Location	Possible sensitising agents
Periorbital	Airborne allergens, nail polish, contact lens solution
Umbilicus	Nickel hypersensitivity to belt/jean button
Neck	Antiseptic in soap, cosmetics
Hairline	PPD in hair dye, hair perming solution
Hands	Latex or rubber accelerators in gloves, nickel, fragrances, protein contact dermatitis in food preparation, irritant contact dermatitis due to water

This is the most common form of occupational dermatitis and the commonest cause of hand eczema (Fig. 57.5). Unlike ACD, ICD is not immunologically mediated. The mechanism involves disruption of the epidermal permeability barrier and a direct cytotoxic effect depending on the irritant. Patients with pre-existing epidermal barrier dysfunction such as atopic eczema are at higher risk. The occupation of the individual may also be a risk factor, especially those working as builders, hairdressers, gardeners, healthcare workers and chefs. Irritants include detergents, oils, water, inorganic acids, alcohols and plastics. Preventative skin care is key and this includes the use of barriers such as emollients or cotton gloves in addition to avoiding suspected irritants.

Fig. 57.5 Contact dermatitis to cement in a building worker

(courtesy of M. Carr).

Seborrhoeic dermatitis

This common disorder is usually confined to areas with high sebum production. The likely aetiological mechanism is overgrowth of the commensal yeast Malassezia furfur (Pityosporum ovale). The clinical features are pink-yellow greasy patches with ‘bran-like’ scale which occur in the sebaceous-rich scalp, nasal folds, medial eyebrow, pre-sternal region and flexural sites. In the first few months of life, it manifests as coherent scaling of the scalp with inflammation and ooze, known as ‘cradle cap’. In adults, the symptoms are usually mild with a chronic, relapsing course. Extensive and severe seborrhoeic dermatitis can be seen in patients with underlying HIV infection or Parkinson’s disease. Treatment usually includes topical imidazoles.

Discoid eczema

Discoid eczema is also known as ‘nummular dermatitis’ and is a type of chronic eczema presenting with disseminated coin-shaped eczematous lesions of the extremities. Middle-aged males are most commonly affected.

Stasis eczema

Stasis eczema is also called stasis dermatitis, gravitational dermatitis or varicose eczema. It is a clinical component of chronic venous insufficiency seen in addition to other features which include varicose veins, skin discolouration, peripheral oedema, leg discomfort and non-healing ulcers. Clinical features include scaly eczematous plaques confined to the lower legs. Multiple topical medicines and dressings often lead to a secondary ACD. Management of stasis eczema should address the underlying cause.

Asteatotic eczema

Asteatotic eczema, also called eczema craquele, usually affects the lower legs and appears as dry, cracked skin likened to ‘cracked paving’. This is associated with increasing age, low humidity and frequent bathing. Treatment consists of emollients and mildly potent topical steroids.

Treatment

First-line treatment of eczema should include an emollient and soap substitute for washing. Topical steroids are used for anti-inflammatory effect. Systemic treatments for adult atopic eczema include oral prednisolone, ciclosporin and azathioprine. If there is a secondary bacterial infection, then this should be treated with oral antibiotics. The antibiotic(s) should be chosen based on sensitivity determined by wound swab.

Emollients

Emollients, topical hydrating agents consisting of fat or oil to soften the skin, are the mainstay of eczema management. Emollients are effective first-line treatments for all types of eczema, and regular, liberal use will reduce topical steroid requirements. The greasier products have more emollient effect (see Fig. 57.6). They are often underused and the need to educate the patient regarding use of sufficient quantities is vital. Dry skin is aggravated by soap and bath products, and therefore an emollient soap substitute for washing is advisable.

Fig. 57.6 Commonly used emollients used in dry skin conditions

(adapted from MeReC, 1998).

Topical corticosteroids

Topical steroids act as anti-inflammatory agents and are extremely useful and important in managing eczema. In recent years, the public have veered from overuse of topical steroids causing long-lasting side effects, to high levels of anxiety regarding possible side effects concerning their use. This can commonly lead to under treatment in children. Therefore, patient/carer education regarding appropriate topical steroid use is a crucial part of eczema management.

Topical steroids are classified into four main groups according to potency: mild, moderately potent, potent and very potent (Table 57.2). The choice of topical steroid is dependent on the site and severity of skin disease. Potent and very potent steroids should be avoided on delicate sites such as the face, genitals and flexures. The periorbital region should be treated with caution due to the thin skin increasing the likelihood of absorption and risk of cataracts or glaucoma. Treatment should be reviewed regularly and tailored accordingly. It is also important to remember that any form of occlusion will increase the absorption of steroid applied.

Table 57.2 Comparative potencies of topical corticosteroid preparations

Side effects are mainly local and include striae (stretch marks), telangiectasia (visible dilated small blood vessels), epidermal thinning, purpura (bruising), acne and perioral dermatitis. Lower frequency side effects include poor wound healing, spread or worsening of untreated infections and hypertrichosis. Hypopigmentation is a temporary side effect of long-term topical steroid use and is frequently exploited in illegal ‘skin bleaching’ agents. Rarely, adrenal suppression or Cushing’s syndrome due to systemic absorption may occur.

Local and systemic side effects are extremely rare with appropriate use and duration of topical steroid treatment. Patients should be advised to spread preparations thinly either once or twice daily. The recommended amount used can be quantified using a fingertip unit (Fig. 57.7). The quantity in this unit is sufficient to cover an area the size of two adult palms. Table 57.3 details the quantities for application to different sites required for twice-daily treatment for 1 week.

Fig. 57.7 Recommended amount of a topical steroid corresponding to one fingertip unit.

Table 57.3 Minimum quantity of topical application required for twice daily treatment for 1 week

Calcineurin inhibitors

The past decade saw the introduction of topical calcineurin inhibitors for the treatment of chronic eczema. These non-steroid immunomodulators inhibit calcineurin phosphatase which is important in T-lymphocyte activation. The main side effect is burning or stinging on initial application, but this usually improves after a few days. Although a theoretical risk of increased malignancy exists with these agents, studies have not shown an association between exposure to topical calcineurin inhibitors and increased rates of cutaneous malignancy. Calcineurin inhibitors should not be used on infected skin and are generally not very useful in severely inflamed eczematous skin. Their greatest value appears to be in maintenance therapy.

Tacrolimus ointment (Protopic®) is a calcineurin inhibitor derived from the oral transplant medicine FK506. The 0.1% and 0.03% preparations are indicated in the treatment of moderate to severe atopic dermatitis in adults and children over the age of 2 years. Tacrolimus is now also used in clinical practice as a second-line agent for other steroid responsive dermatoses.

Pimecrolimus 1% cream (Elidel®) is indicated for short-term or intermittent long-term use in mild to moderate atopic dermatitis. Studies have shown that it is effective, well tolerated and has minimal adverse effects in the long-term control of eczema in children aged over 2 years (Langley et al., 2008). Furthermore, this has resulted in the reduced use of topical steroids leading to a lower risk of steroid-induced side effects (Kapp et al., 2002).

Antihistamines

Pruritis is the most distressing feature of eczema. Oral antihistamines have no direct effect on pruritis in eczema; their main effect is sedation. Sedating antihistamines may cause day time drowsiness, and caution should be taken when driving and also if prescribed to school age children.

Topical imidazoles

Ketoconazole as a shampoo or cream is effective in reduction of Pityosporum ovale on the skin and is therefore useful in the treatment of seborrhoeic dermatitis. As the disease runs a chronic, relapsing course regular or intermittent use is usually necessary.

Coal tar preparations

Tar creams and ointments can be used in the management of hyperkeratotic, lichenified eczema. These are less cosmetically acceptable than other topical preparations, but coal tar is an effective anti-pruritic.

Bandaging

In children with atopic eczema, occlusion with bandages is useful to prevent scratching and potentiate the action of ointments and creams on the skin. Wet wrapping involves the application of emollients and steroids under a double layer to keep the inner layer moist. Parents can be trained to apply these bandages at home.

Systemic therapies

Systemic steroids

Oral prednisolone can be used as a short-term treatment in the management of severe acute eczema that needs rapid control. Long-term treatment with oral steroids is now rarely used due to the risk of side effects including hypertension and osteoporosis.

Ciclosporin

Ciclosporin is a systemic immunosuppressant that blocks activation of T-lymphocytes. It is effective as a short-term bridging therapy in severe chronic adult eczema and has a rapid onset of action. Intermittent courses at doses of 2.5–5 mg/kg/day are useful, but dose-related renal nephrotoxicity is inevitable and limits treatment duration to a maximum of 8–12 months. Other side effects include hypertension and increased risk of malignancy. A detailed patient history is required to determine if there is a previous history of gynaecologic or prostate malignancy. During treatment with ciclosporin, patients also require close monitoring of renal function and blood pressure.

Azathioprine

Azathioprine is a purine analogue that inhibits DNA synthesis and can be effective as monotherapy in adult eczema. Bone marrow suppression and toxicity are the major concerns. A higher risk of marrow suppression occurs in individuals with low levels of thiopurine methyltransferase (TPMT), and this should be assessed at screening. Patients with borderline TPMT levels require a lower dose of azathioprine. Patients with low levels of TPMT should not be offered this treatment.

Methotrexate

Methotrexate is occasionally used in unresponsive adult atopic eczema, but randomised controlled trials are lacking. A small prospective trial has shown that methotrexate can be effective and well tolerated as a second-line therapy for the treatment of moderate to severe atopic eczema in adults (Weatherhead et al., 2007).

Mycophenolate mofetil

Mycophenolate mofetil is an oral systemic agent that prevents T- and B-cell proliferation, thereby reducing inflammatory cytokine release. This can be used as an alternative in severe adult atopic dermatitis where azathioprine or ciclosporin are contraindicated. Side effects are gastro-intestinal upset, bone marrow suppression and an increased risk of infection.

Phototherapy

Phototherapy can be effective in select cases of atopic dermatitis. Narrow-band UVB is the therapy of choice (Gambichler et al., 2005; Meduri et al., 2007). The potential side effects of all types of phototherapy include burning, premature ageing and a small increased risk of skin cancer. A small proportion of patients have photosensitive eczema, and this should be determined by taking a detailed patient history before prescribing phototherapy treatment. A treatment course requires a patient to attend two or three times a week for at least 6 weeks.

Dietary supplements

Current evidence suggests that probiotics are not an effective treatment for eczema and may carry a small risk of adverse events such as infection and small bowel ischaemia. There is no evidence for use of evening primrose oil. The use of Chinese herbal medications in atopic eczema is under close scrutiny, and conflicting results have been obtained. Liver function should be monitored as hepatitis is a known side effect of some Chinese herbal medicines.

Interactions with drugs used in the treatment of eczema and psoriasis are shown in Table 57.4.

Table 57.4 Interactions with drugs used in the treatment of eczema and psoriasis

	Interacting drug	Outcome
Methotrexate	Aspirin	Increased plasma concentration and toxicity of methotrexate
	NSAIDs	Increased plasma concentration and toxicity of methotrexate
	Probenecid	Increased plasma concentration and toxicity of methotrexate
	Phenytoin	Increased bone marrow toxicity
	Sulphonamides	Increased toxicity
	Trimethoprim	Increased antifolate effect of methotrexate
Azathioprine	Allopurinol	Enhanced effect and toxicity of azathioprine
	Warfarin	Inhibition of anticoagulant effect
	Cimetidine	Enhanced myelosuppression
	Indometacin	Increased risk of leucopenia
Ciclosporin	NSAIDs	Increased risk of nephrotoxicity
	Aminoglycosides	Increased risk of nephrotoxicity
	Co-trimoxazole	Increased risk of nephrotoxicity
	Ciprofloxacin	Increased risk of nephrotoxicity
	Ketoconazole	Increased plasma concentration of ciclosporin
	Itraconazole	Increased plasma concentration of ciclosporin
	Erythromycin	Increased plasma concentration of ciclosporin
	Oral contraceptives	Increased plasma concentration of ciclosporin
	Calcium channel blockers	Increased plasma concentration of ciclosporin
	Phenytoin	Decreased plasma concentration of ciclosporin
	Carbamazepine	Decreased plasma concentration of ciclosporin
	Rifampicin	Decreased plasma concentration of ciclosporin
Acitretin	Methotrexate	Increased plasma concentration of methotrexate

(courtesy of M. Carr)

Patient care

It is important to recognise that eczema affects many aspects of a patient’s life and has considerable effects on the family. Quality-of-life factors affected include body image, irritability and loss of sleep due to profound itch and limitations to work and hobbies (Fig. 57.8). A multidisciplinary approach is often needed in overcoming these issues, and healthcare workers including primary care doctors, dermatologists, specialist nurses, pharmacists and teachers may be involved. Patients with eczema should aim to lead as normal a life as possible, and school staff and employers can play an important part in achieving this goal.

Fig. 57.8 The social and psychological effects of chronic eczema.

Patient and parental education is important as treatments are designed to control and manage the disease. Although atopic eczema is likely to improve throughout childhood, expectations of an immediate cure need to be addressed. Advice and support through contact with other patients and their families can be obtained from the National Eczema Society (www.eczema.org). An algorithm for the management of eczema is shown in Fig. 57.9.

Fig. 57.9 Algorithm for the management of eczema.

Psoriasis

Psoriasis is a chronic inflammatory disorder of the skin and joints. The current prevalence in Europe and North America is estimated to be between 1% and 3%. The usual presentation is with well-demarcated red plaques with an overlying scale.

Aetiology

The aetiology of psoriasis is a combination of genetic and environmental factors. In most cases, there is a genetic predisposition and up to 70% of patients report a family history of psoriasis. Recent advances in genome-wide association studies have led to the identification of at least nine chromosomal psoriasis susceptibility loci. Multiple genes are likely to influence disease susceptibility, severity and clinical subtype. The strongest association is with HLA-CW*06.

Precipitating factors

Non-inherited factors also have a role in triggering psoriasis in predisposed individuals. These are described as follows.

Infections

Bacterial infections have been implicated as triggers for psoriasis. Streptococcal infections, particularly pharyngitis, frequently precede the onset of guttate psoriasis. HIV infection can aggravate psoriasis. The severity of the psoriasis is greater in this patient population.

Drugs

Drugs can exacerbate or induce psoriasis in predisposed individuals. The most common causative agents are lithium, ß-blockers, anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), tetracyclines and rapid withdrawal of systemic corticosteroids.

Alcohol and smoking

Excess alcohol consumption may exacerbate established psoriasis. Additionally, psoriasis is associated with high rates of alcoholism due to the psychological stresses of the disease.

Smoking is strongly associated with palmoplantar psoriasis; up to 95% of patients with this variant are smokers at disease onset. Smoking cessation should be actively addressed due to a likely improvement in disease status and associated risk reduction of ischaemic heart disease. It has been suggested that psoriasis, particularly if severe, may be an independent risk factor for atherosclerosis, myocardial infarction and stroke (Mehta et al., 2010).

Emotional stress

Anecdotal observations and frequent patient reports identify stress as an important trigger factor for psoriasis. Clinical evidence has demonstrated that the onset and severity of psoriasis can correlate with prior stress (Kirby et al., 2008). Furthermore, psychological distress and depression can occur as a consequence of psoriasis.

Koebner phenomenon

The Koebner phenomenon refers to psoriatic lesions which occur at sites of injury to the skin, such as a cut, burn, scratch or surgical scar, in patients with psoriasis.

Pathology and clinical features

The clinical features of psoriasis, well-demarcated, erythematous scaly plaques, are explained by the histological features (Fig. 57.10). Common sites affected include the scalp, buttocks, elbows, knees and nails.

Fig. 57.10 Chronic scaly plaque psoriasis on an elbow

(courtesy of M. Carr).

Histologically, the epidermis is thickened (acanthosis), with a thickened upper horny layer (hyperkeratosis) which is reflected by the clinical features of thick, scaly skin. The build of scale is due to increased epidermal turnover. The differentiation of cells through the epidermis terminating in the keratin horny layer normally takes approximately 40 days. Epidermal turnover in psoriatic skin may be as rapid as 7 days. In the dermis, the capillaries are dilated, tortuous and closer to the surface of the skin. This explains Auspitz’s sign which is the appearance of pinpoint bleeding after scraping off psoriasis scales.

Inflammatory cells are present in all layers of psoriatic skin; granulocytes are predominant and form microabscesses in the epidermis. Lymphocytes and Langerhans cells are also increased. The presence of lymphocytes in the epidermis led to hypotheses of an immunological cytokine-mediated process causing epidermal hyperproliferation and changes in vascular structure. T-cells, dendritic cells and cytokines such as tumour necrosis factor alpha (TNFα), interleukin (IL)-12 and IL-23 all contribute to its pathogenesis. This is confirmed by the therapeutic effect of drugs that suppress T-lymphocyte function, such as ciclosporin, in psoriasis.

Clinical types

Psoriasis vulgaris

Psoriasis vulgaris, also known as chronic plaque psoriasis, is the most common variant. It can occur at any age but most often begins in young adulthood and has a chronic relapsing course. The typical psoriatic lesion is a red, sharply demarcated plaque with overlying silvery scale. The distribution is usually symmetrical and involves extensor sites such as the elbows and knees. The sacrum, scalp and nails are also commonly affected. The plaques may itch but not usually to the severity of eczematous plaques. Treatment is aimed at management of disease rather than cure.

Guttate psoriasis

Guttate psoriasis is more commonly seen in children and young adults and is characterised by a widespread scaly eruption of small ‘teardrop-like’ scaly plaques (Fig. 57.11). The presentation is often acute and can appear 10–14 days after a streptococcal upper respiratory tract infection. Topical treatments or UVB phototherapy are usually effective. Spontaneous resolution is common; however, guttate psoriasis may be the first manifestation of psoriasis in predisposed individuals.

Fig. 57.11 Guttate psoriasis showing Koebner phenomenon in scratch mark

(courtesy of M. Carr).

Scalp psoriasis

Involvement of the scalp may be the only manifestation of psoriasis in some patients, but may also occur in psoriasis vulgaris. This appears as scaly demarcated plaques extending to the hairline and around the ears. Hair loss is rare.

Psoriatic nail disease

The nails are frequently affected in psoriasis. In a small proportion of patients, the nails are the only area affected. Changes include nail pitting, nail ridging, onycholysis (separation of the nail from the nail bed), hyperkeratosis under the nail and complete nail destruction. These symptoms can be cosmetically disfiguring. Topical treatments are rarely effective for psoriatic nail disease. Systemic treatments such as methotrexate, when prescribed for generalised psoriasis, may also improve nail disease.

Palmoplantar psoriasis

At these sites on the palms and soles, there is sharp demarcation of the involved areas (Fig. 57.12). Palmoplantar psoriasis can take two forms: either inflamed hyperkeratotic fissured skin which can be very painful or sterile pustules on an erythematous base which dry to leave small brown macules (palmoplantar pustulosis). The pustular form is much commoner in smokers.

Fig. 57.12 Pustular psoriasis of sole

(courtesy of M. Carr).

Flexural psoriasis

Psoriasis can occur at flexural sites such as the axillae, groin, submammary areas and genitalia. Due to friction and moisture within skin folds, lesions differ in appearance from classical psoriasis and tend to be red and glazed rather than scaly. Affected areas tend to be clearly demarcated. Secondary infections, particularly with Candida are common. Potent steroids are not advised at these sites due to the high risk of skin atrophy.

Erythrodermic psoriasis

Erythroderma, or exfoliative dermatitis, is a severe, potentially life-threatening condition in which more than 90% of the body surface is red and scaly (see Fig. 57.13). This can occur as a consequence of either eczema or psoriasis. Skin function is impaired and patients suffer dehydration, electrolyte imbalance, temperature dysregulation and serious secondary infection. These patients need urgent hospital admission, medical supportive therapy and topical treatment. Initially, bland emollients such as white soft paraffin and mild to moderate topical steroids should be used. Underlying conditions, such as psoriasis, can then be treated with appropriate systemic agents.

Fig. 57.13 Erythrodermic psoriasis,

courtesy of St John’s Institute of Dermatology, London.

Generalised pustular psoriasis

This is an acute, unstable form of psoriasis manifesting as widespread sheets of tiny sterile pustules on an erythematous base. The patient is usually systemically unwell with fever and general malaise. Pustular psoriasis may be precipitated by the withdrawal of systemic or very potent topical steroid. Therefore, oral steroids are avoided in the management of stable psoriasis.

Psoriatic arthropathy

Approximately 25% of psoriatic patients suffer with an associated arthropathy. There are five patterns of psoriatic arthropathy; monoarthopathy, rheumatoid arthritis-like, osteoarthritis-like, sacroiliitis-like and arthritis mutilans. Rheumatoid factor is negative in these patients. Some treatments effective for skin psoriasis are also effective in psoriatic arthropathy including methotrexate, and biological agents with action against TNFα.

Treatment

Many patients with psoriasis have mild disease and require only emollient therapy to prevent drying and fissuring of the elbows and knees. Other treatment options should take into account the type of psoriasis, patient occupation and lifestyle factors as well as disease severity. This will ensure improved patient compliance and better outcome.

Topical therapy

First-line treatment of mild to moderate psoriasis should include an emollient as well as a topical treatment. Mild to moderate topical steroids are useful for delicate skin sites such as the face and flexures. Dithranol and tar products are effective, but limitations of use include irritation, messy application and potent odour. Topical treatments may be technically difficult to apply to the scalp area; patient education and demonstration is key. Topical vitamin D analogues are well tolerated.

Vitamin D analogues

Vitamin D analogues inhibit keratinocyte differentiation and production. The most commonly prescribed Vitamin D analogue is calcipotriol. This is commonly used within primary care for mild localised psoriasis and is available as a lotion, ointment, cream or scalp treatment. Patients should be advised to avoid use on delicate skin sites such as the face and flexures due to irritation. Hypercalcaemia due to systemic absorption can occur if the maximum weekly dose exceeds 100 g. Efficacy may be enhanced when used in combination with a topical steroid.

Steroids

Topical steroids are cosmetically acceptable and easy to apply. Mild to moderately potent steroids are of greatest value in acutely inflamed psoriasis to reduce inflammation. Reduction of inflammation is important as it then allows other treatments to be introduced that would otherwise irritate acutely inflamed plaques. Topical steroids have a number of limitations. The use of potent steroids on large areas of psoriasis is associated with risks of local atrophy and systemic absorption. Furthermore, there is a rebound effect on withdrawal. Potent steroids should be reserved for localised disease, such as thicker acral sites, often in combination with salicylic acid if there is hyperkeratosis. In general, very potent steroids should be avoided.

Coal tar

Along with dithranol, coal tar is one of the oldest topical treatments for psoriasis. Coal tar has anti-inflammatory, antibacterial, anti-pruritic and antimitotic effects. A variety of preparations are available including bath preparations, shampoos, creams and ointment. Coal tar concentrations of 1–10% can be used, but use of higher concentrations should occur in a supervised setting. Coal tar in combination with topical steroids can be effective, for example Alphosyl HC®. The efficacy of tar is enhanced when used with UVB light therapy (Goerkerman regimen). The main limitations of tar are irritation of delicate skin sites, odour and temporary staining of skin and clothing. The theoretical risk of carcinogenesis due to polycyclic aromatic hydrocarbons has not been demonstrated in long-term clinical practice.

Dithranol

Dithranol (anthralin in the USA) is a synthetic anthracene derivative which has an anti-proliferative and anti-inflammatory effect on the skin. It is one of the older treatments used for stable, chronic plaque psoriasis. Although effective, practical drawbacks include burning and irritation of normal skin, staining of clothes as well as a strong odour. In current practice, dithranol is most commonly used as a short contact regimen within a dermatology day centre setting. The starting concentration of dithranol is usually 0.5% which can be increased slowly if tolerated up to 3%.

Salicylic acid

This is useful to reduce scale, particularly while treating hyperkeratosis of the palms and soles. It can be mixed with coal tar, steroid or urea.

Topical retinoids

Retinoids are less effective than vitamin D analogues in the treatment of psoriasis. Irritation is a possible side effect to therapy.

Topical treatment of psoriasis at special sites

Scalp

Tar shampoo is effective in mild scalp psoriasis. However, a descaling agent is required as part of therapy for thicker plaques. Coconut oil compounds, peanut oil and greasy emollient with salicylic acid can be used as descaling agents. A topical steroid can then be applied for inflammatory disease. Treatment does require considerable time and commitment from the patient.

Genitals

The genital regions are prone to irritation and mild to moderate topical steroids can be used. In addition, it is also important to inform patients that treatments used on other parts of the body may be too potent and irritant for genital areas.

Nails

Before treatment of psoriasis, fungal infections of the nails should be excluded. Topical treatments often have poor efficacy in psoriasis affecting the nail, and systemic therapy is preferred.

Phototherapy

The majority of psoriatic patients exhibit improvement of symptoms on sunny holidays, with only 10% of patients reporting deterioration in symptoms on sun exposure. Phototherapy has an immunosuppressive effect on skin and has been used in the treatment of psoriasis for over 80 years. Narrow-band UVB (311–313 nm) is preferable to broadband UVB (290–320 nm) due to increased safety and reduced risk of burning.

PUVA

PUVA (psoralens plus UVA light) has a valuable role in the treatment of stable moderate to severe psoriasis. Psoralens are drugs that are activated by long-wave ultraviolet light (320–400 nm), thereby interfering with DNA synthesis and reducing epidermal turnover. The two psoralens available in the UK are 8-MOP (methoxypsoralen) and 5-MOP. These are taken orally 2 h before exposure to UVA light. The eyes are always protected due to the risk of cataracts and patients are given sunglasses to wear for 12 h after treatment. The treatment is usually given twice a week for a 6-week period. Total cumulative dosage is carefully monitored.

The commonest adverse effect is nausea due to ingestion of oral psoralens. The most serious adverse effect is an increased risk of long-term cutaneous malignancy. Those with fair skin types and on past or present immunosuppresion are at greatest risk. Due to these risks, PUVA is usually reserved for patients resistant to UVB therapy.

Systemic therapy

Systemic therapy is indicated in severe widespread psoriasis, intolerant of or rapidly relapsing after topical therapy and phototherapy. Objective measures of disease severity and impact on quality of life are used routinely to assess need for systemic therapy and treatment response and include the Psoriasis Area and Severity Index (PASI) and the Dermatology Quality of Life Index (DLQI). Systemic treatments commonly prescribed in psoriasis include methotrexate, acitretin and ciclosporin. Drug interactions are important and a detailed patient drug history is important. New biologic agents are used in severe disease which is unresponsive to oral immunosuppressant treatment. Common adverse effects and monitoring requirements of systemic treatments of eczema and psoriasis are presented in Table 57.5.

Table 57.5 Common adverse effects and monitoring requirements for systemic treatments of eczema and psoriasis

Therapy	Adverse Effects	Monitoring requirements
Methotrexate	Hepatic fibrosis; myelosuppression; nausea; pulmonary fibrosis; teratogenic (contraindicated in both males and females for 4 weeks before and 3 months after treatment)	FBC
		U&E
		LFT
		Pro-collagen III peptide (P3NP)
		±Liver biopsy
		Chest X-Ray (screening)
Hydroxyurea	Myelosuppression; skin reaction; teratogenic; liver toxicity (narrow therapeutic window)	FBC
		U&Es
		LFT
Ciclosporin	Renal nephrotoxicity	FBC
	Hypertension	U&E
	Gingival hypertrophy	LFT
		Lipid profile
		Blood pressure
		Urinalysis
Acitretin	Teratogenic (including up to 2 years post-treatment)	FBC
	Dryness of mucous membranes and skin	U&E
	Hyperostoses, increased serum triglyceride	LFT
	Occasional hepatotoxic reaction	Lipid profile
Fumaric Acid Esters	Gastro-intestinal side effects	FBC
	Flushing	U&E
	Lymphopenia	LFT
	Proteinuria	Urinalysis
	Renal failure
Azathioprine	Myelosuppression	TPMT pre-treatment
	Deranged liver function	FBC/U&E/LFT
	Gastro-intestinal effects

U&Es, urea and electrolytes; LFTs, liver function tests; FBC, full blood count; TPMT, thiopurine methyl transferase genetic polymorphism screening.

Methotrexate

Methotrexate is a folic acid antagonist used in moderate to severe psoriasis. In males and females of non-childbearing potential, this tends to be the first-line systemic agent. It is also effective in psoriatic arthropathy. Methotrexate is given as a once weekly oral low dose regimen, with an initial test dose of 5 mg increasing up to 30 mg weekly. Acute toxicity occurs due to the effect of methotrexate on folic acid metabolism of rapidly dividing cells in the bone marrow and gastro-intestinal tract. This can cause myelosuppression or gastro-intestinal bleeding. In such cases, folinic acid rescue can be used to oppose the folate antagonist effect at a dose of 120 mg folinic acid over 12–24 h intravenously or intramuscularly in divided doses, followed by 15 mg/kg orally every 6 h for 48 h. Hepatic fibrosis is the commonest long-term risk and regular monitoring of liver function is necessary. Some patients complain of nausea and other gastro-intestinal side effects as well as lethargy. Folic acid 5 mg taken on the days methotrexate is not prescribed can reduce these adverse effects.

Patient monitoring in methotrexate therapy is detailed in Table 57.5. Liver function tests do not reliably predict hepatic fibrosis; supportive investigations are therefore required. Liver biopsy remains the gold standard. Recently, the measurement of serum pro-collagen three peptide levels has led to a reduction of liver biopsies for detection of hepatic fibrosis in these patients (Chalmers et al., 2005).

Acitretin

Acitretin, a vitamin A derivative that inhibits epidermal proliferation, is effective for disorders of keratinisation including chronic plaque psoriasis. The starting dose is usually 25–30 mg daily for 2–4 weeks increasing to 75 mg daily for short periods and according to clinical response. Mucocutaneous side effects, hair loss and lethargy are common. Acitretin should be avoided in women of childbearing potential because of the teratogenic risk. However, it is a safer option for patients with chronic infection for whom immunosuppression is contraindicated. Patients should be warned that a rebound response is occasionally seen when stopping treatment, and therefore a long-term maintenance dose is usually advised.

Ciclosporin

Ciclosporin is an effective treatment for all variants of psoriasis with a fairly rapid mode of action. The dose is 2–5 mg/kg. Similar to eczema management, continuous ciclosporin treatment for more than 1 year is not advised due to renal nephrotoxicity. Adverse events include hypertension, hypertrichosis, paraesthesia, tremor and increased risk of infections. There is also of an increased risk of skin cancer in conjunction with ciclosporin use in patients who have previously had phototherapy.

Hydroxyurea/hydroxycarbamide

Hydroxyurea/hydroxycarbamide is a drug with similar effects on bone marrow and germ cells to methotrexate but without the hepatotoxic effects. Relapse occurs on stopping treatment.

Fumaric acid esters

Fumaric acid esters have been used since the early 1960s and affect both keratinocytes and T-cell activity. It is licensed in Europe, but not in the UK, for severe, relapsing, chronic, plaque psoriasis. The main side effects are gastro-intestinal upset and flushing.

Biologic therapy

Biologic therapies or ‘biologics’ are drugs designed to block specific molecular steps important in immune-mediated disease. They have been used successfully in rheumatoid arthritis, inflammatory bowel disease and are now licensed for use in chronic plaque psoriasis. Their use is recommended for patients with severe plaque psoriasis defined as a PASI ≥ 10 and DLQI > 10 who have failed at least two standard systemic agents including methotrexate, ciclosporin and acitretin or one systemic agent and phototherapy (Smith et al., 2009).

TNFα antagonists

TNFα is a pro-inflammatory cytokine that plays a central role in the pathogenesis of psoriasis. The tumour necrosis factor antagonists: infliximab, adalimumab and etanercept all have potent immunosuppressant action and have proven efficacy in severe psoriasis. Serious adverse effects include infection, in particular reactivation of tuberculosis, exacerbation of severe cardiac failure, demyelinating disease and a potential risk of malignancy (solid organ tumours and lymphoma). Careful patient selection and regular monitoring are important.

Etanercept

is a genetically engineered receptor fusion protein with affinity for soluble TNFα. The dose is 25 mg twice weekly via subcutaneous injection. Higher doses of 50 mg twice a week are used in psoriatic arthropathy. The most frequent side effects are injection site reactions.

Infliximab

is a chimeric monoclonal antibody against TNFα. It is also used in Crohn’s disease, ulcerative colitis, ankylosing spondylitis and rheumatoid arthritis. Clinical trials have demonstrated rapid onset and good efficacy in psoriasis. Infliximab is administered at a dose of 5 mg/kg by intravenous infusion every 8 weeks after a loading dose at weeks 0, 2 and 6. Observation and nursing care on a day unit are therefore required.

Adalimumab

is humanised monoclonal antibody against TNFα that is administered in a bolus of 80 mg subcutaneously and then 40 mg on alternate weeks.

Other biologic agents used in psoriasis

Ustekinumab

is the newest available biologic agent used in the treatment of psoriasis. It is a fully human monoclonal antibody that prevents IL-12 and IL-23 from binding receptor proteins. A dose of 45 mg (or 90 mg in patients weighing >100 kg) is administered subcutaneously at week 0, 4 then every 12 weeks. In light of the limited patient exposure to this treatment, ustekinumab is reserved for use as a second-line biologic agent where TNF therapy has failed or cannot be used.

Efaluzimab,

a T-cell modulator, was withdrawn in 2009 due to an increased risk of progressive multifocal leucoencephalopathy.

A treatment algorithm for psoriasis is shown in Fig. 57.14.

Fig. 57.14 Treatment algorithm for psoriasis.

Patient care

Psoriasis is a chronic disease associated with significant psychosocial disability and reduction in quality of life. As well as effects related to depression; impact on body image and sexual relationships should be considered. Coexistent psoriatic arthropathy may have a severe impact on function and lead to significant time away from work or education. Support and understanding of individual patients’ needs and lifestyles will improve adherence to treatment. Psoriasis can be associated with alcohol misuse, and a drug and alcohol history should always be sought. Systemic and biologic treatments require regular attendance and blood tests, and therefore patients with poor attendance records may not be suitable for such treatment. Ultimately, responsibility lies with the patient to ensure regular treatment.

The chronicity of this disease may lead to treatment ‘fatigue’ and frustration with messy topical therapies. There are numerous alternatives and newer formulations are generally less messy. Treatments can be expensive and information on the entitlement to benefits to replace clothing ruined by ointments or washing machines worn out by constant use is available. The Psoriasis Association (www.psoriasis-association.org.uk) provides an excellent service for this, together with practical advice from fellow sufferers about day-to-day problems.

Case studies

Case 57.1

A 3-year-old child with known atopic eczema is seen in clinic with a widespread, excoriated, dry rash (see Fig. 57.15). Her eczema symptoms started at the age of 6 weeks. Her sleep has always been poor due to the marked itch symptoms at night. She has had two recent courses of oral antibiotics for presumed bacterial skin infection. Her normal skin treatment involves hydrocortisone 1% ointment to affected areas twice daily. Her parents are concerned regarding the possible triggers of her eczema flares and are keen to pursue possible allergy testing.

Fig. 57.15 Case study 1 – a young child with moderate/severe atopic eczema

courtesy of St John’s Institute of Dermatology, London.

Question

What advice could be given to the child’s parents?

Answer

Fig. 57.15 shows a young child with moderate/severe atopic eczema. Ill-defined, dry, erythematous patches of eczema are visible. A few of the patches around her ankles appear crusty and eroded. This may represent secondary infection.

Management should include regular topical emollient therapy. The correct quantities should be emphasised. A regular soap substitute should be prescribed.

Wound swabs should always be taken before prescribing an oral antibiotic for presumed infected eczema.

A moderately potent steroid ointment should be administered daily, along with a regular, greasy topical emollient. When a moderately potent or potent topical steroid is prescribed for a child, medical follow-up must be arranged. Regular use of potent steroids is not advised and will lead to local side effects including skin atrophy. If the treatment is ineffective, a short admission to hospital or regular day care should be arranged for further intensive topical treatments or dressings.

Time should be spent explaining to the parents the aetiology of atopic eczema. Although eczema is usually a chronic disease with no ‘cure’, it should also be explained that approximately 60% of children will have minimal or no symptoms after the age of 16.

Allergy testing is commonly requested by parents, but as most children will grow out of their symptoms as well as food sensitivities, formal testing is not always appropriate. Allergy testing may involve blood tests, including RAST tests, and skin prick tests. These may not be a pleasant experience for a young child. A positive result does not directly correlate with the effect of allergen avoidance on the course of atopic eczema. High street or internet allergy tests have no benefit in atopic eczema.

Case 57.2

A 22-year-old male nurse attends outpatients complaining of dry, painful eczema affecting his hands. He had previously suffered with childhood eczema and asthma. Since starting his new job, his symptoms have developed causing severe pain, fissures, itch and dry skin. His finger pulps are particularly affected. He attended occupational health and was then advised to see a dermatologist.

Question

What is the likely cause of his symptoms and what advice should be given?

Answer

The aetiology of hand dermatitis is often complex and multi-factorial. An atopic predisposition, irritant factors as well as allergic contact type IV hypersensitivity may all play a part. In view of his atopic eczema during childhood, he is at greater risk of irritant and ACD than the general population. The need for this patient to constantly wash his hands with antiseptic hand wash and excessive contact with water is likely to be an exacerbating factor. Alternatives to antiseptic washes include a moisturising soap substitute, for example Dermol 500®.

A potent topical steroid and emollient with a good barrier effect should be prescribed. Tape impregnated with a steroid preparation, for example Haelan® tape may be useful to protect fissured areas on his hands. Patch testing would be the next step to investigate a possible allergic contact component to his symptoms.

Young adults with moderate or severe eczema should be given career guidance to avoid occupations at higher risk of leading to ICD, for instance hairdressing, domestic cleaning or working in a healthcare environment that requires constant hand washing.

Case 57.3

A 28-year-old male management executive with lifelong atopic eczema has attended with worsening severity of his eczema. He has been using emollients and moderately potent topical steroids for many years and feels that these are no longer having an effect. Over the past year, he has required two short courses of oral steroids. His sleep is affected and he cannot afford to take any further time off work.

Question

What are the treatment options for this man?

Answer

This patient needs effective treatment before he becomes erythrodermic. High-dose systemic steroids over a 2-week period may have a rapid effect but are not a long-term option. His topical regime should be explored to ensure adequate quantities of emollient are being used. In addition, his aims, expectations and medical issues should be explored with a view to possible systemic treatment.

If more than a few weeks of treatment are anticipated, ciclosporin is a possible treatment option. Pre-treatment screening should include blood pressure, urinalysis and blood tests including renal function. A short course of ciclosporin treatment no longer than 12 months would alleviate his symptoms, improve his mental well being and give him a break from his chronic skin disease. If longer-term systemic management is anticipated, azathioprine would be an option, but efficacy would only be evident after approximately 8 weeks of treatment.

Case 57.4

A 9-year-old boy with known atopic eczema presented with a vesicular, blistering eruption over his face and trunk (see Fig. 57.16). His mother noticed the blisters 48 h ago and brought him to hospital as he was unwell and feverish. He had been using topical steroids and emollients regularly for his moderate atopic eczema. His sister has recently been suffering with cold sores.

Question

Fig. 57.16 shows the young patient with eczema herpeticum. What advice would you give this patient and his mother?

Fig. 57.16 Case study 4 – a young patient with eczema herpeticum

courtesy of St John’s Institute of Dermatology, London.

Answer

Eczema herpeticum, Kaposi’s varicelliform eruption, is an important and serious complication that can occur in eczema patients. This is a medical emergency and early treatment with aciclovir may prove lifesaving. This widespread eruption occurs following inoculation of herpes simplex virus to skin damaged by eczema. This then spreads rapidly and can affect the eyes and lungs. It usually manifests in young children with atopic eczema. Typically, the tiny blisters, vesicles, develop in large numbers on eczematous skin and patients are systemically unwell. The blisters or erosions appear ‘punched out’ and may be pustular. Eye involvement, as suggested in Fig. 57.16, necessitates urgent ophthalmological review as herpes simplex ocular infection can lead to corneal ulceration, stromal keratitis, iritis and permanent visual loss.

Children with atopic eczema and their parents should be educated to recognise the signs and symptoms of eczema herpeticum.

Case 57.5

A 33-year-old electrician presents to clinic with a 5-month history of a mildly itchy eruption occurring around the nasal area and eyebrows (see Fig. 57.17). He describes it as occasionally scaly and is very concerned regarding the cosmetic appearance. On examination, he also has mild scale and erythema affecting the scalp. The dandruff shampoos he usually purchases from his local community pharmacy have been ineffective. The diagnosis is seborrheic dermatitis.