To the Editor:
Atopic dermatitis (AD) is a chronic inflammatory disorder that frequently develops during childhood, with a prevalence of 12% to 37%.1, 2 Treatment often involves topical corticosteroids; however, there is concern, often on the part of parents, regarding potential effects on bone in children.2 Little is known about the risk of fracture in children with AD on topical corticosteroids. The objective of this study was to utilize a population-based cohort to examine the association between topical corticosteroid use and subsequent fracture risk among children diagnosed with AD prior to age 4.
The study was conducted using the Rochester Epidemiology Project (REP), a centralized infrastructure that collates the medical records of Olmsted County, Minnesota residents.3 We identified patients who received their first diagnosis of AD prior to age 4 years, during 2004 through 2017. Prescriptions for topical corticosteroids were identified using the resources of the REP. Bone fractures were identified using diagnosis codes, excluding pathological fractures in neoplastic disease, skull, or facial bone fractures. The primary analysis evaluated topical corticosteroid exposure as a binary time-dependent covariate in a Cox proportional hazard model using age as the time scale. A landmark analysis was performed as a sensitivity analysis; each patient’s 4th birthday was defined as the landmark or starting point.4 Patients who had a fracture prior to age 4 or whose last clinical follow-up was prior to age 4 were excluded from the landmark analysis, and exposure status prior to age 4 was evaluated as a baseline covariate in a Cox model.
A total of 3542 patients met inclusion criteria (Figure 1). Two-thirds (2384 [67.3%]) received a topical corticosteroid prescription prior to age 4. Of the 3542 patients, 451 (12.7%) had a fracture after AD diagnosis, at a median age of 7.4 years (IQR, 3.8–10.0 years). The use of topical corticosteroid, evaluated as a time-dependent covariate, was found to be associated with a non-significant 17% increase in the risk of fractures (unadjusted HR 1.17, 95% CI 0.94–1.44, p=0.16; HR adjusted for age and sex 1.16, 95% CI 0.94–1.43, p=0.18).
Figure 1:
Flow chart showing cohort identification and patient characteristics for both the primary analysis and landmark analysis.
The landmark analysis consisted of 2499 patients (Figure 1), of which 1722 (68.9%) had a prescription for a topical corticosteroid prior to age 4. A total of 333 (13.3%) patients had their first fracture after AD diagnosis, at a median age of 8.7 years (IQR, 6.7–10.9 years). Figure 2 depicts the cumulative incidence of a fracture among those with versus without topical corticosteroid exposure prior to age 4 (unadjusted HR 1.00, 95% CI 0.80–1.26, p=1.00; HR adjusted for age and sex 1.00, 95% CI 0.80–1.26, p=0.99), demonstrating no association between topical corticosteroid use and fracture.
Figure 2:
Cumulative incidence of fracture among patients with atopic dermatitis diagnosis prior to age 4 who were exposed to topical corticosteroids and those unexposed to topical corticosteroids, based on a landmark analysis.
“Corticophobia”, or fears related to topical corticosteroid use, is highly prevalent in parents of children with AD ages 0–5 years, which has implications for disease control.5 Our findings may be reassuring to parents, as children diagnosed with AD prior to age 4 and prescribed topical corticosteroids did not have a significantly increased fracture risk.
Limitations of this study include the retrospective design, predominantly Caucasian population, evaluation of ever/never exposure to topical corticosteroids rather than cumulative exposure, the lack of an active comparator design and lack of multivariable analyses. Future studies are required to address confounding covariates such as the presence of asthma, the number of visits for AD, systemic corticosteroid exposure, and cumulative exposure to topical corticosteroids.
Footnotes
Conflicts of interest: None declared
IRB approval status: Reviewed and approved by the Mayo Clinic Institutional Review Board; ID # 19-001137
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