A causal association between isotretinoin and inflammatory bowel disease has yet to be established.

OBJECTIVES: Case reports have described a possible association between isotretinoin and inflammatory bowel disease (IBD). We critically appraised the literature on this association to assess whether it supports a causal relationship.

METHODS: We systematically searched for case reports, case series, and clinical trials assessing this association. We then applied the Hill criteria to evaluate causality.

RESULTS: Twelve case reports and one case series reported an association between isotretinoin use and subsequent development of IBD. Cases occurred in seven countries over a 23-year period and differed with respect to reported isotretinoin dose, duration of treatment before development of disease, whether disease developed on or off medication, and clinical presentation of disease. No prospective or retrospective studies have examined the relationship between isotretinoin and IBD. An estimated 59 coincident cases of IBD would be expected in isotretinoin users each year, assuming no increased risk. Alternative explanations may account for the sequence of events seen in case reports. Strength, specificity, and consistency of the association are lacking.

CONCLUSIONS: Current evidence is insufficient to confirm or refute a causal association between isotretinoin and IBD. Additional prospective or well-designed retrospective (e.g., case-control) pharmacoepidemiological studies are needed to definitively establish causality.