Dermatology - Clinical features, Diagnosis, Treatment

INTRODUCTION

Skin diseases are extremely common, although their exact prevalence is unknown. There are over 1000 different entities described, but two-thirds of all cases are the result of fewer than 10 conditions. In developing countries infectious diseases such as tuberculosis, leprosy and onchocerciasis are common, whereas in developed countries inflammatory disorders such as acne and eczema are common. Some conditions may be part of normal development, e.g. acne; others may be inherited, e.g. Ehlers-Danlos syn-drome; still others are part of a systemic disease, e.g. the rash of systemic lupus erythematosus. The most common skin conditions and those which can be fatal, e.g. malignant melanoma, pemphigus, will be described in this chapter. The structure and functions of the skin are summarized in Figure 18.1.

SKIN AND SOFT TISSUE INFECTIONS

Infections of the skin and soft tissues beneath are common. The majority are caused by the Gram-positive cocci, Staphylococcus aureus (part of the normal microflora of the skin) and Streptococcus pyogenes. Sometimes infection is introduced by an animal bite or a penetrating foreign body and in these cases more unusual organisms can be found.

Cellulitis is a spreading infection involving the deep subcutaneous layer and is the most common skin infection leading to hospitalization. It falls into a continuum of skin infections that includes impetigo (superficial vesiculo-pustular infection in children), folliculitis (multiple erythematous lesions with a central pustule localized to the hair follicles) and carbuncles (abscesses in the subcutaneous tissue that drain via hair follicles). The last three infections are usually caused by Staph. aureus.

Cellulitis and erysipelas

Cellulitis preferentially involves the lower extremities. Risk factors include lymphoedema, site of entry (leg ulcer, trauma, presence of tinea pedis

Fig. 18.1 Structure and function of the skin.

■ Physical barrier against friction and shearing forces

■ Protection against infection, chemicals, ultraviolet radiation

■ Prevention of excessive water loss or absorption

■ Ultraviolet-induced synthesis of vitamin D

■ Temperature regulation

■ Sensation (pain, touch, temperature)

■ Antigen presentation/immunological reactions/wound healing.

- ‘athlete's foot'), venous insufficiency, leg oedema and obesity. It is usually caused by a streptococcus, rarely a staphylococcus, and sometimes com-munity acquired MRSA. Erysipelas is the term used for a more superficial infection, often on the face. In the majority of cases it is caused by group A beta-haemolytic streptococci.

Clinical features

Cellulitis presents as erythema in the involved area, with poorly demarcated margins, swelling, warmth and tenderness. There may be a low-grade fever. In erysipelas the area is raised and erythematous and sharply demarcated from normal skin.

Diagnosis

The diagnosis is clinical. Patients should also be evaluated for risk factors for cellulitis (see above) which may prevent recurrence if treated. In the majority of cases, culturing blood or skin aspirates does not reveal a patho-gen. Deep venous thrombosis is the main differential diagnosis.

Treatment

Treatment is with phenoxymethylpenicillin and flucloxacillin (or erythromycin if penicillin allergic, all 500 mg four times daily). If disease is widespread treatment is given intravenously for 3-5 days followed by at least 2 weeks of oral therapy. If cellulitis is recurrent, low-dose antibiotic prophylaxis (e.g. phenoxymethylpenicillin 500 mg twice daily) is given to prevent lymphatic damage caused by each attack.

Necrotizing fasciitis

This is a deep-seated infection of the subcutaneous tissue that results in a fulminant and spreading destruction of fascia and fat but may initially spare the skin. There is a high mortality. Spreading erythema, underlying crepitus and systemic toxicity (out of proportion to the skin findings) follow severe pain at the site of infection. Type 1 is caused by a mixture of aerobic and anaerobic bacteria and is usually seen following abdominal surgery or in diabetics. Type 2, caused by group A streptococci, occurs in previously healthy patients. Treatment is urgent surgical debridement and aggressive broad spectrum antibiotic treatment with benzylpenicillin and clindamycin (+metronidazole in type 1).

Gas gangrene

This is a deep tissue infection with Clostridium spp., especially C. perfringens and follows contaminated penetrating wounds. Toxins produced by the organism cause muscle necrosis with severe pain and tissue swelling, gas production and sepsis with rapid progression to shock. Treatment is urgent surgical debridement and intravenous antibiotics. Clostridial species are sen-sitive to a combination of benzylpenicillin and clindamycin. However, it may be difficult to differentiate gas gangrene from necrotizing fasciitis and treat-ment is initially with broad spectrum antibiotics (see above).

Fungal infections

Dermatophytes is the common label for the three types of fungus that cause infections of the outer layer of skin, hair and nails. The main genera respon-sible are Trichophyton, Microsporum and Epidermophyton. All are spread by direct contact from other humans or from infected animals or indirect contact with exfoliated skin or hair; communal showers, swimming baths and the sharing of towels or sportswear aids transmission. Types of dermatophyte infections are:

■ Tinea corporis - ringworm of the body usually presents with slightly itchy, asymmetrical, scaly patches which show central clearing and an advancing, scaly, raised edge.

■ Tinea faciei - ringworm of the face often arises after the use of topical steroids. It tends to be more erythematous and less scaly than trunk lesions.

■ Tinea cruris - ringworm of the groin presents as well demarcated red plaques with an arc-like border extending down the upper thigh.

■ Tinea pedis - athlete's foot is confined to the toe clefts where the skin is white, macerated and fissured or is more diffuse causing a scaly erythema of the soles spreading on to the sides of the foot.

■ Tinea manuum - ringworm of the hands presents with a diffuse ery-thematous scaling of the palms with variable skin peeling and skin thickening.

■ Tinea capitis - scalp ringworm is commoner in children. There is a spectrum from mild diffuse scaling with no hair loss to circular scaly patches with associated alopecia and broken hairs.

■ Tinea unguium - ringworm of the nails presents as asymmetrical whiten-ing or yellowish black discoloration of one or more nails with nail plate thickening and crumbly white material under the nail.

A host immune response in these infections is associated with the appear-ance of vesicles and pustules and sometimes an exudate.

Diagnosis is clinical and by microscopy of scrapings from skin, hair or nail. Fungal culture medium is used to identify the species. Localized ringworm is treated with topical antifungal cream (clotrimazole, miconazole, terbinafine or amorolfine applied three times daily for 1-2 weeks). Oral antifungal therapy (itraconazole 100 mg daily, terbinafine 250 mg daily for 1-2 months) is used to treat more widespread infection.

Candida albicans

This is a yeast that is sometimes found as part of the body's flora, especially in the gastrointestinal tract. It takes hold in the skin where there is a suitable warm moist environment, such as in the groin, interdigital clefts of the toes and around the nails. Infection can mimic ringworm but in the groin there are small circular areas of erythema in front of the advancing edge (satellite lesions). Treatment of localized infection is with topical antifungal cream or systemic antifungal therapy (itraconazole 100 mg daily for 3-6 months) for nail infection. Candida can also infect mucosal surfaces of the mouth or genital tract particularly in patients taking antibiotics (due to suppression of protective bacterial flora) or in immunosuppressed patients where infection can also be wide-spread and life-threatening.

COMMON SKIN CONDITIONS

Acne vulgaris

This is a common condition occurring in adolescence and frequently continu-ing into early and middle adult life.

Clinical features

Increased sebum production by sebaceous glands, blockage of pilosebaceous units, follicular epidermal hyperproliferation and infection with Propionibac-terium acnes all contribute to produce the clinical features of open com-edones (blackheads) or closed comedones (whiteheads), inflammatory papules and pustules. Other features that may be present include hyper-trophic or keloidal scarring, and hyperpigmentation, which occurs predomi-nantly in patients with darker complexions. There is a tendency for spontaneous improvement over a number of years.

Management

Acne should be actively treated to avoid unnecessary scarring and psycho-logical distress. The aims of treatment are to decrease sebum production, reduce bacteria, normalize duct keratinization and decrease inflammation. There are a variety of approaches, the choice of which depends on the sever-ity of the disease. Regular washing with acne soaps to remove excess grease is helpful (normal soaps can be comedogenic). ‘Picking' should be discouraged.

First-line therapy Topical agents such as keratolytics (benzoyl peroxide), topical retinoids (tretinoin or isotretinoin), retinoid-like agents (adapalene) and antibiotics for inflammatory acne (erythromycin, clindamycin) are used in mild disease.

Second-line therapy Low-dose oral antibiotics, e.g. oxytetracycline, minocycline, erythromycin, trimethoprim, often help but must be given for 3-4 months. Hormonal treatment with cyproterone acetate 2 mg/ ethinylestradiol 35 μg (co-cyprindol) is useful in women if there is no con-traindication to oral contraception.

Third-line therapy with an oral retinoid (isotretinoin or acitretin) is given if the above measures fail, there is nodulocystic acne with scarring or there is severe psychological disturbance. Retinoids are synthetic vitamin A ana-logues that affect cell growth and differentiation. Although effective they are highly teratogenic and are absolutely contraindicated during pregnancy. All women of childbearing age should have a pregnancy test and contraceptive advice prior to treatment and pregnancy testing repeated monthly during the

4-month course. Over 90% of individuals will respond to therapy and 65% of people will obtain a long-term ‘cure'.

Psoriasis

Psoriasis is a common chronic hyperproliferative disorder characterized by the presence of well-demarcated red scaly plaques over extensor surfaces such as the elbows and knees, and in the scalp. There is an equal sex incidence with age of onset occurring in two peaks: 16-22 years and 55-60 years.

Aetiology

The condition is polygenic (nine genetic psoriasis susceptibility loci have been identified) but is dependent on certain environmental triggers (infection with group A Streptococcus, drugs such as lithium, ultraviolet light, high alcohol use and stress). It is thought that psoriasis is a T-lymphocyte driven disorder to an unidentified antigen(s). T cell activation results in upregulation of Th1-type T cell cytokines, e.g. interferon-Y, interleukins (IL-1, -2, -8), growth factors (TGF-α, TNF-α) and adhesion molecules (ICAM-1).

Clinical features

■ Chronic plaque psoriasis is the most common. Well-demarcated, salmon-pink silvery scaling lesions occur on the extensor surfaces of the limbs, particularly the elbows and knees (Fig. 18.2). Scalp involvement is common and is most often seen at the hair margin or over the occiput. New plaques of psoriasis occur at sites of skin trauma (‘Kobner phenomenon').

■ Flexural psoriasis - red glazed non-scaly plaques confined to flexures such as the groin, natal cleft and sub-mammary areas. The rash is sometimes misdiagnosed as candida intertrigo, but the latter will nor-mally show satellite lesions.

■ Guttate (‘raindrop-like') psoriasis occurs most commonly in children and young adults An explosive eruption of very small circular or oval plaques appears over the trunk about 2 weeks after a streptococcal sore throat.

Fig. 18.2 Psoriasis of the knees.

■ Erythrodermic and pustular psoriasis is the most severe and may be life-threatening. There is widespread intense inflammation of the skin which may be associated with malaise, pyrexia and circulatory disturbances.

Associated features

Nail involvement occurs in 50% of patients with psoriasis and is manifest as pitting of the nail plate, onycholysis (separation of the nail from the underlying vascular bed), yellow-brown discoloration, subungual hyperkeratosis and, rarely, a damaged nail matrix and lost nail plate. Arthritis occurs in 20% of patients (p. 292).

Management

Topical treatment For mild disease, reassurance and treatment with an emollient may be all that is necessary. Emollients (e.g. aqueous cream, emulsifying ointment, white soft paraffin) hydrate the skin and may have an anti-proliferative effect. More specific topical treatments for chronic plaque psoriasis on the extensor surfaces of the trunk and limbs include vitamin D3 analogues (e.g. calcipotriol, calcitriol, tacalcitol) that affect cell division and ditferentiation, coal tar (antiscaling and anti-inflammatory properties), tazaro-tene (a vitamin A antagonist, i.e. a retinoid) and corticosteroids in combination with other treatments. Topical dithranol (inhibits DNA synthesis) can also be helpful but it causes staining of the skin and clothing and it may prove difficult to use at home on a regular basis. Salicylic acid acts as a keratolytic and is particularly useful for scalp psoriasis.

Phototherapy Ultraviolet A radiation (UVA) in conjunction with a photo-sensitizing agent, oral or topical psoralen, (PUVA) is usually highly effective for treating extensive psoriasis. Repeated treatments exaggerate skin ageing and carry the risk of UV-induced skin cancer.

Systemic therapy is with oral retinoic acid derivatives (acitretin or etreti-nate), immunosuppression (methotrexate, ciclosporin) or biological agents (TNF-α blockers and efalizumab, an anti-CD11a monoclonal antibody). They are used in resistant disease or for severe erythrodermic or pustular psoriasis. The retinoic acid derivatives are teratogenic and in women on childbearing age the possibility of pregnancy must be excluded before treatment and effective contraception must be used during treatment and for 3 years afterwards.

Urticaria/angio-oedema

These are inflammatory predominantly dermal processes in which degranula-tion of mast cells is the final common pathway. The involved skin in urticaria (hives, ‘nettle rash') is red and swollen due to vasodilatation and increased vascular permeability. The predominant symptom is itch. Similar processes operate in angio-oedema but involvement is predominantly below the dermis and the swelling is less red and not itchy.

Aetiology

Viral or parasitic infection, drug reactions (NSAIDs, penicillin, ACE inhibitors, opiates), food allergy (strawberries, food colourings, seafood) or, rarely, sys-temic lupus erythematosus are all causes but in most cases the underlying cause is unknown. Physical urticarias can be caused by cold, deep pressure, stress, heat, sunlight or water. Hereditary angio-oedema is a rare autosomal dominant condition due to a mutation in the C1-esterase inhibitor, a compo-nent of the complement system. There are recurrent episodes of non-pruritic, non-pitting subcutaneous or submucosal oedema typically involving the arms, legs, hands, feet, abdomen (nausea, vomiting, pain) and sometimes larynx (respiratory difficulty and sudden death).

Management

Urticaria is managed by avoiding precipitating factors (including opiates and salicylates which degranulate mast cells) and oral non-sedating antihista-mines (H1 blocker), e.g. cetirizine 10 mg daily. Sedating antihistamines, H2 blockers and dapsone are added if necessary. Intramuscular adrenaline and intravenous hydrocortisone are used in angio-oedema involving the mouth or throat. Hereditary angio-oedema is treated with C1 esterase inhibitor con-centrates and fresh frozen plasma in the acute setting. Maintenance treat-ment is with the anabolic steroid stanozolol or danazol, which stimulates an increase in synthesis of C1 esterase inhibitor.

Eczema

Eczema (dermatitis) is characterized by superíicial skin inflammation with vesicles (when acute), redness, oedema, oozing, scaling and usually pruritus. The most common type of eczema is atopic eczema.

Atopic eczema

Aetiology

There is a significant hereditary predisposition. The primary defect is thought to be an abnormal epithelial barrier function allowing antigenic and irritant agents to penetrate the barrier and come into contact with immune cells. Loss-of-function mutations in the epidermal barrier protein filaggrin predis-pose to atopic eczema in Caucasian individuals. An initial selective activation of Th2-type CD4 lymphocytes drives the inflammatory process with Th0 and Th1 cells predominating in the chronic phase. There are high levels of serum IgE antibodies, although their significance in contributing to the pathogenesis is unclear. Exacerbating factors include strong detergents and chemicals, cat and dog fur and some dietary antigens.

Clinical features

There are itchy, erythematous scaly patches, especially in the flexures such as in front of the elbows and ankles, behind the knees and around the neck (Fig. 18.3). Scratching can produce excoriations and repeated rubbing pro-duces skin thickening (lichenification) with exaggerated skin markings. Pig-mented skin may become hyper- or hypopigmented and extensor surfaces are often involved (reverse pattern). Broken skin may become secondarily infected by Staph. aureus (appearing as crusted weeping impetigo-like lesions) or herpes simplex virus causing multiple small blisters or punched out lesions (eczema herpeticum) which can occasionally be fatal.

Management

Known irritants should be avoided. Regular use of emollients, such as aqueous cream or emulsifying ointments, is useful in hydrating the skin. Topical corticosteroids form the mainstay of treatment. Mild steroids (e.g. 1% hydrocortisone) are used for the face and more potent steroids (e.g. betam-ethasone, fluocinolone) are used on the body and soles. Topical immuno-modulators such as tacrolimus and pimecrolimus are particularly helpful for treatment in sensitive areas such as the face and eyelids. Antibiotics are indicated for bacterial superinfection and bandaging helps absorption of treatment and acts as a barrier to prevent scratching.

Second-line treatments in severe non-responsive cases include oral pred-nisolone, azathioprine and ciclosporin.

Exogenous eczema (contact dermatitis)

In this condition there is acute or chronic skin inflammation, often sharply demarcated, produced by substances in contact with the skin. It may be

Fig. 18.3 Atopic eczema behind the knees.

caused by a primary chemical irritant, or may be the result of a type IV hypersensitivity reaction. Common chemical irritants are industrial solvents used in the workplace, or cleaning and detergent solutions used in the home. With allergic dermatitis there is sensitization of T lymphocytes over a period of time, which results in itching and dermatitis upon re-exposure to the antigen.

Clinical features

An unusual pattern of rash with clear-cut demarcation or odd-shaped areas of erythema and scaling should arouse suspicion and, in combination with a careful history, should indicate a cause. Patch testing, where the suspected allergen is placed in contact with the skin, is often useful in identifying a suspected allergen.

Management

Causative agents should be removed where possible. Steroid creams are useful for short periods in severe disease. Antipruritic agents are used for symptomatic relief of itching.

CUTANEOUS SIGNS OF SYSTEMIC DISEASE

Erythema nodosum

Erythema nodosum is an acute and sometimes recurrent paniculitis which produces painful dusky blue-red nodules over the shins or lower limbs, with occasional spread to the thighs or arms. Causes are listed in Table 18.1.

Clinical features

Painful nodules or plaques up to 5 cm in diameter appear in crops over 2 weeks and slowly fade to leave bruising and staining of the skin. Systemic upset is common, with malaise, fever and arthralgia.

Table 18.1 Common causes of erythema nodosum
Streptococcal infection*
Drugs (e.g. sulphonamides, oral contraceptive pill
Sarcoidosis*
Idiopathic*
Bacterial gastroenteritis, e.g. Salmonella, Shigella, Yersinia
Fungal infection (histoplasmosis, blastomycosis) diseases
Tuberculosis
Leprosy
Inflammatory bowel disease*
Chlamydia infection
*Indicates commonest causes.

Management

Symptoms should be treated with NSAIDs, light compression bandaging and bed rest. Recovery may take weeks, and recurrent attacks can occur. Dapsone, colchicine or oral prednisolone is used in resistant cases.

Erythema multiforme (EM)

EM is an acute self-limiting condition affecting the skin and mucosal sur-faces. A cell mediated cutaneous lymphocytotoxic response is present. Chil-dren and young adults are most commonly affected. The cause is unknown in 50% of cases but the following should be considered:

■ Infections: herpes simplex virus and mycoplasma are the most common causes. Others are EBV, orf, HIV

■ Drugs (e.g. sulphonamides, anticonvulsants)

■ Autoimmune rheumatic conditions, e.g. SLE

■ Wegener's granulomatosis

■ Carcinoma, lymphoma.

Clinical features

Symmetrically distributed erythematous papules occur most commonly on the back of the hands, the palms and the forearms. There may be a central lesion surrounded by pale red rings ('target lesions'). Eye changes include conjunctivitis, corneal ulceration and uveitis. Occasionally there is severe mucosal involvement leading to necrotic ulcers of the mouth and genitalia (EM major).

Management

The diagnosis is based on the appearance of the skin lesion and a history of risk factors or related disease. The disease usually resolves in 2-4 weeks. Treatment is symptomatic and involves treating the underlying cause. Rarely, recurrent erythema multiforme can occur. This is triggered by herpes simplex infection in 80% of cases, and oral aciclovir can be helpful. In resistant cases, azathioprine (1-2 mg/kg daily) is used.

Differential diagnosis

EM falls within a spectrum of drug-induced skin reactions that includes toxic epidermal necrolysis (widespread separation of the epidermis from the dermis) and the variant, Stevens-Johnson syndrome (damage is restricted to the mucosal surfaces with <10% bullous involvement of the skin).

Pyoderma gangrenosum

This condition presents with erythematous nodules or pustules which fre-quently ulcerate. The ulcers, which are often large, have a classic bluish black undermined edge and a purulent surface. The main causes are inflam-matory bowel disease, rheumatoid arthritis, haematological malignancy (myeloma, lymphoma, leukaemia) and primary biliary cirrhosis. In 20% of cases no cause is identified.

Management

The underlying condition should be treated. High-dose topical and/or oral steroids are used to prevent progressive ulceration. Other immunosuppres-sants such as ciclosporin are sometimes used.

Acanthosis nigricans

There is thickened, hyperpigmented skin predominantly of the flexures which can appear warty or velvety. It is associated with obesity, under-lying malignancy (especially gastrointestinal) and hyperandrogenism in females.

Neurofibromatosis

Type 1 (von Recklinghausen's disease) neurofibromatosis is an autosomal dominant disease caused by mutations in the NF1 gene (encoding for a protein, neurofibromin) on chromosome 17. Clinical features include multiple fleshy skin tags and deeper soft tissue tumours (neurofibromas), ‘café-au-lait' spots (light-brown macules of varying size), axillary freckling, scoliosis, and an increased incidence of a variety of neural tumours, e.g. meningioma, eighth-nerve tumours and gliomas. Type 2 is caused by a mutation in the gene encoding for the protein Merlin or Schwannomin (chromosome 22) and presents with bilateral acoustic neuromas, other neural tumours and cutaneous neurofibromas.

Tuberous sclerosis (epiloia)

An autosomal dominant condition which in most cases is due to a mutation in either the TSC1 gene (encodes hamartin) or the TSC2 gene (encodes tuberin). There is mental retardation, epilepsy and cutaneous abnormalities. The skin signs include adenoma sebaceum (reddish papules around the nose, periungual fibroma (nodules arising from the nail bed), shagreen patches (flesh-coloured plaques on the trunk), ash-leaf hypopigmentation and café-au-lait patches. There may be pitting of dental enamel.

Other diseases

Chronic kidney disease, liver disease and endocrine diseases all may have skin manifestations which are discussed in the relevant chapters.

OTHER DISEASES AFFECTING THE SKIN

Marfan’s syndrome

Marfan's syndrome is an autosomal dominant disorder associated with muta-tions in the fibrillin 1 gene on chromosome 15. Abnormalities of collagen synthesis cause fragility of the skin and bruising. The most obvious abnor-malities are skeletal: tall stature, arm span greater than height, arachnodac-tyly (long spidery fingers), sternal depression, hypermobile joints and a high arched palate. There is often upward dislocation of the lens as a result of weakness of the suspensory ligament. Cardiovascular complications (ascend-ing aortic aneurysm formation, aortic dissection and aortic valve incompe-tence) are responsible for a greatly reduced life span.

Ehlers-Danlos syndrome

Inherited defects of collagen lead to fragility and hyper-elasticity of the skin, with easy bruising, ‘paper-thin' scars and hypermobility of the joints. The walls of the aorta and gut are weak and may rarely rupture with catastrophic results.

BULLOUS DISEASE

Primary blistering diseases of the skin are rare. Skin biopsy for light and electron microscopy together with immunofluorescence is necessary for diagnosis. Much more common causes of skin blistering are chickenpox, herpes, impetigo, pompholyx eczema and inset bite reactions.

Autoimmune bullous diseases

Pemphigus vulgaris Autoantibodies against desmoglein 3, an adhesion protein of the keratinocyte membrane, disrupt intraepithelial junctions result-ing in formation of cutaneous and mucosal blisters (particularly oral mucosa) which evolve into erosions. Blisters can be extended with gentle sliding pressure (Nikolsky's sign). Blistering and erosions disrupt the skin's main functions (p. 804) and the disease can be fatal. Treatment is with high-dose oral prednisolone (60-100 mg daily) or pulsed methylprednisolone. Immuno-suppressants (azathioprine, mycophenolate mofetil, cyclophosphamide, ciclosporin) are used long-term as steroid sparing agents. Intravenous immu-noglobulin infusions and rituximab (p. 254) have also been used.

Bullous pemphigoid Autoantibodies against hemidesmosomal proteins (BP230 and BP 180) disrupt the dermal-epidermal junction leading to forma-tion of large tense bullae often around skin flexures. Mucosal involvement is uncommon. Treatment is with high-dose oral prednisolone (30-60 mg daily) and immunosuppressants (see above).

Mechanobullous disease (epidermolysis bullosa, EB)

This is a group of inherited disorders with blisters in the skin and mucous membranes after minor trauma. EB simplex is due to mutations of cytoskel-etal proteins (keratin 5, keratin 14) within the basal layer of the epidermis and is generally a mild disease. EB dystrophica is a more severe disease and due to a mutation in the COL-7A1 gene causing a loss of collagen V11 in the basement membrane. There is blistering with scarring, joint contractures, and involvement of the nails, mucosae and larynx. Squamous cell carcinoma is a complication and results in death in early adult life. The most severe form, junctional EB, causes death in infancy or early childhood.

MALIGNANT SKIN TUMOURS

All of these are related to sun exposure.

Basal cell carcinomas (BCC, rodent ulcer)

These are the most common malignant skin tumours. They are common later in life and occur on sun exposed areas, although rare on the ear. Most present as a shiny pearly nodule which may go on to ulcerate (Fig. 18.4). They rarely metastasize but can invade surrounding local structures. Treatment is by surgical excision. Radiotherapy, photodynamic therapy, cryotherapy or 5% imiquimod cream are used for the flat, diffuse superficial forms.

Squamous cell carcinoma (SCC)

This is a more aggressive tumour than BCC and it can metastasize. It presents as rather ill-defined nodules that ulcerate and grow rapidly. Solar keratoses (erythematous silver-scaly papules with a red base) and Bowen's disease (isolated scaly red plaques resembling psoriasis) are pre-malignant. Multiple tumours may occur in patients who have had prolonged periods of immunosuppression. Treatment of SCC is with excision or occasionally radiotherapy.

Malignant melanoma

This is the most serious form of skin cancer as metastasis can occur early and it causes a number of deaths even in young people. The clinical signs

Fig 18.4 Ulcerating basal cell carcinoma.

listed in Table 18.2 help distinguish malignant from benign moles. Four clini-cal types exist:

■ Lentìgo maligna melanoma- a patch of lentigo maligna (slow-growing macular area of pigmentation often on the face occurring in the elderly) develops a nodule signaling invasive malignancy

■ Superíicial spreading malignant melanoma- large flat irregularly pigmented lesion which grows laterally before vertical invasion develops

■ Nodule malignant melanoma- rapidly growing pigmented (rarely non-pigmented) nodule which bleeds or ulcerates

■ Acral lentiginous malignant melanomas - pigmented lesions on the palm, sole or under the nail.

Treatment

This is by wide surgical excision: 1 cm margin for thin melanomas (<1 mm) and 3 cm margin for thicker melanomas (>2 mm). Staging (by tumour thickness, metastasis and lymph node status) helps predict prognosis and 5-year survival. Metastatic disease responds poorly to treatment of all modalities.

Table 18.2 Clinical criteria for the diagnosis of malignant melanoma

ABCDE criteria (USA)

Asymmetry of mole

Border irregularity

Colour variation

Diameter

Elevation

The Glasgow 7-point checklist

Major criteria

Change in size

Change in shape

Change in colour

Minor criteria

Diameter > 6 mm

Inílammation

Oozing or bleeding

Mild itch or altered sensation

Cutaneous T cell lymphoma (mycosis fungoides)

This is a rare type of skin tumour with a benign course. Scaly patches, resembling eczema or psoriasis, often on the buttocks, come and go or persist for many years. In elderly males, the disease may progress and be accompanied by lymphadenopathy and blood involvement (Sézary syn-drome). Early cutaneous disease can be left untreated or treated with topical steroids or PUVA (p. 809). More advanced disease may require radiotherapy, chemotherapy, immunotherapy or electron beam therapy.

Kaposi’s sarcoma

This is a tumour of vascular and lymphatic endothelium that presents as purplish nodules and plaques in elderly males (especially Jewish people from Eastern Europe), as an endemic form in males from central Africa, and in patients with HIV infection (p. 54). Infection with herpes virus type 8 has an aetiological role. Treatment is with radiotherapy, immunotherapy or chemotherapy.

Dictionary of terms

There are excellent on-line medical dictionaries with definitions for thousands of medical words and conditions. Sites for two of them are: http://www.medterms.com http://cancerweb.ncl.ac.uk/omd/

Adenoma A benign epithelial neoplasm in which the cells form recog-nizable glandular structures or in which they are clearly derived from glandular epithelium.

Adjuvant Term applied to chemotherapy or hormone therapy given after local treatment, in tumours where dissemination is undetectable but can be assumed to have occurred. If effective, it should lead to an increase in cure rate or overall disease-free survival.

Aerobic In microbiology refers to growing, living or occurring in the pres-ence of molecular oxygen. Bacteria that require oxygen to survive (aerobic bacteria).

Afterload The load against which the cardiac muscle exerts its contractile force, i.e. the peripheral vascular tree.

Agonist A drug that has attinity for and in some way activates a receptor when it occupies it.

Alkaptonuria Inborn error of amino acid metabolism caused by a defect in the enzyme homogentisic acid oxidase. There is ochronosis (accumula-tion of a blue-black pigment in connective tissues) and arthritis. The slate blue-black pigmentation is most apparent in the sclera of the eyes, the external ears, and the tympanic membranes.

Allogeneic transplantation When another individual acts as the donor. Alopecia Hair loss from areas where it is normally present.

Alport’s syndrome Hereditary disorder characterized by progressive sensorineural hearing loss, nephritis and renal failure, and, occasionally, ocular defects; transmitted as an autosomal dominant or X-linked trait. Ambulant (ambulatory) Able to walk; may be used to describe patients who do not require a wheelchair or are not confined to bed.

Anaerobic Lacking molecular oxygen. Growing, living or occurring in the absence of molecular oxygen, pertaining to an anaerobe.

Angiography A radiographic technique where a radio-opaque contrast material is injected into a blood vessel for the purpose of identifying its anatomy on X-ray.

Anisocytosis Increased variation in the size of the red blood cells. Annular lesions Lesions occurring in rings.

Antagonist A drug that binds to a cell receptor and does not activate it.

Antibody An immunoglobulin molecule that has a specific amino acid sequence by virtue of which it interacts only with the antigen that induced its synthesis in cells of the lymphoid series (especially plasma cells), or with antigen closely related to it.

Antigen Any substance, organism or foreign material recognized by the immune system as being ‘non-self', which will provoke the production of a specific antibody. disease and rheumatological disease which is not associated with a vasculitis.

Antioxidant An enzyme or other organic substance that has the ability to counteract the damaging effects of oxygen in tissues. It has been suggested that antioxidant vitamins such as vitamin E may provide protection against certain diseases, including atherosclerosis.

Aphasia (dysphasia) A disturbance of the ability to use language, whether in speaking, writing or comprehending. It is caused by left frontoparietal lesions, often a stroke:

■ Broca's aphasia (expressive aphasia) is due to a lesion in the left frontal lobe. There is reduced fluency of speech, with comprehension relatively preserved. The patient knows what he/she wants to say but cannot get the words out.

■ Wernicke's aphasia (receptive aphasia) is due to a left temporo-parietal lesion. The patient speaks fluently but words are put together in the wrong order, and in the most severe forms the patient speaks complete rubbish with the insertion of non-existent words. Comprehension is severely impaired.

■ Global aphasia is due to widespread damage to the areas concerned with speech. The patient shows combined expressive and receptive dysphasia.

Apoptosis Programmed cell death, as signalled by the nuclei in normally functioning cells when age or state of cell health dictates.

Apraxia Loss of the ability to carry out familiar purposeful movements in the absence of paralysis or other motor or sensory impairment.

Ataxia Is due to failure of coordination of complex muscular movements despite intact individual movements and sensation.

Atrophy Thinning (e.g. of the skin).

Autoantibody An antibody that reacts with an antigen which is a normal component of the body.

Autocrine Autocrine signalling is where a cell secretes a chemical mes-senger that binds to receptors on the same cell leading to changes in the cell, see also paracrine or endocrine signalling.

Autologous When the patient acts as his or her own source of cells.

Autosomal dominant Requires only one affected parent to have the trait to pass it on to offspring.

Autosomal recessive Mutation carried on an autosome (i.e. a chromosome not involved in sex determination) that is deleterious only in homozygotes (identical alleles of the gene are carried). Both affected parents must have the trait to pass it on to their offspring.

Bone marrow Is obtained for examination by aspiration from the anterior iliac crest or sternum. In many cases a trephine biopsy (removal of a core of bone marrow tissue) is also necessary.

Bulla A large vesicle.

Bursa A closed fluid-filled sac lined with synovium that functions to facili-tate movement and reduce friction between tissues of the body. Bursitis is inflammation of a bursa.

Carcinoma A malignant neoplasm arising from epithelium.

Caseating Developing a necrotic centre.

CD (cluster differentiation) antigens Antigens on the cell surface that can be detected by immune reagents and which are associated with the differentiation of a particular cell type or types. Many cells can be identi-fied by their possession of a unique set of differentiation antigens, e.g. CD4, CD8.

Chagas disease caused by the parasite Trypanosoma cruzi. Transmitted to animals and people by blood-sucking triatomine bugs present only in the Americas. Acute symptoms are mild and non-specific but persist to chronic disease (cardiomyopathy, megaoesophagus, megacolon) if untreated. Treatment is with benznidazole and nifurtimox.

Cheyne-Stokes respiration An abnormal breathing pattern in which there are periods of rapid breathing alternating with periods of no breathing or slow breathing.

Choledochal cyst A congenital anatomical malformation of a bile duct, including cystic dilatation of the extrahepatic bile duct or the large intra-hepatic bile duct. Classification is based on the site and type of dilatation. Type I is most common.

Chronic granulomatous disease A recessive X-linked defect of leucocyte function in which phagocytic cells ingest but fail to digest bacteria, result-ing in recurring bacterial infections with granuloma formation.

Chronotropic Positively chronotropic means to increase the rate of contrac-tion of the heart; negatively chronotropic is the opposite.

Clone A population of identical cells or organisms that are derived from a single cell or ancestor and contain identical DNA molecules.

Clubbing Broadening or thickening of the tips of the fingers and toes with increased lengthwise curvature of the nail and a decrease in the angle normally seen between cuticle and finger-nail. Causes include congenital, respiratory (lung cancer, tuberculosis, bronchiectasis, lung abscess or empyema, lung fibrosis), cardiac (bacterial endocarditis, cyanotic con-genital heart disease), and rarely gastrointestinal (Crohn's disease, cirrhosis).

Clubfoot (talipes equinovarus) A deformed foot in which the foot is plantar flexed, inverted and adducted.

Congenital Something that is present at birth. It may or may not be genetic (inherited).

Constructional apraxia Inability to copy simple drawings: often seen in hepatic encephalopathy when the patient is unable to copy a five-pointed star.

Contraindication Any condition, especially a disease or current treatment, which renders some particular line of treatment undesirable.

C-reactive protein (CRP) Is synthesized in the liver and produced during the acute-phase response. It is quick and easy to measure and is replac-ing measurement of the ESR in some centres.

Crust Dried exudate on the skin.

Cryoglobulins Immunoglobulins that precipitate when cold or during exer-cise. They may be monoclonal or polyclonal, e.g. mixed essential cryo-globulinaemia, and result in a cutaneous vasculitis or occasionally a multisystem disorder.

Cryptogenic A disease of obscure or unknown origin.

CT scan (computed axial tomography) CT combines the use of X-rays with computed analysis of the images to assimilate multiple X-ray images into two-dimensional cross-sectional images (‘slices'). With helical or spiral CT scanning, computer interpolation allows reconstruction of standard transverse scans to make 3-dimensional images. Often a contrast agent is given by mouth or intravenously to highlight specific areas. Risks of CT scanning are exposure to radiation, and allergies and renal impairment after intravenous contrast agents.

Cytokines Soluble messenger molecules which enable the immune system to communicate through its different compartments. Cytokines are made by many cells, such as lymphocytes (lymphokines) and other white cells (interleukins). Examples of cytokines, other than interleukins, include tumour necrosis factor (TNF), interferons and granulocyte colony-stimu-lating factor (G-CSF).

Dextrocardia The heart is in the right hemithorax, with the apex directed to the right.

DIDMOAD syndrome (Wolfram’s syndrome) Hereditary association of dia-betes insipidus, diabetes mellitus, optic atrophy and deafness.

Distal A term of comparison meaning farther from a point of reference; it is the opposite of proximal.

Doppler ultrasound A form of ultrasound that can detect and measure blood flow. Doppler ultrasound depends on the Doppler effect, a change in the frequency of a wave resulting from the motion of a reflector, i.e. the red blood cell in the case of Doppler ultrasound.

Down’s syndrome Chromosome disorder associated either with a triplica-tion or translocation of chromosome 21. Clinical manifestations include mental retardation, short stature, flat hypoplastic face with short nose, prominent epicanthic skinfolds, small low-set ears with prominent anti-helix, fissured and thickened tongue, laxness of joint ligaments, pelvic dysplasia, broad hands and feet, stubby fingers, transverse palmar crease, lenticular opacities and heart disease. Patients with Down's syn-drome have an increased risk for leukaemia, thyroid disorders, coeliac disease and early onset Alzheimer's disease.

Dupytren’s disease Collagen cords form in the palm which eventually thicken and shorten causing flexion contractures of the hand. Ring and little fingers most commonly affected. Associated with increasing age, alcoholism, diabetes and epilepsy. Treatment for those with severely impaired hand function is fasciotomy,

Dysarthria Disordered articulation. Any lesion that produces paralysis, slowing or incoordination of the muscles of articulation, or local discom-fort, will cause dysarthria. Examples are upper and lower motor lesions of the lower cranial nerves, cerebellar lesions, Parkinson's disease and local lesions in the mouth, larynx, pharynx and tongue.

Dysplasia Abnormal cell growth or maturation of cells.

Ecchymoses Bruises >3 mm in diameter.

Ectopic Located away from its normal position, such as an ectopic pregnancy.

Empirical Based on experience. Empirical treatment refers to treatment given to an individual that is based on the experience of the physician in treating previous patients with a similar presentation. It is not completely ‘scientific' treatment.

End-diastolic volume The volume of blood in the ventricle at the end of diastole.

Endemic Present in a community at all times.

Endocrine Endocrine signalling refers to cells secreting hormones into the bloodstream to exert their action on cells distant to the cell of origin, see also autocrine and paracrine signalling.

Endogenous Related to or produced by the body.

Enzyme-linked immunosorbent (ELISA) assay A serologic test used for the detection of particular antibodies or antigens in the blood. ELISA technol-ogy links a measurable enzyme to either an antigen or antibody. In this way it can then measure the presence of an antibody or an antigen in the bloodstream.

Epidemic An outbreak of a disease affecting a large number of individuals in a community at the same time. The number of people affected is in excess of the expected.

Epidemiology The study of the distribution and determinants of health-related states and events in populations.

Epitope That part of an antigenic molecule to which an antibody or T-cell receptor responds.

Erythema Redness.

Erythrocyte sedimentation rate (ESR) The rate of fall of red cells in a column of blood; a measure of the acute-phase response. The speed is mainly determined by the concentration of large proteins, e.g. fibrinogen. The ESR is higher in women and rises with age. It is raised in a wide variety of systemic inflammatory and neoplastic diseases. The highest values (>100 mm/h) are found in chronic infections (e.g. TB), myeloma, connective tissue disorders and cancer.

Erythroderma Widespread redness of the skin, with scaling.

Euthanasia The illegal act of killing someone painlessly, especially to relieve suffering from an incurable disease.

Excoriation Linear marks caused by scratching.

Exogenous Developed or originated outside of the body.

Exudate Fluid rich in protein and cells, which has leaked from blood vessels and been deposited in tissues.

Factitious Artificial, self-induced.

Familial Mediterranean fever Inherited disorder more common in those of Mediterranean descent. Recurrent episodes of abdominal pain (due to peritoneal inflammation), fever and arthritis.

Fissure A cleft, groove or slit, e.g. an anal fissure is an ulcer in the anal canal.

Fistula A tunnel or abnormal passage connecting two epithelial surfaces, frequently designated according to the organs or parts with which it communicates, e.g. a vesico-colic fistula connects the bladder to the colon.

Fitz-Hugh-Curtis syndrome Inflammation of the liver capsule associated with genital tract infection - occurs in about 25% of patients with pelvic inflammatory disease. Neisseria gonorrhoeae and Chlamydia trachomatis are the main causes. Women present with sharp right upper quadrant pain with or without signs of salpingitis. Diagnosis is often clinical and treatment is with appropriate antibiotics.

Gaucher’s disease Inherited (autosomal recessive) disorder of lipid metab-olism caused by a deficiency of the enzyme p-glucocerebrosidase. Clini-cal features include hepatosplenomegaly and sometimes neurological dysfunction.

Generic drugs Non-proprietary drugs. They should usually be used when prescribing in preference to proprietary titles.

Hallucinations Perceptions that occur in the absence of external stimuli and while an individual is awake. They may involve any of the senses, including hearing (auditory hallucinations), vision (visual hallucinations), smell (olfactory hallucinations), taste (gustatory hallucinations), and touch (tactile hallucinations). Hallucinations may be drug induced or caused by chronic alcohol excess, temporal lobe epilepsy, psychotic illnesses, or certain organic disorders, such as Huntington's disease.

Histocompatibility antigens Genetically determined isoantigens present on the membranes of nucleated cells. They incite an immune response when grafted on to genetically disparate individuals, and thus determine the compatibility of cells in transplantation.

Howell—Jolly bodies DNA remnants in peripheral RBCs seen post-splen-ectomy and in leukaemia and megaloblastic anaemia.

Human leucocyte antigens (HLA) Human histocompatibility antigens determined by a region on chromosome 6. There are several genetic loci, each having multiple alleles, designated HLa-A, HLa-B, HLa-C, HLa-DP, -DQ and -DR. The susceptibility to some diseases is associated with certain HLA alleles (e.g. HLa-B27 in 95% of patients with ankylosing spondylitis), although their exact role in aetiology is unclear.

Hyperplasia The abnormal multiplication or increase in the number of normal cells in normal arrangement in a tissue.

Hypertrophy The enlargement or overgrowth of an organ or part due to an increase in size of its constituent cells.

latrogenic Induced inadvertently by medical treatment or procedures, or activity of attending physician.

Idiopathic Of unknown cause.

Idiosyncratic Relates to idiosyncrasy - an abnormal susceptibility to a drug or other agent which is peculiar to the individual.

Incidence An expression of the rate at which a certain event occurs, as in the number of new cases of a specific disease occurring during a certain period.

Incubation period Period between transmission of the infecting organism and the start of symptoms.

Inotropic Positively inotropic means increasing the force of cardiac muscle contraction.

Insidious Subtle, gradual, or imperceptible development. May be used to refer to the onset of symptoms or signs before the diagnosis of a disorder.

In vitro Outside of the body in an artificial environment such as a test tube.

In vivo Within the body.

Kawasaki’s disease An acute febrile illness (lasting more than 5 days) of unknown aetiology that occurs mainly in children. Features include damage to the coronary arteries which is reduced by treatment with aspirin and intravenous Y-globulin.

Macule A flat circumscribed area of discoloration.

Maculopapule A raised and discolored circumscribed lesion.

Magnetic resonance imaging (MRI) Uses the body's natural magnetic properties to produce detailed images from any part of the body. It does not involve radiation. Gadolinium is used as an intravenous contrast medium - rarely causes nephrogenic systemic fibrosis (p. xx) in patients with renal impairment. MRI scanning is potentially life-threatening for patients who have had medical or surgical (or accidental) metal implants (e.g. pacemakers, metallic clips, metal valves and joints) because of potential movement within a magnetic field. A metal check (including foreign bodies in the eye) should be done before requesting an MRI. Some implants are MRI safe and some are not. Most MRI departments will have a comprehensive safety check list of such devices and implants.

Marfan’s syndrome Autosomal dominant connective tissue disorder asso-ciated with mutations in the fibrillin 1 gene on chromosome 15. Up to one-third are new mutations. Clinical features include tall stature, long thin digits (arachnodactyly), high-arched palate, hypermobile joints, lens subluxation, incompetence of aortic and mitral valves, aortic dissection and spontaneous pneumothorax.

Ménétrier’s disease (giant hypertrophic gastritis) Gastritis with hyper-trophy of the gastric mucosa. Characterized by giant gastric folds, dimin-ished acid secretion, excessive secretion of mucus, and hypoproteinaemia. Symptoms include vomiting, diarrhoea and weight loss.

Metaplasia A change in the type of cells in a tissue to a form which is not normal for that tissue.

Methaemoglobinaemia A condition in which the iron within haemoglobin is oxidized from the ferrous (Fe2+) state to the ferric (Fe3) state, resulting in the inability to transport oxygen and carbon dioxide. Clinically, there is cyanosis. May be congenital or acquired (after exposure to certain drugs and toxins).

Mirizzi’s syndrome Obstructive jaundice caused by compression of the common hepatic duct by a stone in the cystic duct or the neck of the gall bladder.

Multidisciplinary team (MDT) A group of healthcare professionals working in a team with clear protocols and management pathways leading to more tailored and efficient patient care. For instance the core elements of a lung cancer MDT would be respiratory physicians, thoracic surgeons, specialist nurses, radiologists, oncologists and palliative care physicians. The specialist nurse usually acts as the key source of support and infor-mation for the patient, bridging the gap to the clinical team.

Mutation A change in a gene, such as loss, gain, or substitution of genetic material, that alters its function or expression. This change is passed along with subsequent divisions of the affected cell. Gene mutations may occur randomly for unknown reasons or may be inherited.

National Institute for Health and Clinical Excellence (NICE) This is part of the National Health Service (NHS) in the UK and its role is to provide patients, health professionals and the public with authoritative, robust and reliable guidance on current ‘best practice'.

nd Notifiable disease.

Necrosis Morphological changes indicative of cell death and caused by the progressive degradative action of enzymes; it may affect groups of cells or part of a structure or an organ.

Nephrogenic systemic fibrosis (see MRI) Formation of connective tissue in the skin which becomes thickened, coarse and hard and may lead to contractures and joint immobility. Systemic involvement, e.g. of lung, liver, muscles and heart can occur.

Nodule A circumscribed large palpable mass >1 cm in diameter.

Objective Structured Clinical Examination (OSCE) Examination based on planned clinical encounters in which the candidate (student, doctor or nurse) interviews, examines, informs, or otherwise interacts with a stand-ardized patient (SP). SPs are individuals who are scripted and rehearsed to portray an actual patient with a specific set of symptoms or clinical findings. SPs may be able-bodied individuals or actual patients with stable findings.

Oligoarticular Affecting a limited number of joints.

Oncogene Gene coding for proteins which are either growth factors, growth factor receptors, secondary messengers or DNa-binding proteins. Muta-tion of the gene promotes abnormal cell growth.

Osmolality The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent.

Osmolarity The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution.

Papule A circumscribed raised palpable area.

Paracrine Paracrine signalling is where a cell secretes a chemical mes-senger that binds to receptors on cells nearby, see also autocrine and endocrine signalling.

Pathognomonic A symptom or sign that, when present, points unmistak-ably to the presence of a certain definite disease.

Persistent vegetative state A condition of life without consciousness or will as a result of brain damage.

Petechiae Bruises < 3 mm in diameter.

Phenotype The appearance and function of an organism as a result of its genotype and its environment.

Plaque A disc-shaped lesion; can result from coalescence of papules.

Poikilocytosis Increased variation in the shape of the red blood cell.

Polychromasia Blue tinge to red blood cells in the blood film caused by the presence of young red cells.

Polymerase chain reaction (PCR) Technique for rapid detection and analy-sis of DNA and, by a modification of the method, RNA. Using oligo-nucleotide primers and DNA polymerase, minute amounts of genomic DNA can be amplified over a million times into measurable quantities.

Positron emission tomography (PET) scanning Allows the imaging of structures by virtue of their ability to concentrate specific molecules that have been labelled with a positron-emitting isotope, e.g. a glucose ana-logue (that is not metabolized by the cell) tagged with fluorine (FDG). Metabolically active cells including malignant cells utilize and import more glucose than other tissues and thus take up FDG more avidly. False positives occur with active infections or inflammatory processes.

Prevalence Total number of cases of a disease in existence at a certain time in a designated area.

Prognosis A forecast as to the probable outcome of an attack or disease.

Promyelocytes, myelocytes and metamyelocytes Immature white cells seen in the peripheral blood in leucoerythroblastic anaemia.

Prophylaxis Prevention of disease.

Proximal A term of comparison meaning nearer or closer to a point of refer-ence; for example, proximal myopathy is weakness of muscles nearest to the trunk, e.g. quadriceps.

Purpura Extravasation of blood into the skin; does not blanch on pressure.

Pustule A pus-filled blister.

Radioimmunoassay (RIA) Any system for testing antigen-antibody reactions in which use is made of radioactive labelling of antigen or anti-body to detect the extent of the reaction.

Refractory Resistant to or not responding readily to treatment.

Rhabdomyolysis The destruction of skeletal muscle cells. May be due to electrical injury, alcoholism, injury, drug side-effects or toxins.

Scales Dried flakes of dead skin.

Serum The cell-free portion of blood from which fibrinogen has been sepa-rated in the process of clotting. Serum is the supernatant obtained by high-speed centrifugation of whole blood collected in a plain tube.

Sinus A blind track opening onto the skin or a mucous surface.

Stomatocyte A red blood cell with a central slit (stoma).

Syndrome A set of signs or a series of events occurring together that point to a single condition as the cause.

Target cells (‘Mexican hat cells’) Red blood cells with central staining surrounded by a ring of pallor and an outer ring of staining. They occur in thalassaemia, sickle cell disease and liver disease.

Telangiectasia A visible, dilated blood vessel creating small focal red lesions in skin, mucous membranes or gut.

Teratogenic Possessing the ability to disrupt normal fetal development and causing fetal abnormalities.

TNM classification (tumour, node, metastasis) Staging system for many cancers. T is the extent of primary tumour, N is the involvement of lymph nodes and M indicates the presence or absence of metastases. For instance T0-T4 indicates increasing local tumour spread.

Transudate A plasma-derived fluid that accumulates in tissues/cavities as a result of venous and capillary pressure.

Tumour suppressor genes Genes whose protein products induce the repair or self-destruction (apoptosis) of cells containing damaged DNA. Unlike oncogenes, they restrict undue cell proliferation.

Turner’s syndrome Females with chromosomes 45X instead of the normal female chromosomes, 46XX. Growth failure, gonadal dysgenesis, widely spaced nipples, webbed neck, cardiac abnormalities, intelligence usually normal.

Vesicle A small, visible, fluid-filled blister.

Von Hippel-Lindau syndrome Autosomal dominant disorder characterized by cerebellar and retinal neoplasms, clear cell renal carcinoma, phaeo-chromocytoma, pancreatic tumours, and inner ear tumours. Associated with germline mutations of the VHL tumour suppressor gene.

Weal A transiently raised reddened area associated with scratching.

Xenotransplantation Transplantation of organs or tissues between differ-ent species.

Zoonosis Transmission of a disease from an animal or non-human species to humans. The reservoir for the disease is not human.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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