Microscopic colitis related to food supplement containing turmeric: a review of 3 cases.

Microscopic colitis is a chronic inflammatory disorder of the colon characterized by microscopic changes in the intestinal lining. Turmeric, a commonly used spice, is generally regarded as beneficial for digestive and articular health thanks to its anti-inflammatory properties. No cases of microscopic colitis under a food supplement containing turmeric has been previously described in the literature. This article highlights 3 cases where the consumption of a specific turmeric-based supplement caused microscopic colitis. Each of them complained about profuse watery diarrhea shortly after initiating the food supplement containing turmeric. Ileo-colonoscopies with biopsies confirmed the diagnosis of microscopic colitis, with two cases classified as lymphocytic colitis and the third as collagenous colitis. Following the discontinuation of the supplement, all patients experienced a resolution of their symptoms within a few days. Subsequent control biopsies for the three patients confirmed the resolution of microscopic colitis.

What do we know today about drug-induced microscopic colitis? A case of lymphocytic colitis on olmesartan.

Microscopic colitis is part of the differential diagnosis of chronic watery diarrhea. Colonoscopy discloses a normal looking mucosa, therefore its diagnosis is based on histology of colonic biopsies. Two main phenotypes are distinguished: collagenous colitis and lymphocytic colitis. A third entity, incomplete microscopic colitis or unspecified microscopic colitis has been reported in the literature. It affects preferentially women over 60 years of age and its association with certain drugs is increasingly established. In case of suspected drug-induced microscopic colitis, identification of the responsible drug is a key to management. After discontinuation of the suspected drug, the gold standard of treatment is budesonide both for induction and for maintenance in case of clinical relapse, as is often the case after discontinuation. Therapy with immunomodulators, biologics, or surgery is reserved for refractory forms of microscopic colitis after multidisciplinary consultation. Through the clinical case of colitis on olmesartan, we will review the latest recommendations on drug-induced microscopic colitis.

Autoimmune and immune-mediated inflammatory diseases after exposure to acid-suppressive medication: A systematic review and meta-analysis.

BACKGROUND: Pharmacovigilance risk signals have proposed a relationship between the use of acid-suppressive medications and the development of certain autoimmune and immune-mediated inflammatory diseases. OBJECTIVE: A systematic review and a meta-analysis was performed. METHODS: We reviewed MEDLINE (Ovid) and Scopus for comparative observational studies between these diseases and previous exposure to proton-pump inhibitors (PPI), H2-receptor antagonists (H2RA), and antacids. The protocol was registered on the PROSPERO database (CRD42020192715). RESULTS: From 3,191 citations, 25 articles were eligible and covered 16 diseases. Microscopic colitis (MC) was studied the most (7 studies). In a random-effects meta-analysis, there was low certainty evidence (GRADE approach) of a non-significant relationship between exposure to any PPIs and MC (meta-OR 3.28, 95% CI 0.98-11.0, I2 98.2%, six studies, 4,436 PPI-exposed MC patients). Moderate certainty evidence pointed towards large odds of collagenous colitis after exposure to lansoprazole (meta-OR 14.5, 95% CI 9.37-22.3, I2 10.2%, three studies, 1,725 lansoprazole-exposed patients). After PPI exposure, the risk of rheumatoid arthritis was slightly increased based on low certainty evidence from two cohort studies totaling 475 diagnoses (meta-RR 1.62, 95% CI 1.12-2.34, I2 34.5%). CONCLUSIONS: In patients with MC, it would be reasonable to carefully review the indication of PPI, especially in CC patients using lansoprazole.

Characteristics and outcomes of cancer patients with pre-existing microscopic colitis after exposure to PD-1 and PD-L1 inhibitors.

PURPOSE: Immune checkpoint inhibitors (ICIs) are frequently associated with adverse events, often affecting the gastrointestinal tract. We conducted this study to determine the characteristics and outcomes of cancer patients with pre-existing microscopic colitis (MC) who underwent ICI treatment. METHODS: In this retrospective study, we identified 10 patients with pre-existing MC who received ICIs at our center 01/2010-06/2020. Clinical characteristics and disease outcomes were recorded. RESULTS: Of 124 screened patients with MC before ICI exposure, 10 had sufficient data to be included in the study. Melanoma (40%) and lung cancer (30%) were the most prevalent cancer types, with 70% of stage IV cancer. Patients received either anti-programmed death 1 regimen (8, 80%) or anti-programmed death ligand 1 agent (2, 20%). Six patients (60%) had collagenous colitis, and 4 (40%) had lymphocytic colitis. The median time from MC diagnosis to ICI initiation was 4 years, with 1 patient on budesonide within 2 months of ICI initiation. Eight patients (80%) developed colitis exacerbations after ICI  and required selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI to colitis exacerbation was 14 days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of 8 patients who had colitis exacerbation, 6 resumed ICI therapy afterward; with 5 receiving concomitant vedolizumab for secondary prophylaxis. CONCLUSION: Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.

Drug Exposure and Risk of Microscopic Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Microscopic colitis (MC) is a chronic inflammatory bowel disease characterized by watery diarrhoea and a normal radiological and endoscopic appearance. Concern regarding a potential association between drug exposure and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association. METHODS: A systematic review and meta-analysis were performed to evaluate the incidence of MC associated with exposure to drug. The PubMed and Embase databases were searched to identify potential studies for inclusion. RESULTS: Twelve case-control studies were included in the meta-analysis. The results showed exposure to NSAID (OR, 1.64; 95% CI: 1.14-2.37; p < 0.001), PPI (OR, 2.36; 95% CI: 1.59-3.52; p < 0.001), SSRI (OR, 2.16; 95% CI: 1.5-3.13; p < 0.001), or aspirin (OR, 2.84; 95% CI: 1.4-5.76; p < 0.001) was related to the incidence of MC; however, such relationships in PPI and SSRI may be modulated by the selection of controls. Furthermore, we did not found a positive association with other drug exposure and MC. CONCLUSION: This meta-analysis indicated that NSAID, PPI, SSRI, or aspirin consumption may increase the risk for MC. Further studies exploring drug-induced microscopic colitis should include control groups with diarrhoea and not only healthy controls.

Adverse event profiles of microscopic colitis in the Japanese Adverse Drug Event Report (JADER) database.

Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. "Colitis microscopic" (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.

Nonsteroidal anti-inflammatory drug exposure and the risk of microscopic colitis.

BACKGROUND: Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. METHODS: A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. RESULTS: In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65-5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found. CONCLUSIONS: In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Secukinumab-Induced Lymphocytic Colitis.

Secukinumab an interleukin-17 (IL-17) monoclonal antibody inhibitor is currently approved for the treatment of rheumatological conditions, such as psoriasis and ankylosing spondylitis. Lymphocytic colitis, a phenotype of microscopic colitis, is a long-term inflammatory condition, is characterized by relapsing diarrhea. The specific entity of drug-induced lymphocytic colitis has been discussed with numerous individual cases being reported from around the world. Secukinumab has been linked with exacerbation of and de novo cases of inflammatory bowel disease. However, lymphocytic colitis in association with this drug has not been documented. The management of drug-induced lymphocytic colitis is complicated, as patients frequently exhibit spontaneous remission of symptoms. Removal of the offending agent has shown some benefit; however, some patients continue to exhibit symptoms months after drug cessation and washout. Although our patient's lymphocytic colitis was benign and responded to the cessation Secukinumab, it is an important diagnosis to consider in patients with new onset relapsing diarrhea treated with biologics.

Quantifying risk factors for microscopic colitis: A nationwide, retrospective cohort study.

BACKGROUND: Microscopic colitis (MC) is associated with several risk factors; however, their relative risk has been variable and not thoroughly evaluated. We aimed to quantify the risk of medical comorbidities and medications associated with MC and treatment offered to these patients. METHODS: A population-based retrospective analysis in International Business Machines (IBM) Explorys (1999-2018), a pooled, de-identified database of 63 million patients in the USA, was performed. Odds ratios (OR) were calculated between MC and other diseases/medications. MC patients were also stratified by age to assess trends of MC in different age groups. RESULTS: A total of 1130 patients had MC in the database. Among medications, non-steroidal anti-inflammatory agents (OR, 20.2) and proton pump inhibitors (OR, 12.1) were associated with highest odds of MC. Among medical comorbidities, infectious gastroenteritis (OR, 26.6) and celiac disease (OR, 22.5) had the highest odds of being associated with MC. Tobacco smoking, psoriasis, Sjogren's syndrome, Clostridium difficile infection, and malabsorption syndromes all conferred odds greater than 10. CONCLUSION: Early identification of MC is critical for minimizing morbidity and mortality. Epidemiologic information can be integrated with current clinical algorithms to more rapidly identify patients at risk.

Medication use and microscopic colitis.

BACKGROUND: Microscopic colitis is an increasingly common cause of watery diarrhoea. Several classes of medications have been associated with microscopic colitis in prior studies. AIMS: To determine the association between the use of previously implicated medications and microscopic colitis. METHODS: This was a case-control study of patients referred for elective, outpatient colonoscopy for diarrhoea. Patients were excluded for inflammatory bowel disease, C difficile, or other infectious diarrhoea. Colon biopsies were reviewed by the study pathologist and patients were classified as microscopic colitis cases or non-microscopic colitis controls. RESULTS: The study population included 110 microscopic colitis cases and 252 controls. The cases were older, better educated and more likely to be female. Cases reported a greater number of loose, watery, or liquid stools, nocturnal stools, more urgency and weight loss compared to controls. There was no association with proton pump inhibitors (PPIs), adjusted OR (aOR) 0.66, 95% CI 0.38-1.13 or nonsteroidal anti-inflammatory drugs, aOR 0.68, 95% CI 0.40-1.17. Cholecystectomy was less common in cases, aOR 0.33, 95% CI 0.17-0.64, but microscopic colitis cases had more frequent bowel movements following cholecystectomy. CONCLUSION: Compared to similar patients with diarrhoea, cases with microscopic colitis were not more likely to have taken previously implicated medications. They had more diarrhoea following cholecystectomy, suggesting that bile may play a role in symptoms or aetiology. We conclude that the appropriate choice of controls is crucial to understanding risk factors for microscopic colitis.

Levodopa/dopa decarboxylase inhibitor associated microscopic colitis: An under-recognized drug reaction.

BACKGROUND: Microscopic colitis is a form of inflammatory bowel disease characterized by profuse non-bloody watery diarrhea. Macroscopic abnormality is not present on colonoscopy, and it requires biopsy for diagnosis. Few cases have been attributed to levodopa/dopa-decarboxylase inhibitor therapy. METHOD: A retrospective cohort study of 21 patients on levodopa/benserazide and one patient on levodopa-carbidopa intestinal gel with clinically suspected or biopsy proven microscopic colitis. RESULTS: All 21 patients on oral levodopa/benserazide had resolution of diarrhea with cessation of the medication. Four patients discontinued levodopa permanently. Two were rechallenged with levodopa/benserazide without symptom recurrence. One patient on oral levodopa/carbidopa developed diarrhea only with intermittent dispersible levodopa/benserazide. 14 were switched to levodopa/carbidopa with resolution of diarrhea in 9 but symptom recurrence in 5. One patient on oral levodopa/benserazide developed profuse diarrhea when switched to levodopa-carbidopa intestinal gel. Of 7/22 patients who had colonoscopy and biopsy, 5 had histopathological proven microscopic colitis. CONCLUSION: levodopa/dopa-decarboxylase inhibitor induced microscopic colitis may be more common than previously suspected, with the potential to affect treatment compliance and therapeutic options.

Medication use and microscopic colitis: a multicentre retrospective cohort study.

BACKGROUND: Medication use has been implicated in the development of microscopic colitis (MC). However, studies have demonstrated inconsistent findings and there exist variations in design. AIM: To measure the association between medication use and MC. METHODS: Patients who underwent a colonoscopy over a 10-year period at two academic medical centres (Columbia University Medical Centre and Mayo Clinic) were identified. Cases were patients with biopsy-proven MC and controls were patients who underwent colonoscopy for evaluation of diarrhoea with biopsies negative for MC. Cases were matched by age, gender and calendar period with up to two controls. Demographics, medication use, smoking history and coeliac disease status were collected. Conditional logistic regression was used with and without adjustment for smoking. RESULTS: A total of 344 patients with MC were matched to 668 controls. After adjusting for smoking, there was an inverse association between MC and use of proton pump inhibitors (PPIs) (OR 0.64; 95% CI 0.47-0.87), H2 blockers (OR 0.46; 95% CI 0.24-0.88) and oral diabetes medications (OR 0.47; 95% CI 0.27-0.81). There was a positive association with nonsteroidal anti-inflammatory drug (NSAID) use and MC (OR 1.63; 95% CI 1.12-2.38). CONCLUSIONS: NSAID use was associated with MC, while use of PPIs, H2 blockers and oral diabetes medications were inversely related to MC. Our use of a control group with diarrhoea, as opposed to healthy controls, may have contributed to these inverse associations. Future studies of drug-induced microscopic colitis should include control groups with diarrhoea, and not only healthy controls.