URTICARIA

Urticaria is common and usually patients present with acute, transient but recurrent, pruritic, erythematous swellings, resulting from localized oedema within the skin. Each weal usually lasts a few minutes to hours and clears leaving no residual marks. The number of lesions varies from one or two to a widespread rash (2.40). Patients may exhibit dermographism (which also occurs in 10% of the normal population; 2.41). The itch of urticaria can be severe. Rarely, urticaria is associated with angioedema of the face or lips and in a more life-threatening pattern with swelling of the tongue and respiratory tract (2.42, 2.43). Similar reactions can occur in other organs including the gastrointestinal tract or joints. The aetiology of urticaria is either obvious - as when associated with specific foods, for example strawberries or sea food - or more commonly unknown. Both immunological and nonimmunological factors may be involved. Most patients require treatment with antihistamines and the rash generally settles quickly. In some cases it can become chronic, recurring for many months or years. Food diaries can be kept and exclusion diets may help in some cases. Patients should be warned to avoid aspirin and foods containing high amounts of azo dyes such as tartrazine, which can potentiate the urticaria (see p. 389). Urticarial lesions that persist for some days and leave bruising marks in the skin are suggestive of underlying vasculitis and need to be investigated more thoroughly.

2.40 Urticaria in close-up, showing characteristic weals, surrounded by an erythematous flare.

2.41 Dermographism is a skin reaction pattern in which the patient responds to anything more than a very light touch with a weal and flare reaction. This can be simply tested with firm finger pressure, as shown in this patient from a well-known London teaching hospital.

2.42 & 2.43 Severe angioedema in a 9-year-old boy after a bee sting. The patient required immediate treatment with adrenalin to overcome a generalized anaphylactic response, and showed gross facial swelling. 2.43 shows the same patient without angioedema.

REACTIVE ERYTHEMAS

Reactive erythema without urticaria may occur in response to many known or unknown stimuli and may take a number of different forms.
Erythema nodosum is primarily an inflammation of the subcutaneous fat (panniculitis), with involvement of the adjacent vasculature. It is an immunological reaction provoked by various infections, drugs, and a variety of other causes (2.44).
The characteristic lesions are tender, red nodules occurring on the lower legs and sometimes the forearms (2.45). Some
patients also have painful joints and fever. The lesions resolve in 6-8 weeks, often leaving a bruise-like appearance. Management depends on the identification and elimination of the underlying cause.
Erythema multiforme is also immunologically mediated. It usually follows an infection or drug therapy, but other factors have occasionally been implicated, and no cause is apparent in up to 50% of cases (2.46). The eruption typically takes the form of annular plaques over the palms, soles, limbs and sometimes over the trunk (2.47). Characteristic `target' lesions made up of two concentric plaques may blister in the centre (2.48). When combined with mucous membrane involvement, erythema multiforme is called the Stevens Johnson syndrome (2.49). Lesions in the tracheobronchial tree in such patients may lead to asphyxia, and conjunctival and corneal involvement may result in blindness. Genital ulcers may cause urinary retention and phimosis or vaginal stricture after they have healed. Severe Stevens-Johnson syndrome may progress to become indistinguishable from toxic epidermal necrolysis, a condition that may also be provoked directly by staphylococcal infection or drug therapy (1.101, 2.149).
Erythema chronicum migrans is another form of reactive erythema, which may be associated with Lyme disease (1.159) or rheumatic fever (5.88).
 

2.44 Some causes of erythema nodosum.

2.45 Erythema nodosum occurring in a classic distribution over the front of the legs and forearms. The appearance reflects the patchy inflammation of subcutaneous fat and small vessels, probably as the result of a type III (immune complex) allergic mechanism. Erythema nodosum has many causes (2.44), of which the most common in the Western world is now drug therapyespecially with sulphonamides. This patient also had arthralgia and a mild fever, and further investigation revealed an underlying diagnosis of sarcoidosis.

2.46 Some causes of erythema multiforme.

2.47 Erythema multiforme is a form of reactive erythema that probably involves both type III and type IV immunological mechanisms. Typically, it starts with a symmetrical eruption of target-like lesions on the hands and feet. These may blister centrally and they spread proximally, the extent depending on the severity of involvement. This patient is severely affected, with multiple confluent lesions. The underlying cause was sulphonamide therapy.

2.48 Erythema multiforme. A close-up view of a typical lesion on the palm. The centre of the target is beginning to blister.

2.49 Stevens-Johnson syndrome, in its severe form, is a widespread erythema multiforme with oral, genital and conjunctival
involvement, and widespread skin lesions, as on this patient's face. This form of the disease is most common in patients with Mycoplasma pneumoniae infection.
 

INFECTIONS AND INFESTATIONS

BACTERIAL INFECTIONS

Surface commensals include diphtheroids and micrococci - mainly Staphylococcus epidermidis. A minority of people carry Staphylococcus aureus in nares, perineum or axillae (2.4). Damaged epidermis predisposes to secondary infection.
Staphylococccal infections include impetigo (1.110), which is highly contagious (impetigo can also be caused by Streptococcus pyogenes). Furuncules (2.50) are boils that may occur singly or in crops; multiple or large lesions suggest underlying diabetes mellitus (1.99). Staphylococci may cause toxic epidermal necrolysis in children (1.101).
Erysipelas (1.106) is a streptococcal infection usually associated with systemic upset. Recurrent attacks may occur, leading to chronic lymphoedema. Necrotizing fasciitis, a rapidly progessive often fatal condition, may also be due to a group A beta-haemolytic streptococcal infection.
Syphilis should be remembered as a cause of skin rashes (see p. 78). The primary chancre is typically a painless ulcer. Secondary syphilis (1.241) must be distinguished from pityriasis rosea, measles, drug eruptions, guttate psoriasis and lichen planus. Tertiary syphilis (1.244) resembles granulomatous conditions such as sarcoid. Patients with tuberculosis (see p. 43) may present with lupus vulgaris, a chronic nodular scarring rash (2.51). Warty tuberculosis or scrofuloderma occur less commonly. Erythema nodosum (2.45) or induratum may be associated with tuberculosis.
Skin lesions in leprosy reflect the patient's immune response (see p. 47)
 

2.50 A boil (furuncle) is caused by a staphylococcal infection of a hair follicle with the accumulation of pus. This results in severe pain, and is usually followed by the spontaneous discharge of yellow pus. A boil in this location carries the risk of septicaemia and cavernous sinus thrombosis (see p. 502).

VIRAL INFECTIONS

Viral warts are caused by the human papilloma virus (more than 50 subtypes exist). Warts are common; their morphology varies with anatomical site and viral subtype. Spontaneous resolution occurs (30% in 6 months) but painful or multiple lesions may need treatment (2.52, 2.53, 8.10, see p. 76).

Herpes simplex types I and lI cause primary (sometimes asymptomatic) and recurrent infections on extragenital and genital sites. Recurrent lesions are preceeded by tingling or pain, usually appear in the same place and are triggered by various factors such as infection or sun exposure. Grouped vesicles on an erythematous base persist for a few days (see p. 26). Secondary bacterial infection may occur. Infection may complicate atopic dermatitis (Kaposi's varicelliform eruption),
Herpes zoster (shingles) is caused by the varicella-zoster virus, reactivated in a sensory nerve root (where it persists after chickenpox). Pain in the affected dermatome precedes the rash of scattered blisters and erythema (see p. 29). Haemorrhagic lesions and scattered lesions elsewhere on the body suggest underlying neoplasia or immunosuppression. Corneal ulcers and scarring may follow involvement of the ophthalmic branch of the trigeminal nerve. Postherpetic pain is common (see also p. 29).
Molluscum contagiosum is caused by a pox virus. The umbilicated pearly lesions (2.54), often multiple, are more common in childhood and resolve spontaneously after becoming inflamed. Residual marks may persist for some months.
Pityriasis rosea occurs in children and young adults (a viral aetiology is suspected but unproven). A herald patch (2.55) precedes subsequent lesions, which tend to be distributed along the rib lines (2.56). The lesions are usually asymptomatic but may be itchy. They persist for 4-6 weeks.
 

2.51 Lupus vulgaris on the cheek. This is a rare presentation of tuberculosis in the Western world, but it still occurs in developing countries and in immunosuppressed patients. The slowly extending lesion is hyperpigmented at its margin, and depigmented in the healing central zone. Ulceration has also occurred. This patient is generally pigmented as a result of Addison's disease, after tuberculous infection of the adrenals (see p. 316).

2.52 Multiple viral warts on the fingers. A florid collection of warts like this should raise the suspicion of a possible underlying impairment in cell-mediated immunity.

2.53 A plantar viral wart, popularly known as a 'verruca'. Single and multiple plantar warts are common, especially in school children who may acquire them from swimming-bath floors. They are characteristically flat with a callus on the surface, but may extend subcutaneously. They are often painful, and should be treated to relieve symptoms and prevent transmission to others.

2.54 Molluscum contagiosum. Note the umbilicated, pearly lesions. The condition occurs in childhood and in otherwise normal adults, but it is particularly common in patients with HIV infection.

2.55 The herald patch in pityriasis rosea commonly precedes the later multiple lesions by several days. It is usually oval, and has a surrounding collar of fine white scales.

2.56 Pityriasis rosea. The herald patch can still be seen, but there is now a widespread itchy skin eruption, largely following the lines of the ribs.

FUNGAL AND YEAST INFECTIONS

Dermatophyte fungi (genera Trichophyton, Microsporum and Epidermophyton) live on keratin and evoke a variable amount of inflammation. Clinical lesions are termed tinea or ringworm. Presentation depends on body site, but it is usually as plaques of scaling erythema, with variable itch (1.4, 2.5, 2.6, 2.7, 2.57, 2.58). Nail involvement causes onycholysis and dystrophy (2.59) and scalp infection patchy hair loss (2.60).

2.57 Tinea corporis. These annular lesions ('ringworm') are on the thigh. Note the scaly margins, which can be scraped and examined for fungal hyphae and spores (2.5-2.7).

2.58 Tinea pedis ('athlete's foot') is a very common infection, especially in those who wear tight or poorly ventilated footwear.

2.59 Chronic dermatophyte infection of the nails and the surrounding soft tissue of the index fingers of the right hand. For comparison, the corresponding fingers of the left hand are shown. The patient was a heavy smoker, and tar staining is evident in the right hand fingers. Finger clubbing is obvious in the fingers of the left hand. This was associated with carcinoma of the bronchus.

2.60 Fungal infection of the scalp, which has resulted in severe pustular inflammation and hair loss in an infant from a deprived background.

Candida infections caused by Candida albicans yeast commonly occur in moist, flexural sites (2.61). Predisposing factors include diabetes mellitus, pregnancy, broad-spectrum antibiotics and obesity (see also p. 61). Chronic candida paronychia may be complicated by additional bacterial infection; wet work or poor. circulation are predisposing factors. Chronic mucocutaneous candidiasis is associated with widespread candida infection of the skin, mucous membranes and nails (2.62).
Pityriasis versicolor is caused by yeasts (Pityrosporum orbiculare) producing widespread scaly lesions on the upper trunk and back (2.63), pale in dark skins and darker in fair skins. Recurrent attacks are common.

2.61 Candidiasis of the skin (intertriginous candidiasis) below both breasts in an obese diabetic.

2.62 Nail changes in a patient with chronic mucocutaneous candidiasis. There is onycholysis, a yellow-brownish pigmentation, with pitting and ridging, and the nails are soft, friable and easily split. Chronic mucocutaneous candidiasis normally begins in childhood, is associated with a defect in cell-mediated immunity and may be associated with autoimmune endocrine disorders including hypoadrenalism, hypothyroidism or diabetes mellitus. In adults the condition may occur in the presence of a thymoma. Lengthy, intensive treatment is required to eliminate this fungal nail infection.

2.63 Pityriasis versicolor. Typical lesions in a 28year-old woman.

INFESTATIONS

Infestations result from invasion of the body by arthropods, including insects, mites and ticks. Only a few are discussed here, Insect bites are reactions to injected antigens, causing weals, persisting papules and sometimes blisters (2.64). Lesions may occur in recurrent crops (papular urticaria), and are often secondarily infected.
Scabies is caused by the mite Sarcoptes scabei var. bominis (2.8). Transmission occurs through close body contact. The adult mite lays eggs in burrows in the skin (2.65). Sensitization to the mites results in a widespread secondary eczema (2.66) and severe pruritus, worse at night. Household contacts must be treated to prevent recurrences.
Lice infestations are caused by Pediculus humanus (var. capitis and corporis) and Phthirus pubis. The lice suck blood, causing pruritus, scratching and secondary infection. Their eggs, known as nits, are attached to.hairs (or clothing with body lice, (2.67). Head lice occur irrespective of cleanliness, whereas body lice are found on the vagrant or unhygenic. Pubic lice are commonly sexually transmitted.

2.64 Insect bites producing a bullous reaction in an 8year-old child.

2.65 Scabies. Typical burrows on the finger.

2.66 Scabies with secondary infected eczema in a boy from Papua.

LICHEN PLANUS

Lichen planus accounts for only 1-2% of new referrals to the dermatology clinic. It affects both sexes equally and usually occurs in those aged 30-60 years.
The classic presentation is easy to diagnose with `purple, pruritic, polygonal papules'. These commonly occur on the wrists, low back, ankles (where they may be chronic and hypertrophic) and feet (2.68) but lesions may be widespread. If severe, lesions may blister. The Koebner phenomenon may be seen (2.69).

2.68 Lichen planus. The polygonal papules on the dorsum of the foot are typical of the chronic form of the disorder, and the lesions are commonly itchy. Dystrophic nail changes are common in lichen planus.

2.69 Koebner's phenomenon in lichen planus. Typical lesions may occur in a scratch when the disease is active, as here along the lines of bramble scratches.

2.70 Oral lesions are relatively common in lichen planus. The classic appearance is of white reticulations on the buccal mucosa, as here, but the disease may also take an erosive form and similar lesions may occur on the tongue. Biopsy is usually advisable to confirm the diagnosis.

Mucosal lesions are common and may present before or without those on other affected sites. Mouth lesions are diagnostic, with lacy white striae on the buccal mucosa (2.70). Ulceration may occur. Genital lesions especially affect the vulva or the glans and shaft of the penis.
Hair loss may occur, sometimes with irreversible scarring alopecia (2.71). Nail changes include irregular coarse pits or linear streaks, or adhesions between the skin and the nail plate, causing pterygium formation.
The histology is characteristic and should confirm the diagnosis if required.
Most cases settle within 1-2 years, but the rash may recur or become chronic. Post-inflammatory hyperpigmentation may persist. Topical or systemic steroid treatment may be required in severe cases.
The aetiology is unknown. There are interesting similarities between lichen planus and the skin lesions of chronic graftversus-host disease, which suggest an autoimmune aetiology. An association with primary biliary cirrhosis and other autoimmune diseases has also been reported.
Lichenoid reactions, mimicking lichen planus, may result from therapy with drugs such as gold, chloroquine, methyldopa and thiazide diuretics, or after contact with colour photograph developer.

2.71 Lichen planus in the scalp of a 68-year-old man. There is depigmentation and scarring caused by biopsy-proven lichen planus that was active for over 30 years.

Bullous Disorders

Blisters develop when fluid collects between layers of the epidermis, or between the epidermis and dermis, as a result of inflammation (external or internal) or shearing forces. They are a feature of many conditions, for example dermatitis (p. 89), herpes simplex (p. 26) and insect bites (p. 98). The bullous disorders are distinguished by characteristic immunofluorescent staining either within the epidermis or at the dermoepidermal junction, in conjunction with the appropriate clinical features.
Dermatitis herpetiformis is an uncommon disorder in which groups of intensely itchy blisters appear on elbows (2.72), shoulders, buttocks (2.73) and knees. There may be an associated gluten enteropathy (see p. 372). Skin biopsy characteristically shows subepidermal microabscesses or blisters (2.2) and immunofluorescence shows granular IgA deposits in dermal papillae (2.3). Patients with this disorder have a high association with HLA B8 (85-90%) and DRw3. Although the disease is well controlled with dapsone and a gluten-free diet, treatment may be long term as the condition persists for many years, and there is some evidence to suggest a risk of small bowel lymphoma, as in coeliac disease.
Bullous pemphigoid is a condition predominantly affecting elderly patients in which large tense itchy blisters appear on any body site (2.74). The blisters may be preceded by pruritus alone or with an urticarial type rash. Skin biopsy shows subepidermal blisters and immunofluorescence shows linear IgG (occasionally IgA) and C3 at the dermoepidermal junction (2.75). The pemphigoid antigen is located within the hemidesmosomes but there is no evidence to date that the antibody is directly pathogenic; it mayhave a role in activating complement pathways that then cause local inflammation. Circulating anti-basement membrane antibodies are present in up to 75% of patients, but the titre does not reflect disease activity. Oral lesions are uncommon. The disease runs a chronic, often self-remitting course over months to years. Treatment with prednisolone and azathioprine can be helpful.
Pemphigus gestationis (formerly known as herpes gestationis) is a rare dermatosis of pregnancy resembling pemphigoid clinically and histologically (2.76). It remits post partum, but tends to recur with subsequent pregnancies.
Pemphigus vulgaris is a severe, chronic disorder affecting middle-aged to elderly patients. Many patients present with oral lesions before developing the skin lesions, which are predominantly erosions as the blisters are flaccid and easily ruptured (2.77, 2.78). Lesions occur predominantly on the trunk, face or pressure points, but all body sites can be affected. Skin biopsy shows intraepidermal blisters and immunofluorescence shows diffuse staining between epidermal cells, with IgG and C3 (2.79). Circulating autoantibodies are generally present and the titre reflects disease activity. Evidence is accumulating that this antibody, directed towards one of the desmosomal proteins, desmoglein, is pathogenic in the condition. The course of this disease is prolonged, often with serious complications despite therapy. The condition can be caused by drugs, such as penicillamine, captopril and rifampicin.
Blisters are a common feature of porphyrias (see pp. 349). Inherited blistering diseases are an uncommon group of disorders occurring in infancy or childhood. Recent advances in molecular biological techniques have enabled the cause of many of these conditions to be determined. Epidermolysis bullosa simplex is a group of disorders characterized by splitting of the basal cells of the epidermis, above the dermoepidermal junction. Many of these disorders have been shown to be caused by point mutations in the cytoskeletal proteins, the keratins, in particular keratins K5 and K14, which provide resilience to the basal epidermal cells. This condition is inherited as an autosomal dominant disorder, although many cases are sporadic. In the more severe, and less common, inherited blistering diseases known as dystrophic epidermolysis bullosa, the blister forms at or below the dermoepidermal junction (2.80). These disorders are due to point mutations in either laminin V a protein integral to the basement membrane, or collagen VII, which connects the basement membrane to the underlying dermal structures. These variants of epidermolysis bullosa may be either dominantly or recessively inherited.

2.72 Dermatitis herpetiformis on the elbow. This 65-year-old man had a history of a recurrent eruption of vesicles and crusts on his elbows, head, neck and lower back. The lesions are intensely itchy, and the vesicles are easily ruptured by scratching.

2.73 Dermatitis herpetiformis in the sacral and buttock areas. The vesicles have been ruptured by scratching, and are healing, leaving pigmented scars.

2.74 Pemphigoid. Some of the blisters have become haemorrhagic, as often occurs.

2.75 Direct immunofluorescence in pemphigoid reveals IgG deposition ;n the basement membrane (arrow) in perilesional skin biopsies. Granular deposition of C3 is often observed.

2.76 Pemphigus gestationis. This rare disorder presents with vesicles and bullae during pregnancy or the puerperium. It resembles bullous pemphigoid, but can sometimes be distinguished from it by immunofluorescence techniques. The condition tends to recur in subsequent pregnancies.

2.77 Pemphigus vulgaris in a 13year-old boy. The blisters rupture easily, and are often associated with similar lesions on mucous membranes, especially in the mouth.
 

2.78 Pemphigus vulgaris blisters are thin and painful, with an intraepidermal split. They often become secondarily infected.

2.79 Direct immunofluorescence in pemphigus vulgaris, showing intercellular epidermal deposition of IgG. 0 and occasionally IgM may also be deposited.

2.80 Epidermolysis bullosa (dystrophic form). From early childhood, minor trauma has caused blistering in this patient. The blisters heal with scarring, as shown here. Note also the dystrophic nail changes.

ACNE

Acne vulgaris is a very common chronic inflammatory disorder of the pilosebaceous unit. It occurs in adolescence, usually earlier in girls, and may persist for some years (infantile acne may also occur rarely). It results from a combination of factors: there is increased sebum production (this alone does not cause acne), together with infection and inflammation due to Propionibacterium acnes within the sebaceous glands, where breakdown of fatty acids triggers inflammation. Increased endorgan sensitivity within the sebaceous gland to normal levels of androgen hormones may account for hormonal influences; acne may be associated with hirsutes and obesity in the polycystic ovary syndrome (see p. 322). Duct abnormalities and obstruction at the epidermal opening of the pilosebaceous unit also have a role. The face (2.81), back (2.82) and chest are affected with a range of lesions from small papules and pustules to comedones and deeper, painful cysts, on a background of seborrhoea. Subsequent scars may be depressed (2.83) or hypertrophic, but adequate treatment should prevent scar formation.
Less commonly, drug-induced acne may follow treatment with corticosteroids, androgenic hormones, oral contraceptives, anticonvulsant drugs, bromides or iodides.
Acne rosacea occurs in an older age group than acne vulgaris and has a vascular component to it. Flushing, often precipitated by hot foods, warm environment or sunlight, occurs in association with small papules and pustules over the forehead, cheeks and chin in a symmetrical pattern (2.84, 9.45). Seborrhoea is not necessarily present. Despite the obvious
improvement with antibiotic therapy (topical or systemic) no dnfective cause has been demonstrated; skin microflora are often normal and an association with the mite Demodex folliculorum (a skin commensal) has not been substantiated. Rosacea lymphoedema may develop and become persistent and rhinophyma (2.85) may develop. Inflammatory ocular conditions, - most commonly conjuctivitis but also rosacea keratitis, a more serious complication - may occur in up to 50% of patients and may precede the skin manifestations. The rash is exacerbated by topical steroids and sometimes aggravated by sunlight. Rosacea must be distinguished from seborrhoeic dermatitis, perioral dermatitis and the facial rash of systemic lupus erythematosus.

2.81 Acne vulgaris usually involves the face. This 17-year-old shows the typical features of moderately severe acne. He has many papular and pustular lesions at different stages of evolution, and the older lesions are healing with scarring.

2.82 Acne vulgaris on the shoulders and back - another common site. Again, a wide range of lesions are seen, including some large pustules, and scarring is occurring on healing.

2.83 Acne scars - a close-up view. In this patient, the scars are depressed, but hypertrophic scars may also occur.

2.84 Acne rosacea. This patient shows typical papules and pustules, superimposed on a generally erythematous facial skin. His eyes are normal, but keratitis may occur.

2.85 Rhinophyma usually occurs as a long-term complication of acne rosacea. The nose is characteristically red and bulbous. The 'strawberry' appearance results from hyperplasia of the sebaceous glands and connective tissue. The follicle openings become prominent.

DISORDERS OF PIGMENTATION

Most disorders of pigmentation result from excess or insufficient melanin, the dominant pigment in the skin. Other pigments include haemosiderin, bilirubin and carotene.
Congenital disorders of pigmentation include freckles, simple lentigines and cafe-au-lait patches in neurofibromatosis (2.86). Less common conditions include oculocutaneous albinism (defective melanin production that affects hair, eyes and skin, sparing pigmented naevi, 2.87), incontinentia pigmentil (initial blisters leave whorled pigmentary lesions in adult life) and lentigines round the mouth in Peutz-Jeghers syndrome (2.88). Xeroderma pigmentosum patients show excessive freckling in light-exposed areas (see p.117). Urticaria pigmentosa occurs in childhood as scattered brownish-pink macules that urticate on rubbing.
Vitiligo (2.89) develops in 1% of the population. The white patches show total loss of melanocytes. A personal or family history of other autoimmune disorders may be present.
Hyperpigmentation may be a sign of underlying endocrine disease, such as Addison's disease, acromegaly, Cushing's syndrome or hyperthyroidism. Patchy facial pigmentation (chloasma or melasma) is common in pregnancy or with oral contraceptives. Tumours may cause diffuse pigmentation through ectopic adrenocorticotrophic hormone (ACTH) production or localized pigment changes such as acanthosis nigricans (2.90).
Hyperpigmentation is seems in cirrhosis, renal failure, haemachromatosis (slate grey colour; 9.52) and porphyria (7.157). Connective tissue disorders such as systemic lupus erythematosus, dermatomyositis or morphoea may cause local or diffuse pigment changes.
Drugs causing pigmentation include antimalarials, phenothiazines, hydantoin, minocycline, busulphan, cyclophosphamide, bleomycin and arsenic. Psoralens, used for photochemotherapy, produce a deep tan.
Exogenous causes of pigmentation include carotene (carotenaemia) and compounds containing silver (argyria). Tattoos are a common form of exogenous pigmentation.
Post-inflammatory hypopigmentation or hyperpigmentation may result from inflammatory conditions such as lichen planus, dermatitis (2.91), or discoid lupus erythematosus, especially in darker-skinned subjects.

2.86 Neurofibromatosis (von Recklinghausen's disease, type I, see p. 514). Note the subcutaneous nodular tumours arising in the sheaths of peripheral nerves, the pigmented pedunculated tumours on the skin surface and the brown (cafe-au-lait) patches.

2.87 Albinism. This child has typical white skin and hair. His eyes were also affected; he had pink irises and photophobia.

2.88 Peutz-Jeghers syndrome. Dark brown pigmentation is found particularly on the lips and around the mouth, but also on the hard and soft palate, buccal mucosa and, occasionally, on the feet and hands. There is an association with multiple intestinal polyps, some of which undergo malignant transformation.

2.89 Vitiligo is often first noticed in the hands, but may be found throughout the body. It is characterized by multiple, well-demarcated areas of hypopigmentation that progressively enlarge. It is often associated with other autoimmune disorders, and - in about one-third of cases-there is a family history.

2.90 Acanthosis nigricans in an Asian patient. Patchy velvetybrown hyperpigmentation and thickening of flexures develops. In older patients, this is often a marker of underlying malignant disease, but the condition may occur in diabetes and other endocrine disorders and as an isolated abnormality.

2.91 Hyperpigmentation and lichenification are common complications of chronic atopic dermatitis. Note the thinning of the skin around the gross lesions, which results from inappropriate use of topical corticosteroid therapy.

DISORDERS OF KERATINIZATION

Keratinization disorders result from abnormalities of epidermal maturation, with scaling and thickening of the skin, with or without inflammation. Gene defects have now been identified in several of these conditions, and study of these disorders has helped to clarify the mechanisms of differentiation in the normal epidermis and in other disorders of keratinization.
Ichthyosis vulgarisis a common (1:300) autosomal dominant condition of scaly skin that appears in early childhood (2.92). The scales are small and spare the flexural areas, and the condition improves with age. There is an association with keratosis pilaris. X-linked ichthyosis occurs in early infancy, with larger, darker scales and flexural involvement and persist in adult life. The gene defect is located on the X chromosome and affected individuals have a defect in the enzyme steroid sulphatase. This and lamellar ichthosis, a rare condition (in some families a gene defect in the enzyme transglutaminase has been identified), may present as a `colloidion baby' at birth. Bullous ichthyosiform erythroderma and the milder variant ichthyosis bullosa of Siemens are two rare forms of ichthyosis that occur with blistering in early life. These conditions are now known to be due to mutations in the genes for keratins Kl, K10, or K2e, proteins present in the upper layers of the epidermis.

Keratoderma of palms and soles may be inherited or acquired Various patterns such as punctate, striate or diffuse thickening
occur. Rarely, diffuse keratoderma (tylosis) has been associated in some families with underlying neoplasia (2.93). Some forms
of keratoderma are due to mutations in keratin genes K6 and K9 (this protein is only found in palm or sole skin).
Acquired ichthyosis is usually associated with underlying conditions such as Hodgkin's disease, other lymphomata, sarcoid or malabsorption.
Keratosis pilaris is a common abnormality of keratinization at the hair follicle ducts that presents in childhood as roughened areas on upper outer arms and legs (2.94). The face a eyebrows may be affected.
Darier's disease (keratosis follicularis) is a rare autosomal dominant condition that appears in the mid-teens as small scaly
reddish-brown papules on chest, back, scalp or flexures (2.95).  Histology is diagnostic. Nail abnormalities include linear streaks and notching, and punctate lesions may be seen on hands or feet. The gene defect has been located but the candidate protein has yet to be identified.

2.92 Ichthyosis vulgaris is a dominant condition that causes scaly skin from early childhood onwards. Its name reflects the resemblance of the skin to scaly fish skin.

2.93 Keratoderma of the palm in a 5year-old girl with familial tylosis.

2.94 Keratosis pilaris on the outer surface of the upper arm. In this common disorder, the hair follicles are plugged with keratin, giving the skin a rough texture. The disorder is only of cosmetic importance.

2.95 Darier's disease. In this clorrinanl familial disorder there are large numbers of hard reddish papules, which may coalesce.

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