Current Topics of Strategy of NSAID-Induced Small Intestinal Lesions

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.

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“…18 5) alterations in the innate immune system to include tumour necrosis factor (TNF) activation. 19,20…”

Section: Epidemiologymentioning

confidence: 99%

Review article: drug‐induced small bowel injury

Hamdeh

Micic

Hanauer

2021

Aliment Pharmacol Ther

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“…Unnecessary use of PPIs should be discontinued unless the patient has indications for PPI use, such as peptic ulcer, reflux esophagitis, or a history of UGIB. Because mucoprotective agents, including rebamipide, irsogladine, and misoprostol, are helpful in the protection and healing of NSAID‐induced enteropathy, it is necessary to administer a mucoprotective agent together in patients requiring PPI use 31 . Our strategy will help reduce the risk of LGIB while simultaneously providing maximum beneficial effects on the UGI tract.…”

Section: Discussionmentioning

confidence: 99%

Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta‐analysis

Jung

Park

2023

UEG Journal

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BackgroundSeveral studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated.MethodsWe searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta‐analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non‐users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti‐inflammatory drugs (NSAIDs) was also performed.ResultsTwelve studies with 341,063 participants were included in this meta‐analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]] = 1.42 [1.16–1.73]; hazard ratio [HR] [95% CI] = 3.23 [1.56–6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI] = 1.64 [1.49–1.80]; HR [95% CI] = 6.55 [2.01–21.33]). In the bleeding site‐specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI] = 1.54 [1.30–1.84]).ConclusionsPPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.

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“…Indeed, some reports describing the risk of PPIs on the small intestinal injury in human have been recently published although the interaction between NSAIDs and PPIs use for small intestinal bleeding have been still under controversial. ( 36 – 39 ) Therefore, we consider that mucosal protection, which is independent of acid-suppression, will be necessary to prevent NSAID-induced enteropathy for patients receiving long-term treatment with aspirin.…”

Section: Discussionmentioning

confidence: 99%

Effect of egualen sodium hydrate on small-intestinal mucosal damage induced by low-dose aspirin: a prospective randomized clinical trial

Iguchi

Kakimoto

Kuramoto

et al. 2018

J. Clin. Biochem. Nutr.

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Low-dose aspirin, which is widely used to reduce the risk of cardio- and cerebrovascular thrombosis, often induces gastroenteropathy by increasing the permeability of the mucosa. However, therapeutic strategies for patients with low-dose aspirin-induced small intestinal injury have not been determined. We evaluated the preventative effect of egualen sodium hydrate, a gastro-protective agent that suppresses indomethacin-induced small-intestinal damage in rats, against small-intestinal mucosal damage induced by low-dose aspirin in healthy adult male volunteers. Participants were randomly allocated to receive aspirin 100 mg/kg daily (control group, n = 10) or aspirin 100 mg/kg plus egualen sodium 30 mg daily (egualen sodium group, n = 10). Small intestinal mucosal injury was evaluated by capsule endoscopy two weeks after initiation of drug administration. Fecal analyses (occult blood test, immunochemical test, transferrin measurement and calprotectin measurement) were carried out before and after treatment. Egualen sodium significantly suppressed the total number of small intestinal injuries detected by capsule endoscopy and the positive ratio for the fecal occult blood test. Daily use of 30 mg of egualen sodium showed a preventative effect on low-dose aspirin-induced small intestinal injury. Since acid suppression therapy was reported to exacerbate NSAIDs-induced enteropathy via dysbiosis, egualen sodium may be useful for patients treated with low-dose aspirin.

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Current Topics of Strategy of NSAID-Induced Small Intestinal Lesions

Cited by 9 publications

References 53 publications

Review article: drug‐induced small bowel injury

Review article: drug‐induced small bowel injury

Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta‐analysis

Effect of egualen sodium hydrate on small-intestinal mucosal damage induced by low-dose aspirin: a prospective randomized clinical trial

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