Impact of Dose Reduction of Topical Steroids to Manage Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis

Swallowed topical corticosteroids (STS) are a highly effective medical option to treat eosinophilic esophagitis (EoE) ,but are also associated with potential side effects related to systemic absorption, including adrenal suppression or insufficiency (AI). This study aimed to examine children with EoE treated with STS who developed AI and assess whether the dose of STS, type of STS, or other factors may be associated with the development of AI.This study reviewed children with EoE who had a diagnosis of adrenal insufficiency and were cared for at Children’s Hospital of Colorado between 2012 and 2021. Patients were included if they had a diagnosis of EoE treated with STS and received a diagnosis of AI (defined by peak cortisol of <18 µg/dL on low-dose ACTH stimulation testing) or a prescription for injectable form of hydrocortisone for stress dosing. Subjects receiving treatment with systemic steroids at the time of AI diagnosis were excluded. Controls were obtained from a prior study of AI in EoE and included STS-treated EoE subjects with normal morning cortisol or ACTH stimulation testing.This was a retrospective case-control study. Data collected on each subject included demographics, concomitant atopic diagnoses, STS prescribed dosage, steroid modalities (inhaled, intranasal, swallowed), laboratory data, and peak esophageal eosinophil counts (Eos/HPF). Each topical steroid formulation used to treat EoE was standardized to an equivalent dose of fluticasone proprionate per body surface area to be compared. Logistic regression models were used to examine the association of occurrence of AI with STS dose, inhaled steroid dose, and intranasal steroid dose.Thirty-two patients with STS-treated EoE and AI were identified and compared with 81 STS-treated EoE controls without AI. Among the 16 subjects with recovery of adrenal function, 10 continued STS with a significant average dose decrease of 48% from 1011 to 528 fluticasone equivalent μg/m2 (P = .01). The dose reduction in the 8 subjects who did not recover from AI was less at 30%, from 721.9 to 502.5 fluticasone equivalent μg/m2 (P = .313). Eight of the 32 patients with AI who were also receiving extended release (ER) budesonide for treatment of concomitant lower eosinophilic GI disease were noted to have a 7-fold higher total daily steroid dose and thus were analyzed separately. Excluding the patients who were also on ER budesonide, there was no significant difference in the STS dose nor total daily steroid dose between the 24 cases with AI compared with the 81 controls without AI. Following AI diagnosis, STS dose reduction was associated with recovery of adrenal function in 66%, but the percentage of subjects with active EoE increased from 35% to 66%. Logistic regression showed a trend toward significance on the contribution of inhaled steroids on risk of developing AI.In patients with STS-treated EoE, analysis did not reveal a discrete threshold dosage that led to an increased likelihood of AI. Further studies are warranted to identify risk factors for AI development, such as threshold dose for STS exposure or cumulative long-term exposure. Adrenal monitoring is recommended in this population and if AI is diagnosed, dose reduction of STS can lead to adrenal recovery, but may also result in increased disease activity.EoE is a chronic condition that can be treated with STS to maintain symptomatic and histologic remission, but clinicians should be aware of the risk of AI, with incidence estimates ranging from 5% to 10%. Although this study did not identify a discrete threshold dose of STS that increased the likelihood of AI, it does highlight the importance of monitoring after initiation of STS, especially in patients who may be receiving additional corticosteroids in other forms, such as ER budesonide and inhaled corticosteroids. Furthermore, although the normalization of adrenal function in 12 of 20 subjects who continued STS at reduced doses is encouraging, these strategies will need to be balanced against the risk of increased disease activity. The limitations of the study included retrospective nature, inability to determine the cumulative steroid exposure of subjects, small samples, and not having standardized timing of ACTH stimulation testing. Future prospective studies are needed to better identify STS dose thresholds and other factors, such as genetic susceptibility, that place patients at higher risk for AI.