A TREAT in store for those wishing to identify uncertainties in the treatment of severe childhood eczema
Authors: H.C. Williams
Journal: British Journal of Dermatology (2013)

In this month's issue of the British Journal of Dermatology, Proudfoot and a group of European colleagues present the results of a survey (called TREAT) of the current reported use of systemic treatments in children with severe atopic eczema in eight European countries.1 Their treatment survey, which excluded treatment of acute flares, showed large variations in practice in terms of first- and second-choice medications and how long they are used for. The Swedes, for example, like their oral corticosteroids, the Germans are committed to ciclosporin (with the French and Italians following close behind), the Danes have an affinity to azathioprine, and the British can't seem to make their mind up between ciclosporin and azathioprine. The Dutch and the Spanish are evenly split between ciclosporin and oral steroids, and nobody seems to like methotrexate very much at all. Use of both azathioprine and methotrexate was often extended beyond 12 months, whereas ciclosporin tended to be used for only 2–4 months. Such a short duration for ciclosporin is understandable because of the risk of renal damage,2 but it is not clear how such a short duration of treatment can be helpful in the long-term control of a chronic and severe disease. No information is given on the dosing schedule and duration of oral steroids in those surveyed, but the fact that they are widely used outside of the context of acute flares at least 30% of the time in all eight countries is of concern, given the potential for harmful effects from long-term use of oral steroids, including adrenal gland suppression and growth disturbance in children.3 It would have been interesting to know what other European countries such as Romania, Portugal and Poland are up to, but this was beyond the scope and resources of this study. Reasons for Europe's colourful tapestry of clinical practice for severe eczema include licensing issues (ciclosporin is the only systemic agent licensed for use in those over 16 years of age with atopic eczema in Germany and France, for instance), reimbursement rules, a shaky evidence base allowing wide interpretation of existing data for country-level guidelines, and differences in the way that the survey was interpreted and responded to in different countries. Even accounting for all these factors, it is likely that habit, tradition and strongly held views might also play a key role in explaining at least some of the variations observed.4 It is an interesting observation, for example, that fumaric acid esters have been used for a very long time in Germany and the Netherlands for treating psoriasis, and there is a reasonable evidence base to support their use, but it was only relatively recently that their use became more widespread in the U.K.5 Variation in practice is often inversely proportional to the size and quality of the evidence base and is fertile ground for identifying topics for future research. Previous studies on severe eczema in children seem to have been carried out in a way that does not appear to match the needs of users.6 For example, none of the six small controlled trials of systemic therapies for atopic eczema in children have addressed the main therapeutic dilemmas of current practice identified in the TREAT survey.1 Although there is a slightly better evidence base for systemic treatment of severe atopic eczema in adults,7 children are not just small adults – especially in terms of their propensity towards adverse effects such as interference with bone growth – and severe adult atopic eczema may not be the same disease as severe atopic eczema in children.8 Interestingly, the survey has also exposed a widespread cleansing ritual for children being considered for systemic agents that includes detecting and treating nasal carriage of Staphylococcus aureus, skin antiseptics and oral antibiotics. Where is the evidence base for this practice? Apart from the possible exception of bleach baths,9 there is no clear evidence that antistaphylococcal treatment of people with atopic eczema improves their eczema control.10 Nobody doubts that secondary infection with bacteria does occur in children with severe atopic eczema, and it is acknowledged that most of the previous studies of antistaphylococcal therapies have been small and poorly reported, rather than conclusively showing that such strategies are ineffective, but it is unclear whether these observations alone warrant pretreatment ritual cleansing. When it comes to prioritizing the topics identified by surveys of current practice and systematic reviews of high-quality evidence, it is vital that the views of patients and other key stakeholders are taken into account, as was done in a recent U.K. priority setting partnership in eczema research.11 It is clear from the TREAT survey that there is a large variation in practice in the treatment of severe childhood eczema across Europe, which is hard to explain fully. It is possible that all of the treatments currently in use are effective, or it is possible that some are fairly useless or, worse still, harmful. Large-scale multicentre randomized controlled trials of commonly used treatments for severe atopic eczema in children are overdue. It is hoped that much larger studies such as the CREAM study will help to establish the potential value of antistaphylococcal treatments in this troublesome disease.12 Some groups such as the Paediatric Dermatology Research Alliance in the U.S.A. are already showing promising signs of activity in planning studies of systemic treatment for childhood eczema.13 Whether subsequent trials will be undertaken in multiple countries, and whether there will be a series of trials comparing different pairs of treatments or all commonly used treatments at the same time, using an efficient multiarm multistage design,14 will be up to the research community and funders. The recent U.K. priority setting partnership with patients supports the findings of the TREAT survey in showing that the future research agenda for severe atopic eczema should also include nondrug treatment such as educational interventions.1, 11 I appeal to all investigators of future studies to use the same core outcome measures as recommended by the Harmonizing Outcome Measures in Eczema initiative so that results can be compared,15 to ensure that the studies are adequately powered to detect clinically important differences, and to ensure that they are conducted over a period of 6 months or more so that they can pick up key aspects of chronic disease control and insidious adverse effects. Trial protocols should be registered in the public domain before recruitment starts so that readers can see that the study delivered what it actually set out to do,16 and the trial results should be reported honestly, fully and quickly when the results are known.17 It is time for a step change in the way research into paediatric dermatology is identified, prioritized, designed, conducted and reported.18 We owe it to the children whom we serve. The author wishes to thank Dr Joanne Chalmers for comments on an earlier draft. The author has previously commented on the draft TREAT survey questionnaire and was one of the respondents to the survey.