Tacrolimus and pimecrolimus for atopic eczema

2 Clinical need and practice

2.1 Atopic eczema (synonymous with atopic dermatitis) is a chronic relapsing skin condition characterised by intense itching, dry skin, redness, inflammation and exudation. It affects mainly the flexor surfaces of the elbows and knees, as well as the face and neck.

2.2 The term 'atopic' refers to the association with atopy (a state of hypersensitivity to common environmental allergens that may be inherited) and differentiates atopic eczema from other forms of eczema such as irritant, allergic contact, discoid, venous, seborrhoeic and photosensitive eczema, which have different disease patterns and aetiologies.

2.3 Estimates of prevalence vary but suggest that the condition may affect as many as 15–20% of school-age children and 2–10% of adults. The majority of people with atopic eczema (over 80%) experience mild disease, whereas only a small proportion (around 2–4%) have a severe form of the disease. Despite the lower prevalence, the presentation of disease in adults is often more severe and chronic in nature.

2.4 In most people with atopic eczema, the condition begins in early childhood – often in the first year of life, when it can be particularly severe. Findings from the National Child Development Study, developed from the birth cohort of 1958, suggest an incidence of around 50 cases per 1000 in the first year of life, falling to 5 new cases per 1000 per year for the rest of childhood. In around 60% of children, the condition clears by the time they reach their teens. However, the tendency towards dry and irritable skin generally persists and later recurrences are common.

2.5 The aetiology of atopic eczema is complex and not fully understood. Genetic factors are important but environmental factors, such as house dust mites, pollen, tobacco, air pollution and low humidity, may cause its onset and/or exacerbate existing symptoms. More persistent disease has been consistently linked with early disease onset, severe widespread disease in early life, concomitant asthma or hay fever, and a family history of atopic eczema. The condition is exacerbated by soap and detergents, clothes containing wool or certain synthetic fibres, and extremes of temperature.

2.6 The severity of atopic eczema varies enormously, from an occasional dry, scaly patch to a debilitating disease where much of the body is covered by excoriated (scratched and abraded), bleeding and infected lesions. Its course may be continuous for prolonged periods or of a relapsing–remitting nature characterised by acute flare-ups.

2.7 Itching skin (pruritus) is a major symptom of atopic eczema. A vicious circle can occur, where itching and scratching damage the skin and increase inflammation, which in turn increases the itch. Scratching can damage the skin and cause bleeding, secondary infection and thickening of the skin (lichenification).

2.8 The impact of atopic eczema on quality of life can be considerable and it has been shown to vary according to disease severity. In addition to the burden of daily treatment, studies have shown not only that the condition may affect everyday activities, such as work or school, and social relationships, but also that people with atopic eczema may experience anxiety, depression and other psychological problems. Sleep disturbance is common, especially during flare-ups, which in turn can lead to problems with irritability and lack of concentration. Severe atopic eczema in children can also have a significant impact on family life, with parents/carers having to cope with the demands associated with caring for a child with a chronic illness.

2.9 Historically, there have been variations in the clinical definition and diagnosis of atopic eczema. A UK Working Party has developed criteria for use in epidemiological studies, and these are now commonly used, although further validation is required. To qualify as a case of atopic eczema using these criteria, the person must have had an itchy skin condition in the last 12 months, plus three or more of the following criteria:

2.10 There is uncertainty and a lack of standardisation around clinical assessment of disease severity, both in practice and in trial settings. Although a number of scoring systems have been used to categorise the disease as mild, moderate or severe, usually by aggregating scores from a range of symptoms and disease characteristics, none of these scoring systems has been accepted as a 'gold standard' and there is still general debate over their use.

2.11 Atopic eczema in childhood shows a reverse social class gradient, with higher rates in socio-economically advantaged groups and smaller families. There is also evidence of variation in prevalence by region, with the highest rates recorded in the South East and industrialised Midlands, and the lowest rates in Wales and Scotland.

2.12 Management of atopic eczema takes place predominantly in primary care, and aims to relieve symptoms and prevent complications such as infection until remission occurs. This management involves the identification and avoidance of exacerbating factors, skin care and anti-inflammatory treatment. Providing people with good-quality information about these issues is essential to successfully managing and treating atopic eczema. Referral to secondary care is only advised if the condition is severe and has not responded to appropriate therapy.

2.13 Emollients form a standard part of skin care and aim to retain the skin's barrier function (keeping water in and irritants or pathogens out) and prevent painful cracking. Frequent and continuous use is recommended even in the absence of symptoms. Preparations include bath oils, soap substitutes and moisturisers.

2.14 Topical corticosteroids are the first-line treatment for episodic worsening (flare-ups) of atopic eczema. In order to reduce exposure to topical corticosteroids, they are used only intermittently to control exacerbations. Emollients are used with the topical corticosteroids.

2.15 Topical corticosteroids are classified according to their potency. This is determined by the amount of vasoconstriction a topical corticosteroid produces and the degree to which it inhibits inflammation (a more potent product increases suppression to the inflammatory pathway). In the UK, four potencies are recognised: mild, moderately potent, potent and very potent. Across the different potencies, products have different formulations and different strengths (for example, 0.025%, 0.1%, 0.5%) and are available in various preparations (for example, ointment, cream, lotion, foam).

2.16 Treatment regimens for topical corticosteroids vary with disease severity, with clinicians usually recommending use of the mildest potency products possible to treat the condition, in order to minimise the potential adverse effects.

2.17 One of the potential long-term effects of topical corticosteroid treatment is skin atrophy, whereby the skin becomes thin and loses some of its function. This is more likely to occur in areas where the skin is already thin, such as the face and flexures. Although reversible in the short term, prolonged exposure can lead to permanent damage. Signs of atrophy include telangiectasia (abnormal dilation of capillary vessels and arterioles), increased transparency and shininess of the skin, and the appearance of striae (stripes or lines in the skin distinguished from surrounding tissue by colour, texture or elevation). Long-term use of topical corticosteroids on the eyelids has also been associated with the development of glaucoma.

2.18 Systemic adverse effects with topical corticosteroids are rare but include suppression of the pituitary–adrenal axis (which may restrict growth).

2.19 Absorption of topical corticosteroids is higher at certain sites such as the face and flexures, and potent topical corticosteroids are generally avoided in these areas. The more potent topical corticosteroids are also contraindicated in infants younger than 1 year and are avoided in children or used with great care and for short periods. A potent or moderately potent topical corticosteroid may be appropriate for severe atopic eczema on the limbs, but for 1–2 weeks only, followed by a weaker preparation as the condition improves.

2.20 In resistant severe cases, treatment with systemic corticosteroids, phototherapy and systemic use of immunosuppressants, such as ciclosporin, may be required.