Drug-Induced Inflammatory Bowel Disease and IBD-Like Conditions

Abstract

The pathogenesis of inflammatory bowel disease (IBD) is multifactorial and results from an interaction between genetic, immunologic, microbial, and environmental factors. Certain drugs could act as a trigger for the disease and have been implicated in the development of new onset IBD in a number a studies. These relationships are based on case reports and cohort studies, as proving this in the context of randomized controlled trials would be difficult. Drugs that have been linked to causing or worsening IBD include isotretinoin, antibiotics, nonsteroidal antiinflammatory drugs, oral contraceptives, mycophenolate mofetil, etanercept, ipilimumab, and rituximab. Bowel preparation for colonoscopy has also been associated with aphthoid lesions that may be confused with IBD. However, given the source of these reports we have to be cautious in the interpretation of the data before concluding that these drugs trigger IBD and what is being observed is not related to other confounding factors. Different pathogenic mechanisms have been suggested for the different drugs listed above. In order to clarify the confusion a comprehensive literature review was performed with the goal of advancing the knowledge on this subject.

Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2

“…Consistent with this hypothesis are animal models of colitis that use chemical disruption of the epithelial barrier with trinitrobenzene sulfonic acid, dextran sodium sulfate, or nonsteroidal anti-inflammatory drugs (NSAIDs) to elicit inflammation (11). Further, disruption of the intestinal epithelial barrier by exposure of susceptible patients to NSAIDs (blockers of prostaglandin synthesis) is a risk factor for intestinal inflammation (12).…”

Evaluation of the gastrointestinal findings of nodulocystic acnepatients during systemic isotretinoin therapy

“…Since the first detailed report of an association of oral isotretinoin therapy with IBD by Brodin (10) in 1986, a total of 12 cases of isotretinoin-related IBD have been reported in the English literature (11)(12)(13). Many studies concerning the relationship between isotretinoin and IBD have been conducted, but there is no concordance between their results (14). Reddy et al concluded that in a subgroup of patients, isotretinoin might serve as a trigger for IBD (15).…”

Pathogenesis of Ulcerative Colitis and Crohn’s Disease: Similarities, Differences and a Lot of Things We Do Not Know Yet

“…Some medications are suspected to participate in the development and in relapses of IBD [127]. First of all, previous antibiotic use has been suggested to increase the risk of IBD, particularly CD, by altering the intestinal flora.…”

“…Numerous studies have found a positive correlation between the use of NSAIDs and the onset of UC [134], CD [135] or both [136,137]. This can be mediated via several mechanisms, most notably, NSAIDs inhibit the cyclooxigenase (COX) enzyme, thereby decreasing the synthesis of prostaglandins, which are important to mucosal integrity and function [127]. They also alter mucosal microcirculation and cause direct damage to the epithelium, resulting in a permeability increase.…”

“…Oral contraceptives can be capable of provoking IBD by the proinflammatory properties of estrogen and its effects on the mucosal microcirculation [127]. Several publications have reported an increased risk of CD [97,139] or both CD and UC [140] among women using oral contraceptives.…”