, spike like), temperature and smell. It is a good practice if affordable to have thorough examination of the whole body especially for new consultation and for the elderly. Sometimes, examination of the back and buttock of the elderly may pick up unexpected lesions, even the patient himself or herself may not notice them e.g. persistent chronic annular erythematous rash in the buttock found in a case of tuberculoid leprosy. Do not skip examination of the nail, scalp and oral mucous membrane because there may be valuable clues. Making it a habit to examine these sites routinely is important. 3.3. Terminology Used in Dermatology Macule: flat area of altered colour or texture (less than 0.5 cm)
Patch: large macule (more than 2 cm) Papule: elevated solid lesion (less than 0.5 cm) Nodule: elevated solid lesion (more than 0.5 cm) Plaque: elevated area of skin of more than 2 cm in diameter, a disc shaped lesion, formed by extension or coalescence of papules or nodules. Vesicle: fluid filled blister (less than 0.5 cm) Bulla: larger blister (more than 0.5 cm) Pustule: collection of free pus Abscess: localized collection of pus in a cavity (more than 1 cm) Petechia: pinhead size extravasation of blood into skin Ecchymosis: larger extravasation of blood into skin Purpura: blood in skin up to 2 mm in diameter, may be palpable Haematoma: large purpura Wheal or weal: accumulation of dermal oedema Angioedema: diffuse oedema of deep dermis extending to subcutaneous tissue Comedo (comedones): a plug of keratin and sebum wedged in a dilated pilosebaceous orifice Burrow: a small tunnel in the skin that houses scabies acarus Telangiectasia: visible dilatation of small cutaneous blood vessels Poikiloderma: combination of atrophy, reticulate hyperpigmentation and telangiectasia Sclerosis: induration of the subcutaneous tissues Gangrene: death of tissue, usually due to loss of blood supply Scale: flake from the horny layer Crust: dried serum, exudate or tissue fluid Ulcer: whole of the epidermis and part of dermis lost Excoriation: linear erosion or ulcer produced by scratching Erosion: partial loss of the epidermis Fissure: slit in the skin Sinus: channel that permits escape of pus or fluid Scar: result of healing, normal structure replaced by fibrous tissue Atrophy: thinning of skin due to diminution of the epidermis, dermis or subcutaneous fat Stria: linear, atrophic, pink or white lesions due to changes in connective tissue 3.4. Special Techniques Used in Clinical Examination Magnification with hand lens is important to note the fine details of skin lesions: Magnification is essential to examine follicular plugging in lupus erythematosus, Wickham's striae in lichen planus, telangiectasia and
translucence in basal cell carcinoma, changes in colour in malignant melanoma. Tangential shining of examination torch to the skin lesions will enhance and detect elevated skin lesions with ease. Diascopy consists of pressing a transparent slide or plastic spatula over a skin lesion. Examiner will find this of special value to distinguish erythema or purpura. It is useful to detect the glassy yellow-brown appearance of papules in sarcoidosis, tuberculosis and other granuloma. Darier's sign is positive when a brown macular or papular lesion of urticaria pigmentosa becomes palpable wheal after being rubbed with the blunt end of an instrument. Auspitz's sign is positive when slight scratching or curetting of a scaly lesion reveals punctate bleeding points within the lesion which suggests of psoriasis. Nikolsky's sign is positive when a new blister is generated with ease by applying shearing force to skin. 3.5. Examples of Description of Skin Rash "Examination revealed multiple firm, well-defined nodules and plaques ranging from 1 to 4 cm in diameter. They were erythematous and were distributed over the left cheek, shoulders, upper aspect of the back, buttocks and thighs. The remainder of the examination was unremarkable." --Subcutaneous fat necrosis of the newborn. "The physical examination revealed an alert, happy five year old girl with perioral vesicles, pustules, and erosions. In addition, she had a bullous eruption on a slightly erythematous base with erosions and crusts involving the scalp, chin, umbilicus, suprapubic surface, groin, and scrotum. Some of the lesions had a serpiginous border. No oral, ocular, hand or foot lesions were present. Nikolsky sign was negative." --- Chronic bullous dermatosis of childhood. 4. DERMATOLOGY INVESTIGATIONS 4.1. Skin Biopsy Specimen is sent for Histopathology, direct Immunofluorescence study or culture and smear for AFB, fungus. Try to sample a representative lesion, avoiding sites where scar would be conspicuous, avoid keloid prone area i.e. upper anterior chest, avoid legs where healing is slow and histology modified, avoid over bony prominence, place in proper fixative or fresh (as in immunofluorescence staining or culture) and make sure the correct labeling with name, site, history, diagnosis. Discussion with the pathologist is often helpful.
Punch biopsy: 3 to 4 mm tissue punch, specimen not to be crushed with tooth forceps, skin hook may be good in handling the tissue. Scalpel biopsy: elliptical excisional, incisional or shave biopsy. 3/0 nonabsorbable sutures for legs, 5/0 for face and 4/0 else-where. In general, stitches are planned to be removed from the wound in face 4-5 days, from the neck and the scalp in 7 days, from the anterior trunk and arms in 12 to 14 days, from back and legs in 14 to 28 days. Skin splints in the form of SteriStrips can be applied after stitches are removed. They can be kept for two to six weeks after suture removal. 4.2. Wood's Lamp Examination Ultraviolet light of 365 nm wavelength is obtained by passing the beam through a Wood's filter composed of nickel oxide containing glass. The examination has to be done in a dark room. Infected hair in tinea capitis caused by Microsporum canis will fluoresce bright green, skin lesion of active pityriasis versicolor will fluoresce yellow, fresh urine in porphyria cutanea tarda fluoresces a reddish colour, erythrasma will fluoresce coral red, vitiligo lesion appears more white and ashleaf macule in Tuberous sclerosis is more apparent, coral red fluorescence of teeth in congenital erythropoietic porphyria. Make sure that there are no artificial cream or cosmetic are left in the area of skin examined by Wood's light because many creams or dyes will fluoresce under Wood's light. 4.3. Patch Test This tests the type IV hypersensitivity reaction and it is a confirmatory test for allergic contact dermatitis. Trolab standard patch test is used to screen and confirm allergic contact dermatitis. Further breakdown of the test may require patch test with different series e.g. fragrance series. The test materials are applied to the back under aluminium discs with occlusion. The sites are inspected at 48 hours and test materials removed. The sites are re-inspected at 96 hours for delayed reaction. The grading of the reaction will be as follows: No reaction: 0 Doubtful: +/Weak (erythema, non-vesicular): + Strong (vesicular or edematous): ++ Extreme (with ulceration): +++ Irritant reaction: IR Not tested: NT 4.4. Mycology Examination Superficial fungi can be identified by examination of the skin scraping, nail or hair. The scales, nail or hair should be collected onto a slide and a drop of
10 to 20 percent KOH to dissolve the keratin. It can be hastened by gently warming the preparation but never over warm to cause bubbles with artefacts affecting microscopic examination. It takes 10 to 15 minutes to prepare for scales, but it takes longer for nail clipping from 30 to 45 minutes for best preparation. Then it can be examined under low power objective and then the high power objective for detail. The tissue can also be sent for mycology culture. The result may not be available for 3 weeks. 4.5. Mite Examination To identify the burrow in common area e.g. finger webs. With the help of magnifying glass, the acarus may be seen as a tiny grey dot at the end of burrow. It can be removed by a sterile needle. If mites not seen, burrow will be moistened with liquid paraffin or mineral oil and scraping with the scalpel blade and transferred to slide for examination. 4.6. Blood & Urine Tests Just like that in general internal medicine, appropriate tests e.g. muscle enzymes to exclude dermatomyositis, urine sugar test to exclude diabetes mellitus. 4.7. Radiology Examination The commonest tests done are X-ray chest to exclude pulmonary tuberculosis and X-ray joints for psoriatic arthropathy. CT scan is important for exclusion of internal enlarged lymph nodes in cutaneous lymphoma and to exclude brain lesions in a case of neurofibromatosis. 4.8. Other Tests Prick testing is much less helpful in dermatology. It is not done or available in Social Hygiene Clinics. Multiple positive skin tests to commercially prepared diluted antigens may only imply the atopic tendency of the tested subject. Dark-ground examination for suspected genital ulcer to look for Treponema Pallidum can be easily done when equipped with a dark-ground microscope. It is the interpretation of the wet smear which may require some experience. Acetic acid test on genital or cervical papules facilitates detection of subclinical condylomata acuminata. Gauze saturated with 5% acetic acid is wrapped around area for 5 to 10 minutes and the use of colposcope or magnifying hand lens to detect the lesional white papules. Cell cytology (Tzank smear) is not available in the clinic because it requires a good and well trained cytologist for the smear. 4.9. Clinical Photography Clinical photo is the best to document any lesion. One picture worths thousand words of description. Usually all medico-legal cases, biopsy cases, complicated cases and skin cancer cases require the clinical photo as an additional documentation. It is a useful investigation tool for follow-up of
lesions e.g. naevus sebaceous, pigmented naevus. Standard macro lens with fixed magnification in good focus, appropriate flash-lamp (with good battery) or good lighting, with good backgrounds (pure blue or green cloth as background) will make the photo not a waste. Date, site of photo taken and a good filing system are needed to make it a useful and interesting tools for investigation in dermatology. 5. PATTERN OF COMMON SKIN DISEASES IN SOCIAL HYGIENE CLINICS 1) The commonest 20 skin diseases in the statistical return in 1996 in dermatology clinic of Social Hygiene Service. Rank Condition Incidence (new cases) 1 Eczema 4,931 2 Tinea (all types) 1,577 3 Verruca 1,263 4 Acne 764 5 Contact Dermatitis 642 6 Psoriasis 560 7 Urticaria 421 8 Herpes infections 381 9 Pigmentary disorders 329 10 Alopecia 322 11 Naevi (all types) 310 12 Neurodermatitis 292 13 Pityriasis versicolor 210 14 Rosacea 195 15 Skin tags 162 16 Scabies 157 17 Seborrhoeic wart 154 18 Nail dystrophy 86 19 Keratosis (all types) 81 20 Cysts 55 21 Others 2,628 ¡@ Total 15,520 2) Skin malignancies (biopsy confirmed cases) in 1992 to 1996.
Diagnosis Basal cell carcinoma Squamous cell carcinoma Malignant melanoma Bowen's disease Extramammary Paget's Disease Adenocarcinoma Lymphoma/Mycosis Fungoides Kaposi's sarcoma Baso-squamous carcinoma Angiosarcoma & Metastatic carcinoma Sebaceous carcinoma & Trichilemmal carcinoma Other carcinoma of skin Solar keratosis Total
1992 1993 1994 1995 1996 53 10 3 22 5 2 3 0 0 0 0 0 18 59 12 4 18 1 0 9 3 0 0 0 0 15 79 9 0 16 7 0 5 4 0 1 0 0 21 72 10 9 23 1 1 16 3 0 2 0 2 32 84 22 3 23 1 0 9 1 0 3 0 4 54
116 121 142 171 204
PRURITUS Dr. C.S. LEUNG CHAPTER 2 1. PATHOPHYSIOLOGY Itch receptors are unmyelinated, unspecialized free nerve endings, found near to the dermal- epidermal junction. It was widely believed in the past that pain and itch are transmitted by the same nerve pathway, and also low intensity stimulation of unmyelinated polymodal C fibre results in itch sensation whereas high intensity stimulation causes pain. However, in recent experiments, when single unmyelinated C fibres are stimulated two sets of fibres have been identified. Stimulation of most these fibres produce pain sensation, whereas a small number of fibres produce the sensation of itchiness upon stimulation. (Greaves) 2. PERIPHERAL MEDIATORS 1) Histamine
2) Neuropeptides, including substance P - Substance P, together with neuropeptides, is localised in cutaneous sensory nerve endings. They could be depleted by capsacin cream. 3) Other relevant periperhal mediators Arachidonic acid transformation products - Prostaglandin E potentiates itchiness caused by other mediators Platelet activating factor Other vasoactive peptides and proteases Others Finally, it is found that enkephalins, which are opioid pentapeptides, exert a modulatory action on transmission of pain and itchiness. 3. Causes of itchiness Understanding the various causes of pruritus is fundamental to its management. 3.1. Localized Causes Certain skin disease may select to affect a particular site of a body causing localized pruritus. Some of the important examples of localized pruritus are as follows: Scalp: Seborreic eczema and neurodermatitis, psoriasis Eyelid: Airborne irritants or allergens; allergic reactions to cosmetics and nail vanish Fingers: Eczema, scabies, fowl mite infestation Legs: Gravitational and discoid eczema, asteatosis 3.2. General Pruritus 3.2.1. External Causes 1) Climatic: low humidity e.g. due to cold weather or central heating may renders the skin brittle, and allows minor irritant such as soap to penetrate, causing mild inflammation and pruritus. The dry skin of the old aged causing itchiness is common. Excessive dry skin associated with atopic eczema will also lead to itch. High humidity can also cause pruritus secondary to sweat retention in some individuals. 2) Particulate matter: foreign body e.g. glass fibre, hair; industrial exposure to powdered alumina or fibreglass (curtains, draperies, plastic furniture) can cause pruritus. 3) Chemical: some detergent (e.g. optical brighteners in certain washing powders) may cause pruritic dermatosis with little sign. 4) Parasite contact or infestations: scabies or due to mites of pets etc. can cause marked pruritus.
5) Aquagenic pruritus: the condition may be a premonitory symptom of polycythaemia vera, myeloproliferative diseases or even histocytic disorders. 6) Excessive bathing 3.2.2. Skin Diseases Pruritus is a feature of many of skin diseases. Some common skin diseases causing itchiness is listed as follows: Severe Moderate Scabies, pedulosis Psoriasis Insect bites Seborrhoeic eczema Contact dermatitis Fungal infection Atopic eczema Dry skin Urticaria Sunburn Miliaria Lichen planus Dermatitis herpetiformis Generalized pruritus can precede some skin disease such as pemphigoid. 3.2.3. Systemic Causes A wide variety of systemic disease can cause generalized pruritus without diagnostic skin lesions. The incidence of the association of generalized pruritus with significant internal disease is difficult to assess, but it has been estimated to range from 10-50%. 1) Infectious causes (including tropical and intestinal parasites) a) Rubella b) Varicella c) HIV infection d) Trichinosis, tapeworm infection e) Onchocerciasis f) Schistosomiasis g) Fungal infection Generalized pruritus has been associated with localized fungal infection. 2) Endocrine disease a) Diabetes: general pruritus is not a manifestation of diabetes mellitus (Greaves) and the pruritus is usually localized (e.g. itchiness of genitalia or perianal area due to candidiasis; and pruritus of scalp.) b) Hyperthyroidism, hypothyroidism (due to skin dryness) c) Disorders of the parathyroid gland d) Carcinoid syndrome 3) Hepatic disease
a) Pregnancy: intrahepatic cholestasis b) Obstructive jaundice (in biliary tract or extrahepatic, e.g. carcinoma of Ampulla of Vater) c) Primary biliary cirrhosis d) Drug induced cholestasis: intrahepatic biliary obstruction e.g. chlorpromazine, contraceptive pills, testosterone 4) Renal disease Pruritus is common among patients with chronic renal failure. In patients on maintenance dialysis, over 80% are affected. 5) Haematological diseases (including lymphoproliferative disorders) a) Polycythaemia vera: pruritus may occur after contact with water or after a hot bath (the pruritus after a hot shower is not specific for polycythaemia, as it can occur in Hodgkin's Disease, myeloid metaplasia, or other disorders, not to mention the vasodilatation produced by heat may enhance itchiness of almost any causes). N.B.: Aquagenic pruritus may precede the development of polycythaemia vera by several years b) Iron deficiency: Iron deficiency has been often regarded as a cause for pruritus, or even in the absence of anemia. The itch may be due to factors other than the iron deficiency itself. c) Hodgkin's Disease: (about 30% patients feel itchy) Pruritus can be the early or presenting complaint. It can be severe (which may imply a worse prognosis.) Excoriations, papules, prurigo nodules from continuous scratching may be present. Therefore periodic reinvestigation or revaluation of p.u.o. is important. d) Mycosis fungoides e) Lymphosarcoma f) Chronic leukaemia: pruritus is an uncommon presentation of chronic leukaemia, and is more often encountered in the lymphatic than the granulocytic form. g) Myleomatosis h) Paraproteinaemia i) Mast cell disease 6) Occult malignancy a) Haematological and lymphoproliferative disorders as mentioned. b) Pruritus is an important but uncommon manifestation of carcinomatosis. Among the tumors reported to present with generalized pruritus, adenocarcinoma and squamous cell carcinoma of various organ are most common. Though generalized, the itching may be more marked on the legs, upper trunk and the extensor surfaces of the upper limbs.
c) Tumor of brain: associated with pruritus of nostril 7) Autoimmue disease SLE, 'Sicca syndrome' 8) Neurological Tabes may give rise to segmental pruritus. GPI Multiple sclerosis Brain tumor Paroxysmal unilateral pruritus has been recorded with central nervous system disease 9) Psychiatric/Psychogenic Causes Emotional stress and psychological trauma intensifies all form of pruritus and neurosis may be the cause for pruritus. Delusion e.g. delusional parasitosis (a manifestation of monosymptomatic hypochondrical psychosis) of course can be a cause for complaint of pruritus. To make a diagnosis of pruritus (localized or generalized) as psychogenic or psychiatric in origin, cutaneous and systemic causes have to be excluded. 10) Drugs or as a result of therapy Pruritus can be a side effect of a wide variety of drugs. This include the opium alkaloid, CNS stimulant/depressant, niacinamide, cimetidine, aspirin, quinidine, chloroquine. Drugs can also cause pruritus via the mechanism of hepatic cholestasis (e.g. chlorpromazine, testosterone, contraceptive pills). Subclinical sensitivity to any drug may cause pruritus. Pruritus may be a side effect of PUVA. To help in memorizing these systemic causes, the word BLINKED can be remembered. B = Blood disease L = Liver disease I = Infection, immunological or autoimmune disease N = Neoplastic disease, neurological disease K = Kidney disease E = Endocrine disease D = Drug Of course psychiatric or psychogenic cause should not be forgotten. * Pruritus ani deserves mentioning here as the symptom could be due to primary pruritus or associated colonic or anorectal diseases. Common anorectal disease are haemorrhoids and anal fissures. Neoplasia associated in descending order of frequency are rectal cancer, anal cancer, adenomatous polyp and even colonic cancer, also the pruritus associated could be present
longer than that due to primary pruritus or benign anorectal disease. 4. Evaluation 4.1. A, B, C The patient must be evaluated for the A (external causes), B (skin diseases), C causes (systemic causes: which in turn include the BLINKED causes) as mentioned. The evaluation consists of taking a detailed history, physical examination and laboratory investigations. 4.2. History: Detailed History of the Present Illness Besides, the following questions concerning the features of pruritus is relevant: 1) Is the pruritus localized (external cause) or generalized (internal cause)? 2) Is only the exposed skin affected? If yes, this implies an exogenous cause. 3) Are any other family members affected? 4) Is there relationship with occupation? e.g. exposure to fibre glass. 5) Is there any recent history of travel? (tropical infestations?) 6) Is there exposure to plants, animals or chemical? Characteristics of pruritus: 1) Site, whether localized or generalized. 2) Precipitating and relieving factors: e.g. any relation to hot bath such as found in aquaenic pruritus? 3) Severity: the influence on daily activities/sleep. 4) Time relationship: most itchiness are worse at night, esp. scabies. 5) Seasonal variation: asteatotic eczema is usually worse in winter. The history should include assessment of personality, current emotional stress. Past medical history Family medical history 4.3. Physical Examination A complete physical examination is performed with the various possible differential diagnosis (the A, B, C causes) in mind. During the physical examination, particular attention should be paid to vital signs, lymphadenopathy and enlargement of organs etc., with special alertness to any possible connection between cutaneous sign and disease of other organ system. In the absence of obvious localizing signs or symptoms indicating systemic disease, rectal and pelvic examination should be included in the full physical examination. Patient with P.U.O. (pruritus of unknown origin) must be considered for any underlying disorder, e.g. "occult carcinoma" may need to be ruled out in elderly patient presenting with persistent pruritus.
4.4. Laboratory Investigation 1) Haematological: CBP, ESR 2) LFT, RFT, acid phosphatase, serum iron, serum protein electrophoresis, immunoelectrophoresis 3) Thyroid function test/glucose 4) CXR 5) Stool for occult blood, ova/cyst 6) Urine for R/M 7) Skin biopsy 8) Others: e.g. test for HIV antibody, Pap smear, further radiological examination if indicated Further investigations may be necessary depending on the situation. 5. Treatment 1) Treat the underlying cause. 2) General symptomatic treatment a) To reduce or avoid any provocative factors, e.g. dryness of the environment, wearing irritating fabric, overheating, stress, vasodilatation from hot food. b) Topical applications: Emollient, menthol in calamine lotion can be used. 3) Commonly used oral medication: Antihistamine are most useful in conditions in which antihistamine clearly plays a role, e.g. urticaria. Histamine is the most consistent itch mediator known, but it is not always useful as other mediators may also be involved. * Tricyclic antidepressants may be of help in some patients with intractable itching. 4) For treatment of the pruritus of some of the specific disorders, the following measures have been reported to be useful. (Some of these treatments may need further studies and trial for evaluation.): a) Aquagenic pruritus +/- polycythaemia vera (PV) Topical capsacin treatment PUVA (maintenance therapy may be necessary), UVB regional sponging at bathing may be helpful in aquagenic pruritus with PV. Interferon alpha: not only controls the pruritus, also helps to contain the increased haemopoiesis in PV, and lead to better haemopoietic control. Yet some patients may not be able to stand the side effect. Phlebotomy reported to be useful in a case of PV. N.B.: The pruritus usually responds poorly to antihistamine b) Obstructive jaundice cholestyramine is helpful, but is associated with a high incidence of side effects.
new anion resin, BR 350 rifampicin antihistamine naloxone infusion, opiate antagonist Ondansetron, a specific serotonin type 3 (5-HT3) receptor antagonist Flumecinol used in pruritic patients with primary biliary cirrhosis propofol (an intravenous anesthetic induction agent) employed in a subhynotic dose, for short term use. c) Chronic renal disease: Some patients with hyperparathyroidism secondarily to renal failure improve dramatically after subtotal parathyroidectomy. However, only a minority of patients respond and the improvement may only last a few months. Phototherapy by UVB for moderate to severe cases. Emollients may relieve those with a dry skin. Activated charcoal or cholestyramine orally may be helpful. Capsacin cream topically. Ketotifen. Azelastine hydrochloride (an anti-allergic drug/antihistamine) orally. Talidomide for difficult cases. Other treatments including heparin, mexiletine, ion-exchange resin and intravenous lignocaine have been advocated but are of uncertain effectiveness and usually impractical to use. Low protein diet was reported to be useful. Antihistamine and topical steroids are usually not helpful. d) Psychological/psychiatric diseases: psychiatric advice should be sought. After careful consideration, antidepressant and anxiolytic drugs including doxepin and hydroxyzine can be tried. Pimozide has been advocated for delusions of parasitosis. e) Atopic eczema: Doxepin cream. f) Myeloproliferative disorders and other disease: Danazol has been tried in the treatment of refactory pruritus associated with myeloproliferative disorders and other disease e.g. autoimmune disease etc. 5) Other medication/measures that has been employed to treat generalised pruritus: Odansetron (5 HT3 antagonist) transcutaneous nerve stimulation ECZEMA Dr. Y.M. TANG, Dr. H.F. HO & Dr. K.H. YEUNG
CHAPTER 3 1. INTRODUCTION 1.1. Terminology ECZEMA: Use as a clinical descriptive term, it describe a process that is clearly superficial in form and that, early, is erythematous, papulo-vesicular, oozing and crusting and, later, red-purple, scaly, lichenified and possibly pigmented. Epithelial disruption and non-sharp margination are its characteristics. ECZEMA can be defined histologically by the presence of a predominantly lymphohistiocytic infiltrate around the upper dermal blood vessels, associated with varying degrees of spongiosis and acanthosis. The terms 'ECZEMA' and 'DERMATITIS' are regarded as synonymous. 1.2. Table 1: Stages of Eczematous Inflammation Stage Morphology of Symptoms Lesions Examples Treatment
acute contact cold wet intense itch, dermatitis, acute compresses, vesicles, blisters, Acute stinging, nummular eczema, steroid, intense red burning stasis dermatitis, antihistamine, pompholyx, antibiotics red, scale, contact allergy, slight to fissuring, irritation, atopic topical steroid moderate parched dermatitis, stasis emollients, Subacute itch, appearance, dermatitis, nummular antihistamine stinging, scalded eczema, asteatotic antibiotics burning appearance eczema atopic dermatitis, thickened skin, lichen simplex topical steroid lichenified moderate to chronicus, fingertip antihistamine Chronic excoriation, intense itch eczema, antibiotics, fissuring hyperkeratotic emollients eczema 1.3. Table 2: Common Types of Eczema Exogenous Endogenous
Allergic Contact Dermatitis Seborrhoeic Dermatitis Photoallergic Contact Dermatitis Eczematous Polymorphous Light Eruption Infective Dermatitis Dermatophytide ¡@ ¡@ ¡@ ¡@ Asteatotic Dermatitis Discoid Eczema Pityriasis Alba Hyperkeratotic Eczema Gravitational Eczema Juvenile Plantar Dermatosis Eczema Associated With Systemic Disease Eczematous Drug Eruption
2. ATOPIC ECZEMA Atopic eczema (AD) is a characteristic type of chronic dermatitis frequently associated with atopy and an elevated IgE level. There are no single distinguishing features of AD; however, the diagnosis can be made on a combination of history, and morphological findings. 2.1 Epidemiology AD has a world-wide distribution and affects all races. About 3% of children under age 5 years had AD with a male to female ratio of 1.2 : 1. Majority of patients presents within the first 5 years. AD runs in family. About 75% of patients have a personal or family history of other atopic diseases, e.g., allergic rhinitis, asthma, hay fever. 2.2. Aetiology and Pathogenesis The aetiology is unknown and the pathogenetic mechanisms are speculative. However, a number of clinical, pathological and immunological abnormalities are frequently observed in these patients and are briefly discussed below: 1) Elevated IgE
Occur in about 80 percent of AD patients and are directed against a wide variety of antigen like pollens, molds, foods, house dust mites (HDM) and bacterial antigens etc. A high IgE level is not a unique feature of AD but appears to correlate with the clinical severity and falls with remission. 2) Skin Prick Test and RAST Patients with AD often show positive Prick test and RAST to common household allergens like egg, milk, wheat, fish, soy, peanut, pollens, HDM and animal danders etc. However, avoidance of such allergens does not necessarily bring about a clinical response. 3) Bacterial Antigens Staph. aureus colonization occurs in over 50% of AD patients and compared to less than 5% in normal individuals, and is frequently isolated (> 90%) from acute exudative lesions and lichenified plaques. The density of the organism correlates with the severity of eczema and antibiotics that clear Staph. aureus improve eczema. 4) Impaired Cellular Immunity This includes a reduced CD8+ suppressor T cells, a reduced natural killer cell function, a reduced IFN-g production, a reduced response to mitogens; peripheral eosinophilia in some and abnormal neutrophil chemotaxis. 5) Inflammatory Cells and Mediators A very characteristic feature of AD is intense pruritus. It has been shown that an increased population of mast cells occurs in the skin of AD patients which releases histamine, leukotrienes and cytokines much more readily compared with normal subjects. 6) Abnormal Vascular Responses Disturbed vascular reactivity like white dermographism, nicotine blanching, and delayed blanch with methacholine are well documented. 7) Sweat and Sebum Production AD patients tend to produce more sweating than nonatopic controls. It has been suggested that an increase in transepidermal water loss, and a possible deficiency of lipids in the epidermis account for the skin dryness. 2.3. Clinical Features 1) Pruritus Is the hallmark of AD. It is more severe at night and is attributed to the absence of distraction, capillary dilatation, and increased skin temperature. A natural response to itch would be scratching, and scratching results in erosions, weeping, crusts, secondary infections, prurigo papules and lichenification. 2) Dry Skin (Xerosis)
Manifests as scaling, chapping and a feeling of skin roughness. It is worse in winter times due to reduced ambient humidity and coldness. Dry skin is enhanced by frequent use of detergents or defatting substances. 3) Eczematous Lesions The most typical skin sign of infantile AD. They are polymorphic, with an erythematous, papulovesicular, erosive and crusted appearance. 4) Prurigo Is a dome-shaped papule, sometimes with a tiny vesicle on top. Excoriation is frequent. Prurigo papules vary in number and distribution. 5) Lichenification A lichenified plaque is a poorly demarcated, slightly tan to red plaque with grossly accentuated skin markings. Lichenified plaques take long time to resolve. The antecubital and popliteal fossae and the neck are predilected sites. 6) Dennie Morgan Fold Is an extra infraorbital eyelid fold. About 80% is bilateral. Some consider this is a consequence of scratching of the eyelids. 7) Hand and Feet Ivolvement Dry, nonpruritic plaques and recurrent hyperkeratosis and fissuring of the finger pulps (and soles) are common. Linear furrows running across thenar and/or hypothenar eminences referred to as hyperlinearity of palms occurs in about 1/3 to 1/2 of AD patients. Coarse pitting and ridging of nails may occur. 2.4. Four Phases of AD 1) Infantile Phase Lesions first appear on the cheeks, forehead, and scalp, but may occur on the trunk, neck, hands and feet. Eczema with oozing and crusts are more typical. Nocturnal restless, irritability and crying are prominent. When the child begins to crawl, the exposed areas especially the extensor aspects of knees are affected. 2) Childhood Phase At about 18 months, the eczematous lesions tend to be replaced by lichenification. Prurigo papules occur and are very itchy. Elbow and knee flexures, wrists and ankles and neck are commonly involved. The neck may show striking reticulate repigmentation (dirty neck). Hands may be dry and lichenified; sole involvement may mimic juvenile plantar dermatosis. The face is less frequently affected. Problems with schooling may occur. 3) Adolescent/Young Adult Phase Predominant features are pruritus, lichenification, prurigo papules, scratch marks, and crusting. Lesions occur mostly on the face, neck, flexures, and
upper trunk. Localized patches of eczema around the nipple or vermillion of the lips can occur. Psychological difficulties occur in some. 4) Adult Phase AD resolves spontaneously in most patients after age of 20. Majorities of the patients, however, still have sensitive, unstable skin and a higher tendency to develop dermatitis. Full blown AD occurs in only a small percentage of patients throughout adulthood. 2.5. Associations The association of AD with allergic rhinitis, asthma and conjunctivitis is well documented. Eczematous conditions like contact dermatitis, discoid eczema, pityriasis alba, lip-stick eczema and follicular eczema are more frequently seen in atopic subjects. Others like ichthyosis vulgaris, keratosis pilaris, Netherton's syndrome, alopecia areata and vitiligo etc. also have linkage. 2.6. Complications 1) Infection Bacterial especially Staph. aureus, viral, and fungal infections are common, and so as scabies. Eczema herpeticum, which is herpes simplex infection in eczematous skin is characterized by multiple, painful, vesiculopustular lesions; and often become haemorrhagic, eroded and crusted. Affected areas may be very edematous; regional lymphadenopathy occurs and secondary bacterial infection is common. Diagnosis can be established by Tzanck smears or electronmicroscopy from scarping of the skin lesions. 2) Exfoliative Dermatitis This is severe and requires hospitalization. 3) Eye An increased incidence of anterior subcapsular cataract may be due to extensive use of systemic steroid, and to topical steroid applying around the eyes. Keratoconus is corneal degeneration characterized by increasing conicity of the cornea resulting from a raised intraocular pressure. Visual disturbance occurs. 4) Retarded Growth May be attributed to a combination of reduced exercises, infections, and malnutrition secondary to inappropriate dietary restriction; however, frequent use of systemic/topical steroid is perhaps a more important contributing factor. ¡@ 2.7. Criteria for Diagnosis of Atopic Eczema Major criteria Minor criteria Pruritus Dryness
Typical morphology and distribution Hyperlinearity of palms/Keratosis . pilaris of skin lesions. Increased IgE Chronic and relapsing course Early age of onset Personal or family history of atopy Tendency to cutaneous infection Cheilitis Dennie-Morgan infraorbital folds Pityriasis alba Keratoconus/anterior subcapsular cataracts White dermographism etc. There is no single diagnostic feature for AD. However, it has been suggested that a diagnosis of AD can be established with 3 or more major criteria plus 3 or more minor criteria. 2.8. Differential Diagnosis Infantile seborrhoeic dermatitis has an earlier onset than AD. The presence of family history, scratching, possible food intolerance, and high IgE level in AD is absent in seborrhoeic eczema. Allergic contact dermatitis with autosensitisation, psoriasis, candidiasis, dermatophytosis, pityriasis rosea, scabies, nutritional deficiency may at times cause confusion. 2.9. Treatment 1) General Measures a) Explanation Explanation on the nature and management of AD improves compliance and efficacy of treatment. AD runs a long course that can be controlled but not cured. AD improves with increasing age, but patients often have a dry, sensitive skin and avoidance of irritants and trigger factors is always necessary. Good medical compliance is important. Scratching of skin should be discouraged in order to disrupt the itch-scratch cycle; keep nails short. Immunization is given as non-atopic subjects but should be cautious for vaccines derived from eggs if patient is egg-sensitive. Defer vaccination if the child has an acute flare of eczema. Career advice emphasizes the selection of a 'clean' job. Occupations like barber, chef, laboratory technician, car mechanic, nurse and jobs that require contact with chemicals are not suitable. b) Environmental Modification and Avoidance of Trigger Factors Woolly underclothes irritate skin and should be avoided Woolly toys tend to house allergens so as carpets. Pets have the similar problem; their hair and excreta can be allergenic and pets are a source of infestation. Avoid excessive heating in the bedroom as this increases dryness and itchiness. Regular once daily bathing is not strictly required. Over-bathing or over-use
of soaps is detrimental to the sensitive skin. Avoid bathe with hot water, use soap substitutes, avoid vigorous rubbing at the skin and keep the bathing time short. The skin should be mopped dry immediately after bathing and emollients applied. Swimming is permitted but chlorinated water irritates skin and hence immediate showering is required afterwards. Many cosmetic products have the potential to trigger a flare. Foods implicated as allergenic include eggs, milk, wheat, legumes, seafood and peanuts. Few young patients do have a clear relationship between food and eczema flares. In such case, they can try a 3-4 week's period of suspected food elimination. One should aware that unsupervised food restriction in the young may lead to malnutrition. Avoid unnecessary physical and emotional stress. 2) Management of Dry Skin - Emollients and Soap Substitutes Dry skin is more prone to itch and chapping and hence risk of infection and subsequent perpetuation of eczema. A good dry skin care can be achieved by: a) Keep bathing time short and to a minimum necessary b) Use lukewarm water not too hot c) Use soap substitute e.g. emulsifying ointment d) Avoid vigorous rubbing and cleaning at the skin e) Pat dry, and f) Apply emollients e.g., aqueous cream, as soon as after getting out of the bath. Emollients minimize dryness and is the mainstay in treating mild AD. Some emollients are also humectants, e.g. urea cream. Humectants attract water into the skin, and are useful on unbroken skin but can cause stinging. Emollients should be applied as frequently as possible according to patient's need. It is believed that regular and frequent use of emollients can reduce 10-20% of the amount of topical steroids used in the maintenance treatment of AD. Some emollients contain lanolin that may sensitize skin e.g., Alpha keri, oilatum etc. Chapters 35 and 37 give further description on the property and use of emollients. 3) Ichthammol and Tar Preparations (0.5-1%) Ichthammol impregnated bandages are old remedy but are still used for treating childhood eczema in UK. Tar can reduce itch. Tar/steroidimpregnated bandages are useful for chronic lichenified eczema. Tar bath is a useful bath additive in reducing itchiness. Tar compounds can induce folliculitis and photosensitisation; and because of its smell and colour, patient compliance is a poor. 4) Topical Steroids
Is the mainstay of treatment for inflammatory aspect of atopic eczema. The strength and the base used will depend on the stage and location of the eczema. Acute weeping eczema should first be treated with potassium permanganate (KMnO4) compresses followed by a steroid lotion or cream. In chronic eczema, creams and ointments are both suitable. Twice daily application is usually sufficient. Prolonged use of a potent corticosteroid e.g., clobetasol propionate 0.05% over 50 g per week may result in systemic and local side effects. Fear of side effects, however, should not limit the use to a weaker but ineffective corticosteroid. Potent corticosteroids can be used as a short-term measure aiming to obtain initial control, this is then changed over to a weaker steroid suitable for the situation. Chapter 41 gives an overview on topical corticosteroids. "Wet-Wrap"is a newly developed way of using topical steroid under the occlusion of wet tube gauze. It has the combined advantages of applying steroid under occlusion, maintaining moisture and prevent scratching. It is indicated in the chronic, dry, thickened and lichenified type to atopic dermatitis especially in young children. Exudative lesions in acute and subacute eczema is not suitable. 5) Control of Infections Staph. aureus infection is a frequent cause of eczema flare requiring systemic antibiotics, e.g., erythromycin or cloxacillin. Sometimes, a prolonged course of antibiotics may be required. Topical mupirocin twice daily to nasal vestibules and chlorhexidine massaging onto body during bathing can reduce the number of Staph. aureus in a carrier. Systemic antibiotics for treating large area of infected eczema are superior than using large amount of topical antibiotics that carry risk of hypersensitivity and inducing bacterial resistance. Eczema herpeticum needs systemic acyclovir. Molluscum contagiosum, warts and fungal infections should be treated accordingly. 6) Systemic Corticosteroid It is not a routine management of atopic eczema and it should be avoided at times of puberty. Sometimes, a short course of systemic corticosteroid is effective in gaining control of a severe eczema flare. Whenever systemic steroid is used, any infection must be looked for and treated promptly. 7) Systemic Antihistamines Recommended doses can be given during periods of excessive scratching. Avoid excessive doses as hyperexcitability may be quite marked in young children. 8) PUVA
It is useful in chronic lichenified eczema where pruritus is intractable and a useful adjunct to leaving off topical steroids at the time of pubertal growth spurt. Patient selection is important. No PUVA should be given to children under the age of 12 because of risk of cataract in the immature lens and difficulty in co-operation and understanding with the PUVA regime. The same precautions and procedures as PUVA for other conditions should be undertaken. The response of AD to PUVA is not as good as compared with that for treating psoriasis and the total dose required is often larger. The experience in UK showed that approximately one-third showed remission or significant response, one-third remit and relapse, and one-third no response. 9) Immunosuppressives Azathioprine or cyclosporin are helpful in severe cases. Nevertheless, drug toxicity and long-term hazards are a definite risk. They should only be considered for chronic severe AD with poor response to the usual treatment. 10) Hospitalization In severe cases, it can be very helpful. Remove the patient from his environment and potential trigger factors, institute regular and intensive treatments can lead to resolution of the eczema. 2.10. Alternative Treatments 1) Evening primrose oil Which contains linoleic acid and gamma linolenic acid, was found to be effective in some cases in reducing erythema and pruritus; but it may take 23 months to see effect. It is also costly. The precise indications are not clear and it cannot be predicted which patients will respond. It may be tried for patients who failed with conventional therapy. 2) Chinese herbs Recent studies in UK using a certain formulary of Chinese herbs for patients with long-standing, widespread, and non-exudative AD have shown a statistical significant improvement in symptoms and skin signs. At this stage, Chinese herbs do seem to have a therapeutic potential in the treatment of AD but its palatability, efficacy and its safety need further evaluation. 3) Sodium cromoglycate It is given as 100-200 mg qid orally. In general, it is not effective. 4) Behavioral therapy May be a useful adjunct for patients who cause excessive self-mutilation in their families. 2.11. Prevention There is no definite evidence that breast feeding is protective against development of AD. It has been suggested that the early introduction of solid
foods (before age 4 months) does have a deleterious effect, and that a greater variety of foods correlated with an increased probability of developing AD. 2.12. Prognosis Studies investigating the long-term outcome of AD have been unsatisfactory. In general, patients with a family history of AD, associated asthma, hay fever, later-onset disease and the presence of severe dermatitis have higher rates of persistent disease. Many quote 40-50 percent of recovery by age 15 years. 3. OTHER TYPES OF ECZEMA 3.1. Irritant Contact Dermatitis 1) Diagnostic features The affected sites characteristically conform to history of specific contact to a susceptible contactants. Some non-exposed areas are also susceptible to irritant contact dermatitis, e.g., body folds and flexural areas, due to a combination of friction and direct contact with sweat or urine. Once exposure to the irritant ceases, improvement start to occur. 2) Clinical presentation Strong irritant contact dermatitis can occur after a single brief exposure. The latent period is short. Examples are acid and alkaline burns, thermal burns and frost bites. The offending irritant is usually obvious. Weak irritant contact dermatitis develops after multiple exposures, latent period is long. 3) Management The offending irritant should be identified and removed. Soap and detergents should appropriately be minimized. Cool water is less detrimental than hot water. Advice on the use of protective barriers whilst at work, e.g., gloves, protective clothes etc. should be strictly followed by the patient. Restoration of the lipid layer can be accomplished by frequent application of emollients. In case of maceration, wet clothing should be changed frequently, nonporous clothing to be avoided. Inflammatory element can be controlled with topical steroid. 3.2. Allergic Contact Dermatitis 1) Diagnostic features The characteristic distribution of the lesions can often gives a clue to a particular allergen (Table 3). Removal of the suspected allergen leads to resolution of the dermatitis. A positive patch test to a suspected offending contactant support the clinical diagnosis. 2) Clinical presentation a) Both allergic contact dermatitis and irritant contact dermatitis bear similar clinical signs. In acute cases weeping and crusting will be present, while in
chronic cases scaling and fissuring are the dominant findings. Sometimes, allergic contact dermatitis differs from irritant contact dermatitis in that erythema and edema may be more prominent and pruritus more troublesome in the former. b) Systemically induced allergic contact dermatitis: Patients who have been sensitized to topical allergens may develop generalized eczematous inflammation if these allergens or chemically related substances are ingested. e.g. Patient with a history of nickel allergy may get a widespread flare when he takes food rich in nickel; patient sensitized to topical ethylenediamine may develop generalized inflammation following treatment with aminophylline. c) Airborne allergic contact dermatitis and photodermatitis have a similar distribution. Look for sparing in the upper eyelids, areas below the chin, and the Wilkinson's triangles behind the ear. Table 3: Distribution of Allergens Location Material
Scalp and Shampoo, hair dyes, topical medicaments ears Eyelid Face Neck Nail polish, cosmetics, contact lens solution, metal eyelash curlers, topical medicaments Airborne allergens, cosmetics, sunscreen, acne medications, aftershave lotion Necklaces, airborne allergens, perfumes, aftershave lotion Topical medicaments, sunscreens, plants, clothing, undergarments (e.g., elastic waist band, spandex bra), metal belt buckles Deodorant, clothing Watch and watchband Soaps and detergents, foods, poison ivy, industrial solvents and oils, cements, metal, topical
Trunk Axilla Arms Hands
medications rubber gloves Genitals Anal region Lower legs Feet Rubber condom, allergens transfers by hands Haemorrhoid preparations, antifungal preparations Topical medicaments, dye in socks Shoes, cements spilling into boots
3) Management a) The first step is the identification and removal of the contactant. A detailed history and a careful examination is usually sufficient. Patch testing* is indicated for cases in which inflammation persists despite avoidance and appropriate topical therapy. b) For acute inflammation with blisters and intense erythema, cold wet compresses e.g. KMnO4 are highly effective. They should be used for 15 to 30 minutes several times a days until blistering and severe itching is controlled. Prednisolone, in dosage of around 30-40 mg a day in divided doses is used for extensive inflammation. Topical steroids for reduction of local inflammation. * Patch Testing 1) 23 materials in the European Standard Screening Series are employed in Social Hygiene Service (Table 4). More description about Patch test is available in Chapters 1 and 18. Whether or not the allergy demonstrated by the patch test is relevant to the patient's dermatitis must be determined by the critical judgment of the physician. 2) Contraindications to patch testing: a) Acute widespread dermatitis. b) Ongoing systemic steroid therapy. Defer till at least 1-2 weeks after steroid therapy. Table 4: European Standard Screening Series and Examples of Common Sources ¡@ ¡@ Potassium dichromate Neomycin sulphate cement topical medicaments
Thiuram mix Paraphenylenediamine free base Cobalt chloride, 6H2O Benzocaine Formaldehyde Colophony Quinoline mix Balsam of Peru Black rubber mix Wool alcohols Mercapto mix Epoxy resin Paraben mix Paratertiarybutyl phenol formaldehyde resin Fragrance mix Ethylenediamine Dihydrochloride
rubber products (shoes, balloons), pesticides hair dyes, azo dyes, fur dyes, leather dyes, photodeveloper in all almost all trades and industry, nickel and cobalt often occur together topical anaesthetics glues, paper, clothing, cosmetic e.g. shampoo adhesive plasters, paper, plaster, polishes and waxes antiseptics in topical therapeutics cosmetics (perfumes, flavours) rubber products lanolin, vehicles shoes, rubber products glues, pastes, insulator, building material preservatives and vehicles in medicine and cosmetics leather, adhesive and rubber systems stabilizer in medical products medicaments
¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@ ¡@
Quaternium 15 Nickel sulphate
cosmetics earrings, metal tools, clothing accessories, cheap ornaments the allergen in P obconica, which mingle with house dust causing dermatitis.
¡@ ¡@ ¡@
Mercaptonbenzothiazole plant Sesquiterpene lactone mix ¡@
3.3. Common Patterns of Hand Eczema 3.3.1. Pompholyx 1) Recurrent eruptions of minute, non-inflammatory, vesicles on fingers, palms and soles is characteristic. Pruritus is common, sometimes lesions can be painful or it may be asymptomatic. Scratching of vesicles leads to weeping and crusting. 2) Management KMnO4 soaks, oral antihistamines and application of mid to high potency steroids for mild cases. A short course of oral steroid is required for severe cases. Psychological factors are important. Counselling, behavioral modification may be necessary. 3.3.2. Keratolysis Exfoliativa This is a common chronic asymptomatic non inflammatory bilateral peeling of the palms and soles. Its cause is unknown. The eruption is most common during the summer months and often associated with sweaty palms and soles. Scaling starts simultaneously from several points on the palms or soles with 2 or 3 mm in diameter round scales that appear to have originated from ruptured vesicles; however, such vesicles are never seen. The scales continue to peel and extend peripherally, forming larger roughly circular areas that resemble ringworm, while the central area become slightly red and tender. The condition resolves in 1 to 3 weeks and requires no therapy other than lubrication. 3.3.3. Fingertip Eczema A very dry chronic form of the palmar surface of finger tip. Usually of unknown cause, but may be the result of an allergic reaction. One or several
fingers may be involved. Initially the skin is moist; gradually becomes dry, cracked and scaly. The process usually stops shortly before the distal interphalangeal joint is reached. Fingertip eczema may last for months or years and is resistant to treatment. Treatment is by avoiding irritants and frequent lubrication. Topical steroid with or without occlusion may give temporary relief. Tar is an alternative treatment. Allergy and psoriasis may have to be excluded. 3.3.4. Ring Eczema An irritable patch of eczema under a ring and tends to spread to adjacent area. This affects mainly young women soon after marriage or childbirth. If the ring is transferred to the other hand, the eczema will appear at the new site. The cause is due to concentrations of detergent beneath the ring and repeated friction. Removal of the ring often brings remission. 3.3.5. Hyperkeratotic Eczema Plaques of yellow-brown dense scale increase in thickness and form deep interconnecting cracks over the surface, similar to mud drying in a river bed. Occurs on the palms and occasionally soles. Hyperkeratotic eczema may result from allergy or excoriation and irritation, but in most cases the cause is not apparent. Differential diagnoses may be psoriasis and lichen simplex chronicus. They may respond to potent steroid and occlusion, but recurrence are frequent. 3.4. Nummular Eczema 1) Clinical presentation Nummular eczema (discoid eczema) is characterized by circular or oval plaques of eczema with a clearly demarcated margin . The typical lesions are coin-shaped, 1 to 5 cm in diameter itchy plaques. There are commonly distributed on the extremities and can become generalized. Acute lesions may be vesicular; chronic lesions may become scaly, cracked and confluent. 2) Differential diagnoses Allergic or irritant contact dermatitis have primary lesions conform to area exposing to allergens/irritants, and a contact history is often present. Ringworm infection presents as annular, scaly erythematous patches or plaques with central clearing. Psoriatic plaques are well marginated with prominent scales. Irritation is variable. Lesions of chronic superficial dermatitis are dry, indolent patches. 3) Management Treatment is similar to other forms of eczema and depends on the stage of activity. A course of mid to potent topical corticosteroid combined with
topical or systemic antibiotic is effective since infection is commonly associated; however, relapse is not uncommon. 3.5. Asteatotic Eczema (xerotic eczema, eczema craquele)? 1) Diagnostic feature Lesions are mainly distributed over the hands and legs; and consist of minute, thin fissures, with minimal inflammation. 2) Clinical presentation It commonly occurs in the elderly and people with dry skin especially in winter times when the humidity is low. The condition is thought to due to a reduction of in skin surface lipid. Distal parts of the extremities especially the legs are affected. The skin is dry, slightly scaly and criss-crossed on the surface to produce a reticulate pattern. The borders of this reticulation can become erythematous and slightly raised, and finally eczematous. The patient feels itchy, sting and burnt. 3) Management The mainstay of treatment is to reduce moisture loss and to maintain the surface lipid layer. Reducing the bathing frequency to an acceptable level; avoiding hot bath, restricting soap are good measures. Ordinary soaps should be replaced by soap substitute and emollients should be used as frequently as appropriate. Inflammation can be controlled by application of mid potency topical steroid ointment. 3.6. Stasis Dermatitis (Gravitational eczema, Varicose eczema, Venous eczema) 1) Diagnostic feature A history of preceding non-inflammatory swelling, distributed over the ankles and association with varicose veins. 2) Clinical presentation Acute inflammation is characterized by a red, superficial, itchy plaque with weeping and crusting on the lower limbs especially the medial side of lower legs, ankles and calves. This is due to a combination of eczematous changes and cellulitis. A vesicular eruption (id reaction) on the palms, trunk, extremities sometimes accompanies this acute inflammation. In subacute and chronic stages, an increased hydrostatic pressure lead to extravasation of red blood cells from the leg veins. Disintegration of these red blood cells lead to haemosiderin deposition. The skin looks dry, scaly, hyperpigmented and accompanied with white atrophic changes ('atophie blanche'). Ulceration is common in the late stage and is a serious consequence. 3) Aetiology Venous insufficiency is a major factor but not all patients with venous insufficiency develop stasis eczema. Allergic response to an epidermal
protein antigen created through increased venous pressure, susceptibility to minor trauma and irritation are the contributing factors. Patients with stasis eczema are more prone to develop hypersensitivity reaction to topical medicaments. Topical medicaments that contain potential sensitizers such as lanolin, benzocaine, parabens and neomycin should be avoided by patients with stasis disease. 4) Management The dry eczematous inflammation can be managed with lubricants and topical corticosteroids. Moist exudative inflammation and moist ulcers respond to tepid wet compress of KMnO4 solution several times a day. Any infection should be identified and treated promptly. Oral antibiotic appropriate to the organism is more preferable than topical antibiotic which should be avoided. Physiotherapy, elevation of legs and compression stocking are helpful. Patients with varicose veins should be referred to the vascular surgeons for early assessment and prompt treatment. 3.7. Lichen Simplex (Circumscribed Neurodermatitis) 1) Definition Lichenification denotes a cutaneous response to repeated rubbing or scratching. It is characterized clinically by a thickened appearance of the skin, with accentuation of the surface markings so that the affected skin surface resembles tree bark. Lichen simplex is a circumscribed area of lichenification resulting from repeated rubbing and scratching occurring on some predilected sites. This term is used when there is no known predisposing skin disorder. 2) Clinical features Women are more common affected than men. Pruritus is the predominant symptom and is often out of proportion to the extent of the objective changes. During the early stages the skin is reddened and slightly oedematous, and the normal markings are exaggerated. The redness and oedema subsided and the central area becomes scaly and thickened and sometimes pigmented. Almost any sites are affected, but the commonest sites are those that are conveniently reached. The usual sites are the nape of the neck, the lower legs and ankles,. the sides of the necks, the scalp, the upper thighs, the vulva, pubis or scrotum and the extensor forearms. 3) Management A search for a causation should be made before the lichenification is considered to be primary, then a careful psychological history should be taken and the patient given some assistance in reducing her tensions. Topical steroid is the treatment of choice, sometimes with occlusion to enhance absorption and prevent further scratching. Intralesional triamcinolone is
useful for circumscribed chronic lesions. Topical antibiotic may be prescribed if secondary infection is present. 3.8. Seborrhoeic Dermatitis 1) Diagnostic feature Seborrhoeic dermatitis is characterized by a distinctive morphology (red, sharply marginated lesions covered with greasy looking scales) and a distinctive distribution (scalp, face and upper trunk) which are areas rich in sebaceous glands. 2) Clinical patterns a) Adult (may be associated with Parkinsonism and HIV infection) Scalp Dandruff is usually the earliest manifestation. In chronic cases, there may be hair loss which is reversible when the inflammation is controlled. Ears are a common site of involvement. Face Medial sides of the eyebrows, glabella, nasolabial fold, are predilected sites . Blepharitis is a feature. Trunk Petaloid form is commoner than the pityriasiform. Follicular papules with greasy scale that may become confluent, and commonly found over the sternum and interscapular region. b) Infantile The eruptions in infants frequently first appear between the third and eighth weeks of life. It may start in the napkin area, the face and scalp, and occasionally on the trunk outside the napkin area. The rash comprises welldefined areas of erythema and scaling with tiny vesicles. Papular and lichenified lesions are not seen. Typically the infant is well and not irritable (c/w atopic dermatitis). The prognosis is usually good. Most uncomplicated cases clear in 3 to 4 weeks. 3) Differential diagnoses Psoriasis, pityriasis rosea, pityriasis versicolor, drug eruption and lichen simplex in adult. Intertrigo, irritant contact dermatitis, atopic dermatitis, psoriasis, histocytosis X and eczematous eruptions in immunodeficiency disorders in infants. 4) Management a) Adults Ketoconazole shampoo is very effective in removing dandruff. Shampoos that contain salicylic acid, selenium sulphide, zinc pyrithione and tar are alternatives. For thick scalp scale and crust, sulphur salicylic emulsion can be applied before bed and shampooed next morning. Steroid lotion applied twice daily provides symptomatic relief but may relapse.
Lesions on face, chest can be treated by weak topical steroid and antiseborrhoeic shampoo. Washing the affected areas with soap can be a useful adjunct. 2% Ketoconazole cream once a day is highly effective in difficult cases. Scaling of blepharitis may be suppressed by frequent washing with zinc or tar containing antidandruff shampoos. Prolonged use of steroid lotion on the eyelids causes glaucoma and should be avoided. 2% ketoconazole cream once a day should be tried in resistant cases. b) Infants Cradle cap should be oiled regularly with warm olive oil and washed off few hours later with 5% cetrimide shampoo. Erythema and scaling on the body can be treated with weak topical corticosteroid cream +/- topical antibiotic if infection is present. Shampoo that contains salicylic acid or selenium sulphide should be avoided in neonates for the risk of systemic absorption. PSO RI ASI S Dr. K.K LO & Dr. L.Y. HO CH APTE R 4 1. INT RO DU CTI ON Psoriasis is a chronic inflammatory disease of unknown cause. It is now considered to be due to T-lymphocytes mediated disease of abnormal keratinocyte proliferation in genetic predisposed subject. In 1995, Psoriasis is the sixth commonest skin condition found in all new cases attending dermatology clinics of Social Hygiene Service (4.18% of all new cases) and it is one of the common skin diseases worldwide. Although there is no study in the documentation of the exact number of psoriatic patients or prevalence of the disease in Hong Kong, the disease is commonly presented even in the primary care setting. There had been analysis in the figure of some local dermatology clinics of Social Hygiene Service in 1974 to 1976 and comparison with some of the larger cities in China, Taiwan and Japan claiming the number of psoriasis in the Mongoloid race to be around 0.3% or well below 1%. 2. CL INI CAL FE ATU RE Psoriasis is a chronic erythemato-squamous condition characterized by sharply circumscribed salmon pink patches, plaques covered with silvery scales. The onset of the disease is usually gradual and becomes noticeable by the patient from 30 years onwards. However, in patient with family history positive for psoriasis, there may be earlier onset at teenager or even below ten. In these
cases, the prognosis is worse. From a study in China, the majority (97.98%) of the types of psoriases is the psoriasis vulgaris or chronic plague type. We have similar experience in Social Hygiene Service with over 91% of the psoriasis are chronic plaque type (see Table 1). The classification of psoriasis may vary with different author's preference but for simplicity and practicability, we take the following classification for psoriasis: I) Non-pustular psoriasis II) Pustular psoriasis III) Psoriasis with arthropathy. They can be subclassified further into: 2. 1. No n- pu st ula r Pso ri asi s Chronic Plague type Acute Guttate Inverse, flexural Erythrodermic Regional: Scalp, palms & soles, nails Unstable nummular Sebo-psoriasis 2. 2. Pu st ul ar P so rias is Generalized Pustular psoriasis (von Zumbusch) Localized pustular psoriasis of palms & soles 2. 3. Ps or iasi s w ith Ar th ro pa th y 5 Types of arthropathy found: oligoarticular asymmetrical arthritis, symmetrical involving small joints of fingers likes rheumatoid arthritis, classical distal arthropathy involving distal interphalangeal joints, destructive arthritis mutilans and psoriatic spondyloarthropathy which is similar to ankylosing spondylitis. Two interesting phenomena occur in Psoriasis. They are mutually exclusive: Koebner and reverse Koebner responses. Any form of trauma may result in psoriasis appearing in the traumatized areas which is known as Koebner phenomenon or isomorphic response. A degree of healing may occur when a psoriatic plague is traumatized which is the reverse Koebner phenomenon. It also explains why some patient found cryotherapy is useful to suppress psoriasis.
The commonest form of psoriasis is the chronic plague type which usually presents as brightly erythematous scaly plagues at the predisposed areas i.e. the extensor aspect, the tip of elbows, knees, sacral area, the scalp. They may be
associated with no symptoms to moderate pruritus. Excessive dandruff and scaling from the lesional area may be an early complaint. Family history is not very commonly found in this group because the other family members may not have the disease at all or if possess, usually in a very mild degree. Patient may have history of acute guttate psoriasis before but it either never clears or reappears as plague form. The most useful form to confirm the diagnosis is to use the wooden spatula to scrape the surface of the suspected lesion, profuse
silvery scaling can easily be generated . The well demarcated border of the plague, the prominent scaling, other associated findings such as symmetrical distribution with scalp involvement, Auspitz¡¦s sign (to forcibly remove the superficial scaling of top of the psoriatic plague will reveal the fine dots of bleeding points) and the characteristic colour which is also quite obvious in Chinese patients will lead to the diagnosis of the disease without difficulties. The course of the disease is very chronic. We seldom see a case of persistent, sustained long term remission because either remission may not be common (it had been quoted from 20 to 50% when following the psoriatic patient long enough e.g. 50 years), or remitted patient will not turn up in the clinic to thank you, or patients seen by different doctors every time attending Social Hygiene Clinic. It usually waxes and wanes, tend to improve in summer and worsen in winter. However, with correct therapy, majority can lead normal life and there is definitely a chance of spontaneous remission though the younger the onset of the disease, the more likely it will persist till elderly. The presence of a strong positive family history will be another poor prognostic factor. However, other forms of psoriasis though much rare, they do present diagnostic problem occasionally. The erythrodermic psoriasis may be mistaken as other causes for erythroderma such as seborrhoeic eczema, drug eruption, pityriasis rubra pilaris. Flexural psoriasis may lack the prominent silvery scaling because the flexural areas affected usually appear as brightly erythematous, homogenous, well defined and sharply demarcated plaque or patch with or without superinfection with Candida. Acute guttate psoriasis is often preceded by a history of sore throat 10 days to 2 weeks ago. It may be a streptococcal infection. The small guttate maculopapular
scaly lesion still have the characteristic feature of psoriasis and hence there will be no diagnostic problem. Occasionally, pityriasis rosea, pityriasis lichenoides have to be excluded. The course of the disease initially will go into remission in few months time but it can reappear after another attack of infection and many do gradually become a chronic plaque type case. Regional psoriasis involving scalp, palm and soles are relatively common. They are often misdiagnosed as seborrhoeic dermatitis, keratoderma or chronic eczema of hand and feet before the more definite sign of psoriasis appear. Fortunately, the types of treatment do not differ much. Unstable nummular psoriasis can occasionally be seen and they have tendency to change from time to time, to either erythrodermic psoriasis or pustular psoriasis. There is low erythema threshold in this group of patients. Usually they are found in patients with psoriatic arthropathy. Topical irritants or sudden withdrawal of topical steroid may prone this group of patients flaring up of their diseases and they may be required hospitalization for stabilization. Localized pustular psoriasis of palms and soles usually present as symmetrical, monomorphic eruption of small sterile pustular eruption on hands and feet. They are painful rather than pruritic. Very often, brownish thick wall pustules are found. They are resistant to treatment and will be quite disabling. Another form of local pustular psoriasis is asymmetrical involvement affecting distal phalanx with nail destruction. It is called acrodermatitis continua. It may change to generalized pustular form. Generalized pustular psoriasis can present in a psoriatic prone patient who is given systemic steroid for other conditions and upon sudden withdrawal of the steroid, generalized pustular psoriasis will be precipitated for the first time. Occasionally, it develops from the unstable nummular psoriasis or acrodermatitis continua after inappropriate irritant therapy or withdrawal of extensive topical steroid. Pregnancy can sometimes associate with the generalized pustular psoriasis. There are low grade fever, pain and burning sensation over the pustules. Systemic and constitutional upset may be severe. This requires inpatient management with bed-rest and institution of transient systemic therapy. Many doctors may not consider the existence of this condition: sebo-psoriasis or seborrheic psoriasis. Very often, we can encounter conditions in which both psoriatic and seborrheic eczema features are present. We consider this a separate entity because it is not rare. Genetically constituted psoriatics can develop
seborrhoeic eczema lesions at the scalp, eyebrows and regions of ears with characteristic morphology of psoriasis at these sites. Nail involvement is commonly seen in all types of psoriasis which can affect the nail matrix and nail bed leading to pitting, discoloration, subungual hyperkeratosis, onycholysis, splinter hemorrhage. Circular area of discoloration of nail bed resembling an oil drop underneath the nail - oil drop sign is most characteristic for psoriatic nail. Patients with AIDS develop severe recalcitrant form of psoriasis and psoriasis related disease such as Reiter¡¦s disease. The use of etretinate and anti-viral therapy such as zidovudine are necessary to control this type of psoriasis. The clinical features of psoriasis especially chronic plaque type is so obvious and unique that seldom requires further investigations. However, differential diagnosis should be remembered especially for other types of psoriasis. Eczema, psoriasiform drug eruption, lichen planus , discoid lupus erythematosus, lichen simplex chronica, pityriasis rubra pilaris, secondary syphilis, Bowen¡¦s disease, Paget¡¦s disease and superficial fungal infection will mimic chronic plague type psoriasis. Pityriasis lichenoides chronica, pityriasis rosea can resemble guttate psoriasis. Candidal intertrigo, Hailey disease may be mistaken as flexural psoriasis. The keratoderma blenorrhagica (palmoplantar lesions) of Reiter's disease will be indistinguishable from localized pustular psoriasis. 3. IN VESTI GAT ION Skin biopsy is the most useful investigation e.g. in erythrodermic psoriasis. The typical histopathology of psoriasis (non-pustular form) is characterized by: 1) regular elongation of the rete ridges with thickening in their lower portion. 2) elongation and edema of the papillae. 3) thinning of the suprapapillary portions of the stratum malpighii with the occasional presence of a very small spongiform pustule. 4) the absence of granular layer 5) parakeratosis 6) presence of Munro microabscesses. Radiological examination of the affected joints may confirm the psoriatic arthropathy. The following findings are characteristic signs of psoriatic arthropathy: 1) destructive distal interphalangeal arthropathy with bony ankylosis of the interphalangeal joints 2) abnormally wide joint spaces and well
demarcated adjacent bony surfaces 3) bony proliferation of distal phalanx in great toe 4) resorption of tufts of distal phalanges of hands & feet. 4. MA NA GEMENT I N S OC IAL H YG IENE SE RV ICE 4. 1. Ge neral Management of psoriasis requires a complete thorough history not only for the disease activities but also to include information about how the patient perceive and handle this condition in the past, the past treatment, the failed treatment and possible the cause of failure of the treatment. The sex, occupation and social background are all important factors to consider in the management and it will be very true that every patient will present an entirely different problem. The degree of acceptance of the condition by the patient and the knowledge on the condition will also affect the management plan. Dietary manipulation has no place in management of psoriasis. Stress is one of the factor contributory to flare up of the condition though not agreed by all and stress can also be one of result of deteriorating psoriasis. Chinese herbs are not recommended because no single good control study have proven these to be effective alone without using the traditional western anti-psoriatic medication simultaneously. Many harmless placebo have been tried on this condition and it will not be surprising to read one or two reports claiming good effect on psoriasis, the progression of which can be affected by so many factors. Alcohol intake should be discouraged because there is a positive correlation between psoriasis and alcohol intake and alcohol induced liver problems may preclude patient from receiving effective systemic therapy in future. Medications such as lithium, salicylates, iodine, beta blockers, naprosyn and penicillin have been implicated in exacerbating psoriasis. 80% of patients with psoriasis find that sunlight improves their conditions but the rest may find no change or even exacerbation. However, sunburn is always a precipitating factor because the scalded area will heal with new crops of psoriasis (the Koebner's phenomenon). Streptococcal infection if persistent or carried in the deep tonsil crypts should be eradicated with a course of antibiotics. Some of the known aggravating factors if correctable should be removed or avoided. Climatotherapy can only be afforded by the rich and retired patients. 4. 2. To pi cal 4.2.1. Emollient
It is indeed very useful to decrease fissure, cracking and scaling. Aqueous cream, Ung Emulsificant and 10% urea cream are commonly used by Psoriatics. 4.2.2. Tar Pinetar, Coal tar are all useful. They can be in the lotion, shampoo, cream, paste, ointment forms. The commonly used items in Social Hygiene Service are: 3% tar paste, Ung 2-4-2 or Ung 1-2-1, 1% crude coal tar. They are good for the stable chronic plaque type. However, slow action, messy and sticky, poor smell, staining properties are all factors for its low acceptance in patients. Education and persuasion to patients are necessary to insist using the cream for few months' time before giving it up. It is an adjunctive component in the Goeckerman's regimen. 4.2.3. Sulphur and salicylate 2% sulphur salicylate emulsion is a very common prescribed item to thick scalp psoriasis for its keratolytic effect. 4.2.4. Topical steroid It is widely used not only by dermatologists but by the primary care doctors. Moderate potent steroids have to be used to suppress the psoriasis. Good examples are Synalar, Betnovate, Dermovate creams or ointments. However, only careful dermatologists will know when to stop them to avoid tachyphylaxis and rebound of the condition and what to control during the period of withdrawal. The combination of topical corticosteroid and other topical agents, such as tar and salicylic acid is often effective in refractory areas. The use of liposome packaging to increase the delivery of corticosteroids to the epidermis is under clinical trial in psoriasis. 4.2.5. Topical calcipotriol (Daivonex) cream It has similar efficacy as that of potent steroid but lacks the local adverse effect of skin atrophy, rebound phenomena and tachyphylaxis. The main indication is for chronic plague psoriasis. Its main drawback is irritant dermatitis especially over flexural and face area. New calcipotriol formulations, gel and lotions, cause less irritation than ointment. Cutaneous absorption is probably the most worrisome side effect. The 50 m g/g ointment formulation can be used twice daily. 100 gm of this ointment used per week is the maximum safety dosage so as not to induce hypercalcaemia. An arbitrary pulse topical therapy can also be adopted. Topical Calcipotriol ointment or cream is used in weekdays but it is
switched back to potent topical steroid in weekend and off all medication on Sunday. It will help to reduce tachyphylaxis of steroid. 4.2.6. Dithranol 0.25% dithranol in Lassar paste can be tolerated by some patients with plaque type psoriasis at the shins, elbows and knees and with good therapeutic result. However, careful instruction of how to use and olive or mineral oil to remove the paste have to be prescribed as well. In-patient will be a good chance of giving a trial of this preparation. Adjunctive phototherapy as in Ingram regimen will be very helpful but only is possible in in-patient or day care centre. The commercial preparation of 1 to 4% Dithranol ointment is good for the SCAT (Short contact Anthranol therapy). It is because the staining and stinging sensation that most patient dislike this regimen. 4. 3. Sy stem ic T herap y The indications of systemic therapy will vary from one patient to the other because the degree of severity will be perceived differently by different patients with some correlation to the need or occupation of the patient. The choice of treatment depends on a number of factors such as: severity, extent, site of disease compliance, intelligence of patient sex (chance of conception), age of patient presence of other systemic illness or skin conditions financial and time factors, motivations limiting factors from available treatment facilities distance from treatment centre to home or working place the type of psoriasis 4.3.1. Etretinate (Tigason) Avoid using the medication in reproductive female in order to prevent pregnant patient receiving the drug which is teratogenic. Absolute contraception must be practiced in some difficult case and this must be continued for two years after stopping the medication (because of high lipophilic property and long elimination half-life of 80 days). The newer acitretin was found to be of much shorter half life (elimination half-life of 50 hours) but because of some conversion back to etretinate was detected, its enthusiastic future is jeopardized. Avoid treating patients with overt symptoms of ischaemic heart disease or patients that are at definite risk for developing atherosclerosis. Handle patients
with preexisting hyperlipidaemia carefully, it is a relative contraindication. Dietary regulation and recommendations about increase physical activity should be given. Low fat, low calorie diet, avoidance of alcohol intake and increasing physical activity are effective in reduction of hyperlipidaemia induced by the drug. Hyperostoses can be induced after several years of continuous treatment with etretinate. Minor side-effects are unavoidable and dose related. Dryness of the lips, nasal mucosa, eyes, mouth, throat or vagina, painful exfoliative cheilitis, urethritis, balanitis, gingivitis, peeling of finger tips and corneal ulceration, burning sensations in the skin, diffuse alopecia, epistaxis, widespread erythema will be present to various degree. Slight elevation of liver enzymes may be found. Toxic hepatitis may occur especially when it is combined with methotrexate. The long term effect of hyperlipidaemia, hyperostosis resembling diffuse idiopathic skeletal hyperostosis (DISH) will be problematic in psoriatic patients on long term etretinate therapy. The initial dose will be between 0.5 mg and 1 mg/kg/day. The response is very often dose related. Dose reduction is possible when it is used in combination with phototherapy or photochemotherapy. They are one of the most effective combination in clearing psoriasis. Etretinate alone seldom can control psoriasis perfectly and useful adjunctive therapy with phototherapy, PUVA, steroid cream will be very synergistic. It may also be used in generalized pustular psoriasis although methotrexate works as good or better. Etretinate is indicated for moderate or extensive psoriasis, pustular psoriasis and psoriasis resistant and poorly controlled with all forms of topical therapy. Patient should be excluded for the following conditions before initiating treatment: liver disease, hyperlipidaemia, pregnancy or potential pregnancy, previous history of hypersensitivity to retinoid and history of elevate cerebrospinal fluid pressure. Monitoring with fasting lipid level and periodic liver function are required monthly initially and then every few months when stabilized. 4.3.2. Methotrexate It is a magic drug for psoriasis provided adequate monitoring is provided. It is given as once weekly to once biweekly doses. An initial test dose of 2.5 mg was given and complete blood picture and liver function test should be monitored for a few days before the full planned dose is given. Usually 7.5 to 25 mg per week as a single dose can be given according to body weight of patient and response
of disease. Before initiating treatment, renal (renal function tests), hepatic function (history, liver function tests and if feasible a preliminary liver biopsy), and complete blood picture should be taken to ensure no contraindication. Peptic ulcer and infection must be treated before starting therapy. Impaired renal function must be accompanied by dose reduction. Continuous recording of the cumulative dose in a chart together with liver, marrow and renal function will be very helpful. Complete blood picture and liver function test should be taken regularly every month initially and then every 3 to 6 months for monitoring. When the cumulative dose reach 1.5 to 2.0 gm, a liver biopsy is advised and this investigation at present is not replaceable by other methods, e.g. hepatic or CT scan. Early fibrosis and cirrhosis found in biopsy are indications for stopping the therapy whereas fatty change and mild inflammatory changes can allow continual therapy if the condition is compelling. If patient refuse to have the liver biopsy, no more methotrexate should be give. For those who have normal result on liver biopsy, another cumulative dose of methotrexate of 1.5 to 2.0 mg reached before the second biopsy done to monitor the liver function. This usually takes 2 to 3 years. The guidelines for liver biopsy of patients receiving methotrexate is now controversial. Low dose (< 15 mg weekly), long term methotrexate may be less hepatotoxic than previously thought and liver biopsy is not entirely without risk. Therefore risks and cost effectiveness should be carefully balanced. Methotrexate is teratogenic and conception is not advised within 3 months of stopping treatment. Other side effects include: anemia, leukopenia, anagen alopecia, cutaneous erosions, ulceration, reactivation of tuberculosis, septicemia, gastrointestinal bleeding, oligospermia, anorexia, nausea. Despite all these side effects, methotrexate is highly effective for many forms of psoriasis and also psoriatic arthropathy. It is available as 2.5 mg tablets and injection form (for intramuscular injection). 4.3.3. 5-Hydroxyurea Hydroxyurea causes short term reversible marrow suppression and hence complete blood picture must be monitored closely. It is given from 500 mg daily to 1,500 mg daily with a modest fall in hemoglobin expected. Mild GI upset may be associated. It is unfortunately not very effective in many psoriatic patients and it is of slow onset. The therapeutic effect may not be apparent after 2 months of therapy. It can be tried for patient with impaired liver function.
4.3.4. Cyclosporin A (Sandimmun-Neoral) This is a powerful medication. Improvement may be seen within few days with a dose of 3 mg/kg/day. If there is no improvement within 2 weeks, the dose may be increased by 0.5 to 1 mg/kg/day at a 2-weekly interval to a maximal dose of 5 mg/kg/day. Maintenance dose should be reduced to the smallest dose that allows adequate control. Relapse is inevitable after cessation of treatment but fortunately rebound is not a problem. The most important side-effects are dose related hypertension and nephrotoxicity. Hence blood pressure and renal function (creatinine clearance) should be closely monitored in the first few weeks, then monthly. Other sideeffects include gum hyperplasia, hypertrichosis, acral paraesthesia or hyperaesthesia, tremor and dyspepsia. Cyclosporin should not be given to patients with renal dysfunction, uncontrolled hypertension, past or present malignancy, acute infections, pregnancy, lactation and known hypersensitivity. Cyclosporin is expensive but this low dose regimen for psoriasis is the last resort for patients with resistant psoriasis to other therapies or contraindicated for one reason or another. Even if the patient can afford to purchase the medication himself, it should not be used indiscriminately because the theoretical risk of prolonged immunosuppression and possible risk of lymphoproliferative malignancy. 4. 4. Ph ot oth era py a nd P ho toc hemo the rap y 4.4.1. UVB Phototherapy Suberythemogenic doses given 2 to 3 times weekly can clear psoriatic lesions in a few weeks. The compliance of patient depends very much whether the patient can afford to spare time for this form of treatment. The power of Phototherapy unit varies one from the other. In old models, the irradiation time may well be over 10 to 20 minutes but newer models will deliver the MED (minimal erythema dose) within 100 seconds. At the first visit, a test area is needed with increasing doses of UVB to find out the optimal doses. Usually the darker the skin, the greater dose is required for reaching the MED (similar the skin types in Caucasian). It has been estimated in the West temperate regions, the annual UVB dose an outdoor worker receives is 500 MEDs, while an indoor worker receives 200 MEDs. A psoriatic patient on maintenance therapy receives more than 700 MEDs. The long term life-time incidence of non-melanoma skin cancer in patients receiving long term UVB
phototherapy is estimated to be three times to eight times that of normal. Long term follow up later in life is necessary in order to pick up skin cancer. The other side effects include pruritus secondary to xerosis, sun burnt and flare up of Herpes Simples infection. Emollient applied on the skin before irradiation will enhance the therapeutic effect and it will antagonize the drying effect of UVB phototherapy. Cumulative dosage of UVB should be recorded clearly in patient¡¦s record. The addition of etretinate will help to lower the dosage or frequency of UVB phototherapy. In pregnant psoriatic woman, phototherapy may be the best to control psoriasis and least effect on the fetus. 4.4.2. Goeckerman Regimen This is mainly a regimen for in-patient or day care centre patient. It is a timeconsuming but effective methods. The combination of rest, tar, phototherapy all contribute to the success of this form of therapy. Patient is treated either in day care centre or dermatology wards. Experienced dermatology nurse will be essential to carry out this form of therapy. 1% crude coal tar will be applied in the morning and again at afternoon. In the later part of morning the residual tar is removed by bathing with Liquor Picis Carbonis and a suberythemogenic dose of UVB is administered, follow which the tar is reapplied. Tar is best applied with a paintbrush or a wooden spatula covered with layers of tubular cotton gauze. Dressings maybe applied before the tar dries. No powder is needed. The removal of tar is best done by softening the tar with an application of coal tar and salicylic acid ointment, followed by the tar bath. The main complication of this treatment is folliculitis. Majority of the patient will have extensive plaque psoriasis cleared, thinned or controlled after 3 weeks treatment. 4.4.3. Ingram Regimen It is similar to that of Goeckerman regimen except that 0.25% Dithranol in Lassar Paste is applied instead of 1% crude coal tar. It is applied once daily usually after the UVB therapy. It is difficult to spread in applying the paste to the lesions. Since dithranol is a strong irritant and stains linen, accurate localization of the medication is needed to prevent burning of the normal surrounding skin which may be protected by using some barrier cream e.g. zinc cream surrounding the psoriatic lesions. It is not used in pustular psoriasis and unstable psoriasis. Dusting with talcum powder and covering with old nylon
tights helps to prevent the spread of dithranol especially if a modern ointment form is used instead of the lassar paste product. Olive or mineral oil may be needed to remove the stiff paste before going to take the tar bath prior to UVB therapy. It has similar efficacy as that of Goeckerman regimen. 4.4.4. PUVA (Systemic and Topical) 0.6 mg/kg of 8-methoxypsoralen is taken orally by patient 2 hours before irradiation with UVA (320-400 nm). New model of PUVA machine can irradiate the whole body while patient has to stand upright in the chamber. Old model machine can only radiate one side of body at a time but with the advantage that patient can lie down comfortably. Eye protection is important. During irradiation and after taking the drug that day, patient must wear UVA opaque goggles to prevent cataract and acute photosensitivity of the eyes. Patient is required to have treatment at the day care centre two to three times a week. In Chinese patient, the initial dose can be 2 J/cm2 and then step up the dosage carefully by 0.5 J/cm2 each visit till the optimal dose is reached which may be as high as 8 to 15 J/cm2. Acute PUVA burn can result from a too high initial dose for sensitive patient. Usually 15 to 25 treatment will complete one course and maintenance treatment can be given with weekly or biweekly PUVA for 3 more months. If the psoriasis remains quiet, it can be managed with topical therapy only. In later phase, if there is flare up of condition, a new course will be given again. The duration to complete each course will require 2 to 3 months. When cumulative dose of 2,000 J/cm2 reached, PUVA is usually not advised to be continued because of the substantial increase risk of skin cancer. Patients with cutaneous malignancy potential are excluded for PUVA e.g. Arsenic ingestion, radiotherapy. PUVA is of value in generalized pustular psoriasis, erythrodermic psoriasis, chronic palmoplantar pustular psoriasis. The topical PUVA can be given applying similar principle except that the psoralen is given not in oral form but in the form of topical lotion (the Meladinine Paint) which is particularly convenient for local palm and sole psoriasis. However, phototoxic reaction is more common. The UVA is given as soon as 10 to 15 minutes after the application of the paint. It is commonly used to treat Vitiligo which is limited to the face. Very extensive application of the 8MOP paint is not advisable because of the phototoxic effect and absorption of enough 8-MOP requiring protection of the eyes as in systemic PUVA. However, topical PUVA requires no systemic medication and patient with gastrointestinal
upset of 8-MOP will tolerate topical PUVA and smaller dose of UVA delivered with fewer side effects to normal skin. The adverse effects of PUVA are: Erythema, nausea, pruritus, gross freckling (PUVA lentigines), hyperpigmentation, onycholysis, cataract, increase nonmelanoma skin cancer risk, cutaneous pain and burning sensation, precipitate photosensitive condition such as lupus erythematosus, reduction of delayed hypersensitivity and flare up of herpes. 4. 5. Co nc lu si on i n t he Trea tmen t Mo da lit ies i n S oci al Hy gi ene Ser vi ce The commonest form of treatment for mild psoriasis is topical steroid. For moderate plaque type psoriasis, the topical therapy is usually an adjunctive therapy and the combination of etretinate and phototherapy of photochemotherapy usually have the best result. For severe cases, admission to hospital is necessary for management because bed rest and away from work can already lead to more stable condition. Moreover, the trial of in-patient regimen will work at most time. The last resort is Cyclosporin A. All the systemic therapies have to some extent harmful to the body. They should be selected and supervised by experienced dermatologists. Systemic steroid is very effective in controlling psoriasis but it is deliberately not listed because it will do more harm than good in the long term management. Very often, you may find that there are more problems than before when starting a psoriatic patient with systemic steroid. However, systemic steroid will be given to the poorly controlled pustular psoriasis of pregnancy, life threatening erythrodermic or generalized pustular psoriasis. Very rarely, bullous pemphigoid can be associated with psoriasis. Systemic steroid is needed to treat the bullous pemphigoid and psoriasis will also benefit at the induction high dose. However, a steroid sparing agent has to be started early to prevent flare up on reducing the steroid dose after control of bullous pemphigoid. All these conditions should only be given in in-patient under the supervision and advice of consultant dermatologist. 5. OTHE R TRE ATMENT There are some other forms of treatment for psoriasis not practiced in Social Hygiene Service. They are not used because they are either not gaining consistent results or their limited experience with one or two reports of success or requiring special treatment facilities. Some of the initial improvement may be
solely placebo effect. These are mentioned because they signify how disappointing the treatment to some form of psoriasis and that we are always trying to seek new treatment breakthrough for psoriasis. The treatment of psoriatic nail do place a dilemma for dermatologists. Intralesional corticosteroids injecting to the nail matrix may control some nail dystrophy but it is painful and the control is not complete and not always successful. Avulsion of grossly deformed nail will not correct the deformity. Occasionally, methotrexate or PUVA for extensive psoriasis may also improve the nail. Topical treatment: Occlusive dressings with hydrocolloid dressings. Topical methotrexate, cyclosporin, and retinoids, capsaicin have been studied as potential topical treatment of psoriasis. It is hoped that new effective topical treatments allow dose reduction of potent topical steroids and often systemic modalities, therefore reducing potential toxicities. Systemic treatment: Sulphasalazine, ketoconazole, acitretin, Fumaric acid, Fish Oil supplements, Zinc sulphate, Razoxane (withdrawn because of increase incidence of acute myeloid leukaemia), Azathioprine, Colchicine, Antibiotics, Piritrexim (withdrawal because of unexpected high incidence of liver damage), rifampicin, propylthiouracil, benoxaprofen, topical lonapolene, azaribine and zidovudine for AIDS associated psoriasis. Selective UVB phototherapy (UV sources with peak effective output in the 300320 nm range): Psoralen-311 nm therapy: a narrow-band UVB source emitting 311 nm (compared with conventional PUVA: peak emission at 352 nm) are shown to be effective. The 311 nm UVB phototherapy alone is also effective. This source of UVB light has avoided the non-therapeutic but erythemogenic UVB (of wavelengths of less than 300 nm). Low intensity selective UVB phototherapy (LISUP) has been designed for home use but they are probably less effective than conventional phototherapy. The Dead Sea Clinic treatment (heliotherapy) is basically a form of phototherapy: sun exposure followed by bathing in mineral rich sea. (It is claimed to be cost effective and pleasant treatment. As a result, some Scandinavian countries health clinics prefer to fund Dead Sea Therapy over the expensive in-patient care for chronic psoriatics.) Others: Alternative medical treatment such as acupuncture, dietary manipulation programmes, biofeed back, Chinese herbal treatment, homeopathic remedy. Dialysis, Extracorporeal photophoresis, Propylthiouracil Cryotherapy, Yellow
light laser, carbon dioxide laser, dermabrasion, Grenz ray therapy Tab le 1 : T ype o f P so ria si s in 1 99 5 ( Derma to log y C lini cs o f S ocia l Hy gie ne Ser vice ) Conditions Chronic plaque Guttate Flexural Erythrodermic Generalized pustular Localized pustular Incidence 558 45 0 1 3 2 % 91.6 7.39 0 0.16 0.49 0.33 4.18
All Psoriasis (all new skin cases) 609 (14,569)
ACNE AND OTHER 1.4. Management Apart from general measures, topical treatment alone is usually adequate for patients with mild acne. For more severe acne, combination of a topical agent and an antibiotic, or with hormonal therapy for female patient, is required. It is better to combine agents having different mode of actions - for example a keratolytic with an antimicrobial. For acne conglobate, isotretinoin is the treatment of choice. 1.4.1. General Measures Educating the patient on the nature of the disease and daily skin care is important. The latter should be in form of face cleansing with ordinary soap and water twice daily. Expensive soap or strong detergent are not necessary. 'Facial' treatment (facial sauna, heat and massage) is not only useless but may also worsen the condition by precipitating the development of inflamed lesions. Oily cosmetics and hair greases are comedogenic and causes prommade acne and should not be used. Squeezing lesions and excessive
cleansing should also be avoided. The psychological aspect of the patient must not be overlooked especially for those with acne excoriee. 1.4.2. Topical Therapy 1) Benzoyl peroxide It is an effective antibactericidal and has some anti-inflammatory action as well. Various strengths (2.5%, 5% and 10%) are available. Since it can cause irritation of the skin patients should be warned and advised to start with the weakest strength. The frequency and duration of exposure can then be stepped up gradually. 2) Retinoic acid It is a comedolytic, and can increase the basal cell mitosis and epithelial turnover. Various strength are available in the gel and cream base (Retin A gel 0.01% and 0.025% ,and cream 0.05 and 0.1%) As it is also an irritant, the same principle of application like benzoyl peroxide is employed. 3) Topical Isotretinoin Isotretinoin for topical application is available recently. Its effect is comparable to topical retinoic acid though it is much less effective than systemic isotretinoin (see below). 4) Azelaic acid It is available as 20% azelaic acid in cream base. It act by both inhibition of the growth of the propionibacteria and decreasing the ductal hypercornification, and is indicated for comedonic, mild to moderately severe papulopustular acne. It is a safe topical agent and can be given to pregnant woman. The cream should be applied twice daily. Although minor degree of irritation is very common, it is generally well accepted by most patients. 5) Topical Antibiotics Although topical antibiotics are less effective than benzoyl peroxide in inhibiting P. acnes, they are less irritant and better tolerated. Both topical erythromycin and clindamycin appear to be safe and effective for the treatment of mild to moderate inflammatory acne. However there is concern on the possible epidemiological consequences of transferred bacterial resistance resulting from the use of topical antibiotics. 6) Other topical agents Sulphur, salicylic acid and resorcinol are agents commonly used in commercial preparations, probably act as keratolytic and are useful in mild acne. Topical steroids are sometimes added into proprietary preparations. Although they are anti-inflammatory and may help to reduce the inflammatory effects of keratolytics, long-term use is not advisable in acne patients (c.f. perioral dermatitis).
1.4.3. Systemic Therapy 1) Antimicrobials Antibiotics act by inhibition of the follicular bacterium, Propionibacterium acnes. Tetracycline and erythromycin have additional anti-inflammatory actions. They should be given for 6 months to exert the full effect, though noticeable improvement may be observed earlier. If the response to one antibiotic is not satisfactory another one can be tried. These drugs can safely be continued on a long-term basis if indicated. However, patients should be made to understand that the treatment is only suppressive and not curative, and relapse may follow withdrawal of the drug. A pustular folliculitis of the face due to Gram-negative superinfection is a rare complication of long-term antibiotic therapy and must be looked out for in case of 'resistance' to treatment. Culture of the pustules should be done in case of doubt. a) Tetracycline This is still the drug of choice, being cheap and effective. It is a bacteriostatic agent which acts mainly by reducing the acne bacteria population on the skin. The usual dose is 1 gm/day in divided dosage and should be taken with an empty stomach. Milk and dairy products should be avoided. Side effects include GI upset, drug eruption (especially fixed drug eruption). This group of antibiotic is absolutely contraindicated in pregnancy and extra caution should be taken in prescribing it to young female patients. b) Minocycline and doxycycline Minocycline is more lipid soluble and penetrates the sebaceous glands better than tetracycline. It has a more persistent effect and bacteria resistance is less common than tetracycline. Both minocycline and doxycycline are probably more effective and better tolerated, but more expensive, than tetracycline. They can be given as a single daily dose (100 mg/day) or in a divided twice daily dosage. Both drug can cause GI upset and drug eruption like tetracycline. Other side effects of minocycline include dizziness and various types of pigmentary change. There is also a recent report revealing that minocycline is more frequently associated with immunologically mediated reactions like chronic active hepatitis and lupus erythematosus than other anti-acne antibiotics. c) Erythromycin This is as effective as Tetracycline but resistance develops more rapidly. The drug is safe in pregnancy, and is preferred to tetracycline for married woman. d) Dapsone: previously very useful for treating cystic acne before isotretinoin is available. Dosage is 100 mg daily. This may cause haemolytic anemia in G6PD deficiency patients.
e) Septrin: this has been proven effective for acne that does not respond to conventional therapy. The dosage is one to two tablet twice daily. Because it can produce severe allergic reactions such as erythema multiforme as well as blood dyscrasia, it is only recommended for use in refractory patients for relatively short periods (6 months or less). f) Ampicillin is used mainly for gram negative folliculitis. 2) Hormonal therapy This is indicated for women with acne especially for those patients with features of androgen excess like hirsutism and androgenic alopecia. Possibilities of androgen excess secondary to diseases like polycystic ovarian disease should not be overlooked. Diane 35 (Dianette): is a combination drug of an anti-androgen, cyproterone with an estrogen, ethinyl estradiol. It is indicated only for women and especially for those who would consider oral contraceptive pill for contraception. Cyproterone is teratogenic and the drug is contraindicated in pregnancy. It is also not used for patients with other risk factors like familial history of cardiovascular diseases or diabetes mellitus. Patients on dianette should be followed up regularly for pap smear and blood pressure. Spironolactone: is an effective competitor of androgen receptor as well as an inhibitor of 5-a-reductase. The dosage range from 50 mg to 200 mg per day. Polymenorrhoea may be a problem when high dose is given. Others: Keotconazole has antiandrogen activity but is limited by its serious side effects. Cimetidine is a mild antiandrogen and is not clinically useful. Administration of gonadotropin releasing hormone agonist as a form of medical castration should only be undertaken by endocrinologists or gynecologists. 3) Retinoid 13 Cis-retinoic acid (Roaccutane) is a vitamin A derivative with a potent effect on sebaceous glands. The drug is the treatment of choice for nodulocystic acne, for acne that is unresponsive to adequate conventional therapy, and particularly for acne causing scarring. It is given in a dosage of 0.5-1 mg/kg/day orally. Studies have been shown that optimal long-term benefit can be achieved by using the higher dosage regime especially in younger patients and in patient with predominantly truncal disease. There is also evidence that when patients have received a total cumulative dose of more than 120 mg/kg, they have a better chance of achieving long-term remission. In practice the cure rate approaches 90% if given for 4 months with the 1 mg/kg dosage. Occasionally longer duration of therapy may be needed for resistant cases. This drug is teratogenic and it is unwise to prescribe the drug to female patients without concomitant adequate
contraception, and contraception should be continued for at least 1 month after cessation of therapy. Its side effects include dryness of the skin and lips, epistaxis, arthralgia and myalgia, and temporary hyperlipidemia and abnormal liver function test. Headaches can occur, and benign intracranial hypertension has been reported. 1.4.4. Other Specific Therapy 1) Surgery Unsightly scars and persistent cysts, when they are no longer inflamed, may be excised. Dermabrasion may be of value for depressed scars and can be considered when the disease is inactive. Pigmentary changes after dermabrasion is a problem in colored race. Laser surgery has also been used to improve acne scars and pigmentation. 2) Treatment of Comedones Blackheads can be removed with a comedones extractor. The use of light cautery after the application of EMLA as a local anaethestic has been shown to help patients with multiple macro-whiteheads. 3) Collagen injection of scars Purified bovine dermal collagen injection can give good cosmetic results for some acne scars. This is an expensive procedure and injection need to be repeated to maintain the improvement. There is also a small risk of hypersensitivity reaction. 4) UVB irradiation: UVB irradiation to the face in sufficient doses to produce mild erythema and desquamation of the skin can improve acne in some patients, but response to treatment is variable. 5) Systemic steroids: very useful in arresting the inflammatory lesions before isotretinoin is available. Now rarely used except for treatment of acne fulminans. 6) Chemical peeling: superficial peel with glycolic acid has been claimed to useful in treatment of acne. Deeper peel can be employed to alleviate acne scars. Chemical peeling should only be performed by dermatologists experienced in the technique. 7) Intralesional kenacort A: for individual cystic lesion, can reduce the inflammation quickly but there is a risk of leaving a pitted scar. Injection for keloidal acne is another indication. 8) Zinc: Oral zinc therapy had been very popular before but failed to demonstrate significant benefit in many clinical trials. Dosage is Zinc gluconate 200 mg/day. The addition of zinc to topical erythromycin has been shown to enhance the therapeutic efficacy especially on inflammatory lesions. This preparation has been marketed in USA.
URTICARIA Dr. C.Y. LEUNG CHAPTER 6 1. DEFINITION Urticaria is characterized by transient itchy pale dermal swellings secondary to the release of histamine and possibly other vasoactive agents from mast cells. 2. AETIOLOGY The release of histamine, and possibly other vasoactive mediators from mast cells leads to a sudden increase in vascular capillary permeability allowing the escape of fluid from the circulation into the tissues. Mast cells may degranulate in response to a number of stimuli including physical, chemical, pharmacological and immunological. Different mechanisms may be operating in different types of urticaria. The type I hypersensitivity is mediated through the IgE attached to the mast cell which will degranulate on exposure to the specific antigen. Patients suffering from this type of allergic urticaria frequently have a personal or family history of atopy. Mast cells can also degranulate by other nonimmunological stimuli. Certain drugs, for example morphine, codeine, ethanol, polymyxin B, and bacterial, plant or invertebrate toxins can stimulate mast cells to degranulate directly. Other drugs like salicylates and NSAIDs on the other hand act on the mast cell through its action on the cyclo-oxygenase pathway. It has been postulated that food additives such as tartrazine, azo dyes, benzoates and sulphites can provoke urticaria through a similar mechanism. Recently some research workers have demonstrated the presence of IgG auto-antibodies directed against IgE receptor Fc epsilon RI of mast cells and basophils in some patients with chronic idiopathic urticaria, which can activate the mast cells to degranulate. This autoimmune hypothesis of idiopathic chronic urticaria has led to the use of various immune therapies for treatment of the condition (see below). Vasodilatation, dermal oedema and a mild perivascular infiltration of lymphocytes and eosinophils are seen in a typical lesion of urticaria. However in a small number of patients repeated biopsies may show a predominance of neutrophils and eosinophils infiltrate and absence of endothelial damage, representing a late phase reaction. This picture would suggest that other cellular elements and mediators may operate in the pathogenesis of urticaria in some cases. 3. CLASSIFICATION OF URTICARIA
Various types of classifications exist, the following classification adopts a more practical approach. 3.1. Acute Urticaria and Urticaria with an Identifiable Cause In acute urticaria, a self evident precipitating factor is usually present (table 1). Some patients with chronic urticaria may also have a well defined cause although this is uncommon. 3.2. Chronic Idiopathic Urticaria Defined arbitrarily as urticaria that persisted for six weeks or more without any identifiable cause. 3.3. Physical Urticaria cholinergic urticaria symptomatic dermographism delayed pressure urticaria solar urticaria cold urticaria aquagenic urticaria vibratory urticaria 3.4. Angio-Oedema May accompany any types of urticaria. Hereditary angioedema is due to C1 esterase inhibitor deficiency. An acquired form of this enzyme deficiency is also known. ACE inhibitors can provoke angio-oedema through inhibition of the kinin system. 3.5. Others: hereditary urticaria, contact urticaria, papular urticaria, urticarial vasculitis, and urticaria pigmentosa. Table 1: Common Causes of Urticaria Drugs Foods Food additives Infections Inhalants Infestation salicylates, penicillin, ACE inhibitors, NSAID, allopurinol and many others. fish, nuts, egg, strawberries, milk, cheese, wine and many others. azo dyes, benzoates, sulphites and yeast. hepatitis B, infectious mononucleosis, candidosis and focal sepsis. grass pollens, moulds, housedust mites, etc. enterobius, filariasis, ascariasis.
transfusion reaction, drugs
4. CLINICAL FEATURES The lesions in urticaria are usually not difficult to recognize. They are intensely itchy, with a white palpable centre of oedema and a variable halo of erythema . The size and shape can be highly variable and individual lesion usually lasts for several hours, except in urticarial vasculitis and angio-oedema where the lesion may persist longer. Frequently patients do not have any lesion during the visit to the clinic and one has to rely on the description from the patient to diagnose a prior attack of urticaria. The history is very important for the diagnosis of different types of urticaria in particular for physical urticarias. The frequency, duration, severity, and timing of the attacks may give clues to the diagnosis and are essential for subsequent management. A thorough food and drug history should be elicited. The characteristic rash of physical urticaria, if present on examination, together with the typical history would usually allow the diagnosis to be made. In case of doubt, simple tests can be done to confirm the diagnosis (table 2). After making the diagnosis, one should always try to look out for any underlying causes and associated involvements. Focal sepsis, such as dental abscess and urinary tract infection have been reported to cause chronic urticaria. Urticaria can also be the presenting symptom of connective tissue diseases and other features of the disease would usually be evident. Acute urticaria can be just part of the manifestation of serum sickness with systemic symptoms like fever, arthritis and nephritis. Similarly systemic symptoms are also seen in patients with urticarial vasculitis. Table 2: Tests for Physical Urticaria Cholinergic Urticaria Dermographism cold urticaria exercise test, whole body warming light stroke on the skin, dermographometer ice cube test
solar urticaria aquagenic
phototesting water at 25oC compresses
5. INVESTIGATION In most patients suffering from urticaria, the correct diagnosis can be made after history taking and physical examination. A complete blood count together with ESR is adequate for the majority who has no other abnormal physical finding. Other investigations should be done when necessary. 1) complete blood count and ESR: look for eosinophilia 2) Liver function test 3) complement C3 and C4 4) C1 esterase inhibitor level 5) Investigating underlying infections: chest radiograph, urine for culture, stool for ova, throat swab, HbsAg, viral study etc. 6) ANF, RF etc. in suspected connective tissue disease 7) Skin biopsy: urticarial vasculitis, urticaria pigmentosa 8) RAST: controversial as to its usefulness 9) Skin prick test: useful for contact urticaria. Difficult to interpret for chronic idiopathic urticaria 6. ACUTE URTICARIA Patients with acute urticaria are usually seen by their family doctors or by doctors in the A&E department. The cause of the acute attack is often obvious and there may be a history of similar attack. Initial investigations should include the differential white cell count and ESR measurement. The presence of eosinophilia points to parasitic infestation. Other possible causative factors listed above should be sought for. Since the causal factor can usually be withdrawn, subsequent attack can be avoided and long-termed treatment is usually not required. Challenge test is not advisable since acute urticaria is frequently IgE mediated and there is a definite risk of anaphylaxis during the test. Though the prognosis is good in most cases, those with persistent symptoms for weeks may actually be suffering from chronic idiopathic urticaria with an acute onset. Most of these acute episodes can be successfully controlled with antihistamine. In acute urticaria of serum sickness type hypersensitivity, a short course of systemic steroid may be necessary. Parenteral adrenaline is life saving in case of anaphylaxis and bronchial constriction. Resuscitation procedures should be carried out as indicated.
7. CHRONIC IDIOPATHIC URTICARIA Chronic idiopathic urticaria is defined as urticaria lasting longer than 6 weeks, for which no obvious cause can be found. This is the commonest type of urticaria in a dermatology clinic and a study by Champion reported that 80% of urticaria is chronic idiopathic urticaria. Although symptomatic relief can be achieved with drug therapy, a certain percentage of patients may suffer from continuous symptoms for years without true remission. Numerous factors have been suggested for causing this disease including sea food, azo dyes, food preservatives, candida in the gut and trace of penicillin in dairy products. Some patients may benefit from elimination of one of these factors, but for most others the cause of the disease remains obscure. Recently an autoimmune aetiology has also been proposed. By definition, no obvious aetiological factor is apparent and special investigations are nearly always unhelpful. For most patients with chronic idiopathic urticaria, a complete blood count, ESR for screening may be adequate. Stool for ova is indicated if there is eosinophilia. Other tests detailed above should be performed for individual patient as directed by the history and examination. Prick test and intradermal skin test are often positive but are difficult to interpret. Challenge tests with food coloring agents and preservatives if available, are helpful in the management. Although no underlying cause can be found, for the majority of patients their symptoms can be well controlled by drug with minimal disturbance to their daily life. Depending on the patient's tolerance, a sedating or non sedating antihistamine can be prescribed during daytime. Because most patients have more severe attack at night time, an additional nocte dose of more sedating drug like promethazine is helpful. The patient should be encouraged to keep a food diary. Food containing tartrazine dye and preservatives as well as drugs that known to aggravate urticaria should be avoided. In suitable cases, elimination diet can be carried out with the help of a dietitian. Tolerance to antihistamine therapy may develop in a patient whose symptoms are previously under control. This tolerance cannot be overcome by increasing the dosage or by changing to another antihistamine. The cause of tolerance is thought to be due to the down regulation of the H1 receptors. Ketotifen and sodium cromoglycate can be tried and responsiveness to antihistamine may return. Hospital admission may be required for alternative therapy in difficult cases. 8. CHOLINERGIC URTICARIA
A common condition in young adults with intensely itchy and short-lived eruption developing in response to sweating, exercise, emotion and hot foods. It is postulated that an increase in blood temperature triggers a neural reflex which releases acetylcholine from sympathetic nerve endings, in turn activate the mast cell to degranulate. Characteristic small wheals, less than 2 mm in diameter with surrounding red halo are more profuse on the upper trunk and proximal parts of the upper limbs. Thus it is also called micropapular urticaria. Associated systemic symptoms include faintness, headache, wheezing and palpitation. Diagnosis is established from the history and the finding of characteristic rash during an attack. The rash can also be brought up on exercise or whole body warming. These lesions can often be reproduced by intradermal injection of cholinergic drugs, e.g., metholyl or acetylcholine. Treatment is unsatisfactory. Patients, especially those with associated systemic symptoms, should be told to avoid situations that can precipitate an attack. Some patients improve with antihistamine therapy. This can be taken regularly or at times when they anticipate attacks. Fortunately for most patients the condition tends to improve spontaneously. 9. PRESSURE URTICARIA This rather rare condition is not a true urticaria. Delayed cutaneous erythema and oedema and subcutaneous oedema occur in response to the sustained application of pressure to the skin. The lesions itch and burn. They appear between 30 min to 9 hours after the stimulus. A large proportion of these patients have associated chronic idiopathic urticaria. The lesions characteristically occur after certain activities: sitting on hard chairs, carrying bags, leaning against furniture, wearing seat belts and lying on hard mattresses. Swelling of the feet and hands, often indistinguishable from angio-oedema, occurs after walking, jogging, running, climbing ladder and using a screwdriver. During severe attacks, arthralgia and a flu-like illness may accompany the rash. The pathogenesis of pressure urticaria is not known. Histamine is probably not an important mediator of this disease and treatment with antihistamine is useless. Other forms of treatment including the use of NSAIDs and colchicine have been tried with varying results. Systemic steroid is an effective agent but is limited by its side effects. 10. SYMPTOMATIC DERMOGRAPHISM Dermographism means whealing after direct pressure on the skin. The patient notices that the skin itches with linear wheals appearing after
scratching . The itching and whealing reach their maximum in 5-10 minutes after the stimulus and disappear 30-60 minutes later. It is an exaggerated response of the skin to trauma. Lesions frequently appear in areas where clothing is tight and at sites of scratching. Patients can be of any age group but young adults are more often affected. No associated systemic disease has been recognized and no increased incidence in patients with chronic idiopathic urticaria is noted. The diagnosis can be confirmed by using the more sophisticated dermographometer. Any patient who itches and wheals at or below a stroking pressure of 3.5 x 105 Pa has symptomatic dermographism. The tendency to dermographism may last for years but ultimately improve in most cases. 11. SOLAR URTICARIA Solar urticaria is a rare photodermatosis of unknown aetiology. It is occasionally associated with polymorphic light eruption, other urticarias, lymphocytoma cutis or lupus erythematosus. It may also be symptomatic of porphyria cutanea tarda. Patients notice erythema, burning, and urticarial wheals within minutes following exposure to sunlight or other visible light source. Wheals can develop anywhere on the body, mostly in the sun exposed skin. If the whole body is irradiated, severe generalized solar urticaria can occurred with haemodynamic disturbance. The action spectrum of solar urticaria is broad, ranging from UVC, UVB, UVA to visible spectrum. The diagnosis can be confirmed by phototesting with monochromator on areas of the body that are normally covered e.g. the buttock. If monochromator is not available, lesions of solar urticaria can be reproduced outdoor by direct exposure to sunlight or visible light. Avoidance of sunlight is essential in the management. The body should be covered with clothing and the patient should be advised to use an appropriate sunscreen. Antihistamines can produce symptomatic relief. Other treatment modalities that have been used include hardening with UVB, UVA, or visible light, PUVA, and plasmapheresis. 12. COLD URTICARIA Patients with cold urticaria develop whealing on exposure to cold. Wheals typically appears on exposed areas on a cold day. Handling of cold objects also causes immediate local reaction. There may be swelling of the mouth and oesophagus after drinking cold water. If whealing is extensive, cold
urticaria may be associated with systemic symptoms like faintness, wheezing and palpitations. Diagnosis is established by placing an ice cube (wrapped in plastic bag) on the skin for 30 seconds to 10 minutes. Wheals form on rewarming. In some cases, water at 7o C is more effective in bringing out the wheal. It is important to warn patients against swimming in cold water or immersing in cold water as syncope may occur. Antihistamine treatment is partially effective in suppressing symptoms. Cyproheptadine is generally considered to be the drug of choice. Salbutamol and aminophylline can relieve the pruritus of cold urticaria. Unlike antihistamines these drug act by suppressing histamine release from skin mast cells. Doxepin and ketotifen may also be useful. Desensitization to cold has a place in the management of this condition. This should be carried out in the hospital under antihistamine cover. The procedure begins with putting one limb in water at 15 ?C for 5 min, hourly at first and then at longer intervals up to 24 hours. Other limbs and the face can then be treated. The exposure needs to be repeated indefinitely at 24 hours intervals to maintain the effect. It should be remembered that occasionally cold urticaria is secondary to the presence of cryoglobulin, cold hemolysin and cryofibrinogen in the circulation. These condition should be ruled out accordingly. 13. AQUAGENIC URTICARIA This is a rare type of physical urticaria in which brief contact of the skin with water of any temperature causes an immediate urticarial eruption at the site of contact, the morphology of which closely resembles that of cholinergic urticaria. This condition may persist for many years. Aquagenic pruritus is a related but distinct condition in which brief contact of skin with water evokes intense local pruritus without any skin lesion. Patients with this disorder, which is probably quite common in the elderly, are often wrongly labelled as psychoneurosis or senile pruritus. Complete blood count should be checked as this condition may be symptomatic of polycythemia rubra vera. Both disorders involve histamine release from skin mast cells and respond well to antihistamine. UVB therapy is also helpful. 14. VIBRATORY ANGIOEDEMA Vibratory angioedema is an acute short-lived itchy swelling of the skin that occurs within minutes of application of a vibratory stimulus to the skin. This condition is rare and is probably genetically transmitted. It is benign and the familial form is not associated with any other physical urticaria. Affected
patients generally limited their activities to avoid symptoms. The lesions tend to appear after low frequencies vibration (about 10 Hz) like handling a power lawn mower and running, and wheals can be seen within minutes after the stimulus and disappears within an hour. Clapping and riding a motor bike may also produce lesions. The severity of symptoms is proportional to the intensity of the provoking stimulus. If the stimulus is sufficiently strong, facial and/or generalized erythema may occur. Systemic symptoms like headache and dizziness are also reported. Treatment with antihistamine is usually effective. 15. ANGIOEDEMA This is a variant of urticaria where massive oedema involves subcutaneous tissues rather than the dermis. It may involve any part of the body surface like the lips, eyelids, tongue and larynx. This condition can be associated with urticaria of any cause. The hereditary form is caused by a quantitative or functional deficiency of C1 esterase inhibitor and is inherited as an autosomal dominant trait. An acquired form of C1 esterase inhibitor may develop in patients with lymphoproliferative disorders and systemic lupus erythematosus. Hereditary Angioedema In hereditary angioedema attacks are infrequent in childhood, common in adolescence and early adult life and may subside later. It is precipitated by trauma and the lesions may affect the skin, mucosal surface and intestine. Subcutaneous swelling is not itchy and typically persisted for a few days. Intestinal oedema may causes symptoms simulating acute abdomen. Laryngeal oedema may lead to upper airway obstruction and death. The C2 and C4 level are low in between attacks and C3 is normal. There is a low C1 esterase inhibitor level. In acute airway obstruction, subcutaneous adrenaline may be life saving. Fresh frozen plasma should be administered by intravenous infusion or, alternatively a purified C1 esterase inhibitor concentrate can be given. For long term management attenuated androgens stanozolol or danazol can be used for prophylaxis. They act by stimulating hepatic synthesis of C1 inhibitor. Antifibrinolytic agents like tranexamin acid and epsilon aminocaproic acid are less effective as prophylaxis but can be tried in patient who cannot tolerate androgenic steroids. 16. CONTACT URTICARIAS Contact urticaria is a local immediate or delayed erythema or urticarial reaction at the site of epidermal or mucosal contact with a causative agent. It may be associated with generalized cutaneous reactions, rhinitis, asthma, or
anaphylaxis. It is commonly an IgE mediated immediate reaction and non immunological mechanism is also possible. Probably the most important cause of contact urticaria is natural rubber latex present in gloves and other rubber products. Latex contact urticaria symptoms vary from mild itching to bronchial asthma, anaphylaxis, and death. Up to ten allergenic proteins have been isolated from latex. Small molecular wight chemicals may cause contact urticaria. Chemicals like ethylene oxide, isocyanates, chloramine-T, epoxy resins and nickel sulphate can act as hapten and initiate IgE-mediated allergies. This can be confirmed by using skin prick testing. 17. URTICARIAL PIGMENTOSA This condition is in fact not urticaria but is a disorder of mast cell proliferation commonly seen in early childhood. Clinically there is multiple guttate or larger pigmented macules on the trunk and limbs of the baby and urticated lesion may appear on rubbing the pigmented lesions. The biopsy of the skin shows increase in the number of mast cells. 18. URTICARIAL VASCULITIS (refer to the Chapter of Vasculitis) 19. THERAPEUTIC MODALITIES FOR URTICARIA 19.1. Antihistamines This group of drugs has H1 receptor blockers action and is the mainstay of therapy for urticarias. There are many antihistamines available. While the classical ones have been used for many years and are effective and cheap, they have more anticholinergic action and can cause more sedation. The newer antihistamines are more expensive and less sedating. In general there is little difference in the efficacy between the two groups of antihistamines and there is a lot of individual variations in response to treatment. As a guideline one should prescribe an antihistamine that one is familiar with and gradually titrate the dosage according to the response. It is worthwhile to switch to an antihistamine of another class if the response to the first choice is not satisfactory when the maximum dosage has already been given. Alternatively, in order to select out the most suitable agent for the patient, an antihistamines self-assessment questionnaire can be employed. The classical antihistamines (see table 3) can be grouped into 6 classes according to their chemical structures, but the introduction of the newer drugs has greatly complicated this. Table 3: Commonly Used 'Classical' Antihistamines
Generic (Proprietary) Name Dimenhydrinate Diphenhydramine (Benadryl)
Usual Adult Dose 50-100 mg qid 25-50 mg qid
Chlorpheniramine (Piriton) *1 4 mg tid Dexrochlorpheniramine 2-4 mg tid (Polaramine) *2 75 mg bid Pheniramine (Avil) Mebhydrolin (Incidal) 50-100 mg tid
Promethazine (Phenergan) 10-25 mg bid Trimeprazine 10-30 mg qid (Vallergan) 5 mg bd Mequitazine (Primalan) Hydroxzine (Atarax) Cyproheptadine (Periactin) Azatadine (Zadine) 10-25 mg tid 4 mg tid 1-2 mg tid
*1 a short acting, good general purpose drug *2 dextro-isomer of chlorpheniramine *3 causes sedation, suitable for use at night time, e.g. 25 mg nocte *4 with addition antiserotonin action, very useful for cold urticaria Unwanted effects are common with these antihistamines, the commonest being sedation, dizziness, fatigue, insomnia and dry mouth. Paradoxical increase irritability may be seen in children. Alcohol can potentiate the sedative effect and patient should be advised to abstain from drinking while on antihistamine therapy. The anticholinergic action may cause urinary retention and precipitate glaucoma. All antihistamines are not proven safe in pregnancy and one should balance the risk and the possible benefit before
prescribing antihistamines to pregnant woman. Newer antihistamines should always be avoided. Table 4: Low Sedating Antihistamines Usual Adult Dosage Terfenadine 60 mg bd Astemazole 10 mg daily Loratadine 10 mg daily Cetirizine 10 mg daily Acrivastine 8 mg tid Onset 1-2 hours days 1-2 hours 1-2 hours 30 minutes Duration of Action > 12 hours *1 4 weeks *2 24 hours 24 hours 12 hours
Notes: 1. Fatal ventricular arrhythmia has been reported with larger than normal dose, in patients with liver disease and when it is administered with erythromycin or ketoconazole. 2. Very long duration of action. Ventricular arrhythmia reported. Cautious in the elderly. Weight gain may occur during prolonged therapy. Other antihistamines and related drugs: Ketotifen: Antihistamine-like drug with mast cell stabilising effect, worth a try in difficult urticaria and when tolerance to antihistamine therapy appears. Adult dosage: 1-2 mg bd Oxatamide: properties comparable to ketotifen, dosage is 30 mg bd. Doxepin: a tricyclic antidepressant with antihistamine activity. Suitable for administration at night. There is drug interaction with MAOIs, and can cause cardiac arrhythmia. Dosage: 10 mg nocte 19.2. H2-Receptor Blockers The exact mode of action of H2 antagonist in urticaria is still uncertain. In many stubborn cases addition of an H2 antagonist with an antihistamine may be helpful, but there is no ground to give an H2 antagonist alone. Cimetidine: 400 mg bd Ranitidine: 150 mg bd 19.3. Beta-stimulants This is considered as a second line treatment for patients with resistant chronic urticaria and antihistamine tolerance. They act directly on the mast
cell and prevent degranulation. Although they are effective, their use is limited by their side effects, including tremors and tachycardia. Salbutamol: 2-4 mg tid Terbutalin: 0.5 mg tid 19.4. Calcium Channel Blocker Only nifedipine is useful for stubborn urticaria. It acts by stabilising mast cell and inhibit degranulation. Side effects include hypotension and flushing attacks. Nifedipine: 5-10 mg tid 19.5. Anabolic Steroid This has been used in patients suffering from hereditary angioedema. It is also used in cholinergic urticaria. Danazol: 100-600 mg daily Stanozolol: 2.5-10 mg daily 19.6. Systemic Corticosteroid Therapy This is an effective form of therapy for urticaria but long term therapy should be used only in exceptional cases because of its side effects. Systemic steroid therapy is indicated for anaphylaxis and acute urticaria of serum sickness. For chronic urticaria, this should be avoided unless it is given for a short duration to tie over an acute episode. 19.7. Mast Cell-Stabilising Agents Disodium cromoglycate which stabilized mast cell membrane has been found to be useful in atopic asthma when administered via an inhaler. Because the drug is not absorbed in the gastrointestinal tract they are generally not effective for patients with chronic urticaria. However, it may be helpful in cases of urticaria caused by food allergy. Two antihistamine, ketotifen and oxatamide, have additional mast cell stabilising effect but it is not certain whether this additional property is of any clinical significance. 19.8. Immune Modulation Based on the autoimmune hypothesis for chronic idiopathic urticaria, various immune modulation therapies had been investigated for treatment of the condition: plasmapheresis, cyclosporin A and intravenous immunoglobulin. These treatment modalities are still experimental and not yet suitable for routine clinical application. Vitiligo Dr. R. SU CHAPTER 7 1. Definition
An area of acquired cutaneous depigmentation characterized by wellcircumscribed milky white macules devoid of identifiable melanocytes. 2. Aetiological Hypothesis Various theories are suggested as the aetiology of vitiligo; the same mechanism may not apply to all cases. 2.1. Autoimmune Hypothesis Autoimmune destruction of cutaneous melanocytes with total loss of melanocytes and melanin pigment in the skin of the affected area. Lymphocytic infiltration on skin biopsy indicate lymphocytes are involved in the destruction process. Frequently associated with other autoimmune diseases; such as alopecia areata, autoimmune thyroid disorders, Addison¡¦s adrenal disease, atrophic gastritis and pernicious anaemia, diabetes. Serum autoimmune antibodies against melanocyte, thyroid, adrenal, islet-cell, gastric parietal cell, and intrinsic factor have been demonstrated. 2.2. Neurogenic Hypothesis A compound is released at peripheral nerve endings in the skin which is toxic to melanocytes and inhibits melanogenesis. It is postulated that in the dermatomal variant, the affected area shows sympathetic nerve dysfunction. Catechol neurotransmitters probably destroy the melanocytes instead. There is little support for this hypothesis. 2.3. Self-destruct Theory of Lerner Defect of a natural protective mechanism in melanin synthesis within melanocytes, leading to accumulation of toxic precursors (phenolic compounds) which destroy melanocytes. This hypothesis is based on the lethal effects produced by chemical compounds (phenols) on functional melanocytes; the resulting leukoderma is indistinguishable from idiopathic vitiligo.
3. Clinical Presentation Affects around 1% of the population in all races, but more troublesome in dark skin where there¡¦s marked contrast between normal and depigmented areas. Hence the incidence may be apparently higher in pigmented races where the social impact is also greater. Family history of the condition is found in one third of the affected patients. Sex ratio is equal. Half the patients first present before 20 years old. It may be precipitated by injury or sunburn. In light skin individuals, vitiligo may only be discernible in summer, when the vitiliginous area becomes sunburnt.
The main symptom being cosmetic and presents when the patient notices that the affected area fails to tan after sun exposure, unlike the surrounding normal skin. It is an essentially clinical diagnosis, based on the morphology and distribution of the lesions as well as the exclusion of other hypopigmented skin lesions. Vitiligo may rarely be associated with premature greying of hair, retinal pigmentary loss, uveitis, deafness, CNS involvement (Vogt-Koyanagi syndrome). Other associations include: halo naevus, malignant melanoma, alopecia areata, autoimmune thyroid disorders, Addison's adrenal disease, chronic atrophic gastritis, Pernicious anaemia and diabetes mellitus. 4. Diagnostic Hallmarks 4.1. Distribution Localized: Sun exposed areas such as dorsal surface of hands and the face, including peri-orificial and peri-orbital areas. Hyperpigmented areas such as axilla, groin, genitalia, flexures, and nipple. Sites of friction and bony prominences like elbows and knees. Generalized: Widespread Unilateral variant: unilateral segmental pattern seen in children occurs (linear/dermatomal) occasionally. 4.2. Individual Lesions Sharp margin No scale Normal texture and intact sensation Typical: milk white colour Atypical: Trichome vitiligo - an intermediate uniform tan colour - naturally evolves to a typical vitiligo macule Quadrichrome vitiligo - macular peri-follicular or marginal hyperpigmentation seen in repigmenting vitiligo Inflammatory vitiligo - erythematous, raised border similar to that seen in tinea versicolor. 5. Differential Diagnosis of vitiligo and other Hypopigmented lesions Generalized hypomelanosis albinism
hypopituitarism vitiligo piebaldism tubero-sclerosis chemical leukoderma tinea versicolor leprosy pityriasis alba morphea lichen sclerosis post-inflammatory hypopigmentation
Patchy hypomelanosis with inflammation and scaling Patchy hypomelanosis with atrophy or induration
6. Investigation Skin biopsy will show absence of melanocyte and melanin in the affected area, but this is often not necessary as the diagnosis is clinically obvious. Other investigations are considered to exclude associated autoimmune disorders. The extent of the investigations may depend on the history and physical findings. 7. Treatment Educate and encourage relatives, friends and society to overcome the stigma that this is infectious. Acceptance of patient by physicians setting an example (e.g. shaking hands) should be supportive to patient and help to overcome stigma. Reassurance that this is a cosmetic problem and does not affect the patient's health directly. Educate the patient about the nature of the disease, that treatment may be difficult and prolonged, and the results may not be predictable. While the patient should not have unrealistic expectation they need not be discouraged. More important is to take good care of their own skin, concentrate on what can be done even if the condition can not be cured at present. 1) Sunscreen (SPF 15-30) These are recommended for three reasons: 1) Vitiliginous areas are more susceptible to sunburn, 2) Sunburn injury can further extend area of depigmentation (Kobner response). 3) Sun-induced darkening of the surrounding normal skin causes accentuation of the cosmetic disfigurement. Sunscreens which shield both UVB and UVA light should be used.
For the same reason, avoiding outdoor activities under the strong mid-day sun, together with protective clothing, will reduce ultraviolet damage to depigmented skin which is devoid of protective melanin. 2) Camouflage Cosmetics (Covermark, Dermablend etc.) Covermark and Dermablend are cosmetic that can be used to match most skin hues. Quick-tanning preparations containing dihydroxy-acetone may be used to tan the vitiligo a more acceptable colour. It can produce different shades. Instructions and guidance from a cosmetic instructor are required to give the best cosmetic results and safety. These preparations are especially useful on the eyelids where potent topical corticosteroids and ultraviolet-light should not be used. 3) Repigmentation therapies Moderately potent to potent topical corticosteroids e.g. Sicorten Cream (0.5% halometasone) This may be applied to affected area twice daily as a trial. Therapy should be discontinued if repigmentation has not begun after six to twelve months. The patient needs to be seen every 1-2 months to check for signs of cutaneous atrophy from treatment. Caution is needed when applying it to the face and flexures (once daily/alternate day). It should not be applied to eyelids and periorbital areas to avoid the risk of steroid-induced glaucoma and cataract. PUVA Therapy: Topical or systemic (Refer to chapter 17) Topical PUVA involves ultra-violet A irradiation 30 minutes after application of meladinine (topical methoxasalen) to the localized vitiliginous area. Systemic PUVA involves ingestion of methoxasalen (0.6 mg/kg) two hours before irradiation. Treatment should be attempted under the supervision of a dermatologist or those experienced in its use. In inexperienced hands PUVA may carry the risk of phototoxic reaction, ocular damage etc. Careful patient selection is also required. Within the Social Hygiene Service, predominantly facial lesions (except eyelids) of recent onset are considered for PUVA, because they tend to give better results. Some degree of repigmentation occurs in 50-75% of cases compared with 15-20% in controls. The patient undergoes treatment 2 times per week, and needs to avoid sunlight for 2 days after each treatment, using sunscreens both indoor and outdoor. It takes at least 2-3 months to begin having an effect and therapy needs to be continued for at least one year (100-200 treatment sessions) before maximum benefit is reached. Hence a long term commitment to therapy is required, and this must be appreciated by the patient before
embarking on therapy. The physician also needs to take into consideration the patients¡¦ age, sex and disease severity, medical, social, occupational and psychological factors. If perifollicular pigmentation has not appeared after three months of therapy, it is unlikely to occur; treatment might as well be stopped. But once repigmentation has begun, it tends to persist and spread with continuous treatment. However complete repigmentation occurs in 15-20% only. Systemic PUVA is less often used than topical PUVA in vitiligo. Contra-indications for systemic PUVA include: Pregnancy, children <12 year old, photosensitivity, cardiac, hepatic and renal disease, aphakia, and cataracts, and history of skin cancers. 4) Depigmentation therapies using bleaching agents such as 20% monobenzyl ether of hydroquinone (Benzoquin 20%) once or twice daily is indicated when vitiligo is extensive (>50% involvement or near universal). Benzoquin may cause a contact dermatitis, hence as a test before generalized therapy, it should be applied to a single pigmented spot daily for 1 week. Thereafter large pigmented areas are treated twice daily for up to 6 months. The compound is cytotoxic to melanocytes and destroys them. This process which removes pigment from the remaining normal skin is irreversible. The skin becomes albinoid, but the cosmetic appearance is improved substantially. The patient must remember they are sun-sensitive and need protective sunscreen. Experimental Repigmentation modalities: These can be tried in stationary vitiligo which are not extending any further. They have achieved variable success in different individuals. Grafts from uninvolved skin containing viable melanocytes; punch minigrafting using autologous pigmented donor sites is the simplest least invasive surgical approach. Alternatives include growing melanocytes in vitro from the patients¡¦ normal skin, and injecting them into artificially induced blister cavities in the depigmented areas. Repigmentation by tattooing has also been tried with some success. 8. COURSE AND PROGNOSIS Variable and some what unpredictable. May remain static, spread or repigment. But usually the condition is gradually progressive, sometimes extending rapidly over a period of several months and then remaining quiescent for may years. Spontaneous repigmentation is noted in about 1020% of patients. Factors indicating good prognosis for regimentation are: Recent onset < 6 months, in a young individual on the facial area.
Conversely factors which indicate an unfavorable prognosis are: Late onset in life, long-standing persistent lesions, located on the extremities and on the lips. Repigmentation begins within the affected area from the hair follicles where there may be residual melanocytes; or else they occur from the normal pigmented skin immediately adjacent to the vitiliginous area. Once repigmentation begins it tends to continue, albeit slowly and sometimes trivial. CUTANEOUS VASCULITIS Dr. Pedro Sá Cabral CHAPTER 8 1. Introduction Vasculitides compromise heterogeneous entities with diverse aetiologies and manifestations. Vasculitis is strictly defined as a process through which inflammatory destruction of the blood vessel wall occurs. Nowadays, most clinicians use the term vasculitis in a broad sense to mean any condition or process in which the blood vessel wall is inflamed and destroyed. The process may be confined to the skin or involve other organ systems, such as kidney, gut, nerves and joints. 2. AETIOLOGY A causative agent can sometimes be implicated in small and medium vessel vasculitis. Examples include: 1) Drug e.g. Aspirin, NSAID, penicillin etc. 2) Infection, e.g. Hepatitis B, Streptococcus etc. 3) Blood disorder, e.g. essential mixed cryoglobulinaemia. 4) Neoplastic, e.g. multiple myeloma, lymphoma. In large vessel vasculitis, a causative agent is not identified yet. e.g. Temporal arteritis, Takayasu's disease. 5) Connective Tissue Disease e.g. rheumatoid arthritis, Sjogrens, lupus erythematosis, dermatomyositis. 3. HISTOPATHOLOGY 3.1. Major Features The main histopathological features are fibrinoid necrosis of the affected vessel wall and inflammatory cells within the vessel wall. Accompanying extravasation of red cells are frequent and responsible for palpable purpura observed clinically. 3.2. Minor Features The minor histopathological features that often but not invariably accompany vasculitis include: 1) thrombosis occluding the vessel lumen; 2)
associated inflammation and damage to surrounding tissue (e.g. panniculitis, ischaemia, necrosis); 3) direct immuno-flourescence staining showing immunoglobulin IgG, IgM, IgA and C3 deposition within the vessel wall*. 3.3. Vessel Size The small vessels (post-capillary venules) are involved in leukocytoclastic or hypersensitivity (allergic) vasculitis. The medium size vessels are involved in polyarteritis nodosa. The large arteries are involved in giant cell arteritis. PS: Pitfall - Perivascular lymphocytic infiltration without involving the vessel wall itself is commonly seen in many conditions but should not be regarded as vasculitis. 3.4. Type of Inflammatory Cells The type/s of inflammatory cells present differ in different types of vasculitis and differ at different age of the lesion. The different types of inflammatory cells and the clinical conditions in which they are found are outlined below: Leucocytoclastic vasculitis: Neutrophils are predominant. Examples include Henoch-Scholein Purpura, drug-induced vasculitis, erythema elevatum diutinum, granuloma faciale, hypo-complementaemic vasculitis, polyarteritis nodosa. Lymphocytic vasculitis: Lymphocytes are predominant. Examples include: erythema nodosum, lupus erythematosus, lymphoma, pityriasis lichenoides. Eosinophilic vasculitis: Churg-Strauss is an example. Eosinophils are predominant. Granulomatous vasculitis: Wegener¡¥s granulomatosis and Churg-Strauss Angiitis**. Cells include: histiocytes, plasma cells, lymphocytes and occasional giant cells. Giant cells arteritis: This occurs cranial and temporal arteritis and polymyalgia rheumatica. Multinucleated giant cells are predominant. * The optimum specimen selected for biopsy should be a lesion between 1836 hours old. ** Churg-Strauss (Granulomatosis) Angiitis has features of a necrotising granulomatous (with eosinophils) vasculitis. 4. PATHOGENESIS 4.1. Immune Complex Deposition Following exposure to an antigenic stimulus, antibodies (usually IgG or IgM class) are formed and complex with the antigen in the circulation. These complexes circulate without any difficulty until reaching certain sites, where
local factors (e.g. antigen excess in gravitational dependent areas) cause them to deposit and bind to the vessel wall. 4.2. Complement Activation and Consumption The Fc portion of the immunoglobulin molecule binds complement and initiates the complement cascade. Subsequent elaboration of the potent chemotactic factor C5a attracts neutrophils into the vessel wall. Tissue injury occurs as the activated neutrophils phagocytise the immune complexes and thereby release destructive proteolytic enzymes. The resulting inflammation, necrosis, and haemorrhage appear clinically as palpable purpura when they occur on the skin. 4.3. Lymphocytic Infiltration Following exposure to antigenic material, tissue lymphocytes and histiocytes become activated to produce various cytokines and inflammatory mediators. Their interaction with intercellular adhesion molecules on cell surfaces will initiate and regulate cell mediated immunity, leading to further lymphocyte proliferation and macrophage aggregation at the site of inflammation. 4.4. Granulomatous Inflammation and Giant Cell Formation Failure to clear the antigen will perpetuate the inflammatory processes and eventually lead to epitheloid giant cell and granuloma formation. 5. CLINICAL PRESENTATION 5.1. Cutaneous Features Morphology of skin lesions: Persistent urticated lesions, tender palpable purpura, papules, nodules, haemorrhagic bulla, ulcers, atrophie blanche, livedo reticularis, nail foldtelangiectasia, infarct, digital gangrene. Distribution of Skin lesions: Often start on dependent areas initially (e.g. lower legs, buttocks, back) before becoming generalized. This is due to the effect of hydrostatic force on the post-capillary venules, leading to the preferential deposition of immune complexes in these sites. Course of skin lesions: Occur in successive crops, evolving from papules, nodules to palpable purpura which resolve leaving pronounced post-inflammatory hyperpigmentation. Depending on the aetiology, the course may be acute, resolving within few days to few weeks; or it may be chronic and recurrent, persisting from months to years. 5.2. Extra-cutaneous Features General: fever, malaise, mucous membrane ulcers Renal: glomerulonephritis - proteinuria, haematuria, hypertension
Pulmonary: pneumonitis and haemorrhage - haemoptysis, dyspnoea GI tract: malaena, abdominal pain Musculoskeletal: joint pain, myalgia Neurological: mononeuritis multiplex, myelopathy, CVA Eye: iritis, uveitis Cardiac: pericarditis, endocarditis, myocarditis and infarct 6. INVESTIGATION Investigations are performed to: 1) Confirm the diagnosis of vasculitis and determine the predominant cell infiltrate by skin biopsy. 2) Screen for any extra-cutaneous organ involvement and hence the systemic nature of vasculitis. 3) Exclude an offending causative agent and remove it if possible e.g. drug. 4) Screen for and treat any underlying disease processes that may be responsible for the vasculitis e.g. infection, connective tissue disease or malignancy. 1) Skin biopsy for histopathological studies, including immunoflourescent staining. 2) Blood Tests for Complete blood count & Erythrocyte sedimentation rate Antinuclear Factor Screen Rheumatoid Factor Complements C3, C4 Liver and Renal biochemistry profile C-Reactive Protein Anti-streptolysin O titre Cryoglobulins Anticardiolipin Antibody (Quantitative VDRL) Immunoglobulin pattern and Serum protein electrophoresis Hepatitis B Antigen Anti-Neutrophil Cytoplasmic Antibody 3) Throat swab for culture 4) Urinalysis for proteinuria, Red blood Cell, White cell, and Casts 5) Stool for Occult Blood 6) Chest X ray 7) Nerve Conduction Studies and/or Nerve Biopsy N.B.: More invasive investigations like renal or lung biopsy may be relevant but should not be taken lightly unless clearly indicated and in conjunction with the physician. 7. TREATMENT
7.1. Cutaneous 1) Supportive: Bed rest, elevation of dependent parts and avoidance of trauma and cold 2) Anti-inflammatory agents: Include topical steroids, non-steroid anti-inflammatory drug e.g. indomethacin, colchicine 0.5 mg bd or tds, dapsone 50-100 mg qd (esp erythema elevatum diutinum), sulphapyridine, Minocin. 3) Antiplatelet agents: Such as aspirin or dipyridamole are sometimes used. 4) Systemic corticosteroids given as a short course may be useful in an acute severe episode to reduce morbidity and produce early resolution of lesions 7.2. Systemic Systemic vasculitis with widespread involvement of internal organs (e.g. renal, heart, lung) may result in life-threatening complications (e.g. acute renal failure). Prompt treatment with high dose systemic steroids and immunosuppressives, e.g. cyclophosphamide are required to reduce morbidity and are often life-saving. Monitoring of electrolytes, haematological picture, and hepato-renal function is necessary during treatment. 7.3. Life-Threatening Systemic Vasculitis IV Pulse Methylprednisolone, 1 g QD for 3-5 days IV Cyclophosphamide 2 mg/kg/day, for 5-7 days Plasmapheresis, plasma exchange These agents are indicated in emergency situations where immediate control of the disease activity is imperative to prevent mortality and preserve organ (e.g. renal) function. IV Cyclophosphamide may cause haemorrhagic cystitis. Careful monitoring of fluid and electrolyte balance is necessary during administration. Any infection should be identified and treated promptly. 8. APPENDIX: Examples of vasculitis with significant skin involvement 8.1. Leucocytoclastic Vasculitis This is a heterogeneous disorder with hypersensitivity reaction and immune complex deposition, following exposure to an antigen, foreign (e.g. infectious agent, drug) or endogenous. The small vessels (post-capillary venules) are infiltrated with neutrophils and their nuclear debris (leuco-cytoclasis) in the acute stages. Skin lesions occur on gravitational dependent areas: lower extremities of ambulatory patients or sacral area of bed-ridden patients. These include palpable purpura, macules, papules, vesicles, bulla, subcutaneous nodules, ulcers, recurrent or chronic urticaria. The ankles and
lower limb may be swollen. Extra-cutaneous symptoms include fever, malaise, arthralgia, myalgia, haematuria, GI bleeding and neuropathy. Investigations reveal mild leucocytosis and elevated ESR; cryoglobulins and rheumatoid factor may also be detected. Henoch-Scholein purpura (anaphylatoid purpura) is a variant that occurs in children and young adults after an upper respiratory infection. It is characterized by purpuric skin eruptions on the extensor surface of lower limbs and buttocks, arthritis, abdominal pain, and glomerulo-nephritis with haematuria. Raised serum IgA and IgA immune deposits are found on the affected vessel walls. Platelet count is normal and distinguishes this condition from thrombocytopenic purpura. Treatment: 1) Bed rest and elevation of the dependent parts. 2) NSAID to control inflammation and relief joint pain. 3) Monitor for systemic involvement like blood pressure and urinalysis, stool for occult blood etc. 4) Screen and treat the underlying cause if possible. Only when the function of vital organs (e.g. renal) are compromised should systemic steroids be necessary. 8.2. Necrotising Vasculitis 8.2.1. Classic Polyarteritis Nodosa (PAN) This is a multi-system, necrotising vasculitis of small and medium sized muscular arteries with characteristic involvement of renal and visceral arteries. 30% are HBsAg +ve. The mean age of onset is 45 years with a male preponderance (M/F 2.5 to 1). Systemic features include fever, malaise, arthralgia, myalgia, abdominal pain, malaena, CVA, neuropathy, hypertension and renal failure. Cutaneous lesions occur in 50% of cases with painful subcutaneous nodules, purpura, ulcers, infarct and gangrene along the course of arteries and a livedo reticularis pattern. Microscopic PAN is a variant with small vessel vasculitis and focal segmental glomerulonephritis. Investigations include skin biopsy of nodular lesions, sural nerve biopsy and nerve conduction study. Blood tests showed raised ESR, leucocytosis with neutrophilia, anaemia of chronic disease, hypergammaglobulinaemia, and positive Hepatitis B surface antigen. Renal and visceral artery involvement can be demonstrated by small aneurysmal dilatations on visceral angiography. Classic PAN does not involve pulmonary arteries; granuloma and significant eosinophilia are not part of the syndrome. Treatment and course: The clinical course is characterized by progressive deterioration with intermittent acute flare ups. Death usually results from renal failure. The 5
year survival of untreated patients is 13%, but with combined systemic steroid and cyclophosphamide therapy there may be a 90% long term remission rate even after discontinuing therapy. 8.2.2. Cutaneous Polyarteritis Nodosa A more benign form of PAN where vasculitis is chiefly confined to the skin only. Cutaneous manifestation is similar but milder than classic PAN; nodules and livedo, with accompanying fever, arthralgia and neuropathy occasionally. Treatment includes low dose systemic steroids. The prognosis is good with no significant mortality even without treatment. 8.2.3. Churg-Strauss (Allergic Granulomatous) Angiitis Churg-Strauss is a systemic vasculitis that shares many features with classic PAN, but distinguished by the following features: Frequent involvement of the lung. Vasculitis of blood vessels of various types and sizes. Intravascular and extravascular granuloma formation with eosinophilic tissue infiltration. Strong association with severe asthma and peripheral eosinophilia. Skin lesions occur in 70% of cases but renal disease is less common or severe as PAN. The 5 year survival of untreated Churg-Strauss is 25%. The cause of death is often related to cardio-pulmonary involvement as opposed to renal and gastro-intestinal involvement of PAN. Glucocorticoid therapy alone improves 5 year survival to 50%. Combination regimen of cyclophosphamide and alternate day prednisolone is required for more severe cases and may result in high rate of remission approaching that of classic PAN. 8.2.4. Kawasaki Disease (Mucocutaneous Lymph Node Syndrome) This is an acute vasculitis of unknown aetiology that most frequently affects infants and children below 5 years of age. It is probably initiated by an yet unidentified infective agent. The clinical picture is characterized by fever, palpable cervical lymph node, bilateral conjunctivitis, red cracked lips with strawberry tongue, and generalized erythematous desquamative rash especially on extremities. It affects the coronary arteries in up to 30% of cases. Overall mortality is 1-2% due to cardiovascular complications: acute coronary thrombosis and late sequel of coronary artery aneurysm. High dose aspirin remains the mainstay of treatment. Recent studies in Japan and USA have shown that high dose intravenous gamma globulin is effective in reducing coronary artery abnormalities when given early in the course of
the disease. Systemic steroids are contraindicated because they increase risk of coronary complications. 8.3. Livedo Reticularis and Atrophie Blanche Atrophie blanche are peculiar porcelain white scars studded with pepper-like red macules and telangiectasia seen around the medial malleolus of both ankles. They are frequently the result of chronic venous stasis in varicose vein disorder, yet sometimes they represent the healed result of painful vasculitic infarction. Livedo vasculitis associated with atrophie blanche is considered as a distinct entity by North American Dermatologists. Livedo reticularis describes the blotchy, mottled, net-like pattern of skin cyanosis seen in cutaneous vasculitis as a result of reduced and sluggish cutaneous blood flow. A similar but reversible appearance may be seen as a physiological response to cold on the exposed lower limbs of young girls during winter. Livedo reticularis may be secondary to cutaneous polyarteritis, lupus vasculitis, and vasculitis associated with antiphospholipid antibody syndrome. In the latter, livedo may occur together with atrophie blanche. Treatment: The disorder is associated with a decrease in fibrinolytic activity in skin and increase platelet adhesiveness. Phenformin and ethylestrenol in combination are effective because of their enhancement of fibrinolytic activity. Combination of low dose aspirin (300 mg/day) and dipyridamole (50 mg tds) which affect platelet function are helpful. Pentoxifylline (Trental) 400 mg tds has also been used with some success. COLLAGEN-VASCULAR DISEASES Dr. R. SU & Dr. Y.M. TANG CHAPTER 9 1. LUPUS ERYTHEMATOSUS 1.1. Epidemiology In the nineteenth century, a group of diseases of erythematous and atrophic nature was classified as lupus erythematosus (LE). It was thought the skin appearance was due to the gnawing by a wolf (Latin: lupus). Today, the term coins a group of autoimmune diseases that bears various characteristic cutaneous and histological features, and protean systemic manifestations in some. (q.v.) This group of diseases is divided into three major subsets; namely, chronic cutaneous LE (CCLE), also called discoid LE, subacute cutaneous LE (SCLE) and systemic LE (SLE). CCLE affects female and male at a ratio of 2:1, from their second to eighth decade with a mean age of 38 (37.8 in a local study). The incidence of
CCLE is not certain, it is probably under-reported as many cases are trivial and may have escaped diagnosis. Generally speaking, females at a younger age predominate in SLE, blacks and Chinese are more susceptible than whites. An estimated incidence of 6.0-50.8 cases/100,000 population in the western world is noted. 1.2. Essential Features of the Major LE Subsets Discoid plaque is prototypic lesion in CCLE. The lesions frequently occur in the head and neck and exposed areas with sizes varying from a few millimetres to a few centimetres. It begins as erythematous, oedematous scaling papules which spread centrifugally and coalesce into a plaque that exhibits thick and adherent scales. Lifting of the scales produces a carpettack appearance, revealing dilated pilosebaceous orifices occupied by horny plugs (follicular plugging). Healing of lesion usually takes place in the centre producing atrophy, scarring, telangiectasia and pigmentary changes (hypopigmentation in the centre and hyperpigmentation in the active margin). Histopathology of an established lesion shows typical histologic changes. (q.v.) Systemic or serological abnormalities in these patients are absent or minimal and the revised criteria of the American College of Rheumatology (ACR) for SLE are not met. In SCLE, skin lesions are annular or papulosquamous, and they share similar morphology with discoid lesions but healing is not accompanied with scarring and atrophy is minimal or absent. Photosensitivity and serological abnormalities are more frequent than CCLE. The full gamut of LEassociated problems can occur though mild. SLE is a systemic disease characterised by the association of immunological abnormalities and multiple organ involvement. The main clinical features include fever, rashes (especially malar) and arthritis, as well as renal, pulmonary, cardiac and neurological diseases. A diagnosis of SLE is established if four or more of the ACR revised criteria for SLE are satisfied. 1.3. Pathogenesis of and Relationship Among Different Types of LE The pathogenesis of LE is not definitively known. A T-cell mediated injury is implicated in the discoid lesions. Anti-Ro (SSA) has strong implication in the production of disease in photosensitive SCLE and neonatal LE (NLE). Ultraviolet light induces Ro antigen expression on the keratinocytes, targeting it for binding by anti-Ro antibody and/or sensitized T cells. In SLE, many features are a consequence of antibody production and immune complex formation. It is debatable whether CCLE and SLE are distinct entities or represent either end of a disease spectrum. They both share similar clinical, haematological, biochemical and immunological abnormalities. Considering
that: 1) both have different age and sex distribution, 2) presence of laboratory abnormalities in CCLE does not appear to predispose to the development of SLE, 3) immunoglobulins and complements are present in uninvolved skin of SLE but not in CCLE, 4) a patient with CCLE can develop into overt SLE but is rare, and 5) evidence is available that both have different genetics; it would appear that they share similarities but are different diseases. 1.4. Mucocutaneous Features Mucocutaneous lesions of LE are commonly divided into specific and nonspecific types. Table I shows the specific mucocutaneous lesions of LE. They are characteristic of LE and help us infer which particular LE subset the patient suffers; however, the three LE subsets are not mutually exclusive. Table II tabulates the lesions that commonly occur during the course of LE but are not sufficiently specific to be indicative of LE. Table I: Specific LE Lesions Chronic Discoid 1 Hypertrophic 2 Palmar/plantar 3 LE panniculitis 4 Subacute Annular Papulosquamous ¡@ ¡@ Acute Malar rash 5 Bullous SLE 6 ¡@ ¡@
Discoid lesion, though is representative in CCLE, also found in 15% of SLE and 15-30% of SCLE. Hypertrophic lesions are thickened, nodular and warty, and reminiscent of warts, prurigo nodularis, keratoacanthoma or squamous cell carcinoma. Palmoplantar lesions are rare but often symptomatic and erosive, and can impair movement. Lupus panniculitis have a female to male ratio of 3-4:1. Lesions are erythematous, firm, subcutaneous nodules. It is more frequently associated with DLE, and less with SLE, and occurs in scalp, forehead, cheeks, chin, arms, back, buttocks, thighs, breast, eyelids and chest. The overlying skin can be normal, discoid or poikilodermatous. Ulcerations may occur. Malar rash is characterised by erythematous, slightly oedematous patch, with no scars or atrophy over the malar skin. The onset is usually abrupt and lasts for hours, days or weeks. The appearance may simulate a
photosensitivity eruption, dermatomyositis, or other disorders such as seborrhoeic dermatitis or rosacea. The lesion can affect any parts of the skin. Bullous SLE is a rare (< 5%), acquired subepidermal blistering disease occurring in a patient with SLE, in which immune reactants are present at the dermoepidermal junction on either direct or indirect immunofluorescence. Table II: Nonspecific LE Lesions Livedo reticularis 1 Maculopapular lesions Mucinous infiltration Nonscarring alopecia Oral erosions 2 Photosensitivity 3 Vasculitis (urticarial lesions, palpable purpura, gangrene, ulcers etc.) Livedo reticularis describes a lace pattern of cyanotic skin discoloration. It is due to dilatation of subpapillary venous plexuses and occlusion of small vessels feeding the upper cutis and is accentuated by cold. Intraoral discoid lesion is easily confused clinically and histologically with lichen planus. They frequently become erosive, leading to further scarring and infection. The symptoms of photosensitivity refer to an increased redness, swelling, itch and irritation of the pre-existing lesions upon sun exposure. 1.5. Systemic Features About 5% of CCLE and up to half of SCLE patients will have systemic involvement. Most SCLE patients have a relatively mild systemic illness and neurological and renal diseases are uncommon. The features of SLE are protean and sometimes confuse clinicians (Greenwald's hypothesis a ). A summary of the systemic features reported in a local study involving 137 LE cases b (> 90% of patients fulfilled four or more ACR criteria) is depicted in Table III. Table III: Systemic Features of SLE Systemic features of SLE Overall incidence (% of
patients) Arthritis/arthralgia Renal Haematological (thrombocytopenia, pancytopenia, leucopenia, haemolytic anaemia) Serositis Neurological Others Unexplained fever Lymphadenopathy Raynaud's phenomenon 71 69 38 20 26 ¡@ 28 18 15
1.6. Investigations For every patient with skin lesions of LE irrespective of the morphology, an initial work-up should be performed to exclude any systemic involvement. A battery of blood tests include: 1.6.1. Blood Tests Haematology: Haemoglobin, reticulocyte, white cell with differentials, ESR Biochemistry: Renal and liver functions Urinalysis: Red cells and proteins Serology/Immunology: 1) Anti-nuclear antibody (ANA) 2) Anti-double stranded DNA (Anti-dsDNA) 3) Anti-ENA (especially anti-Ro/La) 4) Anti-cardiolipin antibody (ACL) 5) Lupus anticoagulant 6) Immunoglobulins (Igs) 7) Complement levels 8) VDRL test for syphilis
In the absence of specific clinical symptoms and if initial investigations are normal, a half to one yearly monitor of complete blood count, ANA, and urinalysis is adequate. Patients with persistent abnormal test results should be seen more frequently (e.g. 3-monthly) to identify evidence of SLE. Compared with SLE, blood test results in cutaneous LE are usually normal or only mildly deranged. Abnormal test results in cutaneous LE include a low haemoglobin, thrombocytopenia, leukopenia, raised ESR, raised titres of ANA, anti-Ro (SSA)/La (SSB), ACL and biological false positive VDRL test for syphilis. ANA is one of the most common tests requested. It is a group of antibodies that react with one or several nuclear constituents. It is usually detected by indirect immunofluorescence tests where antibodies in the patient's serum react with a substrate (rat liver, monkey oesophagus or HEP-2 human cell line), and after washing and incubation with fluorescein-labelled antihuman Igs. It is then examined under the fluorescence microscope and a patterned fluorescence in the substrate nuclei is revealed. The information on pattern and titre can be obtained from this test. The different patterns of ANA observed correlated with antibodies against specific nuclear antigens and may infer different rheumatological disorders. However, pattern differentiation needs experience, and in the case where antibodies to more than one nuclear constituent are present, the interpretation is even more difficult. Therefore, to identify ANAs by antigen instead of fluorescence pattern is more rewarding. ANA titres are elevated in about 20 to 60% of CCLE, whereas a higher incidence is noted in SLE. It should be noted that a positive low ANA titre can occur in normal individuals and non-LE diseases and hence its presence is not specific for LE. ANA titres fluctuate during the course of a disease. They cannot accurately reflect disease activity and therefore not recommended to gauge progress of LE. Anti-Ro (SSA) antibody is present in 30-50% of SLE (this figure is higher in Orientals b) and up to 95% of SCLE on repeated testing. Hence, absence of these is evidence against the clinical diagnosis of SCLE. Anti-dsDNA and anti-Sm occur in SLE, whereas anti-U1RNP suggests mixed connective tissue diseases. The high titre of anti-Ro in SCLE is said to be related to photosensitivity but the low titre that appears in some cases of CCLE does not indicate the risk of photosensitivity. Lee et al b reported a 69% positive rate for anti-dsDNA antibodies in SLE. 1.6.2. Histopathology The early stage of acute LE rash shows non-specific features, papillary dermal oedema and perivascular lymphocytic infiltrate can be found. Adnexal involvement is lacking. In an established lesion, epidermal atrophy,
liquefaction degeneration, and papillary dermal fibrinoid deposition are noted. CCLE shows epidermal hyperkeratosis with follicular plugging, thinning and flattening of the stratum malpighii, basal cell hydropic degeneration, periappendageal lymphoid cell infiltration, and upper dermal oedema and vasodilatation. SCLE shows similar histological features except that scarring and follicular plugging are absent and epidermal atrophy is not prominent. Lupus panniculitis is characterised by infiltration of fat cells by lymphocytes, plasma cells, and histiocytes. Septal fibrosis, lobular hyalinised sclerosis, and vessel wall hyalinization are evident. Lymphoid follicles are often present. Bullous SLE shows interface dermatitis, superficial ?/font> deep perivascular infiltrate with neutrophil predominance. Mucin deposition in dermis is evident. A subepidermal blister is evident in an established case. Immunofluorescence (IMF) study is not essential for the diagnosis of LE but is helpful when other features are not diagnostic (e.g. a biopsy from an acute LE lesion or scalp with scarring alopecia). Direct IMF study often shows IgG, IgM and complement deposition at the dermoepidermal junction. The lupus band test is positive for nonlesional exposed and sometimes unexposed skin in SLE but this is usually negative in CCLE. 1.7. Diagnostic Pitfalls 1) Discoid lesions are usually specific but at times may be confused with: Polymorphic light eruption (PLE) Rosacea Seborrhoeic dermatitis and psoriasis on the face Tinea faciei Lichen planopilaris, pseudopelade of Brocq, and tinea tonsurans Jessner's lymphocytic infiltration of the skin 2) Papules and plaques of SCLE: Psoriasis Photodrug or polymorphic eruption Erythema centrifugum annulare and dermatophytosis 1.8. Management of Cutaneous Manifestations General: 1) Avoidance of sun: patients should be advised on the avoidance of sun and strong light, the use of broad brim hat and tight woven clothing should be emphasized.
2) Sunscreens to shield out UVB and UVA are required. The sunscreen should have sun protection factor (SPF) >15. More frequent application of sunscreens is necessary at the time of profuse sweating and swimming. 3) Drugs that potentially aggravate LE should be avoided. Topical: 4) Topical steroid: potent topical or intralesional steroid is helpful for localized and mild disease. Mild steroid is sufficient for lesion of NLE. Care should be exercised to avoid side effects induced by prolonged application, the face is most susceptible. Systemic: 5) Antimalarial: Hydroxychloroquine is effective for widespread cutaneous diseases and may prevent new eruptions. It also serves as an adjunct in SLE. The initial dose is 400 mg/day, followed by 200-400 mg/day depending on response. Response usually occurs in four weeks. CBP, RFT and LFT should be monitored and regular examination by ophthalmologist needed. If response to hydroxychloroquine is poor, quinacrine can be tried but yellowish skin discoloration is a notable side effect. 6) Dapsone: is effective for bullous SLE, vasculitis, oral ulcerations. Haemolytic anaemia is a major side effect and should not be used in patients who are Glucose-6-Phosphate dehydrogenase deficient. 7) Thalidomide: Alternative therapy when antimalarial fails or is contraindicated. It is teratogenic and is contraindicated in women of childbearing age. Neuropathy is another important side effect, and patients should receive periodic neurologic assessment and nerve conduction studies. 8) Etretinate: reported to be useful for hyperkeratotic lesions. 9) Prednisolone: Is very useful for cutaneous and systemic diseases. Side effects limit its prolonged use. 10) Immunosuppressives - azathioprine is most commonly used, it is usually given with prednisolone and hence steroid-sparing. It has been reported to be useful for palmoplantar lesions. 1.9. Risk Factors of CCLE for Dissemination and/or Systemic Involvement No single data can accurately predict which patient will have progressive skin disease or internal organ involvement. However, the following history or test results, in different combinations at appropriate settings, should alert the clinicians for close monitoring. 1) Clinical Unexplained persistent fever, Raynaud's phenomenon, arthralgia/arthritis, diffuse alopecia, progressive lower limb oedema, mucocutaneous vasculitis, and CCLE affecting a very young patient.
2) Laboratory tests Anaemia, thrombocytopenia, leucopenia and raised ESR. Positive Anti-dsDNA and/or anti-Sm. Very high ANA titre (some believed a correlation exists with dissemination of skin lesions. It is not an useful indicator of progression to SLE). High titre of ACL. Biological false positive test for syphilis. Low titres of C3, C4. 3) Lupus band test Deposits of IgG, IgM, IgA or all three in nonlesional, non-facial, sunprotected skin is highly suggestive of SLE. 4) Other HLA-B8 females at the ages of 15-40. N.B.: a) Greenwalds' hypothesis of Lupus states that anything happening to a patient with SLE which is not immediately otherwise explicable will automatically be blamed on the lupus, regardless of pathophysiologic validity. b) Modified from Lee SS. Lupus 1993;2:105-109 2. Dermatomyositis This is characterized by skin rash, muscle weakness and tenderness. In addition to skin and skeletal muscle involvement, there may be involvement of muscles of gastrointestinal system (dysphagia and aspiration), heart (cardiomyopathy, arrhythmias), and lung (pulmonary fibrosis). 2.1. Epidemiology Dermatomyositis (DM) is an uncommon condition. Female is twice as commonly affected as male. In young female patients it is associated with autoimmune connective tissue diseases. There may be underlying systemic malignancy, particularly for patients over 40 years old. DM is more often associated with malignancy than polymyositis. Common malignancies include breast, lung, gastrointestinal, ovarian cancer, and in our locality nasopharyngeal carcinoma. The cancer may precede, occur simultaneously, or follow DM. Removal of underlying malignancy may be associated with resolution of DM, and recurrence of malignancy may lead to relapse of DM. 2.2. Clinical Features Presentation and clinical course may be: acute, subacute, chronic. The severity of cutaneous involvement does not correlate particularly well with severity of associated myositis. Muscle involvement without cutaneous features is termed polymyositis. Cutaneous involvement may precede muscle involvement, or occur without apparent muscle involvement.
Muscle involvement include: Muscle pain and tenderness affecting trunk, limb girdles and proximal limbs. Muscle weakness is symmetrical and bilateral. Weakness is progressive, with difficulty rising from low chairs, climbing stairs, and holding arms above shoulder during combing hair. Facial and bulbar muscles are usually spared, but may be affected in cases associated with malignancy or myasthenia. Dysphagia may occur due to oesophageal involvement, arrhythmia and cardiac failure due to myocarditis. Cutaneous features include: Violaceus erythema and oedema of periorbital region, especially upper eyelids. There may be diffuse redness and swelling of entire face, extending to other sun-exposed areas. Photosensitivity, poikiloderma (erythema, pigmentation, telangiectasia, atrophy) of face and upper chest shoulders and arms. Red to violaceous patches and plaques over extensor surface of elbows and knees. Gottron's sign refers to such patches and plaques over knuckles (dorsal surfaces of interphalangeal joints). In LE, similar changes are characteristically located on dorsal phalanges between the phalangeal joints instead. Raynauds phenomenon, periungal erythema and telangiectasia. Lupus like and sclerodermatous skin involvement. Calcinosis, chronic ulcers. Calcinosis universalis in juvenile DM. Childhood form of DM is often slow and progressive, characterized by calcinosis. The calcinosis often involve intermuscular fascial planes, but may be subcutaneous and acral (elbow, knees, fingers) as in adults. Juvenile DM are usually steroid responsive, but often associated with contractures and deformity, leading to functional disability and morbidity. One variant is characterized by vasculitis of muscles and gastrointestinal tract, rapid onset of severe weakness, steroid unresponsiveness and death. Internal malignancy is seldom seen in either type. 2.3. Diagnosis This is essentially clinical, supported by investigations (q.v.). Periorbital heliotrophic rash, especially upper eyelids. Gottrons patches over knuckle. Poikilodermatous rash over sun-exposed areas and extensor surfaces of upper limbs. Peri-ungal erythema and telangiectasia. Proximal girdle muscle tenderness and muscle weakness.
Muscle enzymes are raised, and muscle biopsy shows typical inflammatory changes. Diagnosis is straightforward with classical cutaneous features and documented muscle involvement. However diagnostic difficulty arises when there is no apparent muscle involvement and the skin rash is relatively nonspecific. With time clinical features may become characteristic of DM, but sometimes another diagnosis (e.g. LE) may become apparent instead. The diagnostic implication of adult DM is to screen for underlying malignancy, together with close monitoring and follow up. 2.4. Diagnostic Pitfalls The following conditions may be confused with DM when the clinical presentation is atypical. In such situations, DM needs to be considered and differentiated from such conditions. 1) Cutaneous Features Systemic LE, subacute lupus, mixed connective tissue disease. Rosacea, facial eczema, photosensitive dermatitis, erythema multiforme. Erysipelas, angioedema, lymphatic or SVC obstruction. Radiodermatitis, mycosis fungoides, scleroderma 2) Muscle Weakness trichinosis myasthenia gravis muscular dystrophy toxoplasmosis 2.5. Investigations 1) Diagnosis Diagnosis is essentially clinical, as cutaneous histopathological features are non-specific. There is vacuolar interface dermatitis with sparse superficial perivascular lympho-histiocytic infiltrate, which is consistent but not diagnostic of DM. Immuno-flourescence studies do not show significant immune deposits at dermo-epidermal junction. Skin biopsy may differentiate LE from DM when clinical features are nonspecific, but this is also difficult unless characteristic LE histopathological features are present. (q.v.) 2) Assess extent of involvement a) Muscle enzymes CPK, AST, LDH are performed to document myositis and assess progress during treatment. Muscle enzymes are not specific of DM, it may be elevated in other situations or apparently normal in DM without significant muscle involvement. Twenty four hour urine for creatine may increase sensitivity, but is not readily available. b) Muscle involvement is often focal, and electromyography EMG may help to locate the affected muscles. Random muscle biopsy is subjected to
sampling errors. Magnetic resonance imaging (MRI) has recently been investigated as a sensitive tool for locating subclinical myositis and guide muscle biopsy, even if muscle enzymes and EMG were apparently normal. c) ECG and echocardiography may be necessary as clinically indicated to assess cardiac involvement. Lung function may be need to monitor respiratory muscle involvement. Barium swallow to assess pharyngeal and eosophageal motility, and aspiration. 3) Look for an aetiology Routine and special investigation as directed by thorough history and careful examination. a) Screening for underlying malignancy Stool for Occult Blood CBP, ESR Carcino-Embryonic Antigen, a -Feto Protein IgA-EBV Chest X Ray Skull X Rays for NPC views ENT examination and nasopharyngeal biopsy Careful examinations of gastro-intestinal, breast, pelvic and gynaecological systems, with endoscopy, mammography, and ultrasound pelvis, as indicated. b) Auto-immune screen These investigations may help to differentiate DM from other auto-immune connective tissue diseases and overlapping syndromes, in conjunction with clinical features. ANA is present in both LE and DM. Anti-double stranded DNA, low C3 and C4 (systemic LE). Anti-ENA, Anti-U1RNP (Mixed Connective Tissue Disease). Anti-Ro, Anti-La (Subacute cutaneous lupus and Sjogrens syndrome). Anti PM-Scl (Polymyositis scleroderma overlap syndrome). Anti-Jo1 (histidyl tRNA synthetase) antibody, polymyositis with interstitial lung disease, pulmonary fibrosis. 2.6. Treatment 1) Treatment of skin diseases: Sunprotection: Avoid outdoor activity around mid-day, protective clothing, broad spectrum UVA and UVB sunscreens with SPF>15 Topical steroids Antimalarials: Hydroxychloroquine (below 6.5 mg/kg/day), same as for cutaneous LE.
Systemic steroids are sometimes used but generally more effective in controlling myositis than cutaneous manifestations Systemic steroids may cause steroid myopathy with prolonged use, leading to paradoxical decrease in muscle weakness following steroid dosage reduction. Twenty four hour urine creatine levels are not elevated in steroid myopathy. 2) Treatment of muscle involvement: This should preferably be managed in conjunction with physicians. Bed rest during the acute phase. Physical therapy, physiotherapy especially important in juvenile DM to prevent contractures and deformity. Systemic steroids are the mainstay of therapy for myositis. Initial dose of prednisolone is 1 mg/kg/day, with dose adjusted according to clinical response and muscle enzymes. Methotrexate, azathioprine, cyclophosphamide, cyclosporin as immunosuppressives and steroid sparing agents. Pulse intravenous methyl-prednisolone, plasmapheresis and intravenous immunoglobulin infusion have been tried in acute life threatening stages for rapid control and stabilization. 2.7. Prognosis The prognosis of adult DM is that of the underlying malignancy. Childhood DM usually has less mortality, but substantial morbidity including calcification and contractures especially if not treated early. DM and pregnancy may adversely affect each other. Facial lesions and muscle weakness get worse, fetal loss occurs. 3. Scleroderma Scleroderma describes the thickening and hardening of the skin due to progressive accumulation of dermal collagen, leading to fibrosis and loss mobility of skin. It can exist as cutaneous or systemic form. Cutaneous forms are morphea, linear scleroderma, and generalised morphea, these are confined to the skin as tight indurated plaques. Systemic sclerosis refers to a similar process involving not only the skin but internal organs as well, and may lead to organ failure or even death. Organs affected include lung, gut, kidneys, heart and skeletal muscle. Common causes of death are aspiration pneumonia, pulmonary fibrosis, and renal failure, 3.1. Diagnosis Proximal diffuse (truncal) sclerosis, with skin tightness, thickening and nonpitting induration. Sclerodactyly, with sclerosis affecting only fingers or toes, leading to sausage shaped digits.
Pitted scarring of finger tips due to loss of substance from digital pulp, with tapering of fingertips. Bilateral basal pulmonary fibrosis. Other clinical features include: Raynauds phenomenon, telangiectasia of posterior nail fold, calcinosis of finger tips and matted telangiectasia on face and hands. Skin tightening may lead to mask face, beaked nose, and radial furrows around mouth. There may be generalised hyperpigmentation with hypopigmented patches on the skin. 3.2. Skin Biopsy In the dermis there are thick bundles of collagen running parallel to the skin surface, with entrapment of sweat glands and adenexal structures. The overlying epidermis tends to be thin and atrophic. 3.3. Immunology ANA CREST: anti-centromere antibody positive MCTD: associated with ENA, anti-U1RNP positivity Systemic sclerosis: ANA, Scl 70 antibody positivity 3.4. Sclerodermatous Syndromes Many conditions have widespread induration of the skin. It is beyond scope here to discuss individual conditions, but they should be borne in mind in the differential diagnosis of a sclerodermatous condition. Some conditions are more responsive to treatment than systemic sclerosis. Auto-immune or connective tissue diseases: Generalised morphea Progressive systemic sclerosis CREST syndrome (calcinosis, Raynauds, oesophageal dysmotility, sclerodactyly, telangiectasia) Mixed Connective Tissue Disease (MCTD): DM, SLE, scleroderma Eosinophilic fasciitis Chronic graft versus host disease Environmental agents or drugs: Bleomycin cancer chemotherapy Eosinophilic myalgic syndrome following L-tryptophan ingestion Occupational vinyl chloride, epoxy resin Metabolic or associated conditions: Porphyrias: porphyria cutanea tarda, variegate porphyria, hereditary corpoporphyrias Porphyria like conditions: pseudoporphyria, epidermolysis bullosa acquisita Diabetic chrieopathy, scleredema InfectiInfective, malignant, infiltrative conditions:
Papular mucinosis, scleromyxoedema Primary systemic amyloidosis Cutaneous T-cell lymphoma Lepromatous leprosy 3.5. Treatment Systemic sclerosis is an uncommon condition with a highly variable course. Some progress relentlessly till death, others remain insidious or even improve with time. Many agents have been tried, but to date no single agent has predictably arrest or reverse the fibrosing process. Treatments that have been tried include penicillammine, colchicine, ketotifen, cyclosprine, g -interferon, plamapheresis, PUVA and extra-corporeal photochemotherapy. Treatment is mainly symptomatic, or to prevent complications. Raynauds phenomenon and digital ischaemia may be controlled with calcium channel blockers such as nifedipine, supplemented with pentoxifylline, dipyridamole, intravenous prostacyclin infusion. Cutaneous ulcers may be managed by protective occlusive dressing. Physiotherapy with emphasis on full range of motion of all large joints to prevent contractures and deformity, thereby preserving function. Management of extra-cutaneous involvement should be in conjunction with physicians. Renal hypertension is treated with captopril. Steroids are not effective in systemic sclerosis, but useful for myositis in MCTD and for eosinophilic fasciitis. BL ISTER ING D ISE ASES Dr. C.N. LOOK CH APTE R 10 1. INT RO DU CTI ON Blistering diseases are defined as skin disorders that primarily give rise to vesicles (i.e. 5 mm or less in diameter) or bullae (i.e. over 5 mm in diameter). Blisters are accumulation of fluid lying within or below the epidermis. Blistering diseases can be classified according to the site of cleavage (see Table 1). Only the common conditions will be discussed below. Tab le 1 : C au ses of B li st er in g D is eases A) Subcorneal Blisters: 1) Bullous Impetigo 2) Subcorneal Pustular dermatosis 3) Miliaria Crystallina B) Intra-epidermal Blisters: 1) Acute Dermatitis e.g. eczema, contact dermatitis
2) Pompholyx 3) Herpes infections 4) Fixed Drug eruptions (epidermal type) 5) Friction Blisters 6) Erythema multiforme (epidermal type) 7) Pemphigus Vulgaris C) Subepidermal Blisters: 1) Bullous Pemphigoid 2) Linear IgA Diseases 3) Dermatitis Herpetiformis 4) Erythema Multiforme (dermal type) 5) Fixed Drug Eruptions (dermal type) 6) Epidermolysis Bullosa The diagnosis of blistering diseases can sometimes be aided by physical findings. 1) Morphology of blister: Subepidermal blister occurs between the dermis and the epidermis. It contains thick wall and may contain blood. Intraepidermal or subcorneal blister usually has very thin roof. Intact blisters may not be easily detected but leaving erosions only. Palm and sole blisters usually remain intact because of the thick stratum corneum. Grouped vesicles along a dermatome is characteristic of herpes infection. 2) Site of blister: Pompholyx occurs at palm and soles. Blisters at sites of frequent trauma suggests Epidermolysis Bullosa. 3) Mucosal membrane involvement is frequently found in pemphigus, erythema multiforme and fixed drug eruption. 2. BU LLOU S IM PETIG O Bullous impetigo is usually caused by Staph. aureus while non-bullous type can be caused by Staph. Aureus and occasionally by Strep. pyogenes. More common
in children and mainly affects face and hands. Bullae are flaccid and usually contain pus. When the pustules are ruptured, they give rise to golden crusts. Diagnosis: Swab from pustules for culture Treatment: 1) Topical antibiotics (e.g. fusidic acid cream, mupirocin ointment, chlortetracycline ointment) is good for localized infection. 2) Oral antibiotics (e.g. cloxacillin, erythromycin) for widespread lesions. 3. SU BC OR NEAL P USTUL AR DE RM ATOS IS A chronic, benign, relapsing, pustular eruption with unknown aetiology. Female is more commonly affected than male. The peak incidence occurring at the age of 40-50. The eruption occurs mainly in the groins, axillae, submammary areas and the flexor aspect of the limbs. The face is never affected, nor are the mucous membranes. Lesions usually start off as intact pustules which dry up within a few days, forming crusts or scales. Eruption tends to group together to form clusters with advancing edge. Differential diagnosis: 1) Pustular psoriasis 2) Impetigo Diagnosis: Skin biopsy shows the presence of subcorneal pustules. Treatment: 1) Dapsone: Treatment of choice (50-100 mg/day) 2) Oral Steroid: less effective as compared with dapsone ¡@ 4. MIL IA RI A CR YST ALLIN A This condition occurs in hot and humid climate when babies are wearing too many clothes. It leads to blockage of the sweat ducts. Clinically, numerous monomorphic clear vesicles without surrounding erythema are seen on the skin, usually the trunk. Typically the skin remains dry. The disease is self-limiting. Calamine lotion can be prescribed. Prevention is by avoiding prolonged hot, humid environment and overclothing. 5. AC UTE DE RM ATITI S (A CUTE E CZEMA ) Vesicles are common sign of acute dermatitis. They are usually associated with intense pruritus. Vesicles are easily ruptured because of self scratching and results in multiple excoriations.
Treatment: Refer to Chapter 3. 6. PO MPH OLYX A distinct pattern of acute dermatitis as characterized by acute onset of multiple itchy vesicles +/- bullae at palms and soles. Vesicles seldom rupture because of the thick stratum corneum. Usually, the cause is unknown but occasionally may be secondary to severe tinea infection or contact dermatitis occurring in other part of the body. Treatment: Requires potent topical steroid (e.g. 0.025% fluocinolone). Oral antibiotics (e.g. erythromycin) is indicated if there is evidence of secondary bacterial infection. In very severe case, a short course of oral steroid may be required. 7. HE RPES IN FECT IO NS (HE RPES S IMPLE X/ HER PES ZOSTE R) Pain is the most useful symptom to differentiate blisters caused by herpes infections from other blistering disorders. Eczema or tinea infection gives rise to itchy rather than painful vesicles. In contrast to pemphigus or pemphigoid which may give rise to painful lesions, the vesicles of herpes infections are more localized. Refer to Chapter 14 for clinical features and management. 8. FR ICT IO N BL ISTERS It occurs at hands and feet. Diagnosis can be easily made from history e.g. wearing ill-fitting or new shoes. 9. FI XED D RU G ER UPTI ONS It is presented as well-circumscribed erythematous patches or bullae, frequently occurring at hands, penis and mouth. A characteristic feature is the recurrence of the same skin lesions at the same sites when patients are challenged by the same offending agents again. Lesions heal with circumscribed pigmentation. Histologically, subepidermal or epidermal blisters can occur. Basal cell degeneration and pigmentary incontinence are often seen. The common offending drugs include tetracycline, barbiturates, sulphonamides, phenolphthalein, salicylate and oxyphenbutazone. The disease is self-limiting. Avoidance of offending drug is most important.
10 . E RYT HEMA M ULTI FOR ME 10 .1 . Aet io log y a nd P at ho ge nesi s It is a hypersensitivity reaction to infections (e.g. herpes simplex, streptococcus, mycoplasma) or drug (e.g. penicillins, sulphonamides, barbiturates, piroxicam). 10 .2 . Clini cal Feat ures Typically, discoid well-demarcated erythematous plaques with central blisters or central necrosis can be found at 4 limbs (i.e. target lesions). Occasionally, bullae with erythematous base can occur. Stevens-Johnson syndrome is a severe form of erythema multiforme with mucosal involvement. 10 .3 . Dia gn os is The diagnosis can be confirmed by skin biopsy. The cause can sometimes be found by looking for primary site of infection (e.g. herpes) and by taking a detailed drug history. 10 .4 . Treatme nt For mild cases, giving topical steroid may be all that is needed. For frequent recurrent attacks, one should look hard for the presence of herpes infection. Maintenance oral acyclovir treatment can be considered in the latter. The beneficial effect of oral prednisolone in Stevens-Johnson syndrome is controversial. 11 . PE MPH IG US VU LGA RI S 11 .1 . Intr od uc ti on A potentially life-threatening skin condition. The disease occurs worldwide. The incidence is 0.1-0.5/100,000. The peak incidence is between 4th-6th decade. 11 .2 . Pa th og enes is An autoimmune disease due to binding of circulating antibodies to the epidermal intercellular substance which is desmoglein 3. The binding leads to acantholysis i.e. loss of intercellular adhesion.
11 .3 . C/F It presents as blisters attacking the skin including mucosae (i.e. oral mucosa, conjunctiva). Intact blister is seldom seen because the roof of the blister is thin and is easily ruptured. Ruptured bullae lead to the formation of erosions.
Nikolsky's sign (i.e. rubbing normal skin causes new lesion to form) is characteristic. Eruption tends to develop on the trunk and the face with sparing of the extremities (centripetal distribution). Involvement of the oral mucosa gives rise to painful ulcers. 11 .4 . Inv est iga ti on 1) Skin biopsy for histology This is done to confirm the diagnosis. In order to see the diagnostic features, new, rather than old lesion should be chosen for biopsy. Classically, one should find suprabasal blister with acantholysis in histology. 2) Skin biopsy for Direct Immunofluorescence (IMF) Perilesional skin shows the presence of intercellular IgG deposition within the epidermis. 3) Indirect Immunofluorescence (Serology) Serum from the patient allows the titre of the circulating anti-intercellular antibody to be measured. The titre correlates with the disease activity and is a good parameter for monitoring the disease progress. A more than twofold increase in titre is an indication of relapse. This test is not casually available. It can only be done in a few hospital-based centres with special arrangement. 4) Tzanck test A cytology method revealing the characteristic acantholytic cells. It provides an instant diagnosis. However, it is seldom done since it requires expert cytologist and it also carries a significant false positive as well as false negative rates. 11 .5 . Mana gement Potentially lethal disease. Hospitalization is often required for close monitoring of disease progress. Hospitalization is particularly indicated if any one of the following conditions which signifies severe involvement occurs: 1) Extensive cutaneous involvement 2) Systemic upset 3) Mucosal involvement other than oral cavity 4) High indirect immunofluorescence (IMF) titre. 11 .6 . Top ica l Trea tmen t Potent topical steroids have to be used (e.g. clobetasol propionate). Usually given as an adjuvant therapy. Rarely, when skin lesions are very localized, then topical treatment can be given as a single therapy. For oral lesions, one can try triamcinolone in orabase, intralesional steroids or steroid aerosol.
11 .7 . Sys temi c Treatme nt 1) Oral Steroid Prednisolone is the drug of choice. To control the acute attack, usually it requires a very high dose (i.e. 60-80 mg daily) to start with. Occasionally, > 100 mg of prednisolone has to be prescribed for very severe cases. Steroid may be increased by 50% every 4-7 days until the disease is controlled. The dose of prednisolone is adjusted further to consolidate the remission and is maintained for 2-4 weeks. It can then be gradually tailed down. The control of the disease activity is indicated by no new eruption, low titre of anti-intercellular antibody. Watch out for complications especially silent infection during high dose oral steroid treatment. 2) Steroid-sparing Agents Since a relatively high dose of prednisolone is usually required to control the disease, in order to prevent the long term side effects of oral steroid (e.g. opportunistic infections, osteoporosis), an immunosuppressant can be added for its steroid sparing effect. Commonly used immunosuppressants are: a) Azathioprine (2-3 mg/kg/day) b) Cyclophosphamide c) Methotrexate The major side effects of azathioprine and methotrexate are marrow suppression and hepatotoxicity. Cyclophosphamide may give rise to haemorrhagic cystitis, infertility as well as marrow suppression. Regular monitoring of CBP and LFT is needed when prescribing these steroid sparing agents. Because of the delayed onset of action of the immunosuppressants at 4-8 weeks, they are often commenced together with the oral steroids. 11 .8 . Treatme nt o f R ecal ci tr an t Ca ses 1) Plasmaphaeresis This in-patient treatment is only available in major hospitals. The renal team in the hospital can be consulted for providing the treatment if it is indicated. 2) Pulse Methylprednisolone Therapy 3) Cyclosporin A 4) Dapsone 5) Tetracycline/minocycline + niacinamide 6) Gold 7) Chlorambucil
11 .9 . Ind icat io ns o f T reatme nt Res po nse 1) No new lesion develops 2) Healing of old lesions 3) Dropping circulating antibody titre (indirect IMF) 12 . B ULL OUS PE MPH IGO ID 12 .1 . Intr od uc ti on It is about 2 times more common than pemphigus vulgaris. Usually occurs in old age (i.e. >60). It is present worldwide and affects male to female equally. 12 .2 . Pa th og enes is Production of autoantibody reacting with basement membrane zone which in turns leads to separation of epidermis from the dermis. The target sites are major & minor bullous pemphigoid antigens which are lying in the hemidesmosomes. 12 .3 . Clini cal Feat ures Early lesions in form of urticarial plaques may precede bullae. Presents as large intact blisters at lower abdomen, inner thighs, groin, axilla and flexures. Mucosal lesions are less common and often less severe than Pemphigus Vulgaris. 12 .4 . Inv est iga ti on s 1) Skin biopsy for histology Fresh lesion often demonstrates subepidermal blisters with mixed dermal infiltrates, especially eosinophils. 2) Skin biopsy for Direct Immunofluorescence (IMF) Direct IMF of perilesional skin shows linear deposition of IgG +/- C3 at dermalepidermal junction (Basement membrane zone) 3) Indirect Immunofluorescence (Serology) Circulating IgG or C3 to basement membrane zone can be detected in 75% of patients. The serology titre does NOT correlate with disease activity. Therefore, this test is seldom performed. 12 .5 . Mana gement Rough indication of severity 1) Mild: < 20 lesions 2) Moderate: 20-40 lesions 3) Severe: > 40 lesions If severe, patient needs hospitalization.
Drug Treatment: 1) Localized and mild case: Potent topical steroid (e.g. Clobetasol propionate) alone may control the disease. 2) Generalized disease: Oral steroid The dosage of prednisolone required for controlling the disease is usually less than that of pemphigus vulgaris. One can start off with 40-60 mg prednisolone daily. When the disease is under control, gradually tails it down to maintenance dose. Recalcitrant Cases: Adjuvant Immunosuppressant: e.g. azathioprine, cyclophosphamide, methotrexate, chlorambucil. Bullous pemphigoid is more commonly found in old age. These patients are more prone to the side effects of these drugs. Long term use of chlorambucil is not recommended because of the potential danger of developing acute myeloid leukaemia. Regular monitoring of CBP and LFT are needed. Tetracycline 500 mg qid/minocycline 100 mg bd + niacinamide 500 mg tds Pulse Methylprednisolone Therapy Plasmaphaeresis Cyclosporin A Dapsone 12 .6 . Pro gn os is The disease is often self-limiting. Spontaneous remission occurs in 3-6 years time. 13 . L INEA R IG A D ISE ASE 13 .1 . Intr od uc ti on A rare blistering disorder as characterized by linear IgA deposition in basement membrane zone. 13 .2 . Clini cal Feat ures It has 2 subtypes: 1) Adult type (around 60) 2) Childhood type (average onset around age of 5) Cutaneous Lesions:
1) Adult type: mainly affects trunk, face, perineum, hands and feet 2) Childhood type: perioral region and perineum are common sites Blisters typically occur in clusters. Mucosal Lesions: Besides cutaneous lesions, half of the patients have oral or even ocular involvement as well. 13 .3 . Inv est iga ti on s 1) Skin biopsy for histology In majority of the cases, the picture resembles Dermatitis Herpetiformis. Occasionally, some may simulate Bullous Pemphigoid histologically. 2) Direct Immunofluorescence (Direct IMF) Characterized by linear IgA deposition in basement membrane zone (BMZ). 3) Indirect Immunofluorescence (Indirect IMF) Test for anti-BMZ IgA Ab is not available in Hong Kong. 13 .4 . Treatme nt 1) Dapsone: It is the drug of choice. Response usually occurs within 48 hours. One has to be careful of dose-dependent haemolytic anaemia. Before starting dapsone, check for G-6-P-D level. 2) Prednisolone: Used as an adjuvant therapy to dapsone or when the latter is contraindicated. Usual dosage is 5-30 mg per day. 3) Colchicine: Used in resistant cases. 4) Topical Treatment: Potent topical steroid can be prescribed e.g. fluocinolone 0.025% 13 .5 . Pro gn os is 1) Adult type: most patients remit within 2 years 2) Childhood type: 50% chance of remission within 3 years 14 . D ER MATIT IS HE RPETIF OR MIS 14 .1 . Intr od uc ti on An uncommon skin condition with the peak incidence around 30-40 years of age. Male is more common than female. 14 .2 . Pa th og enes is In western countries, the disease usually associates with coeliac disease (Gluten enteropathy). In Hong Kong, since coeliac disease is extremely rare, this association is not usually observed.
14 .3 . Clini cal Feat ures Lesions are composed of excoriated and scabbed intensely itchy papules. The sites of predilection are extensors of 4 limbs, buttocks and face. Intact vesicles seldom seen since they are ruptured by self scratching. Lesions heal with no scarring. 14 .4 . Dif fe ren ti al Di ag no si s 1) Scabies: Presence of burrows, other family members are affected and sparing of the face are features suggestive of scabies. 2) Acute eczema: Atopic eczema affects flexures more than extensors. 14 .5 . Inv est iga ti on s Skin biopsy for histology: Microabscess in dermal papillae is characteristic. Direct Immunoflorescence: It shows granular IgA deposition in BMZ. Screening for the presence of coeliac disease. 14 .6 . Treatme nt 1) Dapsone: It is the drug of choice. After starting the treatment, symptoms should subside within 48 hours and rash should be cleared up within days. Side effects are haemolytic anaemia, methaemoglobulinaemia. 2) Sulphapyridine/sulphamethoxypyridazine: They are used when dapsone is contraindicated. 3) Gluten Free diet: It is useful only when the disease is associated with coeliac disease. Referring to dietician if required. Dietary restriction is not easy to follow. 14 .7 . Pro gn os is Spontaneous remission rate is low. 15 . EP IDE RM OLYSI S BU LLOSA 15 .1 . Clini cal Feat ures This is a extremely rare group of hereditary blistering disorders which are characterized by blisters and erosions resulting from trivial trauma. Blisters occur soon after birth and mainly concentrate on bony prominence of 4 limbs. An acquired form mimicking Bullous Pemphigoid known as epidermolysis bullosa acquisita (EBA) occurs in adults. Bullae tend to occur at sites of trauma. The IgG in these patients binds to the anchoring fibrils attached to the Lamina densa. EBA may be associated with underlying systemic diseases like SLE, inflammatory bowel disease, amyloidosis and internal malignancy.
15 .2 . Inv est iga ti on s The diagnosis can be confirmed by skin biopsy for histopathology and electronmicroscopy. The latter is also useful in subtyping the disease. EBA can be differentiated from bullous pemphigoid by the sodium chloride split skin test and immunofluorescence on the skin specimen. In EBA, the blister occurs below the split, whereas, the blister occurs on the roof of the split in bullous pemphigoid. 15 .3 . Treatme nt For the hereditary EB, no effective treatment is available at present. Antenatal diagnosis and genetic counselling can be offered. Systemic steroid can be useful in EBA.
ALOPECIA Dr. C.N. LOOK CHAPTER 11 1. DEFINITION Alopecia is defined as excessive or abnormal loss of hairs. 2. PHYSIOLOGY Natural hair loss is a physiological phenomenon. It is not a disease. Only when the loss is excessive or when the pattern of loss is abnormal, then it is pathological. Before one talks about the causes of alopecia, one has to understand the physiology of hair growth (Diagram 1). Diagram 1: Hair Cycle 2-6 years Anagen ---------------------------------------» Catagen | | Hair shedding «---------------------------------Telogen 100 days 90% of our terminal hairs are at anagen phase which is the growing phase. It lasts for 2-6 years. The scalp hair on average grows at the rate of 0.37 mm per day. Catagen is a transient period. Hair matrix cells stop dividing. As a result, there is no hair growth. Less than 10% of our hairs should be in telogen phase which lasts for 100 days (about 3 months). Since on average, each person has about 100,000 hairs. Therefore, less than 10,000 should be in telogen phase and on each
day less than 100 hairs fall off physiologically. 3. SPECIAL POINTS TO LOOK FOR When examining patients with alopecia the following points are worth paying attention to: 1) Pattern of alopecia a) Diffuse alopecia is usually due to telogen effluvium, systemic disorder (e.g. hypothyroidism, Fe deficiency, secondary syphilis), drugs. b) Patchy alopecia is typically seen in alopecia areata, scarring alopecia. c) Marginal alopecia affects the hair margin only. It occurs in alopecia areata or due to hair styling. d) Frontal and bitemporal alopecia is typical of male-type baldness. 2) Sign of scalp inflammation indicates alopecia may be secondary to inflammatory dermatosis (e.g. tinea capitis) 3) Presence of scarring together with alopecia will switch the differential diagnosis towards the cause of scarring alopecia (e.g. DLE, Lichen Planus). 4) Other than the scalp, see if hairs in other areas are also affected (e.g. axillary, pubic regions, eyebrow, eyelashes etc.). 5) Detailed drug history and history of past health are important. 4. CAUSES OF DIFFUSE ALOPECIA WITH NO SIGN OF INFLAMMATION NOR SCARRING 1) Telogen Effluvium a) Post-Partum b) Severe Illness c) Major Operations d) Malnutrition 2) Anagen Effluvium e.g. chemotherapy 3) Male Pattern Baldness 4) Female Pattern Baldness 5) Diffuse Alopecia Areata 6) Drugs e.g. heparin, antithyroid drugs, etretinate, isotretinoin 7) Systemic Disease e.g. Fe deficiency, thyroid disease, secondary syphilis, SLE 8) Ageing: usually causes thinning of hairs 4.1. Telogen Effluvium When a severe insult striking our bodies (severe infection, delivery, major operation) the anagen hairs (> 90% of hair population) will all simultaneously shift to telogen phase. As a result, about 3 months after the insult, more than 90% of the hairs will fall off at the same time giving rise to the condition which is called telogen effluvium.
The diagnosis can be made from a detailed history of the past health. In case when the diagnosis is in doubt, it can be confirmed by the telogen hair count test. It is done by plucking a bundle of hairs and counting for the percentage of telogen hairs present. Normally, the telogen hair count should not exceed 10% of the total hair count. Unfortunately, this test is not available in most centres. For telogen effluvium, no specific treatment is needed since spontaneous remission is the rule. 4.2. Anagen Effluvium Chemotherapy attacks the rapidly dividing cells i.e. anagen hairs. As a result, more than 90% of hairs fall off soon after chemotherapy. Usually, there is no problem with the diagnosis since it is obvious from the history. 4.3. Male Pattern Baldness (Androgenetic Alopecia) 4.3.1. Pathogenesis Even though the exact aetiology is unknown, there are proofs that genetic factor, as evidenced by frequent positive family history, and androgen play an important role in the development of the disease. Eunuchs and castrated males never develop baldness. Under the influence of androgen in a genetically predisposed person, the terminal hairs are gradually transforming into vellus hairs and they eventually fall off. 4.3.2. Clinical Features Typically, it starts off with bitemporal recession and subsequently, thinning or complete loss of hair at the crown. Hair on the occiput and around the sides of the scalp is seldom affected and it seems that hair in those areas are more resistant to the effect of androgen. The diagnosis can often be made by the characteristic pattern of hair loss and the frequently presence of a positive family history. 4.3.3. Treatment No good treatment is available at present. Topical minoxidil may be useful in minority of cases but the effect disappears soon after stopping the treatment and yet it is expensive. It is the only FDA approved drug at presence for the treatment of androgenetic alopecia. Topical ether-in-spirit: the effect is no better than placebo. Hair Transplant: based on donor dominance theory which states that hairs from growing areas will survive and grow when transplanted to bald areas. The operation is tedious and requires expertise. Wigs: quite practical if it is acceptable by the patient. 4.4. Female Pattern Baldness
It is characterized by thinning of hairs at the crown or a diffuse hair loss. Unlike male pattern baldness, there is no bitemporal and frontal recession. If female pattern baldness occurring in a young female, especially with the presence of menstrual disturbance, signs of hirsutism or virilization, excessive androgen activity needs to be excluded e.g. androgen-secreting tumour. Treatment is difficult but one may try cyproterone acetate which is an anti-androgen. 5. CAUSES OF PATCHY ALOPECIA WITHOUT SCARRING Alopecia areata/totalis/universalis Trichotillomania Traction alopecia Tinea capitis (excluding favus) 5.1. Alopecia Areata/Totalis/Universalis These 3 conditions all belong to a spectrum of the same disease. They only differ in the degree of severity. When all the scalp hair is lost, it is called alopecia totalis. If both scalp and body hair are involved, it becomes alopecia universalis. Alopecia areata is the commonest cause of patchy alopecia. 5.1.1. Aetiology The exact aetiology is unknown. Genetic factor and atopy play some role as some patients may have positive family history or history of atopy. It is considered as a kind of autoimmune disease since it has an association with other organ-specific autoimmune disease (e.g. Vitiligo, Hashimoto thyroiditis). The incidence of alopecia areata is high in patients with Down's syndrome and those who are under stress. 5.1.2. Clinical Features The disease affects male and female equally at all age. It is presented as discrete patches of baldness with no scarring and no sign of inflammation. Broken hairs with tapering shafts (i.e. exclamation mark hairs) are diagnostic. Nail pitting may also be present. 5.1.3. Treatment Local Steroid a) Topical Steroid e.g. 0.025% fluocinolone, halometasone b) Intralesional Steroid e.g. triamcinolone These treatment modalities may be useful in dealing with localized disease. Irritants or Contact Sensitizers e.g. dithranol, diphencyprone. DNCB is no longer recommended because of its carcinogenic potential. PUVA/UVB: May show response in some cases but need many treatment sessions. The actual beneficial effect is controversial.
Topical minoxidil: effect is doubtful. Oral prednisolone: it is effective in some cases but has to be reserved for resistant or severe cases (e.g. alopecia universalis or alopecia totalis) because of its potential side effects. Wigs wearing: last solution. 5.1.4. Prognosis The prognosis is usually good since 75% of patients with alopecia areata have spontaneous remission eventually. Signs of Poor Prognosis: Multiple patches Ophiasis (extensive hair loss at occipital area) Eyebrows and eyelashes involvement Alopecia totalis/universalis Young age of onset Presence of atopic disease Frequent recurrent attacks Nail involvement Down's syndrome 5.2. Trichotillomania 5.2.1. Cause The hair loss is due to self-induced twisting and pulling of hairs. It usually occurs in children or adolescents. It may be due to a bad habit, attention seeking or a manifestation of psychological problem. 5.2.2. Clinical Features Patches of alopecia with no sign of inflammation are seen. Unlike alopecia areata, the margin of the lesion is less well defined and there is no exclamation mark hairs. The hair loss is never complete. Short broken hairs of varying length are characteristic. 5.2.3. Diagnosis The disease can be diagnosed clinically. A detailed social and psychological history are essential. 5.2.4. Treatment Often, the disease is self-limiting upon reassurance. Parents have to be interviewed so that the problem can be addressed. Sometimes, referring patient to clinical psychologist or psychiatrist may be helpful. 5.3. Traction Alopecia Alopecia secondary to hair styling, hot-combing to straighten kinky hair. It is rare in Hong Kong. 5.4. Tinea Capitis
Tinea capitis must be considered as one of differential diagnosis as a cause of patchy alopecia in children. The infected hair are brittle and are easily broken. It is associated with inflammation i.e. redness, scaling. Even though for most of the time, the lesion heal without scarring, in severe cases (e.g. kerion), scarring alopecia can occur. Please refer to the chapter on skin infection for details. 6. CAUSES OF DISCRETE PATCHY ALOPECIA WITH SCARRING Congenital e.g. aplasia cutis, naevus sebaceus Post-trauma e.g. burn, injury, radiotherapy Post-infection e.g. kerion, herpes zoster Inflammatory dermatosis e.g. DLE, lichen planus, morphoea: common cause of scarring alopecia Neoplasm e.g. squamous cell carcinoma of skin Idiopathic 6.1. Aplasia Cutis This is a very rare congenital disease and the alopecia is present since birth. 6.2. Naevus Sebaceus It is a kind of epidermal naevus which presents at birth as a yellowish hairless plaque on the scalp. It becomes more warty after puberty. The diagnosis can be confirmed by skin biopsy. It has potential of undergoing malignant change (e.g. basal cell carcinoma). For this reason, excision of the lesion after puberty is recommended. 6.3. Inflammatory Dermatosis Causing Alopecia DLE, lichen planus and morphoea are common causes of patchy scarring alopecia. Sometimes, clinically, it is difficult to differentiate them one from another. One should examine the rest of the body to look for any sign that are related to each of these 3 diseases. Of course, skin biopsy of the lesion on scalp is usually helpful. 6.4. Idiopathic Scarring Alopecia (Pseudopelade) Occasionally, despite thorough examination and investigation, no cause can be attributed to patient's scarring alopecia. If the disease is still active, topical steroid can be tried. NA IL DI SEASES 1. DI SEASES O F NA IL PL ATE Pits Psoriasis, alopecia areata, hand dermatitis, nail biting, lichen planus
Beau's lines, any inflammation affecting soft tissues around nails
Longitudinal ridges: Single Multiple Thickening
Pressure effect e.g. tumour in nail fold Psoriasis, lichen planus, alopecia areata, Darier's disease Psoriasis, onychomycosis, pachyonychia congenita Idiopathic, psoriasis, onychomycosis, trauma, thyroid acropachy, drug induced photoonycholysis e.g. tetracyclines
Onycholysis separation of nail plate from nail bed distally) Subungual hyperkeratosis Koilonychia Colour changes
Psoriasis, onychomycosis, trauma, ischaemia
Iron deficiency, lichen planus, idiopathic Infection: Drugs: Pseudomonas (green) Tetracycline (yellow) Antimalarial (blue) Chlorpromazine (brown) Topical agents: Potassium permanganate Dyes Systemic diseases: Cirrhosis hypoproteinaemia (white) Others: Cigarette smoking (brown) Subungual haematoma (reddish blue) Melanoma (black)
Leuconychia (whiteness of nail): True (affect nail plate) Apparent (affect subungual tissues) Pigmented streaks
Onychomycosis, trauma, congenital Anaemia, hypoproteinaemia
Normal in pigmented skin, malignant melanoma, benign melanocytic naevi, Addison's disease
2. DI SEASES O F NA IL F OLD Paronychia (inflammation of nail fold): Acute Chronic
Trauma Trauma, wet work, drugs e.g. etretinate
Pterygium formation (cuticle Lichen planus, circulatory appears to grow out over the nail disorders, pemphigus with loss of proximal nail fold) Palisading of dilated nail fold capillaries Infarcts at posterior or lateral folds Dermatomyositis, lupus erythematosus, scleroderma Vasculitis, e.g. rheumatoid diseases Viral warts, myxoid cyst, periungual, fibromata, malignant melanoma
Nail fold masses
3. DI SEASES O F NA IL B ED AN D M ATR IX Subungual exostosis Glomus tumour Naevus Malignant melanoma Subungual wart
4. APP RO AC HES TO N AIL D ISE ASES
A thorough history is important. Occupation is clearly relevant in trauma related nail diseases such as chronic paroncyhia. A family history of psoriasis may explain nail changes in the absence of any other cutaneous signs. Beau's lines may be accountable by a previous heart attack. Drug history is especially important in looking for causes of colour changes in nails. All finger nails and toe nails should be examined in good lighting with the digits relaxed. If polish or lacquer is present, it should be removed prior to examination. Particular attention should be paid to the symmetry of the changes. Other signs of skin diseases should be looked for elsewhere in the body e.g. psoriatic nail changes may lead to the discovery of a small patch of psoriasis at the back. Nail clipping for microscopy and fungal culture should be done in suspected onychomycosis. Biopsy is sometimes indicated, e.g., suspect melanoma. Underlying diseases should be looked for in nail diseases associated with systemic illness, e.g., clubbing, leuconychia etc. 5. TRE ATMENT O F CO MM ON N AI L DI SEASES 5. 1. Ac ute Pa ro ny ch ia Bacterial infection (Staph. Aureus, Strep. Pyogenes) is the commonest cause. There is acute swelling, tenderness and collection of pus in the nail fold. A swab should be taken if possible. Give ampicillin 250 mg qid and cloxacillin 250 mg qid for 10 days. Analgesic e.g. panadol should also be prescribed. Consider incision and drainage if swelling and pain does not improve quickly. 5. 2. Ch ro nic Pa ro nyc hi a This is a multi-factorial condition: 1) Irritant dermatosis 2) Infection: candidal; bacterial sometimes 3) Background eczema of psoriasis All of the factors should be eliminated. Protection: Avoid water, detergent, soap if possible. Use rubber glove with inner cotton glove. Emollient: frequent application of blend emollient and use as a soap substitute. Antibiotic: A course of systemic antibiotic should be consider in the first week.
Topical treatment: A combination of topical steroid and antifungal to the nail fold. 5. 3. Na il Di seases i n Pso ri asi s Nail dystrophy in psoriasis is difficult to treat. Patients should be informed of the limited effectiveness of various treatments. General care: Avoid trauma. Keep nail short. Rubber with inner cotton gloves. Use emollient as soap substitutes. Exclude concomitant fungal infection. Steroid: Ultra-potent steroid to the nail fold with or without occlusion. Intralesional steroid is an alternative but is painful. PUVA: Nail disease may improve with systemic PUVA for the whole body. Topical PUVA may worth trying. Retinoids: While subungual hyperkeratosis improves, pitting and onycholysis get worse with etretinate. Others: Topical calciprotriol, topical 1% fluorouracil, topical cyclosporin A have been tried with variable success.
CUTANEOUS MALIGNANCIES Dr. H.F. HO CHAPTER 13 Duties of dermatologists in Social Hygiene Service in the management of cutaneous malignancy: 1) To identify the high risk patients and the suspicious lesions. 2) To confirm the diagnosis. 3) Assess and decide whether the lesion can be adequately treated in our clinic and give the most appropriate accordingly. 4) Refer those which cannot be adequately treated in our clinics and refer them to a multi-disciplinary clinic for further management. Prepare to give opinion regarding choice of treatment. 5) Follow-up of the patient. The management of basal cell carcinoma, squamous cell carcinoma, melanoma and mycosis fungoides will be discussed in chapter. 1. BASAL CELL CARCINOMA 1.1. Introduction Basal cell carcinoma is the most common malignant skin tumour. Three main clinical types of BCC are identifiable:
1) Superficial BCC 2) Nodular BCC: this may appears cystic, or may evolve into a "rodent ulcer" . 3) Infiltrative form - Infiltrative morphoea-form BCC - Infiltrative non-morphea-form BCC 1.2. Diagnosis Diagnosis of skin tumour should include a careful physical examination, not only of the target lesion but also search for the presence of other skin tumours. A general examination paying special attention to regional lymph nodes and organomegaly is necessary, although distant metastasis in BCC is rare. Skin biopsy is indicated to confirm the diagnosis. 1.3. Treatment The treatment goals are: 1) Cure. 2) Cosmesis, when the first goal is reached. Treatment modalities: Common treatments: Curettage and desiccation Surgical excision Mohs surgery Cryosurgery Radiotherapy Evolving treatments: Interferon, photodynamic therapy, oral retinoids, 5fluorouracil. Systemic chemotherapy. These will not be discussed in detail. Choosing the modality will depend on: 1) Tumour factor: BCC are considered to be high risk if: Recurrent Size greater than 1 to 2 cm Long duration, fast growth Indistinct margins Aggressive histological pattern High risk sites: nose eyelids, ears, medial canthus, nasolabial fold, scalp, lip, fingers, toes, genitals. 2) Patient factors: age, medical status, psychological factors, concomitant medications. 3) Availability of the expertise and facilities.
Surgical treatment Excision This is useful for both primary and recurrent lesions, and it enables histological examination of surgical margins. In good hands, cure rates approaches 95%. Cure rate >99% if margins histologically negative. For lesion size more than 1.5 cm or in critical cosmetic sites, other modalities e.g. Mohs surgery, radiotherapy, or excision by plastic surgeon with frozen-section control are more preferrable. Curettage and electrosurgery Commonly used for tumour size less than 1.5 cm. Cure rate approaches 95% in good hands. This is not the appropriate treatment for infiltrative lesion and recurrent lesions in scar tissue. Cryosurgery Useful in primary tumour and sometimes in recurrent lesion, and especially useful in patients with multiple small lesions. Curettage is done to debulk the lesion before freezing. Local anaesthesia is not needed and there is no bleeding and scarring may be less than it is with surgery. No tissue is available for histological confirmation and healing takes several weeks. Tissue needs to frozen 4-6 mm beyond the clinical border . Thermo-couples are necessary for larger lesions and this method is not suitable for infiltrative lesions. Mohs surgery The technique is recommended for recurrent, large, difficult tumour, if it is available. Laser surgery Laser may used to vaporize the tumour or as a scalpel blade for excision and for hemostasis. Non-surgical treatment Radiation therapy This is useful for definitive treatment of primary and recurrent tumour and for palliation of inoperable lesions. It is painless, without postoperative scarring. Potentially carcinogenic, it should be reserved for the older patients. It provides no margin control and radiation dermatitis may develop. 1.4. Follow-up Long-term follow-up is indicated. Physical examination to search for recurrence, new tumours (BCC, SCC, Melanomas etc.). Prevention and education advices should be given. This will include sun avoidance, sunscreen protection, self-examination, dietary modification to reduce calories from fatty sources and addition of b -carotene or multivitamins.
2. CUTANEOUS SQUAMOUS CELL CARCINOMA 2.1. Introduction Being the second most common malignant tumour of the skin, SCC possesses a higher potential for metastasis than BCC (3%-30% in SCC and 0.3%-3% in BCC). Actinic damage is the most important factor but SCCs may also develop in certain geno-dermatosis, immunologically compromised chronic inflammation, UV radiation, ionizing radiation, arsenic poisoning and other chemical agents. 2.2. Diagnosis Histological examination is necessary to confirm the diagnosis. A detailed history and careful examination should be done to search for regional and distant metastasis. A CXR is basic, whereas further investigation should be directed by clinical findings. 2.3. Risk Factors The following factors are associated with increased aggressiveness: Size > 1 cm Rapid growth Ulceration Depth: invasion into subcutis or below Immunocompromised Develop from chronic inflammation or scar Recurrence Site: mucous membrane, ear, temple, scalp, eyelid Histology: Undifferentiated, subcutaneous or below, perineural invasion, lymphatic invasion. 2.4. Treatment The treatment goals are: 1) Cure 2) Cosmesis, when the first goal is reached. Choices of treatments: This should depend on tumour factor (high or low risk); patient factors; and the availability of expertise and facilities. Actinically derived SCC free of the risk factors can be safely treated in our clinics with the following methods of local tumour control. Surgical treatment Excision This is a useful method for primary and recurrent tumours. Surgical margins can be assessed. Curettage and electrosurgery
Primarily for small actinically derived tumour. It is not preferrable for recurrence and deep lesions. Cryosurgery Another alternative to surgery. It is useful for patients with bleeding tendency or those refused surgery for various reasons. For high risk lesions, the following treatments should be considered: Mohs surgery If available, this is one of the most effective methods for high risk lesions. Adjuvant radiation following surgical excision: Adjuvant radiotherapy can be used in combination with Mohs surgery or simple excision in high risk lesions. The advantages is that the in-transit metastasis and subclinical regional lymph node metastasis can be treated. Radiation therapy This can be a definitive treatment for primary or recurrent tumour and also for palliation of inoperable tumours. It can also be used in combination with other methods. Evolving methods This may include photodynamic therapy, interferon, systemic or topical retinoids etc. 2.5. Follow-up This is similar to BCC. 3. MALIGNANT MELANOMA 3.1. Introduction While melanoma is relatively uncommon when compared with BCC and SCC, it is the most frequent cause of death of tumours arising from the skin. Advanced tumour is difficult to treat, whereas early thin lesions are potential curable. Thus early detection and surgical removal of early lesion is the key to improvement of survival. 3.2. Identify the High Risk Patients 1) Family or personal history of melanoma. 2) Skin type 1 or 2, easy to burn, difficult to tan. 3) Tendency to freckle. 4) History of severe sun burn. 5) Many moles or presence of atypical nevi, clinically. (Giant congenital melanocytic naevus ) 3.3. Identify the High Risk Lesions Symptoms: CHANGES in size, shape, height, colour of a lesion. Bleeding, erosion, ulceration, crusting and itching.
Signs: The "ABCDE" of malignant melanoma Asymmetry Border irregularity Colour variegation Diameter greater than 6 mm Elevation Physical examination should not stop at examination of the suspicious lesion. One should examine the area around the lesion and the lymphatic drainage area for metastases, examine for organomegaly, and ask for symptoms of internal metastases. The whole body surface should also be examined carefully, paying attention to areas such as the nail fold and nail plate. 3.4. Diagnosis Biopsy of the suspicious lesion is necessary to confirm the diagnosis and to guide further management. Small lesion: complete excision, elliptical or saucerization with narrow margin with thickness to the level of subcutaneous fat should be aim arrived at. Large lesion: incisional biopsy, choosing the most elevated, dark or suspected area to the level of subcutaneous fat. 3.5. Assessment and Staging History: thorough history paying special attention to brain, chest, bone, gastrointestinal symptoms. Physical examination: the lymphatic drainage area, all other lymph node area, the total skin surface, liver and spleen enlargement. Chest X-ray: This is part and partial of the physical examination. This is the only investigation indicated in stage I disease. Further investigation should be guide by the physical findings and histological examination findings. 3.6. Stage Grouping (American Joint Commission on Cancer Staging System 1992) ¡@ Stage I Stage II Breslow Depth ?1.5 mm > 1.5 mm Lymph Node Metastasis no no Distant Metastasis no no
Stage III Stage IV
3.7. Treatment: The Multidisciplinary Approach Except for stage I conditions; which can be safely treated in our clinic setting, for all stages beyond, the joint effort with the cooperation of surgeon, oncologist, radiologist, dermatologist and nursing specialist is most important. Only treatment of the primary will be discussed here in detail. Adjuvant management of early lesion without evidence of metastasis and management of advanced diseases with metastasis is beyond the scope of this chapter. 3.7.1. Surgical Treatment of the Primary Lesion: Wide Local Excision The principle is to excise the lesion to the underlying muscle fascia with a margin of normal-appearing skin. That "safety margin" is still a controversial and continuously evolving issue, and the surgical guideline from AJCC is quoted here: Breslow Depth < 0.75 mm 0.76 mm - 1.49 mm 1.5 mm - 4 mm > 4 mm Excision Margin 1 cm 1 - 2 cm 1 - 2 cm +/-ELND +/-adjuvant therapy 3 cm =/-adjuvant therapy
The current thought is that a 1 cm margin is appropriate for all lesions but investigations for regional and visceral metastasis should be done for lesions thicker than 1.5 mm and adjuvant treatment should be considered. ELND-Elective Lymph Node Dissection: A controversial issue again and it entails resection of lymph nodes in the drainage region without clinical evidence of involvement. It increases morbidity and has never been proven to improve survival. It is probably not indicated in thin lesions (less than 1.5 mm). Morton¡¥s blue dye technique may help to improve this procedure. 3.7.2. Mohs Micrographic Surgery Not an established method but may be an alternative as an tissue saving technique for lesion on the face. 3.7.3. Cryotherapy
May be considered in lentigo maligna, and lentigo maligna melanoma. 3.7.4. Therapy for Metastatic Disease Various modalities of treatment are available for disease stage III or IV. The more established will be listed but will not be discussed in detail. Moreover, effectiveness of adjuvant therapy for early stages. Surgery: for metastatic lesions. Chemotherapy: Dacarbazine is the most effective single agent. Isolation perfusion: for the treatment of in-transit metastasis. Radiotherapy: for palliative treatment of metastasis. Evolving modalities: melanoma vaccines monoclonal antibodies adoptive immunotherapy gene therapy others 3.8. Follow-Up Life long follow-up is indicated for all patients with melanoma. Frequency of visits should be guided by tumour stages, presence of atypical nevi etc. The duties in the follow-up should include: 1) Examination for recurrence, new lesion, sign and symptoms of metastasis. 2) Education: sun protection, monthly self-examinations of skin and "ABCD" of melanoma. 3) Opthalmological referral for patient with multiple primary, multiple dysplastic nevi and family history of ocular melanoma. 4) Referral of 1st degree relative for examination for melanoma or atypical nevi. 5) Avoidance of pregnancy for 2 years after diagnosis. This is highly controversial, but may be considered in patient with advanced stages of disease, multiple melanoma, or numerous atypical nevi. 4. MYCOSIS FUNGOIDES Mycosis fungoides (MF) is the commonest cutaneous T cell lymphoma. Three clinical stages can be identified: patch, plaque , tumour stage. The erythrodermic stage, which is also called Sezary syndrome (erythroderma, enlarged lymph nodes, and circulating Sezary cells) may develop de-novo or from the earlier stages. 4.1. Diagnosis Skin biopsy: Multiple skin biopsy on lesions of different morphology should be taken.
Histology: One should bear in mind that the histological features is variable and there is some correlation with the clinical features. 4 types have described: Epidermotrophic patches and plaques Epidermatrophic erythroderma Non-epidermotrophic erythroderma Non-epidermotrophic tumours The biopsy specimens may also send for: Immunophenotyping: to demonstrate T cell lineage. Other markers e.g. IL2, Ki1 are helpful in certain circumstances. T cell recepter gene rearrangement study: by PCR, to demonstrate monoclonality. 4.2. Evaluation Careful history, physical examination with mapping of all lesions. Complete blood picture with smear, Liver and renal function, Lactate dehydrogenase level, Anti-nuclear factor. Chest X ray. Biopsy of enlarged lymph nodes. CT scan of abdomen, pelvis and other sites if indicated. 4.3. Staging Several staging schemes have been proposed and are based on cutaneous lesions (patch, plaque, tumour, erythrodermic), presence of lymph node involvement and visceral involvement. This will not be detailed in this chapter. 4.4. Treatment Choice of treatment should be determined by: 1) Clinical stages. 2) Availabilities of facilities and expertise. 3) Patient's preference. For all stages of diseases, symptomatic relief with EMOLLIENT, TOPICAL STEROID, ANTI-HISTAMINE are indispensable. Choices of treatment according to stages: Patches and plaques PUVA, RePUVA is the first line. Topical nitrogen mustard is an alternative if available. Total skin electron beam therapy or PUVA with a interferon are reserved for refractory cases. Tumours Total skin electron beam with local booster radiation to tumours. Extracorporeal photophoresis is an alternative (not available locally). Erythrodermic stage and Sezary syndrome
Photophoresis, if available, is probably the best treatment, and concomitant methotrexate may increase its effectiveness. PUVA may give symptomatic relief but should be administered with care. Other choice of treatment may include a interferon, systemic chemotherapy, retinoids and bone marrow tr CUTANEOUS MALIGNANCIES Dr. H.F. HO CHAPTER 13 Duties of dermatologists in Social Hygiene Service in the management of cutaneous malignancy: 1) To identify the high risk patients and the suspicious lesions. 2) To confirm the diagnosis. 3) Assess and decide whether the lesion can be adequately treated in our clinic and give the most appropriate accordingly. 4) Refer those which cannot be adequately treated in our clinics and refer them to a multi-disciplinary clinic for further management. Prepare to give opinion regarding choice of treatment. 5) Follow-up of the patient. The management of basal cell carcinoma, squamous cell carcinoma, melanoma and mycosis fungoides will be discussed in chapter. 1. BASAL CELL CARCINOMA 1.1. Introduction Basal cell carcinoma is the most common malignant skin tumour. Three main clinical types of BCC are identifiable: 1) Superficial BCC 2) Nodular BCC: this may appears cystic, or may evolve into a "rodent ulcer" . 3) Infiltrative form - Infiltrative morphoea-form BCC - Infiltrative non-morphea-form BCC 1.2. Diagnosis Diagnosis of skin tumour should include a careful physical examination, not only of the target lesion but also search for the presence of other skin tumours. A general examination paying special attention to regional lymph nodes and organomegaly is necessary, although distant metastasis in BCC is rare.
Skin biopsy is indicated to confirm the diagnosis. 1.3. Treatment The treatment goals are: 1) Cure. 2) Cosmesis, when the first goal is reached. Treatment modalities: Common treatments: Curettage and desiccation Surgical excision Mohs surgery Cryosurgery Radiotherapy Evolving treatments: Interferon, photodynamic therapy, oral retinoids, 5fluorouracil. Systemic chemotherapy. These will not be discussed in detail. Choosing the modality will depend on: 1) Tumour factor: BCC are considered to be high risk if: Recurrent Size greater than 1 to 2 cm Long duration, fast growth Indistinct margins Aggressive histological pattern High risk sites: nose eyelids, ears, medial canthus, nasolabial fold, scalp, lip, fingers, toes, genitals. 2) Patient factors: age, medical status, psychological factors, concomitant medications. 3) Availability of the expertise and facilities. Surgical treatment Excision This is useful for both primary and recurrent lesions, and it enables histological examination of surgical margins. In good hands, cure rates approaches 95%. Cure rate >99% if margins histologically negative. For lesion size more than 1.5 cm or in critical cosmetic sites, other modalities e.g. Mohs surgery, radiotherapy, or excision by plastic surgeon with frozen-section control are more preferrable. Curettage and electrosurgery Commonly used for tumour size less than 1.5 cm. Cure rate approaches 95% in good hands. This is not the appropriate treatment for infiltrative lesion and recurrent lesions in scar tissue. Cryosurgery
Useful in primary tumour and sometimes in recurrent lesion, and especially useful in patients with multiple small lesions. Curettage is done to debulk the lesion before freezing. Local anaesthesia is not needed and there is no bleeding and scarring may be less than it is with surgery. No tissue is available for histological confirmation and healing takes several weeks. Tissue needs to frozen 4-6 mm beyond the clinical border . Thermo-couples are necessary for larger lesions and this method is not suitable for infiltrative lesions. Mohs surgery The technique is recommended for recurrent, large, difficult tumour, if it is available. Laser surgery Laser may used to vaporize the tumour or as a scalpel blade for excision and for hemostasis. Non-surgical treatment Radiation therapy This is useful for definitive treatment of primary and recurrent tumour and for palliation of inoperable lesions. It is painless, without postoperative scarring. Potentially carcinogenic, it should be reserved for the older patients. It provides no margin control and radiation dermatitis may develop. 1.4. Follow-up Long-term follow-up is indicated. Physical examination to search for recurrence, new tumours (BCC, SCC, Melanomas etc.). Prevention and education advices should be given. This will include sun avoidance, sunscreen protection, self-examination, dietary modification to reduce calories from fatty sources and addition of b -carotene or multivitamins. 2. CUTANEOUS SQUAMOUS CELL CARCINOMA 2.1. Introduction Being the second most common malignant tumour of the skin, SCC possesses a higher potential for metastasis than BCC (3%-30% in SCC and 0.3%-3% in BCC). Actinic damage is the most important factor but SCCs may also develop in certain geno-dermatosis, immunologically compromised chronic inflammation, UV radiation, ionizing radiation, arsenic poisoning and other chemical agents. 2.2. Diagnosis Histological examination is necessary to confirm the diagnosis. A detailed history and careful examination should be done to search for regional and distant metastasis. A CXR is basic, whereas further investigation should be
directed by clinical findings. 2.3. Risk Factors The following factors are associated with increased aggressiveness: Size > 1 cm Rapid growth Ulceration Depth: invasion into subcutis or below Immunocompromised Develop from chronic inflammation or scar Recurrence Site: mucous membrane, ear, temple, scalp, eyelid Histology: Undifferentiated, subcutaneous or below, perineural invasion, lymphatic invasion. 2.4. Treatment The treatment goals are: 1) Cure 2) Cosmesis, when the first goal is reached. Choices of treatments: This should depend on tumour factor (high or low risk); patient factors; and the availability of expertise and facilities. Actinically derived SCC free of the risk factors can be safely treated in our clinics with the following methods of local tumour control. Surgical treatment Excision This is a useful method for primary and recurrent tumours. Surgical margins can be assessed. Curettage and electrosurgery Primarily for small actinically derived tumour. It is not preferrable for recurrence and deep lesions. Cryosurgery Another alternative to surgery. It is useful for patients with bleeding tendency or those refused surgery for various reasons. For high risk lesions, the following treatments should be considered: Mohs surgery If available, this is one of the most effective methods for high risk lesions. Adjuvant radiation following surgical excision: Adjuvant radiotherapy can be used in combination with Mohs surgery or simple excision in high risk lesions. The advantages is that the in-transit metastasis and subclinical regional lymph node metastasis can be treated.
Radiation therapy This can be a definitive treatment for primary or recurrent tumour and also for palliation of inoperable tumours. It can also be used in combination with other methods. Evolving methods This may include photodynamic therapy, interferon, systemic or topical retinoids etc. 2.5. Follow-up This is similar to BCC. 3. MALIGNANT MELANOMA 3.1. Introduction While melanoma is relatively uncommon when compared with BCC and SCC, it is the most frequent cause of death of tumours arising from the skin. Advanced tumour is difficult to treat, whereas early thin lesions are potential curable. Thus early detection and surgical removal of early lesion is the key to improvement of survival. 3.2. Identify the High Risk Patients 1) Family or personal history of melanoma. 2) Skin type 1 or 2, easy to burn, difficult to tan. 3) Tendency to freckle. 4) History of severe sun burn. 5) Many moles or presence of atypical nevi, clinically. (Giant congenital melanocytic naevus ) 3.3. Identify the High Risk Lesions Symptoms: CHANGES in size, shape, height, colour of a lesion. Bleeding, erosion, ulceration, crusting and itching. Signs: The "ABCDE" of malignant melanoma Asymmetry Border irregularity Colour variegation Diameter greater than 6 mm Elevation Physical examination should not stop at examination of the suspicious lesion. One should examine the area around the lesion and the lymphatic drainage area for metastases, examine for organomegaly, and ask for symptoms of internal metastases.
The whole body surface should also be examined carefully, paying attention to areas such as the nail fold and nail plate. 3.4. Diagnosis Biopsy of the suspicious lesion is necessary to confirm the diagnosis and to guide further management. Small lesion: complete excision, elliptical or saucerization with narrow margin with thickness to the level of subcutaneous fat should be aim arrived at. Large lesion: incisional biopsy, choosing the most elevated, dark or suspected area to the level of subcutaneous fat. 3.5. Assessment and Staging History: thorough history paying special attention to brain, chest, bone, gastrointestinal symptoms. Physical examination: the lymphatic drainage area, all other lymph node area, the total skin surface, liver and spleen enlargement. Chest X-ray: This is part and partial of the physical examination. This is the only investigation indicated in stage I disease. Further investigation should be guide by the physical findings and histological examination findings. 3.6. Stage Grouping (American Joint Commission on Cancer Staging System 1992) ¡@ Stage I Stage II Stage III Stage IV Breslow Depth ?1.5 mm > 1.5 mm any any Lymph Node Metastasis no no present any Distant Metastasis no no no present
3.7. Treatment: The Multidisciplinary Approach Except for stage I conditions; which can be safely treated in our clinic setting, for all stages beyond, the joint effort with the cooperation of surgeon, oncologist, radiologist, dermatologist and nursing specialist is most important. Only treatment of the primary will be discussed here in detail. Adjuvant management of early lesion without evidence of metastasis and management of advanced diseases with metastasis is beyond the scope of this chapter. 3.7.1. Surgical Treatment of the Primary Lesion: Wide Local Excision
The principle is to excise the lesion to the underlying muscle fascia with a margin of normal-appearing skin. That "safety margin" is still a controversial and continuously evolving issue, and the surgical guideline from AJCC is quoted here: Breslow Depth < 0.75 mm 0.76 mm - 1.49 mm 1.5 mm - 4 mm > 4 mm Excision Margin 1 cm 1 - 2 cm 1 - 2 cm +/-ELND +/-adjuvant therapy 3 cm =/-adjuvant therapy
The current thought is that a 1 cm margin is appropriate for all lesions but investigations for regional and visceral metastasis should be done for lesions thicker than 1.5 mm and adjuvant treatment should be considered. ELND-Elective Lymph Node Dissection: A controversial issue again and it entails resection of lymph nodes in the drainage region without clinical evidence of involvement. It increases morbidity and has never been proven to improve survival. It is probably not indicated in thin lesions (less than 1.5 mm). Morton¡¥s blue dye technique may help to improve this procedure. 3.7.2. Mohs Micrographic Surgery Not an established method but may be an alternative as an tissue saving technique for lesion on the face. 3.7.3. Cryotherapy May be considered in lentigo maligna, and lentigo maligna melanoma. 3.7.4. Therapy for Metastatic Disease Various modalities of treatment are available for disease stage III or IV. The more established will be listed but will not be discussed in detail. Moreover, effectiveness of adjuvant therapy for early stages. Surgery: for metastatic lesions. Chemotherapy: Dacarbazine is the most effective single agent. Isolation perfusion: for the treatment of in-transit metastasis. Radiotherapy: for palliative treatment of metastasis. Evolving modalities: melanoma vaccines monoclonal antibodies adoptive immunotherapy
gene therapy others 3.8. Follow-Up Life long follow-up is indicated for all patients with melanoma. Frequency of visits should be guided by tumour stages, presence of atypical nevi etc. The duties in the follow-up should include: 1) Examination for recurrence, new lesion, sign and symptoms of metastasis. 2) Education: sun protection, monthly self-examinations of skin and "ABCD" of melanoma. 3) Opthalmological referral for patient with multiple primary, multiple dysplastic nevi and family history of ocular melanoma. 4) Referral of 1st degree relative for examination for melanoma or atypical nevi. 5) Avoidance of pregnancy for 2 years after diagnosis. This is highly controversial, but may be considered in patient with advanced stages of disease, multiple melanoma, or numerous atypical nevi. 4. MYCOSIS FUNGOIDES Mycosis fungoides (MF) is the commonest cutaneous T cell lymphoma. Three clinical stages can be identified: patch, plaque , tumour stage. The erythrodermic stage, which is also called Sezary syndrome (erythroderma, enlarged lymph nodes, and circulating Sezary cells) may develop de-novo or from the earlier stages. 4.1. Diagnosis Skin biopsy: Multiple skin biopsy on lesions of different morphology should be taken. Histology: One should bear in mind that the histological features is variable and there is some correlation with the clinical features. 4 types have described: Epidermotrophic patches and plaques Epidermatrophic erythroderma Non-epidermotrophic erythroderma Non-epidermotrophic tumours The biopsy specimens may also send for: Immunophenotyping: to demonstrate T cell lineage. Other markers e.g. IL2, Ki1 are helpful in certain circumstances. T cell recepter gene rearrangement study: by PCR, to demonstrate monoclonality.
4.2. Evaluation Careful history, physical examination with mapping of all lesions. Complete blood picture with smear, Liver and renal function, Lactate dehydrogenase level, Anti-nuclear factor. Chest X ray. Biopsy of enlarged lymph nodes. CT scan of abdomen, pelvis and other sites if indicated. 4.3. Staging Several staging schemes have been proposed and are based on cutaneous lesions (patch, plaque, tumour, erythrodermic), presence of lymph node involvement and visceral involvement. This will not be detailed in this chapter. 4.4. Treatment Choice of treatment should be determined by: 1) Clinical stages. 2) Availabilities of facilities and expertise. 3) Patient's preference. For all stages of diseases, symptomatic relief with EMOLLIENT, TOPICAL STEROID, ANTI-HISTAMINE are indispensable. Choices of treatment according to stages: Patches and plaques PUVA, RePUVA is the first line. Topical nitrogen mustard is an alternative if available. Total skin electron beam therapy or PUVA with a interferon are reserved for refractory cases. Tumours Total skin electron beam with local booster radiation to tumours. Extracorporeal photophoresis is an alternative (not available locally). Erythrodermic stage and Sezary syndrome Photophoresis, if available, is probably the best treatment, and concomitant methotrexate may increase its effectiveness. PUVA may give symptomatic relief but should be administered with care. Other choice of treatment may include a interferon, systemic chemotherapy, retinoids and bone marrow transplant. Histological lymph node involvement Treatment is essential palliative: which may include local radiation to local symtomatic disease, systemic chemotherapy, a interferon, retinoids. Visceral involvement Palliative treatment include systemic chemotherapy, interferons, retinoids etc.
PUVA: Primarily indicated in patch and plaque skin diseases, this is not effective in tumor diseases and should be used with care in erythrodermic patients. The administration is essentially similar to PUVA in psoriasis. Sanctuary site lesions will need addition dose or adding of other agents like topical steroid, nitrogen mustard. RePUVA: adding retinoids (Etretinate, isotretinoin) to PUVA gives earlier response and longer period of remission, although the relapse rate and long term survival is the same as PUVA alone. It should considered in patients with poor initial response to PUVA. Total skin electron beam therapy: The delivery of high energy electron to a limited depth of skin and preventing systemic toxicity. While it is effective in patch and plaque diseases, its relative poor cutaneous tolerance makes it the treatment reserved to tumor stage or refractory extensive plaque stages. It is relatively contraindicated in erythrodermic disease because of severe side effects. INFECTION: BACTERIAL, VIRAL, FUNGAL Dr. W.K. FUNG CHAPTER 14 1. COMMON BACTERIAL DISEASES OF SKIN The predominant primary pathogens are the group A Streptococci or Staphylococcus aureus. The clinical pictures vary because of the host factors and the local anatomic infections. 1.1. Impetigo Two clinical types of impetigo occur. The first type is due to group A Streptococci or a mixture of Streptococci and Staph. aureus. It is a disease of young children in which blisters appear on the skin around the mouth. The vesicles and pustules easily rupture, forming a thick, soft, golden-yellow "stuck on" crust, the hallmark of impetigo. The skin lesions may be complicated with deep cellulitis or bacteraemia. Glomerulonephritis may follow impetigo due to Streptococcus pyogenes. The second type of impetigo is bullous impetigo, characterized by rapid progression of vesicles to flaccid large bullae. The bullae eventually rupture, and form thin, light brown crusts. This infection is frequently associated with Staph. aureus of phage group II. 1.2. Ecthyma Ecthyma initially presents as a vesicle or vesicopustule on the lower extremities of children or neglected elderly patients, the skin lesion gradually enlarges to form a ulcer with punched-out appearance. Poststreptococcal glomerulonephritis is a known sequel.
1.3. Erysipelas A spreading infection most commonly due to Group A and B Streptococci presenting as a characteristic brawny, edematous, indurated and well demarcated appearance. The patient may be acutely ill with high fever and toxaemia. Predisposing factors include alcohol abuse, diabetes mellitus, immunosuppression, venous or lymphatic obstruction. 1.4. Acute Cellulitis This is an acute, spreading infection of subcutaneous tissue. There are two main bacteriological forms. The acute pyogenic cellulitis is usually due to group A Streptococci and Staph. aureus. It presents as a markedly red, hot, infiltrated edematous skin lesion and the borders are usually ill-defined. Lymphangitis and lymphadenitis involving local draining lymph glands are frequently found. The second form is the Anaerobic cellulitis which is relatively rare and is usually due to a synergistic infection with both aerobic and anaerobic bacteria. The causal organisms include aerobes (coliforms, Pseudomonas aeruginosa, staph. aureus) and anaerobes (bacteriodes, anaerobic cocci). Two clinical syndromes may develop: 1) Necrotizing Fasciitis This infection usually occurs on the lower extremities, abdominal wall, perineum and operative wounds. The infective-ischaemic process spreads along the fascial plane causing extensive necrosis while the external appearance of the skin remains normal initially. So the damage is more extensive than the extent of the overlying skin. The involved area is swollen, red, warm and painful. Crepitus is often present. The patient is severely ill with fever and septic shock may occur. 2) Progressive bacterial synergistic gangrene This infection is a gangrenous ulceration of the skin due to a mixed bacteria flora. It usually follows abdominal or thoracic infection or trauma. A small, painful, superficial ulcer develops and gradually enlarges to form a ulcer with a rim of gangrenous skin. 1.5. Furuncles, Boils and Carbuncles With the exception of carbuncles, these skin infections are uncomfortable and unsightly rather than serious. Furuncles or boils occur only in areas where there are hair follicles. The lesion is a deep-seated inflammatory nodule, it is tender, hard, red and fluctuate after several days. A carbuncle is a more extensive, deeper, infiltrated lesion and usually occurs at the nape of the neck, the back or thighs. Systemic symptoms such as fever and malaise are often present. All these lesions are caused by infection with Staphylococcus aureus. 1.6. Folliculitis
This is an acute, small, painful pustular eruption of hair follicles. There are two main subtypes: superficial and deep. Bockhart's impetigo is a superficial folliculitis. Small, dome-shaped pustule develops at the opening of a hair follicle surrounded by erythema. It usually occurs on the limbs and the scalp. Deep folliculitis include sycosis barbae and lupoid sycosis. Staphylococcal or Streptococci are the commonest pathogens. Folliculitis can also be caused by Pseudomonas aeruginosa as it is easily contracted from poorly maintained whirlpools or jacuzzis. The clinical presentation is similar to streptococcal or staphylococcal folliculitis. However, the patient may feel unwell, with a low grade fever and lymphadenopathy. Management 1) General skin care 2) Local measures Immobilization and elevation of the involved area to reduce local trauma. Cool, sterile saline dressing daily. Extensive debridement and grafting may be required for the necrotic areas of streptococcal grangrene. Mupirocin or bacitracin ointment may be useful for its antibacterial effects and softening of crusted lesions. 3) Specific measures In mild cases, topical antibiotics are adequate for treatment. In widespread and severe situation, systemic antibiotics are indicated. Penicillin G, Penicillin V, flucloxacillin and erythromycin are good antibiotics for both the streptococcal and staphylococcal infection. Tetracycline should best be avoided in the treatment of known streptococcal disease as resistant strain is not uncommon. Special measures should be aimed at elimination of nasal and skin carriage of Staph. aureus. This include the use of: a) local antibiotic ointment such as fusidic acid ointment in the nasal vestibule. b) intranasal application of mupirocin ointment. c) topical application of chlorhexidine or povidone iodine to eradicate Staph. aureus harbouring in body folds before bathing. d) oral antibiotics such as rifampicin. 1.7. Erythrasma Erythrasma is a superficial bacterial skin infection due to Corynebacterium minutissimum. The lesions are reddish-brown, scaly and finely wrinkled macular patches, usually involve the intertriginuous areas. Axillary and genitocrural areas are commonly involved. The diagnosis is supported by the characteristic "coral-red" fluorescence under wood's light.
Treatment 1) Oral erythromycin 250 mg QID for 1 week. The lesions usually clear within several weeks. 2) Topical therapy includes aqueous clindamycin solution, whitfield's ointment or miconazole cream 2. COMMON VIRAL DISEASES OF SKIN 2.1. Herpes Simplex (HS) The basic lesions are vesicles but these can take many different forms on the mucocutaneous surface. The clinical features are divided into primary disease and recurrent disease. Oral and facial lesions are usually due to Herpes Simplex type 1 while anogenital lesions are mostly due to Herpes Simplex type 2. 2.1.1. Primary Infections Primary infection with herpes simplex occurs primarily by direct exposure through mucocutaneous contact with another infected individual. It is defined as the first infection with the virus in a seronegative patient. The infection can be subclinical but below are listed the symptomatic clinical presentations. 1) Primary gingivo-stomatitis Primary herpetic infection (usually type 1 herpes simplex) of the mouth and pharynx is more common in the children. Vesicles inside the mouth on the buccal mucosa and gums coalesce to form plaques covered with a greymembrane. The vesicles are very painful and the infection may accompany with high fever, tender lymphadenopathy and generalized complaints. 2) Primary genital herpes Primary genital herpes, generally by type 2 virus, is a common sexually transmitted disease characterized by multiple grouped, umbilicated vesicles, oedema, fever, pain and dysuria, with regional lymphadenopathy in men and vulvovaginitis in woman. The incubation period is from 3 to 14 days. 3) Herpetic whitlow Herpetic whitlow refers to painful vesicles with clear serous fluid on the fingers or hands. It is a common occupational hazard for medical and dental personnel. The inoculation usually occurs in areas of abraded or broken skin. The vesicles will subsequently progress to form superficial ulcers. 4) Herpetic keratoconjunctivitis Primary herpes can involve the conjunctive and cornea. The eyelids are usually swollen and there are vesicles and ulcers on them. 5) Aseptic meningitis, encephalitis
6) Primary herpes hepatitis 2.1.2. Recurrent Infections The virus remains in the dorsal root ganglion, from which secondary infections are repeatedly seeded to the skin over a period of years. Recurrent attacks then occur and presents as grouped umbilicated vesicles on an erythematous and somewhat edematous background. 1) Recurrent facial-oral herpes simplex (cold sores) The cold sore usually appears at the vermilion border of the lip. The erythematous papule becomes vesicular and then ulcerates. The open sore heals in 8 to 9 days. Recurrent genital herpes also recur easily and these are mainly due to type 2 virus. The number of recurrences is about 3 or 4 per year. 2) Keratitis Reactivation less commonly affects the eye, recurrent lesions are usually restricted to the cornea and the conjunctiva is not involved. 3) Recurrent lumbosacral herpes simplex Recurrent herpetic lesions appearing on the lumbal area and buttocks may cause "sciatic pain". 4) Herpes infection in the immunocompromised patient Reactivation of herpes is very common in patients with defective cellular immunity from hematological malignancies, Human Immunodeficiency Virus (HIV) infection and those receiving immunosuppressive agents or transplant patients. Herpes infection recurs more frequently, have a more severe and prolonged course and may present atypically e.g. in the form of granuloma. Common causes of recurrent infection 1) Stress 2) Pneumonia 3) Onset of menstrual cycle 4) Sun exposure 5) Mechanical trauma 6) Sexual activity (in genital herpes) Diagnosis 1) Viral culture from scrapped tissues or fluids. 2) Immunofluorescence in scrapings from lesions to detect viral antigens. 3) Electronmicroscopy to demonstrate the virus. 4) Serology which may be useful for diagnosing primary infections is very difficult to interpret in recurrent infections because of high levels of existing antibody and recurrences usually do not cause a rise in titre. So serology is
not routinely performed in the Social Hygiene Clinic. Also, commercially available serological tests cannot reliably distinguish its types 1 and 2 infection. Treatment 1) Facial-oral herpes, Genital herpes a) Topical antibiotic cream. e.g. aureomycin cream b) Topical acyclovir cream c) KMnO4 wet compress d) Oral acyclovir therapy is only used in very severe and extensive situation. e.g. acyclovir 200 mg 5 x daily x 5/7 with 24 hours of active new lesion. e) Oral Famciclovir 125 mg tds x 5/7 or oral valaciclovir is an alternative 2) Herpetic Keratitis a) Idoxuridine 0.5% eye drops. b) Acyclovir ophthalmic ointment. 3) Treatment of herpes infections in the Immunocompromised patient - Intravenous (IV) acyclovir 4) Recurrent infections (>6 attacks per year) - Prophylactic oral dose acyclovir for several months has been shown to reduce severity and frequency of relapse e.g. Acyclovir 400 mg bd. However, the whole course of treatment is quite expensive. 2.2. Herpes Zoster (HZ) The varicella-zoster virus causes the characteristic herpetic lesion similar to herpes simplex. Whereas varicella represents a primary lesion, herpes zoster (shingles) represents reactivation of the virus from the dorsal root ganglion and results in the classic dermatomic distribution. Herpes zoster is a common condition. There is a correlation between age and incidence of the condition. The disease usually affects the elderly and the immunocompromised patients. Constitutional symptoms are followed by tingling and pain, erythema, and vesicle formation in a dermatomic distribution . Major complications of herpes zoster 1) Acute phase a) Ocular involvement-Herpes ophthalmitis b) Secondary infection c) Cutaneous or visceral dissemination 2) Chronic phase a) Post-herpetic neuralgia b) Scarring c) Motor neuropathy, post-infection encephalomyelitis, paralysis
Treatment 1) Topical agents a) Acyclovir cream b) Topical antibiotic cream may be useful in lesions with secondary infection 2) Systemic agents a) Oral acyclovir 800 mg 5 times daily for 1 week b) Oral Famciclovir 250 mg 3 times daily for 1 week c) Oral Valaciclovir 1 gram 3 times daily for 1 week In immunocompromised patient, IV acyclovir treatment is indicated. Indications of systemic anti-viral treatment. a) Patients get skin rashes within 3 days of onset, especially for the elderly group. b) Patients suffer from ophthalmopathy within 3 days of onset. c) Immunocompromised patient whenever vesicles present. 2.3. Molluscum Contagiosum It is caused by a large DNA virus of the pox group. The umbilicated pearly lesions, often multiple, are more common in childhood and resolve spontaneously after becoming inflamed. The lesions occur anywhere on the body. Lesions occurring on the genitalia or lower abdomen in adults are almost sexually transmitted. In children, the lesions can be left behind as it is harmless and involute spontaneously. In adults, either cryotherapy or piercing with a cocktail stick dipped in iodine can be used as treatment. In patients with genital lesions, both the patient and the sexual partner should be screened for other sexually transmitted diseases. 2.4. Warts Viral warts are caused by the Human Papilloma virus (HPV). More than 50 subtypes exist. Warts are contagious and spread easily if there is local breaks on the skin. Their morphology varies with the viral subtype and anatomical site. Spontaneous resolution may occur. 2.4.1. Common Warts They are mostly due to HPV type 2. The lesions are discrete, firm papules with a rough surface . They are usually multiple. 2.4.2. Plane Warts These are usually caused by HPV type 3. The lesions are flat-topped, fleshcolored papules, mainly on the face, hands and limbs. 2.4.3. Plantar Warts (Verucca Plantaris) Plantar warts are common, especially in school-children who may acquire them from swimming-bath floors. HPV1 and HPV2 are the commonest
causative viruses. The lesions are characteristically flat with a callus on the surface and are often very painful. They usually occur on the palm and sole. 2.4.4. Anogenital Warts Please refer to Chapter 30 in STD Section. 2.5. Pityriasis Rosea It usually occurs in children and young adult. A viral atiology is suspected. A characteristic herald patch commonly precedes the later multiple lesions by several days. The herald patch is a single erythematous oval or circular macule of 3 to 4 cm in diameter. Subsequent lesions are similar but much smaller and have a peripheral collarette of scale. They occur in a symmetrical distribution and distribute along the rib lines. The lesions may be asymptomatic or mildly itchy. They persist for 4-6 weeks. Symptomatic treatment for pruritis is achieved by using topical steroid, oral antihistamines or a short course of UVB. All the above measures do not modify the eruptions and the course of the disease. 3. COMMON FUNGAL DISEASES OF SKIN 3.1. Pityriasis Versicolor It is caused by yeasts (Pityrosporum orbiculare and P. ovale) providing widespread fine scaly macules on the upper trunk and back. The colour of the lesions varies. The lesions are pale in dark skin and darker in fair skin. Recurrent attacks are common. The diagnosis is established clinically and can be supported by the faint yellow fluorescence under Wood's light in the affected areas. Treatment 1) Topical treatment a) Imidazoles cream e.g. clotrimazole, miconazole, isoconazole b) Ketoconazole shampoo c) 2.5% selenium sulphide shampoo d) 3% salicylic acid in spirit e) 20% sodium thiosulphate in spirit 2) Systemic treatment a) Oral ketoconazole 200 mg daily for 5 days b) Oral itraconazole 100 mg daily for 5 days 3.2. Tinea Pedis It is a fungal infection of the toe webspaces and the soles. Trichophyton rubrum (T. rubrum), T. Mentagrophytes Var. interdigitale and Epidermophyton floccosum are the commonest causative organisms. There are 3 main clinical patterns.
1) Chronic Plantar Scaling It presents as a "Moccasin" distribution, on plantar surface and the edges of feet. Peeling of skin and scales are common. Hyperkeratosis may develop on weight-bearing areas. 2) Acute Vesicular Tinea Pedis Sudden eruption of pruritic or painful vesicles develop on the soles. The eruption is usually unilateral. This pattern may give rise to Id reaction presenting as symmetrical, vesicular pompholyx at sites distant from the site of active fungal infection. 3) Interdigital Tinea Pedis Peeling, maceration and fissuring occurs frequently in the lateral toe clefts. It is usually very itchy and is more common in people with sweaty feet or occlusive foot-wear. 3.3. Tinea Manuum T. rubrum is the commonest cause. There is unilateral scaling particularly in the skin creases and the nails are usually involved. 3.4. Tinea Unguium Infection of nail and/or the nail bed with dermatophyte fungi is usually due to T. rubrum. It presents as distal nail edge onycholysis with subungual tan crumbly debris, subungual hyperkeratosis and brownish discolouration from secondary colonization by non-pathogenic fungi e.g. Aspergillus. 3.5. Tinea Cruris Tinea cruris presents as itchy advancing red, sharply demarcated skin rashes enlarging from inguinal folds down inner thigh or into pubic area. Central healing followed by post-inflammatory hypopigmentation is its characteristic. It is usually caused by Trichophyton rubrum, Epidermophyton floccosum and T. mentagrophytes var. interdigitale. 3.6. Tinea Capitis Scalp ringworm is uncommon in H.K. nowadays. It appears as scattered scaly patches containing broken hairs. The lesions may be asymptomatic or mildly itchy. In general, the pattern of involvement can be classified as ectothrix, endothrix, kerion and favus respectively. In severe situation, boggy mass of inflamed and purulent skin known as kerion may occur especially by animal infections. Usually human infections produce minor
degrees of erythema and scaling while animal infections cause considerable inflammation. 3.7. Tinea Corporis It refers to the dermatophyte infection of smooth skin. The lesion is identical to that of tinea cruris but occurs on the trunk and limbs. It is easily misdiagnosed as discoid eczema or pityriasis rosea. 3.8. Tinea Faciei It presents as an amorphous, asymptomatic reddish patch, which may be photosensitive. The skin lesion may be mistaken for polymorphic light eruption, lupus erythematosus and contact dermatitis. It is commonly caused by Trichophyton rubrum, T. mentagrophytes and Microsporum species. Outbreak of zoophilic species induced tinea faciei has been found in Hong Kong. Diagnosis 1) Wood's light (more useful in Tinea capitis) 2) Microscopic examination of scrapings and clippings in 10% - 30% KOH 3) Culture Treatment of Tinea infection 1) Topical treatment Imidazole e.g. miconazole (Daktarin), clotrimazole (Canesten, Lotremin), Tionazole (Trosyd), Ketoconazole (Nizoral), Isoconazole (Travogen), Bifonazole (Mycospor) Allylamine e.g. Terbinafine (Lamisil), Natifine (Exoderil) Others e.g. Tolciclate (Tolmicen), whitfield's ointment, mycota, Castellani's paint, Ciclo-piroxolamine (Batrafen), Tolnaftate (Tinaderm), Zinc Undecenoate (Tineafax) 2) Systemic treatment Griseofulvin, ketoconazole, Itraconazole, Terbinafine 3.9. Candidiasis Candida infections caused by yeast-like fungi Candida albicans commonly occur in moist, flexural sites. It is more common at the extremes of age and during pregnancy. Predisposing factors include diabetes mellitus, pregnancy, broad-spectrum antibiotics, obesity, Cushing disease, uraemia, malignant disease and immunodeficiency. It can present as 10 clinical patterns, depending on the site of involvement. They are the oral thrush, angular cheilitis, genital candidiasis (vulvovaginitis), candida balanitis, candida intertrigo, chronic paronychia, chronic onychia, pruritus ani, erosio interdigitalis and candida granuloma. The diagnosis is arrived clinically and confirmed by fungal culture. Treatment
1) Topical treatment Nystatin, imidazole cream, amphotericin lozenges (in oral candidiasis) 2) Systemic treatment Oral fluconazole, itraconazole, ketoconazole INFESTATIONS Dr. T.S. AU CHAPTER 15 1. SCABIES 1.1. Morphology and Biology of the Scabies Mite The adult female mite is 0.4 mm long while the male mite is 0.2 mm long. Copulation occurs in a small burrow excavated by the female mite. The fertilized female enlarges the burrow and begins egg-laying. About 50 eggs are laid by each female mite during its life span of 4 to 6 weeks. The mite shows a preference for certain sites to burrow. They tend to avoid area with a high density of pilosebaceous follicles. Infested patients harbour an average of 11 mites. 1.2. Incidence and Epidemiology The incidence of scabies in developed countries show cyclical fluctuation. It affects all races and social classes world-wide. The interval between the end of one epidemic to the beginning of another is about 10-15 years. Scabies may occur in any age but it is most common in children and young adults. The overall sex incidence is equal. Overcrowding associated with poverty and poor hygiene in under-developed countries encourages the spread of scabies. Transmission is by close physical contact like sharing of a bed. Studies have demonstrated that indirect spread by clothing and bedding is not important. Although scabies is common in school-age children, transmission in schools is unlikely. Outbreaks occur in hospitals, old-age homes and other institutions. Outside the host, free adult mite and eggs can survive 36 hours and 10 days respectively. 1.3. Clinical Features Symptom occurs 3 to 4 weeks after the acquire of the infection. This latency period may not occur if an individual has had a previous infestation. Itchiness is the most obvious symptom of scabies. It is worst at night time when the patient is warm. The pathognomonic sign of scabies is a burrow; it is a short, wavy, dirtyappearing line crossing skin lines. They may occur on the wrists, the borders of the hands, the sides of the fingers and the finger web-spaces , the
feet particularly the instep and in male the genitalia and nodules on scrotum. Burrows are uncommon on the trunk in adult but they may be found in elderly and infants. Pruritic papules which accompany hypersensitivity reaction occur around axillae, peri-areolar regions, periumbilical regions, buttock and thighs. The lesions do not occur above the neck-line. Secondary change like eczematous change frequently give confusion to the clinical picture. Inappropriate use of topical steroid may change the clinical picture to mimic other dermatoses. 1.4. Diagnosis Absolute confirmation can only be made by the discovery of the burrows and microscopic examination. A burrow is gently scraped off the skin with a blunt scalpel, and the material placed in a drop of mineral oil on a microscopic slide. Oil mounting of the specimen sharpens the microscopic image and does not kill the mites which may be present (as potassium hydroxide would). Presence of mites, eggs or fragments of egg-shells confirms the diagnosis . Other diagnostic tests include needle extraction of mite, epidermal shave biopsy and punch biopsy. 1.5. Treatment It is important that all members of the household and all close contacts should be treated simultaneously. Elderly members of the family often resent for treatment but they can be asymptomatic reservoirs of infection. Treatment must be given on two consecutive nights but not for longer. Antiscabies preparations are primary irritants which will eventually cause eczema, patients should be warned about over-use. The patient should first take a bath, and this is followed by a brisk toweling to open the hydrated burrows. Hot bath increases the percutaneous absorption of the drug and may cause toxicity. Benzyl benzoate employed as a 25% emulsion should remain on the skin for 24 hours. The emulsion is most conveniently applied with a 2" paint brush applied to the whole body from the neck down including the genitalia and the soles of the feet. This anointing is repeated on the following morning. On the following evening the patient should take a bath again and has the bed-linen and clothing changed which are then laundered in the usual way. After the scabicidal treatment, pruritus may persist for a further 2 weeks. A topical antipruritic such as crotamiton cream may be applied on residual itchy areas. Postscabetic eczema can be treated with topic steroid.
Secondary infection should be treated with a systemic antibiotic. If eczematisation is severe, a non-irritant scabicide, preferably in an aqueous base, should be used. Treatment of neonates - 6.25% benzyl benzoate emulsion may be used. Other alternatives include 10% crotamiton cream (applied nightly for 2 nights and washed off after the second application), 10% sulphur in petrolatum (applied nightly for 3 nights and washed off 24 hours after the last application) and 5% permethrin cream. Other drugs used: 1) 1% gamma benzene hexachloride (Lindane) - a single application wash off after 12-24 hours is usually recommended. It is not recommended to be used in young children, pregnant and nursing women, and those with neurological diseases. 2) malathion - malathion 0.5% in aqueous base has been used as scabicide. It should be left on the skin for 24 hours. The advantage over BBE is that it is much less stinging and acceptable. 3) permethrin - 5% dermal cream employed as a single application, wash off 8-12 hours. It is of low toxicity, and a single application which is removed in 8-10 hours is adequate. The disadvantage is that it is much more expensive than BBE or malathion. 4) monosulfiram - 25% solution diluted with 2-3 parts of water to be applied daily for 2 or 3 days. 5) crotamiton - 10% crotamiton cream is not highly effective and should not be a first line treatment for scabies. It is at best an adjunctive treatment for post-treatment pruritus and an alternative for BBE in infants and pregnant ladies. 6) topical sulphur e.g. 10% sulphur in petrolatum. 2. CRUSTED SCABIES (NORWEGIAN SCABIES) Crusted scabies is an infestation with Sarcoptes scabiei hominis in which huge number of mites were present. The grossly thickened horny layer is honeycombed with cavities which contain large number of mites, and these are shed into the environment of the patient. Crusted scabies is highly contagious; an undiagnosed case of crusted scabies may lead to large outbreak of common scabies. 2.1. Aetiology and Pathogenesis In common scabies there are few mites probably because of scratching destroys the burrows. In some patients skin anaesthesia secondary to neuropathy or spinal injury obviously do not perceive itch and do not scratch crusted scabies is likely to develop.
Crusted scabies has a predilection for patients with physical debilitation, mental retardation, sensory impairment and immunosuppression. 2.2. Clinical Features Masses of horny debris accumulate beneath thickened and discoloured nails. Large warty crusts form on the hands and feet, and the palms and soles may be irregularly thickened and fissured. Itching is often absent or slight. It may present as exfoliative dermatitis. Differential diagnoses include hyperkeratotic eczema, psoriasis, Darier's disease and contact dermatitis. 2.3. Treatment There is no single treatment for crusted scabies. The general principle is that multiple treatment is needed and sequential use of several agents may be necessary. The following regimen is suggested with the use of 25% benzyl benzoate emulsion (BBE), which is the most commonly used agent in public hospitals in Hong Kong. Ivermectin, given in a single oral dose, is found to be effective in healthy and HIV subjects in a small study. Equipment to prepare: Soft brushes to apply the BBE, tooth brushes to rub away the scales, nail clipper to trim the nails. Treatment is intensive and should be given by nurses well informed and dedicated to give the treatment. BBE is applied from neck include behind the ear down to the toes. Application to the face and scalp is necessary. BBE may also apply to those area but may be too stinging. 0.5% Malathion is a good alternative which is also effective and causing less irritation. Crotamiton is an alternative to malathion to the area, but is much less effective. Nails should be cut short. BBE should be scrubbed into the area under the nail. Scales, which are usually thick under the nail and on flexural area should be gently rubbed away with brushes. Repeat the above steps for 4 consecutive days at least. Repeat examination and isolation for mite on day 5. Continue treatment until identification is negative. Give oral antibiotics which are effective against staphylococcus and streptococcus unless contraindicated, for 7-10 days. Change clothing and bed linen daily and these are treated in method mentioned below. Isolation can be stopped when treatment is completed (e.g. day 5 when identification is negative). Repeat identification procedure one week after treatment is stopped. Repeat scrapings for identification each week as long as the patient is still in ward.
While BBE is cheap and safe, its use in crusted scabies is less reported in the literature. It causes irritant contact dermatitis especially in areas infected or eczematised. The local profile of resistance to BBE is not reported, but since BBE is the most commonly used scabicide locally, resistance to the agent is not surprising. Physician should be prepared for this possibility and ready to use other agents if clinical response is not satisfactory. The microbiologist¡¦s opinion is invaluable. Management of Contacts: Adequate treatment of contacts is as important as adequate management of the target patient. Success of treatment depends on an all-inclusive approach: all individuals in the ward and their family members should be treated, and treated simultaneously, no matter whether they are symptomatic or asymptomatic. 3. PEDICULOSIS CAPITIS 3.1. Epidemiology The infection rate was higher in urban than in rural areas. In the early 1980s, there was a resurgence of infection due to the emergence of the so-called 'super-louse' which was resistant to DDT powder. Lice are more common on children than on adults, and female of all ages are more frequently infected than males. There does not appear to be any direct correlation between hair length and louse infection rates, and it has been suggested that large masses of hair may, in fact, impede transmission of lice from scalp to scalp. The vast majority of head louse infections are acquired by direct head-to-head contact. Spread of lice is encouraged by poverty, ignorance, poor hygiene and overcrowding. Overcrowding is perhaps the most important factor. Transmission of head lice by sharing personal articles such as hair brushes, combs and towels is possible. 3.2. Clinical Features These occur in the long hair of the scalp, but may also invade eyebrows and eyelashes. The characteristic manifestation of head louse infection is scalp pruritus. Secondary bacterial infection may occur as a result of scratching, and concomitant head louse infection must always be considered in cases of scalp impetigo. Pruritic papular lesions may occur on the nape of the neck, and occasionally a generalized non-specific pruritic eruption develops. In severe, neglected cases pus and exudate may produce matting of the hair. Nits are egg-cases. They occur in greatest density on the occipital and parietal regions. Most of the unhatched nits are within 5 mm of the scalp surface. The eggs can be distinguished from dandruff by the fact that they are firmly attached to the hair. Moreover, if the affected hair is cut off and
observed under microscope, the oval egg capsule can be easily identified. Adult lice and nymphs may be seen in heavy infestation. 3.3. Treatment Treatment of pediculosis of the scalp aims at the destruction of the lice and the ova. Other members of the family and the whole class of school children should be examined, otherwise re-infestation will occur. Malathion is effective and has good ovicidal activity. It is adsorbed onto keratin, a process which takes approximately 6 hours, and has a residual protective effect against re-infection for about 6 weeks. Malathion should be left on the scalp for 12 hours before washed off. The insecticide is degraded by heat, and a hot-air dryer should not be used. Treatment should be repeated 2 weeks later when the larvae have hatched out. Lotions are preferable to shampoos, as the latter expose the insects to relatively low concentrations of insecticide which will favour the development of resistance. Empty egg-cases are difficult to dislodge, they persist for some time until they are gradually worn away by repeated washing. They may be removed with a fine-tooth comb or forceps. A cream rinse containing formic acid may facilitate the removal. 4. PEDICULOSIS CORPORIS 4.1. Incidence and Epidemiology Pediculosis corporis is now uncommon in developed countries. It mainly affects the poor and neglect and flourishes in overcrowded, dirty situations where individuals seldom change their clothes. There is great variation in the number of eggs and lice on the clothing. In most cases the number of lice is small but in some thousand of lice may be present. Transmission is mainly by direct close body contact or by sharing infested clothing. Lice on a cooling dead body will look for alternate lodgings, and doctors asked to certify death in a vagrant should be aware of this. 4.2. Clinical Features Intense pruritus is the chief complaint. It is due to sensitization to salivary antigens of the lice. Excoriation with secondary bacterial infection and hyperpigmented changes are common physical findings. When the lice are not feeding, they stay in the clothing. Therefore, it is important to examine the inner lining of clothing including the seams of underpants. Hands and feet are usually not involved and there is a predilection for the upper back. The characteristic distribution helps to distinguish it from
scabies. The principal louse-borne diseases are epidemic typhus, trench fever and louse borne relapsing fever. 4.3. Treatment It is the clothing rather than the patients which require treatment. Destruction of the lice is accomplished by laundering or boiling the clothing and bedding. High temperature laundering of underpants and dry-cleaning of outer clothing are also effective. Tumble-drying is the most effective means of killing both lice and eggs. The patient should bath thoroughly with soap and water. Theoretically, this is sufficient. However, many dermatologists would prescribe gamma benzene hexachloride to treat the body as well. Mass delousing of large number of persons can be carried out successfully by simply blowing DDT powder under the clothing with a hand dust gun. CUTANEOUS TUBERCULOSIS AND ATYPICAL MYCOBACTERIAL INFECTION Dr. L.Y. CHONG CHAPTER 16 1. INTRODUCTION Cutaneous tuberculosis was once a relatively common chronic infection in Hong Kong. In a study done in Social Hygiene Service in 1968, there were totally 177 cases from January 1962 to April 1967. This represented approximately 0.35% of all the skin cases (50,364 cases) seen in Government Dermatological Clinics during the same period. In recent decade, because of improved living environment, BCG vaccination and effective antituberculous drugs, this disease now becomes uncommon in Hong Kong. In a recent 10-year retrospective survey in Social Hygiene Service, there were totally 179 cases of cutaneous tuberculosis from January 1983 to December 1992, representing only 0.067% of the total skin cases (267,089 cases) seen in our clinics during that period. The relative incidences of different clinical types of cutaneous tuberculosis are shown in the following pie chart. Different Types of Cutaneous Tuberculosis Social Hygiene Service, Hong Kong (1983-1992) Lupus vulgaris 6.3% Tuberculosis verrucosa cutis 4.5% Scrofuloderma 4.0% Lichen scrofulosorum 6.3%
Erythema induratum 79.5% Papulonecrotic tuberculid 4.0% It can be shown from these local figures that the true cutaneous tuberculosis is now very uncommon in Hong Kong, representing only 14.8% of all cases. In fact, most of the reported cases are erythema induratum, which accounts for 79.5% of the cases. Erythema induratum is one form of tuberculids and the truth of its tuberculous aetiological origin is still open to debate. 2. AETIOLOGY Cutaneous mycobacterial infections are chronic granulomatous lesions affecting skin at various regions of the body. Micro-biologically they are classified as follows: 2.1. Tuberculous, Pathogenic M tuberculosis M bovis M lepra M africanum 2.2. Non-tuberculous, potentially pathogenic 1) Slow growing M marinum M ulcerans M kansasii M avium-intracellulare M scrofulaceum 2) Rapid growing M fortuitum M chelonei 3. CLINICAL FEATURES There are different clinical presentations in cutaneous tuberculous infections, depending on the virulence and number of bacilli infected, immunological status of the host and the route of infection. Traditionally the clinical types are divided into two groups: 1) True cutaneous tuberculosis Lupus vulgaris Tuberculous verrucosa cutis Scrofuloderma Tuberculous chancre, gumma, cold abscess Miliary tuberculosis 2) Tuberculids Papulonecrotic tuberculid Lichen scrofulosorum Erythema induratum 3.1. True Cutaneous Tuberculosis
This group of cutaneous tuberculosis is infected through direct inoculation from an exogenous source, contiguous or haematogenous spread from an endogenous focus. 3.1.1. Lupus Vulgaris This is a chronic, progressive and tissue-destructive form of cutaneous tuberculosis in patient with moderate or high degree of immunity. It occurs more common in females than in males. The classical lesions consist of reddish-brown plaque with "apple-jelly" colour on diascopy. The lesions progress by peripheral extension and central healing, atrophy and scarring. The areas of predilection are head and neck (80%), followed by arms and legs, then trunk. It can be associated with tuberculosis of lymph node, lung, bone and joint. In long-standing cases, patients may have scarring, deformity, squamous cell carcinoma, basal cell carcinoma or sarcoma. The main differential diagnosis includes discoid lupus erythematosus, sarcoidosis, leprosy, lupoid leishmaniasis, tertiary syphilis, deep fungal or atypical mycobacterial infection, granulomatous rosacea and Wegener's granulomatosis. 3.1.2. Tuberculosis Verrucosa Cutis In the past, this condition was common in Chinese boys over the buttocks and knees. This is mainly due to their habit of playing and squatting in the streets with open-bottom trousers. It usually presents as an indolent, purplish or brownish red, warty and hyperkeratotic plaque lesion. It affects patients with moderate or high immunity through direct inoculation of the tubercle bacilli at sites of trauma. The areas of predilection are therefore over the buttock, knee, elbow, hand and finger. Its progression is usually very slow and spontaneous resolution may occur. This condition must be differentiated from lupus vulgaris, viral wart, mycobacteria marinum infection, chromomycosis, tertiary syphilis and hypertrophic lichen planus. 3.1.3. Scrofuloderma This results from direct extension of an underlying tuberculous focus such as lymph node, bone or joint to the overlying skin, often associated with pulmonary tuberculosis. It is characterized by undermined ulcers, nodules, fistulae, sinuses and scar. The areas of predilection are neck, supraclavicular fossae, axillae and groin. The differential diagnosis mainly includes hydradenitis suppurativa, actinomycosis, sporotrichosis and atypical mycobacterial infection. 3.2. Tuberculids It has been postulated that tuberculids are the result of hypersensitivity reaction to haematogenous dissemination of tubercle bacilli or their toxin in patients with moderate or high degree of immunity. Usually no identifiable
focus of active tuberculosis can be detected and the tissue culture for acidfast bacilli is often negative. There is still much controversy about these conditions. 3.2.1. Papulonecrotic Tuberculid This condition usually presents with symmetrical crops of papular eruption that proceed to central necrosis, ulceration and depressed scar. It occurs predominantly in young adult, most commonly affecting the limbs. There may be history or distant foci of tuberculous infection. The main differential diagnosis includes prurigo simplex, papular eczema, folliculitis, leukocytoclastic vasculitis, pityriasis lichenoides et varioliformis acuta and secondary syphilis. 3.2.2. Lichen Scrofulosorum This is a rare form of tuberculid, presenting with grouped lichenoid papules with perifollicular pattern over the trunk. It is frequently found in children or young adults and may be associated with tuberculosis of lymph node, bone or joint. The lesions often involute slowly in months without scar and then recur. This condition must be differentiated from lichenoid drug eruption, lichen nitidus, keratosis spinulosa, sarcoidosis, lichenoid syphilis and eruptive syringoma. 3.2.3. Erythema Induratum (Bazin) This is a nodular tuberculid presenting with indolent inflamed deep-seated nodule and plaque, occurring bilaterally over the calves or feet. In severe case there may be necrosis, ulceration, depressed scar and pigmentation. It is more common in females than males. Usually there is no evidence of other distant tuberculous foci. The main differential diagnosis is erythema nodosum and other forms of nodular vasculitis. 3.3. Mycobacteria Marinum Infection (Swimming pool or fish tank granuloma) This is a chronic granulomatous infection of the skin caused by M marinum, acquired by inoculation through abrasions. It is more vulnerable in children and adolescents who frequently go to swimming pools, and among fishermen and fishmongers. The lesion commonly occurs on fingers, knuckles, elbows, knees and feet. Clinically it presents as an inflamed nodule, pustule, ulcer or abscess. Sporotrichoid spread may occur. The main differential diagnosis includes lupus vulgaris, sporotrichosis and leishmaniasis. 4. INVESTIGATIONS
4.1. Skin biopsy x histopathology (AFB stain) x tissue culture for M tuberculosis + tissue culture for atypical mycobacterial and deep fungi The histopathological diagnosis and clinical correlation are important because there is only a small percentage of cases with positive smear or culture. When the skin biopsy is performed, one must make sure that adequate tissue has been taken for both histological sections and tissue culture. Repeated skin biopsy may sometimes be necessary to make a final diagnosis. It is also important to specify on the laboratory form if one wants to do a culture for atypical mycobacteria. They require different temperature for growth in culture medium, for example, M marinum requires a temperature of 30-32 degree centigrade within 2-3 weeks. 4.2. Tuberculin Test In Hong Kong, Mantoux test is usually done by starting with 1 unit of PPD intradermally over the forearm. If the result is negative, then the test is repeated with 10 units. The results are interpreted as follows: Diameter of induration Conclusion 5-10 mm suspicious > 10 mm positive > 15 mm strongly positive However this test is of limited diagnostic value locally because of the high incidence of exposure to mycobacteria and early vaccination of BCG. A negative result nevertheless excludes active tuberculosis, except the miliary form and diseases in immunocompromised patients. 4.3. Screening for Extracutaneous Tuberculosis The presence of tuberculosis elsewhere provides supportive evidence in the diagnosis of cutaneous tuberculosis, especially in the tuberculids. Chest Xray is mandatory. Other tests such as sputum, pus or early morning urine for acid-fast bacilli, lymph node biopsy or bronchoscopy should be done if indicated. 5. TREATMENT Combination drugs therapy should be given to all true cutaneous tuberculosis such as lupus vulgaris, tuberculosis verrucosa cutis and scrofuloderma. Controversy exists about whether tuberculids should receive multiple drugs treatment. Papulonecrotic tuberculide is commonly treated with combination therapy, whereas erythema induratum and lichen scrofulosorum can be treated by suppressive therapy with isoniazid alone. The regimens of antituberculous therapy used in Hong Kong are summarized as follows:
5.1. Standard Drug Regimens (totally 6 months) 1) Initial phase (3-4 drugs daily for 2 months) Adult Child a) Isoniazid 300 mg 5-8 mg/kg + b) Rifampicin > 50 kg 600 mg 10-12 mg/kg < 50 kg 450 mg + c) Pyrazinamide > 50 kg 2.0 gm 20-35 mg/kg < 50 kg 1.5 gm or Ethambutol < 60 days 25 mg/kg Not recommend > 60 days 15 mg/kg or Streptomycin 3/4 gm IMI 15-20 mg/kg 2) Continuation phase (2 drugs daily for 4 months) Isoniazid + Rifampicin (same dosage) 5.2. Intermittent Regimen (totally 6 months) 1) Initial phase (3-4 drugs thrice/week for 2 months) Adult Child a) Isoniazid 600-800 mg 15 mg/kg + b) Rifampicin 600 mg 15 mg/kg + c) Pyrazinamide > 50 kg 2.5 gm 20-35 mg/kg < 50 kg 2.0 gm or Ethambutol 30 mg/kg Not recommend or Streptomycin 1 gm IMI 15-20 mg/kg 2) Continuation Phase (2 drugs thrice/week for 4 months) Isoniazid + Rifampicin (same dosage) All patients who have been put on antituberculous therapy should be closely monitored. The biochemical parameters like liver function test, renal function test and complete blood picture should be checked. Liver function test is mandatory and should be monitored at regular interval, as a lot of these drugs have hepatotoxic side-effects. In elderly patient or patient with renal impairment, the dosage of streptomycin should be reduced. Almost all
the anti-tuberculous drugs may cause drug eruptions. Some of these reactions may be serious, such as erythroderma and Stevens-Johnson syndrome. Elderly patient or alcoholic receiving isoniazid should have prophylactic treatment with pyridoxine. Patient who is receiving ethambutol should have regular ophthalmological check up. 5.3. Suppressive Therapy This is used to treat tuberculids such as erythema induratum and lichen scrofulosorum. In the past, it had been used as prophylactic treatment in patient who has been receiving systemic steroid or immunosuppressive drugs for other chronic cutaneous diseases. However, it is now seldomly given for prophylaxis. Isoniazid 300 mg daily for 9 months to 1 year Pyridoxine 10 mg daily as prophylactic measure or 100 mg daily as therapeutic measure against peripheral neuropathy 5.4. Treatment for M Marinum Infection Medical: 1) Cotrimoxazole tab 2 bd x 8-16 weeks 2) Minocycline 100 mg bd x 8-16 weeks 3) Rifampicin + Ethambutol Surgical: 1) Electrodessication 2) Cryotherapy 3) Surgical excision PRACTICAL GUIDELINES FOR PHOTOTHERAPY Dr. L.Y. CHONG CHAPTER 18 Phototherapy is now a well established treatment modality in dermatology. Its application in cutaneous diseases has been much broadened in recent years, though the main use is still in psoriasis. The exact mechanism of action of ultraviolet light on various cutaneous diseases is unknown, but probably through immunosuppressive effect or direct phototoxic effect. In Social Hygiene Service (dermatology) of Hong Kong, it has been used for more than one decade. Although phototherapy is relatively safe if used properly, there is not without risks. Some essential basic knowledge in phototherapy is important before one proceeds to use this treatment modality. 1. ESSENTIAL INFORMATION FOR PHOTOTHERAPY Wavelength of UVA : 320-400 nm; UVB: 290-320 nm Dosimetry
Energy (joule) = Power (watt) x exposure time (second) Fluence (J/cm2 = irradiance (W/cm2) x exposure time (sec) Exposure Time (min) = Dosage / 0.06 x Irradiance (J/cm2) (mW/cm2) Variation of irradiance Irradiance (power density) varies directly with power source and inversely with surface area (therefore inversely with the square of distance from the power source) I1 x D12= I2 x D22 (I = irradiance; D = distance) D12 / T1 = D22 / T2 (T = exposure time) Grading of erythema E0 No erythema E1 Minimally perceptible erythema (faint pink) E2 Marked erythema (red) E3 Fiery red erythema with oedema E4 Fiery red erythema with oedema and blistering NB In pigmented patient, sometimes erythema and oedema may not be seen. Instead of these, patient may complain of hotness and tightness of skin. Erythema is a limiting factor in phototherapy - E1 should not be exceeded. The onset of UVA-induced erythema has a delayed onset of 48 hours after exposure. MPD (Minimal phototoxic dose) = The dose of PUVA required to produce a E1 reaction 48 hours after exposure. MED (Minimal erythemogenic dose) = The dose of UVB required to produce a E1 reaction 24 hours after exposure. Skin types I Always burn, never tan II Always burn, but sometimes tan III Sometimes burn, but always tan IV Never burn, always tan V Moderately pigmented people (Chinese, Indian) VI Black people (West Indies, Africans) 2. PUVA (Psoralen-ultraviolet A) 2.1. Indications 1) Psoriasis PUVA is used mainly in plaque type psoriasis. It is relatively contraindicated for unstable, generalized pustular and erythrodermic psoriasis. Special cautions should be exercised if PUVA is used in these situations as it may
further aggravate the disease. It is also difficult to monitor the dosage of the ultraviolet light in erythroderma. 2) Mycosis fungoides (CTCL) PUVA is a relatively safe and effective treatment in the patch stage and plaque stage of mycosis fungoides. 3) Vitiligo The response to PUVA in vitiligo is better for face than the limbs and trunk. However, in practice only a small proportion of patients has satisfactory response. 4) Others: Severe atopic dermatitis, pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica, prurigo nodularis, polymorphic light eruption, etc. 2.2. Contraindications PUVA is contraindicated or relatively contraindicated in the following conditions: 1) Pregnancy 2) Children < 12-year old 3) Photosensitivity 4) Severe cardiac, hepatic or renal diseases 5) History of skin cancers 6) Aphakia or cataracts 7) Immunosuppressed patients (probably) 2.3. Factors for Consideration in Psoriasis Age & sex Severity (>30% involvement - arbitrary) Previous treatment for psoriasis Concomitant medical illness Social & economic factors 2.4. Before Starting PUVA Consider indications & contraindications Thoroughly inform the patient about the nature of therapy and give the instruction sheet of PUVA to patient Written consent Blood screening if indicated (LFT, RFT, ANF) Body weight 2.5. Initiation of Treatment Starting dose of psoralen should be calculated according to the body weight. (0.6 mg/kg body weight)
Body Weight (Kg) <50 50-65 65-80 80-90 >90
Meladinine (Methoxsalen) (10 mg/tablet) 20 mg 30 mg 40 mg 50 mg 60 mg
(Take medication 2 hours before treatment together with food) Starting dose of UVA is given according to either skin type or phototesting. Skin Type I II III IV V VI Dosage of UVA (J/cm) 0.5 1.0 1.5 2.0 2.5 3.0
(Phototesting: determine the Minimal phototoxic dose and use 80% of MPD as the starting dose) Frequency of therapy: twice per week during clearing phase Increment of dosage at each subsequent visit: Initial: 0.5-1.0 J/cm2 (depends on skin type and starting dose) If no response after 10 treatments: 1.0-1.5 J/cm2 If still no response after 15 treatments: Increase dosage of methoxsalen Defaulter a) Miss one regularly scheduled treatment: dosage should not be increased, use the last dosage b) Miss more than one session: dosage should be reduced by 0.5 J/cm2per session missed (Minimum: starting dose) c) Default for more than two sessions: see doctor before restart the treatment Reaction (inform doctor) a) If trace of erythema occurs, dosage should not be increased but the patient may be treated with previous exposure time. b) If more than trace of erythema occur, or patient complains of hotness and tightness, the areas affected should not be retreated until these subside. When more than 95% clearance (flexible), the last dosage should be maintained, and a maintenance schedule should begin.
If no significant response or still not ready for maintenance treatment after 30 treatments, patient may be designated as treatment failure. 2.6. Frequency of Assessment by Doctor The patient should be seen by doctor two weeks after initiation of treatment, and then every four weeks during active phase. However, patient should be seen by doctor as soon as possible if any reaction occurs. Doctor should specify the starting dosage, subsequent increment and frequency of therapy on the treatment sheet. 2.7. Maintenance Therapy 1) The last clearance dose is maintained at once-weekly interval. 2) If clearing persists for 4 weeks, reduce the frequency to one exposure every 2 weeks (most patients need this frequency for maintenance). 3) If clearing persists for another 8 weeks, reduce to one exposure every month. If it persist for another 4 months, the treatment may be stopped. 4) If there is relapse during maintenance, treatment is increased to twice a week and UVA dose is increased by 0.5-1.5 J/cm2 for each successive treatment. Maintenance is then given at a higher frequency than the one which did not work. 5) During maintenance therapy, if erythema occurs as a result of decreasing pigmentation, the UVA dose should be decreased by 0.25 J/cm2 per treatment until erythema is no longer present. 2.8. Sites for Special Consideration 1) Extremities, especially legs, do not respond as well as the other areas. Additional exposure time up to one fourth of the total may be given with shielding of the other sites. 2) Intertriginous areas, scrotum, perineum, pendulous breasts and abdomen are more sensitive to UV light. If necessary, they may be shielded with folded cloth for one third of the total exposure time until tanning occurs. 3) Hairy scalp does not benefit from PUVA therapy. 4) Face may be shielded with cloth after the first few exposures if it is not affected by psoriasis. 5) Normal skin is more sensitive to UVA than psoriatic skin. 2.9. Precautions that must be taken by Nursing Staff 1) Before treatment a) Ask whether the patient has taken psoralen b) Check whether the patient has erythema c) Check the correct exposure time 2) During treatment a) Make sure that the patient is wearing the protective goggles b) Make sure that accurate exposure time is given
c) Withhold treatment if patient complains of discomfort 3) After treatment a) Remind the patient to wear the sunglasses (Polarised grey - or greentinted) for 8 hours after therapy (both indoor and outdoor), and shield from direct sunlight with sunscreen, suitable clothing, hat or umbrella. b) Check the next follow-up time c) Calculate the cumulative dose given 4) Maintenance of the PUVA machine Check the irradiance of the machine with the UVA photometer every month. Inform the technician to change the fluorescent tubes at the recommended interval (For Waldmann UV3001 & 8001K PUVA machine: after 1500-2000 hours; Daavlin spectra 305/350: 850 hours) or when the irradiance drops. (new lamps of 3001: 10.5 mW/cm2 at a distance of 21 cm; change lamps if output falls below 6 mW/cm2 or when warning message appears in control panel of Daavlin spectra 305/350) 2.10. Complications 1) Excessive erythema If more than E1 occurs, PUVA therapy should be withheld. Patient should be treated as having burns. 2) Pruritus Bland emollients and antihistamines should be given. If the pruritus is severe and persistent, withhold the phototherapy. 3) Nausea The following measures may help to minimize the nausea due to taking of methoxsalen: a) Always take methoxsalen with some food b) Mild nausea: take half the total dose of methoxsalen two and half hours and the remainder two hours before phototherapy c) Severe nausea: take antiemetic half hour prior to ingestion of methoxsalen or decrease the dose of methoxsalen by 10 mg 4) Pigmentation Reassure the patient that it will fade as exposures become less frequent after the clearing phase. 5) Cataract Annual ophthalmological examination is preferred. 6) Premature ageing and potential carcinogenesis in skin Cautions should be taken about these potential risks when the cumulative dose of the UVA over 1500 J/cm2 3. PUVA IN VITILIGO
The treatment is essentially the same as that in psoriasis. Start the dose of UVA as that in type I skin with 0.5 J/cm2, with each increment of 0.25 J/cm2 and a frequency of two to three treatments per week. Try PUVA for 3 months. If there is response, may continue up to one year. However if there is no response, stop it. Patient should be fully informed about the limitation and risk of this treatment modality to avoid overexpectation or false hope. In Social Hygiene Service, because of the shortage of manpower and PUVA machine, a modified regimen using Wood's lamp and topical psoralen has been used for years in vitiligo clinic. However, it is difficult to standardize the exposure time as different models of UV lamps are used and these lamps wear with time. It therefore depends much on the experience of individual therapist with that particular lamp. 3.1. Machine and Specifications Model B-100A Blak-ray Ultraviolet Lamp: Peak wavelength: 366 nm Minimal intensity: 1.020 mW/cm2 at 15 inches Radiation (measured with UVA photometer): at 6 inches is approx 6 mw/cm2 3.2. Patient Selection Those patients with vitiligo on the face of relatively short duration may be offered a trial. The eyelids should be avoided from irradiation. Those with vitiligo of long duration and with involvement on trunk and limbs usually do not respond to the treatment. 3.3. Before starting Topical PUVA for vitiligo 1) Explanation about the procedures and possible complications 2) Written consent 3.4. Dosimetry 1) Start with 30 seconds at a distance of 6 inches 2) Frequency: twice per week 3) Increase 10 seconds each session until E1 occurs 4) Try three months' duration. Continue if there is response; stop if there is no response. 3.5. Procedures 1) Apply topical meladinine 30 minutes before radiation. Apply a thin layer to the site of vitiligo only. Avoid the junction between the normal skin and vitiligo. Avoid application to eyelids. Never dispense the topical meladinine to patient for home application. 2) Warm up the machine for 5 minutes before use. 3) Fix the required distance. 4) Treat with the required exposure time.
5) Wash away the topical meladinine after treatment. 6) Leave the lamp on until all patients are treated, do not shift on and off frequently. 7) If the lamp is shifted off, wait for 5 minutes or more before restart. 3.6. Defaulter 1) Miss one regularly scheduled treatment: dosage should not be increased, use the last dosage 2) Miss more than one session: dosage should be reduced by 10 seconds per session missed (Minimum: starting dose) 3) Default for more than two sessions: see doctor before restart the treatment 3.7. Precautions that must be taken by Nursing Staff 1) Before treatment a) check whether the patient has erythema b) check the correct exposure time 2) During treatment a) make sure that the patient is wearing the protective goggles b) make sure that accurate exposure time is given 3) After treatment a) Advise the patient to avoid sunlight for 2 days Use broad-spectrum sunscreen (Coppertone 45, Sunsense, etc.) both indoor and outdoor b) Check the next follow-up time 4) Maintenance of the machine Check the irradiance of the machine with the UVA photometer every month. Inform the technician to change the bulb at the recommended interval or when the irradiance drops (minimal: 1.020 mW/cm2 at 15 inches distance) 3.8. Frequency of Assessment by Doctor (same as PUVA) 3.9. Complications of Topical PUVA 1) Erythema Local reaction with intense erythema with pain and blistering may occur (either due to over-exposure or photoallergic contact dermatitis). For large area of vitiligo on face, it is better to try the treatment on a small area first. 2) Photosensitivity Photosensitivity of the skin can persist for 48-72 hours after application of topical psoralen. 3) Hyperpigmentation Marked hyperpigmentation may occur at the site of treatment. 4. UVB PHOTOTHERAPY
4.1. Indications 1) Psoriasis 2) PLEVA, Pityriasis lichenoides chronica, Pityriasis rosea 3) Uraemic pruritus 4.2. Regimens for Psoriasis (Chronic Plaque Type) 1) Goeckerman regimen (Tar + UVB) 2) Ingram regimen (Dithranol + UVB) 3) UVB alone 4.3. Goeckerman Regimen - Mainly for inpatient treatment - Average duration of treatment: 28 days - Monitor parameters: thickness, scaling and erythema Procedures: 1) Apply 3-10% Coal tar paste topically to the plaques (or whole body) bd. 2) Daily LPC (Liquor Pica Carbonis) bath. The coal tar paste should be washed away with liquid paraffin one hour before the UVB irradiation. 3) After the UVB therapy in Physiotherapy Department (QMH, QEH), reapply the coal tar. Side-effects of coal tar: 1) Messiness and staining of the clothes 2) Irritation of uninvolved skin 3) Folliculitis especially over flexures 4.4. Ingram Regimen - Mainly for inpatient treatment (Not used in Hong Kong now because the dithranol in lassar paste is no longer available) - Average duration of treatment: 21 days Procedures: 1) Apply dithranol in Lassar paste (start with lowest concentration available: 0.25%) once daily to the plaques ONLY (Avoid the normal skin). The applied paste is then powdered (e.g. using Talcum powder) to harden the surface and prevent spreading to uninvolved skin. The treated areas are then enveloped in Tubegauze and left for 24 hours. Increase the concentration of dithranol if tolerated. 2) Daily LPC bath. The paste is removed with liquid paraffin one hour before the UVB irradiation. 3) After the UVB therapy in Physiotherapy Department, reapply the dithranol again. Side-effects of dithranol: 1) Brown staining of the skin (reversible) 2) Burning, which can be severe
3) Irritation (avoid applying to flexures, face and eyes) 4.5. UVB Therapy 1) UVB machine: fluorescent bulbs with peak emission around 300 nm are commonly used 2) Dosimetry Unlike the relatively standardised regimen in PUVA, the empirical starting dose and subsequent increment of UVB usually has to depend on the recommendations of the manufacturers of different UVB machine, and on the individual therapist's experience, taking account of the skin type of the patient. Another more precise approach is to determine the patient's sensitivity by the phototesting. The aim is to achieve an erythema of E1. During the course of therapy, patient will develop various degree of tanning, which may require an increase of exposure dosage. Starting dosage: 80% of the MED as determined by the phototesting or the starting dose as recommended by the manufacturer (e.g. in Daavlin spectra 726-SP: start with 15 seconds) Subsequent increment: 1/8 (12.5%) of the last dosage 3) Frequency Inpatient: 5 times per week (except Saturday & Sunday) Outpatient: 3 times per week 4) Distance Depend on different machine used. If the distance is changed during the treatment, the correct exposure time should be calculated accordingly. (Waldmann UV100 and Daavlin spectra 726-SP: about 20 cm from the lamps) 5) Maintenance UVB phototherapy is mainly used as clearance schedules on intermittent basis. Effect from long term maintenance is unclear, if being given, most psoriatic patients require one to three exposures each week to maintain a clear state. 4.6. Complications (similar to those of PUVA) 4.7. Machines and Specifications Clinic Model YMT Dermatology Clinic Waldmann UV100 irradiance: approx. 1 mW/cm2 at 20 cm distance
Daavlin spectra 726-SP irradiance: approx. 3 mW/cm2 at 20 cm distance YFS Dermatology Clinic Hohensonne 3030 4.8. Before Starting UVB Phototherapy 1) Explanation about the procedures and possible complications 2) Written consent 3) Phototesting 4.9. Phototesting 1) A template with holes of different size (approx 2 x 2 cm2 is covered to the back 2) Irradiate with different doses of UVB at a fixed distance 3) Read the result 24 hours later and determine the MED 4.10. Dosimetry 1) Start with 80% of MED or as recommended by the manufacturer (usually 15-30 seconds) (if phototesting has not been done) at a fixed distance 2) Frequency: three times per week 3) Increase 1/8 (12.5%) of previous dosage each session, stop the increment if more than faint erythema (E1) occur. 4.11. Defaulter 1) Miss one regularly scheduled treatment: dosage should not be increased, use the last dosage 2) Miss more than one session: dosage should be reduced by 1/8 (12.5%) per session missed. (Minimum: starting dose) 3) Default for more than two sessions: see doctor before restart the treatment 4.12. Precautions that must be taken by Nursing Staff 1) Before treatment a) Check whether the patient has erythema b) Check the correct exposure time 2) During treatment Make sure that the patient is wearing the protective goggles all the time. Patient must be warned beforehand that the goggles should not be taken off at any time during the treatment. 3) After treatment Check the next follow-up time 4) Maintenance of the machine Inform the technician to change the bulb at the recommended interval (Waldmann UV100: should be renewed after approx. 1000 hours; Daavlin spectra 726-SP: 450 hours). 4.13. Frequency of Assessment by Doctor
(same as PUVA) 5. PHOTO-PATCH TEST Photo-patch test is performed for those with photo-allergic contact dermatitis. Most reaction can be elicited by irradiating with UVA. 5.1. Procedures 1) Patch two symmetrical strips of photoallergans on the back of patient: one as control and the other as test strip. 2) Read the result as usual 48 hours later to see whether there is contact dermatitis and then remove the strips. 3) Irradiate one side with 5-10 J/cm2 UVA (PUVA machine or Wood's lamp). The control side must be covered during the irradiation. If the Wood's lamp is used, make sure to measure the irradiance with the photometer and calculate the correct time of irradiation. 4) Read the result again after another 48 hours. HEALTH NURSING IN SKIN CLINICS Ms. M. WONG, Mr. W. LEUNG, Mr. E. WAN & Subordinates CHAPTER 19 1. INTRODUCTION TO NURSING PRACTICE IN SKIN CLINICS Dermatology Nursing is the specialty of compassion and caring for patients together with scientific knowledge of dermatology illness from which patients suffer. A nurse in Skin Clinic of Social Hygiene Service is entitled to be called as a good nurse only if he/she gets enough experience, patience, kindness and effectiveness. To be effective, nurses and doctors must work as a team which is a long and good tradition in the nursing profession of Social Hygiene Service. The essential elements for nursing activities in Social Hygiene Clinics must be maintained here with emphasis on providing our clients with clear and concise explanations and instructions before and after each nursing procedure, and sound advice on the proper use of the prescribed medications. A wrong concept of skin diseases as being mostly contagious must be clarified. Education on the general care of one's skin can be given to our patients and the public by means of individual interviews or group talks. Skin conditions which are generalized, weeping, acute or involving the exposed areas, especially the face, is always very traumatizing psychologically and usually causes the patient to panic. This, however, can be easily overcome by the presentation of empathic, friendly and high knowledgeable attitude of the health personnel who handles the case. 2. INVESTIGATIVE PROCEDURES 2.1. Venepuncture
This issue has been discussed in Section 2A of this chapter but the following points are worth mentioning: 1) As skin diseases often co-exist with internal medical conditions, a variety of serological tests may be needed. Nurses should ensure that the correct specimen bottles and laboratory request forms are used for the tests prescribed. 2) The amount of blood, request form and specimen bottle required may differ from individual investigation and nurses must comply with these different requests to prevent rejection of any incompatible specimen from diverse institutions. 2.2. Skin Patch-Test 2.2.1. Indication To find out patient's allergen(s). 2.2.2. Application of the Test Substances Mark identification on the top of each tape to show the order of the test agents through out the testing procedure. Place the tape on the desk with the chambers facing up and remove the protective paper. Semi-solid test agents are applied directly into the chamber, filling slightly more than a half of the chamber volume. For liquid test agents, place a filter paper disc in the chamber. Moisten the disc thoroughly without surplus and place the test tape onto the skin within a few minutes (dry paper disc may result in weak or false negative reactions). Patient should stand or sit in a relaxed 'normal' position. The tests are applied to healthy skin of the back, (sometimes on the lateral aspects of the upper arms), which is free of ointment and excessive sebum (if present, remove by non-irritant lotion before the application). Apply the tape starting with the lower part and press the chamber from below upwards to let air escape. Press each chamber gently with the finger to ensure an even distribution of the test agents. A blue marker may be used to locate the test sites. Additional non-irritant tape may be applied to take margin for better adherence.
Left Right Patient's Back 2.2.3. Instruction to Patients Skin Patch Test is so designed to find out the patient's allergen(s). The patient is required to come for follow-up on the third and fifth day after the first visit for Skin Patch Test. Rash or itchiness at a particular test site denotes he is allergic to that kind of substance. Do not wet or remove the plastic adhesives until removal by nursing staff or doctor on the third day. Avoid heavy exercise to prevent sweating. Avoid rubbing and scratching the back. Protect his back from direct sunlight. Add ordinary plaster-adhesive to the original ones if it comes off accidentally. Report this to nursing Staff or doctor on the next visit. Come back for follow-up if any reaction occurs on his skin within three weeks of the Test. 2.2.4. Record and Report Patient's details are written down on a "Patch Test Form" and attached to the case record file. He has to come back on the third and fifth day for reading of the test. When the patient comes back for follow-up on the third day, the tape is removed and the Test is read after 30 minutes by nursing staff or attending dermatologist. 2.3. Skin Scraping and Nail Clipping The diagnosis of a superficial fungal infection is made by the observation of fungal elements in infected keratin. This can be achieved by direct inspection of fungal elements by means of bright field microscopy or mycology culture. 2.3.1. Explanation to Patient
Explain the nature and procedures of the investigation to the patient, emphasizing that the skin will be scraped and not cut. No pain will be encountered during the whole process. 2.3.2. Procedure Clean the desired area thoroughly and remove all local application at the scraping site (ether solvent is best). A blunt scalpel is used for skin scraping. Sterilization of the scalpel by heat before and after each procedure is essential. Cool down the scalpel before scraping (avoid burning the patient). Adequate specimen should be obtained from the expanding edges of a lesion as these are the sites of most active infection. Separate scalpels should be used to obtain specimens from different sites for an individual patient to avoid misinterpretation. For nail clippings, nail fragments should be taken from any discoloured, dystrophic or brittle parts of the suspected nail. These should be cut as far back as possible from the free edge of nail and include its full thickness. For hair, specimen from the scalp is best obtained by scraping with a blunt scalpel. The sample should include hair stubs, the contents of plugged follicles and skin scales. Hair may also be plucked from the scalp with epilation forceps. 2.3.3. Microscopy and Reporting Scrape the skin/nail fragment onto the middle part of a glass slide, then cover up with a cover slip. Add a few drops of 30% potassium hydroxide (KOH) to the edges of the cover slip (let KOH oozes towards the prepared skin fragment slowly in order to prevent the cellular pattern being denatured). In case of pityriasis versicolor screening, add a few drops of Parker's stain after instillation of KOH. Warm up the slide on top of a sterilizer till the fragment (Skin) is dissolved. Hairs should be handled with particular care and allowed to soften without direct heat so that the arrangement of spores will not be destroyed. Inspect under bright field microscope. (low power 10X for screening and 40X for confirmation.) Fill in patient's particulars, the site of inspection and result in the microscopic record book as well as the case file record. When examining specimens, it is important to ensure that the tissues obtained have been softened adequately, so a single layer of cells is lined side by side for inspection. For better microscopic viewing, the intensity of
light passing through the aperture of the microscope should not be too strong. It is also necessary to adjust the focus while scanning the slide in search for suspected organisms. The fungal elements will appear and fluoresce as ¡¥green¡¦ branches among the cell layer if present. Dermatophyte hyphae are regular in width, have septa and can show branching. They may be divided into arthrospores. If hairs are infected, the size and arrangement of spores, together with the ability to fluoresce under a Wood's lamp will help in aiding identification of the dermatophyte species involved. Slide may show ectothrix invasion of hair by fungi, or favus hair showing hyphae and air spaces infected by fungi. Parker's stain (equal parts of 30% KOH & Parker's blue-black ink) is particularly useful in demonstrating the fungus (Malassezia furfur) in scales from Pityriasis Versicolor as the organism takes up this stain immediately. Thick-walled yeast 3-8 m in diameter and short angular hyphae can be revealed in the bright field microscopic examination of infected skin scales in Parker's stain. In nail infection (onychomycosis), thick walled, spores and scanty hyphae (spores may be in chain and Parker's stained) can be demonstrated. Confirm the diagnosis with experienced staff or doctor if necessary. Discard the slide into sharp box for disposal. Slides useful for teaching and demonstration purposes are sealed with wax for storage. Cleanse the microscope (the stage and objectives) with xylene after use as KOH is corrosive. 2.3.4. Fungal Culture Put sufficient quantity of skin/nail fragment in the paper wrapper. Write down patient's particulars, site of inspection and etc. onto the paper wrapper. (seal up properly to avoid leakage.) Affix the specimen to the laboratory form and send to the corresponding PI. 3. MINOR OPERATIONS Many skin conditions can be cured by means of surgical removal whereas others may need biopsies for confirmation of diagnosis. Nurses have been delegated to carry out most of these minor surgeries in our service. They are trained on the job for months and are allowed to stand on their own only when the doctor or Nursing Officer in-charge is satisfied with their performance. Formally speaking, experienced skin unit nurses are delegated to perform certain minor surgeries under the supervision of dermatologist. Clear explanation to the patients before each procedure to allay their fear and anxiety. Concise advice to them post-operatively to ensure genuine wound healing is basic requirements in the nursing of these clients. A large
variety of minor operations are performed in our clinics but only the most commonly encountered are discussed here. 3.1. Cauterization and Curettage 3.1.1. Electrocautery This is the employment of a small voltage/current, through a disposable hyfrecator Tip to heat an element with high resistance. It is used to burn the tissue or coagulate small vessels. Examples are common skin Warts and Pyogenic Granuloma. 3.1.2. Curettage This is the use of a 'curette' to remove small, well-defined tumours on sites with a firm base and minimal mobile tissues. Examples are Milia and Molluscum Contagiosum. 3.1.3. Procedures Explanation, consent, positioning and sterile technique should all be observed. Clean and anaesthetize the lesion. (Lidocaton 2%). To reduce the risk of drug allergy, 2 c.c. of the anaesthetizer per site of lesion is the maximum dose used. Identify the edges of the lesion and cauterize the upper most layer (Do not press or puncture the lesion with the disposable hyfrecator Tip while burning as the Tips or extreme heat may damage the under-lying normal structures.) Trim the burnt unhealthy tissues with a pair of scissors and scrape off the residual burnt necrotic tissues with a curette. Repeat steps 3) and 4) to an appropriate depth (the base) until fleshy, normal tissues is reached. Trim and scrape the rim as well. Vigorous use of the cautery may lead to undesirable damage of the underlying structures and unnecessary scarring. For common warts, Unipolar 30 setting of the hyfrecator is recommended. 3.1.4. Advice to Patients Frequent changes of dry flexible fabric dressing strips (e.g. band-aids) are required to absorb exudate. Change dressings whenever it is soaked through. It may take 1-3 weeks for a crust to form. Care must be taken to protect the wound trauma and wet. It probably heals in 3-6 weeks. Bleeding may occur within the first 3 days. Direct pressure onto the site for 5-10 minutes will stop the bleeding. The rate of healing depends on the amount of tissue destruction and the location of the lesion.
The risk of infection is low, but patient should complete all the antibiotics if prescribed by the doctor. Return to the clinic if problem arises. 3.2. Management of Molluscum Contagiosum 3.2.1. Definition It is caused by a DNA poxvirus that infects epidermal cells. Clinically the lesions appear as smooth, doom-shaped papules which are often umbilicated. 3.2.2. Incidence It is a common childhood disease. It may spread among family members but is uncommon. (i.e. may transmit by close body contact.) 3.2.3. Treatment Methods 1) Curettage and Iodine Application - explain the procedure of treatment and nature of the disease to client and their parents or guardians so to obtain their co-operation. - It is done without anaesthesia. - A curette is used to scrape off the molluscum. Ensure the central core composed of molluscum bodies is scraped off. - Apply a tinge of iodine to the wounds with a dressed applicator for disinfection. - Apply pressure onto the wounds for haemostasis and put on dressings if necessary. 2) Application of TCAA (Trichloroacetic Acid 33%) - Explain the procedure and nature of TCAA to the patient and their parents or guardians to gain co-operation and allay any anxiety. - Well protect the vital organs, e.g. the eyes with gauze etc. - Apply vaseline to the surrounding healthy skin for protection. - Apply the TCAA with a dressed applicator to the lesions. 3.2.4. Advice to Patients Healing usually takes a few days. Keep the wounds dry for a day or two, change the dressings or band-aids if wet. Return to the clinic if problem arises. 3.3. Management of Skin Tags 3.3.1. Definition A skin tag is a benign fleshly tumour that is acquired in adult life. It usually appears as a pedunculated flesh-coloured growth. 3.3.2. History Most patient ignore skin tags and accept their presence as a sign of aging.
It is a benign condition and will not become malignant. Some patients request their removal because of irritation or cosmetic appearance. 3.3.3. Procedures Thorough explanation is given so as to gain full co-operation during treatment. It is done without anaesthesia except for very large skin tags where diathermy is indicated for haemostasis. The easiest means of removal is by quickly snipping them off with fine scissors (i.e. excise the root of the skin tag). The small bleeding can be arrested by low power diathermy or manual pressure. 3.3.4. Advice to Patients Healing usually takes a few days. Keep the wounds dry for a day or two. Change the band-aids (if any) if wet. Return to the clinic if problem arises. 3.4. Cryotherapy 3.4.1. Definition This is a deliberate destruction of diseased tissue by ¡¥Cryogen¡¦ - extreme COLD in a controlled manner, i.e. Liquid Nitrogen (-1960 C). -400 C is necessary to kill normal cells by freezing alone, but -250 C is probably adequate to destroy diseased tissue 3.4.2. Rationale A rapid rate of freezing may cause more tissue damage. A prolonged thaw may increase tissue damage. 3.4.3. Technique The cryojet gun is held close to the lesion. A steady spray of liquid nitrogen is directed at the centre of the lesion. The ice-front gradually extends to the edge of the lesion. Timing commences once solid ice is formed over the lesion. Freezing is continued for the required period, normally no greater than 30 seconds. The spray is adjusted to maintain an iceball of a constant size. The lesion is allowed to thaw slowly. If a second freeze is required, the lesion should be allowed to thaw completely before re-freezing. For a malignant tumour, a 5 mm rim of normal tissue should be included around the lesion. Note: Various brands of ¡¥Cryojet¡¦ apparatuses are available from different agencies. When using Cryojet gun to perform procedures, the performer must hold the instrument in an upright position. Once the Cryojet is tilt over
45 degrees, the liquid Nitrogen inside the gun will spill out suddenly and may cause undesirable accidents. 3.4.4. Recommended Freezing Times Lesions Approx. Freezing Time 1) Actinic keratosis 5-10 seconds 2) Seborrhoeic wart 10 seconds 3) Viral warts: Filiform 5 seconds Common 10 seconds Genital 5-10 seconds Plantar 15-30 seconds Periungual 10-15 seconds (beware of damaging the underlying nail matrix) 4) Acquired Pigmented Naevi 20 seconds 5) Superficial basal cell Carcinomata 30 seconds 6) All other malignant tumours Double 30 seconds freeze-thaw cycle 3.4.5. Advice to Patients A thorough medical history should be obtained prior to treatment so to minimize the risk of unwanted reactions. Any deviated abnormalities should be reported to doctors concerned for further evaluation. (e.g. a decrease in platelet count may denote a bleeding tendency after treatment.) During freezing and thawing, one may encounter a burning sensation Analgesics, e.g. Panadol/Dologesic may be taken, before spraying. Blisters may form soon after freezing and are occasionally haemorrhagic. A crust will usually form in 1-2 weeks and will peel off in 3-4 weeks. Dressing may be required to absorb exudate if the blisters rupture. The treated area may initially be erythematous, but this fades leaving a hypopigmented macule. Return to the clinic if tense blisters causing much discomfort are found after treatment. 4. PHOTOTHERAPIES Phototherapy alone or together with ingested Psoralen (Photochemotherapy) has been proven to be effective in the management of many difficult skin disorders. Nurses' role in this issue includes the input of detail information on the treatment regime and advice on the outcome, to the patients. Supervision during the whole course of therapy and patients' compliance with the regime must also be keenly observed. 4.1. PUVA 4.1.1. Pre-treatment Preparation
A clear verbal explanation on the nature of the therapy and the procedures in detail together with an instruction sheet on PUVA treatment must be given to the patient prior to commencement. Obtain written consent. Blood screening for LFT, RFT, ANF. Measure patient's body weight for doctor to assess the Meladinine dosage. Clinical photographs are taken for future assessment. Ensure the patient has taken Psoralen (Meladinine) 2 hours before phototherapy (Psoralen enhances absorption of solar irradiation). Wear ultraviolet-proof sunglasses, suitable clothing, hat or umbrella to protect exposed areas of the body after ingestion of Psoralen. This will prevent excessive exposure to sunlight especially in summer seasons. Observe patient's skin condition before and after each treatment for progress or changes especially any onset of erythema. Check the correct exposure time. 4.1.2. Procedures Tell the patient to remove all clothing and cover the genitalia. The face may be shielded with a towel if it is not affected. For female patients, cover the breasts if not involved. Ensure the patient is wearing the protective goggles. The patient is instructed to stand or lie at a designated distance away from the light source. To give accurate exposure time as prescribed. A nurse is assigned to observe the entire procedure in a special designed observation room through an observation window. Verbal communication during the process is essential as a reassurance to the client. Withhold treatment if patient complains of discomfort and inform the doctor immediately. The lower legs frequently take longer to respond to phototherapy and may need additional exposures. All other areas should be draped during the added treatment. Remind the patient not to move about during the treatment. 4.1.3. After Treatment and Advice Remind the patient to wear sunglasses (which should be prechecked to ensure UVA opaque) for 8 hours after therapy (both indoor and outdoor), and shield from direct sunlight with sunscreens, suitable clothing, hat or umbrella to avoid over absorption of solar irradiation. Apply sufficient emollient onto skin surface to minimize irritation because skin is usually dry after treatment.
Reassure that pigmentation that may occur will fade as exposures become less frequent after the clearing phase. Observe and report any pricking, painful or itching skin sensation occurrence immediately after treatment. Inform the doctor if erythema or discomfort arises. For female patients, advise contraception. If query of pregnancy, inform the doctor immediately to stop the treatment. Check and arrange the next appointment. Calculate the cumulative dose given. 4.1.4. Defaulters Miss one regularly scheduled treatment: dosage should not be increased, use the last dosage. Miss more than one session: dosage should be reduced by 0.5 J/cm per session missed (Minimum: starting dose). Defaulted for more than two sessions: see doctor again before restarting the treatment. 4.1.5. Maintenance of the Machine Check the irradiance of the machine with the photometer every month. Inform the technician to change the fluorescent tubes at the recommended interval or any deviations of intensity from normal range. 4.2. UVB 4.2.1. Pre-treatment Preparations Thoroughly inform the patient on the nature of the therapy. Give the instruction sheet on UVB treatment to him. Obtain written consent. Perform phototesting as stated by Doctor. Check whether the patient has erythema. Check the correct exposure time. 4.2.2. Phototesting A test kit consisting of panels and mittens is affixed to the body or limbs according to the site being chosen for the test. Irradiate with different doses of UVB (10, 20, 30, 40 seconds). (NB delivered dose of UVB will vary with different model.) Read the result 24 hours later and determine the minimal erythemogenic dose (MED). 4.2.3. Procedures Fix the required distance according to different models. Select the UV switch and reflector units. Set the required exposure time with timer switch.
Tell the patient to remove all clothing and cover the genitalia. The face may also be shielded if it is not affected. For female patients, cover the breasts if not involved. Ensure that the patient is wearing the protective goggles. Remind the patient not to move about during treatment. A nurse is assigned to observe the entire procedure in a special designed observation room through an observation window. Verbal communication during the process is essential as a reassurance to the client. After being switched off, the system must be allowed to cool down at least for the set period before restarted. The field size of irradiation should be considered (e.g. if the whole body is treated, the upper and lower parts have to be treated separately). 4.2.4. After Treatment and Advice Reassure the patient that it takes 2-3 months to notice the outcome of the treatment. Apply sufficient emollient onto skin surface to minimize irritation because skin is usually dry after treatment. Avoid direct sunlight and protect himself by sunscreen, clothing, hat and sunglasses. Inform the doctor if erythema or discomfort occurs. Check and arrange the next appointment. 4.2.5. Defaulters Miss one regularly scheduled treatment: dosage should not be increased, use the last dosage. Miss more than one session: dosage should be reduced by 1/8 (12.5%) per session missed. (Minimum: starting dose.) Defaulted for more than two sessions: see doctor again before restarting the treatment. 4.2.6. Maintenance of the Machine Check the irradiance of the machine with the photometer every month. Inform the technician to change the fluorescent tubes at the recommended interval or any deviation of intensity from normal range. 4.3. Topical PUVA for Vitiligo 4.3.1. Pre-treatment Preparations Explain on the procedure and possible complications. Obtain written consent. Check whether the patient has erythema. Check the correct exposure time. Put the date, dose and nurse's signature on the referral and return the referral to the patient before he leaves.
4.3.2. Procedures Thoroughly clean and assist patient to remove all dirt, make-up, sweat or other local applications on the sites to be irradiated. Advice on the untoward out-comes of such treatment, e.g. redness, blistering. A thin layer of Meladinine paint should be applied to the leukodermic patch or bald area by means of a dressed applicator. The paint should be applied at least 30 minutes before Ultraviolet illumination. Warm up the machine for 5 minutes before use. Refrain from applying paint to delicate areas, e.g. eyelid. Make sure no paint gets into the eyes. Both patient and nurse should put on goggles. Give the correct exposure. Wash off the topical Meladinine after treatment and application of sunscreen agent onto the sites is advisable. The treatment can be given twice weekly with an initial dose of 30 seconds at a distance of 15 cm. An increase of 10 seconds per subsequent treatment is recommended until E1 occurs. 4.3.3. Frequency of Assessment The doctor is responsible to prescribe the starting dosage, subsequent increment and frequency of therapy for each case. He will reassess the case two weeks after commencement of treatment, then every four week during active phase, but, patients should be seen by the doctor if any reaction occurs. 4.3.4. Advice to Patients Inform patient of the possible response and complication e.g. redness, blistering, rash and pain. Avoid exposure to sunlight especially on the day and the next of UV treatment. Advise on the use of sunscreens both indoor and outdoor. 4.3.5. Reactions and Defaulters If reaction is mild, maintain the dose of the last treatment. This also applies to those who has defaulted treatment once. If defaulted for more than one session, dosage should be reduced by 10 seconds per session missed. (Minimum: starting dose.) Defaulted for more than two sessions, or if reaction is severe, e.g. severe blistering, excoriation or burning sensation, withhold treatment and the patient should be reassessed by the doctor. 4.3.6. Maintenance of the Machine
Check the irradiance of the machine with the UV photometer every month. Inform the technician to change the bulb at the recommended interval or when the irradiance drops. 5. LASER THERAPY Laser Safety Officer (LSO): one of the nurses in the clinic will be appointed as LSO. His/her duty is to ensure all safety measures are followed in operating with a laser machine. 5.1. The information of Laser Therapy in our Skin Clinic is as follow: At present, there are two types of Laser systems being used in our Service. 1) The VisErase is a free-standing mobile unit which uses a copper vapour as lasing medium for treating a variety of vascular and benign pigmented cutaneous lesions. The copper vapour laser emits green (511 nm) and yellow (578 nm) Lights. 2) HGM Surgica K1 is another type of Laser unit which uses Krypton ion as a convenient source of light for treating cutaneous and vascular pigmented skin lesions. This Laser system emits lights of predominately two wavelengths: 520-530 (green) and 568 (yellow) nanometers. 5.2. Indications 1) Recommended Laser Treatment: Yellow light a) Capillary cavernous haemangioma b) Cherry angioma c) Hereditary haemorrhagic telangiectasia d) Kaposi's sarcoma e) Lymphangioma f) Port wine haemangioma g) Post rhinoplasty red nose h) Rosacea i) Spider telangiectasia j) Telangiectasias 2) Recommended Laser Treatment: Green light a) Naevus of Ota b) Freckle c) Keratosis (Actinic/Congenital/Seborrhoeic/Solar) d) Lentigo f) Neurofibroma g) Naevus h) Viral wart 5.3. Operation of Laser Machine 5.3.1. Manual Turn On of VisErase
Check that the AC power lamp is lit. Turn the key switch to start (fully clockwise). Wait 5 seconds - press the HIGH button - the button should flash. After 10 minutes check that Laser Emission Lamp is lit and that no malfunction is indicated. Laser emission should begin approximately 30-35 minutes after the HIGH button has been pressed and should stabilize after 40-50 minutes. 5.3.2. Manual Turn On of Surgica K1 Check that the main circuit breaker on the back of the unit must be in the ON position. Turn the key switch to the ON position. After approximately 45 seconds, the Laser system can now be switched either to the TREAT or STANDBY modes of operation by depressing the appropriate button on the front panel. When the laser is first turn on, it will go into the STANDBY mode automatically after warming up. One may change to the TREAT mode simply by depressing the green treat button. When in the TREAT mode, the treat button lights up and generates a red aiming beam. Pressing onto the foot switch will light up the Laser head which will then release laser energy to the delivery device. Note * Safety goggles must be worn by all personnel when the laser is in use. * Treatment should not be commenced until the Laser power has stabilized. 5.4. Preparation of Patient Record all the particulars: name, clinic no., laser therapy no., site of treatment and especially contact telephone no. on the treatment progress sheet. Obtain consent form after explaining the procedure and aftercare to the patient by the MO i/c. Take Clinical photo before treatment and every follow up. 5.5. Preparation for Laser Therapy Safety goggles must be worn by all personnel when the laser is used. Protect patient's eyes with safety goggles or eye shield. Provide local anaesthesia (2% Lignocaine without adrenaline) as prescribed. Sometimes a thick layer of EMLA cream (a kind of local anaesthetic agent) with an occlusive dressing is applied to the area to be treated 1 hour before therapy (this allows better absorption). For lesions near to the eyes, Novesin eyedrop is instilled if eye shields are to be used.
A technique for reducing thermal damage to surrounding tissues during laser surgery is to precool the surgical site prior to laser energy exposure if possible. Constant irrigation with saline solution will also carries excessive heat away from the surgical site. Mark the treatment time. Assist the doctor in certain procedures, e.g. light adjustment, vacuum suction of excessive smoke, installation of different lens pieces. A good functioning Smoke Evacuation system should be installed. It is especially useful to provide a germ free environment when performing operations with pathological conditions suspected to be of viral origin. Make sure all windows are shut. No reflection of light is allowed. The door should be locked while the laser is being used. Turn on the warning light whenever therapy is proceeding. 5.6. Manual Turn Off of Laser Machine After treatment for all patients, turn the key switch of VisErase to finish. The Laser will shut down but the cooling fan will continue to operate for about a further 15-30 minutes. The fan will automatically turn itself off at the end of this period. As for Surgica K1, wait 5 minutes for cool down and then turn off the machine. 5.7. Aftercare Following Laser Treatment Inform patient a sunburn like reaction with possible blistering with the first 24-48 hours is expected. A crust or scab may occur after 2-3 days. Advise the patient not to remove it and let it fall off itself. Keep the area clean and dry until the scab/crust falls off. Wash gently with soap and water and apply a thin layer of antibiotic ointment. Avoid direct sunlight or sun exposure to the treated area for 3-6 months. Use at least an SPF of 15 or greater sunscreen, or wear a hat or other protective clothing (preferably both). Reassure the patient that the treatment may take up to three months to adequately judge the true response of the skin condition to the laser treatment. Check and arrange next follow-up time. 5.8. Maintenance of Laser Machine Make sure the AC power lamp is always lit. Do not turn off the main switch for Laser. Do not move the laser while it is operating or within 30 minutes of turning it off. Make sure the castor brakes are locked. The laser unit should be protected from standing in pooled liquid.
Avoid liquid to enter the laser through apertures such as air vent holes. If liquid does enter, terminate use immediately, disconnect power and call for service. Do not place the fibreoptic fibre on the floor, avoid pressing across it with hard objects. Never press the utility mode when controlling the panel. 5.9. Precautions Never look directly at the Laser bean emerging from the aperture on the main assembly or from the fibre, handpiece or scanner if one is fitted. Never operate the laser unless all personnel in the area are wearing approved laser safety goggles. All laser personnel should consider the laser plume to be potentially hazardous, both in terms of particulate matter and infectivity. Operating staff should wear masks and latex surgical gloves. If the laser light is being used near a patient's eyes, additional eye protection must be provided for the patient, i.e. using the eyeshield and anaesthetic eye drops. Always lock the door of the room during treatment. Never look at the laser light reflected, diffused or scattered from reflective surfaces such as glass, mirrors, metal, glossy paint, polished floors, plastic mouldings, window frames or paper. Do not use the laser in the presence of flammable substances, e.g. ether. Never point the laser handpiece at any person except at the treated area. 6. ADVICE ON THE USE OF DRUGS Topical applications have often been mistakenly regarded as less dangerous than drugs ingested and patient tends to use them more frequently than prescribed by the doctor. This actually is extremely hazardous because many of the steroid preparations are of very high potency and may cause irreversible adverse effects if applied too often or on delicate areas such as the face. Other clients may self-treat their newly noticed skin problems with cream or ointment stocked up from previous consultations and result in worsening of the conditions. Therefore, nurses must educate clients on the proper use of all drugs prescribed, with emphasis on the above misconcepts to ensure that untoward effects would not occur. Numerous types of drugs are used in dermatology treatment but only a few topical preparations which require special attentions. They are listed as follows: 6.1. 25% Benzyl Benzoate Emulsion It is used for the treatment of Scabies.
Take a warm soapy bath in the evening. Dry the body thoroughly and use a brush to apply the medication thinly all over the body, sparing only the neck and head. Make sure that the application has included the hands (particularly between the fingers), the umbilical area, the groins, the genitalia (especially the glans for male with prepuce), the area between the buttocks, and the feet (particularly the toe webs). The patient should trim the fingernails and toenails short, this allows easy assess of the medication to the undersurface of the nails. Allow the medication to dry and put on the same old clothing. Re-apply the emulsion to hands every time after hand washing. Next morning, repeat the application without taking a bath, allow the emulsion to dry, no change of clothing required. In the evening, take a warm soapy bath to remove all the medication. Put on clean clothing afterwards. Old clothing and bedding should be treated by boiling for 5 minutes, hot ironing or wrap in plastic bags & put aside for a few weeks before reuse. Relatives or friends who are in close contact with the infected person should also be examined and treatment at the same time if necessary. A total of two applications of the emulsion is sufficient to kill all the mites but itching may persist for 1 to 2 weeks. Over application will only give rise to irritation and cause Contact Dermatitis. Successful treatment depends on the patient conscientiously following the instruction and advice. Return to the clinic if itchiness lasts for more than 2 weeks or in case of other skin eruptions. 6.2. 0.5% Malathion Lotion (Derbac Liquid) This is the drug of choice for the treatment of infestations by lice such as Pediculosis Capitis or Pediculosis Pubis. Treatment should be carried out for all infested personnel at the same time. 6.2.1. For Treating P. Capitis the hair should be cut very short for boys. No shampoo is required prior to treatment. The lotion is rubbed onto the scalp, (paying special attentions to partings, back of the neck, fringes and around the ears) at night, preferably half an hour before going to bed. Wrap the hair with a clean towel and leave it over night. In the next morning, use a dense-toothed comb to comb through the hair in order to remove all the remains of nits and lice. Followed by a thorough ordinary shampoo. Disinfestation of pillow cases, bedding and cosmetic articles should be carried out after procedures by boiling for 5 minutes or hot ironing. Articles that do not withstand heat can be immersed in 2% hypochlorite solution for 30 minutes which will yield the same result.
6.2.2. For treatment of P. Pubis The lotion is rubbed onto the body from umbilicus to mid-thigh, front and back with special attention to the hairy parts including the anal region. Put on old clothing when the lotion is dry. Followed by a bath the next morning so as to wash off all the lotion. Put on new clothing. The old clothing should be treated before reuse (the same procedure as for P. Capitis). Note: for both cases, if signs and symptoms persist for more than a week after treatment, seek for medical advice again. 6.3. 1% Potassium Permanganate Solution This is a commonly prescribed medication for skin problems and if used correctly, helps soothe a lot of conditions, especially the weeping ones. Method of dilution: - The stock lotion, when supplied by the pharmacy is in a 1% dilution and purplish-black in colour. - One portion of this stock lotion is added into 79 parts of water to give a diluted solution of 1 : 8,000 concentration. (colours light purple) - Adding 3 teaspoons of the stock lotion into a water-filled 1.25 litre COKE bottle will give the same dilution. Soak the affected skin in the solution for approximately 10 minutes twice daily. Rinse thoroughly and dry the affected area after soaking. Never use the solution in any higher concentration or more often than prescribed. CUTANEOUS DRUG ERUPTIONS Dr. L.Y. CHONG CHAPTER 23 Cutaneous drug eruptions may be defined as adverse cutaneous lesions as a consequence of administration of drugs. The exact incidence of cutaneous drug eruptions in Hong Kong is unknown. According to the statistics of Social Hygiene Service, drug eruptions account for 0.5% of all new skin cases seen in dermatological outpatient clinics of the Service in 1995. This figure does not include those seen in general outpatient clinics, private sector and hospitals. The true incidence is definitely much higher. The main difficulties of getting a true figure are due to lack of a central registry and loose labelling of drug reactions on the
patients. Adverse effects of drugs are often published in the literatures according to anecdotal reports or badly designed studies. The pathogenesis of drug eruptions may arise as a result of immunological or non-immunological reaction. Some of these reactions are predictable (dose-related) while some are unpredictable (idiosyncratic). Those with an immunological basis may due to different types of hypersensitivity reactions, for instance, allergic type of urticaria may be the result of Type I reaction (IgE-mediated) or Type III reaction (complement dependent immune-complex mediated). Nevertheless, the exact mechanisms of most drug eruptions, including fixed drug eruptions, are unknown. Clinically drug eruptions have a wide range of different morphological presentations. (Table 1) They can be generalized or fixed eruptions and their severity varies from minor to fatal skin reactions. Unfortunately, apart from fixed drug eruption, there is neither pathognomonic clinical feature nor diagnostic investigation in drug eruption. In practice, it is often difficult to identify the culprit with certainty, especially when the patient is taking multiple drugs simultaneously. Diagnosis is mainly based on clinical grounds in which the history plays the most essential part. In the history, the temporal relationship between the taking of drug and the onset of skin eruption is most important. Experience and statistical knowledge about the suspected drugs are also useful as certain drugs (for examples, ampicillin or cotrimoxazole) are more likely to cause drug eruptions, especially in certain diseases (for examples, AIDS or infectious mononucleosis). In the history, the following information should be carefully asked: A detail drug history including the names and dosage of the drugs taken (Drugs should include those prescribed by doctors and any herbal or homeopathic medicines) The temporal relationship between the intake of drugs and the onset of skin lesions (Allergic drug reactions usually develop within 1 to 2 weeks of initiation of treatment) Any previous history of drug allergy, or similar skin lesions after taking similar drugs Any improvement of skin lesions after the suspected drug is withdrawn (The skin eruption is unlikely to be drug-induced if it fails to improve after withdrawal or if it improves even without stopping the drug. However, sometimes it may takes weeks for drug eruption to resolve even when the drug is stopped.) Up to the present moment, there is still no reliable and practical investigation for confirmation of drug eruption. Rechallange test is dangerous and should not be carried out in usual circumstances. Perhaps the
only situations for rechallange test are those with fixed drug eruptions or those with life-threatening conditions in which that particular drug is essential. Skin test has little practical value as it may cause fatal systemic reaction and false positive reaction is common. Other tests such as radioallergosorbent tests (RAST) for drug-specific IgE antibody (penicillin, insulin), histamine release test, leucocyte and macrophage migration inhibition tests, lymphocyte toxicity assay, basophil degranulation test, passive haemagglutination test and lymphocyte transformation test are mainly for research purposes. In mild drug eruptions, withdrawal of the culprits together with symptomatic treatments will be adequate. For patient who is taking multiple drugs which are essential (for instance, antituberous drugs), all drugs should be temporarily withheld. After the skin lesions has subsided, each of these drugs can then be reintroduced one by one under strict observation, usually start with the drug which has lowest incidence of drug reaction. In severe drug eruptions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma or angioedema, reintroduction of the drug is dangerous and immoral. In these situations, other treatment alternatives should be seeked for. Cross-sensitivity between similar drugs should be borne in mind in choosing alternative medication. Desensitization therapy has little practical value. After recovery, it is essential to give the patient a warning card, labelling the offending drug in order to avoid future retaking of the drug. Table 1: Morphological Classification of Drug Eruptions Acanthosis nigricans-like eruption Corticosteroids, Hydantoin, Nicotinic Acid, Pills, Stilbestrol Acneiform eruption Anticonvulsant (phenytoin, phenobarbital, trimethadione), Antituberculous (isoniazid, ethionamide, refampicin), Azathioprine, Chloral hydrate, Corticosteroids, Corticotropin (ACTH), Cyanocobalamin, Cyclosporin, Halogens (bromides, chlorides, iodides, halothane), Haloperidol, Lithium, Pills, Psoralens, Quinine, Scopolamine Acral erythema/red palms Adriamycin (Doxorubicin), Cystosine arabinoside, 5-fluorouracil Acrodynia Mercury Alopecia
Allopurinol, Bromocriptine, Carbimazole, Chlorambucil, Chloramphenicol, Cholesterol lowering agents, Cimetadine, Colchicine, Coumarin, Cytotoxic drugs, Diazoxide, Ethionamide, Fluconazole, Gentamicin, Gold, Heavy metals, Heparin, Hydantoin, Levodopa, Methotrexate, Methyldopa, NSAID (indomethacin, piroxicam), Pills, Phenindione, Propanolol, Sodium valproate, Thiouracil, Vitamin A or Retinoids Anaphylactic Reaction Acetylsalicylic acid, ACTH, Aminopyrine, Meprobamate, Mercurial Diuretics, Para-aminosalicylic Acid, Penicillin, Pituitary Extract, Procaine, Succinylcholine, Tetracycline, Thiouracil Angiitis, Necrotizing Bishydroxycoumarin (Dicumarol) Angioedema Meprobamate, Penicillin, Stilbestrol, Sulfonamides Argyria Silver Salts Arteritis Cyclobarbital, Chlorpromazine, Iodides, Phenylbutazone, Phenytoin, Poison Ivy Extract, Sulfonamides, Thiouracil Black hairy tongue Tetracycline, Penicillin Bowen's Disease Arsenic, Fowler's Solution Bullous eruption Acetylsalicylic acid, Antipyrines, Arsenic, Barbiturates, Bromide, Chloral hydrate, Chlorpromazine, Coumarin, Dilantin, Glutethimide, Hydantoin derivatives, Ibuprofen, Imipramine, Iodide, Phenobarbital, Phenylbutazone, Promethazine, Methadone, Meprobamate, Nitrazepam, Sulfonamides Candidiasis Tetracyclines Chilblains-like erythema Coumarins, Phenindione, Sulindac Cyanosis Acetanilide Depigmentation Chloroquine Eczematous reactions (other than contact eczema) Aminophylline, Antibiotics, Antihistamine, B-blockers, Benzocaine, Bleomycin, Carbamazepine, Chloral Hydrate, Diphenhydramine, Disulfuram, Fluorouracil, Fucidin, Meprobamate, Methaminodiazepoxide,
Minoxidil, Neomycin, Nystatin, Phenothiazines, Procainamide, Procaine, Quinacrine, Quinidine, Resorcin, Streptomycin (cross-reaction with neomycin), Sulphonamide, Thiazide Edema Arsenic, Chlorpromazine, Penicillin, Phenytoin, Promethazine, Chloroquine Elastosis perforans serpiginosa Penicillamine Erythema/exanthem Allopurinol, Ampicillin, Antipyrines, Arsenic, Atropine, Aurothioglucose, Barbiturates, Carbamazepine, Chloral hydrate, Chlorpropamide, Codeine, Corticotropin, Gentamicin, Gold, Griseofulvin, INH, Interleukin-2, Meprobamate, Methaminodiazepoxide, Morphine, Nicotinic Acid, Nitrofurantoin, Opium, Penicillin, Phenothiazine, Phenylbutazone, Pilocarpine, Quinacrine, Quinidine, Quinine, Streptomycin, Sulphonamides, Sulphamethoxypyridazine, Thiazide, Thiamine Chloride, Tolbutamide 1) Maculopapular rash Allopurinol, Chloroquine, Meprobamate, Penicillin, Promethazine, Streptomycin, Sulfamethoxypyridazine 2) Morbilliform erythema Acetylsalicylic acid, Ampicillin, Barbiturates, Bromides, Chlorpromazine, Griseofulvin, Insulin, Meprobamate, Penicillin, Promethazine, Salicylates, Streptomycin 3) Scarlatiniform erythema Barbiturates, Mercury, Morphine, Opium, Penicillin, Phenobarbital, Pituitary Extract, Quinine, Salicylates, Streptomycin, Sulfonamides 4) Toxic erythema Drugs most commonly responsible (up to 5% of patients affected): Allopurinol, Carbamazepine, Cephalosporins, Gold, Nalidixic acid, Penicillins, Sulphonamides Other drugs commonly responsible (1-4% of patients affected): Isoniazid, Para-amino salicylic acid, Phenytoin, NSAIDs, Nitrofurantoin, Streptomycin Erythema multiforme (including Stevens-Johnson syndrome and toxic epidermal necrolysis) Acetylsalicylic acid, Allopurinol, Amidopyrine, Antihistaminics, Antipyrines, Barbiturates, Bromides, Carbamazepine, Chloral hydrate, Cimetadine, Corticotropin (ACTH), Furosemide, Griseofulvin, Hydantoins, Iodides, Mercury, NSAIDs (especially piroxicam), Para-aminosalicyclic Acid, Penicillins, Phenytoin, Phenolphthalein, Phenothiazine, Phenyl-
butazone, Procaine, Streptomycin, Sulfamethoxy-pyridazine, Sulphonamides, Tetracycline Erythema Nodosum Acetylsalicylic Acid, Bromides, Gold, Iodides, Penicillin, Phenacetin, Pills, 13-cis-retinoic acid, Salicylates, Sulfathiazole, Tetracycline Erythroderma (Exfoliative dermatitis) Allopurinol, Aminosalicylic Acid, Arsenicals, Aurothioglucose, Barbiturates, Bismuth, Captopril, Carbamazepine, Cefoxitin, Chlorpromazine, Chloroquine, Cimetadine, Dapsone, Diltiazem, Gold, Griseofulvin, Hydantoin, Iodides, Isoniazid, Lithium, Mercury, Nitrofurantoin, NSAID, Penicillin, Phenothiazines, Phenytoin, Quinidine, Quinacrine, Sodium Thiosulfate, Stilbestrol, Streptomycin, Sulphamethoxypyridazine, Sulphonamides, Sulphonylurea, Tetracycline, Thiouracil, Retinoid Erythromelalgia Bromocriptine, Nifedipine, Pergolide, Verapamil Fixed drug eruption Aminopyrine, Amphetamines, Antihistaminics, Antimony Compounds, Antipyrines, Arsenic, Barbiturates, Bismuth, Chlordiazepoxide, Chloral Hydrate, Chloroquine, Codeine, Dapsone, Gold, Diethylstilbestrol, Digitalis, Ephedrine, Ergot, Hydantoin, Hydralazine, Iodides, Meprobamate, Mercury, Metronidazole, Morphine, NSAIDs, Opium, Para-aminosalcylic acid, Paracetamol, Penicillin, Phenacetin, Phenolphthalein, Phenothiazine, Phenylbutazone, Potassium Chlorate, Quinacrine, Quinine, Reserpine, Salicylates, Streptomycin, Sulfonamides, Sulindac, Tetracyclines, Tetraiodofluorescein Gangrene Coumarin Gingival hyperplasia Cyclosporin, Nifedipine, Hydantoin Hair color changes Carbamate, Chloroquine, Chlorpromazine Henoch-shonlein purpura-like eruption Diltiazem, Frusemide Hirsutism/hypertrichosis Acetazolamide, Anabolic agents, Bromocryptine, Chlorobenzene, Corticosteroid, Cyclosporin, Cyproterone, Danazol, Diazoxide, Digoxin, Diphenylhydantoin, Dyazide, Metyrapone, Minoxidil, Penicillamine, Phenothiazine, Progestogens, Psoralens, Spironolacton, Streptomycin Ichthyosis, acquired Butyrophenone, Nicotinic acid, Triparanol
Jaundice Aurothioglucose, Erythromycin lauryl sulphate, Para-aminosalicylic Acid, Phenobarbital, Thiouracil Keratoderma Gold Keratoses Arsenic, Fowler's Solution, Gold LE-like syndrome Acebutolol, Allopurinol, Aminoglutethimide, Aminosalicylic acid, Captopril, Carbamazepine, Chlorpromazine, Cimetidine, Ethosuximide, Gold, Griseofulvin, Hydantoin, Hydralazine, Isoniazid, Labetolol, Lithium, Mephobarbital, Methyldopa, Minocycline, Penicillin, Phenylbutazone, Phenytoin, Pill, Practolol, Procainamide, Reserpine, Streptomycin, Sulfamethoxypyridazine, Sulphonamide, Tetracycline HCI (degraded), Thiazide, Thionamide, Thiouracil Lichenoid eruption Beta-blocker (Practolol), Bismuth, Captopril, Carbamazepine, Chloroquine, Cholorpropamide, Gold, Hydroxyurea, Meprobamate, Mepacrine, Methyldopa, para-amino-salicyclic acid, Penicillamine, Phenothiazine, Quinine, Quinidine, Streptomycin, Sulphonylurea, Tetracycline, Thiazides Linear Ig-A dermatosis Amiodarone, Captopril, Cefamandole, Diclophenac, Lithium, Vancomycin Livedo reticularis Amantadine Lymphoproliferative disease/Pseudolymphoma ACE-inhibitor, Carbamazepine, Cyclosporin, Dantrolene, Diltiazem, Hydantoin, Pyrazolone, Pyrimethamine Mucosal ulcerations, oral Foscarnet, DDC, Interferon Nail changes Amodiaquin (hyperpigmentation), arsenic (longitudinal white stripes), argyria (dark blue nail bed), Chloroquine (blue-black nail bed), Phenolphthalein (dark blue fixed eruption), tetracycline (yellow nail and yellow fluorescence), demethylchlortetracycline (phototoxic onychomadesis) Ochronosis-like pigmentation Phenol, Quinacrine, Resorcin Onycholysis Demethylchlortetracycline Papular dermatitis
Acetazolamide, Acetylsalicylic acid, Arsenic, Aurothioglucose, Digitalis, Penicillin, Thiazide Pellagra-like eruption Isoniazide Pemphigoid-like eruption 1) Bullous 5-Fluorouracil (topical), Frusemide, Ibuprofen, Penicillamine, Penicillin, Sulphasalazine, PUVA 2) Cicatrical Anti-glaucoma agent (topical), Clonidine, Indomethacin, D-penicillamine, Practolol, Sulphadoxine Pemphigus-like eruption Ampicillin, Captopril, Enalapril, Pencillamine, Penicillin, Phenylbutazone, Pyrazolan derivative, Rifampicin, Sulphydryl groups (pyritinol, thiopronin) Photosensitivity Amiodarone, Chlorthiazide, Chlorpromazine, Chlorpropamide, Cytotoxic (Dacarazine, Methotrexate, Fenofibrate, Fluorescein, 5-fluorouracil, Furocoumarins, Griseofulvin, Nalidixic acid, NSAID (benoxaprofen, piroxicam, naproxen), Phenothiazine, Promethazine, Psoralen (Methoxsalen, Trimethylpsoralen), Quinidine, Quinine, Quinolones, Reserpine, Retinoids, Sulphonamides, Sulphonylureas, Sunscreen (PABA, oxybenzone), Tetracyclines (demeclotetracycline, doxycycline, tetracycline), Tolbutamide, Tricyclic antidepressant (Clomipramine, Carbamazepine) Pigmentation Amiodarone (slatey grey pigmentation on light-exposed skin) Antimalarials (diffuse generalized grey/brown pigmentation; mepacrine causes generalized yellow/orange discoloration resembling jaundice Antipyrines, Bismuth (gums) Clofazimine Chlorpromazine (slate-colored) Chloroquine (bleaching of hair) Cytotoxic drugs (busulphan, bleomycin, cyclophosphamide, fluorouracil, hydroxyurea, may cause generalized brown pigmentation) Gold/silver (chrysiasis) blue/grey pigmentation on light-exposed skin) Minocycline hydrochloride (blue/grey pigmentation on light-exposed skin and in scars) Oral contraceptives (melasma -brownish pigmentation on face) Phenformin (brown pigmentation on light-exposed skin) Phenothiazines (bluish pigmentation on light-exposed skin, especially on the face)
Phenytoin (melasma-like pigmentation on face) Streptomycin, Tetracosactide, Tetracyclines, Thiouracil Zidovudine (AZT) (melanonychia, diffuse cutaneous/oral mucosal pigmentation, acral hyperpigmented macules) Pityriaisis rosea-like eruption Arsenicals, Bismuth, Gold, Barbiturates, Clonidine, Captopril, Isotretinoin, Ketotifen, Methoxypromazine, Metronidazole, Pyribenzamine Polyarteritis nodosa-like eruption Sulfonamides, Thiouracil, Iodides Porphyria (Drugs provoke variegate porphyria): Alcohol, Androgens, Barbiturates, Carbamazepine, Chlordiazepoxide, Chloroquine, Griseofulvin, Hexachlorobenzene, Hydantoin, Meprobamate, Nortriptyline, Pills, Oestrogens, Sodium valproate, Sulphonamides, Sulphonylureas (Drugs provoke porphyria cutanea tarda): above + Busulphan, Quinidine, Quinine, Rifampicin Pseudo-porphyria Amiodarone, Bumetamide, Ciprofloxacin, Frusemide, Nalidixic aid, NSAID, Ofloxacin, Tetracycline Pruritus Alkaloid, Antidepressive, Antimalarial, Atropine, Aurothioglucose, Barbiturates, Belladonna, Bismuth, Cimetadine, CNS stimulant, Cocaine, Codeine, Coumarin, Griseofulvin, Heparin, Insulin, Iodide, Niacinamide, Opiates, Penicillin, Phenobarbital, Procaine, Quinacrine, Streptomycin, Tetracyclines, Thiamine Chloride, Thiouracil Pruritus ani Chloroquine, Codeine, Liver Extract, Tetracyclines Purpura ACTH, Allopurinol, Barbiturates, Carbromal, Chlorpromazine, Corticosteroids, Coumarin, Ephedrine, Griseofulvin, Iodide, Meprobamate, Mercury, Penicillin, Quinidine, Reserpine, Sodium thiosulfate, Sulfamethoxypyridazine, Sulfonamides, Thiazides Purpura Fulminans Acetylsalicylic acid, Coumarin, Iodides Pustular Psoriasis Acetylsalicylic Acid, Antimalarials, Poliomyelitis vaccine Pustuloderma Bromides, Chloral hydrate, Iodides, Penicillin, Macrolide Seborrhoeic dermatitis
Methyldopa, Phenothiazines Scleroderma-like eruption Epoxy resin monomer, Organic solvent, Perchlorethylene, Trichlorethylene, Vinyl chloride monomer Bleomycin, Carbidopa, Penicillamine, Pentazocine, Organic solvent, Sodium valproate, Injection of paraffin or silicone Stevens-Johnson Syndrome Allopurinol, Antipyrines, barbiturates, Chlormezanone, Chloroquine, Chlorpropamide, Cotrimoxazole, Cough Mixtures, Meprobamate, NSAID, Phenacetin, Phenobarbital, Phenytoin, Sulfonamides Stomatitis Aurothioglucose, Bismuth, Chlorpromazine, Dilantin (gingivitis), Fluorides, Methotrexate, Phenobarbital, Streptomycin, Thiouracil Striae Corticosteroids, Isoniazid Telangiectasia Oral contraceptives Toxic Epidermal Necrolysis Acetazolamide, Allopurinol, Aminopyrine, Antihistaminics, Anti-pyrines, Barbiturates, Brompheniramine, Dapsone, Gold Salts, Methyl-salicylate, Nitrofurantoin, Penicillin, Phenolphthalein, Phenylbutazone, Phenytoin, Salicylates, Polio Vaccine, Sulfonamides, Tetracyclines, Tolbutamide Urticaria 1) Immunological mediation Drugs most commonly responsible: Enzymes, Penicillins, Pollen vaccines, Polypeptide hormone, Serum, Sulphonamides Other drugs responsible, but lower incidence: Barbiturate, Carbimazole, Cephalosporins, Cimetidine, Griseofulvin, Insulin, Metronidazole, Phenytoin, Quinidine, Synthetic adrenocorticotrophin, Tetracycline 2) Non-immunological mediation Alcohol, Aspirin and other salicylates, Atropine, Chlortetracycline, Codeine, Dextran, Decamethonium, Morphine, NSAID, Oestrogen, Pilocarpine, Polymyxin antibiotics, Quinine, Radiographic contrast media, Scopolamine, Snake venoms, Thiamine, d-Tubocurare, Vancomycin Vasculitis Anti-influenza, vaccine, Allopurinol, Arsenic, Captopril, Chlorpromazine, Cimetidine, Clindamycin, Corticosteroids, Ethacrynic acid, Gold, Griseofulvin, Guanethidine, Heparin, Hydantoin, Hydralazine,
Indomethacin, Insulin, Iodide, Ketoconazole, Methylthiouracil, Penicillin, Phenothiazine, Phenylbutazone, Phenytoin, Pill, Poison ivy extract, Quinidine, Serum, Streptomycin, Streptokinase, Sulphonamides, Tamoxifen, Tetracycline, Thiazide, Thiouracil, Vancomycin CUTANEOUS DRUG ERUPTIONS Dr. L.Y. CHONG CHAPTER 23 Cutaneous drug eruptions may be defined as adverse cutaneous lesions as a consequence of administration of drugs. The exact incidence of cutaneous drug eruptions in Hong Kong is unknown. According to the statistics of Social Hygiene Service, drug eruptions account for 0.5% of all new skin cases seen in dermatological outpatient clinics of the Service in 1995. This figure does not include those seen in general outpatient clinics, private sector and hospitals. The true incidence is definitely much higher. The main difficulties of getting a true figure are due to lack of a central registry and loose labelling of drug reactions on the patients. Adverse effects of drugs are often published in the literatures according to anecdotal reports or badly designed studies. The pathogenesis of drug eruptions may arise as a result of immunological or non-immunological reaction. Some of these reactions are predictable (dose-related) while some are unpredictable (idiosyncratic). Those with an immunological basis may due to different types of hypersensitivity reactions, for instance, allergic type of urticaria may be the result of Type I reaction (IgE-mediated) or Type III reaction (complement dependent immune-complex mediated). Nevertheless, the exact mechanisms of most drug eruptions, including fixed drug eruptions, are unknown. Clinically drug eruptions have a wide range of different morphological presentations. (Table 1) They can be generalized or fixed eruptions and their severity varies from minor to fatal skin reactions. Unfortunately, apart from fixed drug eruption, there is neither pathognomonic clinical feature nor diagnostic investigation in drug eruption. In practice, it is often difficult to identify the culprit with certainty, especially when the patient is taking multiple drugs simultaneously. Diagnosis is mainly based on clinical grounds in which the history plays the most essential part. In the history, the temporal relationship between the taking of drug and the onset of skin eruption is most important. Experience and statistical knowledge about the suspected drugs are also useful as certain drugs (for examples, ampicillin or cotrimoxazole) are more likely to cause drug eruptions, especially in certain diseases (for examples, AIDS or infectious mononucleosis).
In the history, the following information should be carefully asked: A detail drug history including the names and dosage of the drugs taken (Drugs should include those prescribed by doctors and any herbal or homeopathic medicines) The temporal relationship between the intake of drugs and the onset of skin lesions (Allergic drug reactions usually develop within 1 to 2 weeks of initiation of treatment) Any previous history of drug allergy, or similar skin lesions after taking similar drugs Any improvement of skin lesions after the suspected drug is withdrawn (The skin eruption is unlikely to be drug-induced if it fails to improve after withdrawal or if it improves even without stopping the drug. However, sometimes it may takes weeks for drug eruption to resolve even when the drug is stopped.) Up to the present moment, there is still no reliable and practical investigation for confirmation of drug eruption. Rechallange test is dangerous and should not be carried out in usual circumstances. Perhaps the only situations for rechallange test are those with fixed drug eruptions or those with life-threatening conditions in which that particular drug is essential. Skin test has little practical value as it may cause fatal systemic reaction and false positive reaction is common. Other tests such as radioallergosorbent tests (RAST) for drug-specific IgE antibody (penicillin, insulin), histamine release test, leucocyte and macrophage migration inhibition tests, lymphocyte toxicity assay, basophil degranulation test, passive haemagglutination test and lymphocyte transformation test are mainly for research purposes. In mild drug eruptions, withdrawal of the culprits together with symptomatic treatments will be adequate. For patient who is taking multiple drugs which are essential (for instance, antituberous drugs), all drugs should be temporarily withheld. After the skin lesions has subsided, each of these drugs can then be reintroduced one by one under strict observation, usually start with the drug which has lowest incidence of drug reaction. In severe drug eruptions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythroderma or angioedema, reintroduction of the drug is dangerous and immoral. In these situations, other treatment alternatives should be seeked for. Cross-sensitivity between similar drugs should be borne in mind in choosing alternative medication. Desensitization therapy has little practical value. After recovery, it is essential to give the patient a warning card, labelling the offending drug in order to avoid future retaking
of the drug. Table 1: Morphological Classification of Drug Eruptions Acanthosis nigricans-like eruption Corticosteroids, Hydantoin, Nicotinic Acid, Pills, Stilbestrol Acneiform eruption Anticonvulsant (phenytoin, phenobarbital, trimethadione), Antituberculous (isoniazid, ethionamide, refampicin), Azathioprine, Chloral hydrate, Corticosteroids, Corticotropin (ACTH), Cyanocobalamin, Cyclosporin, Halogens (bromides, chlorides, iodides, halothane), Haloperidol, Lithium, Pills, Psoralens, Quinine, Scopolamine Acral erythema/red palms Adriamycin (Doxorubicin), Cystosine arabinoside, 5-fluorouracil Acrodynia Mercury Alopecia Allopurinol, Bromocriptine, Carbimazole, Chlorambucil, Chloramphenicol, Cholesterol lowering agents, Cimetadine, Colchicine, Coumarin, Cytotoxic drugs, Diazoxide, Ethionamide, Fluconazole, Gentamicin, Gold, Heavy metals, Heparin, Hydantoin, Levodopa, Methotrexate, Methyldopa, NSAID (indomethacin, piroxicam), Pills, Phenindione, Propanolol, Sodium valproate, Thiouracil, Vitamin A or Retinoids Anaphylactic Reaction Acetylsalicylic acid, ACTH, Aminopyrine, Meprobamate, Mercurial Diuretics, Para-aminosalicylic Acid, Penicillin, Pituitary Extract, Procaine, Succinylcholine, Tetracycline, Thiouracil Angiitis, Necrotizing Bishydroxycoumarin (Dicumarol) Angioedema Meprobamate, Penicillin, Stilbestrol, Sulfonamides Argyria Silver Salts Arteritis Cyclobarbital, Chlorpromazine, Iodides, Phenylbutazone, Phenytoin, Poison Ivy Extract, Sulfonamides, Thiouracil Black hairy tongue Tetracycline, Penicillin Bowen's Disease Arsenic, Fowler's Solution
Bullous eruption Acetylsalicylic acid, Antipyrines, Arsenic, Barbiturates, Bromide, Chloral hydrate, Chlorpromazine, Coumarin, Dilantin, Glutethimide, Hydantoin derivatives, Ibuprofen, Imipramine, Iodide, Phenobarbital, Phenylbutazone, Promethazine, Methadone, Meprobamate, Nitrazepam, Sulfonamides Candidiasis Tetracyclines Chilblains-like erythema Coumarins, Phenindione, Sulindac Cyanosis Acetanilide Depigmentation Chloroquine Eczematous reactions (other than contact eczema) Aminophylline, Antibiotics, Antihistamine, B-blockers, Benzocaine, Bleomycin, Carbamazepine, Chloral Hydrate, Diphenhydramine, Disulfuram, Fluorouracil, Fucidin, Meprobamate, Methaminodiazepoxide, Minoxidil, Neomycin, Nystatin, Phenothiazines, Procainamide, Procaine, Quinacrine, Quinidine, Resorcin, Streptomycin (cross-reaction with neomycin), Sulphonamide, Thiazide Edema Arsenic, Chlorpromazine, Penicillin, Phenytoin, Promethazine, Chloroquine Elastosis perforans serpiginosa Penicillamine Erythema/exanthem Allopurinol, Ampicillin, Antipyrines, Arsenic, Atropine, Aurothioglucose, Barbiturates, Carbamazepine, Chloral hydrate, Chlorpropamide, Codeine, Corticotropin, Gentamicin, Gold, Griseofulvin, INH, Interleukin-2, Meprobamate, Methaminodiazepoxide, Morphine, Nicotinic Acid, Nitrofurantoin, Opium, Penicillin, Phenothiazine, Phenylbutazone, Pilocarpine, Quinacrine, Quinidine, Quinine, Streptomycin, Sulphonamides, Sulphamethoxypyridazine, Thiazide, Thiamine Chloride, Tolbutamide 1) Maculopapular rash Allopurinol, Chloroquine, Meprobamate, Penicillin, Promethazine, Streptomycin, Sulfamethoxypyridazine 2) Morbilliform erythema Acetylsalicylic acid, Ampicillin, Barbiturates, Bromides, Chlorpromazine, Griseofulvin, Insulin, Meprobamate, Penicillin, Promethazine, Salicylates, Streptomycin 3) Scarlatiniform erythema
Barbiturates, Mercury, Morphine, Opium, Penicillin, Phenobarbital, Pituitary Extract, Quinine, Salicylates, Streptomycin, Sulfonamides 4) Toxic erythema Drugs most commonly responsible (up to 5% of patients affected): Allopurinol, Carbamazepine, Cephalosporins, Gold, Nalidixic acid, Penicillins, Sulphonamides Other drugs commonly responsible (1-4% of patients affected): Isoniazid, Para-amino salicylic acid, Phenytoin, NSAIDs, Nitrofurantoin, Streptomycin Erythema multiforme (including Stevens-Johnson syndrome and toxic epidermal necrolysis) Acetylsalicylic acid, Allopurinol, Amidopyrine, Antihistaminics, Antipyrines, Barbiturates, Bromides, Carbamazepine, Chloral hydrate, Cimetadine, Corticotropin (ACTH), Furosemide, Griseofulvin, Hydantoins, Iodides, Mercury, NSAIDs (especially piroxicam), Para-aminosalicyclic Acid, Penicillins, Phenytoin, Phenolphthalein, Phenothiazine, Phenylbutazone, Procaine, Streptomycin, Sulfamethoxy-pyridazine, Sulphonamides, Tetracycline Erythema Nodosum Acetylsalicylic Acid, Bromides, Gold, Iodides, Penicillin, Phenacetin, Pills, 13-cis-retinoic acid, Salicylates, Sulfathiazole, Tetracycline Erythroderma (Exfoliative dermatitis) Allopurinol, Aminosalicylic Acid, Arsenicals, Aurothioglucose, Barbiturates, Bismuth, Captopril, Carbamazepine, Cefoxitin, Chlorpromazine, Chloroquine, Cimetadine, Dapsone, Diltiazem, Gold, Griseofulvin, Hydantoin, Iodides, Isoniazid, Lithium, Mercury, Nitrofurantoin, NSAID, Penicillin, Phenothiazines, Phenytoin, Quinidine, Quinacrine, Sodium Thiosulfate, Stilbestrol, Streptomycin, Sulphamethoxypyridazine, Sulphonamides, Sulphonylurea, Tetracycline, Thiouracil, Retinoid Erythromelalgia Bromocriptine, Nifedipine, Pergolide, Verapamil Fixed drug eruption Aminopyrine, Amphetamines, Antihistaminics, Antimony Compounds, Antipyrines, Arsenic, Barbiturates, Bismuth, Chlordiazepoxide, Chloral Hydrate, Chloroquine, Codeine, Dapsone, Gold, Diethylstilbestrol, Digitalis, Ephedrine, Ergot, Hydantoin, Hydralazine, Iodides, Meprobamate, Mercury, Metronidazole, Morphine, NSAIDs, Opium, Para-aminosalcylic acid, Paracetamol, Penicillin, Phenacetin, Phenolphthalein, Phenothiazine, Phenylbutazone, Potassium Chlorate, Quinacrine, Quinine, Reserpine,
Salicylates, Streptomycin, Sulfonamides, Sulindac, Tetracyclines, Tetraiodofluorescein Gangrene Coumarin Gingival hyperplasia Cyclosporin, Nifedipine, Hydantoin Hair color changes Carbamate, Chloroquine, Chlorpromazine Henoch-shonlein purpura-like eruption Diltiazem, Frusemide Hirsutism/hypertrichosis Acetazolamide, Anabolic agents, Bromocryptine, Chlorobenzene, Corticosteroid, Cyclosporin, Cyproterone, Danazol, Diazoxide, Digoxin, Diphenylhydantoin, Dyazide, Metyrapone, Minoxidil, Penicillamine, Phenothiazine, Progestogens, Psoralens, Spironolacton, Streptomycin Ichthyosis, acquired Butyrophenone, Nicotinic acid, Triparanol Jaundice Aurothioglucose, Erythromycin lauryl sulphate, Para-aminosalicylic Acid, Phenobarbital, Thiouracil Keratoderma Gold Keratoses Arsenic, Fowler's Solution, Gold LE-like syndrome Acebutolol, Allopurinol, Aminoglutethimide, Aminosalicylic acid, Captopril, Carbamazepine, Chlorpromazine, Cimetidine, Ethosuximide, Gold, Griseofulvin, Hydantoin, Hydralazine, Isoniazid, Labetolol, Lithium, Mephobarbital, Methyldopa, Minocycline, Penicillin, Phenylbutazone, Phenytoin, Pill, Practolol, Procainamide, Reserpine, Streptomycin, Sulfamethoxypyridazine, Sulphonamide, Tetracycline HCI (degraded), Thiazide, Thionamide, Thiouracil Lichenoid eruption Beta-blocker (Practolol), Bismuth, Captopril, Carbamazepine, Chloroquine, Cholorpropamide, Gold, Hydroxyurea, Meprobamate, Mepacrine, Methyldopa, para-amino-salicyclic acid, Penicillamine, Phenothiazine, Quinine, Quinidine, Streptomycin, Sulphonylurea, Tetracycline, Thiazides Linear Ig-A dermatosis Amiodarone, Captopril, Cefamandole, Diclophenac, Lithium, Vancomycin Livedo reticularis
Amantadine Lymphoproliferative disease/Pseudolymphoma ACE-inhibitor, Carbamazepine, Cyclosporin, Dantrolene, Diltiazem, Hydantoin, Pyrazolone, Pyrimethamine Mucosal ulcerations, oral Foscarnet, DDC, Interferon Nail changes Amodiaquin (hyperpigmentation), arsenic (longitudinal white stripes), argyria (dark blue nail bed), Chloroquine (blue-black nail bed), Phenolphthalein (dark blue fixed eruption), tetracycline (yellow nail and yellow fluorescence), demethylchlortetracycline (phototoxic onychomadesis) Ochronosis-like pigmentation Phenol, Quinacrine, Resorcin Onycholysis Demethylchlortetracycline Papular dermatitis Acetazolamide, Acetylsalicylic acid, Arsenic, Aurothioglucose, Digitalis, Penicillin, Thiazide Pellagra-like eruption Isoniazide Pemphigoid-like eruption 1) Bullous 5-Fluorouracil (topical), Frusemide, Ibuprofen, Penicillamine, Penicillin, Sulphasalazine, PUVA 2) Cicatrical Anti-glaucoma agent (topical), Clonidine, Indomethacin, D-penicillamine, Practolol, Sulphadoxine Pemphigus-like eruption Ampicillin, Captopril, Enalapril, Pencillamine, Penicillin, Phenylbutazone, Pyrazolan derivative, Rifampicin, Sulphydryl groups (pyritinol, thiopronin) Photosensitivity Amiodarone, Chlorthiazide, Chlorpromazine, Chlorpropamide, Cytotoxic (Dacarazine, Methotrexate, Fenofibrate, Fluorescein, 5-fluorouracil, Furocoumarins, Griseofulvin, Nalidixic acid, NSAID (benoxaprofen, piroxicam, naproxen), Phenothiazine, Promethazine, Psoralen (Methoxsalen, Trimethylpsoralen), Quinidine, Quinine, Quinolones, Reserpine, Retinoids, Sulphonamides, Sulphonylureas, Sunscreen (PABA, oxybenzone), Tetracyclines (demeclotetracycline, doxycycline, tetracycline), Tolbutamide, Tricyclic antidepressant (Clomipramine, Carbamazepine)
Pigmentation Amiodarone (slatey grey pigmentation on light-exposed skin) Antimalarials (diffuse generalized grey/brown pigmentation; mepacrine causes generalized yellow/orange discoloration resembling jaundice Antipyrines, Bismuth (gums) Clofazimine Chlorpromazine (slate-colored) Chloroquine (bleaching of hair) Cytotoxic drugs (busulphan, bleomycin, cyclophosphamide, fluorouracil, hydroxyurea, may cause generalized brown pigmentation) Gold/silver (chrysiasis) blue/grey pigmentation on light-exposed skin) Minocycline hydrochloride (blue/grey pigmentation on light-exposed skin and in scars) Oral contraceptives (melasma -brownish pigmentation on face) Phenformin (brown pigmentation on light-exposed skin) Phenothiazines (bluish pigmentation on light-exposed skin, especially on the face) Phenytoin (melasma-like pigmentation on face) Streptomycin, Tetracosactide, Tetracyclines, Thiouracil Zidovudine (AZT) (melanonychia, diffuse cutaneous/oral mucosal pigmentation, acral hyperpigmented macules) Pityriaisis rosea-like eruption Arsenicals, Bismuth, Gold, Barbiturates, Clonidine, Captopril, Isotretinoin, Ketotifen, Methoxypromazine, Metronidazole, Pyribenzamine Polyarteritis nodosa-like eruption Sulfonamides, Thiouracil, Iodides Porphyria (Drugs provoke variegate porphyria): Alcohol, Androgens, Barbiturates, Carbamazepine, Chlordiazepoxide, Chloroquine, Griseofulvin, Hexachlorobenzene, Hydantoin, Meprobamate, Nortriptyline, Pills, Oestrogens, Sodium valproate, Sulphonamides, Sulphonylureas (Drugs provoke porphyria cutanea tarda): above + Busulphan, Quinidine, Quinine, Rifampicin Pseudo-porphyria Amiodarone, Bumetamide, Ciprofloxacin, Frusemide, Nalidixic aid, NSAID, Ofloxacin, Tetracycline Pruritus Alkaloid, Antidepressive, Antimalarial, Atropine, Aurothioglucose, Barbiturates, Belladonna, Bismuth, Cimetadine, CNS stimulant, Cocaine,
Codeine, Coumarin, Griseofulvin, Heparin, Insulin, Iodide, Niacinamide, Opiates, Penicillin, Phenobarbital, Procaine, Quinacrine, Streptomycin, Tetracyclines, Thiamine Chloride, Thiouracil Pruritus ani Chloroquine, Codeine, Liver Extract, Tetracyclines Purpura ACTH, Allopurinol, Barbiturates, Carbromal, Chlorpromazine, Corticosteroids, Coumarin, Ephedrine, Griseofulvin, Iodide, Meprobamate, Mercury, Penicillin, Quinidine, Reserpine, Sodium thiosulfate, Sulfamethoxypyridazine, Sulfonamides, Thiazides Purpura Fulminans Acetylsalicylic acid, Coumarin, Iodides Pustular Psoriasis Acetylsalicylic Acid, Antimalarials, Poliomyelitis vaccine Pustuloderma Bromides, Chloral hydrate, Iodides, Penicillin, Macrolide Seborrhoeic dermatitis Methyldopa, Phenothiazines Scleroderma-like eruption Epoxy resin monomer, Organic solvent, Perchlorethylene, Trichlorethylene, Vinyl chloride monomer Bleomycin, Carbidopa, Penicillamine, Pentazocine, Organic solvent, Sodium valproate, Injection of paraffin or silicone Stevens-Johnson Syndrome Allopurinol, Antipyrines, barbiturates, Chlormezanone, Chloroquine, Chlorpropamide, Cotrimoxazole, Cough Mixtures, Meprobamate, NSAID, Phenacetin, Phenobarbital, Phenytoin, Sulfonamides Stomatitis Aurothioglucose, Bismuth, Chlorpromazine, Dilantin (gingivitis), Fluorides, Methotrexate, Phenobarbital, Streptomycin, Thiouracil Striae Corticosteroids, Isoniazid Telangiectasia Oral contraceptives Toxic Epidermal Necrolysis Acetazolamide, Allopurinol, Aminopyrine, Antihistaminics, Anti-pyrines, Barbiturates, Brompheniramine, Dapsone, Gold Salts, Methyl-salicylate, Nitrofurantoin, Penicillin, Phenolphthalein, Phenylbutazone, Phenytoin, Salicylates, Polio Vaccine, Sulfonamides, Tetracyclines, Tolbutamide Urticaria
1) Immunological mediation Drugs most commonly responsible: Enzymes, Penicillins, Pollen vaccines, Polypeptide hormone, Serum, Sulphonamides Other drugs responsible, but lower incidence: Barbiturate, Carbimazole, Cephalosporins, Cimetidine, Griseofulvin, Insulin, Metronidazole, Phenytoin, Quinidine, Synthetic adrenocorticotrophin, Tetracycline 2) Non-immunological mediation Alcohol, Aspirin and other salicylates, Atropine, Chlortetracycline, Codeine, Dextran, Decamethonium, Morphine, NSAID, Oestrogen, Pilocarpine, Polymyxin antibiotics, Quinine, Radiographic contrast media, Scopolamine, Snake venoms, Thiamine, d-Tubocurare, Vancomycin Vasculitis Anti-influenza, vaccine, Allopurinol, Arsenic, Captopril, Chlorpromazine, Cimetidine, Clindamycin, Corticosteroids, Ethacrynic acid, Gold, Griseofulvin, Guanethidine, Heparin, Hydantoin, Hydralazine, Indomethacin, Insulin, Iodide, Ketoconazole, Methylthiouracil, Penicillin, Phenothiazine, Phenylbutazone, Phenytoin, Pill, Poison ivy extract, Quinidine, Serum, Streptomycin, Streptokinase, Sulphonamides, Tamoxifen, Tetracycline, Thiazide, Thiouracil, Vancomycin CUTANEOUS MANIFESTATION OF INTERNAL DISEASE Dr. H.H.L. CHAN & Dr. W.K. FUNG CHAPTER 22 Dermatology and internal medicine do not have as much overlap as other specialties such as endocrinology. Nonetheless, some dermatologists still consider their role in internal medicine as ¡¥the last line of defense¡¦. There are some truth in their statement, indeed from time to time we do encounter patients that present to us with cutaneous manifestation of systemic disease. Recognition of these cutaneous signs are therefore, of up most important. In this chapter, various aspect of dermatology will be discussed in greater details. 1. CUTANEOUS MARKER OF INTERNAL MALIGNANCY Cutaneous manifestation of underlying malignancy can be classified as follow: Malignant involvement of the skin Genodermatoses Paraneoplastic dermatoses
Environmental carcinogens 1.1. Malignant Involvement of the Skin Metastases from visceral tumour can sometimes occur as a result of direct extension from an underlying neoplasm. Incidence of this condition is about 2% and the cause correspond to the same malignancy that were most frequent in the population. These include carcinoma of the stomach, lung and breast. Paget's disease of the breast, clinically present as a patch of eczema or moist eroded area of the nipple, is often associated with an underlying adenocarcinoma of the breast. Carcinoma en cuirass another condition associated with breast carcinoma, manifested clinically as an area of leathery thickening caused by fibrosis and lymphatic blockage. Adnexal tumour is known to be associated with extramammary Paget's, a condition that usually presented as an area of erythematous moist patches in the groin or the perianal are. Systemic haematological malignancy can also involve the skin. For example, Hodgkin's lymphoma can present as pruritis and ichthyosis whereas gingival hypertrophy is seen in monocytic leukaemia. Cutaneous metastasis can also occur and is presented as plum-colour nodules or plaques. 1.2. Genodermatoses Genetic conditions can predispose at risk individuals to develop internal malignancy. These conditions can broadly be classified into four types: primary immunodeficiency gastrointestinal polyposis chromosomal instability others In primary immunodeficiency, patients are more susceptible to infections as well as the development of haematological malignancy. Others associated features may also be present, these include cerebellar ataxia, as seen in ataxia telangiectasia, or eczema as in the case of Wiskott-Aldrich syndrome. Other conditions in this category include severe combined immunodeficiency and Burton's agammagloblinemia. A group of genodermatoses have in common gastrointestinal harmartoma, cutaneous signs and internal neoplasm. The more commonly known of these conditions include Gardner's and Peutz-Jeghers. Gardner's syndrome is an autosomal dominant condition may present in childhood as multiple benign skin tumour, such as lipoma or fibroma. When these patients reach the third to fourth decades, they develop large bowel polyps which are usually thought to turn malignant later in life.
Peutz-Jeghers syndrome is also dominant in inheritance and patients presented with lentigo in the perioral area as well as bowel hamartoma. Intestinal obstruction can occur. Interesting, these patients have an increase risk of developing non-gastrointestinal tract tumours that include bronchial and breast carcinoma. The risk of developing gastrointestinal tract tumour is also increase. Other syndromes that are classified into the same category as Peutz-Jeghers include Cowden¡¦s disease, Muir-Torre syndrome, HowelEvans syndrome and Multiple endocrine neoplasm type III. Certain conditions are associated with chromosomal instability as a result of which excessive DNA damage can occur leading to an increase risk of internal malignancy. This group of conditions include Bloom's syndrome, Werner's syndrome, Fanconi's anaemia and Dyskeratosis congenita. There are other genodermatoses that are less well defined but associated with internal malignancy. These include neurofibromatosis, haemochromatosis and Gorlin's syndrome. Neurofibromatosis is relatively common. It is inherited as an autosommal dominant condition and is known to be associated with malignant schwannoma, phaeochromocytoma and carcinoid tumour. Hepatocellular carcinoma can occur in haemochromatosis especially in elderly male with cirrhosis. Gorlin's syndrome affects young patient with multiple basal cell carcinomas, odontogenic cysts and skeletal abnormalities. Medulloblastoma is a known association. 1.3. Paraneoplastic Dermatoses In this category, cutaneous signs occur as a result of circulating factor(s) produced by the tumour. The following conditions are considered by Poole to suit the above criteria: Acanthosis palmaris - Acanthosis nigricans Acquired ichthyosis - Amyloidosis Bazex' syndrome - Carcinoid Clubbing - Coagulopathies Cryoglobulinaemia - Cronkhite-Canada syndrome Cushing's - Dermatomyositis Erythema gyratum repens - Erythroderma Hyertrichosis lanuginosa - Leser-Trelat sign Pemphigus - Swee''s syndrome Necrolytic migratory erythema Several important topics are presented. Acanthosis nigricans can occur in obesity, hyperinsulinaemia, Cushing's syndrome and adenocarcinoma of the stomach. Several features help to distinguish the benign type from the malignant form. In the malignant form, there are mucosal involvement, pachydermatoglyphy and the disease tends
to be more extensive. Besides gut tumours, others known neoplastic associations include lung, breast, uterus, ovary and prostate. Leser-Trelat sign is the sudden appearance of multiple seborrhoeic keratoses in association with an underlying malignancy. Leser-Trelat and acanthosis nigricans can occur together and they may share similiar aetiology. Cushing's syndrome can occur either due to excessive ACTH production by a pituitary tumour or as a result of ectopic ACTH production. Small cell carcinoma of the bronchus, pancreatic tumour and carcinoid tumour can all produce ectopic ACTH. Common features seen in ectopic ACTH production includes marked muscle wasting, severe hyperpigmentation and hypokalaemia. Carcinoid tumours are neoplasm that derived from amine precursor uptake and decarboxylation (APUD) cells. These cells produce a wide range of chemical mediators that include serotonin, histamine and substance P. Gut and lung are the main site of their origin. The main symptoms are flushing, diarrhoea, abdominal pain and wheezing. Dermatomyositis is most commonly associated with carcinoma of the breast and bronchus in the western world. Interesting in our local environment, nasopharyngeal carcinoma is more commonly associated with dermatomyositis. Paraneoplastic pemphigus is an recently discovered phenomenon characterised by the development of erythema multiforme like erosion and extensive mucosal involvement in patients with an underlying neoplasm. Lymphoreticular malignancy were the most commonly associated neoplasm. 1.4. Environmental Carcinogens Nicotine stain is undoubtedly the most commonly seen cutaneous sign of carcinogen exposure. Arsenic exposure can increase the risk of internal malignancy such as lung, bladder, kidney and prostate. Signs of previous arsenic exposure include hyperkeratotic lesions in palms and soles, diffuse truncal hyperpigmentation and multiple squamous cell carcinomas. 2. CONNECTIVE TISSUE DISORDER Cutaneous abnormalities are commonly seen in connective tissue disease. In this section, we shall concentrate on the cutaneous manifestation of these disorders. 2.1. Lupus Erythematous 2.1.1. Cutaneous manifestation of lupus are as follow: Discoid lupus: lesions present as urticarial patch, scaly patch (follicular plugging), scarred patch, with pigmentary changes. The palms can be involved with atrophy, erosion or hyperkeratosis.
During acute flare up of systemic lupus erythematous, patient often develops transient maculopapular butterfly rash affecting both cheeks. In subacute lupus (SCLE), the eruption can be urticarial (annular), papulosquamous (psoriasiform). Mucosal involvement is also commonly seen and these include ulceration or nosebleed. Scalp involvement is not uncommon and both diffuse or scarring alopecia can be seen. Vascular lesions seen in lupus include: Raynaud's phenomenon, nail fold telangiectasia and infarct, splinter haemorrhages, chilblain LE, acquired C1 esterase deficiency, vasculitis, urticarial vasculitis, purpura, thrombophlebitis, livedo reticularis, phospholipid syndrome, Degos syndrome and calcinosis. Others less common cutaneous manifestations are Bullous LE, LE profundus, erythema multiforme (Rowell), LE/Lichen planus overlap and anteoderma. 2.1.2. American Rheumatology Association criteria for the diagnosis of systemic lupus erythematous: (4 or more are necessary for the diagnosis) Malar rash; discoid lupus erythematous; photosensitivity; oral ulcers; arthritis; serositis; renal disorder; central nervous systems disorders; haematological disorders; immunological disorders; antinuclear antibody. 2.1.3. Investigations Urine for microscopy, 24 hours urine for protein and creatinine, completed blood picture, renal and liver function tests, ESR, C-reactive protein, complement levels, antinuclear factor, anti-double stranded DNA, anti-ENA. Skin biopsy for histology and immunofluorescence. 2.1.4. Significance of Serologic Testing Antinuclear factor: in 90% of systemic lupus erythematous (SLE) Anti-DS DNA: only in SLE cases (40%) Anti-single-stranded DNA: in various collagen vascular diseases; in DLE cases, suggest disease progression Anti-Ro: subcutaneous lupus, neonatal lupus, C2 deficient lupus, late onset lupus overlap Anti-Sm: only in SLE cases (about 20%) Anti-RNP: frequently associated with systemic sclerosis Anti-histone: drug induced lupus Anti-cardiolipin: associated with venous and arterial thrombosis, fetal wastage and livedo with or without ulcer
2.2. Dermatomyositis 2.2.1. Diagnostic Criteria: (4 out of 5, for dermatomyositis cutaneous changes must present) Proximal symmetric progressive muscle weakness Elevated muscle enzyme Consistent electromyography (EMG) Consistent muscle biopsy Cutaneous disease 2.2.2. Classification Primary dermatomyositis Primary polyomyositis Αssociated with underlying malignancy Οverlaps syndrome Childhood dermatomyositis Amyopathic dermatomyositis 2.2.3. Cutaneous Signs Pathognomic signs: Heliotrope rash, Gottron's papules, Dowling's line. Others: periungual telangiectases, cuticular hypertrophy, photosensitivity, poikiloderma. 2.2.4. Other Findings Proxmial muscle weakness and tenderness, dysphagia, cardiac and pulmonary disease. 2.2.5. Investigations Elevated muscle enzymes, EMG, muscle biopsy, MRI for early muscle changes, antibodies, ECG, pulmonary function test. 2.2.6. Significance of Serologic Findings PM-1: polyomyositis and scleroderma overlap Jo-1: pulmonary fibrosis Ku: sclerodermatomyositis Mi-2: one in four patients with dermatomyositis 2.3. Scleroderma Scleroderma is defined as thickening or hardening of the skin 2.3.1. Classification 1) Systemic disease Diffuse scleroderma; acrosclerosis; CREST syndrome; overlap syndrome. 2) Localised scleroderma Morphea Linear scleroderma: En coup de sabre; Romberg's disease (with facial atrophy)
Generalised morphea 3) Sclerodermoid conditions Genetic: Progeria, Werner's syndrome Occupational: vibration, silicosis Metabolic: congential porphyria, carcinoid Immunologic: Chronic graft verse host Chemical: Polyvinyl chloride, bleomycin Malignancy: carcinoid, bronchoalvelolar Postinfectious: Lyme Neurologic: limb immobilization 2.3.2. Diagnostic Criteria Developed by the American Rheumatism Association Major criteria: Proximal scleroderma Minor criteria: Sclerodactyly, digital pitted scars, loss of subcutaneous of the finger pad, bibasilar pulmonary fibrosis. (97% certain of the diagnosis if one major or two minor criteria are present) 2.3.3. Others Findings Pulmonary, Gastrointestinal, Musculoskeletal, Cardiac, Renal. 2.3.4. Serologic Findings Anti-RNP: mixed connective tissue disease Anti-centromere: CREST syndrome Anti-topoisonmerase I (anti-Scl-70) progressive systemic sclerosis Nucleolar ANA 2.3.5. Related Conditions Mixed connective tissue disease, eosinophilic fasciitis, tryptophan induced disease. 3. ENDOCRINE ABNORMALITIES Endocrine abnormalities often present with cutaneous signs. Recognition of which can lead to earlier diagnosis and prompt treatment. In this section, we will discuss the clinical manifestation of endocrinological disorders. 3.1. Diabetes Mellitus 1) Necrobiosis lipoidica diabetorium (NLD) It occurs in about 0.3 percent of patient with diabetes mellitus and is more common in young female patients. It usually presents as symmetrical, well defined plaques on both shins and feet. Sometimes, it may appear on the face, arms and trunk. The plaques are irregular and are brown-red on violaceous in colour. The epidermis is atrophic and delicate vessels occur over the surface. In chronic stage, the lesion may develop into painful ulcer. Treatment of NLD is very unsatisfactory. The course of the lesions do not
correlate with normalization of hyperglycaemia. Intralesional steroids are sometimes useful. 2) Diabetic dermopathy Multiple asymptomatic discrete atrophic brown macules are common on the shins. These are known as diabetic shin spots (or diabetic dermopathy). 3) Granuloma annulare Well defined, annular lesions with the margin made up of multiple discrete flat topped papules. These lesions are commonly found over the backs of the hands, feet, ankle and limbs. Though it responds well to intralesional steroids, it easily recurs. The generalize form has a stronger association with glucose intolerance than the localize variant. 4) Lipoatrophy/Lipohypertrophy Lipoatrophy refers to depression of the skin due to repeated injections of impurified insulin preparations. It usually occurs in children and young women. Lipohypertrophy is due to subcutaneous deposition of fat in situ of skin having repeated injections. 5) Bullous diabeticorum Subepidermal blisters may occur on the lower legs of diabetics but the cause is unknown. 6) Diabetic cheiroarthropathy (sclerodactyly) In 40% of juvenile IDDM patients, tight thickened and waxy skin develop over the dorsum of the hands. Subsequently, it results in contracture of the proximal interphalangeal joints. Others: 7) Infections 8) Kryle's disease 9) Eruptive xanthoma 10) Drug eruptions 11) Acanthosis nigricans 3.2. Thyroid Diseases 1) Hyperthyroidism The skin is warmth and moist due to hyperdynamic circulation. The hair is fine and friable. On the face, there may be telangiectasia and facial flushing. On the hands, there may be palmer erythema and onycholysis of nails. In Grave's disease, clubbing of fingers (thyroid acropachy) may occur. Others possible associated skin manifestations include pruritis, dermographism and urticaria. In Grave's disease, pretibial myxoedema occurs in 5 per cent of this group of patient. It presents as well-defined plaques or nodules with prominent
follicles and peau d' orange appearance. It commonly appears over the anterior aspect of the shins and is usually bilateral. 2) Hypothyroidism On the face, there may be non-pitting oedema around the eyes. The lateral third of the eyebrow may be thinned. The scalp and body hair is dry and brittle. Diffuse or partial alopecia may occur. In general, the skin is cool, dry and with a yellow tint. The nails are brittle and there are longitudinal ridges. Purpura and ecchymoses are not uncommon. 3.3. Adrenal Diseases 1) Adrenal Insufficiency Diffuse hyperpigmentation is noticed but is more marked on pressure points such as the knees, knuckles, ischial tuberosities and in intertriginous areas. The palmar creases are darkened. Mucous membranes including the vagina, anus and mouth are commonly pigmented. New scars are easily pigmented, too. There are longitudinal pigmented lines in the nails. 2) Cushing's Syndrome Typical features include: moon face, buffalo hump, central obesity but with thinning of extremities. Skin atrophy is very common and is frequently associated with ecchymoses and purpura. There are striae, mainly on the flanks of the abdomen, arms and thighs. These striae are usually broader and are purplish then the striae of pregnancy, obesity and adolescence. Decreased vascular tone may appear as purplish mottling on the lower limbs (cutis marmorata). Hypertrichosis occurring on the face, upper lip, chin and lateral cheeks is common. Hirsutism due to over-production of adrenal androgens may occur in females. Acne of monomorphic type is common on the face and back. In general, patient with cushing¡¦s syndrome is more susceptible to cutaneous infections such as pityriasis versicolour, trichophyton rubum and candidosis. 3.4. Pituitary Diseases 1) Panhypopituitarism The skin is dry, smooth, soft and pale.
The face may be puffy, facial fold is decreased. Fine wrinkles are commonly found around the eyes and mouth making the patient look older. The scalp hair is dry, fine and generally thin. Characteristically, there is uniform loss of body hair. Axillary hair is affected first and public hair loss takes longer to develop. Loss of beard hair may appear, too. Finally, the nails are fragile, thin and opaque. 2) Acromegaly On the face, the acromegalic appearance is very typical and presents as frontal bossing, widening of the nose, coarsening of the skin, and enlargement of the lips. The facial, neck and scalp creases are accentuated. Infrequently, overgrowth of the dermis results in ridging of the skin of the scalp (cutis verticis gyrata). Soft tissue swelling of the hands and feet are very common. The sebaceous glands and sweat glands are enlarged. Sessile or pedunculated fibromas are found in 20 to 30 percent of patients. Acanthosis nigrican is found in about 10 percent of cases. 3.5. The Porphyrias Porphyrias result from either acquired or inherited enzymatic abnormalities in haem synthesis. Haem is synthesized from glycine and succinyl coenzyme A in a complex series of reaction. Eight enzymes are involved in this complicated pathway. Most of the human porphyrias are due to the deficient activity of the corresponding enzymes. Porphyrias are of dermatologic interest because several of them have distinct cutaneous manifestations that may arrive the diagnosis clinically. Porphyrias are classified by the primary site of expression of the specific enzyme defect and the abnormal porphyrin profile of patients with these orders. There are 2 types: the erythropoietic porphyria and the hepatic porphyria. 1) The erythropoietic porphyria (EP) It includes the congenital erythropoietic porphyria and erythropoietic protoporphyria. Congenital Erythropoietic porphyria (Gunther's disease) This is an extremely rare autosomal recessive disorder and is due to a decreased activity of uroporphyrinogen cosynthetase. Photosensitivity is quite significant and presents as blisters, vesicles and bullae in sun-exposed areas. These skin lesions heal slowly with scarring, atrophy and mutilating deformities. Hyperpigmentation and hypertrichosis are common. Bone abnormalities such as resorption of distal phalanges and sclerodacyl may occur. Haemolytic anaemia and splenomegaly may be present. Erythrodontia (red-stained teeth) in both deciduous and permanent teeth is pathognomonic
of erythropoietic porphyria. The urine also fluoresces reddish. The diagnosis is made from the early onset of severe cutaneous photosensitivity associated with red fluorescent urine and erythrodontia. The treatment is usually preventive. Avoidance of sunlight must be emphasized. Splenectomy may be useful in dealing with intractable hemolytic anaemia. Erythropoietic protoporphyria (EPP) An autosomal dominant disorder which is characterized by cutaneous photosensitivity, cholelithiasis and potentially severe liver disease. The acute episodes of photosensitivity include itching, burning or pruritis in sunexposed areas and occur within minutes after sun-exposure. These are followed by erythema, oedema, urticarial lesions and rarely purpura a few hours later. Chronically damaged skin may heal with superficial pitted and linear scars especially on the cheeks and nose. Pseudorhagades, thickened and leathery skin over the knuckles and fingers together with the wrinkles give an appearance of premature aging. The diagnosis is made by detecting elevated levels of free protoporphyria in the red blood cell and/or faeces. Photoprotection is essential. Beta-carotene has been found helpful in preventing or minimizing the symptoms of cutaneous photosensitivity reactions. In severe end-stage liver failure, liver transplantation will be the last resort. 2) The Hepatic Porphyria The hepatic porphyria includes porphyria cutanea tarda, acute intermittent porphyria, variegate porphyria and hereditary corproporphyria. Porphyria Cutanea Tarda (PCT) PCT is due to the decreased activity in uroporphyrinogen decarboxylase and is divided into two categories. Type I (symptomatic, acquired) PCT is characterized by the deficiency of the enzyme in the liver only. Type II (hereditary) PCT is inherited in an autosomal dominant fashion and the uroporphyrinogen decarboxylase is decreased approximately 50 percent in all tissues. Vesicles and bullae appear on sun-exposed areas or in areas subjected to repeated trauma. Increased skin fragility is common and lesions usually heal with milia formation. Hypertrichosis (non-virilizing) is a useful diagnostic sign. Hyperpigmentation, sclerodermoid plaques and scarring alopecia are not uncommon. Ethyl alcohol, estrogen hormones, hexachlorobenzene, chlorinated phenols and iron have been associated with the exacerbation of PCT. Patients with PCT excrete increased amounts of porphyrins in the urine, which give rise to pink-red fluorescence under wood's lamp examination. In equivocal situation, quantitative 24 hour urine uroporphyrin and coproporphyrin determinations and stool protoporphyrin and coproporphyrin determinations should be performed. Drugs that may
have triggered the disease must be strictly avoided. Phlebotomy is a safe, effective and relatively simple method of therapy for PCT. In some patients who are not suitable for phlebotomy, may respond to antimalarials. e.g. chloroquine and hydroxychloroquine. Variegate Porphyria (VP) VP is an autosomal dominant disease and is quite common among the white. The clinical manifestations of VP include those of AIP and PCT, either or both of which may occur in the same individual. However, the skin manifestations do not correlate with the acute attacks in most patients. The diagnosis is made as shown by the elevated urinary ALA and PBG levels during acute attacks of VP but characteristically fall to normal levels between attacks. Precipitating factors and drugs should be avoided. Photoprotection for photosensitivity is a must. Hereditary Coproporphyria (HCP) HCP is an autosomal dominant disorder and is due to deficiency of coproporphogen oxidase activity in red blood cells and lecuocytes. It is an extremely rare disease. The acute attacks are similar to those of AIP but are milder than that of AIP. Cutaneous photosensitivity occurs in 20 percent of cases. HCP is characterized by increased excretion of coproporphyrin III in urine and faeces. Avoidance of drugs, glucose loading and hematin infusions may be helpful in dealing patients with HCP. CUTANEOUS LASER THERAPY Dr. L.Y. CHONG & Dr. H.H.L. CHAN CHAPTER 21 1. INTRODUCTION 1.1. Definition The word laser is the abbreviation of Light Amplification by the Stimulated Emission of Radiation. Laser light is characterised by monochromaticity, spatial coherence and high intensity. 1.2. Applications in Dermatology Different laser systems, each with its own unique properties, are now used for a wide range of dermatological conditions. These systems are named after the media that are used to produce the laser lights. They include carbon-dioxide, argon, organic dyes, heavy metal vapour, krypton, neodymium-YAG, ruby, and alexandrite lasers. (Table 1) In practice, dermatological applications of laser technology can be divided into three categories: surgery (cutting, haemostasis) and vaporisation; selective photothermolysis of superficial vascular disorders;
selective photothermolysis of pigmented lesions and tattoos. 2. LASER BIOPHYSICS 2.1. Joules, Watts, Fluence and Power Density Radiation energy is measured in Joules (J) and is directly proportional to the quantity of photons of the radiation. The rate of energy exposure is measured in Watts (W) where 1W = 1J/s. The total amount of energy exposed to a surface is known as the fluence (energy density) and is expressed in term of Joules per metre square (J/m2). In laser surgery, fluence determines the total volume of tissue damage. The rate of tissue damage depends on the power density of the laser beam. Power density or irradiance is defined as the rate of energy delivery per unit area (W/cm2). Power density of a laser beam is directly proportional to its output but inversely related to its spot size and can be calculated as follow: Power density (W/cm2) = Power output (W)/Spot size (cm2) 2.2. Properties of Laser Light Laser light has the following characteristics: A high degree of monochromaticity: The active medium determines the emission wavelength which is restricted to a very narrow band. A high degree of coherency: This is due to the fact that all light waves are in phase. Laser light is highly directional with a low degree of divergence. High intensity: The amplification process allows the emission of high-energy level laser. 2.3. Laser Beam Modalities Laser beams can be continuous, pulsed, superpulsed, or Q-switched. Continuous lasers (CW) produce beams with a constant output. The beam can be interrupted by a shutter controlled by the operator, resulting in the production of shuttered continuous wave (mechanical pulse). Pulsed lasers emit beams 'compressed' into high intensity pulses. Each pulse last about several hundred microseconds, generating energy 100 times more than that of the CW lasers. Better understanding of the concept of selective photo-thermolysis has resulted in the development of laser systems with very short pulses and high peak power. These are the Q-switched lasers. This refers to the use of techniques such as an electromagnetic switch to stop laser passing through the cavity abruptly. This blockage is then suddenly removed allowing the production of pulses with short duration (in the range of nsec) and high irradiance (1,000,000 W/cm2). 2.4. Laser Delivery Systems
Three systems are currently being used to deliver laser light from the optical cavity to the tissue: articulated arms, fiber optics, and automatic scanning devices. 1) An articulated arm involves the use of rigid tubes with reflective mirrors at each connecting end. 2) Fibreoptics are fibres consisting mainly of quartz and are used to transmit light. 3) Manual control of laser light delivery is subjective and can be inaccurate even in experience hands. Micromanipulator improves the accuracy of laser light delivery and can be connected to the fiber optics or the articulated arm through a microscope. Automatic scanning devices involve the use of computer-controlled micromanipulator that deliver laser light in a controlled manner. 2.5. Skin Optics The interaction of light radiation with skin is determined by the optical properties of skin constituents and on the wavelength of the incident light. In the epidermis and stratum corneum, radiation with wavelengths below 300 nm is absorbed rather than reflected. Different chromophores will absorb radiation of specific wavelengths. Protein, urocanic acid, melanin and nucleic acid are the main chromophores for radiation in the ultraviolet C and B range (< 320 nm). Melanin also absorbs radiation with wavelengths between the range of 320-1,000 nm. Water is the dominant chromophore for radiation of higher wavelengths (> 1,000 nm). Radiation with wavelengths greater than 300 nm have a greater degree of penetration and can therefore reach the dermis. In the dermis, most of the transmitted radiation is scattered from the collagen bundles back to the environment. Some degree of dermal absorption by chromophores such as haemoglobin and bilirubin do occur. Radiation such as ultraviolet A, blue, green, and yellow light are absorbed by haemoglobin. The term "optical window" refers to the ability of radiation to penetrate deep into skin tissue because of low absorption and low scattering. This applies to radiation with wavelengths between 600-1,300 nm. Melanin is the main chromophore at this spectrum. 2.6. Skin Chromophores and Laser Using lasers light with wavelengths that match that of the skin chromophores, selective tissue damage can be achieved. Light emitted by the ruby laser (694 nm) or Nd:YAG laser (1,064 nm) can be absorbed by melanin containing cells leading to their destruction.
Argon and yellow light lasers are absorbed by haemoglobin and can be used for the treatment of vascular lesions. The carbon dioxide laser has a wavelength of 10,600 nm which is absorbed by water and is therefore nn-selective. 2.7. Types of Interactions Between Laser Light and Skin Laser, like other electromagnetic radiation, can produce photothermal, photomechanical and photochemical reactions in skin. Photothermal interactions, are derived directly from heat generated by laser. If skin is heated to temperature just below 50o C, the consequent thermal tissue damage is still reversible. At higher degrees (50-100o C), coagulation of protein occurs leading to irreversible thermal damage. At even higher temperature (>100o C), vaporisation of tissue occurs. This takes place when the water component of the affected tissue reaches its boiling point and vaporised. The type of thermal tissue damage induced (coagulation or vaporisation) depends on the power density, there is, high energy pulses cause tissue to pass its boiling point and produces vaporisation. The extent of thermal damage is directly proportional to the amount of heat dissipated from the target site to the surrounding tissue. Heat requires time to diffuse outward and cause thermal damage. The extent of thermal damage, therefore, depends upon the rate of heating which is determined by power density and exposure time. If the exposure time is shorter than the target's thermal relaxation time (defined as the time required for a target to cool from the temperature achieved immediately after laser irradiation to half that temperature), heat will not be able to diffuse out. This allows the thermal damage to be limited to the target site. Selective tissue damage restricted to the target site can be achieved using a laser with a wavelength that is specifically absorbed by the target tissue, where it is converted to heat resulting in a thermal injury. This is referred to as Selective photothermolysis. As the thermal relaxation time of an object is inversely related to its size, lasers with ultra-short pulses emitting high energy have been developed. In photomechanical interactions, high energy-level pulse laser disperses the target tissue by rapid thermal expansion and local vaporisation. A good example of this reaction is the use of Q-switched ruby laser in the removal of tattoo. High energy impulses from the laser disperses the ink particles and the dermal macrophages that contain them. The main role of laser induced photochemistry is photodynamic therapy for the treatment of cancer. This involves the
use of laser, in conjunction with a topical or systemic photosensitizer, in producing the beneficial effects. In summary, the principle of laser therapy is to emit a specific wavelength of photon energy is to the target tissue, aiming to have optimal absorption of energy by the target tissue, while minimizing the destruction of the surrounding normal tissue. Three basic elements have to be considered: Firstly, a specific wavelength that is optimally absorbed by the target structure (depending on absorption curve of the chromophore); secondly, an exposure duration less than the time necessary for cooling of the target structure (using pulsed or Qswitched mode); and thirdly, sufficient energy fluence must be delivered to reach a destructive temperature in the target. 3. CLINICAL APPLICATION OF SPECIFIC LASER SYSTEMS 3.1. Carbon Dioxide (CO2) laser: Surgery and Vaporisation The CO2 laser has a wavelength of 10,600 nm (i.e. within the invisible infrared spectrum). It is used in conjunction with a coaxial heliumneon laser beam which is visible and acts as a guide light. Water is the main chromophone of CO2 lasers. Ninety percent of the skin is made up of water and the effect of the CO2 laser is therefore non-specific. CO2 lasers can be operated either as a cutting tool ["light knife"] or as an ablation tool ["laserbrasion"]. As mentioned above, the rate of thermal damage is related to the power density (which is inversely proportional to the spot size for any given energy.) For CO2 lasers to act as a cutting tool, high power density leading to instant and precise tissue vaporisation is necessary. To achieve this, the CO2 laser is placed close to the tissue surface (generally, less than 1 inch) so that the beam is focused (0.1-0.2 mm in diameter) and has a high power intensity (50,000-75,000 W/cm2). As the beam incises tissue, It will also seal blood vessels and lymphatics, allowing control of haemostasis. This makes it useful for patients with bleeding disorders or patients in whom adrenaline is contraindicated. It is also useful in patients with pacemakers in whom electrosurgery is contraindicated. Furthermore, because of its ability to seal nerve endings, patients tend to suffer less postoperative pain. The CO2 laser sterilises at the same time and is also useful for the debridement of infected ulcers or burns. The CO2 laser may also be used to vaporise tissue by positioning the laser further away from the skin surface than for cutting so that the beam is defocused (1-2 mm in diameter) and the power density low
(150-500 W/cm2). The power density is adjusted so that it is low enough to achieve rapid complete tissue vaporisation without charring. Many applications for CO2 laser vaporisation have been reported. (Table 2) However, with advances in technology, newer laser systems have proved to be superior to the CO2 laser in some of these conditions. By combining the two operational modes (excision and vaporisation) of CO2 laser, patients with rhinophyma can be effectively treated. In these cases, excess soft tissue is initially excised in a relatively bloodless field using the focused laser beam. Remaining tissue can then be contoured by tissue vaporisation. The resulting char can be removed by cotton gauze soaked in hydrogen peroxide. The process of tissue vaporisation and cleansing by hydrogen peroxide can be repeated until a satisfactory cosmetic result is obtained. Complete healing by secondary intention usually takes about 2-4 weeks. The most frequent complication of CO2 laser therapy is hypertrophic scarring. Others include hypopigmentation, dilated pores, postoperative haemorrhage, infection and excessive growth of granulation tissue. Another important hazard is the laser smoke ('plume') that occurs as a consequence of tissue vaporisation, viable human papillomavirus DNA has been isolated. An adequate smoke evacuation unit is essential. 4. LASERS FOR TREATING VASCULAR LESIONS (Table 3) 4.1. Argon Laser Argon lasers have been reported to be effective in the treatment of both vascular and pigmented lesions. They emit continuous, or shuttered continuous wave systems and use argon gas as the active medium. These systems emit light in the blue-green spectrum of the electromagnetic radiation. Haemoglobin and melanin are the principal chromophores of the argon laser. Haemoglobin is only partially sensitive to the argon laser emissions. This leads to a significant degree of scattering of laser energy in the dermis. In addition, a proportion of the light is absorbed by the melanocytes. This results in unwanted epidermal damage such as burning and blistering, and a reduction in the amount of energy reaching the dermal vessels. Furthermore, argon lasers generate low power emissions, resulting in non-selective thermal damage with an increased incidence of dermal fibrosis and scarring.
Argon lasers continue to have a role in the treatment of mature, hypertrophic port wine stains in adults. Other vascular lesions that have been successfully treated by the argon laser include small haemangiomas, cherry angiomas, telangiectasias, angiokeratomas and venous lakes. Because argon laser light is absorbed by melanin, these systems have been applied for the treatment of melanocytic pigmented lesions such as pigmented naevus, freckles and lentigines. Argon lasers have also been used as energy sources for other laser systems, for example, the continuous dye laser. 4.2. 577 or 585 nm Dye Lasers Dye lasers emit wavelengths that are selectively absorbed by oxyhaemoglobulin rather than epidermal melanin. In these systems, various organic dyes are used as the active medium to generate yellow light with wavelengths of either 577 or 585 nm. Pulsed dye lasers have been shown to be highly successful in the treatment of port wine stains. Lesions that show a better response are those that are located on the neck, lateral face and eyelids. Macular lesions and lesions in children also tend to be more responsive. Age is not a limiting factor for the use of these systems. Superficial vascular lesions other than port wine stains also respond to the pulsed dye laser. Telangiectasia especially those that occur after sclerotherapy for varicose veins are particularly responsive. The dye laser is also used for the treatment of proliferative haemangiomas that obstruct vital structures such as the eye. Complete resolution is obtained if the lesion is treated at an early stage. Others vascular lesions treated include poikiloderma of Civatte, facial spider angiomas, and the telangiectatic component of rosacea and pyogenic granuloma. Pulsed dye laser has also been successfully employed in the treatment of viral wart, although the precise mechanism by which this is achieved remains speculative. Hexascans are automated scanning devices that can be connected to argon-pumped tunable dye lasers for the treatment of large areas of superficial vascular malformations. In contrast to the pulsed-dye laser, it is effective in the treatment of hypertrophic port-wine stains and thicker haemangiomas but paler lesions tend to be less responsive. It can also be applied to the treatment of other cutaneous vascular lesions. Complications following the use of the pulsed dye laser are relatively uncommon. Purpura can be cosmetically disfiguring but will fade over a two weeks period. Acute changes such as the level of discomfort,
scaling, vesiculation or crusting are energy dependent and can be reduced by careful monitoring of the tested area. Local anaethesia using EMLA may sometimes be necessary to relieve the associated discomfort and should be applied 60 minutes preoperatively. Scarring occurs in less than 1% and is often associated with rubbing or scratching the lesion after the procedure. Hypopigmentation or hyperpigmentation is not uncommon and usually resolves after a few months. Hexascans do not cause purpura, but its other side effects are otherwise similar. 4.3. Copper Vapour Laser In these systems, pieces of copper metal placed in a ceramic tube are melted to form vapour. Neon gas is added to improve the discharge quality of the medium. The system produces yellow light with a wavelength of 578 nm and green light at 511 nm. Yellow light is suitable for the treatment of vascular lesion, whereas green light is used for pigmented conditions. Although both the dye and copper vapour systems emit radiation of similar frequencies, there are several important differences between them. The laser light delivered by the copper vapour system is rapidly pulsed with a pulse duration of 20 ns. The time between each pulse is 67 us, giving a frequency of 15 KHz. In contrast to the pulsed-dye system which generates 100 mJ of energy per pulse, the energy output per pulse of the copper vapour laser is only 0.2 mJ. Summation of pulses is therefore necessary to induce the desirable degree of tissue damage. To limit the thermal damage, a mechanical shutter with different shutter speed is used. The spot sizes of copper vapour systems are also much smaller (100-1,000 um). These properties of the copper vapour laser have resulted in clinical responses quite different from that of the pulsed-dye systems. Copper vapour lasers seem to induce vasoconstriction rather than intravascular coagulation as seen in the pulsed-dye system. They can, therefore, be used in combination with pulsed-dyed lasers in the treatment of large vascular condition such as hypertrophic or cobblestone port wine stains. The small spot sizes of the copper vapour lasers make them ideal for the treatment of disorders of small blood vessels such as facial telangiectasia. The green light mode of copper vapour laser has a wavelength of 511 nm and is largely absorbed by melanin. It can be used for the treatment of superficial pigmentary conditions. 4.4. Krypton Laser
These systems use Krypton gas as the active medium and generate yellow light with a wavelength of 568-575 nm as well as green light at 520-530 nm. Their clinical applications and complications are very much similar to that of the argon laser and copper vapour laser. 5. LASERS FOR TREATING PIGMENTED LESIONS AND TATTOOS (Table 4) The concept of selective photothermolysis has revolutionized the role of the laser in cutaneous surgery. This has led to the development of laser systems which are now increasingly employed in the treatment of pigmented lesions and tattoos. These are the Q-switched Nd-YAG laser, the Q-switched ruby laser, the 510 nm pulsed dye laser and the Alexandrite crystal laser. Melanin and tattoo pigment are the main chromophores and are rapidly heated leading to fragmentation into small particles. Some of these small particles are removed by phagocytosis, whereas some of the epidermal pigments are removed transepidermally. As phagocytosis is an important means of pigment removal, an interval is of at least three weeks is necessary before accurate evaluation can be made. Further lightening of lesions results from a change in the optical properties of the pigment following fragmentation 5.1. Q-switched Neodymium:Yttrium-Aluminum-Garnet (Nd-YAG) Laser This system uses a YAG crystal doped with 1-3% neodymium ions as the active medium and is powered by a high intensity flashlamp. This leads to the generation of laser with a wavelength in the invisible infrared portion of the spectrum (1 064 nm). This light beam is poorly absorbed by melanin, haemoglobin and water but well absorbed by blue-black exogenous pigment. The laser can therefore penetrate up to 1 cm into the skin with minimal epidermal damage. The nonselectivity of continuous wave Nd-YAG laser has led to the frequent development of adverse effects that include scarring and pigmentary changes. By modifying the system with Q-switching, selective photothermolysis of exogenous blue-black pigment can be achieved. At this wavelength, a spot size of 2 mm with energy level between 510 J/cm2 is often used. By using a potassium titanyl phosphate crystal, the wavelength of Q-switched Nd-YAG laser can be halved to 532 nm (green). At this wavelength the beam is well absorbed by red, orange and purple ink. These pigments usually respond poorly to treatment by the Q-switched ruby laser. As melanin also absorbs light
of this wavelength, this system has been used successfully for the treatment of benign epidermal lesions. The fluence used is usually around 2-4 J/cm2 with a spot size of 2 mm. Safety procedures for Nd-YAG laser are similar to those for the carbon dioxide laser except eye protection. Nd-YAG laser penetrates the clear goggles that are used for the eye protection for CO2 laser. Polycarbonated safety glasses are necessary to prevent corneal and retinal damage. The main complications seen in the use of Qswitched Nd-YAG laser are pigmentary changes. These occur more frequently in the use of 532 nm laser as the 1064 nm wavelength penetrates deeper and is poorly absorbed by melanin. Sun protection like the use of sunscreens is a helpful measure. As the response varies between individuals, treatment of a test area is advisable. Scarring can also rarely occur and tends to be associated with scratching to, or trauma at the lesion postoperatively. 5.2. Q-switched Ruby Laser Since the development of the carbon dioxide and argon laser, the role of ruby laser in dermatology has diminished substantially. By modifying the system with the Q-switched device, the ruby laser has re-established itself as an important tool for the treatment of pigmented lesions. The beam has a wavelength of 694 nm and is actively absorbed by melanin, blue-black and green pigment. Spot diameters of 4-8 mm and fluences that range from 4-12 J/cm2 can be used. For amateur tattoos, 4-6 treatment sessions are needed whereas professional tattoos may require 8-10 and occasionally even 20 treatment sessions. The Q-switched ruby laser is effective for the removal of blue and blue-black inks. Occasionally green and brown pigment may also respond to Q-switched ruby. Whitening of the lesions often occurs immediately after laser treatment and lasts about 20 minutes, this represents epidermal and dermal vacuolisation secondary to thermal induced steam formation. Gradual fading of the lesions, over a 5-6 week period, may then follow. In general, lower energy levels (4-7 J/cm2) and less treatment sessions (1-2 sessions) are needed for the treatment of benign pigmented lesions. In patients who do not respond to Q-switched ruby laser, other laser such as the Q-switched Nd-YAG laser can be tried. Safety guidelines are essentially the same as for carbon dioxide laser and Q-switched Nd-YAG laser. Purpura and even punctate bleeding can occur at the treatment site if high energy intensity is used. Other complications are similar to those seen with the Q-switched 532 nm
Nd-YAG laser. Transient texture change is not unusual and usually resolves after 6-8 weeks. Pigmentary change, usually hypopigmentation, can occur in up to 50% of the patients. The majority of these patients recover completely within 6 months of their treatment, although permanent hypopigmentation can occur. Darkening after cosmetic tattoo treatment may also be seen. Scarring is rare and is associated with trauma or infection. 5.3. Alexandrite Laser This is the third Q-switched laser system designed for the treatment of tattoos. It has a wavelength of 755 nm and a pulse duration of 100 ns. A spot diameter of 3 mm is usually used with fluences that range from 4-8 J/cm2. The beam is well absorbed by blue, black and green pigment, but absorbed poorly by red ink. The wavelength of this system enables deep penetration and allows the removal of pigments in the dermis. Smaller, superficial and recent tattoos are likely to respond quicker to the Alexandrite laser. Unlike the other Q-switched laser systems, tissue splattering does not occur with the Alexandrite laser. This is likely to be due to the differences in power density of the three systems. Although the fluences are similar, the wider pulse duration of the Alexandrite system means that it has the lowest surface power density (160 mw/cm2 as compared to 400 mw/cm2 with the Q-switched ruby laser, and 1,000 mw/cm2 with the Q-switched Nd-YAG laser). This is important as tissue and blood splattering carry the potential risk of disease transmission such as HIV and hepatitis B. Immediate whitening also occurs in the use of the Alexandrite laser. The use of higher energy levels can cause purpura and punctuate bleeding. Others complications are similar to those seen in Q-switched ruby laser. 5.4. 510 nm Pulsed Dye, Argon, Copper Vapour, Krypton Lasers The low degree of penetration of these lasers result in poor efficacy except for superficial pigmented lesions. They are mainly used in the treatment of freckles, lentigines, seborrhoeic keratosis and melanocytic naevi. The result in treating naevus of Ota, chloasma or other dermal pigmented disorders are poor. The 510 nm pulsed dye laser is however effective in the removal of tattoos containing red, purple, yellow and orange pigment. 6. LASER THERAPY IN SOCIAL HYGIENE SERVICE
Laser therapy had been started in Social Hygiene Service since this form of hi-tech treatment had been introduced to the field of dermatology in Hong Kong. However, due to the constringency of resource, there are only two laser machines available in the service, leading to a lot of limitations in the treatment. At the moment, copper vapour laser is available in Yung Fung Shee Dermatological Clinic while krypton laser in Yaumatei Dermatological Clinic. (Table 5) These two laser machines are able to emit yellow light and green light, thus they can be used to treat a variety of vascular and epidermal pigmented lesions. They are good in treating telangiectasia and purplish-dark hypertrophied portwine stain in adult. However they are not suitable to treat the portwine stain in children because of the relatively high incidence of scarring. They are also ineffective in treating dermal pigmented lesions, such as naevus of Ota, chloasma and tattoo. Both these two machines in Social Hygiene Service are mainly manual-driven, therefore the treatment depends much on the experience of the operators. Good judgment of treatment endpoints are important in order to achieve good result. (Table 6) The power and the spot size of the handpiece of these two machines are relatively small, hence it is very time consuming in treating large area of lesions like portwine stain. Laser therapy has been promoted and in fact has been proven as an effective treatment modality in a lot of dermatological conditions. However, they are not without risks and their end results are variable in individual patient. Before starting the treatment, the operator needs to consider carefully about the indications and the possible risks. (Table 7) One should be very cautious in dealing with patients who have keloid tendency, who are prone to post-inflammatory pigmentary changes and who are demanding persons. Cerain areas are considered as "dangerous areas" where scarring is more likely to occur, such as angle of jaws, mandibular area, presternal area, shoulders and upper arms. Risks and limitations of various forms of therapy should be fully explained to the patients, so that they will have psychological preparation and will not have over-expectation before the treatment. Precautions that should be taken by the trained operators and nurses during the laser therapy (Table 8, 9), as these are important to the safety of both medical personnel and patients. Clinical photograph with good quality should be taken before and after the treatments for
comparison and documentation. Finally, full explanation about the after-care should be given to patients in detail in order to minimized the complications. (Table 10) Table 1: Classification of Laser Machines Carbon dioxide 10,600 nm Infrared Argon 488, 514 nm blue-green Organic dye (rhodamine, 504 nm green fluorescein, coumarin, acridine red) (400-1,000 nm) 577, 585 nm yellow Copper vapour, 511 nm green copper bromide 578 nm yellow Krypton 521, 530 nm green 568 nm yellow Neodymium:YAG (yttrium-aluminum-garnet) 1064 nm infrared KTP (potassium-titanyl -phosphate) (double frequency YAG) 532 nm green Ruby 694 nm red Alexandrite 755 nm red ¡@ Table 2: Clinical Applications of the Carbon Dioxide Laser Lesions where the CO2 laser is potentially the treatment of choice: Actinic cheilitis, bowenoid papulosis, cutaneous resurfacing procedures, epidermal nevus, rhinophyma, sublingual keratosis Lesions where the use of CO2 laser may offer better results or facilitate the procedure: Tumours: squamous cell carcinoma in-situ, superficial multifocal basal cell carcinoma, neurfibromas, giant trichoepitheliomas, seborrheic keratosis, syringomas, xanthelasma. Infection: extensive or large condyloma acuminatum, verruca vulgaris, recalcitrant wart, debridement of burns or infected ulcer, cutaneous infection such as leishmaniasis. Vascular: adenoma sebaceum, cherry angioma, lymphangioma circumscriptum, angiokeraomas, pyogenic granulomas, granuloma faciale.
Other: cosmetic excisional surgery, lichen planus of the penis, HaileyHailey disease, chondrodermatitis nodularis helicis chronicus, oral florid papillomatosis, xanthelasma Lesions that better results can now be achieved using newer lasers: Cafe-au-lait spots, ephelides, labial lentigines, lentigines, port wine stain, tattoos, telangiectasia Table 3: Lasers Used in the Treatment of Vascular Lesions Characteristics: ¡@ Active medium Power source Wavelength (nm) Pulse duration Spot size (mm) Depth of penetration at 50% (um) Skin Chromophores Argon Argon gas Electric current 488, 514 0.2-20 s 0.2-5 200-300 Blood, melanin Pulsed dye Orange dye Copper vapour Copper metal + neon gas
Flashlamp Electric current 577, 585 400-500 us 2-7 400, 600 Blood, melanin 511, 578 20 ns 0.1-1.0 300-400
Clinical Applications: Portwine stain , telangiectasias, cherry angioma, rosacea, pyogenic granuloma, spider naevi, venous lake, angiofibroma, angiokeratoma, lymphangioma
Table 4: Lasers Used in the Treatment of Pigmented Lesions and Tattoos Characteristics: ¡@ Q-NdQ-Ruby Q-Alex Pulsed YAG dye Wavelength (nm) Pulse duration (ns) Peak power (mW/cm2) at fluence 2 J/cm2 4 J/cm2 8 J/cm2 10 J/cm2 800 1,000 Spot diameter (mm) 2 400 500 4-8 160 200 3 1,300 3 300 532, 1,064 10-20 694 20-40 755 50-100 510 100-500
Depth of penetration 400/1,600 1,200 at 50% (um) Skin chromophores
Melanin, Melanin Melanin, Melanin blood blood Clinical Applications: Freckle, lentigo, melanocytic naevus, seborrhoeic keratosis, cafe-aulait, mucosal melanosis, naevus of Ota, melasma, Mongolian?/FONT>s spot, tattoo QS: Q-switched, Alex: Alexdandrite, Nd-YAG: Neodymium: YttriumAluminum-Garnet ¡@ Table 5: Laser Machines Available in SHS Copper Vapour Dermatological Laser System in YFS Dermatology Clinic (Visiray-VisErase VCM-03) Specifications: Green (511 nm): 0.9 W (at 0.4 mm spot size) Yellow (578 nm): 0.7 W (at 0.4 mm spot size)
Spot Size: 0.1 mm, 0.15 mm, 0.4 mm, 0.8 mm Focused beam Exposure Modes: Continuous, Pulse Air cooled Krypton Dermatological Laser System in YMT Dermatology Clinic (HGM-SURGICA K1) Specifications: Green (520-530 nm): 2.0 W (at 1.0 mm spot size) Yellow (568-575 nm): 1.0 W (at 1.0 mm spot size) Spot Size: 0.1 mm, 1.0 mm Collimated beam Exposure Modes: Continuous, Pulse Internal water cooled Table 6: Operating Techniques Method: Tracing with the handpiece (for example: telangiectasia) Painting with the handpiece (for example: portwine stain) Recommended starting power and spot size (use the minimal power as possible): VisErase VCM-03 - 0.4 W with 0.4 mm spot size (Continuous wave) SURGICA K1 - 0.7 W, 0.20 seconds pulse duration, with 1 mm spot size (Pulsed) Treatment endpoint: Tissue Temperature Tissue change Clinical observation 50 degree C Protein denatured Blanching (whitening) 100 degree C Water vaporized Shrinkage (greying) 100-150 degree C Tissue carbonized Charring (Blacking) > 175 degree C All vaporized Smoky plume,Blubbling sound Reduced in volume Level reached Clinical observation Epidermis Grey Papillary dermis Pink (superficial dermal capillaries) Reticular dermis White with yellow spots (sebaceous glands) Table 7: Complications & Hazards of Laser Possible complications of laser therapy: 1) Immediate erythema, oedema, pain, exudation, purpura 2) Secondary infection
3) Pigmentary changes: hyperpigmentation, hypopigmentation 4) Textural changes, atrophy 5) Scarring, keloid Potential Hazards of Laser Machine: 1) Hazard to eye Retina, especially macula: permanent visual loss (Suitable protective eye goggles, eye-shields) 2) Hazard to skin Severe burns & scarring (Training & experience) 3) Electrical hazard High voltage: life threatening (Strictly follow the safety precautions) 4) Hazards from fumes & vaporized tissues HPV, HIV (Fume evacuator, good ventilation, mask) Table 8: Precautions in Laser Therapy 1) ALWAYS wear safety goggles with recommended filters whenever the laser is in use. Operator's goggles: VisErase VCM-03 - Green: Orange filter - Yellow: Grey filter SURGICA K1 - Green/Yellow: Green filter Patient's goggles: Red filter 2) ALWAYS lock the door of the room during treatment. 3) NEVER look directly into the laser beam; or at scattered or reflected laser light. 4) NEVER point the laser handpiece at any person except at the treated area. 5) NEVER remove any covers from the cabinet of the machine and attempt to repair. 6) NEVER use the laser in the presence of flammable anaesthetics. 7) NEVER step on or abruptly bend the fibre-optic cable. 8) NEVER move the laser machine during operation or within 30 minutes of turning off for VisErase VCM-03. 9) Do NOT turn off the machine immediately after treatment. Wait for 30 minutes for VisErase VCM-03 and 5 minutes for SURGICA K1. 10) Do NOT turn off the main electrical switch.
Table 9: Procedures that must be Taken by Nursing Staff Before treatment: 1) Turn on the laser machine for warm up 40 minutes for VisErase VCM-03 45 seconds for SURGICA K1 2) Written consent after explanation of the procedures 3) Take clinical photograph 4) Ensure the patient having eye-protection 5) Prepare local anaesthetics if necessary Lignocaine (without adrenaline) Emla cream (1 hour before treatment with Tegederm occlusion) Novesin eyedrop if eye-shields are necessary 6) Lock the door and turn on the warning lamp During treatment: 1) Ensure that the patient has eye-protection all the time 2) Measure the treatment time 3) Plume suction if necessary After treatment: 1) Apply antiseptic cream (silver sulphadiazine, fucidin) or emollient (aqueous cream) for the patient 2) Arrange follow-up appointment 3) In between treatment, keep the machine at Standby mode for SURGICA K1 4) After treatment for all patients, wait for 30 minutes for VisErase VCM-03 and 5 minutes for SURGICA K1 before turn off the machine Table 10: Aftercare Following Laser Treatment 1) Expect a sunburn-like reaction with possible blistering within the first 24-48 hours. Pain is usually minimal and can be relieved with either Panadol and/or cool soaks with a wash cloth. 2) A crust or scab may occur and should last for 7-14 days. Do not pick off the scab!! Just let it fall off at its own pace. 3) Keep the area clean and dry until the scab/crust falls off. Wash gently with soap and water and apply a thin layer of moisturizer or antibiotic ointment. 4) Once the scab/crust has come off the area may look pink and even slightly depressed or indented. Both the pinkness and depression should improve over the next several weeks to months. 5) Avoid direct sunlight or sun exposure to the treated areas for 3-6 months. Use at least an SPF of 15 or greater sunscreen, or wear a hat or other protective clothing (preferably both). Be aware that
unprotected sun exposure can result in an uneven repigmentation, producing brown spots that can take months to fade away and in rare cases may be permanent. 6) Be patient!! It may take up to three months to adequately judge the true response of your condition to the laser treatment. DON'T HESITATE TO CALL IF YOU HAVE ANY QUESTIONS OR PROBLEMS!!
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