Pathogenesis Of Microscopic Colitis Research Articles

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.

Increased Mast Cell Counts and Degranulation in Microscopic Colitis.

Objectives Microscopic colitis (MC) is characterized by chronic diarrhea, normal colonoscopy findings, and mucosal inflammation in colonic biopsies and can be classified as collagenous colitis (CC) or lymphocytic colitis (LC). However, the pathogenesis of MC is largely unknown. In this study, we aimed to study mast cell counts and activation in MC. Methods We investigated 64 biopsy samples from the surgical pathology database of Indiana University Health, which met the diagnostic criteria for CC or LC along with 20 control samples collected from 2014 to 2015. The specimens were used for the quantification of mast cells by examining the presence of intracellular and extracellular tryptase by immunohistochemistry. Results In the lamina propria, the mast cell count was higher in both CC and LC groups than the control (mean highest count, 39/high-power field (HPF) vs. 30/HPF vs. 23/HPF; P < 0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (P < 0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (P < 0.01). Extracellular tryptase was present in 10% of control subjects as compared to 41% of CC (Conclusions The increased mast cell count and degranulation are identified in MC, suggesting that mast cell activation might be involved in the pathogenesis of MC.

Genome-Wide Association Study of Microscopic Colitis in the UK Biobank Confirms Immune-Related Pathogenesis.

Background and AimsThe causes of microscopic colitis are currently poorly understood. Previous reports have found clinical associations with coeliac disease and genetic associations at the human leukocyte antigen [HLA] locus on the ancestral 8.1 haplotype. We investigated pharmacological and genetic factors associated with microscopic colitis in the UK Biobank.MethodsIn total, 483 European UK Biobank participants were identified by ICD10 coding, and a genome-wide association study was performed using BOLT-LMM, with a sensitivity analysis performed excluding potential confounders. The HLA*IMP:02 algorithm was used to estimate allele frequency at 11 classical HLA genes, and downstream analysis was performed using FUMA. Genetic overlap with inflammatory bowel disease [Crohn’s disease and ulcerative colitis] was investigated using genetic risk scores.ResultsWe found significant phenotypic associations with smoking status, coeliac disease and the use of proton-pump inhibitors but not with other commonly reported pharmacological risk factors. Using the largest sample size to date, we confirmed a recently reported association with the MHC Ancestral 8.1 Haplotype. Downstream analysis suggests association with digestive tract morphogenesis. By calculating genetic risk scores, we also report suggestive evidence of shared genetic risk with Crohn’s disease, but not with ulcerative colitis.ConclusionsThis report confirms the role of genetic determinants in the HLA in the pathogenesis of microscopic colitis. The genetic overlap with Crohn’s disease suggests a common underlying mechanism of disease.

Microscopic colitis: a narrative review with clinical approach.

Microscopic colitis (MC) is diagnosed in presence of microscopic alterations of colonic mucosa, in patients without macroscopic lesions who referred for chronic diarrhea. The two types of MC are lymphocytic colitis (LC) and collagenous colitis (CC), but it is unclear whether these are the different expression of one unique disease or if they are distinct conditions. Today, although MC represents a consistent health problem, being responsible for a large part of gastroenterological consultations for diarrhea, it remains often underestimated. The detailed pathogenesis of MC has not been determined yet. Probably, it is the result of an interaction between individual, environmental and genetic factors. The most relevant risk factor for the development of MC is the use of certain drugs (such as non-steroidal anti-inflammatory drugs [NSAIDs], proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors, beta-blockers, statins). Smoking is another relevant factor reported as associated with the development of MC. Diagnosis needs the execution of a colonoscopy in patients complaining about chronic diarrhea and abdominal pain. The crucial role is played by histology: MC is characterized by the presence of colonic mucosal lymphocytic infiltrate, with intraepithelial lymphocytes ≥20 per 100 enteric surface cells, in CC there is a typical subepithelial collagen layer, whose thickness is ≥10 μm. We carried out a review of the current literature to rule out what is new on epidemiology, diagnosis and therapy of MC.

Proinflammatory Sulfur-Reducing Bacteria Are More Abundant in Colonic Biopsies of Patients with Microscopic Colitis Compared to Healthy Controls.

Microscopic colitis (MC), a subtype of inflammatory bowel disease, is a chronic condition of unknown etiology. Recent evidence has linked MC with intriguing changes in the stool microbiota, which may be linked to disease pathogenesis. The composition of the mucosal microbiome in patients with MC remains unclear. We performed a cross-sectional study comparing colonic tissue samples from patients with MC to those of healthy controls at the Michael E. DeBakey VA Medical Center. We included adults older than 18 who underwent a colonoscopy with biopsies to evaluate chronic diarrhea. Cases were defined by histology consistent with MC and controls by the absence of histologic disease. We conducted structured chart review to exclude other gastrointestinal diseases and obtain demographic (age, sex, race) and clinical (duration of symptoms and concurrent medications) information for cases and controls. We extracted bacterial DNA from formalin-fixed paraffin-embedded tissue samples and sequenced the v4 region of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering was performed using UPARSE, and OTUs were assigned using the SILVA database. Statistical analysis was performed in QIIME and LEfSe. Comparisons with FDR-adjusted p values of less than 0.05 were considered statistically significant. We included 20 MC patients and 20 controls with mean ages of 62 and 54, respectively. Most cases were White (95%), 60% had symptoms for greater than 12months, and 50% were taking PPIs and NSAIDs at the time of their diagnosis. Compared to controls, MC patients had a significant increase in the proinflammatory sulfur-reducing bacterial family Desulfovibrionales. The Coriobacteriaceae family, abundant in the healthy gut, was significantly decreased in MC cases. There was also an increase in the genus Actinomyces in MC patients on PPI and an increase in the class Bacilli among those taking NSAIDs. Patients with MC have an increase in the proinflammatory family Desulfovibrionales. Actinomyces and Bacilli were associated with medications (PPI and NSAID) known to increase the risk of MC. Our findings may have important implications for understanding the pathogenesis of MC.

Chronic Diarrhea After Infectious Enteritis: Not the Diagnosis You Are Thinking of

Microscopic colitis is described as an inflammatory bowel disease characterized by chronic, non-bloody diarrhea with normal or close to normal endoscopic findings. Histopathological examination reveals two subtypes: collagenous colitis and lymphocytic colitis, which are indistinguishable clinically. Microscopic colitis has a female preponderance, with a mean age at diagnosis of 65 years. The pathogenesis of microscopic colitis is unclear, but it is likely to be multifactorial, involving mucosal immune responses to luminal factors in a genetically predisposed individual. We present two cases of young patients presenting with chronic diarrhea, which began after episodes of infection enteritis, both ultimately diagnosed with lymphocytic colitis. A 30-year-old male presented to the office with diarrhea for 5 months. The change in bowel habits occurred after an episode of apparent food poisoning due to eating oysters. While acute vomiting subsided, he continued to have painless, watery, non-bloody bowel movements 5-6 times per day particularly after meals with nocturnal symptoms. Physical examination, labs and chemistry were unremarkable. Colonoscopy was macroscopically normal. Random colon biopsies revealed increase in lymphoid cells in the lamina propria and intraepithelial regions. A 23-year-old female presented with diarrhea and 10lb weight loss over the preceding six months. Diarrhea was painless, non-bloody, watery, multiple times a day, particularly after meals and waking her from sleep. Medical interview identified a trip to Mexico which preceded her diarrheal illness and during which she suffered from a seemingly self-limited episode of infectious enteritis. Physical exam, CBC, chemistry, serology for celiac disease and stool studies were unremarkable. Colonoscopy was remarkable for mild patchy erythema throughout the colon, biopsies revealed changes consistent with lymphocytic colitis. Loperamide did not improve diarrhea in either case. Both patients were started on budesonide 9mg and tapered over several weeks, which led to full remission of diarrhea and return to normal bowel habits. Simple infectious enteritis can be a predisposing factor for microscopic colitis and should be considered along with post-infectious irritable bowel syndrome when patients do not improve with time and supportive care alone. This diagnosis should be considered in very young patients even though they are not the typical demographic for the disease.2090 Figure 1. Colon Biopsy

Microscopic colitis-microbiome, barrier function and associated diseases.

Microscopic colitis (MC) is a chronic inflammatory bowel disease (IBD) with little in terms of endoscopic abnormalities and is frequently associated with other autoimmune diseases. The peak incidence of the disease is in middle aged or older populations, mostly females. The pathogenesis of MC is complex, multifactorial and poorly understood. Current concepts revolve around innate immunity or microbiome alterations as well as gut barrier dysfunction, all of which lead to the development of subtle inflammatory lesions in gut mucosa. The results of numerous basic and clinical studies involving molecular techniques as well as advanced endoscopic imaging revealed the important role of both intrinsic (e.g., hormonal) as well as extrinsic (e.g., NSAIDs and PPIs) factors in the modulation of gastrointestinal microbiome and MC pathogenesis. Capsule endoscopy as well confocal endomicroscopy imaging, alongside standard endoscopic techniques offer new tools in the evaluation of MC patients and allow their better stratification for novel treatment protocols based on modulation of gut microbiome and barrier function.

P090 Is Epstein–Barr virus infection associated with the pathogenesis of microscopic colitis?

P090 Is Epstein–Barr virus infection associated with the pathogenesis of microscopic colitis?

Is Epstein-Barr virus infection associated with the pathogenesis of microscopic colitis?

BackgroundEpstein-Barr virus (EBV) has been associated with inflammation in the colon, particularly in patients with inflammatory bowel disease (IBD). Even if a relevant plasmocytosis, similar to IBD, is present in microscopic colitis (MC), the frequency of EBV infection in this setting is unknown. ObjectivesWe aimed to compare the frequency of colonic EBV infection in patients with MC, ulcerative colitis (UC), and irritable bowel syndrome (IBS). Study designThe frequency of colonic EBV infection in biopsies of 30 patients with MC, 30 patients with UC, and 30 controls with IBS was retrospectively assessed. PCR was performed to detect viral EBV DNA in colonic biopsies. In situ hybridization was also performed to identify and localize EBV-encoded small RNA1 and 2 (EBERs) within cells. ResultsThe presence of EBV DNA was detected in 27 out of 30 MC patients, in 20 out of 30 UC cases, and in none of IBS group. The frequency of EBV DNA in MC was significantly higher compared with that reported in UC (90.0% vs. 66.7%, p=0.03). EBERs+ cells were observed in 18 out of 30 MC patients, in only 3 out of 30 UC patients (60.0% vs. 10.0%, p<0.001), and in none of IBS group. ConclusionsEBV infection is almost always detectable in the colonic mucosa of patients with MC. Further studies are necessary to confirm this association and to clarify the role of EBV in MC and, more generally, in colonic inflammation.

Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study.

Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited. The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis. A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality. Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001). Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

Evolution of ideas on microscopic colitis

The literature review gives the present-day views of the definition, etiology, pathogenesis, diagnosis, and treatment of microscopic colitis (MC). In the present view, MC is an inflammatory bowel disease of unknown etiology, which is characterized by chronic watery diarrhea, no macroscopic signs of large bowel involvement in the presence of specific pathomorphological changes. There are two major forms of MC, which are similar in its clinical picture, yet, heterogeneous in histological criteria: collagenous colitis (CC) and lymphocytic colitis (LC). As of now, the prevalence of MC is about 100 cases per 100,000 population, which is similar with that in other inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. MC generally prevails in women aged over 50 years. The etiology and pathogenesis of MC have not fully investigated. Watery diarrhea is as a predominant pathognomonic symptom in all the patients with MC. The major histological criterion for the diagnosis of CC is subepithelial collagen lining thickening (more than 10 pm) and that for LC is higher intraepithelial lymphocyte counts (more than 20 intraepithelial lymphocytes/100 epitheliocytes). The topical glucocorticosteroid budesonide is currently the only agent, the efficacy of which has been proven in both inducing and maintaining remission in patients with MC in many clinical trials.

Association of Serotonin Transporter Promoter Polymorphism (5-HTTLPR) with Microscopic Colitis and Ulcerative Colitis

Serotonin (5-HT) release and serotonin reuptake transporter (5-HTT) expression have been reported to be decreased in experimental colitis, in interleukin-10 knockout-associated colitis, and in patients with ulcerative colitis. Serotonin is known to play an important role in the pathogenesis of colitis, but individual genetic variants of 5-HTT gene in microscopic colitis and ulcerative colitis are not known. This study aimed to evaluate the association between the serotonin transporter gene promoter polymorphism (5-HTTLPR) and 5-HT concentration in microscopic colitis (MC) and ulcerative colitis (UC) patients. This prospective case-control study included 41 patients with microscopic colitis (age 19-82 years, mean 35 ± 13.6), 75 patients with ulcerative colitis (age 16-65 years, mean 38.5 ± 11.6), and 100 controls (age 20-64 years, mean 38 ± 11). 5-HTTLPR gene polymorphism was studied by polymerase chain reaction-based assay. 5-HT levels were measured by ELISA. The frequency of the 5-HTTLPR (SS) genotype was significantly lower in MC (12 %) patients compared to controls (30 %) (p < 0.05). When the L/L and L/S genotypes were combined into one group, the frequencies of the non-S genotype were significantly higher than those of S/S genotype between the MC patients and the controls (p < 0.05). 5-HT levels were significantly higher in UC and MC patients compared to healthy controls (p < 0.01). A significant association was observed between LL genotype of 5-HTTLPR polymorphism and microscopic colitis, suggesting that 5-HTTLPR is a potential candidate gene involved in the pathogenesis of microscopic colitis. Serotonin levels were significantly higher in microscopic colitis and ulcerative colitis patients compared to healthy controls.

Cytokine gene polymorphism in microscopic colitis association with the IL-6-174 GG genotype

Microscopic colitis (MC) is a chronic inflammatory disease with unknown pathogenesis. Very little is known about polymorphisms in the cytokine genes in MC. We have investigated the occurrence of well-characterized polymorphisms of interleukins (IL-6, IL-1β, IL-1 receptor antagonist, IL-10) and CD14 in MC. We also determined the serum IL-6 levels. We genotyped 81 patients with MC and 178 controls for polymorphisms of IL-6-174, IL-1β-511, IL-1β-3953, IL-1 receptor antagonist, IL-10-1082 and CD14-159. Serum concentration of IL-6 was measured in 72 patients. Genotype GG of IL-6-174 was more prevalent in MC compared with the controls (P=0.030; odds ratio: 1.941; confidence interval: 1.078-3.495), and the frequency of allele G of IL-6-174 was higher in MC (0.55 vs. 0.47; P=0.036; odds ratio: 1.514; confidence interval: 1.041-2.203). However, after correction for multiple comparisons, the difference became nonsignificant. IL-6 genotype and the serum IL-6 concentration showed no association. The concentration of IL-6 was higher in patients with collagenous colitis than in those with lymphocytic colitis (median 1.73 vs. 1.34 pg/ml, P=0.011). No association between polymorphisms of other cytokine genes and MC was seen. The IL-6-174 gene polymorphism has a possible association with MC, as the IL-6 GG genotype was more frequent in patients with the disease. As this genotype may be linked with an enhanced IL-6 production, we speculate that this polymorphism can influence the pathogenesis of MC by evoking a proinflammatory bias in the mucosal cytokines. The enhanced concentration of IL-6 in collagenous colitis compared with lymphocytic colitis supports a difference in the pathogenetic mechanisms between the two subgroups of MC.

Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case–control study

Microscopic colitis causes chronic watery diarrhoea. Recent studies have suggested an aetiological role for various medications, including proton pump inhibitors, in the pathogenesis of microscopic colitis. To determine whether an association exists between microscopic colitis and proton pump inhibitor use in patients with documented microscopic colitis vs. age- and gender-matched controls. In this retrospective case-control study, cases of microscopic colitis from a secondary and tertiary referral medical centre diagnosed in the last 5 years were reviewed. Demographic characteristics, clinical, histological and endoscopic records, as well as exposure to PPIs and NSAIDs were assessed. Controls from the population were matched to cases by gender and by age. During the investigated period, 136 cases were identified in both hospitals. Of these, 95 cases of microscopic colitis were retrieved for detailed analysis. Exposure to proton pump inhibitors at the time of the histological diagnosis was significantly higher in patients with collagenous colitis than in controls [38% vs. 13%, P < 0.001; adjusted OR of 4.5 (95% CI 2.0-9.5)]. This observation confirms the presumed association between microscopic colitis and PPI use, and it supports the possible aetiological role of PPI exposure in the development of microscopic colitis.

Microscopic colitis

As the diagnosis of microscopic colitis (MC) is made on the basis of histologic criteria, it is crucial to render an accurate microscopic interpretation. Features include 20 or more lymphocytes per 100 epithelial cells, mixed lamina propria inflammatory infiltrate, and preservation of crypt architecture for both lymphocytic and collagenous colitis (CC). CC is further characterized by a collagen band at least 10 mum thick. Although the pathogenesis of MC is poorly understood, medication-induced toxicity to the colonic mucosa is important to recognize, as medication cessation leads to prompt improvement. If MC is mild, symptomatic treatment is all that is needed, because some cases are self-limiting. Budesonide, 9 mg daily for at least 8 weeks, is the best documented treatment of choice for more severe or protracted cases. A 75% response rate has been reported; however, when treatment is discontinued, relapse is common, and longer-term tapering dose therapy often is necessary. There are disadvantages and no advantage to other forms of steroid therapy. Cholestyramine, bismuth, and 5-aminosalicylate derivatives appear to be less efficacious but are reasonable therapeutic options for less severe cases. Use of immunosuppressant therapy such as azathioprine or 6-mercaptopurine should be highly restricted because MC is a benign condition that does not result in other complications. Probiotic therapy with Lactobacillus acidophilus and Bifidobacterium animalis has not been shown to be effective in reducing bowel frequency. Surgical diversion of the fecal stream can control diarrhea and improve histology but is very rarely indicated and should be reserved for highly selected cases of severely symptomatic steroid-refractory MC.

Genetic background of lactose intolerance and implications for diagnosis

with both CC and LC, and if there was associated entempathy. Methods: 32 patients with microscopic colitis (17 CC, 15 LC) diagnosed using objective histological criteria were included. Serum IgA-antiendomysial (AEA) and lgA-human tissue antitransglutaminase (AtTG) antibodies (IIF and ELISA assays, respectively) were investigated, after ruling-out lgA deficiency. The DQ2 hapforype (DQAI*0501 + DQBI*0201) was deterrmned by PCRSSP. This method detects the presence or absence of at least one copy of the haplotype. HLA-DQ2 was also assayed in 50 healthy controls from the general population. Endoscopic biopsies from 2d-3rd portions of duodenum were obtained in DQ2 + patients. The number of intraepithefial lymphocytes (IEL) (N<8 x 20 epithelial cells), their distribution pattern, and the architecture of villi were assessed. Results: 13 of 32 (40.6%) patients with microscopic colitis and 9 of 50 (18%) controls had DQ2 + (p = 0.025). There were no differences between CC and LC (35.3 vs 47%). A LC patient had positive AEA and AtTG, and biopsy with IEL increase (11x20 epithelial cells) without atrophy (Marsh 1); she was diagnosed of CS and a gluten-free diet was started. In the other 30 patients, AEMAtTG were negative. In 7 DQ2 + patients the number of [EL was normal and there was no villous atrophy (in 5 patients endoscopic biopsies were not available). Conclusions: in the present series, the frequency of CS in microscopic colitis patients was 3.2%, lower than that previously described, but higher than that observed in the general population in our country (0.03%). The high frequency of DQ2 haplotype observed in patients with CC/LC confirms the existence of a high genetic susceptibility to CS in these patients, and suggests that class II HLA genes might be implicated in the pathogenesis of microscopic colitis.

Familial occurrence of microscopic colitis: a report on five families.

The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. Familial occurrence of microscopic colitis was identified in five families. In all families a sister-sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.

Familial Occurrence of Microscopic Colitis: a Report on Five Families

Background: The etiology and pathogenesis of microscopic colitis is unknown. Whether genetic predisposition is of importance, as in many other gastrointestinal diseases, is unknown. Familial occurrence of collagenous colitis has earlier been reported only in two families. Methods: Familial occurrence of microscopic colitis was searched for in a Swedish national microscopic colitis register. Results: Familial occurrence of microscopic colitis was identified in five families. In all families a sister- sister relationship was found. Two sisters with collagenous colitis had been living apart in different Nordic countries for many years before developing the disease. In one pair, the smoking sister had collagenous colitis and the never smoking sister had lymphocytic colitis. Conclusions: Considering the relative rarity of microscopic colitis, these findings indicate that a genetic predisposition may be of importance.

Colite lymphocytaire et syndrome de Gougerot-Sjögren. À propos de deux cas

Microscopic colitis describes a subset of patients with chronic watery diarrhea of unknown origin, and normal endoscopic findings and microscopic evidence of an inflammatory infiltrate in the colonic mucosa. We report two cases associated with sicca syndrome. A 56-year-old woman and a 76-year-old man presented with a history of lymphocytic colitis associated with sicca syndrome. Drugs or infectious agents were not implicated in the cause of lymphocytic colitis, suggesting that sicca syndrome may be involved in the pathogenesis of microscopic colitis. These cases suggest that sicca syndrome should be detected in patients with lymphocytic colitis.