Management of atopic dermatitis: nonadherence to topical therapies in treatment of skin disease and the use of calcineurin inhibitors in difficult eczema
Authors: A. Anstey
Journal: British Journal of Dermatology (2009)

Nonadherence (formerly noncompliance) is the commonest cause of treatment failure in the management of atopic dermatitis.1 Why should patients fail to adhere to effective treatments for such a distressing and unsightly disorder? A number of factors are implicated, including widespread steroid disaffirmation,2 and even steroid phobia.3 A systematic review of treatments for atopic dermatitis in 2000 found no randomized, controlled trial evidence to suggest that skin thinning is a problem for correct use of topical corticosteroids.4 Unfortunately, topical corticosteroids are seldom used correctly in atopic dermatitis due to inadequate quantities applied, uncertainty over frequency of application,5 use of lower potency than required, and premature termination of treatment. Additionally, patients may be confused by the prescription of multiple topical products. Eczema management in the U.K. is undertaken mainly by general practitioners, few of whom have specialist training in the management of skin disease or access to expert nursing support. What can be done to address this widespread problem? Gupta et al.6 review nonadherence to topical therapies in this issue of the British Journal of Dermatology, highlighting lessons learnt from oral therapies. Their paper refers to a systematic review on interventions to enhance medication adherence in chronic medical conditions, which concluded that the following were effective: educational/psychosocial interventions and simplification of treatment regimens where possible to shorten the duration of therapy.7 Thus, education of general practitioners and primary care nurses and the use of expert patients may all help to bridge the knowledge gap that often exists in primary care. This in turn should improve patient education about the need to learn how to self-manage their condition. Psychosocial intervention has its place8 but is not widely available in the U.K. and may be hard to access for patients with atopic dermatitis. Simplification and shortening of treatment regimens is possible if effective treatments are prescribed at the outset of management. However, in spite of progress with optimized systemic glucocorticoid therapy,9 long-term topical glucocorticoid therapy continues to be associated with risk; steroid phobia may therefore resist these interventions2, 3 and cause nonadherence. Topical calcineurin inhibitors are increasingly used in the treatment of atopic dermatitis and may be useful in patients with steroid phobia. Initial safety concerns for tacrolimus have not been realized in long-term studies.10 This issue of the British Journal of Dermatology includes a randomized, vehicle-controlled trial on the effects of 1% pimecrolimus cream in the treatment of patients with atopic dermatitis with insensitivity to topical corticosteroids.11 Leung et al. selected patients with atopic dermatitis who were clinically insensitive to topical corticosteroids and studied the relationship between disease severity and colonization with Staphylococcus aureus. Staphylococcus aureus is implicated in the induction of corticosteroid resistance by the action of superantigens on T cells via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway.12 Seventy-three subjects were randomized to 1% pimecrolimus cream or the vehicle cream. Increased S. aureus counts in this study were significantly correlated with worsening clinical severity scores. Furthermore, mean eczema severity scores on the head and neck showed greater improvement with pimecrolimus cream than with vehicle at all observed time points over the 6-week study. What does this mean for routine clinical practice? In the face of apparent steroid resistance, a switch to pimecrolimus cream has both scientific validity and in some patients may result in a useful clinical response. Resistant facial eczema presents particular treatment problems due to anxiety about possible steroid-associated side-effects at such a visible site, and concerns about corticosteroid side-effects on the eye. In this issue of the British Journal of Dermatology, Doss et al.13 report a double-blind head-to-head study comparing the efficacy of 0·1% tacrolimus ointment with 0·005% fluticasone ointment as second-line treatment for adults with moderate to severe facial eczema. Both treatments were effective, with superior rates of response with tacrolimus. Neither treatment produced adverse effects that were unexpected according to the summaries of product characteristics (SPCs). What is the significance of this study? It is important as it provides strong evidence to support the use of tacrolimus ointment as second-line treatment for resistant facial eczema. This may be particularly helpful for steroid-phobic patients, and is reassuring to prescribers concerned about long-term prescribing of topical corticosteroids to the face. Additionally, evidence-based changes in the management of difficult eczema are essential if progress is to be made in decreasing nonadherence.