Systematic review of treatments for atopic eczema.

BACKGROUND: Atopic eczema is the commonest inflammatory skin disease of childhood, affecting 15-20% of children in the UK at any one time. Adults make up about one-third of all community cases. Moderate-to-severe atopic eczema can have a profound effect on the quality of life for both sufferers and their families. In addition to the effects of intractable itching, skin damage, soreness, sleep loss and the social stigma of a visible skin disease, other factors such as frequent visits to doctors, special clothing and¿the need to constantly apply messy topical applications all add to the burden of disease. The cause of atopic eczema is unknown, though a genetic pre-disposition and a combination of allergic and non-allergic factors appear to be important in determining disease expression. Treatment of atopic eczema in the UK is characterised by a profusion of treatments aimed at disease control. The evidential basis of these treatments is often unclear. Most people with atopic eczema are managed in primary care where the least research has been done. OBJECTIVES: The objectives of this scoping review are two-fold. To produce an up-to-date coverage 'map' of randomised controlled trials (RCTs) of treatments of atopic eczema. To assist in making treatment recommendations by summarising the available RCT evidence using qualitative and quantitative methods. METHODS: None DATA SOURCES: Data sources included electronic searching of MEDLINE, EMBASE, the Cochrane Controlled Clinical Trials Register, the Cochrane Skin Group specialised register of trials, hand-searching of atopic eczema conference proceedings, follow-up of references in retrieved articles, contact with leading researchers and requests to relevant pharmaceutical companies. INCLUSION/EXCLUSION CRITERIA: Only RCTs of therapeutic agents used in the prevention and treatment of people with atopic eczema of any age were considered for inclusion. Only studies where a physician diagnosed atopic eczema or atopic dermatitis were included. DATA EXTRACTION: Data extraction was conducted by two observers onto abstraction forms, with discrepancies resolved by discussion. QUALITY ASSESSMENT: The quality assessment of retrieved RCTs included an assessment of: a clear description of method and concealment of allocation of randomisation, the degree to which assessors and participants were blinded to the study interventions, and whether all those originally randomised were included in the final main analysis. DATA SYNTHESIS: Where possible, quantitative pooling of similar RCTs was conducted using the Cochrane Collaboration's methods. Where statistical heterogeneity was found, sources of heterogeneity in terms of study participants, formulation or posology of intervention, and use of co-treatments were explored. Where pooling was not deemed to be appropriate, detailed descriptions of the study characteristics and main reported results were presented along with comments on study quality. RESULTS: A total of 1165 possible RCTs were retrieved in hard copy form for further scrutiny. Of these, 893 were excluded from further analysis because of lack of appropriate data. The 272 remaining RCTs of atopic eczema covered at least 47 different interventions, which could be broadly categorised into ten main groups. Quality of reporting was generally poor, and limited statistical pooling was possible only for oral cyclosporin, and only then after considerable data transformation. There was reasonable RCT evidence to support the use of oral cyclosporin, topical corticosteroids, psychological approaches and ultraviolet light therapy. There was insufficient evidence to make recommendations on maternal allergen avoidance for disease prevention, oral antihistamines, Chinese herbs, dietary restriction in established atopic eczema, homeopathy, house dust mite reduction, massage therapy, hypnotherapy, evening primrose oil, emollients, topical coal tar and topical doxepin. There was no RCT evidence to support any clear clinical benefit on the use of avoidance of enzyme washing powders, cotton clothing as opposed to soft-weave synthetics, biofeedback, twice-daily as opposed to once-daily topical corticosteroids, topical antibiotic/steroid combinations versus topical steroids alone and antiseptic bath additives. There was complete absence of RCT evidence on short bursts of potent versus longer-term weaker topical steroids, dilution of topical corticosteroids, oral prednisolone and azathioprine, salt baths, impregnated bandages, wet-wrap bandages, water softening devices, allergy testing, and different approaches to organisation of care. CONCLUSIONS: COVERAGE: The evidence base for the prevention and treat-ment of atopic eczema has many limitations. It is characterised by a profusion of short-term trials of ‘me too’ products, a lack of common outcome measures which measure things that are important to patientsý poor standards of clinical trial reporting, and a lack of data on questions that physicians and people with atopic eczema deem to be important. Little research has evaluated commonly used treatments compared with each other or in combination. This mismatch is probably due to a combination of the questions not being asked coupled with a lack of independent investment in primary atopic eczema research. RECOMMENDATIONS FOR RESEARCH: Urgent primary research priorities include RCTs of wet-wrap treatments, the clinical benefit of allergy testing, the use of water softeners, the role of specialist nurses, comparisons of tacrolimus and ascomycin against topical corticosteroids, studies of disease prevention, and the use of emollients in preventing disease relapse. Such RCTs should ideally be pragmatic and simple in design, with a few outcome measures that doctors and patients find easy to understand. They should ideally be of 4 months’ or more duration in order to capture the chronicity of disease as well as short-term effects. If such trials are intended to inform primary care, where patients may have milder disease, then they should be conducted in a primary care setting. This review suggests that there is some scope for further secondary research by systematically reviewing some of the major treatment groups such as antihistamines and essential fatty acids in more detail, and some of these are already underway within the Cochrane Skin Group. Future methodological research is needed to increase the clinical relevance and reliability of outcome measures for atopic eczema. The RCT database contained within this report also provides a good opportunity to conduct some general research into the relationship between study quality and treatment benefit. There is much scope for improving the standard of clinical trial reporting in atopic eczema by dermatology journals adopting rigorous checks on clinical trial reporting and by registering ongoing trials with the Cochrane Skin Group.