Collagenous gastritis and collagenous colitis: a report with sequential histological and ultrastructural findings

The case is reported of a young adult man with collagenous gastritis, an extremely rare disorder with only three case reports in the English literature, who subsequently presented with collagenous colitis. Sequential gastric biopsies showed a notable increase in thickness of the subepithelial collagen band. Ultrastructural study of gastric and rectal mucosa showed the characteristic subepithelial band composed of haphazardly arranged collagen fibres, prominent degranulating eosinophils, and activated pericryptal fibroblasts.     

Sequential histologic evaluations in collagenous colitis

To evaluate the histologic manifestations of collagenous colitis and correlate histologic changes with disease behavior, 14 patients who had undergone sequential evaluations during 33±6 months of follow-up were studied. Two hundred twelve tissue specimens from all anatomic regions of the colon (mean, 15±3 samples per patient) were interpretated independently under code by two pathologists. Eight patients (57%) had histologic resolution after 14±4 months of empiric therapy and in only one of these (12%) did symptoms persist. Four patients (29%) had sequential histologic examinations from the same anatomic region that varied from classical collagenous colitis to ilflamed mucosa without a thickened collagen band to normal mucosa. Eight patients (57%) had varying histologic findings from different anatomic regions during the same examination that ranged from classical collagenous colitis to increased inflammation with resolution of the collagen band to normal mucosa. Normal mucosa was found mainly in specimens from the rectosigmoid, and proctosigmoidoscopic examinations alone would have missed the diagnosis of collagenous colitis in 40% of cases. Pathologic interpretations were concordant in 171 of 212 instances (81%). We conclude that histologic resolution of collagenous colitis can occur and it is associated with loss of symptoms. The histologic features of collagenous colitis are distinctive, but they may be patchy and inconsistently sampled. Rectosigmoid biopsies underestimate the diagnosis.Data analysis was performed in part using the CLINFO Data Analysis System.Presented in part at the annual meeting of the American College of Gastroenterology, October 16, 1991, Boston, Massachusetts.     

Concurrent collagenous colitis and multiple heal carcinoids

Summary A case of collagenous colitis in a patient with ileal carcinoid is described. Considerable fibrofatty thickening of the small bowel mesentery was present. The association of these findings appears to be unprecedented. Further observations are required to ascertain that collagenous colitis is one of the protean manifestations of carcinoid tumor.     

Clinical characteristics of collagenous and lymphocytic colitis

Background: Microscopic colitides (MC), collagenous colitis (CC) and lymphocytic colitis (LC) share clinical features, but their mutual relationship is unclear, and clinical comparative studies are rare. We aimed to examine the clinical features in CC and LC by focusing on concomitant diseases. Methods: Patients with MC (30 with CC, 54 with LC) were identified in the pathology databases and by reviewing biopsies. Controls included 84 age‐ and sex‐matched persons. The clinical data collected from patient records were prospectively completed by interviews. Results: The female:male ratio was 2:1 in CC and 5.75:1 in LC. Mean age at diagnosis was 53 in CC and 55.4 years in LC. There were no differences in the pattern of symptoms. Concomitant autoimmune diseases were more common in CC (53.3%) than in LC (25.9%; P?=?0.017). Celiac disease was common in both CC (20%) and LC (14.8%). Bronchial asthma was associated with LC (25.9%), but not with CC (6.7%; P?=?0.042). Colon diverticulosis was rare in MC (16%) compared with the controls (39%; P?=?0.001). Hypolactasia was common in MC (45%; 76% in CC, 54% in LC) compared to its prevalence in the Finnish general population (17%). Conclusions: CC and LC are largely similar clinically, but the differences in the occurrence of autoimmune conditions and bronchial asthma suggest that they differ in immunopathogenesis. MC is associated with reduced lactose tolerance and shows a negative association with diverticular disease, possibly related to the small intestinal pathology and abnormal stool consistency.     

Original research: Incidence of collagenous colitis in NHS Lothian: a population-based study

ObjectiveIncreases in incidence of collagenous colitis (CC) have been documented across Europe; however, previous data from NHS Lothian (1998–2003) demonstrated this to be a low-prevalence area. We aimed to assess incidence of CC in NHS Lothian over time by comparing a more recent cohort (2013–2018) with our existing cohort.MethodsAll histologically confirmed diagnoses of CC between 2013 and 2018 were obtained from the NHS Lothian colorectal pathology department (Western General Hospital, Edinburgh). Case record review was performed to obtain relevant demographic and clinical data. Data were also collected regarding the availability of colonoscopy in NHS Lothian.Results224 cases of CC were diagnosed between 2013 and 2018, compared with 25 between 1998 and 2003. Mean annual incidence rose from 0.5/100 000 population to 4.3/100 000 population. Incidence in females ≥60 years old rose from 2.3/100 000 population to 22.4/100 000 population (p<0.001). The total number of colonoscopies performed increased by 179.1% from 15 262 (1998–2003) to 42 600 (2013–2018), with the number of CC cases per 1000 colonoscopies performed rising from 1.7 to 5.3 (p<0.001).ConclusionWe describe the increasing incidence of CC in Southeast Scotland, with temporal trends comparable to other European countries. The increase is particularly marked in older females and parallels increasing numbers of colonoscopies being performed.     

Role of bile acids and bile acid binding agents in patients with collagenous colitis

BACKGROUND: In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. AIMS: To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. METHODS: Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test. RESULTS: Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests. CONCLUSION: Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.     

Primary AL-amyloidosis,ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study

A 57-year-old woman with AL-amyloid deposits in the heart, gastrointestinal tract and the liver developed ulcerative colitis, which was treated with glucocorticosteroids and 5-aminosalicylic acid, with good response. The AL-amyloidosis was successfully treated with high-dose chemotherapy and autologous stem-cell transplantation. The patient was in good clinical condition for 18 months after treatment, until she developed diarrhea, which was found to be due to collagenous colitis. Two years after treatment of amyloidosis, the patient is in excellent condition, the symptoms of heart failure have stabilized and no adverse effects of the treatment regime have been observed. The bowel diseases are in clinical remission.     

Microscopic colitis: a descriptive clinical cohort study of 795 patients with collagenous and lymphocytic colitis

Objective Microscopic colitis is a common cause of chronic diarrhoea in the Scandinavian countries. This report comprises demographic data, clinical and endoscopic features, and occurrence of coeliac and inflammatory bowel disease (IBD) in a large urban cohort of patients with lymphocytic colitis (LC) and collagenous colitis (CC). Materials and methods A total of 795 patients with microscopic colitis from two hospitals in Stockholm were included. Medical records were reviewed and clinical data, including endoscopic and histological findings, were compiled. Results Forty-three percent had CC (female:male ratio 3.7:1) and 57% had LC (female:male ratio 2.7:1). The mean age at diagnosis of CC was 63 years and of LC was 59 years (p?=?0.005). Clinical features were similar in both entities, but the intensity of symptoms differed. Watery diarrhoea was reported in 55% in CC patients versus in 43% in LC patients (p?=?0.0014), and nocturnal diarrhoea in 28% versus 18% (p?=?0.002). Subtle endoscopic mucosal findings were reported in 37% of the CC patients and in 25% of the LC patients (p?=?0.0011). Colorectal adenomatous polyps were found in 5.3% of all patients. Coeliac disease occurred in 6% and IBD occurred in 2.1% of all patients. Conclusions Clinical features of LC and CC are similar but not identical. CC seems to be a more severe type of bowel inflammation and LC tends to occur earlier in life. Both forms might indeed feature endoscopic findings despite the designation ‘microscopic’. Our study confirms the strong association with coeliac disease.     

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.     

Fecal eosinophil cationic protein as a marker of active disease and treatment outcome in collagenous colitis: A pilot study

Abstract

Background and aims. Fecal calprotectin (FC) is used as a marker for intestinal inflammation in inflammatory bowel disease (IBD) but there is no reliable marker for collagenous colitis (CC). We have previously demonstrated that the mucosal inflammation in CC is characterized by eosinophil activation, which is restored during budesonide treatment, but there is no enhanced neutrophil activity. The aim of this study was to evaluate the use of fecal eosinophil cationic protein (F-ECP) and eosinophil protein X (F-EPX) compared with the neutrophil-derived myeloperoxidase (F-MPO) and FC in patients treated for active CC. Methods. Patients with active CC (n = 12) were studied before and after 3, 7, 28 and 56 days of budesonide treatment. Clinical symptoms and stool frequency were recorded, fecal samples were collected, and F-ECP, F-EPX, F-MPO and FC were measured at each occasion. Results. All but one patient achieved remission. On inclusion 92%, 67%, 67% and 75% of the patients had elevated F-ECP, F-EPX, F-MPO and FC levels, respectively. All markers decreased during the treatment, particularly F-ECP and F-EPX, which decreased after only 3 days. At the end of the study 100%, 92%, 83% and 75% of the patients had normal F-ECP, F-EPX, F-MPO and FC values, respectively. Conclusion. F-ECP demonstrated the best discriminating capacity in detecting active CC. A normalized F-ECP and F-EPX may further be studied as a marker for successful treatment. During budesonide treatment there is a rapid fall in F-ECP and F-EPX, accompanied by clinical improvement, indicating an essential role for the eosinophil participating in the pathophysiology of CC.     

Increased HLA A1 and diminished HLA A3 in lymphocytic colitis compared to controls and patients with collagenous colitis

Lymphocytic colitis is a newly described chronic diarrheal disorder. Although its etiology is unknown, the possibility has been raised that autoimmunity may play a role in both lymphocytic and collagenous colitis, a similar clinicopathologic illness. The frequencies of HLA class I and class II antigens were examined in 24 white patients with lymphocytic colitis and in 47 white patients with collagenous colitis. Frequencies in these two disorders were compared to control white populations and to each other. An increased frequency of HLA-A1 was noted in 16 of 24 lymphocytic colitis patients (66.6%) compared with 1089 of 3942 controls (27.6%) (P<0.005; relative risk 5.2). Furthermore, HLA-A3 was found in decreased frequency in lymphocytic colitis patients: 0 of 24 (0%) compared with 1017 of 3942 controls (25.8%) (P<0.05; relative risk 0.0). Collagenous colitis patients had no significant deviation from control frequencies of HLA antigens. In lymphocytic colitis, there was no significant increase in B8 or DR3 antigens, which are found in linkage disequilibrium with A1 and associated with many autoimmune diseases. Moreover, the frequency of autoimmune-associated class I HLA antigens was not increased in lymphocytic colitis. Statistically significant differences existed between lymphocytic and collagenous colitis in HLA-A1, A3, Bw6, and B7 antigen frequencies. The HLA patterns noted previously in other gastrointestinal disorders, including ulcerative colitis and Crohn's disease, were not apparent in lymphocytic or collagenous colitis. HLA typing provides further evidence that lymphocytic colitis is a distinct form of chronic intestinal inflammatory disease associated with HLA class I phenotypes.Presented in part at the American Gastroenterological Association in May 1988 and published with preliminary data in a previous article (reference 1).Supported in part by The National Foundation for Ileitis and Colitis, by an institutional grant from The Johns Hopkins School of Medicine, and by outpatient GCRC grant RR00722.     

Clinical characteristics and patterns and predictors of response to therapy in collagenous and lymphocytic colitis

Abstract

Background. Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory disorders of the colon. There is a paucity of data on differences in etiology, natural history, and treatment response between CC and LC. Methods. Between 2002 and 2013, we identified new diagnoses of CC and LC using the Research Patient Data Registry in a tertiary referral center. We used chi square or Fischer’s exact test and Wilcoxon rank-sum tests to compare the differences in clinical characteristics, treatment types, and response rates between LC and CC. Results: Through 2013, we confirmed 131 patients with a new diagnosis of microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective treatment for both CC and LC (94% and 80%, respectively). However, there were no statistically significant differences in response to various treatments according to the type of MC (all p > 0.10). Older age at the time of diagnosis was associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95% confidence interval: 1.21–2.56 for every 5-year increase) for both CC and LC. Conclusion. Despite differences in the clinical characteristics, response rates to available treatments appeared to be similar in both LC and CC. Older patients may have a better response to bismuth subsalicylate therapy.     

Expression of nitric oxide synthases and effects of L-arginine and L-NMMA on nitric oxide production and fluid transport in collagenous colitis

BACKGROUND AND AIMS: Luminal nitric oxide (NO) is greatly increased in the colon of patients with collagenous and ulcerative colitis. To define the source and consequence of enhanced NO production we have studied expression of NO synthase (NOS) isoforms and nitrotyrosine in mucosal biopsies from these patients. In addition, effects on colonic fluid transfer caused by manipulating the substrate of NOS were studied in patients with collagenous colitis. PATIENTS: Eight patients with collagenous colitis, nine with active ulcerative colitis, and 10 with uninflamed bowel were included. METHODS: Expression of NOS isoforms was quantified by western blotting. Inducible NOS (iNOS) and nitrotyrosine were localised by immunohistochemistry. Modulation of NOS activity by topical N(G)-monomethyl-L-arginine (L-NMMA) or L-arginine was assessed during perfusion of whole colon. Plasma and perfusate nitrite/nitrate (NOx) was measured by Griess' reaction. RESULTS: Both in collagenous and ulcerative colitis, expression of iNOS was 10(2)-10(3) higher (p<0.001) than in uninflamed bowel and localised primarily to the epithelium. Endothelial NOS was evenly expressed in all groups while neuronal NOS was undetectable. Nitrotyrosine was markedly expressed in active ulcerative colitis but rarely detected in collagenous colitis and never in uninflamed bowel. In collagenous colitis, the output of NOx was markedly increased compared with uninflamed bowel (283 (58) v <37 nmol/min; p<0.01) and fluid was net secreted. L-NMMA reduced the output of NOx by 13-66% (95% confidence intervals) and secretion of fluid by 25-109% whereas L-arginine increased the output of NOx by 3-39% and secretion of fluid by 15-93%. CONCLUSIONS: In collagenous colitis, as opposed to ulcerative colitis, upregulation of iNOS occurs in the absence of nitrotyrosine formation and mucosal damage. Excess generation of NO may be the primary cause of diarrhoea in this condition.     

Lymphocytic and collagenous colitis

Opinion statement  

Collagenous colitis in setting of nonsteroidal antiinflammatory drugs and antibiotics

Collagenous colitis is a newly recognized diarrheal disorder of unknown etiology (1). Over 80% of patients are middle-aged women with no other known predisposing factors (2). We report unusual presentations of collagenous colitis in two men in whom there was closely linked use of nonsteroidal antiinflammatory drugs and antibiotics.Supported in part by a research grant from the National Foundation for Ileitis and Colitis. Dr. Lazenby is the recipient of a fellowship from the National Foundation of Ileitis and Colitis.     

Complications of collagenous colitis

Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue （or collagenous enteritis） may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn＇s disease, may evolve from coUagenous colitis. Submucosal ＂dissection＂, colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease.