Review article: drug‐induced small bowel injury

Abstract

Background: Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects. Aim:To provide an updated literature review detailing medications linked to the development of small bowel injury. Methods:We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports.Results: Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin. Conclusion:Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.

Isotretinoin-Induced Distal Ileitis Mimicking Crohn’s Disease

“…Although not associated with an increased IBD risk, our patient highlights the possibility of isotretinoin inducing small bowel injury, similar to what has been reported with other drugs [8]. As in our case, in patients using isotretinoin who are found to have evidence of intestinal inflammation, without any other obvious cause, it should be considered as a possible instigator.…”

“…However, it may present multiple possible etiologies, such as infections, malignancies, vascular, autoimmune and/or inflammatory disorders [1][2][3]5,6]. Evidence of drug-related inflammation of the small bowel and the remaining gastrointestinal tract has also been described, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a classic example [2,[5][6][7][8].…”

Drug-Related Enteropathy

“…Non-steroidal anti-inflammatory drugs (NSAID) are prescribed for a variety of pain and inflammation-associated conditions such as rheumatologic and orthopedic disorders, migraine as well as post-surgical states, and exert their effects through cyclooxygenase (COX) inhibition with resultant decrease of prostaglandin synthesis. NSAID are associated both with upper and lower GI symptoms, as well as mucosal injury at any part of the GI tract, and symptoms vary widely from dyspepsia and heartburn to diarrhea, bloating and overt GI bleeding [7,8,11,[52][53][54][55]. Despite gastroduodenal damage is the most common clinical presentation in most NSAID long-term users, up to 70% may develop different degrees of mucosal breaks, including erosions, ulcerations, mucosal hemorrhage or even stenosis in distal portions of the small intestine such as jejunum or ileum, as determined by studies using video capsule endoscopy [56,57].…”

“…Acetylsalicylic acid (e.g., aspirin), even at low doses, may induce small bowel mucosal breaks after 2 weeks of therapy, mainly due to direct contact damage. On the other part, selective COX-2 inhibitors (ICOX-2) such as celecoxib and etoricoxib have their effect only over the inflammatory isoform, sparing COX-2 and thus, reducing significantly the risk of mucosal damage, unless they are given for prolonged periods of time, after which may have similar risk to that seen with conventional NSAID [7,11,53,54,58,59]. Several approaches may diminish the risk of NSAID-induced enteropathy, including withdrawal of drugs, use of selective ICOX-2, or NSAID at the lower therapeutic dose and for short periods of time, or combination with probiotics such as Lactobacillus casei, VSL#3, and S. boulardii, as well as misoprostol, a prostaglandin analog.…”

“…Chronic diarrhea is one of those conditions with the broadest differential diagnosis, that includes anatomical and/or physiologic abnormalities of the gastrointestinal (GI) tract, inflammatory or neoplastic conditions, malabsorptive disorders, drug side effects, dysbiosis, functional as well as postinfectious syndromes such as small intestine bowel overgrowth (SIBO), functional diarrhea or post-infectious irritable bowel syndrome (Pi-IBS) [2][3][4][5][6]. One of the most common, albeit rarely unconsidered causes, is drug-side effect [7,8]. A large number of at least 700 drugs have been implicated as cause of chronic diarrhea through a number of different, and sometimes overlapped pathophysiologic mechanisms [9].…”