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Topical steroids may trigger or worsen other skin disorders such as acne, rosacea and perioral dermatitis. In addition to the use of topical steroids for acne treatment, oral medications and oral or topical nonsteroidal anti-inflammatory drugs (NSAIDs) have been studied in the use of the systemic inflammatory response to acne. These drugs include antibiotics such as ceftriaxone and doxycycline, and NSAIDs such as ibuprofen and naproxen. Both drugs have shown promising results in reducing the severity of symptoms in the face and hands of patients with moderate to severe acne.1,2 The goal of this study is to evaluate the effect of isotretinoin, a topical steroid, on the systemic inflammatory response. Methods This is a prospective, randomized, double‐blind, placebo‐controlled study conducted between January 2008 and July 2010 in children aged 7–17 years with mild to moderate acne (Gruvé et al., unpublished data). Children were randomized to receive isotretinoin or placebo and treated by both oral and transdermal applications of isotretinoin or sham with increasing doses. An acne severity score was also obtained. During the first 6 months of treatment, children were followed for acne flares. Follow‐up assessments were conducted at 6, 12 and 24 months. We defined a flare as the first occurrence of at least 4 flare days (in the presence of acne, flares are defined as a single day where a child with acute acne is seen in a clinic). These flare days were scored on the Intranasal Anti‐inflammatory Threshold (IAT) scale (0.5–2) in the presence (no flare) and absence of acne (1 or 2 flare days). The overall incidence of flare was 7.7%; with a mean of 3.3 flare days per patient. The occurrence of flare was significantly higher in the isotretinoin group than the placebo group for both baseline (P < .001) and at 24 months (P = .006). For the study efficacy analysis, we used a multivariable multivariate model, adjusted for the number of flares and severity of acne. This model is based on baseline severity and was used to assign patients to the groups. We then conducted a multivariable linear regression model with a random intercept to estimate the adjusted difference in severity between the groups. The model included 4 major predictor variables. The main predictors were sex, age, race, ethnicity and previous use of isotretinoin or placebo. Age was adjusted for using age×sex×ethnicity Related Article: