Systematic review: adrenal insufficiency secondary to swallowed topical corticosteroids in eosinophilic oesophagitis

Background: Swallowed topical corticosteroids are prescribed for eosinophilic oesophagitis (EoE), but there is a theoretical risk of adrenal insufficiency from their use. Aims: To determine if the use of topical corticosteroids to treat EoE is associated with the development of adrenal insufficiency. Method: We conducted a systematic review of the published literature from January 1, 1950 to April 1, 2017 using Pubmed, Embase, Web of Science and Cochrane Central. Studies and meeting abstracts were included that described patients with EoE who received swallowed topical corticosteroids and any investigation for adrenal insufficiency. Results: The search revealed 1610 unique publications, and 17 met inclusion criteria. There were 7 randomised controlled trials (RCTs), 6 prospective observational studies, 3 retrospective observational studies, and 1 case report. Cortisol measurements were performed on 596 individuals with EoE who received topical corticosteroids. Adrenal testing was abnormal, as defined by each study, in 94/596 patients (crude rate of 15.8%). Only 2 studies were considered to have a low risk of bias, being randomised controlled trials that estimated adrenal insufficiency in the active treatment and placebo groups, before and after treatment. None of the seven randomised controlled trials demonstrated statistically significantly different rates of adrenal insufficiency between topical corticosteroid and placebo over treatment intervals of 2-12 weeks. Conclusion: Topical corticosteroids were associated with adrenal insufficiency in a minority of patients. Most cases came from uncontrolled observational studies, with widely varying definitions of adrenal insufficiency. Longer follow-up and larger controlled studies are needed to quantify the risk of adrenal insufficiency with maintenance topical corticosteroid therapy in EoE.