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A possible aetiological role in the development or exacerbation of inflammatory bowel disease (IBD) has been suggested for a small number of drugs, including antibiotics,1 non-steroidal anti-inflammatory drugs (NSAIDs)2 and, more contentiously, oral contraceptive pills.3 Intriguing and less appreciated is the potential association of IBD with the use of the vitamin A analogue isotretinoin (13-cis-retinoic acid) which is widely prescribed in the treatment of severe acne. A small number of case reports have reported the development of IBD whilst receiving isotretinoin therapy.4–11 A review of adverse events reported to the United States Federal Drug Administration’s (FDA) Medwatch scheme over a 5 year period (1997–2002) revealed 85 cases of IBD, of which the causal association with isotretinoin was considered probable or highly probable in 73% of cases.12 It has been questioned whether this represents a true aetiological link, with the biggest confounder being the overlap in the peak age of the onset of IBD with the age group most commonly prescribed isotretinoin.13 Despite this there is biological plausibility in why such an association may exist. Retinoids have been shown to exhibit diverse effects on epithelial cell turnover, as well as glycoprotein and cytokine synthesis. More recently, advances in our understanding of the immunology of the gut have shown a fundamental role for retinoids in the regulation of the intestinal mucosal immune response.
Here we discuss the literature on the association of isotretinoin therapy with intestinal inflammation and IBD, present an update of epidemiological and pharmaco-vigilance data, and highlight possible underlying mechanisms, based upon recent advances in mucosal immunology.
IBD has not been noted in clinical trials of isotretinoin in the treatment of acne, but the exposure length and number of patients in trials may not have been sufficient. The association has …
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