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HAIR DISORDERS

HAIR LOSS (ALOPECIA)

Hair loss can be diffuse or focal and may not be associated with any underlying inflammation or scarring. Androgenic alopecia is common in men (in whom the incidence approaches 100% in Caucasians) but also occurs in women. The pattern of hair loss includes frontal recession and thinning over the vertex, with more diffuse loss commoner in women. The extent and rate of hair loss are related to undefined genetic and hormonal factors.
Alopecia areata is a common cause of focal hair loss (2.96), characterized by many short exclamation mark hairs at the edges of the lesion. The underlying pathogenesis is a chronic inflammatory process triggered by a variety of environmental factors (e.g. infection) and probably represents a type of organspecific autoimmune disease. Regrowth usually occurs within weeks or months, but further episodes may occur. Alopecia totalis (2.97) and loss of all body hair (alopecia universalis) can occur, and associated fine pitting of the nails may be seen. A family history of alopecia areata occurs in up to 20% of cases and a family or personal history of atopy or other autoimmune disorders may also be present.
Fungal infection of the scalp causes patchy hair loss (2.60). If significantly inflammed, the lesion is called a kerion. Regrowth is usually good but permanent scarring may result from extensive inflammation.
Traction alopecia results from repeated tension on the hairs, as in some Afro-Caribbean and Asian hair styles (2.98).
Trichotillomania is patchy hair loss due to rubbing or pulling, commonly in childhood; hairs are broken off close to the surface.
Scarring alopecia may result from inflammatory dermatoses, such as lichen planus (2.71), discoid lupus erythematosus or scleroderma, and from trauma, burns or irradiation.
Diffuse hair loss after pregnancy, severe febrile illnesses or operations is termed telogen effluvium (loss in telogen growth phase). Cytotoxic drugs such as cyclophosphamide cause anagen effluvium. Iron-deficiency anaemia, hypothyroidism or hyperthyroidism, systemic lupus erythematosus and drugs such as heparin, vitamin A derivatives (retinoids) and oral contraceptives may cause hair loss.

2.96 Severe alopecia areata in a 24-year-old woman. There are no features to suggest infection of the scalp.

2.97 Alopecia totalis developed from severe alopecia areata in this patient. A similar appearance may result from the use of some cytotoxic
chemotherapy for malignant disease.
2.98 Traction alopecia has resulted from the combing involved in maintaining an 'Afro' hairstyle in this patient.

EXCESSIVE HAIR

Hirsutes is an excess of terminal hair growth in a male pattern distribution in women (2.99, 7.58, 7.59). Mild facial hirsutes is common, increasing after the menopause. In younger women, especially when associated with menstrual irregularity or with other signs of virilization, investigations to exclude conditions such as polycystic ovaries, ovarian tumours, virilizing adrenal tumours or Cushing's syndrome and congenital adrenal hyperplasia (heterozygote form) should be considered.
Hypertrichosis, a localized or overall increase in hair, may be drug induced, as with minoxidil, corticosteroids, diazoxide (2.100) or phenytoin, or associated with gross malnutrition, anorexia nervosa or some variants of porphyria. Localized hypertrichosis occurs with some pigmented naevi and in the himbosacral region in association with diastematomyelia (11.115).

2.99 Hirsutism was the presenting symptom in this woman who was found to have an arrhenoblastoma.

2.100 Gross hypertrichosis in a 32-year-old woman who was being treated with minoxidil for severe renal hypertension. Topical minoxidil is now used as a treatment for baldness in some countries.

NAIL DISORDERS

Inherited abnormalities of nails are present in some genodermatoses, such as nail-patella syndrome, pachyonychia congenita (caused by a mutation in keratin K6, K16 or K17 genes) and ectodermal dysplasias. In these conditions often all finger nails and toe nails are affected (20-nail dystrophy). Scarring of nails occurs in some forms of epidermolysis bullosa dystrophica (2.80). Subungual exostoses cause overlying nail dystrophy.

Acute or chronic trauma may cause subungual splinter haemorrhages (3.33) or haematomas, gross thickening of the nail (onychogryphosis) or onycholysis of individual nails. Habit tic nail dystrophy of thumb nails and bitten nails, with damaged cuticles are common.
Yellow nails (2.101) are seen with chronic lymphoedema and in some chronic lung diseases. Other colour changes include leuconychia in liver disease (2.102), half-and-half nails in renal disease, and changes with some drugs such as antimalarials or tetracyclines.
Koilonychia is seen in iron-deficiency anaemia (2.103, 10.6, 10.21). Clubbing of nails (2.59, 2.104, 2.105, 4.2, 4.101, 4.148, 5.5,11.121) is associated with cyanotic heart disease, carcinoma of the bronchus, some chronic lung diseases and some chronicgastrointestinal diseases; alternatively it may be congenital. Beau's lines are horizontal grooves that appear on all nails after severe illness. Splinter haemorrhages may be seen in vasculitis in association with connective tissue diseases (3.33) or in bacterial endocarditis. Onycholysis (2.19, 2.59, 2.62) may be drug induced, due to fungal infection, psoriasis or associated with hyperthyroidism. Median nail dystrophy occurs without skin changes and the cause is unknown. Peripheral vascular disease predisposes to chronic paronychia (2.59, 2.62). Changes occur in dermatological conditions such as psoriasis (2.19), dermatitis, lichen planus, fungal (2.59) and yeast (2.62) infections and alopecia areata. Tumours may develop under or around the nail base, including malignant melanoma (2.106), glomus tumours and myxoid cysts.

2.101 Yellow nail syndrome is a disorder in which there is progressive yellowing and thickening of the nails with absence of the lunula and a degree of onycholysis. There is often an association with chronic lung disease and peripheral lymphoedema.

2.102 Leuconychia (opaque white nails) are a marker of chronic liver disease and of other conditions in which the serum albumin is low, such as nephrotic syndrome. In this patient, marked ridging of the nails is also present.

2.104 Gross clubbing of the nails in a 72-year-old man with carcinoma of the bronchus. Note the so-called 'nicotine sign'staining of the index and middle finger by tar from his heavy cigarette smoking.

2.105 Gross clubbing of the nail. Note the filling-in of the nail fold, the increased curvature of the nail in both directions, giving a 'beaked' appearance, and the increased volume of the finger pulp.

2.106 Subungual melanoma. A persistent dark lesion below a nail should be biopsied, as this is a common site for malignant melanoma.

SKIN TUMOURS

Skin tumours are common and may originate from the epidermis, melanocytes or any of the dermal components. Early detection of malignant tumours is vital

COMMON BENIGN TUMOURS

Seborrhoeic keratoses or basal cell papillomas occur in the middle years, mainly on the trunk and face, with a roughened warty, greasy surface and a superficial, stuck-on appearance (2.107). Lesions may be multiple, sometimes heavily pigmented, and they can be traumatized. They are commonly misdiagnosed as malignant melamonas.
Skin tags are simple papillomas that occur round the neck and in body folds (2.108).

Milia are common on the face or at the site of healed blisters (2.109). They are superficial cysts of sweat ducts. Keratoacanthoma (2.110) is a rapidly growing ulcerating tumour, more common in middle-aged or elderly subjects. It should resolve spontaneously, within 9 months. Clinical distinction from a squamous cell carcinoma can be impossible. If the history is uncertain, biopsy is essential.
Cavernous haemangiomata (2.111) appear at or soon after birth. Single or multiple lesions, of varying size, occur at any site. Ulceration and trauma with haemorrhage can occur but lesions are best left to regress spontaneously unless causing obstruction to vision.
Capillary haemangiomata (port-wine stains) are present at birth and do not fade with age. Cosmetic camouflage or laser treatment may be neded . Unilateral facial hemangioma may be assiciated with cerebral haemangiomata in the Sturge-Weber syndrome (11.129).

Pyogenic granulomas grow rapidly, tend to occur at sites of trauma, may be single or multiple and can recur. Dermatofibromas (2.112) are more common in women, often pigmented, may be multiple and generally occur on limbs. Keloids are persisting areas of exhuberant scar tissue. Certain body sites, individuals and races are predisposed to this reaction. Neurofibromata may be solitary or multiple and associated with cafe-au-lait patches in type I neurofibromatosis (2.86 and see p. 514). Adenoma sebaceum is associated with tuberous sclerosis (11.132)

2.107 Seborrhoeic keratosis (seborrhoeic wart). These benign lesions are increasingly common with age, and they appear predominantly on unexposed Caucasian skin.

2.108 Skin tags in the axilla. These are small benign papillomas.

2.109 Milia on the eyelid. These are harmless, superficial, keratin-filled cysts, which are usually found on the face. In this location, it is important not to confuse these with xanthelasmas (see p. 340).

2.110 Keratoacanthoma on the neck. This ulcerating tumour, with a central keratin plug, grows rapidly but resolves spontaneously. Biopsy may be necessary to exclude a malignant lesion.

2.111 Cavernous haemangioma. 'Strawberry naevi' appear early in life and enlarge progressively. Parents can be reassured that most will resolve spontaneously before puberty.

2.112 Dermatofibroma on the thigh. The lesion is raised, pink and firm, and is surrounded by a halo of hyperpigmentation. These benign lesions are often multiple on the legs and thighs in middle-aged women.

MELANOCYTIC TUMOURS

Congenital melanocytic naevi (moles) appear during the first few years of life. Most people have 20-30; some have many more. The common mole should be uniformly pigmented, with a regular margin (2.113-2.115). A halo of pale skin around a mole may be seen in adolescence. Occasionally congenital moles are large (greater than 1 cm; 2.116), multiple or confluent (bathing trunk pattern). These lesions carry a risk of malignant transformation. Moles deeper in the dermis appear blue in colour (2.117). Moles tend to regress in old age.
If moles change in size, become irregular in shape or pigmentation, itch or bleed they should be regarded as unstable and potentially malignant. Sunburn can irritate and activate moles. During pregnancy, moles tend to increase in size and darken.
Malignant melanomas (2.106, 2.118, 2.119) arise de novo or from pre-existing moles. The incidence of this tumour is increasing, especially in fair-skinned people with high sunexposure. The prognosis is much better if tumours are detected early. Melanoma may develop after some years in a lentigo lesion (2.120). Amelanotic melanomas may be missed, especially in periungual sites. Malignant melanomas may occur in the eye (2.121).

2.113-2.115 Benign melanocytic naevi (moles), showing a range of normal appearances. Pigmentation is even, but may vary from pale (2.113) to dark brown (2.115). There is no hint of malignant change in 2.113. The irregular margin in the lesion seen in 2.114 aroused sufficient suspicion for the lesion to be biopsied Despite the slightly irregular margin, the mole in 2.115 is almost certainly benign; but, if it were to change in shape, pigmentation or size, or if it were to bleed, biopsy would be necessary.

2.116 A large congenital pigmented melanocytic naevus. Note that hairs can grow in melanomas. Large lesions like this should be carefully observed for malignant change.

2.117 A group of blue naevi on the arm. These lesions are usually benign.

2.118 Malignant melanoma. Note the superficial spread in the skin and the varying level of pigmentation. The lesion had also bled. Prognosis depends on the depth of invasion of the tumour in the skin.

2.119 Malignant melanoma on the hand. The centre of the tumour is now amelanotic, but the local invasion remains pigmented and the patient has widespread secondary deposits.

NONEPITHELIAL MALIGNANT TUMOURS

Secondary tumour deposits may occur in the skin. Common tumours that metastasize to the skin include breast (in addition to Paget's disease of the nipple), stomach, bronchus (2.122, 4.178) and kidney. Hodgkin's disease and B-cell lymphomas may have skin lesions (10.92).
Mycosis fungoides is a cutaneous T-cell lymphoma. It commonly manifests itself as a patchy superficial dermatitis (2.123) that evolves slowly into plaques and tumours.
Kaposi's sarcoma is another important skin tumour. Formerly rare outside Africa, it has now become a common complication of HIV infection, especially in homosexual men (see p.16).

2.120 Malignant lentigo. Lentigo is a flat, dark brown lesion on the cheek of an elderly person. It should be regarded as a melonoma-in-situ, and may become frankly malignant, as here.

2.121 A large choroidal malignant melanoma, revealed by ophthalmoscopy. Malignant melanomas may also occur in the iris and conjunctiva. This tumour was treated by enucleation of the eye.

2.122 Skin secondaries, in this case in the scalp from a primary carcinoma of the bronchus. Such lesions are relatively uncommon.

2.123 Mycosis fungoides. The individual lesions grow slowly over a period of years. They are red, thickened plaques, often with fine scales, which are itchy and may later ulcerate.

2.124 Solar keratoses - small, firm and scaly plaques-are commonly found on the extensor aspects of the hands and other exposed areas of skin in elderly people.

2.125 Solar keratosis. These lesions occur after long exposure to sunlight and are potentially malignant, with a latent period of at least 10 years.

PREMALIGNANT AND MALIGNANT EPITHELIAL TUMOURS

Solar keratoses (2.124, 2.125) occur on sun-exposed sites as patches of erythema and scale that gradually thicken. The adjacent skin shows signs of sun damage with wrinkling and loss of elasticity. Common sites are the face, ears and backs of hands. Malignant change occurs in a minority of lesions. Keratoses on the ears must be distinguished from chondrodermatitis nodularis helicis chronica, which is characteristically painful on pressure and almost always unilateral
Bowen's disease (2.126) appears as persistent erythematous slightly scaly patches, which gradually enlarge. The surface is usually flattened and occasionally ulcerates. Patches may be multiple and occur anywhere on the body, especially on lower legs.

Leucoplalcia (2.127) occurs as persistent white patches on mucous membranes, in the mouth or vulva, and may be an indication of underlying dysplasia.
Basal cell carcinomas are slow growing, locally invasive malignant tumours (2.128, 2.129). A pearly margin, telangiectatic vessels and central recurrent ulceration are typical, but variations such as multifocal, pigmented and morphoeic lesions may occur. Basal cell carcinomas are especially common on the head and neck, but can occur on anywhere on the body.
Squamous cell carcinomas tend to occur on sun-exposed sites (2.130), but also in areas of chronic scarring or inflammation. Metastases occur more frequently from lesions at mucous membrane junctions such as on the lip.

2.126 Bowen's disease - a persistent brownish patch that slowly enlarges and may become malignant. A carcinoma may develop under the crust or as a nodule, as here.

2.127 Leucoplakia may take several forms, all involving white patches on mucous membranes. In speckled leucoplakia, white areas alternate with areas of atrophic red epithelium. The risk of malignant transformation is high.

2.128 Multiple basal cell carcinomas. The lesion on the bridge of the nose is
typical of the common presentation as a slowly enlarging nodule. The other lesions demonstrate various stages of progression to ulcerated lesions (rodent ulcers).

2.129 Basal cell carcinoma ulcerates at a later stage, usually with a shallow
ulcer, with a very narrow indurated edge and a smooth shallow base.edge of nose

2.130 Squamous cell carcinoma begins as a small nodule, but slowly grows to produce the typical lesion seen here. The ulcer has thick edges and an irregular granular base; and it usually produces a serous discharge.

VASCULITIS AND CONNECTIVE TISSUE DISORDERS

Vasculitis implies the presence of inflammation within blood vessel walls, with resultant vessel damage, haemorrhage or infarction. The clinical expression of this process depends on the size of vessel involved, from capillaries to small muscular or larger arteries. Circulating factors may initiate the inflammation (immune complexes, cryoglobulins); the vessel damage ranges from endothelial cell swelling to fibrinoid necrosis of the vessel wall or a granulomatous response (as in Wegener's granuloma). The inflammatory infiltrate may involve polymorphonuclear leucocytes or lymphocytes. Skin lesions of vasculitis tend to be purpuric and palpable, may ulcerate and are painful (2.131, 2.132).
Conditions in which vasculitis is the predominant feature include Henoch-Schonlein purpura (2.133; small vessel vasculitis, with purpura, arthritis and glomerulonephritis-see also pp. 290, 460) and polyarteritis nodosa (see pp. 144, 292). Vasculitis may be a feature of other connective tissue disorders, such as systemic lupus erythematosus, drug reactions, malignant disease or infections.

Discoid lupus erythematosus (DLE) manifests itself as chronic plaques, commonly on face, scalp or ears (2.134), with erythema, scaling and follicular plugging. Lesions persist, with scarring and depigmentation, but systemic features are absent.
Systemic lupus erythematosus (SLE) may present with an acute facial rash, of butterfly distribution (3.76, 3.77), often photoaggravated (3.78). Vasculitis may occur (2.132). Other features of systemic lupus erythematosus are described on p. 139.
Rheumatoid arthritis may be associated with vasculitis (2.131) and subcutaneous nodules. It may also be accompanied by pyoderma gangrenosum, a destructive, necrotic ulcerative process that may destroy large areas of skin (2.135). Pyoderma gangrenosum may also complicate other diseases, especially ulcerative colitis, Crohn's disease, myelofibrosis and multiple myeloma.
Systemic sclerosis has several skin manifestations (see p.141).

Morphoea is localized plaques of dermal sclerosis, often pigmented, that appear without other underlying disease. Scarring occurs in the skin (2.136) and may affect adjacent bone, but the condition usually clears spontaneously.
Dermatomyositis commonly occurs with skin features (3.89, 3.90), as may other connective tissue disorders, including relapsing polychrondritis (3.95), Reiter's syndrome {3:58-3.60) and Behcet's syndrome (3.102-3.105).

2.131 Leucocytoclast ic vasculitis. This 57-year-old woman with rheumatoid arthritis developed widespread, painful, palpable purpura on both legs. Initially, the lesions were scattered and discrete, but in this picture some have coalesced and become necrotic in the centre. Leucocytoclastic vasculitis is also known as allergic or hypersensitivity vasculitis or anaphylactoid purpura and it has many possible causes. The lesions result from the deposition of immune complexes in the postcapillary venules.

2.132 Livedo vasculitis in a 23-year-old Asian woman with systemic lupus erythematosus. The characteristic livedo or reticular
appearance reflects the occurrence of small vessel vasculitis at a deeper level of the skin than in leucocytoclastic vasculitis.

2.133 Henoch-Schonlein purpura, associated with swellinq of the left knee and renal involvement in a child aged 4 years. The rash was also present on the back of the legs and the buttocks.

2.134 Discoid lupus erythematosus. Slowly enlarging recalcitrant pink scaly plaques are seen on the face, ears and scalp. The lesions are aggravated by sunlight, and they clear centrally with atrophy and scarring.

2.135 Pyoderma gangrenosum. This West Indian man developed a pustule over the lower leg that progressed to a tender, superficial necrotic ulcer. Note the typical purple undermined edge. The lesion persisted for months and partially responded to topical corticosteroids and minocycline. Eventually, 0 responded to systemic corticosteroids. Pyodernna gangrenosum is usually suggestive of underlying systemic disease, but none was found in this patient

2.136 Morphoea 'en coup de sabre' (resembling the scar from a sabre cut). This form of localized morphoea can involve subcutaneous tissues and even bone. It is a variant of linear morphoea and, if the scalp is involved, can be associated with scarring and subsequent hair loss. Despite the severe local involvement, systemic sclerosis is not seen in this condition.

2.137 Granuloma annulare on the finger. Note the ring of fleshcoloured papules. This condition may occur in otherwise healthy individuals or in patients with diabetes.

OTHER MULTISYSTEM DISORDERS

THE SKIN IN OTHER MULTISYSTEM DISORDERS

A number of other multisystem disorders have cutaneous manifestations or complications. These can be important clues for establishing a diagnosis and should be sought carefully.
Many systemic infections have skin manifestations (see Chapter 1), and a broad range of skin complications has been noted in HIV infection and AIDS (1.34).
Diabetes may be associated with a number of skin conditions, including acanthosis nigricans (2.90), staphylococcal (1.99, 2.50) and candidal infection (2.61, 2.62), gangrene (7.104) and trophic changes, such as ulcers, especially in the skin of the legs. Two specific, and probably related, conditions are seen in diabetics, though they may also occur in nondiabetic patients.
Granuloma annulare occurs as groups of flesh-coloured papules in rings or crescents, most commonly on the extensor surfaces of the hands and fingers (2.137)
Necrobiosis lipoidica occurs as erythematous plaques over the shins (2.138). These gradually develop a waxy appearance and brown pigmentation. Care is needed to prevent skin breakdown and ulceration.

Xanthomas may be the first indication of underlying hyperlipidaemia, either primary or secondary to underlying disorders such as diabetes or renal disease (see pp. 340).
Generalized pruritus is a common presentation to the dermatologist. There may be a dermatological explanation for the itch, such as scabies, but, more often, especially in the elderly, no abnormality is detected in the skin, except scratch marks. Pruritus may be the first presentation of a wide range of conditions, including drug reactions, liver disease such as primary biliary cirrhosis (9.49, 9.50), chronic renal failure, haematological conditions such as anaemia or polycythaemia, hyperthyroidism or hypothyroidism, diabetes or malignant disease such as Hodgkin's disease, and needs careful investigation.
Sarcoidosis has several skin manifestations, some of which, such as lupus pernio, are diagnostic of the condition

2.138 Necrobiosis lipoidica in a 50-yearold woman with diabetes. Note the surface scaling and scarring. Ulceration may occur in more advanced and extensive lesions. Necrobiosis lipoidica is usually a complication of diabetes.

PHOTODERMATOSES

Many skin conditions are affected by ultraviolet radiation, either positively, as when it is used as a therapeutic agent, or adversely as the cause or an exacerbating factor of a rash. Within the ultraviolet radiation spectrum, the ultraviolet A and ultraviolet B wavebands are the most significant, as ultraviolet C is mainly absorbed within the atmosphere. Although most ultraviolet radiation comes from the sun, the use of sunbeds as artificial sunlight has resulted in a rising incidence of ultraviolet-induced disorders.
The wide range of photodermatoses is summarized in 2.139.

Idiopathic photodermatoses should be distinguished from other dermatoses aggravated by ultraviolet radiation or the reactions of normal skin to ultraviolet radiation damage (such as inflammation, tanning, thickening of the epidermis and suppression of local cell-mediated immunity).

Polymorphic light eruption is a common disorder affecting 10-20% of the population, predominantly females. It is generally worse in spring and early summer. The rash develops within a few hours of sun exposure as itchy erythematous papules, plaques or vesicles on exposed sites (2.140).
Chronic actinic dermatitis (also known as photodermatitis or actinic reticuloid) is a rare disorder that usually presents in older men, as a severe chronic dermatitis of exposed sites (2.141), often in association with multiple contact allergies. Other rare photodermatoses include solar urticaria, in which urticarial weals appear within minutes of sun exposure and resolve within 1-2 hours, hydroa vacciniforme, a painful vesicular rash on the face, and actinic prurigo, a persistent itchy papular or nodular eruption on exposed sites; the latter two are more common in children.
Many dermatoses can be photoaggravated including acne rosacea, systemic lupus erythematosus (3.78), lichen planus, and psoriasis and atopic dermatitis in some patients .
Photosensitive drug eruptions may be induced by ultraviolet radiation exposure with, for example, phenothiazines, thiazide diuretics, sulphonamides, or tetracyclines. These reactions may present as either an acute phototoxic reaction (2.142) or as a more chronic photodermatitis (2.141). Several plant f~milies also contain substances that may induce photosensitivity (phytophotodermatitis) in the skin, including cow parsley, hogweed, rue, and bergamot. The sensitivity results from contact with psoralen compounds within the plants (2.143). Bergapten (the active ingredient in oil of bergamot) and other furocoumarins are also found in some perfumes.
Photosensitivity is a common problem in patients with several variants of porphyria (see p. 349), whereas patients with vitiligo or albinism lack the melanin protection in the skin and are liable to both acute and chronic ultraviolet radiation damage.
Patients with the rare inherited disorder xeroderma pigmentosum, who have inherited defects in DNA repair after ultraviolet exposure, are abnormally sensitive to the tumorogenic effects of ultraviolet B.

2.139 Classification of photodermatoses.

2.140 Polymorphic light eruption. This female patient has typical itchy erythematous papules over the forearms and hands. The mechanism of this reaction -the most common form of 'sun allergy'- is not known, but it is provoked by ultraviolet B light in the sunburn range. The reaction commonly occurs on the face and arms, but may also appear in other sun-exposed areas. It may develop at any time from 2 hours to 5 days after sun exposure - most commonly it appears within 24 hours.

2.141 Chronic actinic dermatitis (photoder matitis) is a severe eczematous reaction which is limited to light exposed areas. Notethe typical distribution of a photodermatosis, with sparing behind the ears, under the chin and below the collar line. In this case, the cause was unknown and prevention of exposure to light was the major preventive measure. In many cases, however, a similar reaction may result from photosensitizing drug therapy.

2.142 A phototoxic drug eruption, occurring in exposed skin not covered by footwear. This woman had been treated with doxycycline.

2.143 Phytophotodermatitis most commonly presents as irregular streaks of erythema and hyperpigmentation occurring on the light-exposed parts of the body. On careful questioning, the patient usually gives a history of prior contact with a sensitizing plant. This gardener's skin had been exposed to giant hogweed.

DRUG REACTIONS IN THE SKIN

Skin rashes are the most common sign of adverse reactions to drug therapy, although any organ system can be involved. Many drug reactions are not truly allergic in their nature and it is important to distinguish between the characteristics of nonallergic and allergic reactions (2.144). Drugs that have been frequently implicated in allergic reactions are listed in 2.145.

Drug therapy may lead to a wide range of skin pathologies, but some features are especially suggestive of drug eruptions. The rash is usually widespread and symmetrical. Typically, it develops within 10-14 days of the start of therapy, but it may develop sooner if there has been previous exposure to the same or a similar, drug. Reactions may develop rapidly, within minutes, if a type I hypersensitivity reaction of anaphylaxis, angioedema or urticaria is present. Alternatively, drug eruptions can develop when a patient has been on treatment for some time, perhaps triggered by some additional, intercurrent factor. When a patient is on multiple drug therapy, drugs commonly associated with rashes should be identified, together with those that have been introduced recently, and withdrawal or substitution of alternative therapy carefully planned. It is important to recognize that an allergic reaction may not be caused by the active drug itself; it may be due to a preservative, colouring agent or bulking agent in the tablet or syrup. Factors such as infection may modify the development of a drug reaction, as with the ampicillin rash seen in patients with infectious mononucleosis (1.93).
Morbilliform and maculopapular eruptions are common (2.146, 2.147) and may develop into severe erythroderma (exfoliative dermatitis), clinically indistinguishable from that found in other conditions such as psoriasis (2.21).
True immediate-type hypersensitivity to penicillin and many other drugs may lead to urticaria (2.40), angioedema (2.42) and life-threatening anaphylaxis. Similar reactions may develop as a result of idiosyncratic direct release of inflammatory mediators such as histamine by nonallergic mechanisms, as in asprinsensitive individuals.
Fixed drug eruptions are rashes or solitary skin lesions that recur at the same site each time the causative drug is taken (2.148). Sulphonamides, barbiturates and the laxative phenolphthalein are common causes.
Erythema multiforme may be evoked by drug therapy (see p. 94). It is a component of, and may develop into, the lifethreatening Stevens-Johnson syndrome (see p. 95).
Erythema nodosum (2.45) may be provoked by drug therapy; so too may vasculitic and purpuric reactions. Another major drug reaction is toxic epidermal necrolysis, the'scalded skin syndrome' (2.149). Drug allergy is the most common cause of this syndrome in adults.
Some drugs are used despite a known high frequency of rashes. Gold therapy may be used for its powerful effect in severe rheumatoid arthritis, for example, but it often provokes a psoriasiform eruption, which may persist despite withdrawal of the drug (2.150).
A number of drugs may produce phototoxic or photoallergic reactions, in which the rash appears on light-exposed areas (2.141, 2.142). These patients must be distinguished from those with underlying photosensitivity caused by conditions such as systemic lupus erythematosus or porphyria.

2.144 Differences between non-allergic and allergic drug reactions.

2.145 Drugs frequently implicated in allergic drug reactions.

2.146 Ampicillin rash often presents as a symmetrical erythematous maculopapular eruption. This patient had a history of previous penicillin rashes, which had not been taken into account when the ampicillin was prescribed.

2.147 A morbilliform eruption in a patient treated with co-trimoxazole. The offending agent here is usually the sulphonamide component, and similar rashes may occur when other sulphonamides are administered.

2.148 Fixed drug eruption, so-called because the lesion recurs at the same site after each administration of the causative drug. A common cause, as here, is phenolphthalein, found in various proprietary laxative preparations. The lesion is intensely itchy.

2.149 Toxic epidermal necrolysis, the 'scalded skin syndrome' in an adult. The most common cause is drug allergy, but in children it is more commonly the result of infection (see 1.101).

2.150 Gold sensitivity is most commonly manifest as a psoriasiform eruption. Gold rashes are not uncommon in rheumatoid patients, and they may persist despite withdrawal of gold therapy.

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