title: A causal association between isotretinoin and inflammatory bowel disease has yet to be established.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, CB#7080, Chapel Hill, North Carolina 27599, USA. seth_crockett@med.unc.edu
authors.forename: Seth D
authors.initials: SD
authors.lastname: Crockett
authors.forename: Ajay
authors.initials: A
authors.lastname: Gulati
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kappelman
mesh_terms: D015984:Causality; D003879:Dermatologic Agents / Q000009:adverse effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced*; D015474:Isotretinoin / Q000009:adverse effects*
chemical_list: D003879:Dermatologic Agents; D015474:Isotretinoin