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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease
21 Skin disease
O.M.V. SCHOFIELD
J.L. REES
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Skin disease is common. Surveys in
Skin complaints affect all ages from the neonate to the elderly and cause harm in a number of ways as shown in
The aim of this chapter is to give the reader:
an idea of how to assess the patient with a rash or lesion
advice on appropriate initial management and therapy
theory underlying the mechanisms of some skin diseases and their therapies.
21.1 THE FOUR Ds
Discomfort
Most often itching or pain (e.g. eczema, post-herpetic neuralgia)
Disfigurement
Leading to embarrassment and withdrawal from society (e.g. birth marks, acne vulgaris and psoriasis)
Disability
Leading to loss of work and wages (e.g. dermatitis of the hands and feet)
Death
Rare but still seen (e.g. metastatic melanoma and widespread blistering drug reactions)
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > FUNCTIONAL ANATOMY, PHYSIOLOGY AND INVESTIGATIONS
FUNCTIONAL ANATOMY, PHYSIOLOGY AND INVESTIGATIONS
ANATOMY AND PHYSIOLOGY
The skin of an average adult covers an area of just under 2 m2. The epidermis, a stratified squamous epithelium, is the outermost layer and is predominantly composed of keratinocytes. The epidermis is attached to the underlying dermis by the basement membrane. The dermis contains and supports blood vessels, nerves and appendageal structures such as hair follicles and sweat glands. The predominant cell of the dermis is the fibroblast. It is important to remember that the appendageal structures such as hair follicles and sweat glands, whilst embedded within the dermis, are epidermal in origin. Below the dermis is the subcutis.
EPIDERMIS
Keratinocytes comprise 95% of epidermal cells (see Fig. 21.1). The proliferative compartment of epidermis resides in the basal layer and in the layer immediately adjacent to the basal layer where mitotic figures are also not uncommon. The site of the keratinocyte stem cell is not certain but is likely to be in a specialised region of the hair follicle analogous to the 'bulge' region in the mouse. In areas of skin without hair follicles (glabrous skin) stem cells may be present within the epidermis.
Keratinocytes synthesise a range of structural proteins including keratins and loricrin. There are over 20 different types of keratin, classed into two broad groups: basic (type I) and acidic (type II). Specific keratins form dimers made up of one acidic and one basic molecule that are aggregated to form larger macromolecular structures called intermediate filaments. Intermediate filaments play a key structural role in skin physiology and the expression patterns of the various gene products is highly complex. Genetic diseases that result in mutations of keratins (e.g. simple epidermolysis bullosa, some types of ichthyosis) are characterised by either epidermal fragility (i.e. blistering) or grossly disordered differentiation. As keratinocytes move out of the basal layer they differentiate, producing a variety of different protein and lipid products. Keratinocytes undergo a form of programmed cell death in the granular layer before becoming the flattened anucleate cells that make up the stratum corneum. The epidermis is a site of great lipid production, and the ability of the stratum corneum to act as a hydrophobic barrier is in large part due to the structure of highly proteinaceous dead corneocytes; these have a highly cross-linked protein membrane ('bricks') in a metabolically active layer of lipid ('mortar') also secreted by the corneocytes ('bricks and mortar' model).
Skin is required to have considerable physical resilience as well as being highly active metabolically. Whereas keratins provide structural support for individual keratinocytes, attachments between cells need to be able to transmit and dissipate stress, a function performed by desmosomes. Diseases that target desmosomes, such as pemphigus, result in blistering as the individual keratinocytes separate.
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Three other cell types make up most of the remaining 5% of epidermal cells:
Langerhans cells are dendritic, bone marrow-derived cells that circulate between the epidermis and the local lymph nodes. Their prime function is effective presentation of foreign antigens to lymphocytes, as is seen, for example, in an allergic contact dermatitis reaction. They may also play a part in presentation of tumour antigens, a fact on which researchers have tried to capitalise in the production of anti-melanoma vaccines. Other dendritic cells which are effective at presenting antigen are also present in skin but are in the dermis rather than the epidermis.
Melanocytes, of neural crest origin, are found predominantly in the basal layer; they synthesise the pigment melanin from tyrosine, package it in melanosomes and transfer it to surrounding keratinocytes via their dendritic processes.
Merkel cells are found in the basal layer. They are thought to play a role in signal transduction of fine touch. Their embryological origin is not certain.
Figure 21.1 Structure of normal skin.
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BASEMENT MEMBRANE
The basement membrane (see Fig. 21.1) acts as an anchor for the epidermis but allows movement of cells and nutrients between the dermis and epidermis. It consists of several well-defined layers that are identifiable ultrastructurally and at the molecular level. The cell membrane of the epidermal basal cell is attached to the basement membrane via hemidesmosomes. The lamina lucida is the zone immediately subjacent to the cell membrane of the basal cell which is composed predominantly of laminin. Anchoring filaments extend through the lamina lucida to attach to the lamina densa. This electron-dense layer consists predominantly of type IV collagen; from it extend loops of type VII collagen forming anchoring fibrils that fasten the basement membrane to the dermis.
DERMIS
21.2 FUNCTIONS OF THE SKIN
Function Structure/cell involved
Protection against:
Chemicals, particles Horny layer
Ultraviolet radiation Melanocytes
Antigens, haptens Langerhans cells, lymphocytes, mononuclear phagocytes, mast cells
Microbes Horny layer, Langerhans cells, mononuclear phagocytes, mast cells
Preservation of a balanced internal environment
Prevents loss of water, electrolytes and macromolecules Horny layer
Shock absorber Dermis and subcutaneous fat
Strong, yet elastic and compliant covering
Sensation Specialist nerve endings
Calorie reserve Subcutaneous fat
Vitamin D synthesis Keratinocytes
Temperature regulation Blood vessels, eccrine sweat glands
Lubrication and waterproofing Stratum corneum
Protection and prising Nails
Hormonal Hair follicles
Testosterone synthesis from inactive precursors and testosterone conversion to other androgenic steroids Sebaceous glands
Body odour (more important in animals) Apocrine sweat glands
Psychosocial Hair, nails, appearance and tactile quality of skin
The dermis is vascular and supports the epidermis structurally and nutritionally. It varies in thickness from just over 1 mm on the inner forearm to 4 mm on the back. (By contrast, the epidermis on most sites is only 0.1-0.2 mm thick, except on the palms or soles where it can be several millimetres in thickness.) The acellular part of the dermis consists predominantly of fibres, mostly collagens I and III but also elastin and reticulin, synthesised by the major cell type, fibroblasts. Support is provided by an amorphous ground substance (mostly the glycosaminoglycans, hyaluronic acid and dermatan sulphate), whose production and catabolism may be influenced by hormonal changes and damage from ultraviolet radiation. Apart from fibroblasts, there is a large number of other cell types within the dermis including mast cells, mononuclear phagocytes, T lymphocytes, dendritic cells, nerves and vessels.
EPIDERMAL APPENDAGES: HAIR AND SWEAT GLANDS
Hair, sweat and apocrine glands (found mainly in the axillae) are epidermal structures which invaginate into the dermis. They are formed during the second trimester. Coarse, medullated hair accounts for the terminal hair of the scalp and pubic areas. Short, fine unmedullated hairs make up the remaining body hair. Sebaceous glands usually arise from hair follicles, with their ducts discharging sebum into the upper part of the follicle. Sebum excretion is under hormonal control; androgens and progestogen increase sebum excretion whereas oestrogens have an inhibitory effect. Apocrine glands are those sweat glands found in the axillae, perineum, genitalia and areolae which become functional after puberty under the influence of hormonal changes, particularly androgens. Eccrine sweat glands are found all over the body and their ducts open directly on to the skin surface. They play a major role in humans in thermoregulation and, unusually, are innervated by cholinergic fibres of the sympathetic (rather than parasympathetic) nervous system.
BLOOD VESSELS AND NERVES
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There is an abundant blood supply in the skin arranged in superficial and deep plexi. The skin is well supplied with nerves to both dermis and epidermis. It used to be thought that nerves did not penetrate into the epidermis but this is now known to be false and there are indeed a large number of nerves that appear to interact with Langerhans cells, melanocytes and other components of the epidermis. Blood vessels are supplied by sympathetic autonomic nerves and peptinergic nerves that take part in the axon reflex. The functions of the skin are summarised in
ISSUES IN OLDER PEOPLE
SKIN CHANGES
Skin changes in the elderly include atrophy, laxity, wrinkling, dryness, irregular pigmentation and sparse grey hair.
There are also alterations in immune surveillance and antigen presentation, and reduced cutaneous vascular supply which lead to decreases in the inflammatory response, absorption and cutaneous clearance of topical medications.
These changes make the skin less durable, slower to heal, and more susceptible to damage and disease.
They are brought about by:
age-related alterations in structure and function of the skin
cumulative effects of environmental insults, especially ultraviolet radiation
cutaneous consequences of disease in other organ systems.
DIAGNOSIS AND INVESTIGATION OF SKIN DISORDERS
The key to successful treatment is accurate diagnosis. This requires an appropriate history, thorough examination of the skin including hair and nails (see p. 1088), and occasional use of ancillary investigations such as histopathology.
Some investigative tests can be performed in the clinic with immediate results, but as a general rule clinical skills, especially visual recognition, are perhaps of greater importance than in any other branch of general medicine.
DIASCOPY
In diascopy a glass slide is pressed firmly on the skin lesion. If a red lesion blanches, it implies that the red colour is secondary to blood within the vessels. By contrast, blood outside the vessels, such as that from a bruise or from vasculitis, will not blanch. In some vascular lesions with a convoluted vessel structure, however, blunt pressure from a flat surface will not empty the vessels and the corner of a glass slide needs to be gently placed on the lesion. Even then, it will not always blanch completely. Therefore, success in blanching is a more useful physical sign than failure to blanch. When pressed on to some granulomatous lesions a glass slide reveals an appearance commonly referred to as 'apple jelly nodule'.
EPILUMINESCENCE MICROSCOPY (DERMATOSCOPY)
This refers to surface microscopy using an illuminated magnifying lens or microscope with oil immersion directly on to the skin's surface. It has found most clinical use in the assessment of pigmented lesions. A number of patterns not visible to the naked eye are often revealed, which can support a clinical diagnosis of malignancy in experienced hands.
WOOD'S LIGHT
This involves ultraviolet radiation (wavelength 360 nm) from a light source which has a nickel oxide filter (Wood's filter) to eliminate visible light. Green fluorescence is seen in scalp ringworm due to Microsporum canis, a sporadic ectothrix infection. It evokes coral pink fluorescence of flexural skin in erythrasma, caused by the bacterium Corynebacterium minutissimum. Wood's light also enhances the examination of cutaneous pigmentary abnormalities.
MYCOLOGY SAMPLES
Cutaneous scale, nail clippings and plucked hairs can be examined by light microscopy when mounted in 20% potassium hydroxide. This allows the keratin to be dissolved and fungal hyphae can be identified. If the potassium hydroxide solution contains Indian ink, the typical 'spaghetti and meatballs' hyphae and spores of the yeast Pityrosporum orbiculare can be readily identified in pityriasis versicolor. In addition, samples are sent for identification by culture.
SWABS
Bacterial swabs
Bacterial swabs taken in an appropriate culture medium are sometimes useful. Some caveats do, however, remain. Organisms that grow on the swabs may not be causally implicated in the underlying disease and the growth of many organisms simply reflects the abnormal architecture of the skin and is not necessarily an indication for either systemic or even local antibacterial therapy. Conversely, in some obvious infections of the skin, such as cellulitis, swabs do not reveal the causative agent.
Viral swabs
Blister or pustule samples for herpes simplex and varicella zoster can be visualised within a few hours, either by electron microscopy or by indirect immunofluorescence. Samples are also cultured for identification when conserved in viral culture medium.
PRICK TESTS
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Prick tests are a way of detecting cutaneous type I (immediate) hypersensitivity to various antigens such as pollen, house dust mite or dander. The skin is pricked with commercially available stylets through a dilution of the appropriate antigen solution. After 10 minutes a positive response is indicated by a weal and a flare. The weal is due to a local increase in capillary permeability and the flare a result of activation of the axon reflex. A positive control (histamine) and a negative control (antigen diluent) should be performed. Systemic antihistamines inhibit the magnitude of the reaction. In individuals with a clear history of particular type I hypersensitivity a systemic reaction may follow a prick test and resuscitation facilities should be available. As an alternative, specific IgE levels to antigens can be measured in serum by a specific radioallergosorbent test (RAST).
PATCH TESTS
Patch tests detect type IV (delayed or cell-mediated) hypersensitivity. It is common practice for a 'battery' of around 20 common antigens, including common sensitisers such as nickel, rubber and fragrance mix, to be applied to the skin of the back under aluminium discs for 48 hours. The sites are then examined for a positive reaction 24 hours later and possibly again a further 24 hours later. An eczematous reaction, in the absence of an irritant reaction, suggests a type IV hypersensitivity to that particular allergen. The relevant antigens for a particular clinical case may not be represented in the standard battery of tests and expert advice may be needed. A negative patch test does not exclude a pathogenic role for a particular antigen nor does the presence of a particular response to an antigen mean that this antigen is causing the clinical disease.
HISTOLOGY
Skin biopsies for routine histological examination are usually fixed in 10% formalin and stained with haematoxylin and eosin. Immunocytochemistry may also be performed on formalin-fixed sections but may require frozen sections (see below). Immunocytochemistry is particularly useful for tumour diagnosis and for identification of particular T cell subsets.
IMMUNOFLUORESCENCE
A portion of the skin biopsy can be frozen in liquid nitrogen for direct immunofluorescence (IF). This involves visualising antigens that are present in skin by identifying them with fluorescein-labelled antibodies. Similarly, indirect immunofluorescence can identify circulating antibodies in the serum by an additional step of adding the serum to a section of normal skin or other substrate. Immunofluorescence plays a major role in the diagnosis of the autoimmune bullous disorders.
ELECTRON MICROSCOPY
This investigation has played an important role in the diagnosis of some of the rare blistering disorders such as epidermolysis bullosa, although the availability of a range of antibodies to basement membrane zone antigens has in part replaced it.
PHOTOTESTING
Phototesting involves exposing skin (often on the back) to a graded series of doses of ultraviolet radiation (UVR) of known wavelength, either on one occasion or repeatedly. In many photodermatoses erythema will occur at a lower dose of UVR than occurs in the normal population (e.g. drug-induced photosensitivity), or the time course of erythema may be prolonged (as in xeroderma pigmentosum). Alternatively, UVR will provoke lesions with the morphology of the underlying photodermatosis, such as may occur in lupus erythematosus or solar urticaria. Diagnostic phototesting is an essential component of the investigation of patients with presumed photosensitive drug reactions and idiopathic photodermatoses such as solar urticaria.
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > MAJOR MANIFESTATIONS OF SKIN DISEASE
MAJOR MANIFESTATIONS OF SKIN DISEASE
THE CHANGING MOLE
The largest change in dermatological practice over the last 30 years has been the major increase in patients referred or requesting advice about particular lesions ('is it cancer, doctor?') as compared with rashes. Thirty years ago perhaps 90% of dermatology outpatients had rashes and 10% lesions whereas now the proportion of lesions often exceeds 50%. This reflects the fact that human skin cancer becomes more common as people grow older, and there is an increase in the elderly in many societies, and also the fact that there is an increase in the age-specific incidence rates for most skin cancers. Furthermore, there is greatly increased public awareness and concern about skin cancer, often in response to 'health campaigns'.
The principal clinical concern is to distinguish correctly between benign lesions and melanoma. Melanoma in most of
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21.3 ABCDE FEATURES OF MALIGNANT MELANOMA
Asymmetry
Border irregular
Colour irregular
Diameter often greater than 0.5 cm
Elevation irregular (+ Loss of skin markings)
The situation is complicated by the fact that whilst any one of a number of changes in a pigmented lesion (see
History
Determine the precise nature of the change (see p. 1090). Is it due to the development of itch, inflammation, bleeding or ulceration, or changes in the colour, size, shape or surface of the lesion?
Subtle changes should not be ignored, as many patients are good observers and get to know their own moles well. If the change has settled, could it have been due to a common insult such as nicking a facial naevus when shaving, plucking hairs from a naevus or the irritant effect of a depilatory?
Is the patient worried about change in one or many moles? Paradoxically, concern about many moles should not alert the doctor so much as anxiety over a solitary lesion.
Is there a positive family history of melanoma? Fewer than 10% of melanomas occur in individuals with a strong family history but in some of these families the history of melanoma is quite striking, with up to 50% of individuals developing melanoma. A suspicious mole on a patient with a first-degree relative with a melanoma probably warrants specialist opinion.
Examination
Examine the pigmented lesion carefully. Look at the morphology of the melanocytic naevi at other sites. Examination with a magnifying glass may help. Some dermatologists are keen on dermatoscopes to help define the nature of the lesion. Usually the key clinical question is whether the lesion is a benign melanocytic naevus (see p. 1089) or a malignant melanoma (see p. 1094). Before trying to answer this, the clinician needs to exclude the possibility that it is another type of pigmented lesion:
Lentigo (a benign proliferation of melanocytes; see p. 1087).
Freckle (ephelis; see p. 1087).
Seborrhoeic wart (basal cell papilloma; see p. 1090).
Dermatofibroma. This lightly pigmented firm dermal nodule is common on extremities in young adults. It feels larger than it looks. There is dimpling when the skin is squeezed on both sides (positive Fitzpatrick sign).
Pigmented basal cell carcinoma (see p. 1092). This lesion is usually found on the face of the elderly and is slow-growing. It has a blue-brown hue with an opalescent look. There may be a rolled edge around an ulcer.
Subungual haematoma (see Fig. 21.27, p. 1088).
Melanocytic naevus versus malignant melanoma
The ABCDE 'rule' is better viewed as a guide and reminder of what to consider (see Fig. 21.2). Loss of normal skin markings is not diagnostic but is suggestive of melanoma. Conversely, normal skin markings and the presence of fine hairs dispersed evenly over a lesion, though reassuring, are not certain signs of a lesion's benign nature.
Does the patient have other pigmented lesions?
Ask and examine the patient fully. Some patients (rarely) present with more than one primary melanoma and morphology of other melanocytic naevi may provide useful diagnostic information. Remember that seborrhoeic warts are usually multiple. If a naevus, especially a changing one, appears significantly different (in colour, shape, size etc.) from others, then it should be treated with suspicion.
Management
Figure 21.2 Malignant melanoma. A changing mole which fails the ABCDE test.
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Any changing lesion which is suspected of being a malignant melanoma should be excised without delay, with a clear margin. Depending on the thickness of the tumour further excision may be required.
Some authors argue that if there is any doubt about the diagnosis the patient should be reviewed, or the individual lesion photographed and the patient reviewed in a couple of months and rephotographed. Not all would agree with this management plan, given that melanomas may show only slow or intermittent progression in their early course. A 'wait and see' policy may increase anxiety.
In this clinical context a positive diagnosis is essential. If you are uncertain whether the lesion is a melanocytic naevus or some other pigmented lesion, then it must be excised or specialist help obtained.
Malignant melanoma can break most rules. Listen, look and think. If in doubt, cut out and then check the histology, or seek advice urgently.
ITCH (PRURITUS)
Pruritus is defined as an unpleasant sensation that provokes the desire to scratch. Despite being the major symptom of skin disease apart from disturbance of body image, it remains poorly studied and poorly understood. Although central nervous system lesions can cause itch, the majority of patients seen in clinical practice itch due to a primary disease of the skin.
The nerve endings that signal itch are believed to lie either within the epidermis or very close to the dermo-epidermal junction. Such sensory information is transmitted via C fibres, which have slow conduction speeds via the spinothalamic tract to the thalamus and on to a cortical representation. It was thought for a long time that itch was conducted along the same fibres that conduct pain and that itch may have been a subliminal form of pain. This hypothesis seems increasingly untenable as candidate fibres for itch have recently been identified. There does, however, seem to be an antagonistic or inhibitory relation between pain and itch. Scratching may either cause inhibition of the itch receptors by stimulating ascending sensory pathways which inhibit itch at the spinal cord (Wall's 'gate' mechanism), or interfere with itch fibres lying superficially in skin which may be damaged directly by scratching. Which of these hypotheses is correct is unknown.
As well as primary diseases of the skin, itch may be a result of various systemic diseases such as primary biliary cirrhosis or renal failure. The mechanisms of induction of itch in these cases are unknown but for liver disease there is some experimental evidence that abnormal circulating opioids stimulate itch centrally.
History
Assessment of the itchy patient, particularly in the absence of widespread skin damage secondary to scratching, is one of the most difficult clinical problems in dermatology. Helpful hints from the history include:
The time course of the itching. This should be carefully defined as to whether it is sudden, as in infestations and urticaria, or chronic, as in chronic skin diseases such as eczema.
Localisation of the pruritus, including the site of onset. For example, in an infant with atopic eczema the cheeks are usually the first site to be affected, whereas scabies almost never affects the face or scalp. Is the itch confined to certain sites, as in localised skin disease such as lichen planus and lichen simplex, or generalised, as in eczema and scabies?
Exacerbating factors, such as heat and exercise in cholinergic urticaria, water in aquagenic pruritus and creams in some forms of eczema. In practice heat or warm water will exacerbate a number of different causes of pruritus and may be less useful diagnostic aids than often stated.
Alleviating factors, which are worth noting but are seldom of great diagnostic help. Some patients discover that cooling below 18 degrees inhibits itch (but not pain). Similarly, other patients discover that a scalding hot bath replaces itch with pain which they find preferable. In the short term most patients seem to prefer cutaneous pain to itch.
Involvement of other family members, as in a scabietic infestation. Insect bites usually only affect one member of the family.
General health of the patient. Has it changed, suggesting an underlying medical disorder?
Examination
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Attempt to determine whether there is a primary skin condition or whether the only visible clinical features are due to excoriation with some secondary degree of eczema or infection. Try to classify the patient into one of the three following groups (see
Generalised pruritus associated with skin disease. The most common causes of a widespread itchy rash are eczema, usually atopic, and scabies infestation. These can be difficult to distinguish clinically, particularly in children. Secondary eczematisation occurs in scabies, giving rise to eczema-like lesions all over the body. Examine carefully for scabietic burrows, particularly in the finger and toe webs, along the borders of both the hands and the feet and at the wrists, and extract the mite (see p. 1085) to make a definite diagnosis. After treatment pruritus may continue for several weeks. Pruritus is a common skin complaint in pregnancy and may be due to several causes (see
Local pruritus associated with skin disease. In these cases careful examination may reveal the underlying primary cutaneous disorder such as lichen planus or psoriasis.
Pruritus with no evidence of skin disease. The medical conditions that are sometimes associated with pruritus are listed in
21.4 PRURITUS
Skin diseases associated with generalised pruritus
Eczema
Scabies
Urticaria/dermographism
Pruritus of old age and xeroderma
Skin diseases associated with localised pruritus
Eczema
Lichen planus
Dermatitis herpetiformis
Pediculosis
Pruritus with no evidence of skin disease
21.5 CAUSES OF PRURITUS IN PREGNANCY
Condition Gestation and features Treatment
Obstetric cholestasis 3rd trimester
Associated with abnormal liver function tests Emollients
Chlorphenamine
(chlorpheniramine) Colestyramine
Early delivery
Pemphigoid gestationis 3rd trimester
Pruritus followed by blistering
Starts around the umbilicus Topical or oral steroids
Polymorphic eruption (urticarial papules) of pregnancy 3rd trimester, after delivery
Polymorphic lesions with urticaria Chlorphenamine (chlorpheniramine)
Prurigo gestationis 2nd trimester
Excoriated papules Emollients
Topical steroids
Chlorphenamine (chlorpheniramine)
Pruritic folliculitis 3rd trimester Aseptic pustules on trunk Topical steroids
Many patients are incorrectly labelled as having itch due to a systemic cause when in reality they have a mild degree of xerosis with perhaps irritation from repeated use of soaps, or another cutaneous primary disorder such as dermographism or aquagenic pruritus.
Management
There are no specific anti-itch drugs. Effective remedies for the conditions that lead to itch do exist, however, such as potent H1 blockade for patients with chronic idiopathic urticaria or corticosteroids for individuals with atopic eczema. Nevertheless, in some instances it is not possible either to define the primary condition or to treat it effectively.
21.6 MEDICAL CONDITIONS THAT CAUSE PRURITUS
Medical condition Cause of pruritus Treatment*
Liver disease
Cholestasis Elevated bile salts Colestyramine
Rifampicin
Antihistamines
UVB
Central opioid effect Naloxone
Hepatitis C Unknown
Chronic renal disease Multifactorial:
including secondary
hyperparathyroidism UVB
Oral activated
charcoal
Elevated plasma histamine Capsaicin
Blood disease
Anaemia Iron deficiency Iron replacement
Polycythaemia rubra vera Unknown
Lymphoma Unknown
Leukaemia
Myeloma
Thyroid disease
Thyrotoxicosis Generalised due to dry skin Emollients
Hypothyroidism Localised may be due to Candida
HIV infection Infection, infestation Treatment of opportunistic infection
Eosinophilic folliculitis Local steroids, UVB
Unknown UVB
Malignancy Unknown
Psychogenic Unknown Psychotherapy
Anxiolytics
Antidepressives
* Added to that of primary condition.
A large number of agents can be used to reduce pruritus including emollients, topical menthol, capsaicin, ultraviolet B and long-wavelength ultraviolet A (PUVA) phototherapy (see p. 1079), as well as opioid antagonists such as naltrexone. Their effects are variable, poorly characterised and require further study. Although frequently the subject of ridicule, significant itch may incapacitate, cause embarrassment, disrupt sleep and ruin the patient's self-image. It is easily under-estimated and trivialised as a symptom.
THE SCALY RASH (PAPULOSQUAMOUS ERUPTIONS)
A common presenting complaint in general practice is an eruptive scaly rash sometimes associated with itching. The main causes are listed in
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21.7 SUDDEN SCALY RASHES
Eczema (see p. 1072)
Psoriasis (see p. 1075)
Pityriasis rosea
Lichen planus (see p. 1080)
Drug eruption (see p. 1099)
Pityriasis versicolor
Tinea corporis
History
How long has the rash been present?
Atopic eczema often starts within the first 2 years of life and subsequently fluctuates in extent and severity. Psoriasis can start at any age but usually does so between the ages of 15 and 40 years. Pityriasis rosea affects a similar age group and tends to occur in the autumn and spring. Both pityriasis rosea and drug eruptions have an acute onset, drug eruptions starting within a few days or weeks of taking the drugs. Pityriasis versicolor is a common yeast infection of the body and scalp. It can be acute in onset or persist for many years in the same individual.
Where on the body did it start?
Atopic eczema starts most commonly on the face in infants and then spreads to involve the flexures. However, it can sometimes just affect the extensor surfaces or may be present in coin-like lesions (discoid eczema). Psoriasis is classically present on the extensor surfaces-that is, the elbows and knees. Psoriasis can appear anywhere on the body in small (guttate), medium and large plaques all over the torso and limbs. Lichen planus usually presents as an intensely itchy, localised papular eruption with a characteristic colour and morphology (see p. 1080). Less commonly, it can be widespread and often exhibits the Köbner phenomenon with lichen planus lesions being induced in sites of non-specific trauma (see Fig. 21.17, p. 1080). Pityriasis rosea starts as a single herald patch that can occur anywhere on the body but usually is present on the trunk. This is a solitary erythematous lesion which starts as a papule and enlarges rapidly over a few days. Pityriasis versicolor usually affects the trunk and outer upper arms. Tinea corporis (dermatophyte infection) can occur anywhere on the body and is usually asymmetrical.
How has the rash evolved?
In pityriasis rosea the herald patch is followed in a few days by the appearance of many smaller plaques present mostly on the torso in a 'fir tree' distribution but it can also occur on the neck, extremities and flexures (inverse pityriasis rosea). The herald patch tends to persist throughout the eruption and the whole eruption can last for up to 3 months. Atopic eczema can, at varying stages, be localised or generalised but is a chronic disorder that fluctuates in severity throughout childhood. Psoriasis in the classical form tends to involve the elbows, knees, lower back and scalp. In the guttate (small plaque) variety many small, red, scaly plaques appear on the trunk and may persist for several months. Many cases subsequently develop chronic plaque psoriasis. Tinea corporis is usually a chronic, slowly evolving, often isolated annular lesion. Macular-papular drug eruptions evolve with exfoliation (a shedding of the most superficial portion of the skin) and may leave post-inflammatory hyperpigmentation. Pityriasis versicolor can be very chronic and is often exacerbated by sun exposure; it also becomes more obvious in the tanned individual because of its hypopigmentation and therefore patients often present after their summer holidays. On the other hand, it appears as light brown scaly patches on untanned Caucasoid skin.
Is it itchy?
Atopic eczema is extremely itchy and this is invariably the presenting complaint. Itching is exacerbated by changes in temperature, e.g. on undressing, and contact with irritants such as wool. It is not known why atopic eczema is so itchy and antihistamines have little effect. Drug eruptions and tinea corporis are usually pruritic. Psoriasis and pityriasis rosea are not usually so itchy. The rash of pityriasis versicolor is asymptomatic.
Was there a preceding illness?
Guttate psoriasis is often preceded by a ß-haemolytic streptococcal sore throat. A small percentage of people with pityriasis rosea have a prodromal illness with malaise, headache and arthralgia. A patient who develops a morbilliform drug eruption will usually have the same reaction to that specific drug or to chemically related ones on each challenge. Rashes in response to drugs are not common; however, most patients with infectious mononucleosis treated with amoxicillin will develop an erythematous macular-papular rash. It is essential therefore to take a careful history of medications and preceding illnesses at least 4 weeks prior to the onset of the rash.
Is it associated with any systemic symptoms?
Certain drug eruptions can cause systemic upset with fever, malaise and joint pains and are associated with an eosinophilia. In eczema, superinfection can be associated with systemic symptoms of fever and malaise. Staphylococcus aureus causing secondary impetiginisation is the most common, but a streptococcus can cause similar features. Herpes simplex virus type 1 causes a widespread, severe, painful, erosive skin eruption in patients with atopic eczema (eczema herpeticum), which is a medical emergency requiring inpatient treatment with intravenous antiviral therapy and medical support. Arthritis occurs in 7% of patients with psoriasis (see p. 1011).
Examination
The distribution of the rash can be very useful in discriminating between the various causes of a scaly rash: flexural, extensor surfaces, truncal, palms and soles, or scalp involvement. Morphologically, these conditions are distinguishable by careful assessment with the use of a magnifying lens. Associated skin features that give useful diagnostic clues can be found by complete skin examination (see
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21.8 CLINICAL FEATURES OF COMMON SCALY RASHES
Type of rash Distribution Morphology Associated clinical signs
Eczema Face/flexures Poorly defined erythema and scaling
Lichenification Shiny nails
Infraorbital crease
'Dirty neck'
Psoriasis Extensor surfaces Well-defined plaques with a silvery scale Nail pitting and onycholysis
Scalp involvement
Axillae and genital areas often affected
Pityriasis rosea 'Fir tree' pattern on torso Well-defined erythematous papules and plaques with collarette of scale
Drug eruption Widespread Macular-papular erythematous scaly areas which merge and are followed by exfoliation
Pityriasis versicolor Upper torso and upper shoulders Hypo- and hyperpigmented scaly patches
Lichen planus Distal limbs, esp. volar aspect of wrists
Lower back Shiny, flat-topped violaceous papules with Wickham's striae White lacy network buccal mucosa
Rarely, nail changes
Tinea corporis Asymmetrical, often isolated, red scaly lesions Scaly plaques which expand with central healing Nail involvement (see Fig. 21.29, p. 1089)
ERYTHRODERMA
Eczema, psoriasis, drug eruptions and lichen planus rarely progress to erythroderma, defined as erythema with or without scaling of almost all the body surface. Other causes include cutaneous T cell lymphoma (Sézary's syndrome), the psoriasis-like condition pityriasis rubra pilaris, and rare types of ichthyosis. Erythroderma may occur at any age and is associated with extreme morbidity and rarely mortality. It may appear suddenly or evolve slowly.
Erythrodermic patients may be systemically unwell with shivering, due to loss of temperature control, and pyrexia. The pulse rate may be elevated and the blood pressure low due to volume depletion; examination of the cardiovascular system is therefore essential. Peripheral oedema is a common finding consequent on the erythroderma, low albumin and high-output cardiac failure. Lymph nodes may be enlarged, either reactively, caused by the skin inflammation, or rarely due to lymphomatous infiltration.
URTICARIA (NETTLE RASH, HIVES)
Urticaria refers to an area of focal dermal oedema secondary to a transient increase in capillary permeability. On certain body sites such as the lips or hands the oedema spreads and is traditionally referred to as angio-oedema. By definition the swelling lasts less than 24 hours. Acute urticaria may be associated with angio-oedema of the lips, face, throat and, rarely, wheezing, abdominal pain, headaches and even anaphylaxis. Whilst severe angio-oedema can be life-threatening due to respiratory obstruction, this is exceedingly rare in a dermatological context.
The symptoms and signs of urticaria are due in large part to mast cell degranulation with release of histamine and a variety of other vasoactive mediators. That more than histamine is involved is reflected by the fact that potent histamine blockers, whilst frequently improving the itch of urticaria and the number of weals, do not abolish all the symptoms or signs in many patients (see Fig. 21.3).
21.9 CAUSES OF URTICARIA
Acute and chronic urticaria
Allergens (in foods, inhalants and injections)
Drugs (see
Contact (e.g. animal saliva, latex)
Physical (e.g. heat, cold, pressure, sun, water)
Infection (e.g. viral hepatitis, infectious mononucleosis, HIV infection during seroconversion)
Other conditions (e.g. systemic lupus erythematosus, autoimmunity, pregnancy, intestinal parasites)
Idiopathic
Urticarial vasculitis
Hepatitis B
Systemic lupus erythematosus
Idiopathic
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Figure 21.3 Pathogenesis of urticaria. Mast cell degranulation occurs in a variety of ways. (1) Type I hypersensitivity causing massive degranulation and sometimes anaphylaxis. (2) Spontaneous mast cell degranulation in chronic urticaria. (3) Chemical mast cell degranulation. (4) Autoimmunity, which accounts for 30% of chronic urticaria.
Causes of urticaria are listed in
Clinical features
Two questions may be asked:
How long does the individual lesion last?
<24>
>24 hours (urticarial vasculitis)
How long has the condition been present?
<6>
>6 weeks (chronic urticaria)
In practice the above questions may be less helpful than is sometimes implied. There may be little mechanistic difference between urticaria of a month's duration and that of 6 months' duration. Both may be treated along similar lines. The length of time an individual weal lasts may also be of limited utility. Urticarial vasculitis is much less common than urticaria and many patients are unable to distinguish the development of new weals and disappearance of old ones from individual weals each of which persists for more than 1 day. It is sometimes helpful to draw around a weal with a pen and examine the patient 24 hours later to try to clarify this issue.
A directed history is still the best way to elicit any causes or precipitants of urticaria. A record of possible allergens, including drugs (see
Investigations
Figure 21.4 Widespread acute urticaria. In this case urticaria was due to penicillin allergy.
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These need to be directed at the possible underlying cause as elicited from the clinical history:
full blood count including eosinophil count in cases of underlying parasites
erythrocyte sedimentation rate (ESR), which is elevated in cases of vasculitis
urea and electrolytes, thyroid and liver function tests, which might reveal an underlying disorder
total IgE and specific IgE to possible allergens, e.g. foods such as shellfish and peanuts
antinuclear factor in chronic urticaria or urticarial vasculitis
CH50 as a general guide to complement activation and C3 and C4 levels as evidence of complement consumption via both the classical and the alternative pathways.
C1 esterase inhibitor may be quantitatively reduced or more rarely functionally deficient as in hereditary angio-oedema. A skin biopsy may be helpful if urticarial vasculitis is suspected. Physical urticarias can be confirmed by the appropriate physical challenge. Frequently, no cause can be found for acute episodes, whereas in chronic urticaria the autoimmune pathogenesis will account for the majority of cases.
Management
The practical problem with management of urticaria is that whilst potent non-sedative histamine blockers are available they have little or no effect on the other mediators that also play a contributory role. Non-sedative antihistamines such as loratadine or fexofenadine are effective for perhaps one-third of patients with chronic urticaria, one-third show some moderate benefit whilst the results in the remaining third are minimal. If a patient fails to respond to one of these agents after 2 weeks of therapy, then it may be worth swapping to another non-sedative antihistamine and adding in an H2-blocker such as cimetidine or ranitidine. A number of other agents have been used including mast cell stabilisers or protease and leukotriene inhibitors, although the evidence of efficacy is not clear. Systemic corticosteroids are widely prescribed for urticaria although surprisingly evidence of their benefit is still contestable. Patients with a history of life-threatening angio-oedema or anaphylaxis should carry a self-administered injection kit of adrenaline (epinephrine). The management of anaphylactic shock is described on page 201.
Urticaria may be precipitated by aspirin or non-steroidal anti-inflammatory drugs. If there is a clear history of these agents precipitating attacks, then they should be avoided. Even in the absence of a clear history it may be advisable to suggest alternatives such as paracetamol (codeine can also induce urticaria).
PHOTOSENSITIVITY
Figure 21.5 The electromagnetic spectrum. For many conditions the action spectrum is approximate and may vary between patients. (LE = lupus erythematosus)
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Ultraviolet radiation (UVR, 'sunlight') may improve some skin diseases such as psoriasis and eczema but confusingly may also exacerbate the same diseases and induce a number of specific dermatological conditions-the photosensitive dermatoses or photodermatoses. Usually this is attributable to particular parts of the electromagnetic radiation spectrum including ultraviolet B (UVB) and ultraviolet A (UVA) but rarely visible light may also cause some photodermatoses. The electromagnetic spectrum is shown in Figure 21.5. The causative wavelengths for some of the endpoints are provisional. For instance, UVB is thought to play a more major role in the induction of skin cancer but a role for UVA may also exist. Similarly, skin ageing is due not just to UVA, as is often stated, but also to UVB. Determination of the waveband or wavebands that contribute to sensitivity may be clinically important. For instance, UVB does not pass through window glass whereas UVA does. The practical corollary of this is that patients who are markedly UVA-sensitive need to wear sunblock and be protected even when inside a car or inside a building where there is strong natural light.
Clinical features
The clinical history may give a clear indication that the rash is temporally related to sun exposure, whereas in other cases there is no obvious indication of light aggravation.
Figure 21.6 Bullous photosensitive eruption. Note sharp cut-off at wrists, due to protection by shirt sleeves, and sparing of skin under watch and strap.
When a rash is related to sunshine, then the sites affected tend to be light-exposed ones: the face, particularly the nose and the cheeks but excluding the eyelids, an area under the chin and an area in the shadow of the nose; the dorsa of the forearms and hands, with sparing of the finger webs and palms (see Fig. 21.6).
There are four main groups of photosensitive dermatoses and these are listed in
Management
Once a photosensitive eruption is identified on clinical grounds, an attempt should be made to provoke the lesion using phototesting. This may not always be possible. If a drug is suspected and clinical status allows, phototesting should be carried out whilst the individual is on the drug; this allows phototesting to be repeated once the drug has been stopped. Drug causes for photosensitivity are common and include compounds such as quinine, which are often neglected unless a careful and directed clinical history is taken. Treatment is with avoidance of the drug if appropriate, or with topical or occasionally systemic steroids. In chronic cases of photosensitivity, such as chronic actinic dermatitis, azathioprine 100-150 mg/day may be required as further immunosuppression. The main preventative treatment for the photosensitive dermatoses is avoidance of sun exposure and the use of sunscreens.
Sunscreens
Sunscreens act in two different ways: chemical or physical. Chemical sunscreens absorb specific wavelengths of UV radiation. Physical sunscreens reflect UV radiation and visible light. Most available products are a combination of UVA and UVB chemical sunscreens. If the individual is sensitive to visible light as well as ultraviolet radiation, then the agents that block visible light will be visible and often cosmetically undesirable.
21.10 THE PHOTOSENSITIVE DERMATOSES
Cause Condition Clinical features
Drugs Phototoxic drug eruption Common; exaggerated sunburn occurs minutes after sun exposure
Caused by phenothiazines, amiodarone, tetracyclines
Photo-allergic drug eruption Occurs more than 24 hours after sun exposure; causes a dermatitis or lichen planus-like reaction
Caused by thiazides, enalapril, hydroxychloroquine, phenothiazines, or topical, e.g. fragrances
Can become permanent (persistent light reactor)
Metabolic Porphyrias
Pellagra Particularly porphyria cutanea tarda (see p. 326)
Diarrhoea, dementia, dermatitis due to dietary lack of tryptophan
Exacerbation of pre-existing conditions Lupus erythematosus
Erythema multiforme
Herpes simplex See page 1034
See page 1098
See page 30
Idiopathic Polymorphic light eruption Itchy papulo-vesicular eruption on exposed sites within hours of UV exposure
Solar urticaria Urticaria after 1-hour exposure
Chronic actinic dermatitis Disabling, itchy dermatitis on exposed sites in elderly men
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Sunblocks are often graded in terms of the sun protection factor (SPF), the ratio of the time it takes to induce a certain degree of redness with and without sunblock. A sunblock with an SPF of 2 therefore affords 50% reduction whereas a sun protection factor of 10 blocks 90% of the radiation. It follows that the additional value of sunblocks with a very high sun protection factor become trivial over, say, SPF 15.
BLISTERS
Loss of keratinocyte-keratinocyte adhesion or loss of adhesion of keratinocytes to the basement membrane or of the basement membrane to the dermis leads to a potential space which, because of negative extracellular pressure, fills with fluid: a blister. There is an artificial distinction made by some between small (vesicles, <0.5> 0.5 cm). The site of blister formation within the skin therefore depends on the aetiology and underlying pathogenesis.
21.11 CAUSES OF BLISTERING AT BIRTH
Herpes simplex
Impetigo
Bullous ichthyosiform erythroderma
Epidermolysis bullosa (see
Incontinentia pigmenti
Blisters are an important physical sign with a limited differential diagnosis but they can be very difficult to see. If a blister occurs high up in the epidermis (intraepidermal) and is due to a defect in cohesion of the keratinocytes, then the blister may be so fragile that only an erosion is seen (e.g. pemphigus foliaceus). On the other hand, a blister at the level of the basement membrane, as occurs in dermatitis herpetiformis, might be missed because the roof of the blister is easily destroyed due to the itch and resulting scratch. Blisters in the skin can occur at any age and may be caused by common infections or rare genetic skin diseases that can continue throughout life. The main causes of blistering presenting at birth are listed in
Assessment
The history of the onset of blistering, any predisposing events such as drug ingestion, and family history are of paramount importance. In infants blistering at birth is usually due to infection and more rarely to genetic skin diseases such as epidermolysis bullosa. There are several types of epidermolysis bullosa, as seen in
21.12 DIFFERENT TYPES OF EPIDERMOLYSIS BULLOSA
Type Mode of inheritance Level of blister Abnormal protein Clinical features
Simple Autosomal dominant Epidermal basal cell Keratins 5 and 14 Usually just blisters on palms and soles
No scarring; nails normal; no oral involvement
Rare recessive type associated with muscular dystrophy (plectin mutation)
Junctional Autosomal recessive Lamina lucida Laminin-5 and a6 ß4 integrin Large, raw areas and flaccid blisters at birth
Common around mouth and anus; heal slowly
Nails and oral mucosa involved
Often lethal
May be diagnosed prenatally by chorionic villus sampling
Dystrophic Autosomal dominant Dermis below lamina densa Collagen VII Blisters on knees, elbows and fingers
Healing with scarring and milia
Nails may be involved
Mouth seldom affected
Autosomal recessive Dermis below lamina densa Collagen VII Blisters often present at birth; seen on hands, feet, elbows and knees
Heal with scarring which is so severe that digits may be lost
Milia present
Oral and oesophageal blistering followed by scarring/stricture
Abnormal teeth
Increased incidence of cutaneous squamous cell carcinoma in early adulthood
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Toxic epidermal necrolysis is a severe form of widespread blistering that can occur at any age and is often due to drugs. It is a life-threatening condition as the skin peels off in thin sheets causing severe problems with fluid balance and temperature control as well as pain and infection. Intensive care management is indicated, with careful haemodynamic monitoring and high suspicion of secondary infection. Once the causative agent is removed the skin can rapidly re-epithelialise but toxaemia often leads to death in extensive cases. There is no convincing evidence that systemic corticosteroids work in this condition but there is some recent and persuasive but uncontrolled evidence that intravenous immunoglobulin may be helpful.
21.13 CAUSES OF ACQUIRED BLISTERS
Generalised
Localised With mucosal involvement With no mucosal involvement
Vesicular Herpes simplex Eczema herpeticum Eczema herpeticum
Herpes zoster Dermatitis herpetiformis
Impetigo Epidermolysis bullosa acquisita
Pompholyx
Bullous Impetigo Pemphigus Acute eczema
Bullous cellulitis Bullous erythema multiforme/ Erythema multiforme
Bullous stasis oedema Stevens-Johnson syndrome Bullous pemphigoid
Acute eczema Toxic epidermal necrolysis Epidermolysis bullosa acquisita
Insect bites Bullous lupus erythematosus
Fixed drug eruptions Pseudoporphyria
Porphyria cutanea tarda
Drug eruptions, e.g. barbiturates
21.14 CLINICAL FEATURES AND SKIN BIOPSY FINDINGS IN SOME IMMUNE-MEDIATED BLISTERING SKIN CONDITIONS
Disease Age Site of blisters Nature of blisters Mucous membrane involvement Antigen Circulating antibody (indirect IF) Fixed antibody (direct IF) Treatment
Pemphigus vulgaris 40-60 yrs Torso, head Flaccid and fragile, many erosions 100% Desmoglein-3 (120 kD) IgG IgG, C3 intercellular (epidermal) Steroids
Cyclo-phosphamide
Bullous pemphigoid (see Fig. 21.7) 60s and over Trunk (esp. flexures) and limbs Tense Occasionally BP-220 (part of hemidesmosome) IgG (70%) IgG, C3 at BMZ Steroids
Azathioprine
Dermatitis herpetiformis Young, associated with coeliac disease Elbows, lower back, buttocks Excoriated and often not present No Unknown None Granular IgA in papillary dermis Dapsone
Gluten-free diet
Pemphigoid gestationis Young pregnant female Periumbilical and limbs Tense Rare Collagen XVII (part of hemidesmosome BP-180) IgG C3 at BMZ Steroids
Epidermolysis bullosa acquisita All ages Widespread Tense, scarring Common (50%) Type VII collagen IgG (anti-type VII collagen) IgG at BMZ Poor response to steroids
Cyclo-phosphamide
Methotrexate
Azathioprine
Bullous lupus erythematosus Young, black female Widespread Tense Rare Type VII collagen Anti-type VII collagen IgG, IgA, IgM at BMZ Dapsone
Note Pemphigus is characterised by an intraepidermal level of blistering (superficial). All the other conditions above have a subepidermal level of blistering. (BMZ = basement membrane zone)
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Figure 21.7 Bullous pemphigoid. Large tense and unilocular blisters clustered in and around the axilla.
If there is no evidence of infection and the diagnosis is not apparent from the more common conditions listed in
Pemphigus. This is associated with underlying malignancy including lymphoma in a small proportion of patients ('paraneoplastic pemphigus'). Therefore a complete physical examination is mandatory and investigations including full blood count, erythrocyte sedimentation rate, urea and electrolytes, liver function tests, chest radiograph and any other directed scans should be performed.
Dermatitis herpetiformis. This is associated with coeliac disease (see p. 792) and therefore all patients with this diagnosis should have blood taken for an anti-endomysial and antigliadin antibody screen, and a jejunal biopsy should be performed if indicated.
Epidermolysis bullosa acquisita (EBA). This is associated with inflammatory bowel disease, multiple myeloma and lymphoma (see pp. 808, 938 and 943), and these conditions should therefore be excluded.
Bullous lupus erythematosus. It is important to follow patients with bullous lupus erythematosus for activity of their systemic disease (see p. 1034). There is a high incidence of clinically significant glomerulonephritis (> 90%).
Porphyria cutanea tarda and pseudoporphyria (see pp. 1097-1098).
LEG ULCERS
Ulceration of the skin is the complete loss of the epidermis and part of the dermis. When present on the lower leg, it is usually due to vascular disease and the vast majority (75%) of cases are due in part to venous hypertension. The site of ulceration on the lower leg can give a good indication of the underlying cause (see Fig. 21.8), although this is not an absolute guide. For each cause of leg ulceration there are several different underlying pathologies that have to be considered (see
Figure 21.8 Causes of lower leg ulceration.
21.15
Venous hypertension
See text
Arterial disease
Atherosclerosis
Vasculitis
Buerger's disease
Small vessel disease
Diabetes mellitus
Vasculitis
Abnormalities of blood
Sickle-cell disease
Cryoglobulinaemia
Spherocytosis
Immune complex disease
Neuropathy
Diabetes mellitus
Leprosy
Syphilis
Tumour
Squamous cell carcinoma
Basal cell carcinoma
Malignant melanoma
Kaposi's sarcoma
Trauma
Injury
Artefact
Assessment
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The history of the onset of the leg ulceration and any underlying predisposing conditions should be sought. Then the site and surrounding skin should be carefully assessed. The appropriate investigations should include:
Urinalysis for glycosuria.
Full blood count to detect anaemia and blood dyscrasias.
Bacterial swab to detect pathogens. Systemic antibiotics are only required if there is a purulent discharge, rapid extension, cellulitis, lymphangitis or septicaemia.
Doppler ultrasound to assess arterial circulation if the peripheral pulses cannot be felt. If the ankle systolic pressure divided by the brachial systolic pressure is > 0.8, then there is insignificant arterial disease. (An exception to this rule occurs in some patients with peripheral vascular disease associated with diabetes, in whom arterial calcification of the lower limb vessels produces a spuriously high ankle/brachial index.)
Venography, which is occasionally useful in detecting surgically remediable venous incompetence.
Duplex scanning, if available.
The main conditions and the differences between them are discussed below.
EBM
LEG ULCER-assessment and management of chronic venous leg ulcers
'Peripheral arterial supply should be assessed in all patients by hand-held Doppler. Those individuals with an ankle/brachial pressure ratio (ABP) <> 0.8, graduated compression bandaging is essential for effective treatment.'
Moffat CJ, Oldroyd MI, Greenhalgh RM, Franks PJ. Palpating ankle pulses is insufficient in detecting arterial insufficiency in patients with leg ulceration. Phlebology 1994; 9:170-172.
Fletcher A, Cullum N, Sheldon TA. A systematic review of compression treatment for venous leg ulcers. BMJ 1997; 315:570-580.
The care of patients with chronic leg ulcer. A National Clinical Guideline. Scottish Intercollegiate Guidelines Network,
Further information: www.sign.ac.uk
LEG ULCERATION DUE TO VENOUS DISEASE
Damage to the venous system of the leg results in oedema, haemosiderin deposition, eczema, fibrosis and ulceration.
Aetiology
In the normal leg there is a superficial low-pressure venous system connected to the deep, high-pressure veins by perforating veins. Muscular activity, aided by valves in the veins, pumps blood from the superficial to the deep system and towards the heart. Incompetent valves in the deep and perforating veins result in the retrograde flow of blood to the superficial system ('venous hypertension'), causing a rise in capillary hydrostatic pressure. Fibrinogen is forced out through the capillary walls and fibrin is deposited as a pericapillary cuff. One theory postulates that growth and repair factors are trapped in the macromolecular cuff so that minor trauma cannot be repaired and ulcers develop.
Incompetent veins leading to venous hypertension may be due to previous deep vein thrombosis (see pp. 908 and 953), congenital or familial valve incompetence, infection or deep venous obstruction (e.g. from a pelvic tumour).
Clinical features
The problem usually starts in middle age. Leg ulcers are more likely to occur and to persist in obese people. Varicose veins, although often present, are not inevitable. The first symptom is frequently heaviness of the legs, followed by the development of oedema. Haemosiderin pigmentation and ivory-coloured scarring may then be seen, sometimes associated with venous eczema (see p. 1074). The signs progress to lipodermatosclerosis, firm induration due to fibrosis of the dermis and subcutis, which may produce the well-known 'inverted champagne bottle' appearance. Ulceration, often precipitated by minor trauma or infection, soon occurs. Ulcers are seen typically around the medial malleolus but may encircle the ankle (see Fig. 21.9). If conditions are favourable, the ulcers will heal by granulation with small epithelial islands at the base and epithelial growth from the edges. Healing is often slow and may never be complete. Recurrent ulceration is common even after good healing.
Complications
Figure 21.9 A large venous ulcer overlying the medial malleolus.
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Chronic venous ulcers are invariably colonised by bacteria. Only if infection becomes overt (see above) is systemic antibiotic treatment required. Contact dermatitis to an ointment, dressing or bandage is not uncommon. The usual culprits are preservatives, lanolin and neomycin. Lipodermatosclerosis may cause lymphoedema, leading to hyperkeratosis and the so-called 'mossy foot'. A squamous cell carcinoma developing in a venous ulcer (Marjolin's ulcer) is rarely responsible for its failure to heal.
Management
General management includes dietary advice for the obese and encouragement to take gentle exercise.
Oedema should be reduced by the regular use of compression bandages, keeping the legs elevated when sitting and the judicious use of diuretics.
The exudate and slough should be removed with normal saline solution, 0.5% aqueous silver nitrate or 5% aqueous hydrogen peroxide. If the ulcer is very purulent, soaking the leg for 15 minutes in
Dressings commonly used for venous ulceration include antibiotic-impregnated tulle dressings, non-adhesive absorbent dressings (alginates, charcoals, hydrogels or hydrocolloids) and dry non-adherent dressings.
The frequency of dressings depends on the state of the ulcer. Very purulent and exudative ulcers may need daily dressings whilst the dressing on a clean, healing ulcer may only require changing every week.
Paste bandages, impregnated with zinc oxide or ichthammol, help to keep dressings in place and provide protection.
Surrounding venous eczema is treated by a mild or moderately potent topical corticosteroid. The steroid should not be applied to the ulcer itself.
Oral antibiotic therapy, given in short courses, is only necessary for the treatment of overt infection (see above). An anabolic steroid, stanozolol, may help lipodermatosclerosis but side-effects (fluid retention, hepatotoxicity) may limit its use.
In the absence of any evidence of compromised arterial supply, graduated compression bandages applied from the toes to the knees enhance venous return and have been shown to be most beneficial in the healing of venous leg ulcers.
Vein surgery may help some younger patients with persistent venous ulcers. Pinch grafts may hasten the healing of clean ulcers but do not influence their rate of recurrence.
LEG ULCERATION DUE TO ARTERIAL DISEASE
Deep, painful and punched-out ulcers on the lower leg, especially if they occur on the shin and foot and are preceded by a history of intermittent claudication, are likely to be due to arterial disease. Risk factors include smoking, hypertension, diabetes mellitus and hyperlipidaemia. The foot is cyanotic and cold, and the skin surrounding the ulcer is atrophic and hairless. The peripheral arterial pulses are absent or reduced. Doppler studies are required and then, if arterial insufficiency is confirmed, compression bandaging should be prohibited and advice from a vascular surgeon sought.
LEG ULCERATION DUE TO VASCULITIS
These ulcers start as painful, palpable, purpuric lesions turning into small punched-out ulcers. The involvement of larger vessels is heralded by painful nodules which may ulcerate. The intractable, deep, sharply demarcated ulcers of rheumatoid arthritis are due to an underlying vasculitis (see p. 1040). Management includes treatment of the underlying disorder as well as immunosuppression with, for example, steroids or cyclophosphamide.
LEG ULCERATION DUE TO NEUROPATHY
The most common cause of a neuropathic ulcer is diabetes. The ulcers occur over weight-bearing areas such as the heel. Microangiopathy also contributes to ulceration in diabetes. This is discussed in detail on page 677.
TOO LITTLE OR TOO MUCH HAIR
A patient who complains of too little or too much hair should be treated with sensitivity. These complaints may cause genuine morbidity. The causes are numerous and varied but a systematic approach to the history and examination can easily be used to elicit the correct diagnosis.
Hair undergoes a regular cycle of growth. Each cycle is independent of its neighbours in humans, whereas moulting animals, for instance, have hairs in a synchronous cycle. At any one time and depending on the age and sex of the person, up to 90% of hair follicles can be in anagen, the growing phase, and only 10% in telogen, the resting phase when hairs are normally shed. An alteration in this ratio can lead to an increased rate of hair loss and thus an impression of impending baldness.
ALOPECIA
The term means nothing more than loss of hair. There are many causes and patterns (see
A detailed history, careful scalp examination and complete physical examination should enable a confident diagnosis to be made.
Tinea capitis
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21.16 CLASSIFICATION OF ALOPECIA
Localised Diffuse
Non-scarring
Tinea capitis Androgenetic alopecia
Alopecia areata Telogen effluvium
Androgenetic alopecia Metabolic
Traumatic (trichotillomania, traction, cosmetic) Hypothyroidism
Hyperthyroidism
Syphilis Hypopituitarism
Diabetes mellitus
HIV disease
Nutritional deficiency
Liver disease
Post-partum
Alopecia areata
Syphilis
Scarring
Idiopathic Discoid lupus erythematosus
Developmental defects
Discoid lupus erythematosus Radiotherapy
Herpes zoster Folliculitis decalvans
Pseudopelade Lichen planus pilaris
Tinea capitis/kerion
Fungal scalp infections are becoming increasingly common in urban areas in the
Ectothrix (outside the hair shaft) species of fungi, such as Microsporum audouinii (anthropophilic), show minimal inflammation; Microsporum canis (from dogs and cats) infections are more inflamed and can be identified by green fluorescence with Wood's light. Kerions are boggy, highly inflamed areas of tinea capitis and are usually caused by zoophilic (from animals, e.g. cattle ringworm) species of fungi (e.g. Trichophyton verrucosum).
Treatment is systemic, with either oral terbinafine, griseofulvin or itraconazole. Topical therapy, such as an antifungal shampoo, is recommended as an adjunct and arachis oil is used to remove crusting. Kerions sometimes require short courses of oral steroids in addition to systemic antifungal therapy to reduce the inflammation.
Accurate diagnosis and identification of the culprit fungus allows not only treatment but also control of the spread of infection.
Alopecia areata
Figure 21.10 Alopecia areata. Marked hair loss with diagnostic exclamation mark hairs.
This non-scarring condition appears as sharply defined non-inflamed bald patches, usually on the scalp (see p. 1050). During the active stage of hair loss pathognomonic 'exclamation mark' hairs are seen (broken-off hairs 3-4 mm long, which taper off towards the scalp-see Fig. 21.10). An uncommon diffuse pattern on the scalp is recognised. The condition may affect the eyebrows, eyelashes and beard. Pitting and longitudinal wrinkling of the nail may be seen. The hair usually regrows spontaneously in small bald patches, but the outlook is less good with larger patches and when the alopecia appears early in life or is associated with atopy. Alopecia totalis describes complete loss of scalp hair and alopecia universalis complete loss of all hair. There is an association of alopecia areata with autoimmune disorders, atopy and Down's syndrome.
Androgenetic alopecia
Male-pattern baldness is physiological in men over 20 years old, though rarely it may be extensive and develop at an alarming pace in the late teens. It also occurs in females, most obviously after the menopause. The well-known distribution (bitemporal recession and then crown involvement) is described as 'male-pattern' but this type of hair loss in females is often diffuse.
Investigations
Laboratory tests, including a full blood count, erythrocyte sedimentation rate, urea and electrolytes, liver and thyroid function tests, an autoantibody profile and Treponema pallidum haemagglutination (TPHA) test, should help determine the cause of non-scarring alopecia. More specialised tests, including the hair pluck test where up to 50 hairs are removed with epilating forceps to determine the anagen:telogen ratio, are seldom necessary. Mycological assessment is advisable in cases of localised hair loss with scaling. A scalp biopsy, with direct immunofluorescence, may help to confirm a diagnosis of lichen planus of the scalp or discoid lupus erythematosus.
Management
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Successful treatment of alopecia is difficult and management of these patients includes support and reassurance. Any underlying condition should be treated. Alopecia areata sometimes responds to topical or intralesional steroids such as 0.3 ml triamcinolone (10 mg/ml). Some patients with androgenetic alopecia may be helped by systemic finasteride or topical 2% minoxidil solution. In females, anti-androgen therapy such as cyproterone acetate is used. A wig may be the most appropriate treatment for extensive alopecia. Scalp surgery and autologous hair transplants are expensive but sometimes effective in androgenetic alopecia.
HIRSUTISM
Hirsutism is the growth of terminal hair in a male pattern in a female. It should be distinguished from hypertrichosis, which describes the excessive growth of terminal hair in either sex in a non-androgenic distribution.
Hirsutism is often racial (e.g. Mediterranean Caucasians and Asians) and familial. Some degree of hirsutism is common after the menopause. The cause of most cases of hirsutism is unknown and only a small minority have a demonstrable hormonal abnormality.
Investigations
Full endocrinological investigations are required if hirsutism:
occurs in childhood
is of sudden onset
is accompanied by signs of virilisation
is associated with menstrual irregularity or cessation.
In addition to the screening tests for hyperandrogenism (see p. 709), Cushing's syndrome needs to be excluded (see p. 721).
Management
Depilatory creams, waxing, electrolysis, bleaching and shaving are often used for physiological hirsutism.
Any remediable cause should be corrected by medical and surgical methods, sometimes with the help of the endocrinologist or gynaecologist (see p. 710). Oral anti-androgens may be helpful.
VULVAL ITCH (PRURITUS VULVAE)
Pruritus vulvae is a distressing symptom that can occur at any age and can be difficult to diagnose. Chronic scratching of the vulval area leads to lichenification which, in this site, can be asymmetrical and associated with quite marked oedema and swelling. The history is important to give an indication of the underlying cause. Pre-existing skin disease, such as atopic eczema, psoriasis or fungal infections, needs to be sought and an autoimmune history might be associated with lichen sclerosus et atrophicus. It is important to determine if there is a previous history of sexually transmitted diseases, particularly genital warts or cervical dysplasia found on colposcopy. The main dermatological causes of itch in the vulval area are candidiasis (consider underlying diabetes), tinea cruris (dermatophyte infection), eczema (including contact dermatitis), psoriasis, lichen sclerosus and, less commonly, lichen planus. These can usually be differentiated by careful examination, bacteriological and mycological assessment and a search for evidence of similar skin disease elsewhere on the body. A well-defined, bright red plaque on the vulva can indicate psoriasis, particularly with skin, scalp or nail signs of this condition; oral lesions are often seen in lichen planus and this condition is often followed by marked post-inflammatory hyperpigmentation; lichen sclerosus is characterised by ivory papules that coalesce into pale plaques, with an atrophic surface (reminiscent of crinkly cigarette paper). There is sometimes associated haemorrhagic blistering. Lichen sclerosus often forms a 'figure of eight' around the vulva and perineal area and can cause scarring of the vulva with loss of normal contours culminating in stenosis of the introitus secondary to labial fusion. Biopsy for histology is occasionally needed to differentiate these conditions and in lichen sclerosus to assess any malignant change in, for example, non-healing areas.
Histology is always needed in the next group of itchy vulval lesions, neoplasia. Most tumours of the vulva can provoke the symptom of itch-in particular, vulval (squamous) intraepithelial neoplasia (VIN) and extramammary Paget's disease. Lesions of VIN can be solitary or multiple and may appear red, white, pigmented, warty, moist or eroded. As well as being itchy, VIN can be painful, particularly with superficial dyspareunia. There may be very little to see with the naked eye and then vulvoscopy is needed. In younger women there is a strong association of VIN with the papillomavirus, immunosuppression and possibly smoking. Extramammary Paget's disease is rare, is usually asymmetrical and can be painful. It presents as a moist, red, scaly patch often mistaken for eczema; hence the importance of biopsy in 'unresponsive eczema'.
Finally, it has been shown that a proportion of vulval itch is psychogenic; certainly vulval disease can be associated with psychological distress so careful consultation and an understanding doctor are essential to a correct diagnosis of this condition.
ISSUES IN OLDER PEOPLE
COMMON SKIN DISEASES
About 40% of individuals over the age of 60 years have significant dermatological problems.
The most common diseases in this age group are:
skin cancers
leg ulcers, a major cause of morbidity in the elderly
blistering disorders
herpes zoster (shingles) and post-herpetic neuralgia
inflammatory skin diseases, e.g. asteatotic, varicose and seborrhoeic eczema, psoriasis
lichen sclerosus
scabies
lymphoedema
pruritus of old age
drug-related rashes.
pages 1056 - 1071
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > ECZEMA
ECZEMA
The terms 'eczema' and 'dermatitis' are synonymous. They refer to distinctive reaction patterns in the skin, which can be either acute or chronic and are due to a number of causes.
Integration link: Pathology of eczematous dermatitis
Taken from Robbins & Cotran's Pathologic Basis of Disease 7e
Histopathology
In the acute stage oedema of the epidermis (spongiosis) progresses to the formation of intraepidermal vesicles, which may enlarge and rupture. In the chronic stage there is less oedema and vesiculation but more thickening of the epidermis (acanthosis); this is accompanied by a variable degree of vasodilatation and T-helper lymphocytic infiltration in the upper dermis.
Clinical features
There are several patterns of eczema (see
Atopic eczema
Atopy is a genetic predisposition to form excessive IgE which leads to a generalised and prolonged hypersensitivity to common environmental antigens, including pollen and the house dust mite. Atopic individuals manifest one or more of a group of diseases that includes asthma, hay fever, urticaria, and food and other allergies, and this distinctive form of eczema. These atopic conditions tend to run true to type within each family. Atopic eczema has clear diagnostic criteria, which are listed in
21.17 CLASSIFICATION OF ECZEMA
Atopic
Seborrhoeic
Discoid
Irritant
Allergic
Asteatotic
Gravitational
Lichen simplex
Pompholyx
21.18 THE ECZEMA REACTION
Acute
Redness and swelling, usually with ill-defined margins
Papules, vesicles and, more rarely, large blisters
Exudation and cracking
Scaling
Chronic
May show all of the above features, though it is usually less vesicular and exudative
Lichenification, a dry leathery thickening with increased skin markings, is secondary to rubbing and scratching
Fissures and scratch marks
Pigmentation changes (hypo- and hyper-)
21.19 DIAGNOSTIC CRITERIA FOR ATOPIC ECZEMA
Itchy skin and at least three of the following:
History of itch in skin creases (or cheeks if <>
History of asthma/hay fever (or in a first-degree relative if <>
Dry skin (xeroderma)
Visible flexural eczema (cheeks, forehead, outer limbs if <>
Onset in first 2 years of life
Aetiology. The inheritance of atopic eczema is controversial. The disorder is concordant in 86% of monozygotic twins but in only 21% of dizygotes. Atopic diseases show maternal imprinting-that is, they are inherited more often from the mother than from the father. A polygenic mode of inheritance is likely. More than one genetic locus has been identified that might play a role in the inheritance of atopy and more specifically atopic eczema.
The prevalence of atopic eczema is rising and has increased between twofold and fivefold over the last 30 years. It now affects 1 in 10 schoolchildren. Environmental factors, such as exposure to allergens either in utero or during childhood, have been shown to have a role in the aetiology of atopic eczema.
Pathogenesis. The pathogenesis of atopic eczema is complex and still incompletely understood. It is best considered as an interplay of genetic susceptibility that causes epidermal barrier dysfunction and abnormal immune responses, which are then stimulated by different environmental factors.
EBM
ATOPIC ECZEMA-are there intervention strategies that reduce the incidence of atopic eczema?
'Specific nutritional restrictions in maternal diet during pregnancy have no effect on the incidence of atopic eczema in an infant at hereditary risk and may adversely affect maternal and/or fetal nutrition. Breastfeeding, however, appears to reduce the prevalence of atopic eczema in early childhood.'
Kramer MS. Maternal antigen avoidance during pregnancy for preventing atopic disease in infants of women at high risk (Cochrane Review). Cochrane Library, issue 1, 2001.
Saarinen UM, Kajosaari M. Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old. Lancet 1995; 346:1065-1069.
Chandra RK. Five year follow-up of high risk infants with family history of allergy who were exclusively breast-fed or fed partial whey hydrosylate, soy, and conventional cow's milk formulas. J Pediatr Gastroenterol Nutr 1997; 24:380-388.
Further information: www.cochranelibrary.com
21.20 ATOPIC ECZEMA: DISTRIBUTION AND CHARACTER OF RASH
Infancy
The eczema is often acute and involves the face and trunk
The napkin area is frequently spared
Childhood
The rash settles on the backs of the knees, fronts of the elbows, wrists and ankles (see Fig. 21.11)
Adults
The face and trunk are once more involved; lichenification is common
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Figure 21.11 Atopic subacute eczema on the fronts of the ankles of a teenager. These are sites of predilection, along with the cubital and popliteal fossae, in atopic eczema.
Clinical features. The cardinal feature of atopic eczema is itch, and scratching may account for many of the signs. Widespread dryness of the skin is another feature. The distribution and character of the rash vary with age, as shown in
21.21 COMPLICATIONS OF ATOPIC ECZEMA
Superinfection most often with bacteria (Staphylococcus aureus) but also importantly with viruses. Herpes simplex virus causes a widespread severe eruption-eczema herpeticum. Papillomavirus and molluscum contagiosum superinfections are also more common and are encouraged by use of local steroids
Irritant reactions due to defective barrier function
Sleep disturbance, loss of schooling and behavioural difficulties
Children with atopic eczema have an increased incidence of food allergy, particularly to eggs, cow's milk, protein, fish, wheat and soya. These foods cause an immediate urticarial eruption rather than exacerbating their eczema
Seborrhoeic eczema
This condition which is characterised by a red scaly rash classically affects the scalp (dandruff), central face, nasolabial folds, eyebrows and central chest. It is due to Pityrosporum ovale infection of the skin. In its milder forms it is the same as dandruff, whereas when severe it may resemble psoriasis. Sebum may be permissive for the development of the rash but otherwise the name is a poor one. Treatment of P. ovale with anti-yeast agents improves the rash although the course may need to be repeated. Seborrhoeic eczema is a feature of AIDS and can be very severe in this condition.
Discoid eczema
This is a common form of eczema recognised by discrete coin-shaped lesions of eczema seen on the limbs of young men, associated with alcohol excess, and of elderly men. It can occur in children with atopic eczema and tends to be more stubborn to treat.
Irritant eczema
Detergents, alkalis, acids, solvents and abrasive dusts are common causes. There is a wide range of susceptibility to weak irritants. Irritant eczema accounts for the majority of industrial cases and work loss. The elderly, those with fair and dry skin, and those with an atopic background (personal or family history of asthma, hay fever or eczema) are especially vulnerable. Napkin eczema in babies is common and due to irritant ammoniacal urine and faeces.
Strong irritants elicit an acute reaction at the site of contact whereas weak irritants most often cause chronic eczema, especially of the hands, after prolonged exposure.
Allergic contact eczema
This is due to a delayed hypersensitivity reaction following contact with antigens or haptens. Previous exposure to the allergen is required for sensitisation and the reaction is specific to the allergen or closely related chemicals. Common allergens and their origin are listed in
The eczema reaction occurs wherever the allergen is in contact with the skin and sensitisation persists indefinitely. It is important to determine the original site of the rash before secondary spread obscures the picture, as this often provides the best clue to the contactant. There are many easily recognisable patterns, e.g. eczema of the earlobes, wrists and back due to contact with nickel in costume jewellery, watches and bra clips; or eczema of the hands and wrists due to rubber gloves. Oedema of the lax skin of the eyelids and genitalia is a frequent concomitant of allergic contact eczema (see Fig. 21.12).
21.22 SOME COMMON ALLERGENS
Allergen Present in
Nickel Jewellery, jean studs, bra clips
Dichromate Cement, leather, matches
Rubber chemicals Clothing, shoes, tyres
Colophony Sticking plaster, collodion
Paraphenylenediamine Hair dye, clothing
Balsam of Peru Perfumes, citrus fruits
Neomycin, benzocaine Topical applications
Parabens Preservative in cosmetics and creams
Wool alcohols Lanolin, cosmetics, creams
Epoxy resin Resin adhesives
Asteatotic eczema
This is frequently seen in the hospitalised elderly, especially when the skin is dry; low humidity caused by central heating, over-washing and diuretics are contributory factors. It occurs most often on the lower legs as a rippled or 'crazy paving' pattern of fine fissuring on an erythematous background.
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Figure 21.12 Allergic contact eczema. This was caused by the application of an antihistamine cream. The acute eczematous reaction and bilateral periorbital oedema are typical.
Gravitational (stasis) eczema
This occurs on the lower legs and is often associated with signs of venous insufficiency (oedema, red or bluish discoloration, loss of hair, induration, haemosiderin pigmentation and ulceration).
Lichen simplex
This describes a plaque of lichenified eczema due to repeated rubbing or scratching, as a habit or in response to stress. Common sites include the nape of the neck, the lower legs and the anogenital area.
Pompholyx (dyshidrotic eczema)
Recurrent vesicles and bullae occur on the palms, palmar surface of the fingers and soles, and are excruciatingly itchy. This form of eczema can occur in atopic eczema and in irritant and contact allergic dermatitis. It can be provoked by heat, stress and nickel ingestion in a nickel-sensitive patient but is often idiopathic.
Investigation of eczema
(For details of tests see pp. 1055-1056.)
Patch tests
These are performed in suspected cases of contact allergic dermatitis (see p. 1073).
IgE and specific IgE
These are occasionally performed to support the diagnosis of atopic eczema and to determine specific environmental allergens, e.g. pet dander, horse hair, house dust mite, pollens and foods.
Prick tests
The indications are the same as for specific IgE but are less commonly performed.
Bacterial and viral swabs for microscopy and culture
These are useful tests in suspected secondary infection. Skin swabs for bacteriological assessment will invariably reveal the presence of bacteria, and antibacterial treatment should be reserved for those cases with evidence of clinical infection. In the case of recurrent impetigo in a child with atopic eczema, bacterial swabs should be taken from carrier sites (nares, axillae and groin) from both the affected individual and all household members.
General management of eczema
The main points are listed in
21.23 GENERAL MANAGEMENT FOR ALL TYPES OF ECZEMA
Explanation, reassurance and encouragement
Avoidance of contact with irritants
Regular use of greasy emollients
Appropriate use of topical steroids
Topical steroids
Lotions (aqueous base) and creams (oil/water mixture) are preferable in acute eczema and ointments (in an oily base) in chronic cases; they are usually applied twice daily. Only 1% hydrocortisone should be used on the face and in infancy. Even in adults it is seldom necessary to prescribe more than 200 g of a low-potency steroid (e.g. 1% hydrocortisone), 50 g of a moderately potent steroid (e.g. 0.05% clobetasone butyrate) or 30 g of a potent steroid (e.g. 0.1% betamethasone valerate, 0.1% mometasone furoate) per week. Very potent topical steroids (e.g. 0.05% clobetasol propionate) should not be used long-term. The side-effects of strong or extensive local steroid therapy should be borne in mind when patients are applying these preparations for years on end. They include skin thinning (with striae, fragility and purpura), enhanced or disguised infections, and systemic absorption (causing suppression of the hypothalamic- pituitary-adrenal axis and even Cushingoid features). There are no absolute guidelines for the amount of topical steroid that should be used but care should be taken on certain sites such as the face and flexures. The best rule is to use the least potent steroid for the shortest possible time that is effective. Often one finds that topical steroids are being under-used and are therefore ineffective.
Other topical immunosuppressants, including tacrolimus and pimicrolimus, have just become available for use. Early reports of their efficacy are encouraging.
Bland emollients (e.g. emulsifying ointment) are used regularly, both directly on the skin and in the bath. They not only prevent excessive water loss from an already dry skin, but also help to reduce the amount of local steroid used. Emollient soap substitutes (e.g. aqueous cream) are also helpful. Sedative antihistamines (e.g. alimemazine tartrate (trimeprazine tartrate)) are of value if sleep is interrupted.
Specific measures
Atopic eczema
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Explanation and patient support are increasingly provided for these patients through general practice, dermatology clinics, community liaison nurses and patient support groups such as the National Eczema Society in the
EBM
ATOPIC ECZEMA-are topical steroid/antimicrobial combinations better than topical steroids alone?
'RCTs show no evidence that combinations of topical antimicrobial agents and steroids are better than topical steroids alone in improving the clinical signs and symptoms of atopic eczema.'
Ramsay CA, Savoie JM, Gilbert M, et al. The treatment of atopic dermatitis with topical fusidic acid and hydrocortisone acetate. J Eur Acad Dermatol Venereol 1996;
Wachs GN, Maibach HI. Co-operative double-blind trial of an antibiotic/corticoid combination in impetiginised atopic dermatitis. Br J Dermatol 1976; 95:323.
Seborrhoeic eczema
Antipityrosporal agents such as ketoconazole shampoo form the basis of treatment, supplemented with weak corticosteroids if needed. Treatments may need to be repeated at intervals.
Irritant eczema
This is best treated by the regular use of emollients, avoidance of irritants and protective clothing, e.g. gloves.
Contact allergic eczema
Avoidance of the culprit allergen is the most important treatment for this form of eczema and may involve lifestyle changes such as a new job or giving up hobbies. Measures used for irritant eczema are also helpful.
Gravitational eczema
Local steroids (see above) should only be applied to eczematous areas and ulcers should be avoided. Sensitisation to topical antibiotics (neomycin) and preservatives (e.g. chlorocresol) is common in this form of eczema. Associated peripheral oedema should be eliminated by elevation of the leg and graded compression bandages.
ISSUES IN OLDER PEOPLE
ECZEMA
With advancing age, the skin becomes less pliable and drier. This increases the tendency for irritant dermatitis.
Topical steroid usage causes more local side-effects, such as purpura or ecchymoses, in the elderly individual.
Widespread eczema is potentially life-threatening in the elderly, particularly when combined with other illnesses.
pages 1072 - 1075
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > PSORIASIS AND OTHER ERYTHEMATOUS SCALY ERUPTIONS
PSORIASIS AND OTHER ERYTHEMATOUS SCALY ERUPTIONS
Psoriasis and lichen planus will be described here in detail; other scaly conditions were covered on pages 1059-1060.
PSORIASIS
Psoriasis is a non-infectious, chronic inflammatory disease of the skin, characterised by well-defined erythematous plaques with silvery scale which have a predilection for the extensor surfaces and scalp, and by a chronic fluctuating course.
The prevalence is approximately 2% in European populations. Accurate figures for many other parts of the world are not available but there seems to be consistent evidence that the prevalence of psoriasis is lower in people of African origin and lower still in some Asian communities such as the Japanese. Psoriasis may come on at any age but is unusual before the age of 5; the oldest recorded onset was in a patient aged 107. There appear to be two epidemiological patterns of psoriasis. The first shows an onset in the teenage and early adult years; such individuals frequently have a family history of psoriasis and there is an increased prevalence of HLA Cw6. In a second epidemiological grouping disease onset is in an individual's fifties or sixties, a family history is less common and the HLA group Cw6 is not so prominent. Some authors refer to these two groupings as type 1 and type 2 psoriatics.
The clinical course of psoriasis is very variable. As a general rule the earlier the age of onset and the more severe the initial presentation, the more severe the lifetime course of the disease.
Aetiology
Basic defect
There are two key pathophysiological aspects to the abnormalities in psoriatic plaques. Firstly, the keratinocytes hyperproliferate with a grossly increased mitotic index and an abnormal pattern of differentiation involving the retention of nuclei in the stratum corneum (in normal skin the dead stratum corneum cells do not have nuclei). Secondly, there is a large inflammatory cell infiltrate comprising polymorphs, T cells and other inflammatory cells. It is uncertain which of these characteristics is primary. Traditionally, psoriasis was viewed as a primary disorder of cell turnover but in recent years there has been increased support for the hypothesis that the hyperproliferation may be secondary to the inflammatory infiltrate and that the increase in keratinocyte proliferation is a consequence of inflammatory cell mediators or signalling.
There is a large familial component to psoriasis. Formal estimates from twin studies suggest a hereditability of around 80%. In monozygotic twins perhaps one-third of pairs will be concordant for psoriasis. Put another way, two-thirds of monozygotic twins will not be concordant despite an apparently identical or near-identical genetic background.
The mode of inheritance of psoriasis does not fit a clear Mendelian pattern and is therefore described as genetically complex. Empirical estimates suggest that if one parent has psoriasis, then the chance of a child being affected is in the order of 15-20%. If both parents have psoriasis the probability of a child being affected is 0.5. Both these estimates are increased if one sibling already has the disease. Genome scanning linkage and association studies have indicated various chromosomal areas of susceptibility including the HLA region.
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Disordered cell proliferation in psoriasis is reflected by the increase in the number of mitoses visible in the psoriatic plaque. The transit time-that is, the time it takes for keratinocytes in the basal layer to leave the epidermis-is shortened in psoriasis from perhaps 28 to 5 days. Whilst it used to be thought that the cell cycle was actually reduced in psoriasis more recent data suggest that it is just that the proportion of cycling cells (rather than cells that are in G0) is increased. There are some data suggesting that the non-plaque skin also shows an elevated rate of proliferation, although any increase above background rate is modest. These data have not been confirmed in all studies. The nails of patients with psoriasis, even when clinically unaffected, do, however, grow more quickly than those of controls.
The importance of keratinocyte hyperproliferation initially received support from the demonstration that cytostatic drugs such as methotrexate were clinically useful. However, more recent data suggest that methotrexate may exert its effects primarily through an influence on the immune system.
The evidence implicating a key role for an immune pathogenesis relates to:
the association with certain HLA groups (HLA Cw6)
the success of certain immunosuppressive drugs (such as ciclosporin) in improving the clinical state of the disease
reports of the development of psoriasis in recipients of bone marrow transplants from donors with a history of psoriasis.
The precise molecular mechanisms operating in psoriasis are, however, poorly understood. A large number of theories have been advanced over the last 30 or 40 years claiming that one particular mediator may be a key or rate-limiting factor in psoriasis. The majority of these explanations have not stood the test of time; nor have they provided useful therapeutic insight.
Precipitating factors
Psoriasis is a chronic disease characterised by variation in both temporal and spatial extent. Most of this variation cannot be explained. At any one time perhaps 10% of people who have received the diagnosis of psoriasis have no lesions and perhaps 15% may report remissions of up to 5 years or more. Some factors, however, are thought to precipitate an exacerbation of the disease and these are listed in
Figure 21.13 The histology of psoriasis.
21.24 FACTORS CAUSING FLARE-UPS OF PSORIASIS
Trauma
When the condition is erupting lesions appear in areas of skin damage such as scratches or surgical wounds (Köbner phenomenon)
Infection
ß-haemolytic streptococcal throat infections often precede guttate psoriasis
Sunlight
Rarely, ultraviolet radiation may worsen psoriasis
Drugs
Antimalarials, ß-blockers and lithium may worsen psoriasis and the rash may 'rebound' after stopping systemic corticosteroids or potent local corticosteroids
Emotion
Anxiety precipitates some exacerbations
Pathology
The histology of psoriasis is depicted in Figure 21.13.
Clinical features
Stable plaque psoriasis
This is the most common type. Individual lesions are well demarcated and range from a few millimetres to several centimetres in diameter (see Fig. 21.14). The lesions are red with dry, silvery-white scaling, which may be obvious only after scraping the surface. The elbows, knees and lower back are commonly involved.
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Other sites of predilection include:
Scalp. Scalp is involved in approximately 60% of patients with psoriasis. The reason why the scalp is so commonly involved is not clear. One possibility relates it to Köbnerisation from P. ovale infection of the skin. (P. ovale is the cause or precipitant of dandruff or seborrhoeic dermatitis.) Psoriasis of the scalp typically shows well-demarcated, easily palpable areas, but on occasion a diffuse, fine scaling difficult to distinguish from classical seborrhoeic dermatitis may be present. Temporary hair loss is not uncommon and rarely permanent focal hair loss may occur.
Nails. Involvement of the nails is common, with 'thimble pitting', onycholysis (separation of the nail from the nail bed-see Fig. 21.15) and subungual hyperkeratosis.
Flexures. Psoriasis involving the natal cleft, and submammary and axillary folds is not scaly but red, shiny and symmetrical (see Fig. 21.16).
Palms. Psoriasis here is often difficult to recognise, as individual plaques may be poorly demarcated and barely erythematous. It is often impossible to differentiate between psoriasis and eczema of the palms.
Figure 21.14 Large, sharply circumscribed plaques of psoriasis. The silvery scaling of the lower (untreated) plaque is typical.
Guttate psoriasis
Figure 21.15 Coarse pitting of the nail and separation of the nail from the nail bed (onycholysis). These are both classic features of psoriasis.
Figure 21.16 Flexural psoriasis. Note the glistening but not scaly rash.
This is most commonly seen in children and adolescents and may follow a streptococcal sore throat. In many patients this will be the first clinical indication of the disease. The rash often appears rapidly. Individual lesions are droplet-shaped, small (seldom greater than 1 cm in diameter) and scaly. Bouts of guttate psoriasis may clear in a few months but respond well to early treatment with phototherapy. The majority of these patients will develop plaque psoriasis later in life.
Erythrodermic psoriasis
The skin becomes universally red or scaly, or more rarely just red with very little scale present. As in other forms of erythroderma temperature regulation becomes problematic with a danger of either hypothermia or hyperthermia developing. Precipitants for erythroderma may not be evident but inappropriate use of dithranol, tar or phototherapy is a known factor.
Pustular psoriasis
There are two varieties of pustular psoriasis. The first is the generalised form which is rare but very serious. The onset is usually sudden with large numbers of small sterile pustules erupting on a red base. The patient may rapidly become ill with a swinging pyrexia coinciding with the appearance of new pustules. Such patients will usually require urgent assessment and hospital admission to a dermatology ward. More common is a localised form of pustular psoriasis which primarily affects the palms and soles. This eruption is chronic and comprises small sterile pustules which lie on a red base, and resolve to leave brown macules or scaling in their wake. The relation between pustular psoriasis of the palms and the soles (palmoplantar pustulosis) and psoriasis remains disputed by some, although the majority agree that they are indeed related.
Arthropathy
Between 5 and 10% of individuals with psoriasis appear to have a chronic inflammatory arthropathy (see p. 1011).
Investigations
Few are indicated. Biopsy is seldom necessary and often contributes little where there is clinical doubt (for example, in attempting to distinguish between psoriasis of the palms and eczema of the palms). Throat swabbing for streptococci or other evidence of recent infection may occasionally be useful. Skin scrapings and nail clippings may help to exclude dermatophyte infection where the clinical diagnosis is uncertain. Assessment of all but minor joint symptoms may require assessment by a rheumatologist.
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Management
General measures
Explanation, reassurance and instruction are vital but easily neglected; they must be based on insight into the patient's state of mind. In the vast majority of cases psoriasis is not life-threatening and therefore if the treatment appears worse than the disease, then the treatment should be stopped. Often patients need encouragement to take many of the important decisions themselves, albeit with advice from the physician. Two patients, even with identical patterns of psoriasis, don't have the same experience of the disease.
There is little robust evidence to support the statement that stress exacerbates psoriasis or is causally involved. Certain studies suggest that alcohol consumption is greater amongst some psoriasis patients, but it is not clear whether this is a cause or a result of the disease. What is clear is that doctors need an awareness of the impact that this disease can have on many individuals. For instance, many fathers will, with embarrassment, admit that they cannot take their young children swimming because of the alarm their rash causes to other swimmers. Similarly, blood on the sheets and the ubiquitous scale on bedclothes and carpets may act against many personal relationships. It is said that 'Girls with scalp psoriasis don't wear navy clothes' (the scale being more prominent when viewed against a dark background).
Treatment
Treatment can be classed in four broad categories:
easily applied topical agents such as emollients, corticosteroids, vitamin D agonists, or 'weak' tar or dithranol preparations
ultraviolet therapies such as PUVA and ultraviolet B
systemic agents such as retinoids or immunosuppressives such as ciclosporin
intensive inpatient or day-patient care with topical agents and ultraviolet radiation under medical supervision.
Traditionally, therapies such as inpatient dithranol, when combined with ultraviolet radiation in the Ingram's regimen, were capable of inducing clearance of the disease, i.e. all or >95% of the psoriasis disappeared. The patient remained clear of disease until relapse occurred. The duration of remission varied considerably from less than 1 month to over a year. By contrast, many more acceptable treatments such as calcipotriol do not clear psoriasis; rather they reduce the thickness, scaling and redness of individual plaques. Depending on the clinical context and extent of disease, patient and physician need to choose the appropriate endpoint of treatment. This is often a compromise between side-effects, practical considerations such as time available to attend hospital, and disease extent.
Topical agents
A large number of topical agents have been used to treat psoriasis. Emollients have a modest effect in terms of reducing scale and diminishing itch. Many patients feel more comfortable using emollients than not using them.
Dithranol. Traditionally, the gold standard of therapy was treatment with dithranol or crude tar. Dithranol originally came into use in the late 19th century and is now known to be a potent producer of free radicals. Unsurprisingly, when applied to normal skin dithranol is proinflammatory and stimulates hyperproliferation, but for reasons that remain unclear it normalises differentiation and inhibits proliferation when applied to psoriatic plaques.
Dithranol is used in two main regimens. The first is Ingram's regimen; the plaques are covered with low concentrations of dithranol in a zinc oxide paste following a tar bath and ultraviolet radiation exposure, and then covered in talcum powder and bandages and left in situ for 24 hours. More recently, short-contact dithranol therapy has been developed in which higher concentrations are applied for between 15 and 30 minutes and then washed off. The main clinical limitation of dithranol is its proinflammatory action on normal skin. This presents as 'burning' with pain and erythema, which peaks 72 hours after application. Dithranol also results in a brown staining of the skin and can cause a purple discoloration in individuals with light hair colour. In general, use of dithranol as an inpatient therapy has diminished over the last 20-30 years due to low patient acceptability, the invention of new phototherapy modalities and lack of inpatient beds. As with tar, attempts have been made to make dithranol easier to use and more patient-friendly but efficacy is reduced; these attempts have been largely unsuccessful.
Tar. Tar, particularly crude tar, has been shown to be effective in the treatment of psoriasis. There are certain similarities with dithranol in that tar is proinflammatory and has different effects on the plaque compared with normal skin. Unfortunately, as for dithranol, attempts to define the exact therapeutic mechanism and dissociate efficacy from side-effects have been unsuccessful. It remains true that the more cosmetically acceptable the preparation, the lower its efficacy.
Calcipotriol. More recently, a number of other topical preparations have been developed which have become clinically popular. Calcipotriol is a vitamin D agonist which is highly acceptable cosmetically; it seldom clears a plaque of psoriasis but tends to reduce the thickness of the plaque and diminish the scaling. It is applied twice daily and, providing no more than 100 g is used each week, does not cause hypercalcaemia or hypercalciuria. Patients like calcipotriol because it is odourless, colourless and does not stain. Irritation, which is usually transient, is the main side-effect.
Tazarotene. A vitamin A agonist (retinoid), this has also come into clinical use recently and has many properties in common with calcipotriol. It tends not to induce clearance and may cause irritation, but is easy to use and diminishes the induration, scaling and redness of plaques.
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Corticosteroids. The frequency of use of corticosteroids varies considerably between different countries. In the
Ultraviolet and PUVA therapy
Ultraviolet therapy. Ultraviolet radiation (UVR) forms the mainstay of management of patients with moderate to severe psoriasis. As could be predicted given the known biology of UVR, the main risk of ultraviolet therapies lies in burning in the short term and in the induction of skin cancers in the long term.
There are two main therapeutic modalities in use. It has been known for almost a century that ultraviolet B (UVB) administered therapeutically improves the condition of many patients with psoriasis. To some degree this mirrors the natural improvement that many patients with psoriasis notice in summer. In the past broadband UVB radiation given 3-7 times a week formed part of the Ingram's regimen using dithranol.
More recently, a particular type of UVB radiation produced by the Philips TL01 lamp (narrowband UVB) has become a very popular modality of treatment delivered 2-5 times a week on an outpatient basis. This lamp peaks at 311 nm and was developed specifically following work showing that shorter wavelength (<311>311 nm) were also relatively ineffective. The long-term safety of this lamp is, however, less clear. Some argue that it may be more carcinogenic than broadband UVB therapy while others believe it is less carcinogenic. The results of long-term observation are awaited.
PUVA therapy. Psoralens are natural photosensitisers found in a number of plants. In the early 1960s topical preparations of psoralen used in combination with ultraviolet A (UVA) were reported to have therapeutic effects on psoriasis. In the early 1970s a large randomised trial showed that oral psoralen together with long wavelength ultraviolet A (PUVA) was a dramatically effective treatment for individuals with chronic plaque psoriasis. Psoralen molecules intercalate between the two strands of DNA and upon excitation with UVA photons cross-link the DNA strands. In this sense PUVA therapy is not a 'light therapy'; rather, psoralen is a pro-drug that upon oral administration is distributed throughout the body but is only activated by ultraviolet radiation in those sites that are exposed to UVA (skin and eye-the latter should be protected).
PUVA treatment induces clearance to a greater degree than intensive dithranol therapy and has revolutionised the management of patients with psoriasis. The short-term side-effects are minimal. The therapy can be delivered between 2 and 5 times a week and clearance expected in the majority of individuals within 8 weeks. Clearance will occur in more than 75% of individuals. Some individuals may develop nausea in response to the psoralen, and because the psoralen is also present in the eye individuals need to wear UVR-resistant sunglasses for 24 hours after therapy. The long-term hazards of PUVA therapy give cause for concern but are not surprising because PUVA is by its mechanism of action known to be mutagenic. In patients who have received a large amount of PUVA therapy, particularly 'maintenance therapy' (continuous PUVA lasting for 6 months to a year), there is an elevated risk of squamous cell carcinoma and basal cell carcinoma. Recent work suggests that the risk of melanoma may also be increased although this single study requires confirmation. Instead of being used orally, psoralens can also be applied to the bath before irradiation with UVA (so-called bath PUVA). A few different psoralen photosensitisers are available that vary in their characteristics.
EBM
TREATMENT OF PSORIASIS-phototherapy
'RCTs show that oral PUVA therapy clears chronic plaque psoriasis in >75% of patients. Clearance rates and the length of remission following PUVA are similar to those obtained with inpatient treatment with the Ingram's dithranol regimen. RCTs show that TL01 UVB phototherapy twice weekly is less effective at inducing clearance of psoriasis and produces a shorter remission than oral PUVA given twice weekly.'
Gordon PM, Diffey BL, Matthews JN, Farr PM. A randomized comparison of narrow-band TL-01 phototherapy and PUVA photochemotherapy for psoriasis. J Am Acad Dermatol 1999; 41:728-732.
Parrish JA, Fitzpatrick TB, Tanenbaum L, Pathak MA. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. N Engl J Med 1974; 291:1207-1211.
Systemic treatment
Three main systemic agents are used for the management of patients with severe psoriasis: methotrexate, oral retinoids and ciclosporin.
Methotrexate. Methotrexate has been available for the last 40 years and can be very useful therapeutically. In dermatological practice it is administered once a week at much lower doses than those used in haematology. It seems likely that its mechanism of action involves a cytostatic effect on the immune system rather than a primary effect on keratinocyte or epidermal hyperproliferation. The main hazards of methotrexate are that it is an immunosuppressive, may dangerously depress the white cell count without careful monitoring, and in the long term is associated with hepatic fibrosis and potentially cirrhosis, particularly if individuals continue to drink alcohol. Liver biopsies are required in many if not all patients.
Oral retinoids. Oral retinoids such as acitretin are also effective in some patients with psoriasis. They tend to be particularly effective in pustular psoriasis of the palms and soles but are widely used to improve plaque psoriasis. The drugs do not appear to have a quick mode of action but are often combined with other therapies including PUVA treatment. There are some theoretical reasons for arguing that retinoids may diminish the chances of skin neoplasia and these are often employed to justify their use in individuals receiving PUVA. Systemic retinoids are potent teratogens and following use of acitretin pregnancy is not safe for at least 2 years.
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Ciclosporin. Ciclosporin was the first of a number of potent immunosuppressives to find a role in the management of a minority of patients with psoriasis. Unfortunately, these agents are known not to be active topically in psoriasis (at least not in clinical practice) and therefore their oral use carries considerable risks in terms of nephrotoxicity and the potential for elevated risks of neoplasia, particularly of the cervix and skin and lymphoma. Despite ciclosporin being effective in inducing and maintaining clearance of individuals with psoriasis continuous use of this drug will be difficult to justify in the vast majority of patients. Long-term surveillance data are not available in this particular patient group.
Intensive inpatient care
Intensive inpatient treatment with dithranol or tar is less common than previously. In many parts of the world this is because beds for management of patients with skin disease are not available to the same degree that they once were. Ingram's regimen will produce clearance in 80% of psoriatics in 3 weeks. Such a regimen still remains the gold standard in terms of both efficacy and safety. Set against this is the fact that many individuals are reluctant to come into hospital for such a period of time. The balancing of risk between known safe inpatient treatments and potentially more toxic outpatient treatments still gives cause for concern.
LICHEN PLANUS
Lichen planus is a rash characterised by intensely itchy polygonal papules with a violaceous hue involving the skin and less commonly the mucosae, hair and nails.
Aetiology
The cause is unknown but an immune pathogenesis is suspected as there is an association with some autoimmune diseases such as myasthenia gravis (see p. 1183), and with thymoma and graft-versus-host disease. Rashes with clinical and histological features of lichen planus can occur in chronic active hepatitis, hepatitis B and C infections, and in patients taking drugs, the most common culprits being gold and other heavy metals, sulphonamides, penicillamine, antimalarials, antituberculous drugs and thiazide diuretics. They also occur in those handling colour developers.
Pathology
There is hyperkeratosis, a prominent granular layer, basal cell degeneration and a heavy T lymphocyte infiltration in the upper dermis. Degenerating basal cells may form colloid (apoptotic) bodies. The T cell-basal cell interaction leaves a 'sawtooth' dermo-epidermal junction. The picture suggests an immune reaction to an unknown epidermal antigen.
Clinical features
Figure 21.17 Lichen planus. Glistening discrete papules involving the volar aspects of the forearm and wrist. Note the lesions along scratch marks (Köbner phenomenon).
Lichen planus tends to start on the di stal li mbs, most commonly the volar aspects of the wrists (see Fig. 21.17), and the lower back. Intensely itchy, flat-topped, pink-purplish papules appear and some develop a characteristic fine white network on their surface (Wickham's striae). New lesions may appear at the site of trauma (Köbner phenomenon) and the rash may spread rapidly to become generalised. Individual lesions may last for many months and the eruption as a whole tends to last about 1 year, often leaving marked post-inflammatory pigmentation. Mucous membrane involvement, comprising an asymptomatic fine white lacy network or pinhead-sized white papules, occurs in about two-thirds of patients (see p. 1050). The nails are usually normal but in 10% they may be affected, with changes ranging from longitudinal grooving to destruction of the nail fold and bed. Variants of the classic picture are rare but often challenging diagnostically. They include annular, atrophic, bullous, follicular, hypertrophic and ulcerative types.
Diagnosis
This is usually clear-cut clinically but a skin biopsy can be helpful. Other erythematous scaly conditions should be considered in the differential diagnosis, including guttate psoriasis, pityriasis rosea, pityriasis lichenoides and drug eruptions.
Management
The condition is usually self-limiting, although rarely, particularly with oral lichen planus, it may persist for more than 10 years. Potent local corticosteroids may help with intense itch but systemic corticosteroids may be indicated. Topical corticosteroids applied to the buccal mucosa may also be required. A variety of other therapies have been used including ciclosporin, retinoids and phototherapy.
ISSUES IN OLDER PEOPLE
PRACTICAL PROBLEMS OF INFLAMMATORY SKIN DISEASE
Quality of life is affected due to distress and discomfort.
Skin disease is potentially more life-endangering in the elderly: for example, erythroderma.
Skin disease is cosmetically unattractive, causing depression and increased social isolation.
Irritation, soreness and itching cause sleep disturbance and increasing confusion.
Older people may be reluctant to seek help because they are anxious that they may be perceived as not coping.
Older people may have difficulty administering topical treatments, e.g. opening jars and tubes and applying creams during bathing; there is an increased risk of slipping in an oily bath.
They have less access to information on skin care.
pages 1075 - 1080
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > DISORDERS OF THE PILOSEBACEOUS UNIT
DISORDERS OF THE PILOSEBACEOUS UNIT
ACNE VULGARIS
Acne is almost ubiquitous in the teenage years, differences between individuals being a matter of severity of disease and facility with which scarring develops. Peak severity is in the late teenage years but acne may persist into the third decade and beyond, particularly in females. The main clinical issues relate to under-treatment and lack of clinical interest or insight into the patient's condition.
Aetiology
There are three pathogenetic factors (see Fig. 21.18):
The first is elevated sebum excretion. There is a clear relation between severity of acne and sebum excretion rate. In the complete absence of sebum acne does not occur. The converse, however, is not true; acne may improve in the third and fourth decades despite a high sebum excretion. Sebum excretion is therefore necessary for the development of acne but is not sufficient to cause acne on its own. The main determinants of sebum excretion are hormonal, accounting for the onset of acne in the teenage years. Androgens are the principal sebotrophic hormones but progestogens also increase sebum excretion whilst oestrogens reduce it. In the absence of other clinical features or frank virilism the vast majority of patients with acne have a completely normal circulating endocrine profile.
The second factor in the pathogenesis of acne is infection with Propionibacterium acnes. This bacterium colonises the pilosebaceous ducts and acts on lipids to produce a number of proinflammatory factors.
The third factor is occlusion or blockage of the pilosebaceous unit.
Figure 21.18 The pathogenesis of acne.
Whilst there is some evidence for a familial component for sebum excretion the genetics and epidemiology of acne are poorly understood.
Clinical features
Lesions are usually limited to the face, shoulders, upper chest and back. Seborrhoea (greasy skin) is often clinically obvious. Open comedones (blackheads) due to plugging by keratin and sebum of the pilosebaceous orifice, or closed comedones (whiteheads) due to accretions of sebum and keratin deeper in the pilosebaceous ducts, are usually evident. Inflammatory papules, nodules and cysts occur (see Fig. 21.19A), with one or two types of lesion predominating. Scarring may follow.
There are a number of descriptive terms applied to clinical variants of acne. Conglobate acne refers to severe acne with many abscesses and cysts, marked scarring and sinus formation. Acne fulminans refers to the presence of severe acne accompanied by fever, joint pains and markers of systemic inflammation such as a raised ESR. Acne excoriée refers to the effects of scratching or picking, principally on the face of teenage girls with acne. Infantile acne is rare and is thought to be due to the sebotrophic effects of maternal hormones on the infant.
Figure 21.19 Unpleasant cystic acne in a teenager. A Before treatment. B After prolonged systemic antibiotic treatment.
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A mild form of acne dominated by the presence of comedones may be due to exogenous substances such as tars, chlorinated hydrocarbons or oily cosmetics. A primarily pustular rash may also be seen in those being treated with corticosteroids, lithium, oral contraceptives and anticonvulsants. These forms of acne are usually clinically distinct from the usual variety developing in adolescence.
Individuals with moderate or even severe acne very rarely have any other systemic illness. However, individuals with polycystic ovary syndrome (see p. 712) are more likely to have severe acne and clinical hints-for instance, from menstrual irregularities-require investigation. If there is associated cutaneous virilism or other features of an androgen-secreting tumour, further investigations and expert endocrinological assessment are warranted.
Investigations
Investigations are rarely required. It is important, however, to enquire about the details of previous treatments and particularly about the duration of previous therapies; for example, antibiotics are commonly prescribed for too short periods of time. It is also necessary to understand the patient's expectations and to determine how realistic they are.
Management
The therapy of acne was revolutionised with the advent of systemic retinoids and is now more straightforward and rewarding. In individuals with fairly minor disease, particularly those dominated by the presence of comedones, topical agents such as benzoyl peroxide or tretinoin should be used. Both these substances have irritant activities, a factor which may be important in their therapeutic effect, and instructions need to be given as to how to use them. They may initially be applied for short intervals of time and the strength and duration gradually increased. Although a number of other topical remedies, including washes, soaps and antiseptics, are recommended, evidence for their effectiveness is not convincing. Patients with anything but minor degrees of acne will require therapy with antibiotics, either systemic or local. Local antibiotics (clindamycin or erythromycin) are used more widely than previously; many might consider their use prior to systemic antibiotics or in persons with relatively minor disease.
The principal oral antibiotic is oxytetracycline, taken on an empty stomach not with food, and given in a dose of up to 1.5 g a day if tolerated. In general, oxytetracycline has a good safety profile even with long-term use. Minocycline may be used if the response to oxytetracycline is inadequate or because of the ease of dosing. It is, however, associated with autoimmune hepatitis and remains a second- rather than first-choice drug.
Before an antibiotic is deemed not to have worked the individual must be treated continuously for up to 3 months. If after 3 months there is little response to oxytetracycline the patient should be changed to erythromycin up to 1 g per day in divided doses. Patients need to remain under review. In women, oestrogen-containing oral contraceptives can be a useful adjunct in therapy. There is a small reduction in sebum secretion with oral oestrogens. The addition of an oral anti-oestrogen, cyproterone acetate, is occasionally used in doses of 50-100 mg daily on days 5-14 of the cycle to enhance the effects of sebum reduction. If these topical and systemic agents fail to produce a sufficient clinical response within 3-6 months the patient should be referred for specialist opinion and consideration for treatment with isotretinoin (13 cis-retinoic acid).
Isotretinoin has revolutionised the treatment of severe acne or moderate acne in patients unresponsive to other therapy. When used at a dose of 0.5-1 mg/kg this drug inhibits sebum excretion by >90% over 4 months. Although sebum excretion gradually returns to normal over the course of the year after the drug is stopped, the clinical benefit is prolonged for much longer. Many patients with acne will not require any further treatment for their acne but in a minority a second course of isotretinoin may be required.
Side-effects, especially drying of the skin and mucous membranes, are common but well tolerated and relate to the drug's effects on the function of modified sebaceous glands on the lips, and on lipid biosynthesis in interfollicular epidermis. Rarely, abnormalities of liver function occur and limit treatment. Isotretinoin may elevate serum triglycerides and levels should be checked before therapy and monitored during therapy. Depression and indeed suicide have been reported, although the role of the drug is difficult to disentangle from the role of the underlying disease; it is currently under investigation. The major consideration before the drug is prescribed is that, like all systemic retinoids, isotretinoin is highly teratogenic; females must have a negative pregnancy test before treatment and be on effective contraception for at least a month before the course begins, during the course and for 1 month after it finishes.
EBM
ACNE VULGARIS-use of retinoids
'Studies of the use of topical and systemic retinoids in acne vulgaris have shown that (1) adapalene is more rapid in onset and better tolerated than tretinoin in mild to moderate acne; (2) oral isotretinoin is clinically better and more cost-effective in moderate and severe acne.'
Wessels F, Anderson AN, Kropman K. The cost-effectiveness of isotretinoin in the treatment of acne. Part 1. A meta-analysis of effectiveness literature.
Cunliffe WJ, Poncet M, Loesche C, Verschoore M. A comparison of the efficacy and tolerability of adapalene 0.1% gel versus tretinoin 0.025% gel in patients with acne vulgaris: a meta-analysis of five randomised trials. Br J Dermatol 1998; 139:48-56.
Physical measures
Cysts can be incised and drained under local anaesthetic. Intralesional injections of triamcinolone acetonide (0.1-0.2 ml of a 10 mg/ml solution) hasten the resolution of stubborn cysts. Scarring following acne is seen a lot less commonly if patients receive adequate care. Small, deep acne scars can be excised and other forms of more extensive but shallower scars can be treated by carbon dioxide laser.
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Figure 21.20 Rosacea. The colour is distinctive and the papulo-pustular rash involves the cheeks, centre of forehead and chin.
ROSACEA
Rosacea is a persistent facial eruption of unknown cause characterised by erythema and pustules. Sebum secretion is normal.
Clinical features
The disorder is most common in middle age. The cheeks, chin and central forehead are affected (see Fig. 21.20). Intermittent blushing is followed by fixed erythema and telangiectasia. Dome-shaped papules and pustules but no comedones occur. Rhinophyma, with erythema, sebaceous gland hyperplasia and overgrowth of the soft tissues of the nose, is sometimes associated. Blepharitis and conjunctivitis are complications.
Diagnosis
This is often obvious on clinical grounds but acne, seborrhoeic eczema, photosensitivity and systemic lupus erythematosus must be distinguished.
Management
The pustular component of rosacea normally responds very well to oral oxytetracycline. Once the disease is controlled (usually within a few months) the dose can be diminished but some individuals may need to stay on the antibiotics long-term or require repeated courses. Topical metronidazole also shows some efficacy in rosacea, although it may cause irritation. The erythema and telangiectasia do not respond to antibiotic therapy.
pages 1081 - 1083
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > SOME COMMON SKIN INFECTIONS AND INFESTATIONS
SOME COMMON SKIN INFECTIONS AND INFESTATIONS
FUNGAL INFECTION OF THE SKIN (RINGWORM)
Dermatophytes are fungi capable of causing skin infections known as ringworm or dermatophytosis. The causative fungi belong to three genera (Microsporum, Trichophyton, Epidermophyton); they can originate from the soil (geophilic) or animals (zoophilic), or be confined to human skin (anthropophilic).
Clinical forms of cutaneous infection include tinea corporis (involvement of the body), tinea capitis (scalp involvement, see p. 1069), tinea cruris (groin involvement) and tinea pedis (involvement of the feet). Fungal infection of the nails (onychomycosis) is dealt with on page 1089.
Tinea corporis
The clinical features of tinea corporis are variable and so this condition should be considered in the differential diagnosis of the red scaly rash (see p. 1059). Classically, the lesions are erythematous, annular and scaly, with a well-defined edge and often central clearing. They may be single or multiple and are usually asymmetrical. The degree of associated inflammation depends on the causative fungus and host immunity. Microsporum canis and Trichophyton verrucosum are common culprits and are zoophilic (from dogs and cattle respectively). Inadvertent topical steroid application leads to worsening of the signs (tinea incognito).
Tinea cruris
This common world-wide ringworm affects the groin and is usually caused by Trichophyton rubrum. Itchy erythematous plaques extend from the groin flexures on to the thighs.
Tinea pedis (athlete's foot)
This is the most common form of ringworm in the
Diagnosis
In all cases of suspected dermatophyte infection, the diagnosis should be confirmed by skin scraping or nail clippings (see p. 1055).
Treatment
Treatment can be topical (terbinafine or miconazole cream) or systemic (terbinafine, griseofulvin or itraconazole).
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PAPILLOMAVIRUSES AND VIRAL WARTS
Viral warts are extremely common and most people suffer from one or more at some point during their life. Genital warts occur most commonly during the sexually active years. Warts are a result of infection with the DNA human papillomavirus (HPV), of which there are over 90 subtypes on the basis of DNA sequence analysis. Different subtypes appear to be responsible for several different clinical wart variants but this is not of great practical importance in terms of skin wart therapy.
Transmission is by direct contact with the virus, in either living skin or fragments of shed skin, and is encouraged by trauma and moisture (e.g. in swimming pools, fishmongers etc.). Genital warts, usually due to specific HPV subtypes, are spread by sexual activity, and show a clear relationship with cervical and intraepithelial cancers of the genital area. In particular, HPV 16 and 18 appear to be able to inactivate tumour suppressor gene pathways and lead to squamous cell carcinoma of the cervix or intraepithelial carcinoma of the genital skin. In contrast with genital warts, the relation between HPV of the skin and subsequent skin cancer remains unclear. Individuals who are systemically immunosuppressed, such as those who have received organ transplants, show greatly elevated risks of skin cancer and also a much higher prevalence of infection with HPV. What remains unclear is whether HPV is causally involved in the development of neoplasia or merely reflects the underlying systemic immunosuppression.
Clinical features
Common warts appear initially as smooth, skin-coloured papules. As they enlarge their surface becomes irregular and hyperkeratotic, producing the typical warty appearance. They are most common on the hands but may also be seen on the face, genitalia and sun-exposed surfaces of the arm and leg. Multiple warts are common. Plantar warts (verrucae) are characterised by a rough surface protruding only slightly from the skin and are surrounded by a horny collar. On paring, the presence of capillary loops distinguishes these plantar warts from corns. Plantar warts may be painful and disabling.
Other varieties of wart include mosaic warts (mosaic-like plaques of tightly packed individual warts-see Fig. 21.21); plane warts (smooth, flat-top papules seen most commonly on the face and backs of hands which frequently may hyperpigment and consequently be misdiagnosed); facial warts (often filiform); and genital warts which may be papillomatous and protuberant.
Management
Viral warts will, in the vast majority of normal individuals, resolve spontaneously. However, this may take several years and there is often considerable pressure for treatment. The majority of treatments are based on destruction of keratinocytes, irrespective of whether they are HPV-infected or not. Despite the frequency of the condition, there is a paucity of randomised trials looking at the effectiveness of the various treatments or at the order in which they are used.
Figure 21.21 Mosaic plantar wart. A plaque of closely grouped warts on the sole of the foot.
Most practitioners would try to avoid treating warts that are asymptomatic or not causing distress. Initial treatment should be with salicylic acid or salicylic and lactic acid combinations, together with frequent and regular paring of the hyperkeratotic skin. Such treatment needs to continue for at least several months before convincing effects will be apparent. If it fails, or as an alternative, warts can be treated by cryotherapy using liquid nitrogen. Such therapy is, at some sites and in particular individuals, accompanied by significant pain, and will need to be repeated at intervals of 2-4 weeks, although the optimum strategy is not defined. Over-aggressive treatment with cryotherapy, particularly on the hands, can lead to significant complications including tendon rupture and a high morbidity over the ensuing days. Warts close to or under the nails can be a particular problem. Liquid nitrogen treatment may exacerbate them (due to inflammatory swelling), and skilled cutting of the nail and electrodesiccation, or other destructive therapy, may be necessary.
Viral warts can be a particular problem in individuals who are immunosuppressed following organ transplantation. The prevalence of warts in this group approaches 100% after 5 years and therapy appears less effective than in immunocompetent individuals. In the immunosuppressed not only are warts particularly unsightly, but painful verrucae can limit mobility and require intensive treatments. Individuals who have received large amounts of psoralen and UVA (PUVA) for their psoriasis also show an elevated prevalence of viral wart infection.
Beyond the treatments mentioned above, a number of other treatments have been claimed to be effective in some individuals and in particular clinical contexts; these include systemic retinoids, intralesional injections of bleomycin or interferon, and the application of contact sensitisers such as diphencyprone or dinitrochlorobenzene to the warts. The immunomodulator, imiquimod, is useful in treating stubborn anogenital warts (see p. 105).
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SCABIES
Figure 21.22 Scabies. Pustules at a common site in a child. Burrows were present but cannot be seen at this distance.
Scabies is caused by the acarus, Sarcoptes scabiei, and is a common world-wide public health problem with an estimated global prevalence of 300 million. The infestation causes considerable discomfort and can lead to secondary infection and complications such as post-streptococcal glomerulonephritis. Scabies spreads in households and environments where there is a high frequency of intimate personal contact. Diagnosis is made by identifying the scabietic burrow, usually found on the edges of the fingers, toes or sides of the hands and feet. Extraction of the mite using a blunt needle can be difficult but is helpful in ensuring the correct diagnosis, appropriate treatment and compliance. Inappropriate application of scabietic treatments can cause considerable irritation in other conditions. In small children the palms and soles can be involved with pustule formation (see Fig. 21.22). Involvement of the genital area in boys is pathognomonic. The main symptom is itch (see p. 1058). The clinical features include secondary eczematisation elsewhere on the body; the face and scalp are never involved except in the case of infants. Even after successful treatment the itch can continue, and occasionally nodular lesions persist.
Topical treatment of scabies is usual and involves the affected individual and all asymptomatic family members/physical contacts to ensure eradication. Two applications one week apart of an aqueous solution of either permethrin or malathion to the whole body, excluding the head, is usually successful. In some clinical situations such as poor compliance, immunocompromised individuals and heavy infestations (Norwegian scabies), systemic treatment with ivermectin (200 µg/kg) as a single dose would be appropriate.
LICE
Head lice (Pediculosis capitis)
Figure 21.23 Head lice. 'Nits' (empty egg cases) adhere strongly to the hair shafts.
Infestation with head louse, Pediculus humanus capitis, is common and highly contagious. Head lice are spread by direct head-to-head contact. Itching of the scalp is the main symptom; scratching leads to secondary infection and cervical lymphadenopathy. The diagnosis is confirmed by identifying the living louse or nymph on the scalp or on a black sheet of paper after careful fine-toothed combing of wet hair that has had conditioner applied. The empty egg cases ('nits') are easily seen along the hair shaft (see Fig. 21.23). These are characteristically difficult to dislodge.
Treatment is recommended for the infected individual and any infected household/school contacts. Eradication in school populations has proved difficult and it is likely that this is due to compliance as well as resistance to certain treatments. The standard pharmacological treatments for head lice are malathion, permethrin and carbaryl in a lotion or aqueous formulation, which are applied on two separate occasions at 7-10 days' interval. Many health boards advise rotational treatments within a community to avoid resistance. Regular 'wet-combing' (physical removal of the live lice by regular combing of slippery, conditioned wet hair) does not seem to be as effective as pharmacological treatments.
Involvement of the eyebrows/eyelashes is best treated by topical Vaseline twice daily for at least a fortnight.
Crab lice (Pthirus pubis)
These are usually sexually acquired, with pruritus as the main symptom. An aqueous-based treatment of either malathion or carbaryl is the treatment of choice. This should be applied on two occasions to the whole body as body hair can also be infested. Contacts should also be treated.
pages 1083 - 1085
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > PRESSURE SORES
PRESSURE SORES
Pressure sores are caused by prolonged pressure-induced ischaemia, when the interface pressure between the patient's body and its supporting surface exceeds capillary closing pressure. Up to 5% of patients over 70 years old in hospital develop pressure sores, but this may rise to 30% in those with a fractured neck of femur. The morbidity and mortality of those with deep ulcers are high.
Aetiology
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The main risk factors for pressure sores include:
immobility, e.g. coma, neurological disease with paralysis, surgery, pain, over-use of sedatives, depression
hypotension, e.g. shock, dehydration
reduced oxygen availability, e.g. anaemia, fever, infection
peripheral vascular disease, including diabetic microangiopathy
malnutrition, e.g. malignant cachexia, alcoholism
skin condition, e.g. atrophy due to age or steroids, dry/cracked and moist/chapped condition.
Clinical features
The sore starts as a localised area of erythema and progresses to a superficial blister or erosion. If the cause is not corrected, deeper damage occurs; a black eschar develops which, when removed or shed, leaves a deep and penetrating ulcer, often colonised by Pseudomonas aeruginosa. The skin overlying bony prominences, such as the sacrum, greater trochanter, ischial tuberosity, calcaneal tuberosity and lateral malleolus, is especially susceptible.
Management
This is not easy but the following are important:
prevention by regular repositioning of immobile patients and pressure-reducing mattresses in those at high risk
treatment of risk factors including malnutrition
débridement of necrotic tissue either by surgery or by enzymatic necrolysis
systemic antibiotics for spreading infection
dressings to keep the wound wet and enhance granulation (see ulcers, p. 1067); regular cleansing with normal saline or 0.5% aqueous silver nitrate; semi-permeable dressings such as OpSite
consideration of plastic surgical reconstruction when the ulcer is clean.
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > DISORDERS OF PIGMENTATION
DISORDERS OF PIGMENTATION
DECREASED PIGMENTATION
OCULOCUTANEOUS ALBINISM
Albinism results from a range of genetic abnormalities leading to reduced melanin biosynthesis in skin and eyes but where the number of melanocytes is normal. It differs from cutaneous hypopigmentation in that there is, by definition, ocular involvement. There are a number of different forms of albinism, and considerable variation even within one genetic type. Albinism is usually inherited as an autosomal recessive trait. Type 1 albinism is due to a defect in the tyrosinase gene whose product is rate-limiting in the production of melanin. Such individuals at birth have an almost complete absence of pigment in the skin and hair with a resulting pale skin and white hair, and also failure of melanin production in the eye, in the iris and retina. Patients have photophobia, poor vision not correctable with refraction, rotatory nystagmus, and an alternating strabismus associated with abnormalities in the decussation of nerve fibres in the optic tract. A second form of albinism is due to a defect in the P gene which encodes an ion channel protein in the melanosome. Like type 1 albinos patients may have a gross reduction of melanin in the skin and in the eyes, but may be more mildly affected than some type 1 albinos. Establishing the subtype of albinism requires genetic analysis as there is considerable heterogeneity in the phenotype of the various subtypes (it is not always easy to guess the type of albinism).
Oculocutaneous albinos are at grossly increased risk of sunburn and skin cancer. In Equatorial regions many albinos will die from squamous cell carcinoma or melanoma in early adult life. Albinos may, however, show pigmented melanocytic naevi and may freckle in response to sun damage. There are other extremely rare forms of albinism such as rufous and brown albinism.
Management
Avoidance of sun exposure is important, and may involve protective clothing, hats and an alteration of lifestyle if possible to avoid the
VITILIGO
Vitiligo is an acquired condition in which circumscribed depigmented patches develop; it affects 1% of the population world-wide.
Aetiology
Unlike albinism, where melanocytes are present but the production of melanin is abnormal, vitiligo involves focal areas of melanocyte loss. There may be a positive family history of the disorder in those with generalised vitiligo and this type is associated with autoimmune diseases such as diabetes, thyroid and adrenal disorders, and pernicious anaemia. Trauma and sunburn may precipitate the appearance of vitiligo. A number of hypotheses have been advanced to explain the pathogenesis, none of which is entirely satisfactory. One popular theory is that the melanocytes are the target of a cell-mediated autoimmune attack. Why only focal areas are affected remains unexplained.
Clinical features
Segmental vitiligo is restricted to one part of the body, but not necessarily a dermatome. Generalised vitiligo (see Fig. 21.24) is often symmetrical and frequently involves the hands, wrists, knees and neck as well as the area around the body orifices. The hair of the scalp and beard may also depigment. The patches of depigmentation are sharply defined and, in Caucasians, may be surrounded by light brown 'café au lait' hyperpigmentation. Some spotty perifollicular pigment may be seen within the depigmented patches and is sometimes the first sign of repigmentation. Sensation in the depigmented patches is normal (compare tuberculoid leprosy, p. 87). The course is unpredictable but most patches remain static or enlarge; a few repigment spontaneously.
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Figure 21.24 Vitiligo. Widespread patches in a youngster with a strong family history of autoimmune diseases.
Management
This is unsatisfactory. Protecting the patches from excessive sun exposure by clothing or sunscreen may be helpful in reducing episodes of burning and potentially of skin cancer in the long term. Camouflage cosmetics may also be helpful, particularly in those with dark skin. Phototherapy with PUVA or more recently TL01 phototherapy has been used. Although repigmentation may occur during phototherapy, there is an absence of randomised controlled trials to inform clinical practice. PUVA therapy in particular has been widely used but because it increases pigmentation in normal skin, except in very dark-skinned individuals, the cosmetic effect may actually be worse than without treatment. When depigmentation occurs it is frequently as small foci of dark areas of skin surrounding hair follicles within the vitiliginous area. The absence of whiteness of the hairs in the area of vitiligo is a good prognostic feature.
PHENYLKETONURIA
This rare metabolic cause of hypopigmentation has a prevalence of about
HYPOPITUITARISM
Hypopigmentation is due to decreased production of pituitary melanotrophic hormones (see p. 736). The complexion has a pale, yellow tinge; there is skin atrophy and thinning or loss of the sexual hair.
INCREASED PIGMENTATION
This is mostly due to hypermelanosis but other pigments may occasionally be deposited in the skin. Orange discoloration may suggest carotenaemia; a bronze colour, haemochromatosis (see p. 870); and other hues, drug eruptions (see
21.25 DRUG-INDUCED PIGMENTATION
Drug Appearance
Amiodarone Slate-grey, exposed sites
Arsenic Diffuse bronze pigmentation with superimposed raindrop depigmentation
Bleomycin Often flexural, brown
Busulfan Diffuse brown
Chloroquine Blue-grey, exposed sites
Clofazimine Red
Mepacrine Yellow
Minocycline Slate-grey, scars, temples, shins and sclera
Phenothiazines Slate-grey, exposed sites
Psoralens Brown, exposed sites
LOCALISED HYPERMELANOSIS
Freckles
These lesions, also known as ephelides, are sharply demarcated light brown-ginger macules of up to 5 mm in diameter. They are most prominent on exposed sites; they multiply and become darker with sun exposure. The melanin in the basal cell layer of the epidermis is increased without melanocytic proliferation.
Lentigines
These are dark brown macules ranging from 1 mm to 1 cm across. Although discrete, their outline may be irregular. Lentigines occur in childhood but are most common after middle age on the backs of the hands ('liver spots') and on the face. They have an increased number of melanocytes which produce excessive melanin.
Multiple lentigines are seen on and around the lips, buccal mucosa and fingers in the Peutz-Jeghers syndrome (associated with small intestinal polyposis and intussusception-see p. 822).
DIFFUSE HYPERMELANOSIS
Endocrine pigmentation
Chloasma describes discrete patches of facial pigmentation which occur in pregnancy and in some women taking oral contraceptives. Diffuse pigmentation, sometimes worse in the skin creases, may be a feature of Addison's disease (see p. 726), Cushing's syndrome (see p. 721), Nelson's syndrome and chronic renal failure (see p. 600). In all of these cases it is due to an increase in the levels of pituitary melanotrophic peptides (see p. 736).
Drug-induced pigmentation
See Box 21.25 for a list of some drugs which may cause hyperpigmentation; this is not always due to hypermelanosis alone but may sometimes be due to deposition of the drug or its metabolite, either of which may be complexed with melanin.
pages 1086 - 1087
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > DISORDERS OF THE NAILS
DISORDERS OF THE NAILS
The condition of the nails may reflect both local and systemic disease, and omission of this part of the general examination could result in some important diagnostic clues being overlooked.
The nail plate arises from the nail matrix and lies on the nail bed (see Fig. 21.25). The keratinous plate is produced by cells of the matrix and, to a much lesser extent, the bed. Finger nails grow about 1 cm every 3 months and toe nails at about one-third of this rate.
NAIL FOLD DISORDERS
Figure 21.25 The nail plate and bed.
Figure 21.26 Dermatomyositis. The erythema, dilated and tortuous capillaries in the proximal nail fold and the Gottron's papules on the digits are important diagnostic features (see p. 1038).
Examination of the nail folds should accompany examination of the nails. Paronychia describes inflamed and swollen nail folds. Chronic paronychia is seen most commonly in those with a poor peripheral circulation, in those involved in wet work, in diabetics and in those who are over-enthusiastic when manicuring their cuticles. Ragged cuticles and dilated or thrombosed capillaries in the proximal nail folds are important pointers to connective tissue disease (see Fig. 21.26).
NAIL PLATE DISORDERS
These may be isolated abnormalities due to congenital disease or trauma, or may reflect other diseases, either systemic or just involving the skin. Longitudinal ridging and beading of the nail plate is not abnormal and increases with age. Similarly, occasional white transverse flecks (striate leuconychia) are seen frequently in normal nails and are due to airspaces within the plate and not, contrary to popular belief, to insufficient calcium.
CONGENITAL DISEASE
Pachyonychia congenita is a rare autosomal dominant condition. Some families have been shown to have mutations in keratins. The nails are grossly thickened, especially at the free edge, and discoloured from birth.
TRAUMA
Splinter haemorrhages
These are fine linear dark brown flecks running longitudinally in the plate. They are most commonly due to trauma but may be seen in nail psoriasis. They are also a sign of subacute bacterial endocarditis (see p. 464).
Subungual haematomas
These may appear as a crimson, purple or grey-brown discoloration of the nail plate, most frequently that of the big toe (see Fig. 21.27). Sometimes, but not always, there is a history of trauma. The abnormality appears suddenly and the nail folds remain uninvolved (cf. subungual malignant melanoma, p. 1094). As the nail grows out, a normally coloured band develops proximally.
Habit-tic dystrophy
This is common, and is due to the habit of picking or fiddling with the proximal nail fold of the thumb. This produces a ladder pattern of transverse ridges and furrows up the centre of the nail.
Figure 21.27 Subungual haematoma.
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Chronic trauma
Chronic trauma from ill-fitting shoes and from sport may cause malalignment and thickening of the nails, known as onychogryphosis, and lead to ingrowing toe nails.
THE NAIL IN SYSTEMIC DISEASE
Koilonychia
This is a concave or spoon-shaped deformity of the plate which is a sign of iron deficiency (see Fig. 21.28A). It is seen most often in countries where malnutrition is prevalent.
Beau's lines
These are transverse grooves which appear at the same time on all nails, a few weeks after an acute illness, moving out to the free margins as the nails grow (see Fig. 21.28B).
Digital clubbing
In its most gross form this is seen as a bulbous swelling of the tip of the finger (see Figs 21.28C and D) or toe. The normal angle between the proximal part of the nail and the skin is lost. Causes include:
respiratory-bronchogenic carcinoma, asbestosis (especially with mesothelioma), suppurative lung disease (empyema, bronchiectasis, cystic fibrosis), fibrosing alveolitis
cardiac-cyanotic congenital heart disease, subacute bacterial endocarditis
other-inflammatory bowel disease, biliary cirrhosis, thyrotoxicosis, familial.
Figure 21.28 The nail in systemic disease. A Koilonychia. B Beau's lines. C and D Digital clubbing.
Whitening of the nails
This is a rare sign of hypoalbuminaemia. 'Half and half' nails (white proximally and red-brown distally) are seen in some patients with renal failure. Rarely, drugs (e.g. antimalarials) may discolour nails.
THE NAIL IN SOME COMMON SKIN DISEASES
Psoriasis
This may cause coarse pitting of the nail plate, onycholysis (separation of the nail plate from the nail bed) and subungual hyperkeratosis (see Fig. 21.15, p. 1077).
Eczema
Shiny nails may signify frequent rubbing of eczematous skin elsewhere. When eczema involves the distal phalanges the nail may be deformed, with transverse ridging and thickening of the plate.
Lichen planus and severe alopecia areata
These may cause trachyonychia, a fine roughness and white discoloration of the nail plate.
Dermatophyte infection
This causes yellow-brown discoloration and crumbling of the plate which starts at the free margins and spreads proximally (see Fig. 21.29). Usually only a few nails are infected and frequently only on one foot or hand.
Figure 21.29 Dermatophyte infection. This causes discoloration and crumbliness of the nail plate.
pages 1088 - 1089
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > SKIN TUMOURS
SKIN TUMOURS
The increasing number of patients over 70 years old is paralleled by an increasing incidence of skin cancer. Only the most common benign tumours and a few malignant ones will be described in this section.
BENIGN TUMOURS
MELANOCYTIC NAEVI
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Melanocytic naevi (moles) are localised benign proliferations of melanocytes which are probably clonal. Their cause is unknown but may relate to abnormalities of the normal migratory pattern of the melanocytes during development. Moles are a usual feature of most human beings and it is quite normal to have 20-50. The number reflects both genetic and environmental characteristics. Interestingly, a locus close to the P16 gene which has been implicated in some cases of familial melanoma and other familial cancers (pancreas) appears to exert an effect on mole number. Individuals with high sun exposure also show more moles, i.e. there is clear evidence for both genetic and hereditary factors. With the exception of congenital melanocytic naevi (which are present at birth or appear shortly after birth), most melanocytic naevi appear in early childhood, at adolescence, and during pregnancy or oestrogen therapy. New lesions appear less often after the age of 20.
Clinical features
Acquired melanocytic naevi are classified according to the microscopic location of the clumps of melanocytes in the skin (see Fig. 21.30). Junctional naevi are usually circular and macular; their colour ranges from mid- to dark brown and may vary within a single lesion. Compound and intradermal naevi are similar to one another in appearance; both are nodules of up to 1 cm in diameter, though intradermal naevi are usually less pigmented than compound naevi. Their surface may be smooth, cerebriform or even hyperkeratotic and papillomatous, and they are often hairy.
Using a variety of different criteria, some naevi have been labelled atypical or dysplastic. Unfortunately, the terms have not been precisely defined and are often used to describe a clinical appearance as well as a histological feature. Such abnormal naevi have been found in some individuals with a dramatically increased risk of melanoma. However, even within these families the abnormal melanocyte phenotype does not clearly segregate with the propensity to melanoma. Such abnormal naevi are often profuse, large and irregularly pigmented and most obvious on the trunk. They may be present on the scalp and the palmar-plantar surfaces as well as the buttocks. Some may appear slightly pinkish and show an inflamed halo. Unfortunately, the clinical significance of individuals with such naevi remains poorly defined; most authorities view these people as being at an increased risk of melanoma but clear criteria for management and follow-up are not available.
Whereas about 30-50% of malignant melanomas develop from melanocytic naevi, the converse is far from true and only a minute percentage of melanocytic naevi become malignant. Malignant change is most likely in large congenital melanocytic naevi (where the risk may correlate with the size or mass of the melanocyte lesion) and possibly in those families who have been diagnosed as showing large numbers of atypical naevi with a history of melanoma. Although the skin is open to easy observation, the value of self-examination has not been validated in randomised control trials. A change in a mole may well be a harbinger of melanoma but of course more frequently it is not. In the majority of Caucasian populations, any change in a mole is thought by many to warrant medical opinion (see
Figure 21.30 Classification of melanocytic naevi. Classification is based on microscopic location of the clumps of naevus cells.
21.26 SIGNIFICANT CHANGES IN MELANOCYTIC NAEVI
Itch
Enlargement
Increased or decreased pigmentation
Bleeding
Irregularity of surface or edge
Inflammation
Ulceration
Alteration in shape
Management
Melanocytic naevi are normal and do not require excision except when malignancy is suspected or when they repeatedly become inflamed or traumatised. Some individuals wish to have them removed for cosmetic reasons.
SEBORRHOEIC WARTS (BASAL CELL PAPILLOMA)
Seborrhoeic warts are common benign epidermal tumours. They are described as seborrhoeic because they often appear oily but in reality they have nothing to do with sebaceous glands. Although they may be a cosmetic problem their principal significance lies in the differential diagnosis of melanoma or other skin tumours.
Clinical features
Figure 21.31 Multiple seborrhoeic warts.
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Seborrhoeic warts are rare before the age of 35. Initially they may become visible as macular pigmented areas. They may then become markedly elevated and are most commonly found on the trunk and face (see Fig. 21.31). The sexes are equally affected. They may show a range of appearances and vary in colour from yellow to very dark brown, and in shape from fairly flat to a protuberant and 'stuck-on' appearance; they may even be pedunculated. Their surface often appears rather greasy and may show some sealing with pinpoint keratin plugs which can be of diagnostic use in excluding melanoma.
Investigations
Biopsy is rarely necessary but malignant melanoma may on occasion be indistinguishable on clinical appearance alone.
Management
Seborrhoeic warts may be left alone but if they cause cosmetic embarrassment then they can be treated by curettage under local anaesthetic or by cryotherapy. Sometimes seborrhoeic keratoses are particularly itchy and therapy of a number of lesions may be required.
KERATOACANTHOMA
This is quite a striking benign keratinocyte tumour characterised by a period of rapid growth of a lesion that may be 4 or 5 cm across or even larger, with a central keratin plug in a dome-shaped nodule (see p. 1051). Spontaneous resolution will occur but it may take months and often results in an unsightly scar which could be improved by excision of the lesion. Clinically and histologically the lesion resembles that of a squamous cell carcinoma but shows a different natural history. If there is any doubt the lesions are better managed as squamous cell carcinomas. To make a positive diagnosis of keratoacanthoma a large biopsy reflecting the architecture of the lesion is required.
MALIGNANCY: INCIDENCE AND RISK FACTORS
In most Caucasian populations non-melanoma skin cancer (principally comprising basal and squamous cell carcinoma) is the most common human malignancy. Each year one million Americans develop new basal cell carcinomas. Fortunately, the majority of these tumours are easy to diagnose and can be managed relatively simply with a low morbidity and an extremely low mortality.
The main risk factor for most forms of skin cancer is exposure to ultraviolet radiation in the absence of adequate melanin pigmentation. The evidence for the important role of environmental ultraviolet radiation and pigmentation is:
The body site distribution of skin cancer with the frequently or intermittently exposed sites predominating.
The increased risk of tumours in those with pale skin and the low rates in those with black skin.
The increased tumour rates in those with pale skin who have migrated to areas of high sun exposure (such as red-headed individuals from the
The grossly elevated risks of skin cancer in individuals with a focal defect in the ability to repair ultraviolet radiation DNA damage. Such individuals with xeroderma pigmentosum have an increased risk of both non-melanoma and melanoma skin cancers as well as a variety of other clinical features involving the central nervous system. Their defect in DNA repair is almost completely confined to the inability to repair ultraviolet-induced damage (rather than, say, X-ray radiation) and they therefore illustrate the important step of ultraviolet radiation-induced damage.
Although ultraviolet radiation is the major environmental determinant of skin cancer, the various tumour types show different body distribution. For example, squamous cell carcinomas and actinic keratosis mirror the sites of highest cumulative ultraviolet radiation exposure, with the backs of the hands and the scalps of bald-headed individuals showing the greatest tumour density. In contrast, basal cell carcinomas tend to be disproportionally common on the face, perhaps reflecting their appendageal origins. There is a different body site distribution for melanoma, with tumours relatively more common on areas of skin that may have received intermittent sun exposure. This has led to the suggestion that intermittent sun exposure or episodes of burning may be important, although the epidemiological evidence in favour of burning rather than other aspects of exposure is inconclusive.
The attributable risk of other causes of skin cancer is by contrast small, but ionising radiation or systemic immunosuppression (as seen in people who have received heart or kidney transplants) greatly increases squamous cell cancer risks.
EBM
SKIN CANCER-role of sunscreens
'RCTs show that in certain populations where ambient UVR is high sunblocks reduce the incidence of actinic keratoses, the number of squamous cell carcinomas and the number of melanocytic naevi in children.'
Gallagher RP, Rivers JK, Lee TK, et al. Broad-spectrum sunscreen use and the development of new nevi in white children: a randomized controlled trial. JAMA 2000; 283:2955-2960.
Green A, Williams G, Neale R, et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous-cell carcinomas of the skin: a randomised controlled trial. Lancet 1999; 354:723-729.
EBM
SKIN CANCER-are there any intervention strategies to prevent skin cancer in immunosuppressed individuals?
'Patients receiving immunosuppression following organ transplant are at high risk of non-melanoma skin cancer (NMSC), and studies suggest that systemic retinoids reduce or delay the onset of NMSC in this group. Before and after studies also suggest retinoids decrease NMSC rates in patients with xeroderma pigmentosum.'
Bavinck JN, Tieben LM, van der Woude FJ, et al. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal transplant recipients: a double-blind, placebo-controlled study. J Clin Oncol 1995; 13:1933-1938.
Kraemer KH, DiGiovanna JJ, Moshell AN, et al. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med 1988; 318:1633-1637.
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PRE-MALIGNANT TUMOURS
ACTINIC KERATOSIS
Actinic keratoses are small, scaly, red areas on sun-exposed sites that show focal areas of dysplasia on histological examination (see Fig. 21.32). They are extremely common and frequently multiple; in some surveys over half the population aged over 40 in
Figure 21.32 Numerous actinic keratoses in a white patient who had lived for years in the tropics.
Management
Actinic keratoses are treated easily and effectively with liquid nitrogen. If there are a large number of lesions, then the topical cytotoxic 5-fluorouracil may be required. Lesions which do not respond to treatment may require curettage or excision and reconsideration of their nature.
INTRAEPIDERMAL CARCINOMA (BOWEN'S DISEASE)
Clinical features
This usually presents as a slow-growing, red, scaly area with some resemblance to a plaque of psoriasis, on the lower leg of elderly females. Histology reveals full-thickness dysplasia. They may occur on other sites (see Fig. 21.33), and occasionally develop into squamous cell carcinomas. They should be viewed as being considerably more suspicious than an isolated actinic keratosis.
Figure 21.33 Intraepidermal carcinoma (right cheek). This persistent psoriasis-like plaque recurred after the original (anterior) lesion was treated by freezing.
Investigations and management
An initial incisional biopsy may be required and the treatment is local destruction. Alternatively, the lesions may be managed with curettage and subsequent histology. Curettage, however, will not usually allow a squamous cell carcinoma to be positively diagnosed or excluded (because the tissue architecture is not preserved). An alternative is cryotherapy; even more recently photodynamic therapy has been introduced in which a photosensitiser is applied topically in the presence of blue light.
MALIGNANT TUMOURS
BASAL CELL CARCINOMA (BCC)
This is the most common human cancer. Rates are five times higher than for squamous cell carcinoma in European countries. Classically, lesions are slow-growing and ulcerated, with a pearly and telangiectatic edge; they occur on the face of an elderly individual. The tumour invades locally but rarely metastasises. In practice it is managed as though it does not metastasise unless it is particularly large or has been present for a long time. 'Rodent ulcer' is a term commonly used for slowly expanding ulcerative basal cell carcinoma. The malignant cells resemble basal keratinocytes.
Clinical features
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The most common type is the nodulo-ulcerative form. The earliest lesion is a small, glistening, skin-coloured papule, often with fine telangiectatic vessels on the surface, which slowly enlarges. Central necrosis may occur, leaving an ulcer surrounded by a rolled pearly edge (see Fig. 21.34). Without treatment lesions may reach 1-2 cm in diameter over 5-10 years. Slow but relentless growth causes local tissue destruction. Sometimes this type of tumour becomes cystic or pigmented. The morphoeic variant of basal cell carcinoma is a slowly expanding, yellow or grey waxy plaque with an ill-defined edge. Fibrosis often follows ulceration and crusting, and the lesion may appear as an enlarging scar. The superficial (multifocal) variant is seen most often on the trunk; it appears as a slowly enlarging pink or brown scaly plaque with a fine 'whipcord' edge and may resemble a patch of intraepidermal carcinoma (see above). If left, it may grow to 10 cm in diameter.
Management
The majority of basal cell carcinomas are easily treated with local destruction. Metastasis is extremely rare; nevertheless, caution should be exercised-for instance, in tumours close to the eye margins where local invasion can cause considerable management difficulty, or in tumours which can track down nerves such as the infraorbital.
The choice of modality of treatment is dependent on local expertise and interest and involves either surgery, cryotherapy or radiotherapy. Depending on tumour subtype all are equally effective in expert hands. Surgery is, however, increasingly seen as the first choice as it allows proper histological assessment of the tumour and examination of tumour margins. Curettage and cautery also show a good result for some small lesions, particularly if they are superficial and not close to the eye. Cryotherapy has a significant morbidity when used for anything other than superficial lesions. Radiotherapy was used extensively in the past but is less popular now. Fractionated doses of radiation can reduce the morbidity of radiotherapy but in general a surgical excision results in a better cosmetic effect with lower morbidity.
Figure 21.34 Basal cell carcinoma. A slowly growing pearly nodule just below the inner canthus. The central crust overlies an ulcerated area.
The importance of control of tumour margins is widely debated. Many authorities believe that Mohs' surgery, in which the complete margins of the excised tissue are examined histologically, is of benefit but the present indications for this approach are subject to debate and there is an absence of robust clinical studies. Whatever modality of treatment is used, in expert hands the cure rate should be greater than 90%. Tumour recurrences can subsequently be treated. Some tumours can be very misleading in terms of clinical assessment of their margins and should be examined by a dermatological surgeon. If the primary tumour is not completely excised a wait-and-see policy is often recommended, depending on the clinical context.
SQUAMOUS CELL CARCINOMA (SCC)
Squamous cell carcinoma is the second most common skin cancer after BCC and like other forms of skin cancer is increasing in age-specific incidence.
Aetiology
The risk factors for squamous cell carcinoma are similar to basal cell carcinoma: namely, exposure to ultraviolet radiation, pale skin, or rarely exposure to other carcinogenic factors such as X irradiation or arsenic injection. Squamous cell carcinomas may arise in long-standing areas of inflammation such as around a chronic cutaneous ulcer, or in patients with scarring genetic syndromes of the skin such as dystrophic epidermolysis bullosa in which up to 50% of patients may develop squamous cell carcinoma. Squamous cell carcinomas also show a greatly elevated incidence in individuals who are receiving chronic immunosuppression following organ transplantation (particularly kidney and heart) and in individuals who have been treated with large amounts of PUVA therapy.
Clinical features
Squamous cell carcinoma is a proliferative tumour that has a history of growth over a few months. Varying clinical presentations include keratotic nodules (see Fig. 21.35), exophytic erythematous nodules, infiltrating firm tumours and ulcers with an indurated edge. Histology also varies from well-differentiated tumours to anaplastic. SCCs of the lip behave more aggressively and show a greater frequency of metastasis. It is often said that SCC of the pinnae may also be more aggressive, although whether this reflects inadequate primary treatment is not clear.
Figure 21.35 Squamous cell carcinoma. A warty nodule with induration of the adjacent skin.
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Management
As with basal cell carcinoma a number of modalities may be used including aggressive curettage and cautery, excision or radiotherapy. In general excision with assessment of adequacy of margins is the preferred option because of the definite risk of metastasis. Surgical excision with a 3-4 mm margin has a cure rate of 90% or more. As with BCC, radiotherapy can be used in selected cases.
MALIGNANT MELANOMA
Malignant melanoma, like other forms of skin cancer, has shown an increase in incidence over recent decades. This increase persists even when changes in the age structure of the population are accounted for. Melanomas show a significant mortality with a case fatality of approximately 20-25%. Therapy for metastatic melanoma is extremely poor and therefore interest has concentrated on primary prevention and early detection. The main risk factors for melanoma are ultraviolet radiation exposure, pale skin, naevi number and family history. Fewer than 10% of melanomas occur in the context of a significant family history but within this group there are rare kindreds in whom the lifetime risk of melanoma may approach 50%. The body site distribution of melanoma is different from that of other skin tumours, suggesting that some aspect of the relation between ultraviolet radiation and tumour occurrence is as yet not fully understood. The increase in melanoma incidence with ambient ultraviolet radiation exposure is also not as steep as that seen for squamous cell carcinoma; for example, a threefold increase in environmental ultraviolet radiation exposure may increase squamous cell carcinoma rates by a factor of 9 but melanoma by a factor of 3.
Clinical features
The classification of invasive malignant melanomas is shown in
21.27 CLASSIFICATION OF CUTANEOUS MALIGNANT MELANOMA
Type of invasive melanoma Presence of preceding in situ/radial growth phase
Superficial spreading +
Lentigo maligna +
Nodular -
Acral lentiginous +
Figure 21.36 Superficial spreading melanoma. The radial growth phase was present for about 3 years before the invasive amelanotic nodule developed within it. Note the irregular outline, asymmetrical shape and different hues, including depigmented areas signifying spontaneous regression.
Two-thirds of invasive melanomas are preceded by a superficial and radial growth phase characterised by an expanding, irregularly pigmented macule or plaque. Its margin is usually irregular with reniform projections (see Fig. 21.36). Lentigo maligna (in situ changes of malignancy only) and lentigo maligna melanoma occur most often on the exposed skin of the elderly. A speckled macular lentigo maligna may have been present for many years before a nodule of invasive melanoma appears within it. The in situ phase of superficial spreading melanoma, the most common type in Caucasians, seldom lasts for longer than 2 years, usually shows much colour variation and is often palpable. Acral lentiginous melanoma occurs on the palms and soles and the absolute incidence rates are the same in all populations; by contrast, the rates at other body sites are low in Blacks and in the Chinese and Japanese. These facts suggest that this variant of melanoma is not related to ultraviolet radiation exposure. Nodular melanoma develops as a pigmented nodule with no preceding in situ phase. All changing pigmented lesions deserve careful examination remembering the 'ABCDE' features of malignant melanoma (see p. 1057). About 30-50% of melanomas appear to develop in a preceding melanocytic naevus (see p. 1057). A change in any naevus should raise suspicion of malignant transformation.
True amelanotic melanomas occur but are rare; flecks of pigmentation can usually be seen with a lens. Subungual melanomas present as painless, expanding areas of pigmentation under a nail and usually involve the nail fold.
The clinical stages of malignant melanoma are shown in
The diagnosis should be established by local excision biopsy of the suspected lesion.
Management
21.28 CLINICAL STAGES OF MALIGNANT MELANOMA
Stage I Primary lesion only
Stage II Regional nodal disease
Stage III Distant disease (nodal or visceral)
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Surgical excision is usually required although very rarely radiotherapy may play a role. The extent of normal tissue that needs to be removed around a melanoma remains a subject for debate. Most would agree that a clear margin needs to be present so that there is little doubt that the tumour is fully excised; the deeper the tumour, the more caution is warranted. The majority of tumours can be excised without the need for grafting. The role of local lymph node dissection in the absence of evidence of tumour spread is uncertain. Palpable local nodes in stage II patients should be removed by block dissection. Chemotherapy is only curative exceptionally but may play an important palliative role in those with stage III disease or earlier. Interferon alpha may have a role in individuals at high risk of metastasis.
EBM
SURGERY FOR MELANOMA-is there an optimal margin for primary excision of melanoma of different breslow thicknesses?
'RCTs have found that more radical surgery (4-6 cm excision margins) provides no greater benefit in reducing local recurrence or increasing survival than less radical surgery (1-2 cm excision margins). Recommended excision margins for malignant melanoma depend on their Breslow thickness: melanomas <> 1 mm in depth need a 2 cm margin.'
Roberts DL, Anstey AV, Barlow RJ, et al. on behalf of the Melanoma Study Group.
Prognosis
There are a number of useful prognostic indicators in melanoma. Those with clinical stage III disease fare least well (less than 10% survive 2 years); those with stage I disease have a 70% chance of surviving 5 years. The thickness of the tumour (measured microscopically by Breslow's method, which gives the distance between the granular cell layer and the deepest part of the tumour) is a reliable predictor of the prognosis for patients with stage I disease. The prognosis is excellent for those with tumours less than 1 mm thick (over 90% survive 5 years), but becomes less good with thicker tumours. The 5-year survival of patients with tumours greater than 3.5 mm thick is about 50%. In general, females fare better than males and tumours at certain sites (e.g. lower leg) are less aggressive.
CUTANEOUS T-CELL LYMPHOMA (MYCOSIS FUNGOIDES)
In contrast to B-cell lymphomas which usually present as sudden focal skin tumours, cutaneous T-cell lymphoma develops slowly over many years from a plaque stage often resembling psoriasis through to nodules and then a systemic stage. The diagnosis of cutaneous T-cell lymphoma requires a high index of suspicion particularly in patients who are deemed to have unusual forms of eczema or psoriasis and who failed to respond to treatment. The treatment of individuals with cutaneous T-cell lymphoma is, however, symptomatic with no evidence that the various modalities of treatment alter prognosis. Study of these individuals is hampered by difficulties in disease nosology, disease heterogeneity and the long natural history, sometimes over 20 or 30 years.
In the early stages of cutaneous T-cell lymphoma either systemic or local corticosteroids may be indicated; alternatively, PUVA or TL01 phototherapy may be employed. However, once lesions have moved beyond the plaque stage other modalities, including electron beam radiation or systemic antilymphoma regimens, may be required. Such patients require careful collaboration between dermatologists, pathologists and haematological oncologists.
ISSUES IN OLDER PEOPLE
SKIN TUMOURS
Seborrhoeic warts are benign skin tumours that occur predominantly in the elderly. They may cause quite distressing pruritus.
Pre-malignant lesions, including actinic keratoses and intra-epidermal carcinomata, occur most frequently in the elderly.
Cutaneous squamous cell carcinomata occur most commonly in the elderly, usually on a background of sun-damaged skin.
Lentigo maligna (in situ melanoma) and lentigo maligna melanoma are the most usual melanomas that occur in the elderly. They are generally seen on the face or other sun-exposed sites and often present as a long-standing pigmented lesion that is changing in colour, shape or size.
pages 1089 - 1095
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > DERMATOLOGICAL SURGERY
DERMATOLOGICAL SURGERY
The workload of dermatologists has changed considerably over the last 20-30 years with an increase in the number of lesions compared with rashes. In part this is explained by changes in the epidemiology of skin cancer, referral changes and the increased demand for cosmetic removal of many lesions. If one includes the assessment of patients with potential skin cancer and their follow-up, dermatologists might spend anywhere between 20 and 90% of their time on surgical aspects of the discipline (depending on a practitioner's particular interests).
There are a large number of surgical procedures that can mostly be carried out under local anaesthetic. The choice of procedure is important; for example, inappropriate excision of lesions such as seborrhoeic keratoses results in scar formation when they should have been treated with cryosurgery or curettage.
BIOPSY
Skin biopsies are usually taken under local anaesthetic but a general anaesthetic may be necessary in some children. It is best to select an early or typical lesion on a non-exposed site. An ellipse biopsy or in certain instances a punch biopsy that removes a cylindrical portion of skin may be used. Learning which part of a rash to biopsy, and whether an ellipse or punch biopsy will suffice, comes with experience but is often critical. A common reason for unhelpful or even misleading histology is biopsy of an inappropriate part of the rash. For instance, biopsies of secondarily excoriated lesions, even in the clinical context of a blistering disease, will often be unhelpful.
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Sutures are removed depending on site and other factors (i.e. 5-7 days for the face and 10-14 days for the back). Certain body sites are associated with particular risks. Thus biopsies on the upper torso of young persons are likely to result in keloids, biopsies over the scapula tend to leave unsightly scars, and biopsies on the lower legs of elderly people are at risk of poor healing and ulceration with a resulting high morbidity. The statement that there is no such thing as 'minor surgery' remains an instructive maxim.
CRYOTHERAPY
Cryotherapy is usually performed in one of two ways: either as an application of liquid nitrogen with a cotton wool bud or using a jet gun. Liquid nitrogen can be used to treat a wide range of lesions from viral warts through to actinic keratoses and invasive tumours such as basal or squamous cell carcinomas. The cosmetic effects and morbidity are variable. If neoplasia is suspected it may be wiser to carry out an incisional biopsy first. In general superficial or 'stuck-on' lesions will require a less intense therapy and are more acceptable to the patient. Melanocytic naevi should not be treated with liquid nitrogen.
CURETTAGE
Curettage refers to scraping with a small, spoon-shaped implement (curette) across the lesion, not only as a definitive treatment but also as a way of obtaining histological material. Naturally the histological material may be compromised in the sense that epidermal structures are over-represented and the anatomy of the lesion as it descends into the dermis is not preserved. It may therefore be difficult to determine whether a lesion with intraepidermal dysplasia shows any evidence of invasion (i.e. is a squamous cell carcinoma rather than an intraepidermal carcinoma or actinic keratosis). Curettage is, however, suitable for many seborrhoeic keratoses, actinic keratoses or areas of intraepidermal carcinoma. Some superficial basal cell carcinomas are well treated with curettage but some variants such as the morphoeic forms should be treated with expert surgical excision.
SURGICAL EXCISION
The advantage of surgical excision for the removal of tumours or suspected tumours is that it provides adequate histological material for examination and evidence of excision margins. Depending on body site, there are a range of procedures to minimise the resulting defect, including undermining, Z-plasties, flaps and grafts. On sun-exposed sites in many patients, particularly the elderly, healing by secondary intention can lead to a surprisingly good result.
LASER THERAPY
Laser therapy exploits the fact that certain pigments such as melanin or blood absorb certain wavelengths of electromagnetic radiation more readily than others. A variety of lasers have been produced which allow relatively selective destruction of particular structures containing the absorbing pigment. By concentrating the light into short pulses the damage is restricted to a particular area. The choice of laser for a particular lesion requires specialist knowledge but because melanin and blood have overlapping spectrums the choice generally focuses on minimising 'collateral' damage. Some lasers are better for dealing with primarily vascular lesions such as port wine stains, while others are more useful for pigmented lesions or for destruction of exogenous pigments such as tattoo pigments or drug deposits (e.g. minocycline).
By contrast with the vascular laser the carbon dioxide laser emits infrared light which is absorbed by tissue water. When crudely used the carbon dioxide laser is therefore similar to a diathermy but the depth of lesion can be controlled to a fraction of a millimetre; the procedure can therefore be useful for resurfacing and for face lifts. A general anaesthetic is required for such procedures.
MISCELLANEOUS PROCEDURES
Keloids may require corticosteroid injections after freezing or excision. Silicone sheeting also may flatten keloids although the mechanism is obscure. Scars and wrinkles can be filled using collagen or silicone. Liposuction can be used to remove fat, and tissue folds around the eyes can be easily excised. Small acne scars can be excised and larger, more superficial lesions treated with a carbon dioxide laser. Areas of depigmentation in vitiligo or piebaldism may be treated with epidermal grafts from normal skin. Photodynamic therapy refers to the application of porphyrins to skin followed by exposure to light, allowing controlled destruction of some tumours such as superficial basal cell carcinomas. It appears that tumours absorb more of the topically applied porphyrin than normal skin and so permit some targeting of damage.
pages 1095 - 1096
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Home > 2 SYSTEM-BASED DISEASES > 21 Skin disease > THE SKIN IN SYSTEMIC DISEASE
THE SKIN IN SYSTEMIC DISEASE
Skin reactions can be linked with an underlying systemic disease in a number of ways, as shown in
NEUROFIBROMATOSIS: TYPE 1
Light brown (café au lait) macules can be seen in healthy people and are also a feature of:
Albright's syndrome (polyostotic fibrous dysplasia), where the margins are very irregular
Bloom's syndrome.
The skin markers of von Recklinghausen's neurofibromatosis include scattered and discrete café au lait macules, axillary freckling and a variable number of cutaneous neurofibromata (see p. 1206). The tumours may be small and superficial, or large and deep. Small circular pigmented hamartomas of the iris (Lisch nodules) appear in early childhood.
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21.29 SKIN REACTIONS IN SYSTEMIC DISEASE
Part of a multisystem disease
Genetically determined (e.g. neurofibromatosis and tuberous sclerosis)
Xanthomas
Amyloidosis
Porphyria
Sarcoidosis
A non-specific and not invariable reaction pattern to a systemic disease
Urticaria
Erythema multiforme
Annular erythemas
Erythema nodosum
Pyoderma gangrenosum
Sweet's syndrome
Generalised pruritus
A sign of internal malignancy
Dermatomyositis
Generalised pruritus
Acanthosis nigricans
Superficial thrombophlebitis
A sign of internal organ failure
Liver-generalised pruritus, pigmentation, spider naevi and palmar erythema
Kidney-generalised pruritus and pigmentation
Pancreas (diabetes mellitus)-necrobiosis lipoidica
A result of a common genetic link with the systemic disorder
Dermatitis herpetiformis and gluten-sensitive enteropathy
Psoriasis and some types of arthropathy
The cause of the systemic disease
Exfoliative dermatitis causing high-output cardiac failure
A result of treatment of the systemic disease
Drug eruptions
NEUROFIBROMATOSIS: TYPE 2
See page 1206.
SEGMENTAL NEUROFIBROMATOSIS: TYPE 5
The cutaneous features of café au lait macules and neurofibromata are found in a dermatomal distribution. This is due to mosaicism of the NF-1 gene.
TUBEROUS SCLEROSIS
This is an autosomal dominant condition with hamartomas affecting many systems.
The classic triad of clinical features comprises mental retardation, epilepsy and skin lesions but not all are invariably present. The skin signs include small white oval (ash leaf) macules, pink or yellowish papules on the centre of the face (adenoma sebaceum), peri- and subungual fibromata, and connective tissue naevi (cobblestone-like plaques at the base of the spine, sometimes called shagreen patches).
XANTHOMAS
These deposits of fatty material in the skin, subcutaneous fat and tendons may be the first clue to primary or secondary hyperlipidaemia (see p. 308).
Various clinical patterns are seen which correlate well with the underlying cause. They include:
eruptive yellow papules on the buttocks (eruptive xanthomas)
yellowish macules or plaques (plane xanthomas)
small yellow-grey plaques around the eyes (xanthelasma palpebrarum)
nodules over the elbows and knees (tuberous xanthomas)
subcutaneous nodules attached to tendons, especially those on the dorsal aspect of the fingers and the Achilles tendons (tendinous xanthomas).
When xanthomas are detected the fasting blood lipids and the electrophoretic pattern of plasma lipoproteins must be measured, though abnormalities will not always be detected.
AMYLOIDOSIS
This is described on page 327. Skin lesions are uncommon in systemic amyloidosis secondary to rheumatoid arthritis or other chronic inflammatory diseases.
Deposits of amyloid in the skin, often appearing as waxy plaques around the eyes, are prominent in primary systemic amyloidosis and in amyloid associated with multiple myeloma. 'Pinch purpura', appearing where the skin is traumatised, is due to amyloid infiltration of blood vessels and may also be a striking feature.
PORPHYRIA
The classification and metabolic abnormalities of the porphyrias are found on page 325. Certain porphyrias can affect the skin.
Porphyria cutanea tarda
Figure 21.37 Cutaneous hepatic porphyria. Recent skin fragility and blistering on the backs of the fingers.
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This porphyria usually starts in adulthood and can be inherited and precipitated by alcohol, iron overload, oestrogens, hepatitis C and HIV disease. Some cases are acquired and are associated with underlying liver disease such as cirrhosis and hepatic tumours. The cutaneous features are increased skin fragility, blistering (see Fig. 21.37), erosions and milia occurring on light-exposed areas such as the backs of the hands. Facial hypertrichosis and hyperpigmentation may also be seen. Diagnostic tests for porphyria are detailed on pages 325-327.
Erythropoietic protoporphyria
This is a rare porphyria that starts in childhood, with burning and pain on light-exposed areas. Scars occur, particularly on the nose. Examination of the red cells, plasma and stool for raised protoporphyrins is confirmatory.
Variegate porphyria
Cutaneous features are similar to those of porphyria cutanea tarda. Systemic features are the same as those of acute intermittent porphyria (see p. 327).
Hereditary coproporphyria
Around 30% of these patients are photosensitive. Systemic features are the same as those of acute intermittent porphyria.
Pseudoporphyrias
Sun-bed usage, non-steroidal anti-inflammatory drugs (particularly naproxen) and renal failure can give rise to skin lesions that mimic the photosensitive porphyrias, particularly porphyria cutanea tarda. The pathogenesis is as yet unclear.
SARCOIDOSIS
This is covered in detail on page 552.
Skin lesions are seen in about one-third of patients with systemic sarcoidosis. The clinical features include erythema nodosum, granulomatous deposits in long-standing scars, dusky infiltrated plaques on the nose and fingers (lupus pernio), and scattered brownish-red, violaceous or hypopigmented papules or nodules which vary in number, size and distribution.
Integration link: Immune complex in erythema multiforme
Taken from Robbins & Cotran's Pathologic Basis of Disease 7e
ERYTHEMA MULTIFORME
As its name implies, this is a reaction pattern of multiform erythematous lesions. The precipitating factor may not be found in some cases but attacks are provoked by the factors listed in
Clinical features
21.30 PROVOKING FACTORS IN ERYTHEMA MULTIFORME
Herpes simplex infections
Other viral infections, e.g. orf, and mycoplasma
Bacterial infections
Drugs, especially sulphonamides, penicillins and barbiturates
Internal malignancy or its treatment with radiotherapy
The multiform erythematous lesions may be urticaria-like and some have obvious 'bull's-eye' or 'target' lesions. Blisters may be seen in the centre or around the edges of the lesions. In some cases blisters dominate the picture; the Stevens-Johnson syndrome is severe bullous erythema multiforme with emphasis on mucosal involvement including the mouth, eyes and genitals, with constitutional disturbance.
Management
Severe cases are usually managed with tapering courses of systemic corticosteroids after treatment, if possible, of the primary cause.
ERYTHEMA NODOSUM
This characteristic reaction pattern is due to a vasculitis in the deep dermis and subcutaneous fat. It may be provoked by the factors listed in
21.31 PROVOKING FACTORS IN ERYTHEMA NODOSUM
Infections
Bacteria (streptococci, tuberculosis, brucellosis and leprosy), viruses, mycoplasma, rickettsia, chlamydia and fungi
Drugs
o e.g. Sulphonamides and oral contraceptives
Systemic disease
o e.g. Sarcoidosis, ulcerative colitis and Crohn's disease
Clinical features
Painful, palpable, dusky blue-red nodules are most commonly seen on the lower legs. Malaise, fever and joint pains are common. The lesions resolve slowly over a month, leaving bruise-like marks in their wake.
Management
The underlying cause should be determined and treated. Bed rest and oral non-steroidal anti-inflammatory drugs may hasten resolution. Tapering systemic corticosteroid courses may be required in stubborn cases.
PYODERMA GANGRENOSUM
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Figure 21.38 Pyoderma gangrenosum. A large indolent ulcer in a patient with rheumatoid arthritis. Note healing in one part.
Pyoderma gangrenosum (PG) predominantly occurs in adults between the ages of 25 and 54 years. It is an eruption that starts as an inflamed nodule or pustule which breaks down centrally and rapidly progresses to an ulcer with an indurated or undermined purplish or pustular edge (see Fig. 21.38). Lesions may be single or multiple and are classified as ulcerative, pustular, bullous and vegetative. Although PG may arise in the absence of any underlying disease, it is often associated with a systemic disease, such as inflammatory bowel disease, arthritis (both rheumatoid arthritis and seronegative arthropathies), immunodeficiency and immunosuppression including HIV disease, monoclonal gammopathies and leukaemia. The management of PG includes investigations for possible associated systemic disease. There are no diagnostic features on biopsy and therefore the diagnosis is primarily clinical. Local therapy includes pain relief, prevention of secondary bacterial infection and dressings. Systemic therapy includes oral steroids in a tapering dose, dapsone 50-150 mg/day, minocycline 100 mg/day, sulfasalazine (4-6 g daily), and ciclosporin (5 mg/kg). Once the patient is clear of disease, recurrences are only intermittent.
ACANTHOSIS NIGRICANS
This is a velvety thickening and pigmentation of the major flexures, particularly the axillae. There are several types of acanthosis nigricans. The most common form is a weight-dependent mild acanthosis nigricans (obesity-associated). When the patient loses weight the cutaneous features regress. Secondly, acanthosis nigricans can be associated with various syndromes, some of which have insulin resistance as a feature. Finally, acanthosis nigricans can be associated with malignancy, particularly gastric (60%). Pruritus is a feature of malignancy-associated acanthosis and regression occurs after the tumour is excised. Acanthosis nigricans sometimes recurs with metastatic disease.
NECROBIOSIS LIPOIDICA
This condition is important to recognise because of its association with diabetes mellitus. Less than 1% of diabetics have necrobiosis, but more than 85% of patients with necrobiosis will have or will develop diabetes.
Figure 21.39 Necrobiosis lipoidica. An atrophic yellowish plaque on the skin of a diabetic.
Typically, the lesions appear as shiny, atrophic and slightly yellow plaques on the shins (see Fig. 21.39). Underlying telangiectasia is easily seen. Minor knocks may precipitate slow-healing ulcers. No treatment is very effective. Topical and intralesional steroids are used, as is long-term PUVA.
GRANULOMA ANNULARE
This is a common cutaneous condition of uncertain aetiology; any association with diabetes is now thought to be coincidental. Dermal nodules occur singly or in an annular configuration. They are asymptomatic but cause consternation because they commonly occur on highly visible sites such as the hands and feet. Histologically, palisading granulomata are found in the dermis. Intralesional steroids can be helpful, but the natural history is spontaneous resolution after a few months to a couple of years.
DRUG ERUPTIONS
Cutaneous drug reactions are common and almost any drug can cause them. Drug reactions may reasonably be included in the differential diagnosis of most skin diseases. Although the mechanisms are poorly understood, drug eruptions may be classified as shown in
Figure 21.40 Drug eruption. A weird but symmetrical erythematous scaly rash with a distribution suggesting a degree of photosensitivity. The rash persisted until the recently prescribed sulphonylurea was withdrawn.
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21.32 DRUG ERUPTIONS AND THEIR MECHANISMS
Mechanism Example
Non-immunological (non-allergic)
Unwarranted pharmacological effect Striae due to corticosteroids; mouth ulcers due to methotrexate
Drug overdosage or failure to metabolise or excrete the drug Morphine rashes in patients with liver disease
Drug interaction Warfarin toxicity when coadministered with aspirin or phenylbutazone
Idiosyncratic reaction (an odd reaction which may be genetically Drug-induced variegate porphyria
determined and is peculiar to an individual)
Phototoxic reaction Chlorpromazine-induced light reactions
Altered skin ecology Tetracyclines causing vaginal candidiasis
Exacerbation of pre-existing skin condition Lithium and ß-adrenoceptor antagonist (ß-blocker) worsening of psoriasis
Immunological (allergic)
Immediate hypersensitivity Penicillin-induced urticaria
Immune complex reaction Drug-induced vasculitis or erythema multiforme
Delayed hypersensitivity Drug-induced exfoliative dermatitis or photo-allergic reactions
21.33 DRUG ERUPTIONS AND SOME DRUGS WHICH MAY CAUSE THEM
Name of reaction pattern Clinical features Drugs which commonly cause reaction
Toxic erythema Erythematous plaques
Morbilliform, sometimes with urticarial or erythema multiforme-like elements Antibiotics (especially ampicillin)
Sulphonamides, thiazide diuretics, phenylbutazone, para-aminosalicylic acid (PAS)
Urticaria Itchy weals, sometimes accompanied by angio-oedema Salicylates, codeine, antibiotics, dextran and ACE inhibitors
Erythema and scaling Small, scaly, pink papules to large, scaly, red papules Antibiotics (especially penicillins and sulphonamides), anticonvulsants, ACE inhibitors, barbiturates, gold and penicillamine
Allergic vasculitis Painful, palpable purpura followed by necrotic ulcers Sulphonamides, phenylbutazone, indometacin, phenytoin and oral contraceptives
Erythema multiforme Target-like lesions and bullae on the extensor aspects of the limbs Sulphonamides, phenylbutazone and barbiturates
Purpura Widespread purpura not due to thrombocytopenia or a coagulation defect Thiazides, sulphonamides, phenylbutazone, sulphonylureas, barbiturates and quinine
Bullous eruptions May be associated with erythema and purpura
May occur at pressure sites in drug-induced coma Barbiturates, penicillamine, nalidixic acid
Exfoliative dermatitis Universal redness and scaling, shivering Phenylbutazone, para-aminosalicylic acid (PAS), isoniazid and gold
Fixed drug eruptions Round, erythematous and sometimes bullous plaques develop at the same site every time the drug is given
Pigmentation left in wake Tetracyclines, quinine, sulphonamides and barbiturates
Acneiform eruptions Rash resembles acne (see p. 1081) Lithium, oral contraceptive, androgenic or glucocorticoid steroids, antituberculosis and anticonvulsant drugs
Toxic epidermal necrolysis Rash resembles that of scalded skin (see Fig. 21.41) Barbiturates, phenytoin, phenylbutazone and penicillin
Hair loss Diffuse Cytotoxic agents, acitretin, anticoagulants, antithyroid drugs and oral contraceptives
Hypertrichosis Diazoxide, minoxidil and ciclosporin A
Photosensitivity Rash limited to exposed skin Thiazides, tetracyclines, phenothiazines, sulphonamides, nalidixic acid and psoralens
Pigmentation Irregular melanin pigmentation on face
Slate-grey colour of exposed skin
Diffuse yellow coloration of skin
Streaky depigmentation of hair Oral contraceptives
Phenothiazines
Mepacrine
Chloroquine
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Clinical features
The most common types of drug eruption and their cause are listed in
Investigations
There are no specific investigations which help. Prick tests and in vitro tests for allergy are too unreliable for routine use. Readministration, as a diagnostic test, is usually unwise unless the reaction is mild and there is no suitable alternative drug.
Figure 21.41 Toxic epidermal necrolysis. In this case it was due to an anticonvulsant.
21.34 DIAGNOSTIC CLUES TO DRUG ERUPTIONS
Past history of reaction to suspected drug
Introduction of suspected drug a few days before onset of rash
Recent prescription of a drug commonly associated with rashes (e.g. penicillin, sulphonamide, thiazide, allopurinol, phenylbutazone)
A symmetrical eruption which may fit with a well-recognised pattern caused by one of the current drugs
Management
The first step is to withdraw the suspected drug(s). This may not be easy, or even possible, if there is no alternative available. The decision will depend on many factors, including the severity and nature of the drug reaction, its potential reversibility and the probability that the drug caused the reaction. Supportive treatment with antihistamines or a tailored course of systemic corticosteroids may be indicated, depending on the type of skin reaction. The emergency treatment of anaphylactic shock is described on page 201.
FURTHER INFORMATION
Barker J. Psoriasis. J R Coll Physicians Lond 1997; 31:238-240. Medline Similar articles
Farr PM. Ultraviolet phototherapy [Review] [25 refs]. J R Coll Physicians Lond 1997; 31:250-253. Medline Similar articles
Freedberg IM, Eisen AZ, Wolff K, et al. Dermatology in internal medicine. In: Freedberg IM,
Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med 1999; 340:1341-1348. Medline Similar articles Full article
Greaves MW, Wall PD. Pathophysiology of itching. Lancet 1997; 349:133. Medline Similar articles
Greaves MW, Wall PD. Pathophysiology and clinical aspects of pruritus. In: Freedberg IM,
Hanifin JM, Tofte SJ. Update on therapy of atopic dermatitis. J Allergy Clin Immunol 1999; 104:S123-S125. Medline Similar articles
Kanj LF, Wilking SV, Phillips TJ. Pressure ulcers. J Am Acad Dermatol 1998; 38:517-536. Medline Similar articles
Larsen FS. The epidemiology of atopic dermatitis. In: Burr ML, ed. Epidemiology of clinical allergy.
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