The colitis may be microscopic, but the diarrhea is not: update on the treatment of microscopic colitis and immune checkpoint inhibitor colitis.

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.

Microscopic colitis found together with celiac disease in a female population is associated with one episode of lymphocytic colitis.

BACKGROUND: Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. METHODS: Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. RESULTS: MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020-17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042-1.506; p = 0.058). CONCLUSION: Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.

[Clinical cases of microscopic colitis: Diagnosis and treatment issues. Case report].

Currently, there is an increase in the incidence of microscopic colitis. There are difficulties in diagnosing this disease due to the variability of histological signs, variability of morphological changes in the mucous membrane of the colon in different parts of the colon, and the combination in one patient of not only various forms of microscopic colitis, but also other intestinal diseases. The article describes the differential diagnosis, an example of its staging and successful treatment of various forms of microscopic colitis with budesonide (two clinical cases presented).

Diagnosis and Pharmacological Management of Microscopic Colitis in Geriatric Care.

Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥ 60 years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected.

WARNING TO DELAY IN DIAGNOSING MICROSCOPIC COLITIS IN OLDER ADULTS. A SERIES OF CASES.

BACKGROUND: Microscopic colitis (MC) is a chronic inflammatory bowel disease causing non-bloody diarrhea, and several cases are undiagnosed as a hidden cause of chronic diarrhea. OBJECTIVE: We aimed to report the symptoms, delay diagnosis and the treatment of MC in a case series. METHODS: All patients were treated at a Gastroenterology reference office from May 2022 to June 2023. Personal history including preexisting disorders, use of medications and smoking habits were collected. The delay between the onset of symptoms and the correct diagnosis was informed. All patients consented to use budesonide MMX (Corament®) off label. RESULTS: During the study period, six Caucasoid patients were diagnosed with MC, five females and one male, between the ages of 65 and 74. All patients had comorbities and were taking multiple prescription drugs. Laboratory findings showed negative serology for celiac disease for all patients, normal levels of albumin and vitamin B12. The delay between the symptoms and the MC diagnosis varied from 2 months to 6 years. All patients had a previous diagnosis of irritable bowel syndrome. All patients were in complete clinical remission during the treatment and referred no side effects of the drug. CONCLUSION: Older females using high-risk medications are suggestive of MC. Preventing delay in the diagnosis of MC is crucial to improvement in patients´ quality of life. Budesonide MMX appears to be effective, safe and well-tolerated. BACKGROUND: • Microscopic Colitis is a chronic inflammatory bowel disease causing non-bloody diarrhea. BACKGROUND: • Several cases are undiagnosed and can be a hidden cause of chronic diarrhea. BACKGROUND: • Treatment with budesonide MMX (Corament®, off label) was effective and safe.

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

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

Microscopic Colitis and Celiac Disease: Sharing More than a Diagnostic Overlap.

Microscopic colitis (MC) is an emergent group of chronic inflammatory diseases of the colon, and celiac disease (CD) is a chronic gluten-induced immune-mediated enteropathy affecting the small bowel. We performed a narrative review to provide an overview regarding the relationship between both disorders, analyzing the most recent studies published at the epidemiological, clinical and pathophysiological levels. In fact, MC and CD are concomitantly prevalent in approximately 6% of the cases, mainly in the subset of refractory patients. Thus, physicians should screen refractory patients with CD against MC and vice versa. Both disorders share more than a simple epidemiological association, being multifactorial diseases involving innate and adaptive immune responses to known or unknown luminal factors based on a rather common genetic ground. Moreover, autoimmunity is a shared characteristic between the patients with MC and those with CD, with autoimmunity in the latter being quite well-established. Furthermore, CD and MC share some common clinical symptoms and risk factors and overlap with other gastrointestinal diseases, but some differences exist between both disorders. More studies are therefore needed to better understand the complex mechanisms involving the common pathogenetic ground contributing to the CD and MC epidemiological association.

Factors associated with long-term clinical outcome in microscopic colitis.

BACKGROUND AND AIMS: Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis. METHODS: We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis. RESULTS: Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide (p = .0002) and achieving histologic remission (p = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response (p = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present (p = .0002). CONCLUSIONS: In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.

Coeliac Disease and Microscopic Colitis: The Largest Study Assessing Prognosis and Risk of Hospital Admission.

Microscopic colitis (MC) and coeliac disease (CD) are common associated gastrointestinal conditions. We present the largest study assessing hospitalisation in patients with MC and the effect of a concomitant diagnosis of CD. Data were retrospectively collected between January 2007 and December 2021 from all patients diagnosed with MC and compared to a database of patients with only CD. In total, 892 patients with MC (65% female, median age 65 years (IQR: 54-74 years) were identified, with 6.4% admitted to hospital due to a flare of MC. Patients admitted were older (76 vs. 65 years, p < 0.001) and presented with diarrhoea (87.7%), abdominal pain (26.3%), and acute kidney injury (17.5%). Treatment was given in 75.9% of patients, including intravenous fluids (39.5%), steroids (20.9%), and loperamide (16.3%). Concomitant CD was diagnosed in 3.3% of patients and diagnosed before MC (57 versus 64 years, p < 0.001). Patients with both conditions were diagnosed with CD later than patients with only CD (57 years versus 44 years, p < 0.001). In conclusion, older patients are at a higher risk of hospitalisation due to MC, and this is seen in patients with a concomitant diagnosis of CD too. Patients with MC are diagnosed with CD later than those without.

Microscopic Colitis: A Diagnostic Challenge in Patients with Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Irritable Bowel Syndrome (IBS) is one of the most frequently diagnosed gastrointestinal disease with a prevalence of 4.1% in the general population. It is diagnosed using the Rome IV criteria. Microscopic colitis (MC), collagenous/lymphocytic colitis is a cause of chronic, watery, non-bloody diarrhea. It is a real challenge to diagnose MC in patients with IBS. The aims of the study were to determine the prevalence of MC in patients initially diagnosed with IBS, as well as to correlate fecal calprotectin levels with the endoscopic findings and microscopic inflammation in MC. METHODS: This is a retrospective study conducted in a single tertiary center with over 89 IBS patients for a period of 4 years. The patients included were patients diagnosed with IBS predominant diarrhea (IBS-D) and mixed IBS (IBS-M) using the Rome IV criteria. Total colonoscopy was performed in these patients, multiple biopsies being taken and calprotectin levels were measured. RESULTS: Out of a total of 89 IBS-D patients, 58 patients (65.2%) had no microscopic lesions, 12 patients (13.5%) had diverticular disease, 9 patients (10.1%) had non-specific chronic inflammation of the colon mucosa and 10 patients (11.2%) were diagnosed with MC. The calprotectin levels ranged from 49 µg/g to 213 µg/g. Of a total of 10 patients diagnosed with MC, 6 (60%) of them had calprotectin levels <100 µg/g and 4 (40%) had calprotectin levels >100 µg/g. The fecal calprotectin levels were higher in patients diagnosed with MC compared to those who had no microscopic lesions at the histological exam and it was also correlated with the grade of colonic microscopic inflammation. CONCLUSIONS: Microscopic colitis is less familiar to physicians and can be clinically misdiagnosed as IBS-D. An early and correct diagnosis is important for an accurate therapy.

Frequency And Risk Factors Of Microscopic Colitis As A Cause Of Chronic Watery Diarrhoea.

BACKGROUND: Microscopic colitis (MC) is one of the most underdiagnosed conditions leading to chronic watery diarrhoea in patients worldwide. This is the first study of this kind in Pakistan and we aimed to calculate the frequency as well as study the risk factors behind the disease. METHODS: This was a prospective cross-sectional study in a tertiary care hospital in Pakistan. A total of 58 participants with chronic watery diarrhoea who had normal colonoscopy were recruited for the study and biopsies were obtained for diagnosing MC. RESULTS: 2 participants out of 58 (3.4%) had biopsy proven microscopic colitis; one patient had a lymphocytic colitis variant and the other had a collagenous colitis variant. The average score based on the MC scoring system was 7.53 in the entire study group. The patient with lymphocytic colitis had a score of 06 while the patient with collagenous colitis had a score of 8. CONCLUSIONS: The frequency of microscopic colitis was found to be 3.4% of all cases of chronic watery diarrhoea. A link between MC and autoimmune diseases was also observed. However, we had a limited sample size and encouraged future studies to employ a larger sample size to get a multifaceted look at the disease process.

Microscopic colitis: Case series and literature review / Colitis microscópica, serie de casos y revisión de la literatura

Abstract Introduction: Microscopic colitis is a benign and multifactorial disease characterized by watery diarrhea and histological alterations in the colonic mucosa. The incidence of this disease is increasing, being diagnosed more frequently. Materials and methods: In this retrospective study, patients were examined employing colonoscopy and biopsy due to a diagnosis of chronic diarrhea in a gastroenterology unit throughout 22 months. Their diagnosis of colitis was confirmed by clinical picture and microscopic analysis. Results: In the study period, a total of 2849 colonoscopies were performed, 116 in patients with chronic diarrhea. We identified 15 patients with microscopic colitis, 12 were men (80 %), and only three were older than 60 (20 %). Conclusion: Unlike the world literature, this study found that microscopic colitis in our patients affects the male sex primarily (male/female ratio: 4/1) and occurs in young people, with an average age of 47.5 years (range: 21-82 years).

Resumen Introducción: la colitis microscópica es una enfermedad benigna y multifactorial caracterizada por la presencia de diarrea acuosa y alteraciones histológicas en la mucosa colónica. La incidencia de esta enfermedad viene en aumento y su diagnóstico se realiza cada vez con mayor frecuencia. Métodos: estudio retrospectivo en el que se revisaron los pacientes por medio de colonoscopia y biopsias por diagnóstico de diarrea crónica en un período de 22 meses en una unidad de gastroenterología, y en quienes mediante la clínica y el análisis histológico se confirmó el diagnóstico de colitis microscópica. Resultados: en el período de estudio se realizó un total de 2849 colonoscopias, 116 en pacientes con diarrea crónica. Se identificaron 15 pacientes con colitis microscópica, 12 fueron hombres (80 %) y solo hubo 3 mayores de 60 años (20 %). Conclusión: a diferencia de lo informado en la literatura mundial, en este estudio se encontró que la colitis microscópica en nuestros pacientes compromete especialmente al sexo masculino (relación hombre/mujer: 4/1) y se presenta en personas jóvenes, con un promedio de edad de 47,5 años (rango de 21 a 82 años).

Colitis microscópica, un diagnóstico en aumento / Microscopic Cholitis, An Increasingly Frequent Diagnosis

Resumen Actualmente, la colitis microscópica agrupa tres subgrupos de patologías, las clásicas son la colitis linfocítica (CL) y la colitis colagenosa (CC), que histológicamente se distinguen por la presencia o ausencia de engrosamiento subepitelial; el tercer subgrupo corresponde a la colitis microscópica incompleta (CMI), que incluye a pacientes que no cumplen los criterios clásicos de colitis microscópica, pero que presentan cambios histológicos similares. Aunque se considera una enfermedad con baja prevalencia e incidencia, los estudios presentados en los últimos años evidencian un incremento leve de esta patología. Se han mencionado como factores causales los inmunológicos e infecciosos y se ha relacionado con el consumo de algunos medicamentos y de cigarrillo. Clínicamente se caracteriza por la presencia de diarrea acuosa crónica, que en algunos pacientes puede cursar con períodos de estreñimiento. Los tres subgrupos presentan manifestaciones clínicas similares, por lo que su diagnóstico generalmente es histológico. La colonoscopia con toma de biopsias es el pilar diagnóstico y se debe complementar con hemograma, examen parasitológico, estudios inmunológicos (anticuerpos antinucleares, IgG) y de función tiroidea. El tratamiento se basa en la suspensión de medicamentos relacionados, cambios en los hábitos alimenticios y en el uso de medicamentos, como los esteroides, subsalicilato de bismuto, 5-ASA y colestiramina. En la gran mayoría de los pacientes, la mejoría se logra con un bajo porcentaje de recidivas.

Abstract Microscopic colitis currently includes three subgroups. The classical ones are lymphocytic colitis and collagenous colitis which are distinguished histologically by the presence or absence of subepithelial thickening. The third subgroup is Incomplete Microscopic Colitis which includes patients who do not meet the classical criteria for Microscopic colitis but who have similar histological changes. Although prevalence and incidence are low, recent studies show that it has become slightly more common. Causative factors mentioned include immunological and infectious issue, and it has been related to some medications and to cigarette smoking. Clinically it is characterized by watery diarrhea which sometimes oscillate with periods of constipation. The three subgroups have similar clinical manifestations, so their diagnoses are usually histological. Colonoscopy with biopsy is the diagnostic pillar, and should be complemented by complete blood count, a parasitological examination, immunological studies (antinuclear antibodies, IgG) and thyroid function. Treatment is based on the suspension of related medications, changes in eating habits, and the use of medications such as steroids, bismuth subsalicylate, 5-ASA and cholestyramine. Improvement is achieved in the vast majority of patients, and recurrences are rare.

Diagnóstico y manejo de la colitis microscópica / Diagnosis and management of microscopic colitis

Microscopic colitis (MC) is a clinical condition characterized by chronic watery diarrhea, normal colonic mucosa and characteristic histological findings. It is composed of two main entities: collagenous colitis (CC) and lymphocytic colitis (LC). Its incidence has been increasing, currently accounting for between 8 to 16% of studies for chronic diarrhea. It is more frequent in elderly women and is strongly associated with other autoimmune disorders. Its pathogenesis is not very well understood, but it supposes the immune activation secondary to the exposure of the colonic mucosa to different luminal antigens, mainly drugs. Management includes suspension of the potential causative agent and the use of anti-diarrheal medications. Oral budesonide has proven to be effective in induction and maintenance of remission, but with a high rate of recurrence upon discontinuation. Immune-modulators drugs such as azatioprine and metrotrexate have been tested in patients dependent to corticoids with variable results. Antibodies against tumor necrosis factors (TNF) are under studies, with promising results.

La colitis microscópica (CM) es una condición clínica caracterizada por diarrea crónica acuosa con mucosa colónica normal y hallazgos histológicos característicos. Está compuesta por dos entidades principales: la colitis colágena (CC) y la colitis linfocítica (CL). Su incidencia ha ido en aumento, siendo en la actualidad la responsable del 8 a 16% de los casos por diarrea crónica. Es más frecuente en mujeres de edad avanzada con una fuerte asociación a otras enfermedades autoinmunes. Su etiopatogenia no es del todo conocida, pero se cree juega un rol la activación inmune secundaria a la exposición de la mucosa colónica a diferentes antígenos luminales, principalmente fármacos. Dentro del manejo se incluye la suspensión del potencial agente causal y el uso de fármacos antidiarreicos. La budesonida oral ha demostrado alta efectividad en la inducción y mantención de la remisión, pero con una alta tasa de recurrencia al suspenderla. Fármacos inmunomoduladores como azatioprina y metrotrexato se han probado en pacientes corticodependendientes con resultados variables. El uso de anticuerpos monoclonales anti factor de necrosis tumoral (TNF) se encuentra en estudio, con resultados prometedores.

Prevalence, Pathogenesis, Diagnosis, and Management of Microscopic Colitis

Microscopic colitis (MC), which is comprised of lymphocytic colitis and collagenous colitis, is a clinicopathological diagnosis that is commonly encountered in clinical practice during the evaluation and management of chronic diarrhea. With an incidence approaching the incidence of inflammatory bowel disease, physician awareness is necessary, as diagnostic delays result in a poor quality of life and increased health care costs. The physician faces multiple challenges in the diagnosis and management of MC, as these patients frequently relapse after successful treatment. This review article outlines the risk factors associated with MC, the clinical presentation, diagnosis and histologic findings, as well as a proposed treatment algorithm. Prospective studies are required to better understand the natural history and to develop validated histologic endpoints that may be used as end points in future clinical trials and serve to guide patient management.