Diagnosis Of Microscopic Colitis Research Articles

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

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. 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. 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 4years, with 1 patient on budesonide within 2months 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 14days, 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. Our findings suggest that ICI exposure increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy.

Letter to the editor: response to 'Epidemiology and seasonal pattern in hospitalizations for microscopic colitis'.

We read with great interest the letter to the editor by Al-Taee et al. [1] on the seasonal pattern and epidemiology of hospitalizations for microscopic colitis (MC). Their study reviewed the 2016 National Inpatient Sample (NIS) and discussed all admissions for MC occurred between August and December, suggesting a seasonal pattern of MC. To further study this phenomenon, we analyzed NIS data from 2016 to 2019. Using ICD-10 codes, we identified all hospitalizations with a primary diagnosis code of MC (K52.83). We stratified hospitalizations into months and analyzed seasonal trends. We identified 5190 hospitalizations with a primary diagnosis of MC between January 2016 to December 2019. As described by Al-Taee et al. [1], MC was more commonly seen in southern (31.21%) and midwestern regions (30.25%). Females accounted for more than 80% of hospitalizations. Most patients admitted with a primary diagnosis of MC were White (88.34%) and elderly (70.81%). The prevalence of MC with regard to sex and race was comparable to that of 2016. The mean length of stay in these patients was 4.87 (+/-1.2 days), whereas total hospitalization charges were $37 247 (±1065.61). In 2016, admissions for MC were noted only between August and December, as discussed by Al-Taee et al. [1] However, starting in 2017, we noted admissions every month from January to December. The results are provided in Fig. 1. We excluded patients in 2016 and evaluated the consecutive years for a seasonal effect. We noticed that most admissions occurred in July (n = 500; 9.6%), followed by October (n = 460; 8.86%) and April (n = 450; 8.6%). The lowest number of admissions occurred in November (n = 310; 5.97%). Admissions for MC each month are presented in Fig. 1. There were 1195 admissions (24.81%) in the spring, 1315 in the summer (27.33%), 1195 in the fall (24.81%), and 1110 (23.05%) in the winter. Although Al-Taee et al. [1] reported that most admissions occur from August to December, our study revealed a slight predominance in the summer. Another study by LaSala et al. [2] reported a seasonal pattern of lymphocytic colitis, with higher cases in summer and fall, compared with winter months.Fig. 1.: Monthly admissions for microscopic colitis between 2016 to 2019.The limitations of this study were the same as that of the retrospective cross-sectional study by Al-Taee et al. [1] as the data source is the same for these two studies. Given the variable results in the two studies, it is too early to conclude that there is a definite seasonal pattern for MC. However, larger epidemiological studies may provide further information. Acknowledgements None. Conflicts of interest There are no conflicts of interest.

S190 Complete Colonoscopy vs Flexible Sigmoidoscopy to Diagnose Microscopic Colitis

Introduction: Microscopic colitis (MC) is a diagnosis made via biopsy, typically requiring a colonoscopy. Current European guidelines recommend performing a colonoscopy as rectal biopsies alone could miss the diagnosis. The purpose of the study is to retrospectively analyze the data on patients diagnosed with MC and determine if complete colonoscopy with right and transverse colon biopsies is needed to make a diagnosis or if flexible sigmoidoscopy with rectal and left sided biopsies would suffice Methods: We performed a retrospective review of data from 1/1/1999 to 1/12/2019 on patients with a pathologic diagnosis of MC at Gundersen Health System. This study was conducted after the approval by the Gundersen Health System institutional review board. We included 342 patients with a histological diagnosis of either collagenous, lymphocytic, or MC. No patients were excluded. We compared the frequencies of left sided versus random colonoscopy biopsy diagnosis of microscopic colitis using Kappa coefficient as a measure of interrater reliability for agreement. A p-value was calculated to evaluate for significant difference. (Table) Results: Out of 342 patients, 129 patients had positive pathologic diagnosis from left sided biopsy sites alone while 184 patients had positive biopsy results from random biopsy sites. This frequency indicates 53.8% of the diagnoses for MC could be missed by performing left sided biopsies alone. The Kappa coefficient of -0.7896 indicates no agreement between obtaining a pathologic diagnosis from left sided biopsy compared to random with a (p < .0001). None of these patients were using budesonide at the time of biopsy. Conclusion: This study highlights agreement with current European guidelines for the recommendation of doing a complete colonoscopy for the diagnosis of MC. Prior studies including Tanaka M, et al. and Offner FA, et al. have shown consistent results with 30 patients but our study included a larger patient population. Having a Kappa coefficient of -0.7896 indicates moderate disagreement between positive biopsy diagnosis from left and random biopsy sites. While this study may not change current guidelines, it adds validity to them and highlights the importance of performing a colonoscopy and not just flexible sigmoidoscopy to diagnose microscopic colitis. Table 1. - Patient Characteristics Patient Characteristics Frequency Collagenous Colitis 113 Lymphocytic Colitis 218 Microscopic Colitis 11 Tubular Adenomas 7

S135 Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing

Introduction: Bile acid sequestrants (BAS) may be an effective non-corticosteroid treatment in patients with microscopic colitis (MC), but data are lacking. We evaluated the effectiveness of BAS therapy in MC and assessed the utility of bile acid testing to predict response. Methods: Adults diagnosed with MC and treated with BAS at Mayo Clinic Rochester (1/1/2010 - 12/31/2020) were identified. Response was assessed at 12 +/- 4 weeks after initiation of BAS therapy and defined as: complete (resolution of diarrhea), partial (≥50% improvement in number of bowel movements), nonresponse (< 50% improvement), and intolerance (discontinuation due to side-effects). Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs (total bile acids (BA) >2,337 μmol/48 hours, primary BA >10%, or primary BA >4% with total BA >1,000 μmol/48 hours). Univariate and multivariable logistic regression was used to identify predictors of response to BAS. Results: A total of 282 patients were identified [median age 59 (20-87) years; 88.3% women] with a median duration of follow-up of 4.5 (0.4-9.1) years (Table). Prior to BAS therapy, 278 (98.6%) were treated with another medication (loperamide, budesonide, bismuth subsalicylate, or mesalamine) for MC. Patients were treated with the following BAS: 183 (64.9%) cholestyramine, 61 (21.6%) colesevelam, and 38 (13.5%) colestipol. Clinical outcomes with BAS were: 139 (49.3%) complete response, 46 (16.3%) partial response, 70 (24.8%) no response, and 27 (9.6%) intolerance. In patients with complete or partial response to BAS, 65/185 (35.1%) were on a concomitant medication for MC. The dose of BAS did not vary between response and non-response groups (p=0.51). A total of 90/282 (31.9%) had bile acid testing and 51/90 (56.7%) had a positive test. Age at MC diagnosis, smoking history, baseline diarrhea severity, history of cholecystectomy, use of prior MC medications, and abnormalities on bile acid testing did not predict response to BAS. After BAS discontinuation, 77/185 (41.6%) responders had recurrence at a median of 21 (1-172) weeks. Conclusion: In one of the largest cohorts evaluating BAS treatment in MC, we demonstrate that nearly two-thirds had a partial or complete response to these agents. Additional research is needed to determine the role of bile acid malabsoprtion in MC, as well as the subset of patients that are most likely to benefit from BAS therapy. Table 1. - Baseline Characteristics in Microscopic Colitis Patients With and Without Bile Acid Testing Median (range) or n (%) Characteristics All Patients(n = 282) Bile Acid Testing Performed(n = 90) No Bile Acid Testing Performed(n = 192) p-value Age 59 (20-87) 57 (23-87) 60 (20-87) 0.35 Sex, female 249 (88.3%) 82 (91.1%) 167 (87.0%) 0.31 Race, white 276 (97.9%) 89 (98.9%) 187 (97.4%) 0.53 Subtype, lymphocytic colitis 139 (49.3%) 52 (57.8%) 87 (45.3%) 0.06 Bowel movements, number 6 (3-20) 6 (3-20) 5 (3-15) 0.45 Body mass index (kg/m2) 25.4 (16.2-47.0) 24.5 (16.2-47.0) 25.7 (16.7-46.4) 0.21 Smoking history 95 (33.7%) 37 (41.1%) 58 (30.2%) 0.17 Cholecystectomy 69 (24.5%) 28 (31.1%) 41 (21.4%) 0.08 Celiac disease 20 (7.1 %) 5 (5.6%) 15 (7.8%) 0.39 Previous medications* 278 (98.6%) 88 (97.8%) 190 (98.9%) 0.44 *Medications for microscopic colitis prior to bile acid sequestrant treatment.

S185 Characteristics and Outcomes of Cancer Patients With Pre-existing Microscopic Colitis After Exposure to Immune Checkpoint Inhibitors

Introduction: 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 the 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. Most patients (90%) received anti–programmed death ligand 1 monotherapy. 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 subsequently requiring selective immunosuppression. One patient received a compassionate-use fecal transplantation. The median time from ICI initiation to colitis exacerbation was 14 days, with 40% and 50% of patients experiencing grade 3 diarrhea and grade 2 colitis, respectively, and leading to hospitalization in 3 patients. Six patients received steroids and vedolizumab with no colitis recurrence. Of the 8 patients who had colitis exacerbations, 6 resumed ICI therapy afterwards; with 5 receiving concomitant vedolizumab for secondary prophylaxis. (Table) Conclusion: Our findings suggest that ICI exposure in patients with pre-existing MC increases the risk of exacerbation of underlying colitis necessitating and responding to potent immunosuppression therapy. Table 1. - Colitis characteristics after ICI (N=10) Characteristic Value MC status after ICI initiation, no. (%) Persistent symptoms 2 (20) Exacerbation of colitis 8 (80) Median time from ICI initiation to colitis exacerbation, days (IQR) (N=8) 14 (8-128) Highest grade of diarrhea after ICI initiation, no. (%) 1 4 (40) 2 2 (20) 3 4 (40) Highest grade of colitis after ICI initiation, no. (%) 0 2 (20) 1 3 (30) 2 5 (50) Median duration of initial colitis exacerbation symptoms, months (IQR) (N = 8) 4 (2-6) Hospitalization, no. (%) 3 (30) Median duration of hospitalization, days (IQR) (N = 3) 5 (4.5-7) ICU admission for colitis, no. (%) 0 (0) Positive lactoferrin, no. (%) (N = 9) 6 (67) Median peak fecal calprotectin, mcg/gm (IQR) (N = 8) 368 (119-591) Treatment of colitis exacerbation, no. (%) (N = 8) Mesalamine 1 (12.5) Systemic corticosteroids 8 (100) Vedolizumab/ustekinumab (in addition to systemic corticosteroids) 8 (100) Fecal microbiota transplantation 1 (12.5) Endoscopic presentation after ICI initiation, no. (%) (N = 7) Mucosal ulceration 1 (14) Nonulcerative inflammation 1 (14) Normal 5 (72) Presence of histologic inflammation 6 (86) Subsequent recurrent colitis – no. (%) 2 (25) Mortality due to MC, no. (%) 0 (0) Abbreviations: GI, denotes gastrointestinal; ICU, intensive care unit; IQR, interquartile range; MC microscopic colitis.

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

BackgroundMedication 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.MethodsA 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.ResultsIn 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.ConclusionsIn 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.

Clinico-pathological Evaluation of Chronic Diarrhea with Microscopic Colitis: A Cross-sectional Study

Introduction: Chronic diarrhea is common in the older population accounting for 7-9 % which often markedly affects their quality of life. The causes are many and include infectious, endocrine, metabolic, neoplastic, functional, drugs. Microscopic Colitis (MC) has emerged as a distinct diagnostic entity, where the colon appears endoscopically normal, but the biopsy reveals characteristic features in the mucosa. It has two histological forms i.e, Collagenous Colitis (CC) and Lymphocytic Colitis (LC). Aim: To study the clinico-pathological spectrum of lesions in random colonic biopsies of patients with chronic diarrhea having normal colonoscopy. Materials and Methods: This cross-sectional study was conducted in Department of Pathology at JSS Hospital, Mysuru, Karnataka, India, from October 2017 to September 2019. Multiple random biopsies were taken from 80 patients with chronic diarrhea who had normal colonoscopy. The slides were stained with Hematoxylin and Eosin (H&amp;E) and Masson’s Trichrome Stain (MTS). The histological features were studied under light microscopy and using computer-assisted image analysis. The Chi-square test was used to statistically analyse the data. Results: The age of patients ranged from 11-82 years with a mean age of 43 years. Out of total 80 patients, 65 (81.25%) of the cases had non specific inflammation, 14 (17.4%) had microscopic colitis and one patient (1.25%) had probable eosinophilic colitis. The histological features were observed in computer-assisted image analysis using morphometry and interpreted by two pathologists with agreement. Conclusion: Random biopsies are required for the diagnosis of microscopic colitis in the absence of macroscopic abnormalities on colonoscopy, which may affect the treatment strategy. A histologic examination combined with histochemical stain MTS and interpretation utilising computerized image analysis program with morphometry is more effective in cases with diagnostic uncertainty.

Autoimmune diseases in microscopic colitis: A Danish nationwide case-control study.

The association between autoimmune diseases and microscopic colitis remains uncertain. To describe the association between autoimmune diseases and microscopic colitis by using a matched case-control design based on nationwide registry data. All adult Danish patients with a diagnosis of microscopic colitis from 2001 to 2018 were identified from nationwide registries. Odds of autoimmune diseases were compared between cases with microscopic colitis and sex- and age-matched controls from the background population in a 1:10 ratio and evaluated by logistic regression calculating odds ratios (OR) with 95% confidence intervals (CI) adjusted for comorbidity. Analyses were stratified according to sex, age and the subtypes of lymphocytic and collagenous colitis. We identified 15597 cases with microscopic colitis and matched to 155910 controls. In total, 3491 (22%) of patients with microscopic colitis had concomitant autoimmune disease compared to 16521 (11%) of controls (OR, 2.46; 95% CI, 2.36-2.56). Adjusting for comorbidities reduced the OR to 2.09 (95% CI, 2.01-2.19). Analyses showed increased ORs with 16 different autoimmune diseases, particularly of gastrointestinal and endocrine origin, and connective tissue disorders. The highest ORs were for coeliac disease (OR=10.15; 95% CI, 8.20-12.6), Crohn's disease (OR=2.47; 95% CI, 2.10-2.91) and ulcerative colitis (OR=6.73; 95% CI, 6.20-7.30). In stratified analyses younger age at diagnosis and collagenous colitis were associated with higher odds. Using nationwide registry data, microscopic colitis was associated with a wide range of autoimmune diseases, especially of gastrointestinal origin. The results suggest an autoimmune predisposition to microscopic colitis.

S3234 The Association of Microscopic Colitis and Primary Sclerosing Cholangitis

Introduction: Microscopic colitis (MC) and primary sclerosing cholangitis (PSC) are immunological disorders. The association of ulcerative colitis (UC) with PSC is well-known. Patients with PSC without UC could have MC. We studied clinical features and outcomes in patients with MC and PSC. Methods: Patients with MC and PSC were retrospectively identified from January 1st, 1980 to December 31st, 2020. Details including demographics, mode of diagnoses, treatment and response to MC therapy, presence of UC or Crohn’s disease, complications and risk of neoplasia were gathered. Results: Twelve patients (8 male; median age 54.4 years [range 22.6-75.3]; 7 with lymphocytic colitis, 5 with collagenous colitis) were found. Nine (75%) were diagnosed with MC after PSC (median 2.5 weeks [range 0-1221.5]). Six of 12 (50%) were symptomatic for MC with diarrhea, and 6 (50%) were incidentally found to have MC during screening for IBD or dysplasia. One patient had an adenomatous polyp, no patient had flat dysplasia or cancer, and none underwent colon resection. Six (50%) who were asymptomatic for MC required no treatment, treatment data was missing for 1 symptomatic patient, the remaining 5 symptomatic patients were treated with budesonide (3), prednisone (1), and bismuth subsalicylate (1). All experienced complete resolution of diarrhea. One had pre-existing UC that transformed to MC after 8 years and another transformed from chronic colitis to MC after 1 year. Diagnosis of PSC was made by ERCP in 6 patients (50%), liver biopsy in 4 (33.3%) and MRCP in 3 (25%). Cholangitis developed in 5 patients (41.6%), strictures requiring stenting in 7 (58.3%), cirrhosis in 4 (33.3%) and cholangiocarcinoma in 2 patients (16.6%). No patient required a liver transplant, 1 (8.3%) died one year after PSC diagnosis due to cholangiocarcinoma. CONCLUSION: Concomitant diagnosis of MC and PSC was uncommon. Most patients were male, which is typical for PSC but atypical for MC. Microscopic colitis was often found incidentally by colonoscopy done to rule out IBD. Half the patients did not have symptoms of MC and required no treatment. Patients that were treated for MC had a complete resolution of symptoms. Primary sclerosing cholangitis tended to have complications. The association of PSC with UC is well-known. When managing patients with PSC and unexplained diarrhea or patients with MC and abnormal liver chemistries, MC-PSC should be considered.

Epidemiology and Clinical Outcomes of Microscopic Colitis: Preliminary Results From the Loyola University Microscopic Colitis Registry (LUMiCoR).

Microscopic colitis (MC) is a common cause of chronic diarrhea with limited long-term data. We searched the pathology records at our institution from 2008 to 2018 to identify cases of MC. Total sample included patients with either a diagnosis of MC or incomplete MC (MCi).Chart review was performed and data were summarized for descriptive statistics. Logistic regression was used to estimate the unadjusted effects of predictors on MC. A total of 216 patients (88.32% white, 80.56% females, mean age 67.12 +/– 15.79) were studied; 50.00% had CC, 40.28% had LC and 9.72% had MCi. Majority (52.31%) were smokers and 21.84% of females were using some form of hormonal therapy. The odds of LC in reference to CC were significantly higher for those using tricyclic antidepressants (TCAs) (OR: 3.23, 95% C.I: 1.18–8.80, p = 0.02). The odds of smoking, statins, aspirin and beta-blocker use were decreased in MCi in reference to CC (all p < 0.05), 29 (74.35%) patients with unresolved symptoms underwent repeat colonoscopies with biopsies. One case of MCi resolved, 8 (72.73%) out of 11 cases of LC resolved, 2 (18.18%) continued to be LC and 1 (9.09%) transformed to CC, 8 (47.06%) out of 17 cases of CC resolved, 8 (47.06%) continued to be CC and 1 (5.88%) transformed to LC. Majority of patients had CC. TCA use resulted in increased odds of LC in reference to CC. Biopsies from repeat colonoscopies in some patients revealed changes in the pathological diagnoses raising the question of interchangeability of MC (CC to LC and vice versa).

Microscopic colitis.

Microscopic colitis (MC) is an inflammatory disease of the large intestine associated with urgent watery diarrhoea. MC may occur in people of all ages, although the disease primarily affects older women. Once believed to be rare, MC is now known to be a common cause of chronic watery diarrhoea in high-income countries, affecting 1 in 115 women and 1 in 286 men during their lifetime in Swedish population-based estimates. An inappropriate immune response to disturbances in the gut microenvironment is implicated in the pathogenesis of MC. Evidence also supports an underlying genetic basis for disease. The diagnosis of MC relies on clinical symptoms and microscopic assessment of colonic biopsy samples. MC is categorized histologically into collagenous colitis, lymphocytic colitis and their incomplete forms. The mainstay of treatment includes the use of budesonide, with or without adjunctive therapies, and withdrawal of offending drugs. Emerging studies suggest a role for biologicals and immunosuppressive therapies for the management of budesonide-refractory or budesonide-dependent disease. MC can have a substantial negative effect on patient quality of life. The outlook for MC includes a better understanding of the immune response, genetics and the microbiome in disease pathogenesis along with progress in disease management through robust clinical trials.

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019

PREVALENCE OF MICROSCOPIC COLITIS IN PATIENTS FULFILLING ROME IV CRITERIA OF IRRITABLE BOWEL SYNDROME DIARRHEAL TYPE

Background: Diarrhea predominant irritable bowel syndrome (IBS-D) is a common functional disorder of the gastrointestinal tract shares similar symptoms and endoscopic findings with microscopic colitis (MC) with a major difference in treatment. IBS-D is diagnosed using criteria based on clinical symptoms, while histological evidence is mandatory for MC diagnosis. There is a continuous debate about the value of endoscopically normal colonic mucosa biopsies in IBS-D patient investigation. Objective: To determine the prevalence of MC in patients meeting Rome IV criteria of IBS-D. Patients and methods: A cross-sectional survey was performed in the Department of Hepatogastroenterology and Infectious Diseases, Al-Azhar University Hospitals. One hundred patients attended the outpatient clinics from January 2020 to April 2020 fulfilling Rome IV criteria for diagnosis of IBS-D was prospectively enrolled. Patients aged from 18 to 65 years old. Patients with other causes of chronic diarrhea were excluded. The studied patients were subjected to full history taking, extensive clinical examination, thorough laboratory investigations and complete colonoscopy with multiple biopsies were taken from endoscopically normal looking mucosa at different parts of the colon, and processed for histopathological examination. Results: The mean age of participants was 40.7 ± 11.01 years. Fifty three cases were males (53%) and 47 were females (47%). Twenty out of 100 patients were diagnosed as MC, 18 (90%) of them were lymphocytic colitis (LC) and 2 patients (10%) were collagenous colitis (CC). The mean age in MC patients was 50.8 ± 7.3 years. Nocturnal diarrhea and weight loss were only seen in cases diagnosed as MC (15 out of 20 patients 75%) and 15 out of 20 patients (75%) respectively. There was a significant difference between normal biopsy & MC patients as regard inflammatory markers C-reactive protein(CRP) and Erythrocyte sedimentation rate (ESR), but their levels were still within normal range. Conclusion: MC is not an uncommon disease that is often diagnosed in elderly people. It can be easily confused with IBS-D and histopathological examination of colonoscpic biopsies obtained from the normally appearing mucosa is the only way for differentiation. In cases with IBS-D, nocturnal diarrhea and weight loss increase the possibility of MC and require colonoscopic biopsy evaluation. In patients with IBS-D criteria mild increase in inflammatory markers (CRP and ESR) may occur, but these markers are non-specific and don't direct us for MC diagnosis.

PREVALENCE OF MICROSCOPIC COLITIS IN PATIENTS FULFILLING ROME IV CRITERIA OF IRRITABLE BOWEL SYNDROME DIARRHEAL TYPE

Background: Diarrhea predominant irritable bowel syndrome (IBS-D) is a common functional disorder of the gastrointestinal tract shares similar symptoms and endoscopic findings with microscopic colitis (MC) with a major difference in treatment. IBS-D is diagnosed using criteria based on clinical symptoms, while histological evidence is mandatory for MC diagnosis. There is a continuous debate about the value of endoscopically normal colonic mucosa biopsies in IBS-D patient investigation. Objective: To determine the prevalence of MC in patients meeting Rome IV criteria of IBS-D. Patients and methods: A cross-sectional survey was performed in the Department of Hepatogastroenterology and Infectious Diseases, Al-Azhar University Hospitals. One hundred patients attended the outpatient clinics from January 2020 to April 2020 fulfilling Rome IV criteria for diagnosis of IBS-D was prospectively enrolled. Patients aged from 18 to 65 years old. Patients with other causes of chronic diarrhea were excluded. The studied patients were subjected to full history taking, extensive clinical examination, thorough laboratory investigations and complete colonoscopy with multiple biopsies were taken from endoscopically normal looking mucosa at different parts of the colon, and processed for histopathological examination. Results: The mean age of participants was 40.7 ± 11.01 years. Fifty three cases were males (53%) and 47 were females (47%). Twenty out of 100 patients were diagnosed as MC, 18 (90%) of them were lymphocytic colitis (LC) and 2 patients (10%) were collagenous colitis (CC). The mean age in MC patients was 50.8 ± 7.3 years. Nocturnal diarrhea and weight loss were only seen in cases diagnosed as MC (15 out of 20 patients 75%) and 15 out of 20 patients (75%) respectively. There was a significant difference between normal biopsy & MC patients as regard inflammatory markers C-reactive protein(CRP) and Erythrocyte sedimentation rate (ESR), but their levels were still within normal range. Conclusion: MC is not an uncommon disease that is often diagnosed in elderly people. It can be easily confused with IBS-D and histopathological examination of colonoscpic biopsies obtained from the normally appearing mucosa is the only way for differentiation. In cases with IBS-D, nocturnal diarrhea and weight loss increase the possibility of MC and require colonoscopic biopsy evaluation. In patients with IBS-D criteria mild increase in inflammatory markers (CRP and ESR) may occur, but these markers are non-specific and don't direct us for MC diagnosis.

P054 Utilization of Biologic Therapy in Patients With Microscopic Colitis Not Responding to Standard Therapy.

BACKGROUND: Microscopic colitis (MC), consisting of collagenous colitis (CC) and lymphocytic colitis (LC), is a notable and often under-recognized cause of diarrheal disease. Standard of care treatment includes the use of anti-diarrheal agents and steroids. However, patients with refractory disease not responding to standard therapy will require escalation of therapy, often to a biologic agent. Data on this population are limited. METHODS: We performed a retrospective, multicenter study of patients diagnosed with MC refractory to steroids requiring treatment initiation with an anti-TNF, anti-integrin, or anti-IL-12/23 from July 2006 to June 2020. Patients with comorbid, rheumatologic, dermatologic, or oncologic disease requiring a biologic agent were excluded. Data regarding disease history and prior and current treatment characteristics were collected. The primary outcome was steroid-free response to biologic therapy defined as cessation of steroids after biologic initiation without further use for a minimum of 90 days. The secondary outcome was duration of steroid-free response, defined as the time to re-initiation of steroids. Patients with CC and LC were compared, and statistical analyses were conducted using the Mann-Whitney U test and Fisher's exact test. RESULTS: Thirty two patients with MC were identified, of whom 19 had CC and 13 had LC. The patients had a median age of 60.5 years, and 93.8% were female. Treatments prior to biologics included budesonide (100%), prednisone (50%), cholestyramine (68.8%), bismuth (37.5%), methotrexate (25.0%), thiopurine (21.9%), and 5-ASA (37.5%). Median (IQR) calprotectin and CRP within 3 months of biologic treatment initiation were 61.5 mcg/g (15.6–109.6) and 1.6 mg/L (1.0–2.6), respectively. The median time from diagnosis of MC to biologic initiation was 1,095 days overall, with 1,642 days for those with CC and 851 days for those with LC (P = 0.03). No additional significant differences in clinical characteristics or prior treatments were found among those with CC vs LC. All patients were started on a biologic: vedolizumab (n = 16), adalimumab (n = 10), infliximab (n = 6). Overall, steroid-free response was observed in 71.2% of patients. Steroid-free response was observed in 75.0% of patients on vedolizumab (n = 16), 70.0% of patients on adalimumab (n = 10), and 66.7% of patients on infliximab (n = 6). The overall duration of steroid-free response had a median days (IQR) of 391 (120–741): vedolizumab 400.5 (260–533), adalimumab 120 (82–491), and infliximab 1,475 (759.5–1,625). There was no significant difference in steroid free response between patients with LC vs CC (61.5% vs 79.0%, P = 0.25), though steroid-free response with vedolizumab was observed in 88.9% of patients with CC and 57.1% of patients with LC (P = 0.26). Patients with CC experienced a shorter median days (IQR) duration of steroid-free response compared to patients with LC: 131 (81–508) vs 524.5 (389–1,101), P = 0.07). Additionally, the duration of steroid-free response with adalimumab was median (IQR) 120 days (82–120) for patients with CC vs 616 days (491–741) for patients with LC (P = 0.05). CONCLUSION: Anti-TNFs and anti-integrins may be treatment options for patients with MC not responding to standard therapy.

Increasing Incidence of Microscopic Colitis in a Population-Based Cohort Study in Switzerland

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that presents with chronic, nonbloody watery diarrhea and only few or no endoscopic abnormalities. Histologic examination discriminates lymphocytic colitis (LyC; presence of ≥20 intraepithelial lymphocytes per 100 surface epithelial cells) and collagenous colitis (CC; colonic subepithelial collagen band >10 μm in diameter).1,2 MC not otherwise specified describes a subgroup of patients who do not fulfill the diagnostic criteria for either CC or LyC.1,2 Population-based epidemiologic data regarding MC are scarce. We aimed to evaluate the clinical presentation at diagnosis, incidence, and prevalence of MC in Cantons of Vaud and Fribourg, Switzerland.

S0233 The Role of Breath Testing in Microscopic Colitis

INTRODUCTION: Microscopic colitis (MC) is a diarrheal illness difficult to differentiate from other gastrointestinal disorders. Historical cues and understanding of disease prevalence are critical to the evaluation of MC patients experiencing continued symptoms despite adequate treatment or histologic improvement. This study examines the prevalence of concomitant small intestine bacterial overgrowth (SIBO) and carbohydrate malabsorption in a MC population. METHODS: Records were reviewed from 6/2015 to 6/2020 at a single-center private gastroenterology practice. Patients with MC were identified by ICD10 codes and grouped into either collagenous (CC) (K52.831), lymphocytic (LC) (K52.832), or other microscopic colitis (K52.839). Patient demographics, surgical history, disease activity, medications, fecal calprotectin, date of initial diagnosis, and breath testing results were recorded in a HIPAA compliant dataset. Data were analyzed using chi-squared, Fisher’s exact, Pearson correlation, and T testing where indicated. RESULTS: 223 MC patients were reviewed with 67 included based on the presence of SIBO hydrogen (H2) breath testing: 50 with LC, 10 with CC, 4 with CC and MC, and 3 indeterminate. The average age at MC diagnosis was 64.9 ± 14.6, with a higher prevalence of females (73.1%) and whites (78.9%). SIBO positive rates were 19/54 (35.2%) in the LC group and 5/14 (35.7%) in the CC group (P = 0.97) (Figure 1). There was no difference in SIBO positivity between age groups (< 70 vs > 70, P = 0.82), genders (P = 0.33), or ethnicities (P = 0.35). SIBO rates in patients with active MC (defined as > 3 watery bowel movements daily) did not differ from patients in remission (30.6% vs 28.6%, P = 0.89). The average fecal calprotectin (FC) in the SIBO positive group was 84.4 mg/mg, compared to 262.6 mg/mg in the SIBO negative group (P = 0.31) (Figure 2). Concurrent carbohydrate malabsorption was observed in 47.4% of SIBO positive patients, compared to 61.1% in the SIBO negative group (P = 0.33) (Figure 3). CONCLUSION: This retrospective cross sectional study illustrates rates of SIBO positivity in the MC population are similar to symptomatic patients in the general population (Figure 1). There was no difference in positive rates between the LC and CC groups, limited by a small CC sample size. Furthermore, carbohydrate malabsorption was frequently superimposed on the MC diagnosis, highlighting the need to consider H2 breath testing for both SIBO and carbohydrate malabsorption in symptomatic MC patients who are unresponsive to therapy.Figure 1.: Similar rates of SIBO positivity were observed between collagenous and lymphocytic colitis (35.2% vs 35.7%, P = 0.97). Rates of bacterial overgrowth in the general population are estimated 2-22%, though our study’s rates of positive SIBO breath testing correlate with rates from a Vizuete et al, which found SIBO positivity in 32.9% of patients with “flatulence, eructation, and gas pain”. No statistical difference in SIBO positivity was seen between age groups (39.1% (< 70) vs 36.4% (> 70), P = 0.82), genders (27.8% (M) vs 40.8% (F), P = 0.33), or ethnicities (43.3% (white) vs 25.0% (non-white), P = 0.35).Figure 2.: There was no difference in SIBO positive rates between patients with active microscopic colitis (described as at least 3 bowel movements per day) versus patients in remission (30.6% vs 28.6%, P = 0.89). When comparing SIBO positive to negative patients, there was no difference in the percentage of patients on steroid therapy at the time of breath testing (12.0 vs 14.3%, P = 0.79).Figure 3.: Carbohydrate malabsorption was frequently observed in all tested patients (56.4%). Positive rates of fructose/lactose/sucrose intolerance were observed more frequently in the SIBO negative group (47.4% vs 61.1%, P = 0.33). There was no observed difference between collagenous colitis patients (CC) and lymphocytic colitis patients (LC) with regard to rates of individual carbohydrate malabsorption.

S3022 Gluten Free Diet: A Treatment Modality for Idiopathic Lymphocytic Gastritis

INTRODUCTION: Lymphocytic gastritis (LG), defined as 25 lymphocytes per 100 gastric epithelial cells, is found in less than 1% of endoscopic biopsies. It can be idiopathic or secondary to a variety of diseases, commonly celiac disease (CD) and Helicobacter pylori (H. pylori). Treatment of secondary LG is aimed at treating the underlying cause, but there is limited literature on the treatment of idiopathic LG. CASE DESCRIPTION/METHODS: A 25-year-old male with Immunoglobulin (Ig) A deficiency presented for chronic diarrhea. He denied smoking, alcohol use, or use of any medications. Workup was negative for anti-Tissue Transglutaminase IgA and IgG, Giardia IgA, and pancreatic elastase levels. Esophagogastroduodenoscopy (EGD) and colonoscopy demonstrated gastritis and diffuse colonic nodularity. Gastric biopsies revealed lymphocytic gastritis without H. pylori. Duodenal biopsies showed increased intraepithelial lymphocytes without crypt hyperplasia or villous atrophy. Colonic biopsies showed patchy lymphoid nodular inflammation insufficient for diagnosis of microscopic colitis. Genetic testing for celiac disease, namely HLA DQ2 and DQ8, was negative. He was diagnosed with idiopathic LG and was initiated on a GFD with improvement in frequency of bowel movements. Months later, patient presented with recurrence of diarrhea. Hydrogen breath test was positive; rifaximin was initiated for small intestinal bacterial overgrowth with improvement in frequency of bowel movements. Patient continued adherence to a GFD, and subsequent EGD showed resolution of gastritis and histologic resolution of LG. DISCUSSION: Our case demonstrates that patients with idiopathic LG can have symptomatic, endoscopic, and histologic recovery following introduction of a GFD. In cases of disease relapse, overlapping conditions should first be considered before attributing relapse to treatment failure of GFD. Furthermore, one can consider gluten sensitivity as a spectrum of disease based on serologic and histologic findings. While CD, classically associated with gluten sensitivity, has both serologic and histologic findings, there also exists a condition called Non-Celiac Gluten Sensitivity that does not have serologic or histologic evidence of CD but may also benefit from a GFD. Idiopathic LG falls in the middle of the spectrum with only histologic findings and, likewise, can be treated with a GFD. Further studies are required to determine whether a GFD is an effective and definitive treatment of idiopathic LG.

Distribution of histopathological features along the colon in microscopic colitis

The diagnosis microscopic colitis (MC) consisting of collagenous colitis (CC) and lymphocytic colitis (LC) relies on histological assessment of mucosal biopsies from the colon. The optimal biopsy strategy for reliable diagnosis of MC is controversial. The aim of this study was to evaluate the distribution of histopathological features of MC throughout the colon. Mucosal biopsies from multiple colonic segments of patients with MC who participated in one of the three prospective European multicenter trials were analyzed. Histological slides were stained with hematoxylin-and-eosin, a connective tissue stain, and CD3 in selected cases. In total, 255 patients were included, 199 and 56 patients with CC and LC, respectively. Both groups exhibited a gradient with more pronounced inflammation in the lamina propria in the proximal colon compared with the distal colon. Similarly, the thickness of the subepithelial collagenous band in CC showed a gradient with higher values in the proximal colon. The mean number of intraepithelial lymphocytes was > 20 in all colonic segments in patients within both subgroups. Biopsies from 86 to 94% of individual segments were diagnostic, rectum excluded. Biopsies from non-diagnostic segments often showed features of another subgroup of MC. Conclusively, although the severity of the histological changes in MC differed in the colonic mucosa, the minimum criteria required for the diagnosis were present in the random biopsies from the majority of segments. Thus, our findings show MC to be a pancolitis, rectum excluded, questioning previously proclaimed patchiness throughout the colon.

Random colonic biopsies in macroscopically normal colonoscopies: is there any benefit? A two-centre audit of current practice.

Recent guidelines from the British Society of Gastroenterology published in April 2018, recommended performing random colonic biopsies (RCB) in endoscopically normal colonic mucosa when investigating chronic diarrhoea in adults to rule out microscopic colitis; however, cost effectiveness was not accounted for due to poor evidence base. There is now more evidence that RCBs are of low yield and of significant cost. A two-centre audit of current practice was conducted at Rockingham General Hospital and Fremantle Hospital in Western Australia, aiming to determine the yield of RCB in macroscopically normal mucosa for microscopic colitis, from 1 January 2009 to 30 June 2018, with comparisons of practice and results between gastroenterologists and general surgeons. Variability in the indications (diarrhoea and non-diarrhoea indications) for RCBs was determined and the cost of consumables, additional endoscopy time and histopathology analysis were calculated. A total of 872 normal colonoscopies with RCBs were included; 48.7% of colonoscopies with RCB were for diarrhoea. Only 1.5% of RCBs were positive for microscopic colitis; 3.1% of patients with diarrhoea had microscopic colitis. Only one patient received pharmacologial treatment as a result of the test. The calculated cost per positive diagnosis of microscopic colitis was $10 862.42. RCBs from normal colonic mucosa have poor yield and are costly. Local guidelines should be updated, so RCBs are performed only in patients with a high degree of suspicion of an organic cause of chronic diarrhoea.