Category Archives: Dermatology

Diseases of the hair and nails

Both hair and nails are composed of keratin and are derived principally from the epidermal layer. Each may be affected by the same type of disease process, e.g. lichen planus, or altered by conditions that affect primarily the epidermis.

DISORDERS OF HAIR GROWTH

The extent and distribution of body hair is largely determined genetically. At the time of puberty, terminal hair growth occurs in males on the beard area, over the upper lip, chest, abdomen and thighs. Androgens determine the extent of secondary sexual patterns of hair growth during adolescence in both sexes. In females any marked alteration in the extent of hair growth or hair loss at times other than at puberty or the menopause may reflect serious endocrine disturbance.

Hirsuties

Hirsuties is defined as an excessive growth of hair of male type and distribution in females. In many parts of the world an excess of body hair is accepted as a racial characteristic or may, in addition, be seen as a family trait. In the Western World, excess body hair in females is considered less acceptable and women may become selfconscious about the extent of their hair growth. Most hirsute females do not have recognizable clinical or biochemical evidence of endocrine disease, though this must be excluded by a careful history, examination and hormone profile where appropriate. Some drugs alter the texture and extent of hair growth; these include cortisone, minoxidil, diazoxide, hydantoins and cyclosporin. Here the hair growth is non-androgenic in pattern and the term hypertrichosis is used. Methods of hair removal include abrasion with mittens that have a roughened surface, shaving and plucking, but these give short-term relief. Depilatory creams and waxing should not be used frequently on facial hair but may be used elsewhere, such as on the legs. Bleaching facial hair with peroxides will produce an acceptable appearance for fine hair. Coarse hairs are best dealt with by electrolysis but this needs to be performed by skilled personnel and may produce scarring, especially if acne is a concurrent problem on the chin. With severe hirsutism, antiandrogens (e.g. cyproterone acetate) or prednisolone (5 mg at night and 2.5 mg in the morning) may be used to produce a slowing of hair growth so that mechanical removal need not be so frequent or vigorous.

Hair loss

Hair loss that occurs to the extent that scalp skin becomes  abnormally visible is termed alopecia. It may be permanent, when the hair follicles are damaged by scarring (e.g. in lichen planus or discoid lupus erythematosus), or may recover if the follicles are left intact (e.g. in some endocrine diseases or alopecia areata).

Diffuse hair loss

Hairs are lost in the telogen phase. Normally about 100 hairs are shed each day. In severe illness or following pregnancy there is an increase in the number of hairs entering the telogen phase (telogen effluvium). Hair loss is seen 3-4 months after the event when the new anagen hair pushes out the old telogen hair. Nail growth may be affected in the same way.
Other causes of diffuse hair loss include endocrine disease such as hyperthyroidism or hypothyroidism and androgen overactivity in both males and females. Iron deficiency, rapid weight loss associated with dieting, and drugs such as lithium or vitamin A and its derivatives also produce diffuse and treatable hair loss.

Androgenetic alopecia

This is premature hair loss in both males and females over the vertex of the scalp. Increased Sa-reduction of testosterone to dihydrotestosterone (DHT) occurs in frontal, but not occipital, hair follicles. DHT is responsible for miniaturization of follicles, fine hair growth ensues and there is a shortening of the anagen phase of hair growth.

Alopecia areata

This occurs in both sexes and all races and is usually seen in young adults or children as a well-defined patch of hair loss. Only 25% of cases are seen over the age of 40 years and 25% of patients give a family history of the condition.

AETIOLOGY. There is often a personal or family history of atopy. Alopecia areata occurs in association with autoimmune diseases such as thyrotoxicosis, Addison’s disease, pernicious anaemia and vitiligo. The association of alopecia areata with such diseases suggests that immune changes are important in the pathogenesis. It is also seen in association with Down’s syndrome and hypogammaglobulinaemia. CLINICAL FEATURES. Patches of hair loss can occur over any part of the body, e.g. the beard area or eyebrows, but the scalp is most frequently affected. Asymptomatic loss may first be noticed by a relative or hairdresser. Patches tend to regrow over the course of several months within the scalp margin in adults. An extension into the actual hair margin (ophiasis) is often less quick to recover. Children with an atopic background may lose all their scalp hair (alopecia totalis) and the prognosis in such patients should be guarded; alopecia totalis is seen· less frequently in adults. Loss of hair from all body sites(alopecia universalis) may occur by extension from other  sites but can also occur acutely. The extension of hair loss occurs in a peripheral fashion; at the advancing edge, broken hairs (exclamation mark hairs) provide evidence of disease activity. Diffuse loss of hairs in alopecia areata is an infrequent occurrence and may be difficult to differentiate from other causes of hair loss. Regrowing hair appears as a fine, depigmented downy growth. Areas of alopecia principally affect pigmented hair and premature greying is seen after diffuse hair loss.

TREATMENT

 Large doses of corticosteroids will produce a regrowth of hair, but relapse often occurs after treatment is stopped. Topical corticosteroids may also help to speed the rate of regrowth of hair. Other treatment modalities, effective in small numbers of patients, include PUV A therapy and topical minoxidil. This is available as a 2% solution. It will induce hair growth in about onethird of individuals but this tends to fall out on cessation of treatment.

Premature male-pattern baldness

Recession of the hair margin is an ageing characteristic of primates. This may appear early in males but such a pattern of loss in young females may indicate serious androgenicity. Vertical thinning is seen in association with margin recession in both sexes. In young women there is often evidence of androgen excess, which may be treated by antiandrogen therapy over an interval of a year with some recovery. The primary defect is atrophy of the hair follicle. It is due to a number of factors other than excess androgen activity, for antiandrogen therapy is not always effective in stimulating strong terminal hair growth in females.

Abnormalities of the hair shaft

The hair shaft may become twisted, beaded or broken, leading to hair loss. Short, unruly or broken hair is then the primary complaint. Similar patterns of loss will be seen with drying of the hair or the effect of weathering, cosmetics, bleaching agents or grooming.Traction Traction associated with fashion, traditional or ethnic  practices, such as hot combing, braiding or plaiting, may also cause a localized hair fall, especially over the temporal region. Straightening or relaxing the hair, undertaken by those with naturally curly hair may, in addition, produce permanent root damage.

DISEASES OF THE NAilS

The nail plate grows continuously, although the rate slows with advancing years, and with some generalized diseases. Growth of finger-nails is normally at a rate of about 1 cm every 3 months, so that renewal of a fingernail may take 6 months, and toe-nails, which grow moreslowly, may take from 18 months to 2 years. An increase in the rate of growth of the nail plate occurs in psoriasis and other skin diseases.
The nail plate arises from the matrix and lies on the nail bed that also contributes to its growth. The hard outer layer is formed from the proximal matrix and the bulk of the nail, composed of soft keratin, is produced by the distal matrix.
The nail matrix lies within a fold of epidermis, so that dermatoses or infections that involve the posterior nail  fold may also cause abnormalities of the  nail plate; these include chronic paronychia, fungal disease, eczema and psoriasis. These nail changes have been discussed in the appropriate sections.
Congenital defects of the nail occur in conjunction with abnormalities of the epidermis, teeth or skeleton. Nail disorders in generalized diseases

Clubbing

Connective tissue diseases

Short and brittle nails occur in severe circulatory disorders, e.g. Raynaud’s phenomenon, especially in association with systemic sclerosis. Pterygium formation also occurs when a thin skin-fold merges with the cuticle, widening it by several millimetres. Chronic paronychia may persist despite all therapeutic manoeuvres in patients with severe digital ischaemia. Nail fold capillary dilatation and distortion or the absence of capilla ries, usually with severe Raynaud’sphenomenon, is seen in systemic sclerosis. Ragged cuticles  containing haemorrhages are often most pronounced in patients with dermatomyositis.

YeIIow nail syndrome

The nail plate is thickened, yellow in colour, smooth and with an increased lateral curvature. The rate of growth the nail is reduced. Such nails are seen in association with chronic oedema of the hands, feet, ankles or face, congenital lymphoedema, pleural effusions, chronic sinus
infection and thyroid disease.

 White bands

Distal white bands that are parallel to the lunula and separated from this and each other by a normal pinkcoloured portion are seen in patients with hypoalbuminaemia. The nails return to normal when the level of protein is restored.

Half-and-half nails

This is the name given to nails in which the proximal nail is pale or white and the distal portion is red or brown in colour; these nails occur in renal failure.

Brown streaks

Longitudinal brown streaks are commonly seen in black patients when pigment cells are incorporated into the nail matrix. Alteration of pigment beneath the nails that is localized and not related to obvious trauma in whiteskinned patients may require a biopsy of the nail to exclude subungual melanoma.

Onycholysis

Onycholysis or separation of the distal edge of the nail from the vascular nail bed will cause whiteness of the free edge and this most commonly follows trauma or faulty or excessive manicure. Psoriasis is another common cause and similar changes may be seen in thyrotoxicosis or following photo-onycholysis produced by photoactive drugs such as tetracycline or psoralens, as well as in porphyria. Splinter haemorrhages
These are most frequently caused by trauma to the nail;
infective endocarditis, SLE and psoriasis are less common causes.

Koilonychia

Spoon-shaped nails or koilonychia is seen in association with iron deficiency anaemia but it may also follow trauma, e.g. in garage mechanics who regularly fit tyres.

Chronic paronychia

This is due to chronic infection from Candida albicans. It is rarely a manifestation of an underlying systemic disease such as hypoparathyroidism, multiple endocrine disease or chronic iron deficiency.

Transverse lines

Transverse lines (Beau’s lines) related to acute physical or psychiatric illness or the use of cytotoxic drugs represent a temporary arrest of growth. They may be associated with an arrest of hair growth and subsequent fall (telogen effluvium).

Blue discoloration of the nail

This may be seen in hepatolenticular degeneration (Wilson’s disease) as blue lanulae.

Effects of drugs

A number of drugs, including antimalarials such as chloroquine, may cause a blue/black discoloration of the nail plate. Mepacrine may stain the nail plate blue and fluoresces green on examination by Wood’s light. Argyria occurring as an occupational disease or following, for . example, the use of silver-containing nose drops will stain the nails a grey/blue colour. Phenothiazine produces a blue/black coloration that is often accentuated in summertime.

Cytotoxic drugs

Diffuse, longitudinal or horizontal melanonychia affecting the nail base or nail plate may occur in association with pigmentary changes of the surrounding skin with doxorubicin, busulphan, cyclophosphamide and daunorubicin therapy.

Diseases of collagen and elastic tissue

The skin contains collagen types I, III and V within the dermis, type IV in the basement membrane, type VII in the anchoring fibrils and type VIII in the endothelium . Abnormalities of these can give rise to various
skin disorders. Ehlers-Danlos syndrome This is a heterogeneous group of diseases in which at least nine different varieties have been described. Hyperextensibiliry, fragility and bruising of the skin occur to a varying degree with each of the diseases and it is accompanied by the hypermobility of joints. Fragility of blood vessels occurs, and rarely aortic rupture.
The patterns of inheritance are varied and can be utosomal recessive, autosomal dominant or X-linked recessive.
The skin is velvety to the touch an hyperextensible but recoils normally on stretching. Trauma or laceration of the skin can lead to tissue-paper scars and poor wound healing. Pseudotumours may occur over the elbows and knees; they consist principally of fat, but may show signs of calcification.

Solar elastosis

Degradation of elastric fibrils in the skin normally occurs with ageing. This usually begins in early adult life but changes are more noticeable in the sixties and seventies. The clinical features are characterized by yellowish papules or plaques and wrinkling and are usually associated with pigmentation and keratoses on exposed skin. Cutis laxa (generalized elastolysis) This is a rare disease in which there are a number of variants. These are inherited as autosomal recessive, Xlinked recessive or dominant traits. A defect in the crosslinking of elastin is suggested, but other abnormalities, including copper deficiency, have been reported. The subsequent changes in the skin, sometimes gross, may be evident at birth or arise at the time of puberty. The disfiguring changes may be severe with extreme laxity of the facial skin and massive folds over the trunk that have no recoil on stretching. Joint hypermobility is not a common feature.

Pseudoxanthoma elasticum

This is a generalized disorder of elastic tissue. The pathogenesis is unknown, and both autosomal dominant and recessive modes of transmission are seen. The skin, eyes and vascular structures are involved. Cutaneous features are seen in childhood and are most evident over flexural surfaces and at the sides of the neck. Initially there is an accentuation of skin lines or folds and this is followed by thickening around yellowish diamondshaped papules, producing a peau d’orange or pluckedchicken appearance. The skin may be lax and hang in folds. The skin demonstrates very little elastic recoil on stretching. The mucous membranes may also be affected. Long-term and high-dose treatment with D-penicillamine produces similar cutaneous features.Widespread vascular changes are associated with  fibrous proliferation and the deposition of calcium in the media of the arteries. Intermittent claudication and angina pectoris occur at an early age as a result. Gastrointestinal bleeding may be a troublesome feature. Splits in Bruch’s membrane, which contains both elastin and collagen and separates the choroid from the retina, are demonstrated as angioid streaks on ophthalmoscopy.

Marfan’s syndrome

A biochemical defect for this disease has not been identified, and some features of the condition may be seen in association with the Ehlers-Danlos syndrome or with homocystinuria. Inheritance is usually in an autosomal dominant manner. Striae distensae are the only common dermatological sign, and the most impressive changes affect the skeleton. The facial appearance of affected patients may be distinctive, with elongation and asymmetry. A high-arched palate, although frequently described, is not a common feature. A tall stature, long thin digits and alteration in the body proportions are seen; the distance from the soles to the pubis (lower segment) is greater than the distance from the pubis to the vertex (upper segment). The arm span, measured from the extended fingers, often exceeds the height of the patient.

J0 INTs. A laxity ofligaments may give rise to dislocation of joints such as the jaw or patellae. Steinberg’s sign occurs when the thumbs are adducted over the palm and their tips are seen to cross the ulnar border of the hand. Inguinal or femoral hernias are often seen. RESPIRATORY SYSTEM. Pulmonary changes include hernia of the diaphragm, emphysema and spontaneous pneumothorax.
CARDIOVASCULAR SYSTEM. Cardiovascular symptoms follow the degeneration in the media of vessel walls. The aortic valve ring may dilate and produce an incompetent valve, with the mitral valve frequently involved, producing the billowy or prolapsed valve syndrome (see p. 597). Aneurysm formation may occur, usually in the ascending aorta, and may be followed by dissection and/or rupture.

EYES. Weakness of the suspensory ligament of the lens may cause dislocation; this is a common clinical feature of the disease.

Sunlight and the skin

Controversy exists about the adverse effects of UV radiation exposure on the skin. However, damage can occur in four ways:
1 UVB (medium wavelength 280-310 nm) reaching the earth’s surface is increased by depletion of the stratospheric ozone layer. Synthetic chlorofluorocarbons e.g. some aerosols and refrigerators reaching this zone further compromise this important barrier function. A 1% decrease in the ozone layer has increased UVB levels at the earth’s surface by 2% with a concomitant rise in non-melanoma skin cancer of 2%. Increased levels of UVB are now being recorded in Europe. 2 Increased use of UVA (long wavelength 310-400 nm) for recreational tanning may expose individuals to more than five times the amounts reaching the earth’s surface at the equator. UVB is also generated in varying amounts by UVA lamps increasing the potential to cause skin cancer.
3 UVA accelerates skin ageing changes, augments the effects of UVB and penetrates into the dermis. It can affect the Langerhans cell, damage connective tissue and trigger photosensitivity diseases.
4 Evidence now exists that UV radiation affects immune responses in the skin in animals and humans and may have an effect on more general immunoreactivity. The effects of UV light on the skin may be beneficial or damaging. The formation of vitamin D from sterol precursors in the skin is dependent on sunlight, and UV light exposure may be used with benefit in the treatment of chronic skin conditions such as acne, eczema and psoriasis.
Damaging effects, however, occur with chronic irradiation, giving rise to changes in connective tissues that produce ageing, wrinkling, altered texture, dryness and changes in skin pigmentation. Epidermal changes include hyperkeratosis, dysplasia and malignancy.

PHOTODERMATOSES

These can be divided into:
• Eruptions in which sunlight has a primary role
• Diseases in which sunlight is a trigger or an exacerbating factor

Primary photosensitivity

Polymorphic light eruption

The term ‘polymorphic’ refers to the difference in the morphology of the eruption between one patient and another. The lesions tend, however, to be monomorphic in anyone individual.
Lesions are usually papulovesicular. Eczema, urticarial plaques or purpuric changes are less common. The rash is seen after a few hours of sun exposure and is inost common on the chest and arms, the backs of the hands or lower legs. The eruption usually occurs in spring and early summer and improves as summer progresses and the skin ‘hardens’. Fair-skinned individuals are most commonly affected by intense sunlight but those who have previously tanned easily and are of a darker complexion can also be affected. The papules may be associated with weeping and intense pruritus lasting for 5-10 days. The reaction can most readily be produced in the clinic or laboratory using high-intensity UV light at a wavelength of 320–420 nm. Pretreatment during spring-time with 12-18 treatments of PUV A may prevent the disease. Hydroxychloroquine given in doses of 400 mg daily for 2-3 weeks before and during sun exposure may prevent attacks. Topicalcorticosteroids such as betamethasone and high-factor sun-blo cking creams (factors 15-30) also help to minimize the disease.

Hutchinson’s summer prurigo

This rare disease usually has its onset before puberty. It affects both exposed and unexposed skin and may last throughout the year. Lesions are often excoriated and the necrotic papules may be quite disfiguring. The wavelengths responsible are usually in the sunburn range (290-320 nm). Sunscreen creams should be used but these do not offer sufficient protection in most cases. (3-Carotene given by mouth may help a few patients. Actinic reticuloid (chronic actinic dermatitis) This is a rare condition affecting older men in which the gross thickening, coloration and texture of exposed skin may resemble lymphomatous infiltration, both clinically and on microscopy. Many patients have had eczema previously and a significant proportion of these patients alsohave a positive patch test to materials such as rubber or  plants.
Clinical features include eczematous and purpuric lesions on non-exposed skin such as the legs, arms and trunk. Light sensitivity may be such that during active phases of the disease the only respite for patients is found in a darkened room. Protective clothing, sun-barrier creams, systemic steroid therapy, azathioprine, cytotoxic drugs and hydroxychloroquine may be required in combination to produce improvement.

Secondary photosensitivity

Topical agents

The application of perfumes (e.g. those contaimng bergaptine), sulphonamides and antimicrobial agents e.g. halogenated salicylanilides) may produce photosensitive reactions. The latter group of compounds have largely been withdrawn.
Plant extracts such as psoralens, commonly found in the family Umbelliferae, are used in photo chemotherapy (PUVA therapy). However, phytophotodermatitis may occur when the leaves of such plants (e.g. giant hogweed, wild parsley) abrade the skin surface. Psoralen compounds are absorbed into the skin and then activated by natural long-wavelength UV radiation. The linear configuration of the lesions should provide the clue to diagnosis.

Systemic agents

Systemic agents associated with photosensitivity include tetracyclines (chiefly chlortetracycline), thiazides (frusernide), phenothiazines, psoralens and retinoids.

Disease states

Sunlight can exacerbate SLE. Antibodies produced against DNA denatured by UV light form immune complexes in the skin and other organs. In porphyria, porphyrins deposited in the skin are activated by UV light.

Disorders of pigmentation

There are many factors that alter the hue of a normal skin. The principal pigments are melanin and haemoglobin or its breakdown products. Carotene, if taken in large amounts in the diet, is concentrated in subcutaneous fat and in keratin, giving a yellow coloration to the skin. The skin can also change its colour by deposition of abnormal substances or by alteration of melanogenesis. These substances include drugs, bilirubin, haemosiderin, heavy metals and the deposition of metal salts, dyes and inlcs in tattooing. In practice, patients are most concerned with alterations in the degree of melanin pigmentation. This is especially so in those races who have a greater deposition of melanin in their skin as a normal characteristic. Alteration in the degree of pigmentation in those with pigmented skins may be striking and give rise to much personal and social stress.

HYPOPIGMENTATION

Generalized hypopigmentation (albinism)

Albinism is inherited as an autosomal recessive disorder of melanin synthesis. This disorder produces a milky white skin, white hair, blue eyes and photophobia. There are different types, but in the commoner types there is a defect or inhibition of tyrosinase biosynthesis. In phenylketonuria (see p. 864) there is a failure to convert phenylalanine to tyrosine and hypopigmentation of the skin, hair and eyes -occurs.

Localized hypopigmentation

Localized absence of melanocytes is seen in vitiligo. In postinflammatory hypopigmentation some melanocytes are seen but these have reduced activity. In pityriasis versicolor the lipophilic yeast Pityrosporum orbiculare produces substances that have an inhibiting effect on melanocytes. This condition can be treated with itraconazole. Industrial processes may expose the skin and melanocytes to substances, such as phenols, that are also toxic to the pigment-producing cells.

Vitiligo

This is a common skin disease affecting approximately 1% of the population. It has a familial incidence. Melanocytes are lost from affected areas of skin. The reason is unclear but hypotheses include the following:
AUTODESTRUCTION OF MELANOCYTES by the products of melanin synthesis.
AUTOIMMUNE DAMAGE TO MELANOCYTES. Antigens have been detected on the surface of melanocytes and anti melanocyte antibodies have been detected in the sera of some patients. There is also an association of vitiligo with other diseases that demonstrate organspecific
antibody production, such as diabetes mellitus, thyroiditis and pernicious anaemia.
NEUROGENIC DYSFUNCTION has been invoked as an important factor in the production of rare naevoid patterns of the disease that tend to affect the limbs.

CLINICAL FEATURES

More than half the patients notice a loss of pigment before the age of 20 years. Areas of pigment loss are usually symmetrical and often annular in outline, though other shapes and patterns are seen. These areas tend to enlarge peripherally and present a convex edge to the normal pigmented skin. The initial areas of involvement often include the fingers, hands, face and genitalia. These regularly traumatized areas of skin may show evidence of the Koebner phenomenon (see p. 1000) when the disease is in an active phase. In endemic areas confusion may occur with leprosy and lead to social isolation.

TREATMENT

This is unsatisfactory. Traditional therapy in places such as the Middle East includes the use of psoralens obtained from plant sources and applied topically or taken in tablet form. These substances enter into the skin and are then activated by sunlight. PUV A therapy used in the treatment of psoriasis is derived from these observations. Many treatments with PUV A therapy are required for vitiligo and there is concern over the long-term effects of the continuing use of high-intensity UV light for long periods, especially in younger patients. Potent topical corticosteroids, probably through their action as antiinflammatory agents, may induce repigmentation when applied to new lesions of vitiligo and a trial over a limited area of skin for a period of 6-8 weeks is warranted. There may be spontaneous recovery, especially in children. Pinch grafts of normal skin have been used but with active disease the Koebner effect involves donor sites.Postinflammatory

hypo pigmentation

This may follow trauma to the skin from chemicals or physical agents or following inflammatory skin diseases. It is a noticeable feature in some patients with eczema. Mild hypopigmentation on the cheeks of children may be associated with scaling and erythema. Inflammatorychanges are usually seen in winter-time and are associated with conditions of low humidity and drying winds. The tanning of surrounding skin in summer will often make the eruption appear more striking, especially in dark-skinned children (pityriasis alba). Pityriasis versicolor may also tend to present in the summer for similar reasons.

TREATMENT

The intensity of local inflammatory changes will be reduced with topical corticosteroids. Soap substitutes and emollients should be used when dryness of the skin is evident

HVPERPIGMENTATION

Hyperpigmentation is most commonly seen following sun exposure but may also follow inflammatory changes in the skin. It is often much more evident in those races whose skins are already heavily pigmented. Epidermal naevi may contain an increased number of melanocyte  and be pigmented. Melanin deposited in the dermis will often produce a blue discoloration of the skin, which is seen in the following:
• Mongolian blue spot on the backs of children, more especially those of Asian origin
• Naevus of Ito (on the neck)
• Naevus of Ota (on the face)
• Blue naevus

Brown-coloured naevoid lesions

IN NEUROFIBROMATOSIS, cafe-au-laitpatches and axillary freckling are seen.
ALBRIGHT’S SYNDROME produces extensive light brown discoloration of the skin over the trunk, buttocks and thighs that is often asymmetrical and affects children of preschool age.
XERODERMA PIGMENTOSUM is associated with a freckling type of hyper pigmentation on the face or other sunexposed sites. In those patients with severe disease it is associated with solar damage and cutaneous malignancy, which may be evident early in childhood.
FRECKLING on the skin of fair-skinned and otherwise normal persons increases with the length of sun exposure. Histological sections appropriately stained demonstrate an increase in the size and shape of melanosomes within the melanocyte.

Lentigines

These are circumscribed dark brown macules that are less than 0.5 cm in diameter. There is a localized increase in the number of melanocytes seen on light microscopy and the degree of pigmentation is often much more intense clinically than that seen with freckles. A generalized distribution of lentigines may be seen as part of a syndrome that includes cardiac defects (Leopard or Moynahan’s syndrome). In the Peutz-legher syndrome (orofacial lentiginosis) (see p. 213) lesions are localized to the face and hands and there is an association with intestinal
polyposis.

Generalized hypermelanosis

Liver disease

In haemochromatosis there is a grey/black component to the hyperpigmentation that is more evident in sunexposed areas of skin. Hypermelanosis may also be pronounced in patients with primary biliary cirrhosis. Endocrine disease
ADDISON’S DISEASE. Pigmentation may be diffuse but it is often much more pronounced on sun-exposed or traumatized skin, e.g. beneath bra straps or over the buccal mucosa in the mouth. Both adrenocorticotrophic hormone (ACTH) and melanocyte-stimulating hormone (MSH) are increased but ACTH plays the dominant role in producing the pigmentation.
HYPERTHYROIDISM may rarely produce a similar pattern of hyperpigmentation.
ACROMEGALY, CUSHING’S SYNDROME and ACTH therapy may also be associated with pigmentation that may be particularly pronounced in patients with sella turcica enlargement following adrenalectomy (Nelson’s syndrome), when multiple lentigines and oral hyperpigmentation are also seen.
PREGNANCY AND THE ORAL CONTRACEPTIVE PILL may both produce an increase in pigmentation on the neck, the areolae of the breasts, over the abdominal skin and genitalia. Involvement of the face (melasma) may cause the patient to seek medical advice.
NEOPLASTIC DISEASE AND CACHEXIA can produce a general darkening of the skin colour; more marked changes occur with ectopic ACTH production.

Other diseases

ACANTHOSIS NIGRICANS is most commonly seen as localized hyperpigmentation of the neck, axillae, groins or facial skin, but the changes may be generalized and profound. Velvety overgrowth of the skin at the flexures may be accompanied by filiform growths around the face, mouth or over the tongue, and by a curious roughness of the palmar or plantar skin (tripe palms). These changes are seen in middle-aged patients with visceral malignancies such as carcinoma of the stomach, but other types of neoplasia such as lymphomas have also been reported in association with these typical cutaneous features. Acanthosis nigricans can, however, occur without an underlying malignancy, with obesity in juveniles and together with endocrine diseases.

Untitled

RENAL FAILURE is associated with hypermelanosis and an increase in MSH-like reactive hormone production is seen in some patients. A yellow/brown, widespread coloration of the skin often occurs; scaling and irritation may also be seen. The relief of itching is difficult to achieve
in such patients.
SYSTEMIC SCLEROSIS may produce localized pigmentary  changes in sites such as the nape of the neck or over the shoulder girdle, but hyperpigmentation may be profound and generalized in some patients. Thickening of the skin is usually present and should offer a clue as to the primary diagnosis.
CHEMICAL DEPOSITION in the skin may occur as an occupational hazard, e.g. in those who process silver (argyria).
MERCURIALS may produce hypermelanosis, and gold  when injected or taken by mouth may cause blue/black pigmentation, most evident on sun-exposed sites (chrysiasis) .
HAEMOSIDERIN, the iron-containing pigment, may also stimulate localized melanin production. This occurs on sites such as the legs of patients with varicose eczema following the loss of red cells into the skin. Mucocutaneous discoloration may also be seen with chronic lead poisoning.

Drugs

Mepacrine imparts a yellow colour to the skin but the sclera are spared. Chloroquine and chlorpromazine may produce bluish-grey coloration of the skin, especially in areas exposed to the sun. Arsenicals ingested over a long interval cause macular hyperpigmentation together with areas of hypopigmentation (rain-drop appearance).

Vascular and Lymphatic Disorders

Venous ulcers

These are confined to the lower limbs and many are postthrombotic. The increased hydrostatic pressure in the veins resulting from incompetent valves is reflected by increased capillary blood pressure. Leakage of plasma under pressure gives rise to perivascular fibrin deposition which may lead to a decrease in oxygen supply, but direct skin oxygen measurements do not support this view.

There is a fall in oxygenation when an ulcerated limb is exercised, so that ambulant patients experience sustained hypoxia of the skin. Nutrition of the skin is then affected and leads to ischaemia and eventual ulceration. Ulcers around the ankle are often accompanied by:

• Hyperpigmentation following extravasation of red cells and haemosiderin deposition
• Dermatitis and excoriation due to pruritus
• White atrophy (atrophie blanche) caused by hyalinization of skin vessels producing scars in the overlying skin
• Secondary infection with possible cellulitis or thrombophlebitis The differential diagnosis of leg ulcers is shown in Table 20.5.

Some cutaneous markers of malignant disease.

Some cutaneous markers of malignant disease.

Arterial ulcers

Ulcers occurring in skin away from the ankle region are more commonly associated with arterial disease. They may accompany venous hypertension in the legs, especially in the elderly. Cold, atrophic skin with loss of hair, impalpable peripheral pulses with a history of claudication may suggest the diagnosis. The ulcers usually have a punched-out appearance and are often very painful. Doppler studies may help to determine the degree of arterial insufficiency in an affected limb.

Venous insufficiency
Arterial insufficiency

Infective
Bacterial
Post cellulitis
Desert sore
Mycobacterial
Tuberculosis
Buruli ulcer
Leprosy
Swimming pool granuloma
Mycotic
Superficial or deep fungal
Spirochaetal
Syphilis
Yaws

Neuropathic
Diabetes mellitus

Haematological
Sickle cell disease
Spherocytosis

Neoplastic
Epithelioma
Kaposi’s sarcoma
Basal-cell carcinoma

Vasculitis
Rheumatoid, systemic lupus erythematosus
Pyoderma gangrenosum
Trauma or artefact

Causesof leg ulceration.

MANAGEMENT OF ARTERIAL AND VENOUS ULCERATION

GENERAL MA AGEMENT consists of reducing leg venous hypertension. This can be helped by wearing support bandages when standing or by elevation of the limbs when sitting or lying. Exercise should be encouraged and, if the patient is obese, weight reduction recommended.

DERMATITIS should be treated with bland non-steroidal applications such as zinc and salicylic acid paste . Impregnated bandages containing zinc and applied moist can dry out and stiffen to provide occlusion and support.

ULCERS should be cleaned with normal saline or a wealc potassium permanganate solution. A non-adhesive absorbent dressing should be applied with an elasticated bandage up to the knees. These dressings may be viscous materials, alginates, semi-permeable films, hydrogels or hydrocolloids. These are expensive but covering the wound with a permeable membrane will diminish pain and encourage re-epithelialization.

Clean granulating ulcers should have non-adherent dressings applied and left undisturbed for increasing periods as the ulcer heals. A debriding agent (e.g. hydrophilic polysaccharide beads) or surgery may be necessary to remove dead tissue. Pinch grafting may also be necessary. The grafts are removed from the thigh and dotted over the ulcers and left undisturbed for 10 days.

INFECTION. Local antibiotics should be avoided ifpossible. Ps. aeruginosa infection accompanies nonpermeable occlusive dressings. Systemic antibiotics may be required for cellulitis.

FOLLOW-UP care and preventative measures are most important and elastic stockings may always be
necessary.

VARICOSE VEINS. Treatment may be necessary.

Pressure sores (decubitus ulcers)

These occur in the elderly, immobile, unconscious or paralysed patients. They are due to skin ischaemia from sustained pressure over a bony point. Normal individuals feel the pain of continued pressure and even during sleep, movement talces place to change position continually.

1 The majority of pressure sores occur in hospital: (a) 70% in first 2 weeks of hospitalization
(b) 70% are in orthopaedic patients especially those on traction
2 20-30% occur in the community
3 80% of patients with deep ulcers involving the subcutaneous tissue die in the first 4 months

Altered sensation of the skin increases the risk of ulceration and patients with diseases that affect the circulation and tissue nutrition also are predisposed, e.g. rheumatoid

Pyoderma gangrenosum

Pyoderma gangrenosum

Multiple myeloma
Other paraproteinaemias. especially IgA
Arthropathy (rheumatoid and spondylarthropathies)
Inflammatory bowel disease
Acute leukaemia
Polycythaemia vera
NB No cause is found in 50% of cases

Conditions associated with pyoderma gangrenosum

CLINICAL FEATURES

Lesions most commonly arise as inflammatory pustules or papules that appear on the trunk and limbs. They may rapidly enlarge over several days to produce large necrotic ulcers with a crescentic or polycyclic outline and sloughy base, which undermines a raised purplish prominent rim.

Other patients may have a more slowly progressive indolent ulcer.

Less frequently, but especially in association with acute myelogenous leukaemia, ulceration may be superficial and arise as necrotic bullae.

TREATMENT

Rapidly progressive and painful lesions are accompanied by systemic symptoms and require doses of prednisolone 80-100 mg. Azathioprine may be used in combination or alone. The underlying condition should be treated. Tetracyclines, colchicine and clofazimine have been shown to be of benefit in a few patients. Indolent ulcers may respond to topical therapy and intralesional steroid injections.

Antiphospholipid antibody syndromes

Antiphospholipid antibodies including the lupus anticoagulant (LA) and anticardiolipin (ACL) are associated with thrombosis, central nervous disease and spontaneous abortion with or without SLE.

CUTANEOUS MANIFESTATIONS 

• Livedo reticularis, livedo reticularis with cerebrovascular accidents (Sneddon’s syndrome)
• Thrombophlebitis
• Cutaneous gangrene and necrosis of digits
• Skin ulcerations
• Lesions resembling vasculitis, nodules, macules
• Cutaneous necrosis/infarction
• Subungual splinter haemorrhages

Drug eruptions

Cutaneous eruptions account for one-third of all sideeffects of drugs. It is sometimes difficult to differentiate an eruption due to a drug from one produced by the underlying illness. On occasions the effects of both are relevant to the onset of the rash, for example patients prescribed ampicillin for infectious mononucleosis will often develop a widespread morbilliform rash. Patients often take many drugs together and it may be difficult to incriminate one agent in the production of the rash. In vitro testing of drugs in these situations is inadequate in establishing or predicting the likelihood of the drug causing the cutaneous side-effect.
The drugs mentioned below are only examples. If there is doubt about an eruption, the most likely drug to produce this should be stopped.
Urticaria Urticaria may be associated with a type I IgE reaction and anaphylaxis in patients who are hypersensitive, for example, to penicillin. Urticaria can also occur in the serum sickness syndrome, IgG immune complexmediated reactions occurring 1-2 weeks after drugs or serum, or lastly, by direct release of histamine. The latter include:
• Codeine, opiates and tubocurarine
• Radiological contrast media
• Aspirin and NSAIDs, e.g. indomethacin may trigger
blood vessel hyperreactivity by affecting the production of arachidonic acid metabolites
• Angiotensin converting enzyme inhibitors, e.g. captopril and enalapril, may also potentiate effects of bradykinins

Allergic vasculitis and purpura

Drugs that produce vasculitis may activate the alternative pathway of complement or produce cryogiobulins and immune complexes in the serum. Antibody, principally 19A, may be deposited around damaged vessels in the kidney and skin. Purpuric lesions appear most frequently on the extremities and may be accompanied by urticaria, blisters, necrosis of the skin and ulceration. Drugs that have been associated with this disease include allopurinol, sulphonamides, gold, hydralazine, quinidine, methyldopa, captopril and amiodarone. Drugs that cause a lupus erythematosus-like syndrome include isoniazid, f3-adrenergic receptor antagonists, penicillamine and lithium.
Purpura may be seen following drug-induced thrombocytopenia (see p. 324). Drugs may combine with the platelets to form an antigen; antibody formation follows, leading to platelet destruction.
Erythema nodosum and erythema multiforme Erythema nodosum and erythema multiforme may be induced by drugs; these are considered on p. 1005. Erythematous morbilliform eruptions These maculopapular erythematous reactions are the commonest type of drug eruption. They usually occur up to 2 weeks after starting the medication and are widespread on the trunk and over pressure sites such as the thighs, knees and elbows. Diffuse erythema may be accompanied by pruritus and followed by desquamation. An accompanying fever may cause confusion with viral illnesses. Paired sera for viral antibodies may help to
establish the correct diagnosis in retrospect. All penicillins, sulphonamides, phenytoin, gold and gentamicin are agents most likely to induce this type of reaction.
Lichen planus-like or lichenoid eruptions.

Photosensitizing agents

Toxic epidermal necrolysis

This is the most serious type of drug-induced disease. It can be distinguished on histological grounds from the condition seen in children, which produces a similar clinical picture and is induced by staphylococci (see p. 19). There is superficial peeling of all the skin which follows several days after fever, malaise and rhinitis. Some features may overlap those of Stevens-Johnson syndrome. The agents most likely to cause such disease are NSAIDs, penicillins, sulphonamides, allopurinol and barbiturates. Fixed drug eruption
The pathogenesis of this type of reaction is unknown. The face, hands and genitalia are most commonly affected. Bright red, sometimes purpuric or even blistered plaques or annular lesions are seen. An accompanying burning discomfort is present. The lesions are fixed in site and appear within hours of the offending drug’s administration. They will occur at exactly the same sites if the drug is given again at another time. Postinflammatory hyperpigmentation is a striking feature.
Phenolphthalein in laxatives or as a colouring in sweets is a common cause. Other agents include tetracycline, sulphonamides, phenacetin, salicylates, the oral contraceptive pill and chlordiazepoxide.

Pigmentation

Pigmentation that occurs with oral agents. Exacerbation of pre-existing skin diseases Pre-existing skin diseases may be exacerbated by drugs. Examples include lithium carbonate and l3-receptorantagonists, which will exacerbate psoriasis.  Lupus erythematosus-like rash.

Acneiform eruptions

These are papulopustular eruptions but usually without comedones. The major drugs involved are corticosteroids, oral contraceptives, androgens, iodides, anticonvulsants and isoniazid.
Eczematous reactions These can be caused by sulphonamides, sulphonylureas for example. Sensitization can be by topical application.

Porphyria Cutanea Tarda

Only the changes seen in porphyria cutanea tarda are considered here. Similar changes in the skin may be seen with variegate porphyria and hereditary coproporphyria. Cutaneous lesions occur on exposure to sunlight. These consist of increased fragility of the skin over the dorsum of the hands, fingers and face and are associated with erythema, blistering and scarring. Hypertrichosis on the sides of the face and between the eyebrows and hair margin is common and may be associated with facial skin thickening and loss of hair (pseudoscleroderma). Hyperpigmentation or loss of pigment may also be seen on the facial skin. Itching may be troublesome.

Cutaneous amyloidosis

Cutaneous forms of the disease may be widespread on the skin and mucosal surfaces or localized to particular areas. The skin is involved in about 40% of patients who have systemic amyloidosis in association with diseases such as myelomatosis.

The gums may appear nodular and waxy and bleed easily on trauma. Pale yellow-brown papules may appear over the basal conjunctivae and at other mucosal sites and purpura is seen following mild trauma. Sites of predilection elsewhere on the skin include the eyelids, the nasolabial folds, the sides of the neck, and the flexural surfaces. Thickened indurated plaques may rarely affect the chest, abdomen or hands. Cutaneous changes are rare in the hereditofamilial patterns of disease.

Cutaneous disease where there is no evidence of systemic spread is seen in two forms: macular and lichen amyloidosis.

Macular amyloidosis

Macular amyloidosis is quite commonly seen on the shoulders, neck or upper back of patients of Asian origin. The hyperpigmented macular changes have a rippled appearance likened to the changes seen on a sandy beach at low tide. Patients are only concerned about the appearance of the lesions, which are dark grey/black in colour.

Scarring and blister formation seen with porphyria cutanea tarda

Scarring and blister formation seen with porphyria
cutanea tarda

The amyloid material is difficult to demonstrate on histology using routine methods.

Lichen amyloidosis

Lichen amyloidosis is an uncommon papular eruption that is often pruritic and occurs on the lower limbs. There is no explanation for the appearance of the amyloid material at this site. Other pruritic diseases on the lower legs are often hypertrophic, especially in patients of African or Asian origin. Diseases such as hypertrophic lichen planus and lichen simplex may resemble the disease on superficial inspection. Close examination should, however, distinguish these diseases. The shiny, warty, close-set papules of lichen amyloidosis  are characteristic of the disease.

C N S-RELATED DISEASES

The number of dermatoses that have been associated with diseases of the nervous system is large but most are extremely rare.

Neurofibromatosis

The characteristic cutaneous features are hyperpigmentation (cafe-au-lait spots) and flesh-coloured smooth polypoid swellings, i.e. neurofibromas. Molluscum fibrosum (skin tags) are sessile pink-coloured tumours that are often numerous over the trunk. Plexiform neuromas are uncommon and tend to follow the course of a nerve, usually on the face or neck. In some areas there is overgrowth of skin and subcutaneous tissue in addition and this may give rise to gross disfigurement (elephantiasis
neuromatosa). Oral lesions occur in up to 10% of patients.

Cafe-au-lait spots may suggest the diagnosis in children but there should be more than five in number to support  it. The pigmentary changes must be differentiated from those seen in Albright’s syndrome (see p. 782). In neurofibromatosis the cafe-au-lait spots show histologically the presence of giant melanosomes; these are rare in Albright’s disease.

SEGMENTAL DISEASE. Cafe-au-lait patches and neurofibromata may be confined to a body segment.

Tuberous sclerosis (epiloia)

The cutaneous lesions in tuberous sclerosis are derived from connective tissue and are of several different types.

Adenoma sebaceum are erythematous papules or nodules on the cheeks or within the folds at the sides of the mouth or nose. The turn ours are vascular and fibrous in origin. Periungual fibromas occur as pink, firm, claw-like tumours arising from and around the nail folds. Shagreen patches are flesh-coloured tumours that are firm and plaque-like. They often have a wrinkled surface and are most frequently seen over the lumbosacral region. Areas of macular hypopigmentation occur in ovoid or leaf-like shapes. They may be seen over the trunk or back and are most easily detected by examination with Wood’s light. They appear early in childhood, associated in many cases with mental retardation.

Small erythematous papules on the face and cheeks may be treated with an electrical Hyfrecator or cautery.

Other CNS-related diseases

Naevoid lesions may be seen in conjunction with neurological disease; for example, in the epidermal naevus syndrome, pigmented naevi occur in a linear fashion on the limb or trunk and may be associated with epilepsy or mental retardation.

Gross ichthyotic changes may occur on the skin of patients with spastic diplegia and mental retardation in the Sjogren-Larsson syndrome.

MALIGNANT DISEASES

The skin can be involved by both primary and secondary tumours. Table 20.4 shows some cutaneous markers of malignant disease which may be associated with genodermatoses, paraneoplastic dermatoses or environmental carcinogens, e.g. arsenic, vinyl chloride, ionizing radiation.

Squamous carcinoma

This invasive tumour with the ability to metastasize arises from the epidermis (keratinocytes) or skin appendages. It is most commonly seen on previously damaged (e.g. by ultraviolet radiation) or chronically irritated skin. It has also been associated with certain occupations (e.g. chemical carcinogens inducing cancer of the scrotum) or with certain social customs (e.g. tumours on the legs from radiant heat from fires). Albinism and xeroderma pigmentosum may produce severe actinic damage to the skin and frank malignancy at an early age. Viral disease may predispose to squamous carcinoma and human papilloma virus may be isolated from the skin of patients with epidermodysplasia verruciformis.

Untitled

CLINICAL FEATURES

Tumours are hyperkeratotic and crusted and are usually seen over sun-damaged skin, e.g. on the pinna. Induration of the tissue provides a further clue to the diagnosis. Ulceration may occur if the lesion is on sites such as the lips or genitalia. Papilliferous and more friable tumours may appear on relatively normal skin.

DIFFERENTIAL DIAGNOSIS

Solar keratoses

These occur on sun-exposed and chronically damaged skin especially in those of Celtic origin. They appear as red or brown, rough hyperkeratotic lesions on the forehead, cheeks, ears, backs of hands and on the bald or thinly covered scalp. They represent a maturation defect of keratin and are often more easily felt than seen. Superficial lesions, where the diagnosis from squamous carcinoma is clear, respond to cryotherapy with liquid nitrogen.

Bowen’s disease

Bowen’s disease or intraepidermal carcinoma becomes invasive in approximately 5% of patients. When small superficial psoriasiform lesions or eczematous type lesions occur on the legs of elderly females they may persist  for years and are sometimes accompanied by thickening and marked crusting or a papular component. The diagnosis should be confirmed by histology followed by excision or radiotherapy.

TREATMENT

Treatment is usually by excision or by radiotherapy. Superficial lesions may be treated with cryosurgery.

Malignant melanoma

This tumour, formed by epidermal melanocytes, is rising in incidence throughout the world. This increase has been seen particularly in light-skinned people. The latitude and length of residence of these people in places such as Australia suggest that UV light exposure is important. A single episode of severe sunburn is a significant risk factor, emphasizing the importance of occasional as opposed to constant light exposure. An increase in tumours on skin that has not until recent years been commonly exposed to sun, also indicates that exposure is a significant factor. Inheritance is also important in the dysplastic naevus syndrome, when large multiple and atypical naevi on the trunk show a familial trait and patients may develop multiple primary melanomas.
Malignant change is recognized in pre-existing naevi, especially pigmented naevi, that cover a large surface of the skin, e.g. bathing trunk naevi, and in lentigo maligna.

Lentigo maligna

Lentigo maligna represents an increased number of melanocytes at the epidermodermal junction. It begins as a flat freckle-like lesion, which in time changes colour and pattern as it grows. It occurs on the facial or sun-exposed skin of patients in their sixties or older. It is a precursor of malignant melanoma. Malignant change in a mole should be suspected with a change in size, outline, colour, surface or elevation. Symptoms that include itching, bleeding after minor trauma or an increasing awareness of the tumour should also arouse suspicion.
The prognosis is directly related to the thickness of the tumour assessed at histological examination; patients with a tumour less than 1 mm thick have a 5-year survival rate of more than 90% but for tumours greater than 3.5 mm thick the 5-year survival rate is less than 50%. The prognosis is also related to the site; patients with a tumour on the trunk fair better than those with facial lesions, but worse than those with lesions on the limbs. Public health campaigns are necessary for:

• Prevention by avoiding direct sunlight and in the use of topical sunscreens
• Awareness and early diagnosis of suspected lesions by self-examination, particularly in light-skinned, blueeyed people.

TREATMENT

Excision is performed according to the depth of invasion:
1 ern excision margin for every 1 mm of invasion with a wide excision of deeper invasive lesions followed by skin grafting. Deeply invasive lesions on a limb may be further treated by isolation and arterial perfusion with cytotoxic agents such as mustine hydrochloride. Radiotherapy, chemotherapy and immunotherapy have not yet been shown to materially alter the outlook for those with disseminated disease.

Mycosis fungoides

This is a lymphomatous invasion of the skin by T lymphocytes (CD4+) (see p. 133) that may eventually form cutaneous turn ours. In the final stages of the disease there is spread to lymph nodes and other organs. The name implies mushroom-like growths on the skin but these are a rare and often terminal event. In the Sezary syndrome the area of skin infiltration is greater and 10% or more atypical mononuclear cells appear in the blood. Both of these conditions are classified as aT-cell lymphoma.

CLINICAL FEATURES

The most common presentation of patients seen in the UK is with a pattern of scaling and erythema that may remain confined over areas such as the buttocks, thighs or trunk as rather fixed patches for many years. Tumours may then develop initially as plaques (Fig. 20.22) and then as ulcerating nodules or masses; dissemination follows with visceral spread and death. With an onset in middle life or old age, patients will often die from other causes. Presentation with advanced disease and spread to local lymph nodes is uncommon in the UK but has been described more frequently in the USA.

Untitled

TREATMENT

Topical mustine hydrochloride, PUV A, photophoresis or electron beam therapy may control widespread disease and plaque forms of the disease. The combination of prednisolone and chlorambucil may limit the spread of more advanced disease, but dissemination to the viscera is associated with the terminal phase of the disease. Multiple chemotherapeutic regimens are disappointing in their effect.

Kaposi’s sarcoma

Kaposi’s sarcoma is a vascular, multifocal, malignant tumour. It is seen in:
• Patients with AIDS. The incidence is higher in homosexuals than in haemophiliacs.
• Immunosuppressed patients secondarily to chemotherapy.
• Elderly males of Jewish or Mediterranean origin (classic form).
• Africans: several forms are seen, namely classical, locally aggressive or lymphadenopathic.

CLINICAL FEATURES

The initial lesion appears as a bruise that gradually darkens and becomes raised as a firm nodule (Fig. 20.23). Lesions are not usually painful or itchy initially and can develop at several sites all over the body. Gastrointestinal lesions (approximately 40% of cases) are usually asymptomatic but later liver and lymph node involvement occur.

PROGNOSIS AND TREATMENT

Lesions may progess rapidly, enlarge slowly over years or even regress. Treatment is with radiotherapy or chernotherapy. In AIDS one-third of the patients may show a response but relapse later; prognosis is poor. The prognosis is slightly better in the other forms and in those on immunosuppressive drugs the lesions may regress on stopping therapy.

SARCOIDOSIS

About one-quarter of patients with systemic sarcoidosis have skin lesions. There are many variants:
ERYTHEMA NODOSUM (see p. 1005), a non-specific reaction.

NODULES, PAPULES AND PLAQUES, red/blue or brown are seen particularly on the face, nose, ears and neck in chronic sarcoid. This is the most common specific form seen in Caucasians.

Ragged cuticle and nail-fold capillary dilatation associated with dermatomyositis.

Ragged cuticle and nail-fold capillary dilatation
associated with dermatomyositis.

ANNULAR, MACULAR LESIONS with central depigmentation are less common.
MICROPAPULAR LESIONS are common in Afro- Caribbeans and are usually the same colour as the skin.

They occur around the nasal alae within the vestibules, on the lips or cheeks or over the periorbital .

Lupus PERNIO, an uncommon variant, affects the nose with a diffuse bluish plaque with small papules within the swelling.

WIDESPREAD CUTANEOUS SARCOIDOSIS is often papular or nodular. Occasionally, subcutaneous nodules are found. Sarcoidosis may appear in old scars.

Differential diagnosis of facial lesions includes leprosy and tuberculosis. Blue nodular lesions should be differentiated from lymphomas.

TREATMENT

Most cutaneous forms of sarcoidosis will improve with increasing doses of systemic steroids. Drugs such as methotrexate, mepacrine or chloroquine may help in reducing the dose of steroid required. Intralesional steroids can aid resolution on occasions. Lesions may often recur on withdrawal of drugs.

METABOLIC DISEASE

Diabetes mellitus

Cutaneous abnormalities occur in more than 25% of patients with diabetes mellitus. They may be non-specific, such as infection with candidiasis, or so distinctive that the dermatologist may be able to predict the diagnosis of diabetes mellitus.

Secondary causes of diabetes (see p. 830), e.g. haernochromatosis and liver disease, may in themselves have cutaneous manifestations and these features are described under the appropriate disease heading.
Necrobiosis lipoidica (diabetic forum) The association of this condition with diabetes is unpredictable; 50% of such cutaneous changes occur in nondiabetic patients. Necrobiosis lipoidica is an unusual complication of diabetes and is not necessarily related to other vascular complications. Nevertheless, small-vessel damage is thought to be a central feature of the pathogenesis. There is partial necrosis of dermal collagen and connective tissue and a histiocytic cellular response. It is more common in females, and presents in young adults or early middle life.

Micropapular sarcoidosis affecting the eyelids

Micropapular sarcoidosis affecting the eyelids

The skin over the shins is the site principally involved and pigmentary changes may cause the casual observer to associate the eruption with venous incompetence. On close examination the features are characteristic: erythematous plaques are seen that gradually develop a brown waxy discoloration that is more evident when stretching the skin. The skin’s blood vessels are prominent because of the associated atrophic changes in the dermis. Fibrosis and scarring from previous ulceration may also be seen . Treatment is with support bandaging. The use of an antiseptic powder or spray such as povidone-iodine is useful when the skin is broken. Non-adhesive dressings should be used. Low-dose aspirin may help to improve  the healing of such lesions.

Diabetic dermopathy

This is a common finding on the shins of diabetics. Initially the lesions are erythematous and papular but tend with time to become flat, hyperpigmented and atrophic. The changes are often seen in association with microangiopathy elsewhere. The pathogenesis of these lesions, which are not specific to diabetes mellitus, is unclear, although intimal thickening of small blood vessels has been demonstrated.

Diabetic stiff hands

This condition was first described in patients with juvenile- onset diabetes, but similar changes have been seen in middle-aged diabetics.

Tight, waxy skin principally affects the dorsum of the fingers and is associated with joint stiffness that can limit extensor movements of the small joints (cheiroarthropathy). Histological sections demonstrate thickening of dermal collagen.

Necrobiosis lipoidica.

Necrobiosis lipoidica.

Sderoedema

This condition is seen as a spreading erythema and induration of the skin that starts on the neck and the upper trunk of middle-aged diabetics. These changes are often heralded by a respiratory illness or by streptococcal infection. The lesion may become generalized over the trunk, limbs, hands and feet, although the genitalia tend to be spared. There is a spontaneous resolution with time.

Diabetic bullae

This is an unusual complication in which blisters develop on the feet and occasionally the hands. They are of an acute onset and occur without any obvious preceding trauma. The disease is sometimes associated with an extensive polyneuropathy. Histological section shows a cleft in the region of the lamina lucida but the cause is not known. Blisters clear in 2-5 weeks.

Granuloma annulare

This presents as flesh-co loured papules in annular or crescentic configurations, principally over the extensor surface of the joints of the fingers (Fig. 20.17). The feet, ankles, hands and wrists may be similarly affected. A disseminated pattern is probably triggered by sunlight but often involves covered areas of skin.

The association of such lesions with diabetes mellitus remains controversial; a few cases do not have overt diabetes but only impaired glucose tolerance. The pathology is similar to necrobiosis lipoidica and the two conditions may occur together.

Eruptive xanthomas

These may appear suddenly as crops of yellow papules on the knees, elbows, back and the buttocks. They are associated with hyperlipidaemia and are seen most commonly in diabetics. They resolve with the control of the diabetes and hyperlipidaemia.

Other skin disorders

Infections and lipodystrophies are often seen in diabetes mellitus; they are discussed in Chapter 17. Skin breakdown may occur especially in association with peripheral vascular disease and give rise to gangrene, synergistic (aerobes and anaerobes) necrotizing cellulitis, progressive bacterial synergistic (microaerophilic, streptococci, Staph. aureus or enteric Gram-negative bacilli) gangrene.

Granuloma annulare.

Granuloma annulare.

Naevi and tumours

The skin is a prime target for aberrant growth and tumour formation. It may be in direct contact with ionizing radiation and many chemical substances or microorganisms that may act as inducers of abnormal cellular activity. There are also a large number of different cell types represented within the skin. Many skin tumours are rare and in practice are confined to a few types.

Melanocytic naevus (naevocytic naevus)

This is a tumour produced by cells of neural crest origin, mainly melanocytes. Schwann cells may also contribute to the dermal aspect of these lesions. This is the most common type of skin tumour. It is pigmented and is referred to as a ‘mole’ in lay terms. These turn ours originate as a proliferation of melanocytes at the epidermodermal junction, so that clinically little growth above the skin surface is seen at this stage (junctional naevus).
With time, cells migrate downwards into the dermis and their bulk increases so that tumours become elevated above the skin surface. Both an epidermal and dermal component are now seen (compound naevus). Gradually the epidermal component becomes less obvious and the tumour becomes a cellular naevus; fibrotic changes and a loss of pigment may then cause a lesion to become less evident or disappear.
Such lesions may be present in childhood but they appear more obvious and increase their numbers with puberty. Sun-sensitive individuals tend to produce greater numbers, particularly on exposed areas of skin. There is therefore a greater number over the lateral aspect of the arm compared with the medial side. Pregnancy will also increase the numbers of naevi and the degree of hyperpigmentation.  he average count of melanocytic naevi on a Caucasian from the Western Hemisphere is more than a dozen by the third decade. Junctional naevi and malignant melanomas should be differentiated by size, the even degree of pigmentation, the smoothness of the overlying epidermis and lack of symptoms in the former. Congenital melanocytic naevi are often bigger and may cover large areas of the skin, e.g. as a bathing trunk aevus. These have an irregular surface and an uneven degree of pigmentation. There is an increased potential for malignant change with larger lesions.

Juvenile melanoma (Spitz naevus)

These naevi are solitary pink or reddish-brown lesions on the face or limbs of children. A history of rapid growth is given and for this reason they are often removed.

Dermal melanocytes

A proliferation of naevus cells in the dermis may give rise to blue discoloration of the skin. The mongolian spot in children represents a more diffuse spread of such cells. When these are localized to form a slightly elevated papule, especially in adults, they are called a blue naevus. Basal-cell papilloma (seborrhoeic wart)
This is a benign proliferation of basal cells that produces a raised lesion with a varying degree of pigmentation. The number of these tumours increases with age. The consistency is often greasy and this aspect has led to the misnomer ‘seborrhoeic wart’ -the lesions are not related to sebaceous tissue growth. ‘Senile wart’ is another unacceptable term because the lesions may be seen in young adults.
The face and trunk are the sites most commonly affected. Marked hyperpigmentation may cause confusion with malignant melanoma. Maceration of these tumours from sweating may, in summertime, lead to irritation. The numbers present on the trunk may prohibit their removal in some patients, but readily traumatized or irritant lesions can be removed with a curette and the base cauterized, or they may be frozen with liquid nitrogen.

Keratoacanthoma

This rapidly growing tumour of the epidermis arises most commonly on the skin of the hand and face. The aetiology is unknown; it is possible that trauma initiates the event and viral DNA has been shown in these tumours. There is often evidence of chronic actinic damage of the surrounding skin (Fig. 20.20). The lesions are often pale or flesh-coloured, welldemarcated papules and on occasions appear inflammatory. Usually 0.5-1 em in diameter, they may reach 3- 4 em across in giant lesions. The increase in size is rapid and often alarming to the patient. The greatest diameter is attained in 4-8 weeks; involution then occurs and the centre becomes a keratinous crater. Regression may then become complete over several months but, since a ragged scar may be left, it is often better to remove the tumour by curettage. Histological sections may reveal changes that are difficult to differentiate from a squamous carcinoma.

Untitled

Haemangiomas

Capillary naevus (naevus flammeus)

This is associated with a proliferation of capillaries in the superficial dermal capillary plexus. The salmon-coloured patch may be seen on the face or more commonly on the nape of the neck in up to 40% of infants. They may not fade from the latter site and are often covered by hair. Facial lesions occur on the glabella, forehead and eyelids and tnd to fade away in the first year of life.

Port-wine stain

This is a tumour present at birth that consists of dilated capillary vessels with endothelial cell lining. The face and neck are most commonly affected and there is no natural regression with age. Those patients who experience such growths around the orbit may have in addition a proliferation of vessels on the meninges (Sturge-Weber syndrome) and neurological defects. Camouflage is the only practical method of managing such lesions. Laser therapy is time-consuming, is only available at a few centres, and the best results appear to follow the treatment of such naevi in adults.

Cavernous haemangioma (strawberry naevus)

This tumour is not present at birth, but usually appears in the first month of life. Lesions are often well-circumscribed, round and lobulated and are usually seen on the face, neck or trunk. Growth continues in the first year in many patients; this is followed by slow involution, which is complete in the majority by 4-5 years, so that reassurance is often all that is required. Gross lesions warrant attempts at treatment when, for example, they obstruct the eye and threaten the development of binocular vision. The bulk of such tumours may be reduced by systemic steroids or sclerosants. Some naevi show features of both capillary and cavernous tissue within a single tumour. Cherry angioma (Campbell de Morgan’s spot) Campbell de Morgan’s spots are angiokeratomas that appear as pin-point lesions or naevi of several millimetres in diameter on the trunk or limbs with an increasing frequency throughout middle-age. Treatment is only required for cosmetic reasons; cautery or diathermy is effective.

Granuloma telangiectaticum

This turnour is a proliferation of dermal vasculature, so that the previous term pyogenic granuloma is a misnomer. Often traurna will initiate this growth on the finger or elsewhere on the skin. In children the trunk is a common site of involvement and there is a tendency for recurrence here from a deep-feeding vascular channel. Bleeding after trauma is a troublesome and worrying feature for some patients and older lesions may become fibrotic. Treatment is by curettage and cautery.

Epidermal naevus

This may appear as a single lesion unassociated with any other developmental abnormality or may occur together with, for example, neurological defects as part of a syndrome. Histologically, there is a proliferation of epidermal structures that are often mixed, so that verrucous, sebaceous, apocrine, eccrine or follicular changes may alloccur. The predominant component will determine the clinical appearances. Some types of naevi may undergo malignant transformation, though this is not common. Sebaceous naevi appear most frequently on the scalp as flesh-coloured, leaf-shaped tumours, which may with time undergo malignant transformation to form basalcell carcinomata.

Histiocytoma (dermatofibroma)

This tumour is composed of blood vessels, histiocytes or dense fibrous tissue, according to the age of the tumour. It usually arises from traurna such as insect bites and is a common turnour on the legs or buttocks of adults, especially females. A firm tender papule develops, forming a button-like tumour on the surface of which the overlying skin can be wrinkled. The brown pigment or rapid growth may cause alarm and confusion with melanoma.

MALIGNANT TUMOURS

There is public concern about the increased numbers of malignant turn ours of the skin and their association with sun exposure. Metastases to any part of the skin can occur from many primary carcinoma sites including breast, stomach, lung and kidney.

Basal-cell carcinoma (rodent ulcer)

This is the most common cancer of the skin and is frequently seen on the face of middle-aged or elderly people in the UK, especially those with fair hair and blue eyes who are sun-sensitive and often of Celtic origin. Such
turnours are seen at a younger age in those living nearer to the equator, but the reasons why turnours appear with such frequency on sites such as the periorbital skin, which is to some degree protected from sunlight, is not clear. Other types of ionizing radiation such as X-rays, for example given to young adults for ankylosing spondylitis, have in the past produced sufficient stimulus for the development of basal-cell carcinomata at the irradiated site after a prolonged interval of 10-20 years. Arsenicals may also cause cutaneous malignancy after a similar induction time.

CLINICAL FEATURES

Lesions are most commonly seen at the sides of the nose and around the orbit as flesh-coloured translucent papules or plaques with superficial dilated blood vessels coursing over the surface; central necrosis with ulceration or crusting is frequent (Fig. 20.21). Scarring or cystic or pigmented lesions are less common. There is a tendency for basal-cell carcinomas to be locally invasive but metastasis is extremely rare.
Basal cell carcinomata and lesions appearing as small brown pigmented papules, which are often numerous, are seen in the basal cell naevus syndrome. Superficial scarring and morphoeic basal cell carcinomas are more difficult to discern at their margins from normal skin; although uncommon they are important as they tend to follow tissue planes and invade an orifice such as the orbit. Treatment with X-rays is less effective
for such tumours.

TREATMENT

Tumours are normally removed surgically or treated with cryotherapy or radiotherapy. However, lesions that become invasive or are less accessible to normal treatments may be removed by chemosurgery. In Moh’s method the tissue is fixed in situ and excised in a systematic fashion and examined immediately under a microscope to determine the presence or absence of tumour.