Skin disease

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Chapter 24 Skin disease

Structure and function of the skin

Approach to the patient

Infections

Bacterial infections

Mycobacterial infections

Viral infections

Fungal infections

Infestations

Papulo-squamous/inflammatory rashes

Eczema

Psoriasis

Urticaria and angio-oedema

Hereditary angio-oedema

Facial rashes

Idiopathic photodermatoses

Erythroderma

Cutaneous signs of systemic disease

Bullous disease

Immunobullous disease

Mechanobullous disease

Skin tumours

Benign cutaneous tumours

Potentially pre-malignant cutaneous tumours

Malignant cutaneous tumours

Disorders of blood vessels/lymphatics

Disorders of collagen and elastic tissue

Disorders of pigmentation

Hypopigmentation

Hyperpigmentation

Drug-induced rashes

Disorders of nails

Disorders of hair

Hair loss

Increased hair growth – hirsutism

Birth marks/neonatal rashes

Human immunodeficiency virus and the skin

Dermatoses of pregnancy

Principles of topical therapy

Introduction

Skin diseases have a high prevalence throughout the world. In developing countries infectious diseases such as tuberculosis, leprosy and onchocerciasis are common, whereas in developed countries inflammatory disorders such as eczema and acne are common. Skin disorders can be inherited, e.g. Ehlers–Danlos syndrome, a part of normal development, e.g. acne vulgaris, or may present as part of a systemic disorder, e.g. systemic lupus erythematosus (SLE). Approximately 25% of the UK population will develop a skin problem and skin disease accounts for 10% of the workload of family doctors. The common reasons that people with a rash present, are itching or pain, disturbed sleep, anxiety, depression, lack of self-confidence (if rash is obviously visible); and interfering with work (such as allergic hand eczema in a chef, builder or hairdresser).

Rarely, skin disease can be fatal. Examples are malignant melanoma, toxic epidermal necrolysis and pemphigus.

Structure and function of the skin

The skin consists of four distinct layers:

1. The epidermis

2. The basement membrane zone

3. The dermis

4. The subcutaneous layer (Fig. 24.1).

Figure 24.1 The structure of the skin (see also Fig. 24.27).

The functions of the skin are summarized in Box 24.1.

The epidermis

The epidermis is a stratified epithelium of ectodermal origin that arises from dividing basal keratinocytes. The downward projections of the epidermis into the dermis are called the ‘rete ridges’. The lower epidermal cells (basal layer) produce a variety of keratin filaments and desmosomal proteins (e.g. desmoglein and desmoplakin), which make up the ‘cytoskeleton’. This confers strength to the epidermis preventing it shedding. Higher up in the granular layer, complex lipids are secreted by the keratinocytes and these form into intercellular lipid bilayers, which act as a semipermeable skin barrier. The upper cells (stratum corneum) lose their nuclei and become surrounded by a tough impermeable ‘envelope’ of various proteins (loricrin, involucrin, filaggrin and keratin). Changes in lipid metabolism and protein expression in the outer layers allow normal shedding of keratinocytes.

Keratinocytes can secrete a variety of cytokines (e.g. interleukins, gamma-interferon, tumour necrosis factor alpha) in response to tissue injury or in certain skin diseases. These play a role in specific immune function, cutaneous inflammation and tissue repair. There is a further layer of protection against microbial invasion – the innate immune system of the skin. This comprises neutrophils and macrophages as well as keratinocyte-produced antimicrobial peptides (called β-defensins and cathelicidins). Expression of these peptides is both constitutive and induced by skin inflammation and they are active against infection and play a role in wound healing. A deficiency of these peptides may account for the susceptibility of people with atopic eczema to skin infection.

Other cells in the epidermis

Melanocytes are found in the basal layer and secrete the pigment melanin. These protect against UV irradiation. Racial differences are due to variation in melanin production, not melanocyte numbers.

Merkel cells are also found in the basal layer and originate either from neural crest or epidermal keratinocytes. They are numerous on finger tips and in the oral cavity and play a role in sensation.

Langerhans’ cells are dendritic cells found in the supra-basal layer. They derive from the bone marrow and express the cytokine CCR6. They are guided to normal skin, which contains a CCR6 agonist called macrophage inflammatory protein 3α. Langerhans’ cells endocytose extracellular antigens in the skin and then migrate to local lymph nodes for T cell presentation and thus act as antigen-presenting cells.

The basement membrane zone (see Fig. 24.27) is a complex proteinaceous structure consisting of type IV, VII and XVII collagen, hemidesmosomal proteins, integrins and laminin. Collectively, they hold the skin together, keeping the epidermis firmly attached to the dermis. Inherited or autoimmune-induced deficiencies of these proteins can cause skin fragility and a variety of blistering diseases (see p. 1221).

FURTHER READING

Borkowski AW, Gallo RL. The coordinated response of the physical and antimicrobial peptide barriers of the skin. J Invest Dermatol 2011; 131:285–287.

Lin JY, Fisher DE. Melanocyte biology and skin pigmentation. Nature 2007; 445:843–850.

Shimomura Y, Christiano AM. Biology and genetics of hair. Annu Rev Genomics Hum Genet 2010; 11:109–132.

Approach to the patient

The history should aim to elicit the following points:

Time course of rash

Distribution of lesions

Symptoms (e.g. itch or pain)

Family history (especially of atopy and psoriasis)

Drug/allergy history

Past medical history

Provoking factors (e.g. sunlight or diet)

Previous skin treatments.

Examination entails looking and feeling a rash (for terminology, see Table 24.1). It should include an assessment of nails, hair and mucosal surfaces even if these are recorded as unaffected. The following terms are used to describe distribution: flexural, extensor, acral (hands and feet), symmetrical, localized, widespread, facial, unilateral, linear, centripetal (trunk more than limbs), annular and reticulate (lacey network or mesh like).

Table 24.1 Morphological description of skin lesions

Investigation. With regard to investigation, clinical acumen remains the most useful tool in dermatology but a variety of tests are useful in confirming a diagnosis (Table 24.2).

Table 24.2 Investigations used in skin disorders

Test	Use	Clinical example
Skin swabs	Bacterial culture	Impetigo
Blister fluid	Electron microscopy, viral culture and PCR	Herpes simplex
Skin scrapes	Fungal culture	Tinea pedis
Skin scrapes	Microscopy	Scabies
Nail sampling	Fungal culture	Onychomycosis
Wood’s light	Fungal fluorescence	Scalp ringworm
Wood’s light	Fungal fluorescence	Erythrasma
Blood tests	Serology	Streptococcal cellulitis
	Autoantibodies	Systemic lupus erythematosus
	HLA typing	Dermatitis herpetiformis
	DNA analysis	Epidermolysis bullosa
Skin biopsy	Histology	General diagnosis
	Immunohistochemistry	Cutaneous lymphoma
	Immunofluorescence	Immunobullous disease
	Culture	Mycobacteria/fungi
Patch tests	Allergic contact eczema	Hand eczema
Urine	Dipstick (glucose)	Diabetes mellitus
Urine	Cytology (red cells)	Vasculitis
Dermatoscopy (direct microscopy of skin)	Assessment of pigmented lesions	Malignant melanoma

Infections

Bacterial infections (see also p. 114)

The skin’s normal bacterial flora prevents colonization by pathogenic organisms. A break in epidermal integrity by trauma, leg ulcers, fungal infections (e.g. athlete’s foot) or abnormal scaling of the skin (e.g. in eczema) can allow infection. Nasal carriage of bacteria can be a source of reinfection.

Impetigo

Impetigo is a highly infectious skin disease most common in children (Fig. 24.2). It presents as weeping, exudative areas with a typical honey-coloured crust on the surface. It is spread by direct contact. The term ‘scrum pox’ refers to impetigo spread between rugby players. Staphylococci or group A β-haemolytic streptococci are the causative agents: skin swabs should be taken.

Figure 24.2 Impetigo – crusted blistering lesions on the chin.

Prevention

Prevention is by good personal hygiene, particularly hand washing with soap.

Treatment

Impetigo is usually treated with oral antibiotics for 7–10 days (flucloxacillin 500 mg four times daily for Staphylococcus; phenoxymethylpenicillin 500 mg four times daily for Streptococcus). Other close contacts should be examined and children should avoid school for 1 week after starting therapy. If impetigo appears resistant to treatment or recurrent, take nasal swabs and check other family members. Nasal mupirocin (three times daily for 1 week) is useful to eradicate nasal carriage, especially in hospital staff. Community-acquired MRSA (in chapter 4) is increasingly recognized as a cause of superficial skin infections and treatment should be governed by bacterial sensitivities.

FURTHER READING

Liu C, Bayer A, Cosgrove SE et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect Dis 2011; 52:285–292.

Bullous impetigo/staphylococcal scalded skin syndrome

Rarely Staphylococcus releases an exfoliating toxin which acts high up in the epidermis: toxin A causes blistering at the site of infection (bullous impetigo), toxin B spreads through the body causing more widespread blistering (staphylococcal scalded skin syndrome, SSSS). The latter is more common in childhood with very low mortality rates. In adults it is often associated with renal disease or immunosuppression, and mortality rates increase to 50%. Both these toxins cleave desmoglein 1 (a desmosomal protein) so mucosal involvement does not occur (this is analogous to pemphigus foliaceous which has the same target antigen, p. 1222).

Staphylococcal scalded skin syndrome.

SSSS can mimic toxic epidermal necrolysis (TEN, see p. 1231). It can be differentiated in two ways: mucosal involvement only occurs in TEN, and skin biopsy shows a more superficial split in SSSS (intraepidermal) than in TEN (subepidermal). Both bullous impetigo and SSSS are treated with anti-staphylococcal antibiotics (e.g. flucloxacillin) and supportive care.

Cellulitis

Cellulitis presents as a hot, sometimes tender area of confluent erythema of the skin due to infection of the deep subcutaneous layer. It often affects the lower leg, causing an upward-spreading, hot erythema, and occasionally will blister, especially if oedema is prominent. It may also be seen affecting one side of the face. Patients are often unwell with a high temperature. It is usually caused by a β-haemolytic streptococcus, rarely a staphylococcus, and sometimes community-acquired MRSA (in chapter 4). In the immunosuppressed or diabetic patient Gram-negative organisms or anaerobes should be suspected.

There may be an obvious portal of entry for infection such as a recent abrasion or a venous leg ulcer. The web spaces of the toes should be examined for fungal infection. Skin swabs are usually unhelpful. Confirmation of infection is best done serologically: antistreptolysin O titre (ASOT) and antiDNAse B titre (ADB).

Erysipelas is the term used for a more superficial infection (often on the face) of the dermis and upper subcutaneous layer that clinically presents with a well-defined edge. However, erysipelas and cellulitis overlap so it is often impossible to make a meaningful distinction.

Necrotizing fasciitis (see p. 116).

Treatment

Treatment is with phenoxymethylpenicillin (or erythromycin) and flucloxacillin (all 500 mg four times daily). If disease is widespread, treatment with antibiotics should be given intravenously for 3–5 days followed by at least 2 weeks of oral therapy. It is also necessary to treat any identifiable underlying cause. If cellulitis is recurrent, low-dose antibiotic prophylaxis (e.g. phenoxymethylpenicillin 500 mg twice daily) is used as each episode will cause further lymphatic damage. Post-cellulitic oedema is common and predisposes to further episodes of cellulitis.

FURTHER READING

Kilburn SA, Featherstone P, Higgins B et al. Interventions for cellulitis and erysipelas. Cochrane Database Syst Rev 2010; 6:CD004299.

Ecthyma

Ecthyma is also an infection due to Streptococcus or Staphylococcus aureus or occasionally both. It presents as chronic well-demarcated, deeply ulcerative lesions sometimes with an exudative crust. It is commoner in developing countries, being associated with poor nutrition and hygiene. It is rare in the UK but is seen more commonly in intravenous drug users and people with HIV infection.

Treatment is with phenoxymethylpenicillin and flucloxacillin (both 500 mg four times daily) for 10–14 days.

FURTHER READING

Jemec GBE. Hidradenitis suppurative. N Engl J Med 2012; 366:158–164.

Erythrasma

Erythrasma is caused by Corynebacterium minutissimum. It usually presents as an orange-brown flexural rash, and is often seen in the axillae or toe web spaces (Fig. 24.3). It is frequently misdiagnosed as a fungal infection. The rash shows a dramatic coral pink fluorescence under Wood’s (ultraviolet) light.

Figure 24.3 Erythrasma (a) of the axilla; (b) showing pink fluorescence under a Wood’s lamp.

Treatment is with oral erythromycin 500 mg four times daily for 7–10 days.

Folliculitis

Folliculitis is an inflammation of the hair follicle. It presents as itchy or tender papules and pustules. Staphylococcus aureus is frequently implicated. It is commoner in humid climates and when occlusive clothes are worn. A variant occurs in the beard area (called ‘sycosis barbae’), which is commoner in black Africans. This is probably caused by the ability of shaved hair to grow back into the skin, especially if the hair is naturally curly. Extensive, itchy folliculitis of the upper trunk and limbs should alert one to the possibility of underlying HIV infection. Folliculitis following use of hot tubs is due to Pseudomonas ovale.

Treatment is with topical antiseptics, topical antibiotics (e.g. sodium fusidate) or oral antibiotics (e.g. flucloxacillin 500 mg or erythromycin 500 mg both four times daily for 2–4 weeks).

Boils (furuncles)

Boils are a rather more deep-seated infection of the skin, often caused by Staphylococcus. These can cause painful red swellings. They are commoner in teenagers and often recurrent. Recurrent boils may rarely occur in diabetes mellitus or in immunosuppression. Large boils are sometimes called ‘carbuncles’. Swabs should be taken to check antibiotic sensitivity as community-acquired MRSA is an increasingly common cause.

Treatment is with oral antibiotics (e.g. erythromycin 500 mg four times daily for 10–14 days) and occasionally by incision and drainage.

Antiseptics such as chlorhexidine (as soap) can be useful in prophylaxis.

Hidradenitis suppurativa

This condition is characterized by a painful, discharging, chronic inflammation of the skin at sites rich in apocrine glands (axillae, groins, natal cleft). The cause is unknown but it is commoner in females and within some families it appears to be inherited in an autosomal dominant fashion. The initial lesion is occlusion of the hair follicle producing an inflammatory reaction that spreads to the apocrine glands. Clinically it presents after puberty with papules, nodules and abscesses which often progress to cysts and sinus formation. With time, scarring arises. The condition follows a chronic relapsing/remitting course and is worse in obese individuals.

Treatment is difficult but weight loss, ‘prophylactic’ antibiotics, oral retinoids, zinc and co-cyprindiol (2 mg cyproterone acetate + 35 µg ethinylestradiol in females only) have been tried. They should be used as for acne vulgaris (p. 1212). Severe recalcitrant cases have been treated with intravenous infliximab, a monoclonal antibody (p. 72). Surgery and skin grafting is sometimes required.

Pitted keratolysis

This is a superficial infection of the horny layer of the skin caused by a corynebacterium. It frequently involves the soles of the forefoot and appears as numerous small punched-out circular lesions of a rather macerated skin (e.g. as seen after prolonged immersion). There may be an associated hyperhidrosis of the feet and a prominent odour.

Treatment. Topical antibiotics (e.g. sodium fusidate or clindamycin, applied three times daily for 2–4 weeks) and topical anti-sweating lotions are effective therapies.

Mycobacterial infections

Leprosy (Hansen’s disease) (p. 130)

Leprosy usually involves the skin, and the clinical features depend on the body’s immune response to the organism Mycobacterium leprae.

Indeterminate leprosy is the commonest clinical type, especially in children. This presents as small, hypopigmented or erythematous circular macules with occasional mild anaesthesia and scaling. This may resolve spontaneously or progress to one of the other types. Biopsy reveals a perineural granulomatous infiltrate and scant acid-fast bacilli.

Tuberculoid leprosy presents with a few larger, hypopigmented (see Fig. 4.28) or erythematous plaques with an active erythematous, often raised, rim. Lesions are usually markedly anaesthetic, dry and hairless, reflecting the nerve damage. Nerves may be enlarged and palpable. Biopsy shows a granulomatous infiltrate centred on nerves but no organisms.

Lepromatous leprosy presents with multiple inflammatory papules, plaques and nodules. Loss of the eyebrows (‘madarosis’) and nasal stuffiness are common. Skin thickening and severe disfigurement may follow. Anaesthesia is much less prominent. Biopsy shows numerous acid-fast bacilli.

Diagnosis and treatment are discussed on page 131.

Skin manifestations of tuberculosis

Tuberculosis can occasionally cause skin manifestations:

Lupus vulgaris usually arises as a post-primary infection. It usually presents on the head or neck with red-brown nodules that look like apple jelly when pressed with a glass slide (‘diascopy’). They heal with scarring and new lesions slowly spread out to form a chronic solitary erythematous plaque. Chronic lesions are at high risk of developing squamous cell carcinoma.

Tuberculosis verrucosa cutis arises in people who are partially immune to tuberculosis but who suffer a further direct inoculation in the skin. It presents as warty lesions on a ‘cold’ erythematous base.

Scrofuloderma arises when an infected lymph node spreads to the skin causing ulceration, scarring and discharge.

The tuberculides are a group of rashes caused by an immune manifestation of tuberculosis rather than direct infection. Erythema nodosum is the commonest and is discussed on page 1216. Erythema induratum (‘Bazin’s disease’) produces similar deep red nodules but these are usually found on the calves rather than the shins and they often ulcerate.

Viral infections

Viral exanthem

This is the commonest type of virus-induced rash and presents clinically as a widespread nonspecific erythematous maculopapular rash. It probably arises due to circulating immune complexes of antibody and viral antigen localizing to dermal blood vessels. The rash can be caused by many different viruses (e.g. echovirus, erythrovirus, human herpes virus-6, Epstein–Barr virus; see chapter 4) and so is rarely diagnostic. The rash will resolve spontaneously in 7–10 days.

Slapped cheek syndrome (erythema infectiosum, fifth disease)

See page 101.

Herpes simplex virus (see also p. 97)

Herpes simplex virus (HSV) occurs as two genomic subtypes. Most people are affected in early childhood with HSV type 1 but the infection is usually subclinical. Occasionally it can present with either clusters of painful blisters on the face or a painful gingivostomatitis. In some individuals cell-mediated immunity is poor and they get recurrent attacks of HSV, often manifest as cold sores. Immunosuppression can also cause a recrudescence of HSV. HSV can also autoinoculate into sites of trauma and present as painful blisters/pustules which may be seen for example on the fingers of healthcare workers (‘herpetic whitlow’).

Primary herpes simplex infection.

HSV type 2 infections are discussed on page 97. Other rare complications of HSV infection include corneal ulceration, eczema herpeticum, chronic perianal ulceration in AIDS patients and erythema multiforme.