Systematic review of published trials: long-term safety of topical corticosteroids and topical calcineurin inhibitors in pediatric patients with atopic dermatitis

Abstract

BackgroundMany clinicians have concerns about the safety of atopic dermatitis (AD) treatments, particularly in children requiring long-term daily maintenance therapy. Topical corticosteroids (TCS) have been widely used for >5 decades. Long-term TCS monotherapy has been associated with adverse cutaneous effects including atrophy, rebound flares, and increased percutaneous absorption with potential for adverse systemic effects. Topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, available for 1–2 decades, are not associated with atrophy or increased percutaneous absorption after prolonged use and have much lower potential for systemic effects. However, since 2006 TCIs have carried a controversial Boxed Warning based on a theoretical risk of malignancy (eg, skin and lymphoma) that has limited TCI use for standard-of-care maintenance therapy.MethodsA comparative systematic search of PubMed was done for long-term (≥12 week) clinical trials of TCS or TCI treatment in patients <12 years with AD. Citations were reviewed for inclusion based on MeSH terms, abstracts, and relevant article text. Studies were excluded if they did not encompass subjects <12 years, or were <12 weeks’ duration, retrospective, meta-analyses, or limited to anecdotal case reports.ResultsOf 27 trials meeting criteria, 21 included 5825 pediatric patients treated with TCIs, and 6 included 1999 patients treated with TCS. TCS studies were limited to low- to mid-potency products, and all but one study lacked a vehicle control. Eight TCI studies were vehicle-controlled, and safety data were well reported, with ≤5 % of patients reporting discontinuation due to adverse effects (DAEs). Cutaneous and systemic adverse events (AEs) were similar in TCI and vehicle groups, with no reports of lymphoma. Safety data in TCS trials were less well reported. DAE incidence was addressed in just 2 trials, and systemic and cutaneous AEs were mostly unreported.ConclusionsData supporting long-term use of TCIs are robust, documenting safety and efficacy, while data supporting long-term TCS use are limited to low- to mid-potency products. Our review identifies a lack of information on the safety of commonly prescribed, long-term monotherapy with mid- to high-potency TCS in pediatric AD, and supports standard-of-care maintenance therapy with TCIs and intermittent use of low- to mid-potency TCS for flares.

Atopic Dermatitis: Early Treatment in Children

“…A recent systematic review of AD patients less than 12 years of age found that the evidence supporting long-term TCS use is limited only to low- to mid-potency agents, and there was a lack of data supporting the use of long-term monotherapy with mid- to high-potency TCS in pediatric AD [60]. In fact, continuous, long-term application of high- and very high-potency agents can lead to significant systemic absorption and increased risk of systemic adverse effects, such as hypothalamic-pituitary-axis (HPA) suppression, especially in children concurrently receiving other forms of steroids for asthma [61].…”

Management of Children with Atopic Dermatitis: A Narrative Review

“…Basically, lowto-mid potency TCS should be used as first-line treatment. No TCS is indicated for > 4 consecutive weeks of use (21).…”

Current Views on the Pathogenesis and Principles of External Treatment of Atopic Dermatitis in Children

“…Другие авторы в обзоре за последние 10 лет [40] сообщи-ли, что местное применение тГКС не приводило к разви-тию глаукомы и катаракты. Тем не менее стоит опасаться длительного нанесения тГКС на тонкую и нежную кожу лица, век, а также в крупных естественных складках [40].…”