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Microscopic colitis is generally identified on random colon biopsies performed for chronic diarrhea, but rarely incidental polyps have histologic features of microscopic colitis. We compared patients with polypoid microscopic colitis to control patients with conventional polyps to determine the implications of polypoid microscopic colitis., Medical records were searched for patients without prior or concurrent microscopic colitis who were found to have polypoid microscopic colitis. For each patient with polypoid microscopic colitis, one patient with conventional polyps was selected as a control. We reviewed the histologic features of each polypoid microscopic colitis specimen, and evaluated endoscopic and clinical findings for polypoid microscopic colitis patients and controls., Twenty-six patients with polypoid microscopic colitis were identified with histologic features of collagenous colitis in 8 patients (31%) and lymphocytic colitis in 18 patients (69%). Polypoid microscopic colitis was unifocal in 14 patients (54%) and multifocal in 12 patients (46%). Patients with polypoid microscopic colitis were older than control patients (median age = 60 years vs 66 years, P  = .04). On follow-up 7 patients with polypoid microscopic colitis (33%) developed chronic diarrhea compared to 3 (12%) controls ( P  = .16). Of patients with follow-up biopsies, 1 patient with polypoid microscopic colitis (13%) and no control patients developed microscopic colitis ( P  = 1)., Polypoid microscopic colitis may be identified in asymptomatic patients and most patients do not develop chronic diarrhea, but some patients with polypoid microscopic colitis develop diarrhea (33% vs 12% in controls) or conventional microscopic colitis on follow-up. Thus pathologists should distinguish polypoid microscopic colitis from conventional microscopic colitis but may inform clinicians of the uncertain association with chronic diarrhea to guide decisions regarding follow-up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Immune-related adverse events (irAEs) constitute a challenge in the clinical management of solid tumors. This study aims to collect real-world data on the occurrence of immune-mediated diarrhea and colitis (IMDC) in advanced non-small cell lung cancer (aNSCLC) treated with immune checkpoint inhibitors (ICIs) and to assess the clinical impact of a multidisciplinary approach (MDA) on IMDC management., Methods: We retrospectively collected data on patients with aNSCLC consecutively treated with ICIs, either as single agent or in combination with chemotherapy, between September 2013 and July 2022. Among patients developing IMDC, we conducted blinded revision of colonic biopsies and evaluated the clinical impact of the introduction of MDA through predefined indicators., Results: Among the 607 patients included, 84 (13.8%) experienced IMDC. Pathological review highlighted a high prevalence of microscopic colitis (28%), with a collagenous pattern linked to longer symptoms duration (P = .01). IMDC occurred more frequently in females (P = .05) and PD-L1 expressors (P = .014) and was correlated with longer progression-free survival (17.0 vs 5.8, P < .001) and overall survival (28.3 vs 9.5, P < .001). The introduction of MDA was associated with increased employment of diagnostical tools such as fecal calprotectin test (P < .001), colonoscopy (P < .001), and gastroenterological evaluation (P = .017) and a significant decrease in both grade 3 conversion rate (P = .046) and recurrence after rechallenge (P = .016). Hospitalization rate dropped from 17.2% to 3.8% (P: ns)., Conclusion: These findings highlight the clinical relevance of IMDC and support the incorporation of a MDA to optimize the clinical management of this irAE to improve patient care. Prospective validation has been planned., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose of Review: Microscopic colitis is an inflammatory disease of the colon that presents as watery diarrhea with minimal to normal endoscopic changes on colonoscopy. It encompasses two common subtypes, lymphocytic colitis and collagenous colitis, which are both treated similarly.Immune checkpoint inhibitor colitis is among the most common immune-related adverse events. Endoscopic and histological findings range from normal colonic mucosa to inflammatory bowel like changes. This review article provides update in treatment and management of microscopic colitis and immune checkpoint inhibitor colitis (ICPi colitis)., Recent Findings: Recent studies on microscopic colitis have focused on the successful use of immunomodulators such as biologics for treatment of budesonide refractory microscopic colitis cases. Microscopic colitis does not confer an added risk for colorectal cancer.With the increasing usage of immunotherapy agents, immune checkpoint inhibitor colitis is becoming more common. ICPi colitis can be successfully managed with steroids, with treatment stepped up to biologics for moderate to severe cases or for mild cases that do not respond to steroids. Immunotherapy agents can be carefully re-introduced in mild cases, after treatment of ICPi colitis., Summary: Biologics can be used to treat budesonide refractory microscopic colitis. ICPi colitis can be managed with steroids and biologics in moderate to severe cases., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Immune checkpoint inhibitors are a class of cancer immunotherapy, with a constellation of side effects that require early recognition and management. We present a patient with metastatic adenocarcinoma started on pembrolizumab a month prior, who was admitted to the hospital for bloody diarrhoea. He underwent flexible sigmoidoscopy with biopsy proven grade 3 immune-mediated diarrhoea and colitis. He developed progressively worsening diarrhoea despite appropriate intravenous corticosteroids therapy, and initiation of corticosteroid-sparing therapy was complicated by discovery of hepatitis B core antibodies indicating a chronic hepatitis B carrier state. We discuss our work-up of new onset haemorrhagic diarrhoea in a patient on immunotherapy for metastatic non-small cell lung cancer, as well as a review of current guidelines for antiviral prophylaxis in these patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The clinical case of a patient in the fifth decade of life with a diagnosis of lymphocytic colitis is presented, who comes for chronic diarrhea, which receives treatment with Budesonide with partial response.

Competing Interests: Competing interests: None declared.

The misdiagnosis of intestinal schistosomiasis is not uncommon given its variety of clinical manifestations and often shares similarities with ulcerative colitis. While endoscopy aids in diagnosis, findings are often non-specific and correlation with histopathological features is crucial in arriving at an accurate diagnosis which is confirmed by the presence of schistosome ova within the lamina propria. In this case study, we report our experience with a 50-year-old woman, who had been residing in Singapore for more than a decade, presenting with recurrent episodes of bloody diarrhoea., (© Royal College of Physicians 2022. All rights reserved.)

Chronic diarrhea is a common reason for consultation in renal transplant patients. Cytomegalovirus infection is the cause of chronic diarrhea of infectious origin in 50% of cases, but coinfection with tuberculosis is rare. We present the case of a renal transplant patient with chronic diarrhea, with a finding of left colon colitis and positive microbiological studies in biopsy for tuberculosis and cytomegalovirus . The patient received valganciclovir and anti-tubercular treatment with adequate evolution. Immunosuppressed patients may have diarrhea secondary to opportunistic infections; therefore, an algorithm for early diagnosis and treatment is recommended.

A 49-year-old woman was referred to our hospital for further evaluation and treatment of diarrhea. Colonoscopic findings revealed indistinct vascular patterns and extensive edema in a colon segment, and white granular mucosa and crack-like appearance in the sigmoid colon and rectum. She was diagnosed with lymphocytic colitis (LC) based on lymphocytic infiltration into the epithelium on histopathological examination. Diarrhea symptoms resolved after long-term medication withdrawal. This medicine's composition was changed 4 years ago and this modification possibly triggered LC.

Background: Eosinophilic colitis (EoC) is a rare form of eosinophilic gastrointestinal disease characterized by diffuse eosinophilic infiltration in the deep lamina propria of colonic mucosa. The pathophysiology is unclear, but EoC has been associated with multiple known risk factors., Aim: The aim of this study was to characterize the clinical characteristics and disease course of patients with EoC at a major cancer center., Material and Methods: We retrospectively reviewed colonic samples obtained between January 2000 and December 2018 from our institutional database and included cases with significant colonic eosinophilia. Baseline clinical data and EoC-related clinical course and outcomes were documented., Results: Forty-one patients were included. One fourth had coexisting autoimmune conditions. Seventy-eight percent had a cancer diagnosis. Half the patients received chemotherapy, with a median duration of 180 days between chemotherapy and EoC onset. Symptoms were present in 76% of patients. Diarrhea was more prevalent in patients who received chemotherapy (85% vs. 42%). Median duration of EoC symptoms was 30 days in patients with cancer and 240 days in those without cancer (P=0.03). Most patients (88%) had normal colonoscopy findings. Fifteen percent of patients required hospitalization. All-cause mortality was 37%, mostly related to underlying malignancy and organ failure., Conclusions: EoC in cancer patients appears to have more diarrhea-predominant symptoms, particularly in patients receiving chemotherapy, but a shorter disease duration compared with patients without cancer. Hospitalization can be required for serious cases. Treatment may be reserved for patients requiring symptom management, as most patients with EoC have good clinical outcomes regardless of treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The biological role of the lipopolysaccharide-responsive beige-like anchor (LRBA) protein associated with the immune system is not to date well known. However, it is thought to regulate the CTLA4 protein, an inhibitory immunoreceptor. Chronic diarrhea, autoimmune disorders, organomegaly, frequent recurrent infections, hypogammaglobulinemia, chronic lung manifestations, and growth retardation are some features of LRBA deficiency. This rare disease is observed as a result of homozygous mutations in the LRBA gene. An 11.3-year-old male patient presented because of short stature and high blood glucose level. He had a previous history of lymphoproliferative disease, chronic diarrhea, and recurrent infections. His parents were first-degree consanguineous relatives. A diagnosis of type 1 diabetes mellitus (T1DM) was added to the preexisting diagnoses of immunodeficiency, recurrent infection, enteropathy, chronic diarrhea, lymphadenopathy, hepatomegaly, and short stature. Genetic analysis revealed a homozygous mutation in the LRBA gene, c.5047C>T (p.R1683*) (p.Arg1683*). Abatacept treatment was started: the patient's hospital admission frequency decreased, and glucose regulation improved. At follow-up, growth hormone (GH) deficiency was diagnosed, although it was not treated because the underlying disease was not under control. Nevertheless, the patient's height improved with abatacept treatment. LRBA deficiency should be considered in the presence of consanguineous marriage, diabetes, immunodeficiency, and additional autoimmune symptoms. LRBA phenotypes are variable even when the same variants in the LRBA gene are present. Genetic diagnosis is important to determine optimal treatment options. In addition to chronic malnutrition and immunosuppressive therapy, GH deficiency may be one of the causes of short stature in these patients.

Purpose: Eosinophilic gastrointestinal disorders are rare in children and present with a broad spectrum of non-specific symptoms. To date, no guidelines for diagnosis, therapy and follow-up are validated. Aim of our study is to focus on eosinophilic colitis (EC), to determine a possible correlation between associated disorders, macroscopic findings and treatment/follow up., Methods: Retrospective study from 2015 to 2019 including all colonoscopies performed at our Institution. Eosinophilic colitis was defined according to the threshold identified by Collins: > 100 Eo/Hpf: right colon, > 84 Eo/Hpf transverse and left colon, > 64 Eo/Hpf sigma and rectum. We excluded colonoscopy in patients with IBD or other diseases causing hypereosinophilia (i.e., parasite infection, GVHD)., Results: Among 399 colonoscopies performed in 355 patients, we made 50 diagnosis of EC, 36 males, 14 females, median age 8.5 (3-17). Symptoms leading to endoscopy were recurrent abdominal pain (66%), chronic diarrhea (64%), and chronic constipation (8%). Two patients presented with GI bleeding and one with weight loss. Macroscopic findings were mostly normal or lymphoid nodular hypertrophy presenting different endoscopic features. In seven children (14%) we found history of allergy and atopy. 22 children present a diagnosis of autistic spectrum disorder (ASD) with a prevalence higher than in the overall population (44% vs 28.5%, p = 0.03). According to symptoms, treatment consist variably of steroids, six food elimination diet, mesalamine. For patients with available follow-up, we found histological persistence of Eosinophils in 75%, even in patients with symptoms relief., Conclusion: This study focus attention on EC as a new challenging pathology. Multicentric randomized clinical trials are needed to understand physiopathological mechanisms to validate a possible endoscopic score and related histological threshold, and to standardize therapy according to clinical features and instrumental findings. The high prevalence of EC in ASD need further specific research.

Background: Immune-mediated diarrhea and colitis (IMDC) is a common immune-related adverse effect related to immune checkpoint inhibitors. We aimed to identify risk factors for chronic IMDC and its prognostic value in cancer outcomes., Methods: We retrospectively collected data on patients with a diagnosis of IMDC between January 2018 and October 2019 and grouped them based on disease duration into acute (≤3 months) and chronic (>3 months) categories. A logistic regression model and the Kaplan-Meier method with log-rank tests were used for biostatistical analysis., Results: In our sample of 88 patients, 43 were in the chronic group and 45 were in the acute group. Genitourinary cancer and melanoma accounted for 70% of malignancies. PD-1/L1 monotherapy (52%) was the more frequently used regimen. We showed that chronic IMDC was associated with proton pump inhibitor use (odds ratio [OR], 3.96; P=.026), long duration of IMDC symptoms (OR, 1.05; P<.001) and hospitalization (OR, 1.07; P=.043), a histologic feature of chronic active colitis (OR, 4.8; P=.025) or microscopic colitis (OR, 5.0; P=.045), and delayed introduction of selective immunosuppressive therapy (infliximab/vedolizumab; OR, 1.06; P=.047). Chronic IMDC also reflected a better cancer response to immune checkpoint inhibitors (30% vs 51%; P=.002) and was accompanied by improved overall survival (P=.035). Similarly, higher doses of selective immunosuppressive therapy were associated with better overall survival (P=.018)., Conclusions: Chronic IMDC can develop among patients with a more aggressive disease course and chronic features on colon histology. It likely reflects a prolonged immune checkpoint inhibitor effect and is associated with better cancer outcome and overall survival.

Background: Diarrhea, a major pathological hallmark of inflammatory bowel disease, is characterized by a significant reduction in the expression and function of key intestinal ion transporters. The adoptive naïve CD4 + T cell transfer colitis is an immune-based, chronic colitis mouse model which resembles human Crohn's disease. Although mice with T cell transfer colitis demonstrate diarrhea, the ion transporter basis of this phenotype has not been explored., Aims/methods: In the current studies, we aimed to determine the mRNA and protein levels of the key NaCl transporters DRA and NHE3 along with the mRNA expression of other transporters in the inflamed intestine., Results: Naïve CD4 + T cells, transferred to Rag2 knockout mice, induced severe colonic inflammation characterized by histological damage and increased mRNA levels of cytokines in the colon with no effect in the ileum. Diarrheal phenotype was a key feature of the excised colons of mice where loose stools were evident. Our results demonstrated that the key chloride transporter DRA, mRNA, and protein levels were significantly reduced in the inflamed colon. However, expression of the key sodium hydrogen exchanger NHE3 was unaffected. The mRNA expression of other important transporters was also determined; in this regard, the sodium channel ENACα and the monocarboxylate transporters MCT1 and SMCT1 mRNA levels were also significantly lower compared to control mice. However, CFTR mRNA was not altered in the colon or ileum., Conclusions: The studies conducted herein for the first time demonstrate the downregulation of important intestinal ion transporters in proximal and distal colon in T cell transfer colitis mouse model, providing valuable evidence for the ion transporter basis of diarrhea in this chronic model of inflammation.

Segmental colitis associated with diverticulosis (SCAD) is a rare variant of chronic colitis that is limited to segments of the left colon that harbor diverticula. Histologically, SCAD is known to mimic chronic idiopathic inflammatory bowel disease. Patients usually present with hematochezia and cramping abdominal pain; SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy. Due to the histologic overlap with ulcerative colitis and occasional Crohn colitis, the implications of an inaccurate diagnosis are significant.

Background/aims: Drug-induced colitis (DiC) is a rarely reported form of colonopathy and data about the clinical and endoscopic characteristics are scarce. The aim was to investigate the phenotype of DiC. Methods: Patients in a retrospective case control study were assigned to either DiC or one of two age- and gender-matched control groups (non-inflammatory controls and inflammatory colitis from other causes) based on histopathological findings. Patients' basic characteristics, symptoms, biochemical results and endoscopic appearance were collected. Statistical analysis included ANOVA, the chi-squared test and two-tailed t-test. Results: A total of 211 patients with DiC were included (97 males, age 62.1 ± 16.1 years, BMI 25.9 ± 6.1 kg m -2 ). In comparison to both control groups, DiC patients presented higher ASA and ECOG-scores and more particularly atherosclerotic comorbidities. The most abundant symptoms were abdominal pain (51.8%), diarrhoea (50.7%) and haematochezia (24.3%). The red blood cell count demarcated anaemia (12.7 ± 2.3 mg/dl) and C-reactive protein was slightly elevated (2.7 ± 5.2 mg/dl). The endoscopic features included erythema (46.9%), oedema (29.9%), erosions (29.9%) and ulcers (14.7%). The inflammation affected the rectum rarely (2.4%) but affected the rest of the colon without predilection in a segmental manner ( p <.05). The severity of DiC was mostly mild (85.7%). Conclusions: The phenotype of DiC differs slightly from that of colitis from other causes. Taking the clinical features into account might help to confirm drug-induced aetiology once the pathologist has raised the suspicion.

Eosinophilic colitis is a rare entity characterized by the presence of a high eosinophilic infiltrate into the colonic wall in symptomatic patients, more often presenting with abdominal pain or diarrhea. These characteristics distinguish eosinophilic colitis from primary colonic eosinophilia, in which patients are asymptomatic. Primary colonic eosinophilia does not need any therapy, while eosinophilic colitis requires a strict treatment, similar to that of the more codified chronic intestinal inflammatory diseases. To date the lack of codified guidelines regarding the diagnostic criteria and the eosinophil threshold values for each colonic segment are the main diagnostic challenge for eosinophilic colitis. In addition, eosinophilic colitis is a diagnosis of exclusion, once all other causes of colonic eosinophilia (food allergens, infections, drugs, etc.) have been excluded. Several treatment options are available for eosinophilic colitis, although the evidence for most of them is limited to case reports and small case series. We examine the epidemiology, etiology, pathophysiology, diagnostic criteria and therapeutic options of eosinophilic colitis reporting recent evidence from the current literature., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: Eosinophilic colitis is a rare condition, with a prevalence rate in the USA of 2-3/100 000 persons (0.003%), but diagnosed in 0.1% of biopsies in those colonoscoped for diarrhoea. Secondary colonic eosinophilia is more common and associated with systemic, colonic and infectious diseases. In this review, the latest advances in diagnosis, treatment and prognosis are summarized and discussed., Recent Findings: What constitutes a 'normal' count of eosinophils is poorly documented but there are recent studies that establish normal colonic eosinophil ranges as well as distinguishing histological and clinical findings in primary eosinophilic colitis and secondary colonic eosinophilia in children and adults. Primary eosinophilic colitis is rare, relatively straightforward to diagnose, but may be difficult to treat. Colonic eosinophilia may be overt in parasite infection and connective tissue disease. More subtle, secondary colonic eosinophilia is a useful biomarker for gastrointestinal diseases, such as inflammatory bowel disease, colonic spirochaetosis and collagenous colitis, but the eosinophilia may more often be overlooked. A limited number of drugs are also known to cause left sided colonic eosinophilia such as clopidogrel, ibuprofen and oestroprogestinic agents., Summary: Advances in our understanding of primary eosinophilic colitis and secondary colonic eosinophilia is progressing and if present, colonic eosinophilia should point the clinician and pathologist to a list of differential diagnoses worth considering to direct optimal management.

Background: Use of the immune checkpoint inhibitor ipilimumab is sometimes complicated by ipilimumab-associated colitis (Ipi-AC), an immune-mediated colitis that mimics inflammatory bowel disease., Objective: We sought to characterize the histopathologic and immunophenotypic features of Ipi-AC and to directly compare these features to ulcerative colitis (UC)., Methods: This is a retrospective cohort study of 22 patients with Ipi-AC, 12 patients with treatment-naïve UC and five controls with diarrhoea but normal endoscopic findings. Immunohistopathologic features were described, and quantitative immunohistochemistry (IHC) was performed for CD4, CD8, CD20, CD138 and FOXP3., Results: Endoscopic findings in both the Ipi-AC and UC groups included ulcerated, oedematous and erythematous mucosa. Involvement of the GI tract was more diffuse in Ipi-AC. As compared to UC, a smaller proportion of Ipi-AC biopsies had basal plasmacytosis (14% for Ipi-AC vs. 92% for UC, P < 0.0001) and crypt distortion (23% for Ipi-AC vs. 75% for UC, P = 0.003), whereas Ipi-AC biopsies had more apoptotic bodies in the left colon (17.6 ± 15.3 for Ipi-AC vs. 8.2 ± 4.2 for UC, P = 0.011). Cryptitis, ulcerations and crypt abscesses were common in both groups. Biopsy specimens from Ipi-AC had a lower density of CD20-positive lymphocytes than UC (275.8 ± 253.3 cells mm -2 for Ipi-AC vs. 1173.3 ± 1158.2 cells mm -2 for UC, P = 0.022) but had a similar density of CD4, CD8, CD138 and FOXP3-positive cells., Conclusions: Ipi-AC is a distinct pathologic entity with notable clinical and histopathological differences compared to UC. These findings provide insights into the pathophysiology of immune-related adverse events (iAEs) from ipilimumab therapy., (© 2018 The Association for the Publication of the Journal of Internal Medicine.)

Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti-programmed death-1 (PD-1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confidence intervals (CI) were estimated using random effects model. Eighteen studies were included: 6 studies (1537 patients) with PD-1 inhibitors and 15 studies (3116 patients) with CTLA-4 inhibitors. The incidence of all-grade diarrhea was 13.7% (95% CI, 10.1%-17.2%) for anti-PD-1 and 35.4% (95% CI, 30.4%-40.5%) for anti-CTLA-4. The incidence of all-grade colitis was 1.6% (95% CI, 0.7%-2.4%) for anti-PD-1, and 8.8% (95% CI, 6.1%-11.5%) for anti-CTLA-4. When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea was 0.58 (95% CI, 0.43-0.77), and the relative risk of all-grade colitis was 0.16 (95% CI, 0.05-0.51). The rate of therapy discontinuation was numerically higher for anti-CTLA-4 therapy compared with anti-PD-1 therapy. Finally, 2 studies compared combination immunotherapy with anti-CTLA-4 therapy alone. The relative risk of developing all-grade diarrhea and colitis with combination therapy was 1.31 (95% CI, 1.09-1.57) and 1.21 (95% CI, 0.73-1.99), respectively. Diarrhea and colitis are frequent toxicities associated with checkpoint inhibitors, and seem to be most common with CTLA-4 inhibitors.

Introduction: Primary eosinophilic colitis (EC) in adults is a rare and poorly studied disease, with 3 case series, 2 database-based studies and 52 case reports published to date., Methods: Retrospective study of all adult EC cases diagnosed in a large tertiary hospital (Hospital Clínico San Carlos, Madrid) between 2006 and 2016. We included all cases with a histopathological diagnosis of EC and we selected only those cases that were clinically recognized primary EC. We report their clinical, endoscopic and histopathological features and review the literature on this topic., Results: We identified 22 primary EC cases. Patients were mostly women (77%) with a mean age of 41 years. 4 patients (18%) had coexistent allergic diseases. Most patients consulted with diarrhea (86%) and 3 patients also suffered from rectal bleeding. Blood tests showed peripheral eosinophilia in 4 cases (18%). 19 patients had no endoscopic lesions, 2 had features of unspecific colitis and one showed features suggestive of IBD. Mean and maximum number of eosinophils per high power field ranged from 16 to 199 and 20 to 253 (mean: 48 and 70). They were mainly located in the lamina propria and most cases were associated with signs of eosinophil activation. Most patients were treated by corticosteroids, diet or budesonide and the result of treatment was generally good. No complications or recurrences were reported., Conclusions: EC etiology and pathogenesis is unknown. Its clinical, endoscopical and imaging features are not specific, and clear histopathological criteria are lacking. Identification of signs of eosinophilic activation could be helpful., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Diarrhea after hematopoietic stem cell transplantation (HSCT) can be life-threatening, and its etiology includes conditioning regimens, graft-versus-host disease (GVHD), infections, and transplantation-associated microangiopathy (iTAM). Cord colitis syndrome (CCS) has been described as a syndrome of culture-negative and antibiotic-responsive persistent watery and non-bloody diarrhea of uncertain pathogenesis and occurs in umbilical cord blood transplantation (UCBT) recipients. We encountered a case similar to CCS that developed severe watery diarrhea after UCBT without any signs of GVHD or infection and responded well to metronidazole (MNZ) treatment. Since CCS is very rare, we herein describe a case of MNZ-effective diarrhea after UCBT.

Colitis can be a life-threatening toxicity for patients treated with immune checkpoint blockade antibodies. With the anticipated widespread use of these reagents, the timely and accurate diagnosis of immune-related colitis becomes increasingly important. To better understand the clinical presentation of colitis from ipilimumab and to assess the use of CT scans of the abdomen/pelvis as a diagnostic tool, we retrospectively analyzed patients with advanced melanoma who received ipilimumab at our institution. Ninety nine (33%) of 303 patients developed diarrhea during therapy, and 46 patients (15%) received corticosteroids for colitis. Of the patients with diarrhea, 48 (48%) underwent colonoscopy and 46 (46%) underwent both CT and colonoscopy. In the 34 patients (34%) with a CT and biopsy, CT was highly predictive of colitis on biopsy (positive predictive value 96%), and the absence of CT findings was predictive of a negative biopsy (negative likelihood ratio 0.2). In patients who had symptoms and CT evaluation, CT was highly predictive of the need for steroids to reach resolution of symptoms (positive predictive value 92%, positive likelihood ratio 7.3). We conclude that CT is a fast, reliable, and noninvasive mode of diagnosing colitis, whereas colonoscopy and biopsy may not be needed to establish that diagnosis. Cancer Immunol Res; 5(4); 286-91. ©2017 AACR ., (©2017 American Association for Cancer Research.)

The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate that GLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD)., (Published by Elsevier Inc.)

Inflammatory bowel disease is a chronic and progressive inflammatory intestinal disease that includes two major types, namely ulcerative colitis and Crohn's disease (CD). CD is characterized by intestinal epithelial hyperplasia and inflammatory cell infiltration. Transfer of CD25 - CD45RB hi CD4 + (naïve) T cells into immunodeficiency mice induces autoimmune colitis with pathological lesions similar to CD and loss of body weight 4 weeks after cell transfer. However, weight loss neither has sufficient sensitivity nor totally matches the pathological findings of CD. To establish an early and sensitive indicator of autoimmune colitis model, the transferred T cell-induced colitis mouse model was modified by transferring luciferase-expressing donor T cells and determining the colitis by in vivo imaging system (IVIS). Colitis was detected with IVIS 7-10 days before the onset of body weight loss and diarrhea. IVIS was also applied in the dexamethasone treatment trial, and was a more sensitive indicator than body weight changes. All IVIS signals were parallel to the pathological abnormalities of the gut and immunological analysis results. In summary, IVIS provides both sensitive and objective means to monitor the disease course of transferred T cell-induced CD and fulfills the 3Rs principle of humane care of laboratory animals.

Background: Chronic diarrhea after kidney transplantation is often attributed to mycophenolic acid (MPA) toxicity. We hypothesize that intestinal infections contribute to the pathogenesis of chronic MPA-associated diarrhea., Methods: In this retrospective study, all patients (n = 726) receiving a kidney transplant between 2000 and 2010 at the University Hospital Zurich were followed until July 2014 for occurrence of chronic diarrhea (≥4 weeks). Infectious triggers at diarrhea onset were assessed by reviewing medical history, stool microbiology, and histology of colon biopsies., Results: In 46 patients (6.3% of the cohort), a total of 51 episodes of chronic diarrhea during MPA treatment were documented. The diarrhea episodes were often severe, as confirmed by significant weight loss. The cumulative incidence of chronic diarrhea was uniformly distributed throughout the post-transplant period, with 2.0%, 5.1%, and 9.6% at 1, 5, and 10 years, respectively. Evidence was found for intestinal infection at diarrhea onset in 38 episodes (74.5%). Occurrence of diarrhea onset showed a seasonal distribution with peaks in April and October/November. Specific antimicrobial treatment alone was associated with a 19% resolution rate only, whereas combination with dose reduction of MPA or switch from mycophenolate mofetil to enteric-coated mycophenolate sodium resulted in a 22.7% and 76.5% resolution rate, respectively. Change to an MPA-free regimen was associated with a 100% resolution rate., Conclusion: These results provide first evidence for a contribution of intestinal infections in chronic post-transplant diarrhea associated with MPA treatment., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 68-year-old man visited an emergency department complaining of dyspnea. He was diagnosed to have Legionella pneumonia with multiple organ failure. Although his multiple organ failure improved, he suffered from persistent abdominal pain and diarrhea with continuous minor bleeding. Colonoscopy revealed a longitudinal ulcer of the rectum, below the peritoneal reflection. He was diagnosed with cytomegalovirus (CMV) colitis. Antiviral therapy with ganciclovir was initiated. He finally underwent a colostomy after a bowel stricture caused an intestinal outlet obstruction, which made oral intake impossible. Based on the present case, we believe that CMV colitis must be considered as one of the differential diagnoses when critically ill patients develop continuous diarrhea and abdominal pain.

We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis.

Objective: To investigate whether traditional Chinese herbal formula Yupingfeng (YPF) powder has an anti-inflammatory effect on colonic inflammation, and to explore the mechanism involved., Materials and Methods: YPF powder was orally administrated to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice at the dose of 3, 6, and 12 g/kg/d for 7 consecutive days. Body weight, stool consistency, histopathological score, and myeloperoxidase (MPO) activity were tested to evaluate the effect of YPF powder on colonic inflammation while colonic enterochromaffin (EC) cell density and serotonin 5-hydroxytryptamine (5-HT) content were investigated to identify the effect of YPF powder on colonic 5-HT availability., Results: The results showed that the body weight of colitis mice was markedly decreased by 10, 12, 14, and 17% at 1, 3, 5, and 7 days (P < 0.05), whereas stool consistency score (3.6 vs. 0.4, P < 0.05), histopathological score (3.6 vs. 0.3, P < 0.05), and MPO activity (2.7 vs. 0.1, P < 0.05) in colitis mice were significantly increased compared to that of the normal mice; YPF powder treatment dose-dependently increased the body weight (7-13% increase) and decreased the stool consistency score (0.4-1.4 decrease), histopathological score (0.2-0.7 decrease), and MPO activity (0.1-0.9 decrease) in colitis mice. Colonic EC cell density (70% increase) and 5-HT content (40% increase) were markedly increased in colitis mice (P < 0.05), YPF powder treatment dose-dependently reduced EC cell density (20-50% decrease), and 5-HT content (5-27% decrease) in colitis mice., Conclusion: The findings demonstrate that the anti-inflammatory effect of YPF powder on TNBS - induced colitis may be mediated via reducing EC cell hyperplasia and 5-HT content. The important role of YPF powder in regulating colonic EC cell number and 5-HT content may provide an alternative therapy for colonic inflammation.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in Autoimmune regulator (Aire), a transcriptional regulator of negative selection in thymus. However, Aire is also expressed in periphery, but the full range of Aire's peripheral function is unknown. Here, we transferred lymphocytes from wildtype donors into lymphopenic recipients with or without functional Aire. Following cell proliferation thus took place in Aire-sufficient or deficient environment. The wildtype lymphocytes hyperproliferated and induced disease in lymphopenic Aire(-/-) but not in Aire(+/+) recipients. The disease was characterized by diarrhea, inflammation, and colitis, and in some recipients pancreatitis, gastritis, and hepatitis was also found. Our results identify Aire as an important regulator of peripheral T cell homeostasis in gastrointestinal tissues. Given a suitable trigger the absence of peripheral Aire leads to dysregulated T cell proliferation and disease., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

We present a case of a patient with a diagnostic dilemma who was referred for possible faecal microbiota transplantation (FMT) for refractory diarrhoea secondary to Clostridium difficile infection (CDI). On detailed history, the patient was exposed to ipilimumab concomitantly while being treated for CDI, and was instead diagnosed with diarrhoea secondary to superimposed ipilimumab-associated colitis. Ipilimumab is an anti-CTLA4 monoclonal antibody approved for use in metastatic melanoma and under trial for other indications. Ipilimumab is associated with several immune-related adverse effects, of which diarrhoea and colitis are the most common. While FMT has shown tremendous efficacy in managing recurrent and refractory CDI, it was not offered in this case due to negative C. difficile testing showing a high degree of suspicion for ipilimumab-associated colitis due to recent drug use. Our patient was successfully managed with fluid resuscitation and steroids, and remains symptom free at last follow-up at 9 months., (2015 BMJ Publishing Group Ltd.)

A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of β-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with β-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids., (2015 BMJ Publishing Group Ltd.)

Primary eosinophilic diseases of the gastrointestinal tract are increasingly being recognised in adults. Bosinophilic colitis is even less understood and presents with highly variable symptoms depending on the depth of mucosal involvement. We are presenting a case of primary eosinophilic colitis presenting with diarrhoea and localized caecal perforation. Pre-operative computed tomography suggested caecal malignancy and possible livier mnetastasis. Patient underwent an emergency laparoscopic right hemicoloectomy and histology revealed eosinophilic colitis. Post- operative period was complicated by pulmonary embolism and deep vein thrombosis. Secondary causes of eosinophilia were appropriately investigated and excluded. She made a good recovery and a post-operative colonoscopy looking for other areas of eosinophilia was normal.

Blastocystis is a common parasite and regarded as one of the etiologic agents of irritable bowel syndrome, colitis and chronic diarrhea. Our study was undertaken in order to identify different subtypes of Blastocystis isolated in patients with irritable bowel syndrome and colitis, as well as with chronic diarrhea and to evaluate their pathogenic potential. Seventy-three subjects (10 asymptomatic infected subjects, 49 subjects harboring Blastocystis or associated with other etiologic agents like bacteria, yeasts, protozoa, helminthes and 14 subjects with unknown etiologic agents) were investigated by in vitro parasitological and bacteriological stool samples followed by PCR subtyping of Blastocystis using STS primers, immunological markers (total serum IgA and IgE antibody levels), Helicobacter pylori antigen rapid test and fecal occult blood test. Also, among 49 subjects, there were 12 subjects harboring Blastocystis as the single etiologic agent. Subtyping proved that only three subtypes of Blastocystis were identified as following: subtype II (66.66%) in single infected subjects, subtype I (16.66%) in mixed infection with subtype II and subtype IV (8.33%) in single infected subjects. Total serum IgA and IgE antibody levels were in normal range. Subtype II was the most frequent subtype followed by subtype I and subtype IV of Blastocystis isolates in patients with irritable bowel syndrome, colitis, and chronic diarrhea as well as in asymptomatic infected group. Our results suggest that the severity of clinical manifestations depend on factors involving the host and possible parasitic density and not necessarily by isolated subtype.

Fecal microbiota transplantation (FMT) has been shown to be safe and efficacious in individuals with refractory Clostridium difficile. It has not been widely studied in individuals with immunosuppression due to concerns about infectious complications. We describe two solid organ transplant recipients, one lung and one renal, in this case report that both had resolution of their diarrhea caused by C. difficile after FMT. Both recipients required two FMTs to achieve resolution of their symptoms and neither had infectious complications. Immunosuppressed individuals are at high risk for acquisition of C. difficile and close monitoring for infectious complications after FMT is necessary, but should not preclude its use in patients with refractory disease due to C. difficile. Sequential FMT may be used to achieve cure in these patients with damaged microbiota from antibiotic use and immunosuppression., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aim: Eosinophilic colitis (EC) is a rare manifestation of eosinophilic gastrointestinal disorders. Due to its rarity, little information is available on its natural history., Method: From the single population-based pathology database of the Calgary Health Region (comprising a population of 1.28 million in 2008), cases of EC during the period 1996-2008 were identified. Medical records of all adults diagnosed with EC were identified and the pathology reviewed. The patients were then contacted for follow-up using a standardized questionnaire., Results: Seven cases of EC (four in women) were identified, with a median follow-up of 45 (23-79) months. The median age at diagnosis was 42 (22-70) years. Symptoms at diagnosis were abdominal pain (86%), nonbloody diarrhoea (57%), bloody diarrhoea (29%) and significant (>10%) weight loss (29%). Three patients gave a history of allergic reactions to drugs and four reported allergy to cows' milk. Endoscopic findings were nonspecific, ranging from oedema to small aphthous ulceration. An eosinophilic infiltrate was identified in the lamina propria in the initial colonic biopsy in all patients. Over the longer term, three patients experienced spontaneous resolution without treatment. Two continued to have mild diarrhoea and abdominal cramps but did not require medical therapy. Two patients required medical treatment by 5-aminosalicylic acid, with one requiring prednisone and azathioprine maintenance therapy., Conclusion: Eosinophilic colitis is a rare mostly self-limiting disease affecting middle-aged adults. It usually has a mild clinical course and drug treatment is not usually necessary. When required, drug treatment follows the standard medication for other inflammatory bowel disease., (Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.)

A 39-year-old man presented with diarrhea and abdominal pain. At 26 years of age, he was found to have eosinophilia and abnormal liver function parameters, for which prednisolone therapy was started. He subsequently underwent a liver biopsy and endoscopic retrograde cholangiopancreatography, and received a diagnosis of primary sclerosing cholangitis (PSC). On presentation to our hospital, he was further diagnosed with eosinophilic colitis based on aggravation of diarrhea and severe eosinophilic infiltration in the colonic mucosa. We herein report a rare case of concurrent PSC and eosinophilic colitis.