Hyperlipidaemias :

Hyperlipidaemias can present with xanthomas, which are abnormal collections of lipid in the skin. All patients with xanthomas should be investigated for hyperlipidaemia although the most common type called xanthelasma (yellow plaques around the eyes) are usually associated with normal lipids. There are a number of other clinical variants of xanthomas such as (i) tuberous xanthoma (firm orange-yellow nodules and plaques on extensor surfaces), (ii) tendon xanthoma (firm subcutaneous swellings attached to tendons), (iii) plane xanthoma (orange-yellow macules often affecting palmar creases), (iv) eruptive xanthoma (numerous small yellowish papules commonly on the buttocks).

Chronic renal failure :

Chronic renal failure is commonly associated with intractable pruritus. Pallor, hyperpigmentation and ecchymoses are commonly seen. Rarely it is associated with non-inflammatory blisters, pseudo-porphyria cutanea tarda and cutaneous calcification. Long-standing renal transplant patients often suffer with recurrent viral warts and squamous cell carcinomas due to the immunosuppression.

Thyroid disease :

Hypothyroidism may cause dry firm gelatinous (myxoedematous) skin with diffuse hair thinning and a loss of the outer third of the eyebrows. Hyperthyroidism may be associated with warm sweaty skin and a diffuse alopecia. Graves' disease is rarely associated with thyroid acropachy ('clubbing' with underlying bone changes) and pretibial myxoedema (a red-brown mucinous infiltration of the shins which can become lumpy and tender).

Cushing's syndrome:

Cushing's syndrome may cause hirsutism, a moon face, a buffalo hump, stretch marks (striae) and a pustular folliculitis (often called steroid acne) of the skin.

Diabetes mellitus:

Diabetes mellitus can have a number of cutaneous features. Complications of diabetes itself include:
fungal infection (e.g. candidiasis)
bacterial infections (e.g. recurrent boils)
xanthomas
arterial disease (ulcers, gangrene)
neuropathic ulcers.
Specific dermatoses of diabetes include:
necrobiosis lipoidica (a patch of spreading erythema over the shin which becomes yellowish and atrophic in the centre and may ulcerate)
diffuse granuloma annulare (p. 1336)
diabetic dermopathy (red-brown flat-topped papules)
blisters (usually on the feet or hands)
diabetic stiff skin (tight waxy skin over the fingers with limitation of joint movement owing to thickened collagen - also called cheiroarthropathy).

Chronic liver disease:

Chronic liver disease may present with jaundice, palmar erythema, spider naevi, white nails, hyperpigmentation and pruritus.

Porphyria cutanea tarda (PCT, p. 1149) is a rare genetic disorder associated with liver disease usually due to hepatic damage from excessive alcohol consumption or hepatitis C infection: 75% of cases are sporadic, 25% familial. Overall, 20% of cases have underlying hereditary haemochromatosis (p. 386). It presents clinically on exposed skin with sun-induced blisters, skin fragility, scarring, milia and hypertrichosis. Treatment of the cutaneous features is with repeated venesection and/or very low-dose chloroquine plus an avoidance of alcohol. There is anecdotal evidence that specific treatment of hepatitis C (p. 373) will also help the skin, presumably through improving liver function. All forms of PCT are at risk of hepatic carcinoma.

Tuberous sclerosis (epiloia):

Tuberous sclerosis is also an autosomal dominant condition of variable severity which may not present until later childhood. It is characterized by a variety of hamartomatous growths. The three cardinal features are (a) mental retardation, (b) epilepsy, and (c) cutaneous abnormalities - but not all have to be present. The skin signs include:
adenoma sebaceum (reddish papules/fibromas around the nose)
periungual fibroma (nodules arising from the nail bed)
shagreen patches (firm, flesh-coloured plaques on the trunk)
ash-leaf hypopigmentation (pale macules best seen with UV light)
forehead plaque (indurated flesh-coloured patch)
café-au-lait patches
pitting of dental enamel.
Internal hamartomas can arise in the heart, kidney, retina and CNS. Parents of a suspected case should be carefully examined (under UV light) as they may have a forme fruste of the condition which can manifest just as hypopigmented patches. This would have genetic implications for future offspring.

Sarcoidosis:

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. It can present as reddish brown dermal papules and nodules, especially around the eyelid margins and the rim of the nostrils. More polymorphic lesions (papules nodules and plaques) may appear on the body. It is most common in black Africans where it is often accompanied by hypo- or hyperpigmentation. Rarely it can present with a bluish red infiltrate or swelling, especially of the nose or ears, called lupus pernio. Both these types of lesion can be seen anywhere on the body but are common on the face. Erythema nodosum of the shins is sometimes seen in acute-onset sarcoidosis. Erythema nodosum is an immunological reaction and not due to sarcoid tissue infiltration. Swollen fingers from a dactylitis occur. Whilst sarcoidosis may be confined to the skin, all patients should be investigated for evidence of systemic disease
Treatment of cutaneous lesions includes very potent topical steroids (0.05% clobetasol propionate), intralesional steroids, oral steroids and occasionally methotrexate or antimalarials.

Neurofibromatosis type 1 (von Recklinghausen's disease)
Type 1 neurofibromatosis is an autosomal dominant condition with complete penetrance. It often presents in childhood with a variety of cutaneous features. Many cases are new mutations in the NF1 gene. Early signs include café-au-lait spots (brown macules, greater than 2.5 cm in diameter and more than five lesions) and axillary freckling. Lisch nodules (hyperpigmented iris hamartomas) may be seen in the eyes by slit lamp examination. Later on, fleshy skin tags and deeper soft tumours (neurofibromas) appear and they may progress to completely cover the skin causing significant cosmetic disability. Learning difficulties and skeletal dysplasias occur. A number of endocrine disorders may be rarely associated including phaeochromocytoma, acromegaly and Addison's disease.

Pruritus:

The pathophysiology of pruritus is poorly understood but is due to peripheral mechanisms (e.g. skin disease), central or neuropathic mechanisms (e.g. multiple sclerosis), neurogenic (e.g. cholestasis/μ-opioid receptor stimulation, p. 386) or psychogenic mechanisms (e.g. parasitophobia). Evidence suggests that low stimulation of unmyelinated C-fibres in the skin is associated with the sensation of itch (high stimulation produces pain). Histamine, tachykinins (e.g. substance P) and cytokines (e.g. interleukin-2) may also play a role peripherally in the skin. The major nerve pathways for itch and the influence of the central nervous system are not well characterized but opioid μ-receptor-dependent processes can regulate the perception and intensity of itch.
Pruritus (see lichen simplex, nodular prurigo/neurodermatitis) in the absence of a demonstrable rash can be caused by a number of different medical problems

Medical conditions associated with pruritus
Iron deficiency anaemia
Internal malignancy (especially lymphoma)
Diabetes mellitus
Chronic renal failure
Chronic liver disease (especially primary biliary cirrhosis)
Thyroid disease
HIV infection
Polycythaemia vera

Asteatotic eczema and cholinergic urticaria are common causes of pruritus where the rash is often missed. The term idiopathic pruritus or 'senile' pruritus probably overlaps with asteatotic eczema and this is common in the elderly.
Treatment involves avoiding soaps and using symptomatic measures (as for asteatotic eczema). Phototherapy may help intractable cases. Oral opiate antagonists, which act centrally, are under assessment. Underlying medical problems should be treated.

Lupus erythematosus (LE):

lupus erythematosus
There are three clinical variants to this disease but some patients may show features of more than one type.
chronic discoid lupus erythematosus (CDLE)
subacute lupus erythematosus (SCLE)
systemic lupus erythematosus (SLE).
The aetiology is unknown but is due to abnormality in immune function as variable autoantibodies may be found in all types. Very rarely it can be induced by certain drugs such as phenothiazines, hydralazine, methyldopa, isoniazid, tetracycline, mesalazine and penicillin.
Chronic discoid lupus erythematosus (CDLE)
CDLE is the most common type of LE seen by dermatologists and more frequently affects females. Clinically it presents with fixed erythematous, scaly, atrophic plaques with telangiectasia, especially on the face or other sun-exposed sites (Fig. 23.25). Hypopigmentation is common and follicular plugging occurs. Scalp involvement leads to a scarring alopecia. Oral involvement (erythematous patches or ulceration) occurs in 25% of cases.
CDLE can be triggered and exacerbated by UV exposure. A few patients also suffer with Raynaud's phenomenon or unusual chilblain-like lesions (chilblain lupus). Only 5% of cases will go on to develop SLE but this is more common in children. Serum antinuclear antibody (ANA) is positive in 30% of cases.

Skin biopsy shows a dense patchy, dermal lymphohistiocytic infiltrate which often is centred on appendages. Epidermal basal layer damage, follicular plugging and hyperkeratosis may be present. Direct immunofluorescence studies of lesional skin may show the presence of IgM and C3 at the dermoepidermal junction ('lupus band').
Treatment
First-line therapy is with sunscreens and potent topical steroids. Certain oral antimalarials (hydroxychloroquine 100-200 mg twice daily and mepacrine 100 mg daily) can prove very useful and are generally safe for long-term intermittent use. Oral prednisolone is beneficial but its use is limited by its side-effect profile. Azathioprine, retinoids, ciclosporin and thalidomide can be useful in resistant cases.
Prognosis
The disease is usually chronic, although it may fluctuate in severity. CDLE remains confined to the skin in most patients and it will eventually go into remission in up to 50% of cases (after many years).
Subacute lupus erythematosus (SCLE)
SCLE is a rare cutaneous variant of LE. It presents with widespread indurated, sometimes urticated, erythematous lesions, often on the upper trunk. The lesions can also be annular. Photosensitivity is often a prominent feature. Complications, such as arthralgia and mouth ulceration, are seen but significant organ involvement is rare. ANF and extractable nuclear antibodies (anti-Ro and anti-La) are usually positive Treatment is with oral dapsone, antimalarials or systemic immunosuppression (prednisolone and ciclosporin).

Systemic lupus erythematosus (SLE):

The cutaneous involvement of SLE is one of the minor problems of the disease but it may be the presenting feature.
Features include macular erythema over the cheeks, nose and forehead ('butterfly rash', ). Palmar erythema, dilated nail fold capillaries, splinter haemorrhages and digital infarcts of the finger tips may also be seen but are not always noticed by the patient. Joint swellings, livedo reticularis and purpura are occasionally seen. Rarely SLE can be complicated by an atypical erythema multiforme-like rash ('Rowell's syndrome'). Treatment is usually managed by a rheumatologist.

Acanthosis nigricans: Dermatomyositis,Scleroderma:

Acanthosis nigricans presents as thickened, hyperpigmented skin predominantly of the flexures (Fig. 23.24). It can appear warty or velvety when advanced. In early life it is seen in obese individuals who have very high levels of insulin owing to insulin resistance (and this is sometimes termed 'pseudo-acanthosis nigricans'). In older people it normally reflects an underlying malignancy (especially gastrointestinal tumours). Rarely it is associated with hyperandrogenism in females.
Treatment
Topical or oral retinoids (0.5 mg/kg/day) may help (p. 1338) and weight loss is advised in the obese. Any underlying malignancy should be treated.

Dermatomyositis:
The rash is distinctive. Facial erythema and a magenta-coloured rash around the eyes with associated oedema are often present. Bluish red nodules or plaques may be present over the knuckles and extensor surfaces. The nail folds are frequently ragged with dilated capillaries. The diagnosis is made from the clinical appearance, muscle biopsy, EMG and a serum creatine phosphokinase. Skin biopsy is not diagnostic.
There is a childhood form which usually occurs before the age of 10 and which eventually resolves. This type is often associated with calcinosis in the skin and can cause significant long-term functional problems with weak muscles and contractures. Life-threatening bowel infarction can also occur in the childhood form. The adult form usually occurs after the age of 40. Some cases are associated with an underlying malignancy, whereas others appear to reflect a 'connective tissue disease'. This latter group may overlap with scleroderma and lupus erythematosus.
Treatment
Skin disease may respond to hydroxychloroquine (200 mg twice daily) as well as immunosuppressants, e.g. azathioprine or ciclosporin.

Scleroderma
The term scleroderma refers to a thickening or hardening of the skin owing to abnormal dermal collagen. It is not a diagnostic entity in itself. Systemic sclerosis and morphoea both show sclerodermatous changes but are separate conditions.
Systemic sclerosis (often called scleroderma) has cutaneous and systemic features and is discussed fully on page 577.
Morphoea is confined to the skin and usually presents in children or young adults. It is commoner in females and the cause is unknown. Lesions are usually on the trunk and appear as bluish red plaques which progress to induration and then central white atrophy. A linear variant exists in childhood which is more severe as it can cause atrophy of underlying deep tissues and thus can cause unequal limb growth or scarring alopecia.
Rarely, sclerodermatous skin changes may be seen in chronic Lyme disease (acrodermatitis chronica atrophicans), chronic graft-versus-host disease, polyvinyl chloride disease, eosinophilic myalgia syndrome (due to tryptophan therapy) and bleomycin therapy.

Pyoderma gangrenosum:

Pyoderma gangrenosum is of unknown aetiology and presents with erythematous nodules or pustules which frequently ulcerate (Fig. 23.23). The ulcers can be large and grow at an alarming speed. The ulcer has a typical bluish black ('gangrenous') undermined edge and a purulent surface ('pyoderma'). There may be an associated pyrexia and malaise. Biopsy through the ulcer edge shows an intense neutrophilic infiltrate and occasionally a vasculitis but the diagnosis depends mostly on the clinical appearance. The main causes are:
inflammatory bowel disease
rheumatoid arthritis
myeloma, leukaemia, lymphoma
liver disease (primary biliary cirrhosis)
idiopathic (> 20% in some series).

Treatment
This is with very potent topical steroids or 0.1% tacrolimus ointment. High-dose oral steroids may be needed to prevent rapidly progressive ulceration. Oral dapsone and minocycline may help. Other immunosuppressants, such as ciclosporin, are useful in resistant cases. The underlying cause should be treated.

CUTANEOUS SIGNS OF SYSTEMIC DISEASE:

Some dermatoses are associated with a variety of underlying systemic diseases. Furthermore some medical conditions may present with cutaneous features.
Erythema nodosum
Erythema nodosum has a number of underlying causes (Table 23.8). It presents as painful or tender dusky blue-red nodules, commonly over the shins or lower limbs, which fade over 2-3 weeks leaving a bruised appearance (see Fig. 23.39). It is most common in young adults, especially females. It may be associated with arthralgia, malaise and fever. The inflammation involves the dermis and the subcutaneous layer (panniculitis).
Treatment
Table 23-8. Causes of erythema nodosum
Streptococcal infection*
Drugs* (e.g. sulphonamides, oral contraceptive)
Sarcoidosis*
Idiopathic*
Yersinia infection
Fungal infection (histoplasmosis, blastomycosis)
Tuberculosis
Leprosy
Inflammatory bowel disease
Chlamydia infection

*Common causes in the UK
page 1341

page 1342
Symptomatic therapy with non-steroidal anti-inflammatory drugs (avoid in pregnancy), light compression bandaging and bed rest are all that are necessary as the condition resolves spontaneously. The underlying cause should be treated. In very persistent cases dapsone (100 mg daily), colchicine (500 μg twice daily) or prednisolone (up to 30 mg daily) can be useful.
Erythema multiforme
Erythema multiforme (EM) is a hypersensitivity rash of acute onset frequently caused by infection or drugs. A cell-mediated T lymphocytic response is seen in the skin, which causes epidermal cell death.
In 50% of cases, the cause is not found but the following should be considered:
herpes simplex virus (the most common identifiable cause)
other viral infections (e.g. EBV, orf disease)
drugs (e.g. sulphonamide, anticonvulsants)
mycoplasma infection
connective tissue disease (e.g. SLE, polyarteritis nodosa)
HIV infection
Wegener's granulomatosis
carcinoma, lymphoma.
Clinically the lesions can be erythematous, polycyclic, annular or show concentric rings called 'target lesions' (Fig. 23.22). Frank blistering is not uncommon. The rash tends to be symmetrical and commonly affects the limbs, especially the hands and feet where palms and soles may be involved. Occasionally there is severe mucosal involvement leading to necrotic ulcers of the mouth and genitalia, and a conjunctivitis ('EM major' - previously called Stevens-Johnson syndrome - see Box 23.3). The term 'EM minor' may be used for cases without mucosal involvement.

Stevens-Johnson syndrome
This term is now used for a mild form of toxic epidermal necrolysis (p. 1359) which shares similar mucosal lesions to 'erythema multiforme major' but does not show typical target lesions. Both Stevens-Johnson syndrome and toxic epidermal necrolysis are more likely to be drug induced.

Erythema multiforme usually resolves in 2-4 weeks. Rarely, recurrent erythema multiforme can occur and this is triggered by herpes simplex infection in 80% of cases.
Treatment
This is symptomatic and involves treating the underlying cause. Some advocate the use of oral steroids in severe disease but this remains controversial.
Recurrent erythema multiforme can be treated with prophylactic oral aciclovir (200 mg twice daily) even if no cause has been found, as 80% appear to be driven by herpes simplex virus. In resistant cases, azathioprine (1-2 mg/kg daily) is used.

Pemphigus vulgaris:

Pemphigus vulgaris is a potentially fatal blistering disease occurring in all races but commoner in Ashkenazi Jews and possibly in people from the Indian subcontinent. Onset is usually in middle age and both sexes are affected equally. Prior to the development of oral steroids this condition was frequently fatal. The development of autoantibodies against the desmosomal protein, desmoglein 3, is pathogenic in this disease and they can be measured experimentally as markers of disease activity. Rarely the disease can be drug induced (e.g. penicillamine or captopril).
Skin biopsy shows a superficial intraepidermal split just above the basal layer with acantholysis (separation of individual cells). In the rarer variant, pemphigus foliaceous (characterized by anti-desmoglein 1 autoantibodies), the split is higher in the upper epidermis. Both direct IMF of skin (perilesional) and indirect IMF using patients' serum show intercellular staining of IgG within the epidermis.
Clinical features
Mucosal involvement (especially oral ulceration) is common and is the presenting sign in up to 50% of cases. This is followed by the appearance of flaccid blisters, particularly involving the trunk. They tend to be sore rather than itchy. Blistering usually becomes widespread but they rapidly denude; thus pemphigus often presents with erythematous, weeping erosions. Blisters can be extended with gentle sliding pressure (Nikolsky's sign). Flexural lesions often have a vegetative appearance. In pemphigus foliaceous the blisters and erosions often start in a seborrhoeic distribution (scalp, face and upper chest) before becoming more widespread.
Treatment
This is with very high-dose oral prednisolone (60-100 mg daily) or pulsed methylprednisolone, and this may need to be lifelong. Other immunosuppressants such as azathioprine, or mycophenolate mofetil (or occasionally cyclophosphamide or ciclosporin) are used as steroid-sparing agents but they often take many weeks to be effective. Intravenous immunoglobulin infusions may help gain quick control whilst waiting for these other drugs to work. Anti-CD20 monoclonal antibody (rituximab) has recently been reported to help multidrug-resistant cases.
Whilst treatment is normally effective, perhaps up to 10% of patients may die, either because of complications of the disease or more commonly from side-effects of the treatment.
Use of azathioprine.
Azathioprine can cause bone marrow suppression and an allergic hepatitis. Therefore blood count and liver function tests should be regularly monitored during therapy (every 6 weeks). Long-term use with other immunosuppressants causes a slightly increased risk of malignancy, especially of the skin.

Bullous pemphigoid:

Bullous pemphigoid is more common than pemphigus. It presents in later life (usually over 60 years old) and mucosal involvement is rarer. Autoantibodies against a 230 kDa or 180 kDa hemidesmosomal protein ('bullous pemphigoid antigens 1 and 2') play an aetiological role.
Skin biopsy shows a deeper blister (than in pemphigus) owing to a subepidermal split through the basement membrane. Direct and indirect IMF studies show linear staining of IgG along the basement membrane.
Clinical features
Large tense bullae appear anywhere on the skin (Fig. 23.28) but often involve limbs, hands and feet. They may be centred on an erythematous or urticated background and they can be haemorrhagic. Pemphigoid can be very itchy. Mucosal ulceration is uncommon but a variant of pemphigoid exists which predominantly affects mucosal surfaces with scarring (cicatricial pemphigoid).
Treatment
This is with high-dose oral prednisolone (30-60 mg daily) and steroid-sparing agents such as azathioprine or mycophenolate mofetil. Weekly methotrexate is also occasionally used. In general disease control is easier than with pemphigus. Treatment can often be withdrawn after 2-3 years. Pemphigoid treatment frequently causes side-effects, especially as most patients are elderly. Occasionally localized or mild disease can be controlled with superpotent topical steroids, oral dapsone or high-dose oral minocycline.

Linear IgA disease (chronic bullous dermatosis of childhood):

Linear IgA disease is a subepidermal blistering disorder of adults and children. Pathogenic IgA autoantibodies can bind to a variety of basement membrane proteins including ladinin, BP 180 antigen and laminin 5 (see Fig. 23.27). It is the most common immunobullous disease seen in children. Rarely it is drug induced by vancomycin.
Clinical features
Linear IgA disease can present with circular clusters of large blisters, a pemphigoid type of blistering or a dermatitis herpetiformis picture. Mucosal involvement of the mouth, vulva and eyes is not uncommon and can cause scarring. Direct IMF studies of skin show linear IgA deposition along the basement membrane.
Treatment
This is with oral dapsone (50-200 mg daily) or sulphonamides. Occasionally immunosuppression is needed. Many patients show spontaneous resolution after 3-6 years.

Dermatitis herpetiformis :

Dermatitis herpetiformis (DH) is a rare blistering disorder associated with gluten-sensitive enteropathy (coeliac disease). DH and celiac disease are associated with other organ-specific autoimmune disorders.
Skin biopsy shows a subepidermal blister with neutrophil microabscesses in the dermal papillae. Direct IMF studies of uninvolved skin show IgA in the dermal papillae and patchy granular IgA along the basement membrane. The jejunal mucosa usually shows a partial villous atrophy.
Clinical features
Dermatitis herpetiformis is commoner in males and can present at any age but is most likely to appear for the first time in young adult life. It presents with intensely itchy, small blisters of the skin. The lesions have a predilection for the elbows, extensor forearms, scalp and buttocks. The tops of the blisters are usually scratched off; thus crusted erosions are often seen at presentation. Remissions and exacerbations are common.
Treatment
This should always be with a gluten-free diet (GFD). Control of the skin disease can be obtained with oral dapsone (50-200 mg daily) or sulphonamides. If a strict GFD is adhered to, oral medication can often be withdrawn after 2 years. The GFD will need to be lifelong. It protects against the rare complication of small bowel lymphoma.
Use of dapsone.
Dapsone frequently causes a mild, dose-related haemolytic anaemia but the haemolysis can be devastating if there is G6PD deficiency. Liver damage, peripheral neuropathy and aplastic anaemia can also rarely occur, so regular monitoring of a blood count and liver function is needed.

MECHANOBULLOUS DISEASE (EPIDERMOLYSIS BULLOSA, 'EB'):

These are due to inherited abnormalities in structural skin proteins which lead to 'skin fragility'. The resultant blistering tends to arise secondary to trauma and often appears at or shortly after birth. These conditions can be a mild inconvenience, severely disabling or fatal but fortunately are very rare. There are three groups of disorders in which the fundamental gene/protein abnormalities have been characterized. This enables prenatal amniocentesis diagnosis.
Epidermolysis bullosa simplex
This is a group of autosomal dominant genodermatoses characterized by 'superficial' blistering owing to mutations of cytoskeleton proteins within the basal layer of the epidermis, e.g. keratin 5 (chromosome 12q) or keratin 14 (chromosome 17q). Most forms of EB simplex show mild disease with intermittent blistering of the hands and feet, especially in hot weather. The teeth and nails are normal and scarring is absent.
Epidermolysis bullosa dystrophica
This group of genodermatoses is characterized by 'deeper' blistering associated with scarring and milia formation. The level of split is deep within the basement membrane and is due to a mutation in the COL-7A1 gene (locus at chromosome 3p21.1) which causes a loss of collagen VII in the anchoring fibrils. Nails, mucosae and even the larynx are often involved. The autosomal dominant variety is milder but the autosomal recessive type produces severe disease with disabling scarring, fusion of digits, joint contractures and dysphagia. Life expectancy is significantly reduced. Repeated scarring results in the development of multiple squamous cell carcinomas and most die from this complication in early adult life. The average life expectancy after the appearance of the first squamous cell carcinoma is 5 years.
Junctional epidermolysis bullosa
This, the most severe form, is characterized by a split in the lamina lucida of the basement membrane and is due to mutations in various proteins, mainly laminin 5 but also α6β4 integrin or the 180 kDa bullous pemphigoid-2 antigen. It presents at birth with widespread blistering and areas of absent skin. Erosions of the central face and hoarseness from laryngeal involvement are common. Nail and teeth abnormalities are also common. Both a lethal and a rarer non-lethal form of junctional EB exist and they show an autosomal recessive inheritance. The lethal form causes death in infancy or early childhood.
Investigation and treatment
Investigation and treatment of EB should be carried out in a specialist centre. Diagnosis at birth on clinical grounds is difficult and should be avoided. Exact diagnosis depends on ultrastructural analysis of induced blisters in the skin and immunohistochemistry. Only then can prognosis and genetic counselling be given accurately to parents. Prenatal diagnosis is available for the more severe forms of EB.

FURTHER READING
Allen J et al. (2003) Linear IgA disease. British Journal of Dermatology 149: 977-985, 1055-1058.
Cooper et al. (2003) Treatment of resistant pemphigus vulgaris with an anti-CD20 monoclonal antibody (rituximab). Clinical and Experimental Dermatology 28: 366-368.
Diaz LA, Giudice GJ (2000) End of the century overview of skin blisters. Archives of Dermatology 136: 106-112.
Fine J-D et al. (2000) Inherited epidermolysis bullosa comes into the new millennium. Journal of the American Academy of Dermatology 43: 135-137.
Harman KE et al. (2003) Guidelines for the management of pemphigus. British Journal of Dermatology 149: 926-937.
Trent JT et al. (2003) Epidermolysis bullosa: identification and treatment. Advances in Skin & Wound Care 16: 284-290.
Wojnarowska F et al. (2002) Guidelines for the management of bullous pemphigoid. British Journal of Dermatology 147: 214-221.

BENIGN CUTANEOUS TUMOURS:

Melanocytic naevi (moles)

Moles are a benign overgrowth of melanocytes that are common in white-skinned people. They appear in childhood and increase in number and size during adolescence and early adult life. They often start as flat brown macules with proliferation of melanocytes at the dermoepidermal junction (junctional naevi). The melanocytes continue to proliferate and grow down into the dermis (compound naevi), which causes an elevation of the mole above the skin surface. The pigmentation is usually even and the border regular. They eventually mature into a dermal naevus (cellular naevus) often with a loss of pigment.
Blue naevus is an acquired asymptomatic blue-looking mole. It is due to a proliferation of melanocytes deep in the mid-dermis.
Basal cell papilloma (seborrhoeic wart)

This is a common benign overgrowth of the basal cell layer of the epidermis. The lesion can be flesh coloured, brown or even black and often has a greasy appearance. The surface is irregular and warty and the lesions appear very superficial as though stuck on to the skin (Fig. 23.29). Tiny keratin cysts may be seen on the surface. They can be treated with cryotherapy or curettage.
Dermatofibroma (histiocytoma)
Dermatofibromas appear as firm, elevated pigmented nodules which may feel like a button in the skin. A peripheral ring of pigmentation is sometimes seen. They are often found on the leg and are commoner in females. There may be a preceding history of trauma or insect bite. The lesion consists of histiocytes, blood vessels and varying degrees of fibrosis. If symptomatic, excision is required.
Epidermoid cyst (previously 'sebaceous cyst')
Epidermoid cysts present as cystic swellings of the skin with a central punctum. They contain 'cheesy' keratin rather than sebum; thus the old term 'sebaceous cyst' should be avoided. These cysts occasionally rupture causing significant dermal inflammation which is not infected.
Pilar cyst (trichilemmal cyst)
Pilar cysts are smooth cysts without a punctum, usually found on the scalp. They may be multiple and familial.
Keratoacanthoma
Keratoacanthomas are rapidly growing epidermal tumours which develop central necrosis and ulceration (Fig. 23.30). They occur on sun-exposed skin in later life and can grow up to 2-3 cm across. Whilst they may resolve spontaneously over a few months, they are best excised, both to exclude a squamous cell carcinoma (which they can mimic) and to improve the cosmetic outcome.
Pyogenic granuloma (granuloma telangiectaticum)
Pyogenic granulomas are a benign overgrowth of blood vessels. They present as rapidly growing pinkish red nodules which are friable and readily bleed. They may follow trauma and are often found on the fingers and lips. They are best excised to exclude an amelanotic malignant melanoma.

Cherry angioma (Campbell de Morgan spots)
They are benign angiokeratomas that appear as tiny pinpoint red papules, especially on the trunk, and increase with age. No treatment is required.

POTENTIALLY PRE-MALIGNANT CUTANEOUS TUMOURS:

Solar keratoses (actinic keratoses)
These frequently develop later in life in white-skinned people who have had significant sun exposure. They appear on exposed skin as erythematous silver-scaly papules or patches with a conical surface and a red base (Fig. 23.31). The background skin is often inelastic, wrinkled and may show flat brown macules ('liver spots' or solar lentigos) reflecting diffuse solar damage. A small proportion of these keratoses can transform into squamous cell carcinoma but only after many years.
Treatment of lesions is with cryotherapy, topical 5-fluorouracil cream or 5% imiquimod cream.
Bowen's disease
This is a form of intraepidermal carcinoma-in-situ which rarely can become invasive. It presents on exposed skin as an isolated scaly red patch or plaque, looking rather like psoriasis, although it has a rather irregular edge. The lesions do not clear but slowly increase in size with time.
A variant which can show partial or full-thickness dysplasia can involve the epidermis of the mucosa or neighbouring skin - this can affect the vulva, the glans penis and perianal skin. It is termed vulval- (penile-, or anal-) intraepithelial dysplasia. Clinically it can present as non-specific erythema or as a warty thickening. These diseases have a stronger link with HPV and probably have a higher premalignant potential than Bowen's disease. They are commoner in immunosuppressed individuals. The anal form is increasingly reported in HIV-positive patients and extension into the rectum has been reported.

Treatment is with topical 5-fluorouracil, 5% imiquimod cream, cryotherapy, curettage, photodynamic therapy or a tissue-destructive laser.
Atypical mole syndrome (dysplastic naevus syndrome)
This is often familial. A large number of melanocytic naevi begin to appear in childhood, even on unexposed sites. Individual lesions may be large with irregular pigmentation and border, and histologically they may show cytological and architectural atypia but no frank malignant change. Individuals with this condition have an increased risk of developing malignant melanoma. They should have their moles photographed and be regularly reviewed. Suspicious lesions should be excised.
Giant congenital melanocytic naevi
These are very large moles present at birth. They show an increased risk of developing malignant melanoma. Approximately 10% of lesions larger than 20 cm across will develop a malignant melanoma in childhood. Excision should be undertaken if possible.
Lentigo maligna
This is a slow-growing macular area of pigmentation seen in elderly people, commonly on the face. The border and pigmentation are often irregular. Some people regard this lesion as a melanoma-in-situ. There is an increased risk of developing invasive malignant melanoma. Treatment is by excision if possible but 5% imiquimod cream is currently under assessment in the very large lesions where surgery would be so disfiguring.

MALIGNANT CUTANEOUS TUMOURS:

Basal cell carcinoma (rodent ulcer)
Basal cell carcinomas are the most common malignant skin tumour and most relate to excessive sun exposure. They are common later in life on exposed sites although rare on the ear. They present as a slow-growing papule or nodule (or rarely be cystic) which may go on to ulcerate (Fig. 23.32). Telangiectasia over the tumour or a skin-coloured jelly-like 'pearly edge' may be seen. A flat, diffuse superficial form exists and an ill-defined 'morphoeic' variant. Basal cell carcinomas will slowly grow and erode structures if untreated but these tumours almost never metastasize.
Treatment
Treatment is usually with surgical excision with a 3-5 mm border. Radiotherapy, photodynamic therapy, cryotherapy or 5% imiquimod cream can be useful for large superficial forms but follow-up for recurrence is required. Curettage is occasionally used in older patients, although not for central facial lesions as they often recur. Recurrent tumour or morphoeic basal cell carcinoma is best treated with Mohs' micrographic surgery to ensure adequate clearance.

Squamous cell carcinoma:

Squamous cell carcinoma is a more aggressive tumour than basal cell carcinoma as it can metastasize if left untreated. Most relate to sun exposure and daily application of sun cream has been shown to reduce the incidence in Australia. They can arise in pre-existing solar keratoses or Bowen's disease or be due to chronic inflammation such as in lupus vulgaris. Rarely multiple tumours arise because of arsenic ingestion in early life. Multiple tumours occur in people who have had prolonged periods of immunosuppression, such as renal transplant patients where certain human papilloma virus subtypes may be involved in malignant transformation.

Clinically the lesions are often keratotic, rather ill-defined nodules which may ulcerate (Fig. 23.33). They can grow very rapidly. Examination of regional lymph nodes is essential. They are most common on sun-exposed sites in later life. One should have a high index of suspicion for ulcerated lesions on the lower lip or ear.
Treatment is with excision or occasionally radiotherapy. Curettage should be avoided.

Cutaneous T-cell lymphoma (mycosis fungoides):

This is a rare type of skin tumour which often follows a relatively benign course. It presents insidiously with scaly patches and plaques which can look eczematous or psoriasiform. Lesions often appear initially on the buttocks. These lesions may come and go or remain persistent over many years. Patients may well die of unrelated causes. Skin biopsy confirms the diagnosis, showing invasion by atypical lymphocytes. T-cell receptor gene rearrangement studies show that the there is often a monoclonal expansion of lymphocytes in the skin.
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Occasionally the disease can progress to a cutaneous nodular or tumour stage which may be accompanied by systemic organ involvement. In elderly males the disease may progress rarely to an erythrodermic variant accompanied by lymphadenopathy and peripheral blood involvement ('Sézary syndrome').
All patients should be staged at the time of diagnosis to assess for any systemic involvement.
Treatment
Early cutaneous disease can be left untreated or treated with topical steroids or PUVA. More advanced disease of the skin, or systemic involvement, may require radiotherapy, chemotherapy, immunotherapy or electron beam therapy. Bexarotene, an agonist at the retinoid X receptor, can cause regression.
Kaposi's sarcoma
This is a tumour of vascular and lymphatic endothelium that presents as purplish nodules and plaques. There are three types:
The 'classic' or 'sporadic' form (as described by Kaposi) occurs in elderly males, especially Jews from Eastern Europe. It presents as slow-growing purple tumours in the foot and lower leg which rarely cause any significant problem.
The 'endemic' form occurs in males from central Africa and shows more widespread cutaneous involvement as well as lymph node (or occasionally systemic) involvement. Oedema is a prominent feature.
The immunosuppression-related form is more severe and is most common in homosexual patients with HIV (p. 142). Lesions are widespread and often affect the skin, bowel, oral cavity and lungs.
All three types have a strong association with herpes virus type 8 but other factors must be involved as herpes type 8 seroprevalence in the general population is up to 10% in the USA and 50% in some African countries. HAART (p. 143) has significantly reduced the incidence of Kaposi's sarcoma in HIV.
Treatment
Treatment of advanced Kaposi's sarcoma is with radiotherapy, immunotherapy or chemotherapy.

Malignant melanoma:

Malignant melanoma is the most serious form of skin cancer as metastases can occur early and it causes a number of deaths even in young people. As with other types of skin cancer the incidence is continuing to increase, probably because of excessive exposure to sunlight. The history of childhood sun exposure and intermittent sun exposure appears to play a role in the development of malignant melanoma. Other risk factors include atypical mole syndrome, giant congenital melanocytic naevi, lentigo maligna and a positive family history of malignant melanoma. Malignant melanoma is commoner in later life; young adults are also affected. The tumour suppressor gene p16 (on chromosome 9p) is frequently mutated or deleted in melanoma cell lines and its role in atypical mole syndrome/familial melanoma is currently under investigation.
Diagnosis of melanoma is not always easy but the clinical signs listed in Table 23.11 help distinguish malignant from benign moles. Examination with a dermatoscope can further help in detecting malignant lesions.
Four clinical types exist:
Lentigo maligna melanoma is where a patch of lentigo maligna develops a papule or nodule signalling invasive tumour.
Superficial spreading malignant melanoma is a large flat irregularly pigmented lesion which grows laterally before vertical invasion develops.
Nodular malignant melanoma (Fig. 23.34) is the most aggressive type. It presents as a rapidly growing pigmented nodule which bleeds or ulcerates. Rarely they are amelanotic (non-pigmented) and can mimic pyogenic granuloma.
Acral lentiginous malignant melanoma arises as pigmented lesions on the palm, sole or under the nail and it usually presents late.





Integration link: Melanoma - subtypes

Taken from General & Systematic Pathology 4e




Table 23-11. Clinical criteria for the diagnosis of malignant melanoma
ABCDE criteria (USA)
Asymmetry of mole
Border irregularity
Colour variegation
Diameter > 6 mm
Elevation
The Glasgow 7-point checklist
Major criteria Change in size
Change in shape
Change in colour
Minor criteria Diameter more than 6 mm
Inflammation
Oozing or bleeding
Mild itch or altered sensation



Figure 23.34 Nodular malignant melanoma.
Treatment
This consists of urgent wide excision (2 cm margin) of the lesion. Histological analysis will determine the depth of invasion ('Clark's level') and the thickness of the tumour ('Breslow thickness'). These two factors are significant in predicting prognosis and 5-year survival rates: 96% for local lesions, 60% for regional spread and 14% for distant metastases. For localized melanomas the thickness and presence or absence of ulceration are the strongest independent predictors of outcome. Excision and histology interpretation should only be done by experts to ensure optimum treatment and assessment of prognosis. Sentinel node biopsy for patients with thicker lesions is required for predicting prognosis: 15% will be positive without clinical lymphadenopathy. Metastatic disease is best managed by an oncologist with a multidisciplinary team and can involve surgery to lymph nodes, radiotherapy, immunotherapy and chemotherapy. Initial optimism for high-dose alpha-interferon therapy in advanced disease has recently been challenged with a systematic review suggesting no clear benefit.
The role of governments and medical personnel in public health education to discourage sunbathing and to use sunscreens is of the utmost importance in skin cancer prevention.

DISORDERS OF BLOOD VESSELS/LYMPHATICS:

LEG ULCERS
Venous ulcers
Leg ulcers are common in western societies and can have many causes (Table 23.12). Venous ulcers are the most common type in developed countries.
Venous ulcers are the result of sustained venous hypertension in the superficial veins, owing to incompetent valves in the deep or perforating veins or to previous deep vein thrombosis. The increased pressure causes extravasation of fibrinogen through the capillary walls, giving rise to perivascular fibrin deposition, which leads to poor oxygenation of the surrounding skin.
Venous ulcers are common in later life and cause a significant drain on healthcare budgets as they are often chronic and recurrent; they affect 1% of the population over the age of 70 years. They are most commonly found on the lower leg in a triangle above the ankles (Fig. 23.35), and are associated with:
venous eczema (p. 1330)
brown pigmentation from haemosiderin
varicose veins
lipodermatosclerosis (the combination of induration, reddish brown pigmentation and inflammation)
scarring white atrophy with telangiectasia (atrophie blanche).

Treatment
Table 23-12. Causes of leg ulceration
Venous hypertension
Arterial disease (e.g. atherosclerosis)
Neuropathic (e.g. diabetes, leprosy)
Neoplastic (e.g. squamous or basal cell carcinoma)
Vasculitis (e.g. rheumatoid arthritis, SLE, pyoderma gangrenosum)
Infection (e.g. ecthyma, tuberculosis, deep mycoses, tropical ulcer, syphilis, yaws)
Haematological (e.g. sickle cell disease, spherocytosis)
Drug (e.g. hydroxycarbamide (hydroxyurea))
Other (e.g. necrobiosis lipoidica, trauma, artefact)

High-compression bandaging (e.g. Unna boot or four-layer bandaging) and leg elevation are used to try to decrease the venous hypertension. Doppler studies should always be done before bandaging to exclude arterial disease. This treatment is best delivered in the community by appropriately trained nurses. 'Four-layer bandaging' is increasingly popular as this provides high levels of graduated compression (with pressures decreasing up the leg). The choice of ulcer dressing is less critical but one should be chosen to keep the ulcer moist and free of slough and exudate. Up to 80% of ulcers can be healed within 26 weeks. Slower healing rates occur in patients with decreased mobility and if the ulcers are very large, present for longer than 6 months or are bilateral. Diuretics are sometimes helpful to reduce the oedema. Antibiotics are necessary only for overt bacterial infection. Unusual fungal infection ('tinea incognito') is increasingly reported under compression bandaging.
Venous leg ulcers can be very painful so adequate analgesia should be given, including opiates if required. Underlying venous disease is best investigated with duplex ultrasound or plethysmography. Split-thickness skin grafting is used in resistant cases. Life-long support stockings (individually fitted) should be worn after healing as this lessens recurrence.
Surgery for purely superficial venous disease can occasionally be useful for ulcer healing but, in general, venous surgery is unhelpful.
Arterial ulcers
Arterial ulcers may present as punched-out, painful ulcers higher up the leg or on the feet. There may be a history of claudication, hypertension, angina or smoking. Clinically the leg may be cold and show pallor. Absent peripheral pulses, arterial bruits and loss of hair may be present. Doppler ultrasound studies will confirm arterial disease (p. 866) and digital subtraction angiography will further delineate the extent and site of the disease.
Treatment depends on keeping the ulcer clean and covered, adequate analgesia and vascular reconstruction if appropriate.
Neuropathic ulcers
Neuropathic ulcers tend to be seen over pressure areas of the feet, such as the metatarsal heads, owing to repeated trauma. These are most commonly seen in diabetics because of peripheral neuropathy. In developing countries leprosy is a common cause.
Treatment depends on keeping the ulcer clean and removing pressure or trauma from the affected area. Diabetics should pay particular attention to foot care and correctly fitting shoes with the help of a specialist podiatrist (p. 1130).
PRESSURE SORES (DECUBITUS ULCERS, BEDSORES)
These occur in the elderly, immobile, unconscious or paralysed patients. They are due to skin ischaemia from sustained pressure over a bony prominence, most commonly the heel and sacrum. Normal individuals feel the pain of continued pressure, and even during sleep, movement takes place to change position continually. Pressure sores may be graded:
Stage I: non-blanchable erythema of intact skin
Stage II: partial-thickness skin loss of epidermis/dermis (blister or shallow ulcer)
Stage III: full-thickness skin loss involving subcutaneous tissue but not fascia
Stage IV: full-thickness skin loss with involvement of muscle/bone/tendon/joint capsule.
There are numerous risk factors for development of pressure sores (Table 23.13).
The majority of pressure sores occur in hospital. Seventy per cent appear in the first 2 weeks of hospitalization, and 70% are in orthopaedic patients, especially those on traction. Between 20% and 30% of pressure sores occur in the community.
Table 23-13. Risk factors for the development of pressure sores
Prolonged immobility:
paraplegia
arthritis
severe physical disease
apathy
operation and postoperative states
plaster casts
intensive care
Decreased sensation:
coma, neurological disease, diabetes mellitus
drug-induced sleep
Vascular disease:
atherosclerosis, diabetes mellitus, scleroderma, vasculitis
Poor nutrition:
anaemia
hypoalbuminaemia
vitamin C or zinc deficiency

Eighty per cent of patients with deep ulcers involving the subcutaneous tissue die in the first 4 months.
The early sign of red/blue discoloration of the skin can lead rapidly to ulcers in 1-2 hours. Leaving patients on hard emergency room trolleys, or sitting them in chairs for prolonged periods, must be avoided.
Management
Prevention
Prevention is better than cure. Specialist 'tissue-viability nurses' help identify at-risk patients and train other medical staff. Several risk-assessment tools have been devised for the immobile patient based on the known risk factors. The 'Norton scale' and Waterlow Pressure Sore Risk Assessment (Box 23.4) are two such validated systems which produce a numerical score, enabling staff to identify those at most risk.
Treatment
Bed rest with pillows and fleeces to keep pressure off bony areas (e.g. sacrum and heels) and prevent friction.
Air-filled cushions for patients in wheelchairs.
Special pressure-relieving mattresses and beds.
Regular turning but avoid pressure on hips.
Ensure adequate nutrition.
Non-irritant occlusive moist dressings (e.g. hydrocolloid).
Adequate analgesia (may need opiates).
Plastic surgery (debridement and grafting in selected cases).
Treatment of underlying condition.

Box 23.4 Pressure sore risk-assessment tools
Norton Scale for Pressure Sores
Physical Neurology Activity Mobility Incontinence
4 Good 4 Alert 4 Ambulant 4 Full 4 None
3 Fair 3 Apathetic 3 Walks with help 3 Slightly 3 Occasionally
2 Poor 2 Confused 2 Not bound 2 Limited* 2 Usually
1 Very poor 1 Stupor 1 Bedfast 1 Very limited
Immobile 1 Double
Waterlow Pressure Sore Risk Assessment
Build/weight for height Visual skin type Continence Mobility Sex Age Appetite
Average 0 Healthy 0 Complete 0 Fully mobile 0 Male 1 Average 0
Above average 2 Tissue paper 1 Occasionally incontinent 1 Restricted/difficult 1 Female 2 Poor 1
Below average 3 Dry 1 14-18 1 Anorectic 2
Oedematous
Clammy
Discoloured 1
1
2 Catheter/incontinent of faeces 2 Restless/fidgety
Apathetic 2
3 50-64
65-75
75-80 2
3
4
Broken/spot 3 Doubly incontinent 3 Inert/traction 4 81+ 5
Special risk factors Assessment value
1. Poor nutrition; e.g. terminal cachexia 8 At risk 10
2. Sensory deprivation, e.g. diabetes, paraplegia, cerebrovascular accident 6 High risk 15
3. High-dose anti-inflammatory or steroids in use 3 Very high risk 20
4. Smoking 10+ per day 1
5. Orthopaedic surgery/fracture below waist 3

*Norton Scale for Pressure Sores. Low scores carry a high risk
VASCULITIS (see also p. 581)
Vasculitis is the term applied to an inflammatory disorder of blood vessels which causes endothelial damage. Cutaneous vasculitis (confirmed by skin biopsy) may be an isolated problem but occasionally is associated with vasculitis in other organs. The most commonly used classification is based on the size of blood vessel involved (see Tables 10.18 and 10.19).
The cutaneous features are of haemorrhagic papules, pustules, nodules or plaques which may erode and ulcerate. These purpuric lesions do not blanche with pressure. Occasionally a fixed livedo reticularis pattern may appear which does not disappear on warming. Pyrexia and arthralgia are common associations even in the absence of significant systemic involvement. Other clinical features depend on the underlying cause.

The most common cutaneous vasculitis affects small vessels and is called leucocytoclastic vasculitis (LCV) or angiitis. This usually appears on the lower legs as a symmetrical palpable purpura. It is rarely associated with systemic involvement. This can be caused by drugs (15%), infection (15%), inflammatory disease (10%), malignant disease (< 5%) but often no cause is found (55-60%). Extensive investigations are probably best reserved for those with persistent lesions or associated signs and symptoms. Whilst LCV often settles spontaneously, treatment with analgesia, support stockings, dapsone or prednisolone may be needed to control the pain and to heal up any ulceration. Urticarial vasculitis is discussed on page 1335.
LYMPHATICS
Lymphoedema
Lymphoedema refers to a chronic non-pitting oedema due to lymphatic insufficiency. It is most commonly seen affecting the legs and tends to progress with age. The legs can become enormous and prevent wearing of normal shoes. Chronic disease may cause a secondary 'cobblestone' thickening of the skin. Lymphoedema can be primary (and present early in life) owing to an inherited deficiency of lymphatic vessels (e.g. Milroy's disease) or can be secondary because of obstruction of lymphatic vessels (e.g. filarial infection or malignant disease).
Treatment is with compression stockings and physical massage. If there is recurrent cellulitis, long-term antibiotics are advisable as each episode of cellulitis will further damage the lymph vessels. Surgery should be avoided.
Lymphangioma circumscriptum
Lymphangioma circumscriptum is a rare hamartoma of lymphatic tissue. It usually presents in childhood with multiple small vesicles in the skin which weep lymphatic fluid and sometimes blood. They reflect deeper vessel involvement so surgery should be avoided. Cryotherapy or CO2 laser treatment may help the superficial lesions.
FURTHER READING
Cullum N et al. (2003) Pressure sores. Clinical Evidence 9: 2167-2176.
Fiorentino DF (2003) Cutaneous vasculitis. Journal of the American Academy of Dermatology 48: 311-340.
Health Technology Assessment Programme - Systematic Reviews of Wound Care Management (1999) Vol. 3, No. 17 (parts I and II); (2000) Vol. 4, No. 21; (2001) Vol. 5 No. 9. London: Department of Health. Online. Available: http://www.ncchta.org.
Topham EJ et al. (2002) Chronic lower limb oedema. Clinical Medicine 2: 28-31.
Valencia IC et al. Chronic venous insufficiency and venous leg ulceration (2001) Journal of the American Academy of Dermatology 44: 401-421.

DISORDERS OF COLLAGEN AND ELASTIC TISSUE:

Ehlers-Danlos syndrome (see also p. 602)
Ehlers-Danlos syndrome can be subdivided into at least 10 variants. They are all inherited disorders causing abnormalities in collagen of the skin, joints and blood vessels. Clinically this causes increased elasticity of the skin, hypermobile joints and fragile blood vessels causing easy bruising or in some cases internal haemorrhage. The skin is hyperextensible but recoils normally after stretching. It is easily injured and heals slowly with scarring like tissue paper. Pseudotumours may occur at the sites of scarring (such as elbows and knees) consisting mainly of fat, but calcification can occur.
Pseudoxanthoma elasticum
Pseudoxanthoma elasticum is a rare group of disorders characterized by abnormalities in collagen and elastic tissue affecting the skin, eye and blood vessels. The skin may be loose, lax and wrinkled. It can look yellowish and papular ('plucked chicken skin') and tends to lose its elastic recoil when stretched. Skin changes are best seen in the flexures especially the sides of the neck. Non-cutaneous features are not always present but they include recurrent gastrointestinal bleeding, early myocardial infarction, claudication and angioid streaks on the retina reflecting disruption of vascular elastic tissue.
Marfan's syndrome (see also p. 839)
Marfan's syndrome, an autosomal dominant disorder of connective tissue, is described on page 839. The syndrome is characterized by tall stature and long thin digits (arachnodactyly) (Fig. 13.98). The arm span can exceed the height of the patient and a high arched palate may be present. Lax ligaments result in frequent dislocation of joints. Inguinal and femoral hernias are common. Scoliosis and flat feet may be present. Pulmonary changes include emphysema, diaphragmatic hernia and spontaneous pneumothorax. Dislocation of the ocular lens is common. Skin changes are usually absent but striae may develop. Patients with homocystinuria (see p. 602), type III and VI Ehlers-Danlos syndrome (EDS) and 'marfanoid phenotype' have some similar features but often do not develop the life-threatening complications of Marfan's syndrome, so accurate diagnosis by an expert is essential.
Treatment
Patients should be reviewed by an ophthalmologist, an orthopaedic surgeon and a cardiologist to screen for and deal with the above complications. Genetic counselling should be offered to families.
Striae

Striae are visible linear scars due to dermal collagen damage and stretching. Histologically a thinned epidermis overlies parallel bundles of fine collagen. They occur commonly over the abdomen and breasts in pregnancy but also occur on the thighs and trunk in rapidly growing adolescents as well as in some obese individuals. They are also seen in Cushing's syndrome and corticosteroid therapy. Striae are initially reddish blue but fade to white atrophic marks. Puberty-related striae normally disappear completely.
Keloid scars
Keloid scars are characterized by smooth hard nodules (Fig. 23.36) due to excessive collagen production. They may occur spontaneously or follow skin trauma/surgery, and they are often itchy. They tend to affect young adults and are much commoner in black Africans. Sites of predilection include the shoulders, upper back and chest, ear lobes and the chin. Unlike hypertrophic scars (which fade within 12 months) keloids are persistent and may fade with time.
Treatment is with triamcinolone injection, compression with silica gels or surgery but the latter must be followed by steroid injection or superficial radiotherapy or it may make the problem worse.
FURTHER READING
Hu X et al. (2003) ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum. European Journal of Human Genetics 11: 215-224.
Ohtani T et al. (2002) Pseudoxanthoma elasticum. Journal of Dermatology 29: 615-620.
Wordsworth P et al. (2001) The real connective tissue diseases. Clinical Medicine 1: 21-24.

DISORDERS OF PIGMENTATION :

HYPOPIGMENTATION
Vitiligo is a common disorder of depigmentation which probably has an autoimmune aetiology. Sufferers often have relatives with other organ-specific autoimmune disorders. It presents in childhood or early adult life with well-demarcated macules of complete pigment loss. There is no history of preceding inflammation. Patients are very susceptible to sunburn. Lesions are often symmetrical and frequently involve the face, hands (Fig. 23.37) and genitalia. The hair can also depigment. Trauma may induce new lesions. Spontaneous repigmentation can occur and often starts around hair follicles, giving a speckled appearance. However, repigmentation is rare if a lesion has persisted for more than 1 year or if the hair is depigmented. The psychological consequences of vitiligo can be devastating especially in Asian or black African people.

Treatment is very unsatisfactory and has no impact on the long-term outcome. Sunblocks should be used to prevent burning. Potent topical steroids or phototherapy help some individuals. Treatment with 0.1% tacrolimus ointment is currently under assessment, with conflicting early results. If vitiligo is almost universal and fixed, depigmentation with monobenzone may be considered. Finally, referral to a specialist camouflage clinic is often the most helpful 'treatment'.

Post-inflammatory hypopigmentation

This is one of the most common causes of pale skin. It is much more common in people with pigmented skin. It is seen as a consequence of eczema, acne or psoriasis and may even be the reason for individuals presenting to a doctor. Providing the skin disease is controlled, the pigmentation will recover slowly after many months. Post-inflammatory hyperpigmentation can also occur.

Oculocutaneous albinism

This is a group of rare autosomal recessive disorders affecting the pigmentation of skin, hair and eyes. It can affect all races. Melanocytes are in normal number but have abnormal function. Clinically it presents with universal pale skin, white or yellow hair and a pinkish iris. Photophobia, nystagmus and a squint are also present in most cases.

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Treatment involves obsessive protection against sunlight to avoid sunburning and development of skin cancer.

Idiopathic guttate hypomelanosis

This occurs most commonly in black African people and is of unknown aetiology. It presents with small (2-4 mm) asymptomatic porcelain-white macules, often on skin exposed to sunlight. The borders are often sharply defined and angular. There is no effective treatment.

Leprosy (see also p. 80)

Both tuberculoid leprosy and indeterminate leprosy can present with anaesthetic patches of depigmentation and should always be considered in people from endemic regions. Loss of hair and decreased sweating may also be present in the lesions.

HYPERPIGMENTATION

Freckles (ephelides)

These appear in childhood as small brown macules after sun exposure. They fade in the winter months.

Lentigos

These are a more permanent macule of pigmentation similar to freckles but they tend to persist in the winter. Solar lentigos (also called 'liver spots') occur in older people on exposed skin because of actinic damage.

Chloasma

These are brown macules often seen symmetrically over the cheeks and forehead and are most common in women. They can occur spontaneously but are also associated with pregnancy and the oral contraceptive pill.

Metabolic/endocrine effects

A generalized skin darkening can occur with chronic liver disease, especially haemochromatosis. It also is seen sometimes in Cushing's syndrome, Addison's disease (more marked in palmar creases and buccal mucosa) and Nelson's syndrome.

Peutz-Jeghers syndrome (p. 309)

This is an autosomal dominant genetic condition. It presents with brown macules of the lips and perioral region. It is associated with gastrointestinal polyposis which occasionally become malignant.

Urticaria pigmentosa (cutaneous mastocytosis)

This presents most commonly with multiple pigmented macules in children. These lesions tend to become red, itchy and urticated if they are rubbed (Darier's sign). Occasionally lesions may blister and in the rare congenital, diffuse form of the disease the skin can become thickened and leathery.

Occasionally, systemic symptoms are present, such as wheeze, flushing, syncope or diarrhoea, reflecting extensive mast cell degranulation from the skin. Anaphylaxis occurs very rarely and may be precipitated by mast cell degranulators such as aspirin or opiates. The condition spontaneously resolves after some years in children but is persistent in adults.

Skin biopsy shows an excess of mast cells in the skin. Recently a mutation in the proto-oncogene c-kit has been demonstrated, resulting in mast cell proliferation and mast cell apoptosis. Monoclonal antibodies against mast cell markers (tryptase and CD117) on immunohistochemistry confirm the diagnosis.

Treatment of the skin, if required, is with antihistamines or PUVA.

Rarely there may be infiltration of internal organs with mast cells (systemic mastocytosis), especially in adult disease or neonatal disease. This can involve any organ but especially the bone (where it can cause severe pain), gastrointestinal tract, liver and spleen. There is a small risk of developing leukaemia if the bone marrow is heavily infiltrated.

Other conditions with pigmentation

Café-au-lait macules are seen in neurofibromatosis types 1 and 2. They also occur in a wide variety of disorders including tuberous sclerosis, ataxia, telangiectasia, Fanconi's anaemia, multiple endocrine neoplasia type 1, McCune-Albright syndrome.

Multiple lentigines: apart from in Peutz-Jeghers syndrome these are also seen in xeroderma pigmentosum.

Acquired melanocytic naevi are seen in Turner's syndrome (p. 1064) and familial atypical mole-melanoma syndrome (dysplastic naevi, p. 1351).

FURTHER READING

Tharp MD et al. (2003) Mastocytosis. Advances in Dermatology 19: 207-236.

DRUG-INDUCED RASHES:

Drugs can be toxic and teratogenic but they can also cause problems through allergic reactions. This frequently presents in the skin where just about any type of skin rash can arise (Table 23.14) although a widespread symmetrical maculopapular rash is the most common type (Fig. 23.38). 'Fixed drug eruptions' may occur where a rash evolves and resolves at a specific site. The rash is reproduced at exactly the same site after a repeated exposure.

A thorough history is of great value and always think of a drug cause for any skin condition. The use of prick-testing and patch-testing is rarely helpful and not without risk. Drug allergy can only be proven by rechallenging but this is rarely justified as it carries some risks. Rechallenging is occasionally justified for antituberculosis drugs or antiretroviral drugs but this should be carried out as an inpatient as there is a risk of anaphylaxis. Certain individuals (e.g. those with HIV infections) are more susceptible to drug rashes (Fig. 23.39).

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Table 23-14. Morphological types of drug rashes and some common causes

Maculopapular Penicillin/amoxicillin

Urticaria Penicillin, aspirin

Vasculitis Gold, hydralazine

Fixed drug rash Phenolphthalein in laxatives, tetracyclines, paracetamol

Pigmentation Minocycline (black), amiodarone (slate grey)

Lupus erythematosus Penicillamine, isoniazid

Photosensitivity Thiazides, chlopromazine, sulphonamide, amiodarone

Pustular Carbamazepine

Erythema nodosum Sulphonamide, oral contraceptive

Erythema multiforme Barbiturates

Acneiform Corticosteroids

Lichenoid Chloroquine, thiazides, gold, allopurinol

Psoriasiform Methyldopa, gold, lithium, beta-blockers

Toxic epidermal necrolysis Penicillin, co-trimoxazole, carbamazepine, NSAIDs

Pemphigus Penicillamine, ACE inhibitors

Erythroderma Gold, sulphonylureas, allopurinol







Figure 23.38 Morbilliform drug rash due to penicillin allergy.





Figure 23.39 Erythema nodosum in a patient with HIV on co-trimoxazole.

Most rashes will settle spontaneously once the offending agent is removed. The commonest culprits in a hospital setting are antibiotics and chemotherapy agents. The three most serious types of drug rashes are:

erythroderma (p. 1340)

toxic epidermal necrolysis

anticonvulsant hypersensitivity syndrome.

Toxic epidermal necrolysis is characterized by a widespread subepidermal blistering and sloughing of most of the skin. The skin may be itchy but typically takes on a burning quality. Fever and mucosal involvement are common. The internal epithelial surfaces (lung, bladder, gastrointestinal tract) are also involved. Multiorgan failure and sepsis often occur. Toxic epidermal necrolysis can be fatal even after drug withdrawal and intensive care support. Patients should be managed in intensive care or a specialized burns unit. Occlusive cutaneous dressings significantly reduce the pain. Ophthalmological assessment and oral hygiene are necessary. Specific medical treatment with steroids or ciclosporin is controversial. Intravenous immunoglobulin may be beneficial if given early in the disease.

A variant exists called Stevens-Johnson syndrome where the damage is restricted to the mucosal surfaces with milder bullous involvement of the skin.

Anticonvulsant hypersensitivity syndrome is characterized by a generalized mucocutaneous rash, fever and lymphadenopathy with variable arthralgia, pharyngitis, periorbital oedema and hepatosplenomegaly. Rarely pustulation of the skin and conjunctivitis are present. The blood may show a peripheral eosinophilia, lymphocytosis with atypical lymphocytes, and a hepatitic picture. It can progress to multiorgan failure. This reaction occurs typically 3-4 weeks into therapy. It can occur with any of the aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital, primidone and clonazepam). As they often cross-react, all these drugs must be avoided in the future. Sodium valproate is a suitable alternative. There is also potential for cross-reaction with the newer anticonvulsants vigabatrin and lamotrigine.

FURTHER READING

Baba M et al. (2003) The anticonvulsant hypersensitivity syndrome. Journal of the European Academy of Dermatology and Venereology 17: 399-401.

Breathnach SM (2002) Adverse cutaneous reactions to drugs. Clinical Medicine 2: 15-19.

Campione E et al. (2003) High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic epidermal necrolysis. Acta Dermato-venereologica 83: 430-432.

Fiszenson-Albala F et al. (2003) A 6-month prospective survey of cutaneous drug reactions in a hospital setting. British Journal of Dermatology 149: 1018-1022.

Sullivan et al. (2001) The drug hypersensitivity syndrome. Archives of Dermatology 137: 357-364.

DISORDERS OF NAILS:

Nail pitting can be caused by psoriasis, alopecia areata and atopic eczema. A few pits can be present because of trauma.
Onycholysis (distal nail plate separation) is caused by psoriasis, thyrotoxicosis, following trauma and rarely due to a photosensitive reaction to drugs such as tetracyclines.

Koilonychia (thin spoon-shaped nails) can be caused by iron deficiency anaemia or rarely is congenital.

Leuconychia (white nails) is seen in hypoalbuminaemia. A striate congenital leuconychia exists.

Beau's lines (transverse lines) appear as solitary depressions which grow out slowly over many months. They arise due to a severe illness or shock which causes a temporary arrest in nail growth.

Yellow-nail syndrome is a rare disorder of lymphatic drainage. It presents with thickened, slow-growing, yellow nails with associated pleural effusions, bronchiectasis and lymphoedema of the legs.

Onychogryphosis is a gross thickening of the nail which is seen in later life especially in the big toe-nail. There is often a history of preceding trauma. Both psoriasis and fungal infection can also cause nail thickening.

Nail-patella syndrome is an autosomal dominant condition which presents with triangular rather than half-moon-shaped lunulae, especially of the thumb and forefingers. The nail plates may be small or dystrophic. The patellae are hypoplastic or absent. Other skeletal anomalies can be present and renal impairment (glomerulonephritis) occurs in up to 30% of individuals.

Melanonychia (longitudinal brown streaks) are seen as a normal variant in black-skinned patients. In a white patient it may reflect an underlying subungual melanoma, especially if the pigmentation progresses proximally onto the nail fold ('Hutchinson's sign').

Clubbing is discussed on page 884.



FURTHER READING

Baran R, Dawber RPR (eds.) (2001) Diseases of the Nails and their Management, 3rd edn. Oxford: Blackwell Scientific Publications.

BIRTH MARKS/NEONATAL RASHES:

Strawberry naevus (cavernous haemangioma)
Strawberry naevus affects up to 1% of infants. It presents at, or shortly after, birth as a single red lumpy nodule (Fig. 23.40) that grows rapidly for the first few months. Multiple lesions can be present. They will spontaneously resolve with good cosmesis but this may take up to 7 years for complete resolution. Occasionally plastic surgery is needed after resolution to remove residual slack skin. Reassurance of parents is usually all that is required.

Treatment is indicated if:

the lesion interferes with feeding or vision

the lesion ulcerates or bleeds frequently

the lesion is associated with high-output cardiac failure from shunting of large volumes of blood

the lesion consumes platelets and/or clotting factors causing potentially life-threatening haemorrhage ('Kasabach-Merritt syndrome').

The latter two complications are very rare and only tend to occur in large lesions with significant deep vessel involvement.





Figure 23.40 Strawberry naevus (cavernous haemangioma).

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Treatment modalities include intralesional or oral corticosteroids, surgery (for selected lesions), and tunable dye laser (for treating ulceration). Alpha-interferon injections, vincristine or embolization is only used for life-threatening events.

Port-wine stain (naevus flammeus)

Port-wine stain is also called a capillary haemangioma but strictly speaking it is not a haemangioma but is just an abnormal dilatation of dermal capillaries. It presents at birth as a flat red macular area and is commonly found on the face. It does not improve spontaneously and it may become thickened with time. If the lesion is found in the distribution of the first division of the trigeminal nerve it may be associated with ipsilateral meningeal vascular anomalies which can cause epilepsy and even hemiplegia (Sturge-Weber syndrome, p. 1257). If a port-wine stain involves the skin near the eye, glaucoma is a risk and ophthalmic assessment is mandatory.

Treatment of port-wine stains is ideally carried out with the tunable dye laser.

Milia

'Milk spots' are small follicular epidermal cysts. They are small pinhead white papules commonly found on the face of infants. They resolve spontaneously.

Mongolian blue spot

This appears in infants as a deep blue-grey bruise-like area, usually over the sacrum or back, and is occasionally mistaken as a sign of child abuse. It is due to deep dermal melanocytes. It is very common in Oriental children, less common in black Africans and rare in Caucasians. It has usually disappeared by the age of 7 years.

Toxic erythema of the newborn (erythema neonatorum)

Toxic erythema of the newborn is a term used to describe a common transient blotchy maculopapular rash in newborns. The rash is occasionally pustular but the child is not toxic or unwell. It disappears within a few days, spontaneously.

Nappy rash ('diaper dermatitis')

This is an irritant eczema caused by occlusion of faeces and urine against the skin. It is almost universal in babies. The flexures are usually spared, which is a useful differentiating feature from seborrhoeic and atopic eczema. If satellite lesions are present around the edge, it may indicate a superimposed Candida infection. This rash can also occur in the elderly incontinent.

Treatment involves frequent changing of the nappy and regular application of a barrier cream.

Acrodermatitis enteropathica (p. 249)

This is due to a rare inherited deficiency of zinc absorption. It presents 4-6 weeks after weaning, or earlier in bottle-fed babies. There is an erythematous, sometimes blistering, rash around the perineum, mouth, hands and feet. It may be associated with photophobia, diarrhoea and alopecia.

Treatment is with lifelong oral zinc, which seems to override the poor absorption. The response is rapid.

FURTHER READING

Bruckner AL et al. (2003) Hemangiomas of infancy. Journal of the American Academy of Dermatology 48: 477-493.

Harper J, Oranje A, Prose N (eds) (2000) Textbook of Pediatric Dermatology. Oxford: Blackwell Scientific.

DISORDERS OF HAIR :

HAIR LOSS

Hair loss can be due to a disorder of the hair follicle in which the scalp skin looks normal (non-scarring alopecia) or due to a disorder within the scalp skin that causes permanent loss of the follicle (scarring or cicatricial alopecia). This latter form causes shiny atrophic bald areas in the scalp which are devoid of follicular openings. There are many causes of alopecia (Table 23.15).

Androgenic alopecia

Table 23-15. Causes of alopecia

Scarring alopecia Non-scarring alopecia

Discoid lupus erythematosus Androgenic alopecia

Telogen effluvium

Kerion (tinea capitis) Alopecia areata

Lichen planus

Dissecting cellulitis Trichotillomania (self-induced hair-pulling)

X-irradiation Tinea capitis

Idiopathic ('pseudopelade') Traction alopecia

Metabolic (iron deficiency, hypothyroidism)

Drug (e.g. heparin, isotretinoin, chemotherapy)



Androgenic alopecia (male pattern baldness) is the most common type of non-scarring hair loss and depends on genetic factors and an abnormal sensitivity to androgens. It presents in young men with frontal receding followed by thinning of the crown and there is often a positive family history. It also occurs in females but tends to occur at a later age, be milder and show little in the way of frontal recession. If acne and menstrual disturbance are also present, polycystic ovary syndrome and other endocrine disorders of androgens can be present.

Treatment.

This may not be required. Topical 5% minoxidil lotion or oral finasteride (1 mg daily) can help arrest progression and may cause a small amount of regrowth, providing it is used early in disease but the treatment needs to be continued possibly lifelong. Approximately one-third of patients will not respond to either therapy. Finasteride is a selective inhibitor of 5α-reductase type II and it can cause side-effects in 1% of patients such as loss of libido. It should not be used in females as it can affect the sexual development of a male fetus. However, antiandrogen therapy (e.g. cyproterone acetate or spironolactone) helps some women.

Alopecia areata

Alopecia areata is an immune-mediated type of hair loss. It is associated with other organ-specific autoimmune diseases. It presents in childhood or young adults with patches of baldness. These may regrow to be followed by new patches of hair loss. The presence of broken exclamation mark hairs (narrow at the scalp/wider and more pigmented at the tip) at the edge of a bald area is diagnostic. Regrowth may initially be with white hairs and often occurs slowly over months. Occasionally all of the scalp hair is lost (alopecia totalis) and rarely all body hair is lost (alopecia universalis). The nails may be pitted or roughened.

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Treatment has no effect on the long-term progression. Potent topical or injected steroids are of limited use. Topical immunotherapy with diphencyprone, PUVA or topical 5% minoxidil are occasionally tried but often do not help. Wigs can be provided for severe cases and patient support groups are often beneficial.

Traction alopecia

This refers to the 'mechanical damage' type of hair loss that arises from pulling the hair back into a bun or tight plaiting. It is more common in black Africans.

Telogen effluvium

Telogen effluvium refers to the pattern of diffuse hair loss that occurs some 3 months after pregnancy or a severe illness. It occurs because 'stress' puts all the hairs into the telogen phase of hair shedding at the same time. The hair fully recovers and the normal staggered hair growth/hair shedding cycle resumes within a few months.

Dissecting cellulitis

This is a chronic folliculitis affecting predominantly young black males. It presents with papules and pustules over the occipital region of the scalp with hair loss. If severe, the back of the scalp becomes a boggy swelling (discharging pus) with areas of scarring alopecia. It can be complicated by keloid scar formation ('acne keloidalis nuchae').

Treatment is difficult but prolonged courses of low-dose antibiotics are worth trying in early disease. Prolonged courses of isotretinoin can help a few individuals and deep surgical excision can be used in recalcitrant cases.

INCREASED HAIR GROWTH

Hirsutism (p. 1058)

Hirsutism refers to the male pattern of hair growth seen in females. The racial variation in hair growth must be considered. Certain races (e.g. Mediterranean and Asian) have more male pattern hair growth than northern European females. This is not due to excess androgens but may reflect a genetically determined altered sensitivity to them. If virilizing features (deep voice, clitoromegaly, dysmenorrhoea, acne) are present, one should carry out a full endocrine assessment. Hirsutism can cause severe psychological distress to some individuals.

Treatment involves physical methods such as bleaching, waxing, electrolysis and laser therapy. Antiandrogen therapy is occasionally helpful.

Hypertrichosis

Hypertrichosis refers to the state of excessive hair growth at any site and occurs in both sexes. It can be seen in anorexia nervosa, porphyria cutanea tarda, and underlying malignancy and is caused by certain drugs (e.g. ciclosporin, minoxidil).

FURTHER READING

Barth JH (2000) Should men still go bald gracefully? Lancet 355: 161-162.

MacDonald Hull SP et al. (2003) Guidelines for the management of alopecia areata. British Journal of Dermatology 149: 692-699.

Price VH (1999) Treatment of hair loss. New England Journal of Medicine 341: 964-973.

Wendelin DS et al. (2003) Hypertrichosis. Journal of the American Academy of Dermatology 48: 161-179.

HUMAN IMMUNODEFICIENCY VIRUS AND THE SKIN :

HIV infection commonly causes significant dermatological problems. A rash may even be the presenting feature of underlying HIV infection. It is estimated that 90% of HIV-positive patients will suffer with a mucocutaneous disorder during the illness. It is also estimated that up to 30% of people with AIDS will suffer from three different dermatoses. These rashes can often be clinically atypical and difficult to diagnose. One must have a low threshold for skin biopsy and skin culture. On top of this many of the skin problems are resistant to standard treatments. Most of these dermatoses have become less prevalent since the advent of HAART (p. 144).

Cutaneous infection and opportunistic infection

Not surprisingly, infections are increased because of the HIV-induced immune deficiency. Molluscum contagiosum are particularly common especially on the face. They are often multiple and of a 'giant' size measuring over 1 cm across. Molluscum are rarely seen in adults and they can be the presenting feature of HIV. Other viral infections such as extensive ulcerative herpes or widespread viral warts may be seen. Bacterial infections (e.g. staphylococcal boils) and fungal infections (e.g. ringworm and Candida) are also common. Recalcitrant and recurrent oropharyngeal candidiasis is a particular problem.

Opportunistic infections such as cutaneous cytomegalovirus (pustules or necrotic ulcers), sporotrichosis (linear nodules) or cryptococcus (red papules, psoriasiform or molluscum-like lesions) can pose diagnostic difficulties, stressing the need for skin biopsy and culture.

Inflammatory dermatoses

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Inflammatory dermatoses show an increased incidence with HIV infection, probably due to an immune dysfunction or imbalance rather than as a consequence of immune suppression. Severe, extensive seborrhoeic eczema is very common and may be a presenting sign of HIV. Other types of eczema, psoriasis, ichthyosis (dry scaly skin), nodular prurigo and pruritus are all common in HIV infection and can be very severe. Granuloma annulare and lichen planus are probably increased in incidence. The treatment of these conditions is difficult as oral immunosuppressive therapies (e.g. prednisolone, ciclosporin) are best avoided in patients with low CD4 counts. Topical therapies and phototherapy seem relatively safe. Oral retinoids are useful in the management of psoriasis.

'Autoimmune dermatoses'

Bullous pemphigoid, thrombocytopenic purpura, and vitiligo seem to be increased in incidence. The polyclonal stimulation of B lymphocytes by HIV and the resulting abnormal antibody production may be involved in their aetiology. Erythroderma is sometimes seen in HIV disease where skin biopsy suggests a 'graft-versus-host disease' mechanism. This presumably reflects a severe underlying immune dysfunction of T lymphocyte control.

Drug rashes

Adverse drug rashes are much commoner in HIV patients. Reactions to co-trimoxazole, dapsone and antiretroviral drugs appear particularly common. Drug rashes may be severe (especially with nevirapine) resulting in erythroderma or toxic epidermal necrolysis. Other unusual rashes include a striking nail/mucosal pigmentation from zidovudine, paronychia from indinavir and facial lipodystrophy mostly from protease inhibitors.

Cutaneous tumours

Kaposi's sarcoma (p. 142) is much commoner in homosexuals with HIV than in other groups. Basal and squamous cell carcinomas and benign melanocytic naevi are also a little increased in incidence, presumably reflecting a loss of immune surveillance.

'Specific' HIV dermatoses

'Itchy folliculitis' of HIV (also called papular pruritic eruption)

Itchy follicular eruptions are common in HIV as CD4 counts decline. The previously described staphylococcal folliculitis, eosinophilic folliculitis, pityrosporum folliculitis, and demodex mite folliculitis are probably all part of a spectrum and the term itchy folliculitis is useful to encompass these. It presents with intensely itchy papules centred on hair follicles and occurring most commonly over the upper trunk and upper arms. The face is more commonly involved in black patients. Individual lesions frequently have the top scratched off, leaving a crateriform appearance. The aetiology is unknown but may reflect a hypersensitivity reaction as high IgE and eosinophil counts may be present.

Treatment with oral minocycline, potent topical steroids and emollients may help. Phototherapy or oral isotretinoin is useful in resistant cases.

Oral hairy leucoplakia

This is characterized by white plaques with vertical ridging on the sides of the tongue. Unlike with oral Candida, the lesions cannot be peeled off to leave raw areas underneath. It was first recognized in HIV disease but can rarely occur in other forms of immunosuppression. It is thought to be due to co-infection with Epstein-Barr virus.

Treatment with aciclovir, ganciclovir or foscarnet may help.

FURTHER READING

Osborne GE et al. (2003) The management of HIV-related skin disease. Part I: infections. International Journal of STD & AIDS 14: 78-86.

Osborne GE et al (2003) The management of HIV-related skin disease. Part II: neoplasms and inflammatory disorders. International Journal of STD & AIDS 14: 235-240.