Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis

BACKGROUND AND AIMS: It is not known whether lymphocytic colitis and collagenous colitis represent different clinical entities or constitute part of a spectrum of disease. METHODS: Detailed clinical features and histological findings were compared in a large series of patients with confirmed lymphocytic and collagenous colitis. RESULTS: Histological diagnosis was confirmed in 96 patients with collagenous colitis and 80 with lymphocytic colitis. Twenty eight per cent of patients with collagenous colitis and 26% of patients with lymphocytic colitis had overlapping but less pronounced histological features. Both groups were equal in terms of age, use of aspirin and non-steroidal anti-inflammatory drugs, associated autoimmune conditions, arthritis, diarrhoea, and abdominal pain. The male:female ratio was 27:73 for collagenous colitis and 45:55 for lymphocytic colitis (p=0.013). Twenty five per cent of patients with collagenous colitis compared with 14% of patients with lymphocytic colitis were active smokers; only 8.3% of patients with collagenous colitis had stopped smoking compared with 23% of patients with lymphocytic colitis (p=0.013). Drug induced disease was suspected for ticlopidine (two collagenous colitis, four lymphocytic colitis) and flutamide (four lymphocytic colitis). Mean duration of symptoms before diagnosis was two months for lymphocytic colitis and four months for collagenous colitis. Overall prognosis was generally mild; 84% of patients with lymphocytic colitis and 74% of patients with collagenous colitis reported resolution or significant improvement (p=0.033). CONCLUSIONS: Collagenous and lymphocytic colitis are similar but not identical. Patients with lymphocytic colitis present somewhat earlier and are less likely to be active smokers. Symptoms are milder and more likely to disappear in lymphocytic colitis. Ticlopidine and flutamide should be added to the list of drugs inducing colitis.     

Thiol methyltransferase activity in inflammatory bowel disease

BACKGROUND: Luminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes. AIMS: To measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis. PATIENTS: Venepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis. METHODS: TMT activity was measured by high performance liquid chromatography with radioactive detection to measure (14)C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and (14)C S-adenosylmethionine. RESULTS: Erythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (p<0. 001) compared with control cases. TMT activity of rectal biopsies was significantly decreased (p<0.02) in acute but not quiescent ulcerative colitis, Crohn's colitis, or radiation colitis. CONCLUSIONS: Erythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile.     

Collagenous and lymphocytic colitis in Iceland

The aim of this study was to determine the nationwide incidence of collagenous and lymphocytic colitis in Iceland and the location of histopathological changes in the large bowel. All pathology reports of patients diagnosed with or suspected of having collagenous colitis or lymphocytic colitis in the period 1995–1999 were identified. All pathology samples were reevaluated using strict diagnostic criteria. After reevaluation 125 patients fulfilled our diagnostic criteria, 71 as collagenous colitis and 54 as lymphocytic colitis. The mean annual incidence for collagenous colitis was 5.2/100,000 inhabitants, and the mean age at diagnosis was 66.1 years. The mean annual incidence for lymphocytic colitis was 4.0/100,000 inhabitants, the mean age at diagnosis was 68.7 years. Both diseases more commonly involved the colon than the rectum. The incidence of collagenous colitis and lymphocytic colitis is high in Iceland. The mean annual incidence of collagenous colitis is much higher in Iceland than hitherto reported elsewhere.     

Spectrum of microscopic colitis in a tertiary care centre in India

INTRODUCTION: The incidence of microscopic colitis has recently increased. Although collagenous colitis and lymphocytic colitis are the two main subtypes of microscopic colitis, many patients may not fit into either category and are thus included under the header nonspecific colitis. Of late, the spectrum of microscopic colitis has widened to include minimal change colitis, microscopic colitis not otherwise specified and microscopic colitis with giant cells. There is a lack of information concerning the spectrum of microscopic colitis in Asia. METHOD: In a retrospective analysis, case records of 29 patients diagnosed with microscopic colitis between 1999-2005 were analysed. Drug use parasitic infection and common bacterial infections were excluded. Colonoscopic/ sigmoidoscopic examination was done and multiple colonic mucosal biopsies were stained serially with haematoxylin and eosin for detailed histological examination and Masson trichrome for sub-epithelial collagen band. Based on histological criteria, patients were categorised into five subtypes: collagenous colitis (presence of collagenous thickening of surface epithelium basement membrane > 10 microm), lymphocytic colitis (intra-epithelial lymphocytes more than 20 per 100 colonocytes), minimal change colitis (crypt architectural abnormality in the form of cryptitis and crypt dilatation in the absence of increase in intraepithelial lymphocytes and subepithelial collagenous band), microscopic colitis not otherwise specified (increased inflammatory cell infiltrates in the lamina propria in the absence of other abnormalities) and microscopic colitis with giant cells. RESULTS: Mean age of patients was 38.59 years (range 12-62). Of 29 patients with microscopic colitis, 7 (24.1%), 4 (13.8%), 7 (24.1%) and 11 (37.9%) were classified as collagenous colitis, lymphocytic colitis, minimal change colitis and microscopic colitis not otherwise specified, respectively. None of these patients had giant cells. There was no significant correlation between disease type and clinical manifestations. CONCLUSION: Microscopic colitis has a wide histological spectrum. Cases reported as non-specific colitis, may be categorised into definite subtypes of microscopic colitis.     

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.     

Progression of collagenous colitis to ulcerative colitis

Collagenous colitis is a form of microscopic colitis that results in chronic watery diarrhea. The disorder predominantly affects middle-aged women, and its course tends to be benign. It is not thought to be a precursor of overt inflammatory bowel disease; however, apparent progression to ulcerative colitis has been reported on one previous occasion. We describe two further patients with symptoms and histologic features of collagenous colitis who subsequently developed ulcerative colitis. The first patient developed ulcerative colitis 13 months after diagnosis of collagenous colitis, although she gave a 23-year history of profuse watery diarrhea, which had not been adequately investigated. In the second patient, collagenous colitis was diagnosed soon after the onset of watery diarrhea, and 12 months later, progression to ulcerative colitis was documented. Both patients tested positive for perinuclear antineutrophil cytoplasmic antibody after they developed ulcerative colitis; the first patient was initially negative. In conclusion, these two cases, in addition to the one other in the literature, suggest that collagenous colitis and ulcerative colitis may represent extremes in the spectrum of inflammatory bowel disease and that collagenous colitis may evolve to ulcerative colitis. Therefore, progression to ulcerative colitis should be considered in any patient with known collagenous colitis whenever bloody diarrhea occurs, or if red cells, as well as white cells, are noted on stool microscopy.     

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.     

Colorectal cancer in ulcerative colitis. Influence of anatomical extent and age at onset on colitis-cancer interval.

We have examined the age at onset of both ulcerative colitis and colitis-associated colorectal cancer in 100 patients seen at Mount Sinai Hospital between 1959 and 1988. There were 85 patients with extensive colitis and 15 with left sided colitis. There was a strong direct correlation between the age at onset of ulcerative colitis and age at diagnosis of cancer (p less than 0.0001); this correlation was found both in patients with extensive colitis (p less than 0.0001) and in those with left sided colitis (p less than 0.005). Patients with left sided colitis developed both their colitis and their cancers about a decade later than did those with extensive disease, but the mean duration of colitis before diagnosis of cancer was virtually the same (about 21 years) in both groups, irrespective of the age at onset of disease.     

Colitis and Colon Cancer in Cotton-Top Tamarins (Saguinus oedipus oedipus ) Living Wild in Their Natural Habitat

The cotton-top tamarin is a nonhuman primate noted for susceptibility to juvenile onset colitis and subsequent colon cancer. About 80% develop colitis in captive environments outside the tropics. The aim was to determine the prevalence of colitis and colorectal cancer in tamarins living wild in their tropical habitat. Endoscopic biopsy was used to compare severity of colitis, inflammatory/immune cell densities, mucosal dysplasia, and occurrence of cancer in wild tamarins in a tropical habitat with tamarins living captive in a temperate climate. Six colon biopsies from each of 69 captives showed severe colitis in 64.5% of biopsies and moderate colitis in 19.5% . Severe colitis was not found in 88 wild tamarins; 13% had moderate colitis. Densities of polymorphonuclear leukocytes, plasma cells, and mononuclear cells in the lamina propria were related directly to the severity of four grades of colitis (normal, mild, moderate, and severe). Histologic or gross signs of carcinoma were detected in 12 captives and low- or high-grade dysplasia in 15. Neither cancer nor dysplasia was found in any of the wild tamarins. The observations suggest that colitis and cancer in the tamarin model are linked to environmental factors.     

Microscopic colitis is not associated with cholecystectomy or appendectomy

BACKGROUND: Microscopic colitis is a common cause of chronic watery diarrhea of unknown origin. Some patients develop diarrhea after cholecystectomy, and some patients with microscopic colitis have evidence of bile acid malabsorption. However, the association between cholecystectomy and microscopic colitis has not been studied. A protective effect of appendectomy on the development of ulcerative colitis also has been reported, but its relationship with microscopic colitis has not been studied. The aim of this study was to assess cholecystectomy and appendectomy as potential risk factors for the development of microscopic colitis in a nested case-control study. MATERIALS AND METHODS: Using the Rochester Epidemiology Project, we identified all Olmsted County (Minnesota) residents with an initial diagnosis of microscopic colitis between January 1, 1985, and December 31, 2001. Rates of antecedent cholecystectomy or appendectomy in patients with microscopic colitis were compared with age-, gender-, and calendar year-matched community controls through conditional logistic regression. RESULTS: Microscopic colitis was identified in 130 cases. Cholecystectomy preceded the diagnosis of microscopic colitis in 12 cases (9%) compared with 17 (13%) in the control group (odds ratio [OR] 0.7; 95% CI 0.3-1.5). Appendectomy preceded the diagnosis of microscopic colitis in 39 subjects (30%) compared with 28 (22%) in the control group (OR 1.6; 95% CI 0.9-2.7). Similar results were obtained when the analysis was restricted to microscopic colitis subtype (lymphocytic colitis or collagenous colitis). CONCLUSIONS: In this population-based nested case-control study, no significant association was seen between cholecystectomy or appendectomy and the development of microscopic colitis or its subtypes.     

Incidence of collagenous and lymphocytic colitis: a 5-year population-based study

OBJECTIVE: The incidence of collagenous and lymphocytic colitis is not well known. We sought to assess the incidence of collagenous and lymphocytic colitis in a well-defined population during a 5-yr study period. METHODS: From January 1, 1993, to December 31, 1997, all new patients diagnosed with collagenous or lymphocytic colitis living in the catchment area of the Hospital Mutua de Terrassa (Barcelona, Spain) were identified. Since 1993 all patients with chronic diarrhea were referred for a diagnostic colonoscopy. Multiple biopsy sampling of the entire colon was performed when appearance of the colonic mucosa was grossly normal. RESULTS: Twenty-three cases of collagenous colitis and 37 of lymphocytic colitis were diagnosed. The female:male ratios were 4.75:1 and 2.7:1 for collagenous and lymphocytic colitis, respectively. The mean age at onset of symptoms was 53.4+/-3.2 (range, 29-82) yr for collagenous colitis, and 64.3+/-2.7 (range, 28-87) yr for lymphocytic colitis (p = 0.012). The mean annual incidence per 100,000 inhabitants based on the year of onset of symptoms was 1.1 (95% confidence interval [CI], 0.4-1.7) for collagenous colitis, and 3.1 (95% CI, 2.0-4.2) for lymphocytic colitis. A peak incidence was observed in older women in both diseases. A rate of microscopic colitis of 9.5 per 100 normal-looking colonoscopies performed in patients with chronic watery diarrhea was observed. Normal rectal biopsies were found in 43 % and 8% of patients with collagenous and lymphocytic colitis, respectively. CONCLUSIONS: The incidence of lymphocytic colitis is three times higher than that of collagenous colitis. Microscopic colitis should be considered as a major possibility in the work-up of chronic diarrhea in older women.     

Cytomegalovirus colitis followed by ischemic colitis in a non-immunocompromised adult:A case report

We report a rare case of cytomegalovirus(CMV) colitis followed by severe ischemic colitis in a nonimmunocompromised patient. An 86-year-old woman was admitted after experiencing episodes of vomiting and diarrhea. The next day, hematochezia was detected without abdominal pain. The initial diagnosis of ischemic colitis was based on colonoscopy and histological findings. The follow-up colonoscopy revealed a prolonged colitis. Immunohistochemical staining detected CMVpositive cells following conservative therapy. Intravenous ganciclovir therapy led to successful healing of ulcers and disappearance of CMV-positive cells. The prevalence of CMV infection is common in adults. CMV colitis is relatively common in immunocompromised patients; however, it is rare in immunocompetent patients. In our case, CMV infection was allowed to be established due to the disruption of the colonic mucosa by the prior severe ischemic colitis. Our experience suggests that biopsies may be necessary to detect CMV and the prompt management of CMV colitis should be instituted when intractable ischemic colitis is observed.     

INFLUENCE OF TOPICAL EPINEPHRINE APPLICATION ON MICROCIRCULATORY DISTURBANCE IN SUBJECTS WITH ULCERATIVE COLITIS EVALUATED BY LASER DOPPLER FLOWMETRY AND TRANSMISSION ELECTRON MICROSCOPY

Background : The aim of this study was to evaluate the state of local microcirculation in ulcerative colitis. Methods : Rectal blood flow was measured in 26 subjects with ulcerative colitis and in 10 normal subjects by laser Doppler flowmetry before and after topical spray of epinephrine during colonoscopy. Of those subjects, mucosal capillaries were observed by transmission electron microscopy in eight subjects with ulcerative colitis and in four normal subjects. Results : The blood flow was significantly higher in subjects with active ulcerative colitis than in normal subjects or in subjects with inactive ulcerative colitis, with the difference being significantly different in subjects with ulcerative colitis and in normal subjects following topical epinephrine spray. The capillaries were almost devoid of erythrocytes in subjects with active ulcerative colitis and the frequency of capillaries with erythrocytes in subjects with active ulcerative colitis before and after epinephrine application did not differ. Conclusions : These results indicate that the mucosal microcirculation in subjects with active ulcerative colitis showed ischemia and functional disorder. Further, continuous measurement of blood flow in subjects with active ulcerative colitis may be a useful method for evaluating the changes in microcirculation.     

Ischaemic colitis during interferon treatment for chronic hepatitis C: report of two cases and literature review

Ischaemic colitis is known to be a severe emergency complication of interferon (IFN) therapy. However, as ischaemic colitis is an infrequent complication of IFN therapy, limited information is available regarding the safety of resuming IFN therapy after resolution of ischaemic colitis and subsequent recurrence. Here, we report two cases of ischaemic colitis during IFN therapy for chronic hepatitis C. Ischaemic colitis was fully healed within 1 week after its onset and IFN withdrawal, and IFN therapy was resumed following patients' wishes to do so. Ischaemic colitis did not recur after the resumption of IFN therapy, and sustained virological response was achieved in both patients. In this report, we also summarize the findings of 11 cases of IFN-associated ischaemic colitis (nine previously published cases plus our two cases) and review the clinical characteristics of ischaemic colitis during IFN therapy in patients with chronic hepatitis C.     

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.     

Changes of colonic vasoactive intestinal peptide and cholinergic activity in rats with chemical colitis

The vasoactive intestinal peptide concentration was examined in the colonic wall and portal venous plasma of rats with chemical colitis by radioimmunoassay, and the colonic localization was determined with immunocytochemistry. Colonic acetylcholine esterase activity was also measured, and the response of vasoactive intestinal peptide to acetylcholine administration was determined. Colitis was induced by administration of dextran sulfate for three months. The chemical colitis was histologically similar to active human ulcerative colitis. We observed a significant increase of immunostained neurons and nerve fibers and a significant rise in the colonic wall vasoactive intestinal peptide content in chemical colitis rats, while plasma concentrations of the peptide did not change significantly. Colonic acetylcholine esterase activity was significantly elevated in colitis rats compared with control rats. Systemic administration of acetylcholine significantly increased the colonic and plasma vasoactive intestinal peptide concentrations in colitis rats. These findings demonstrated a positive association between colitis activity and an increase of vasoactive intestinal peptide and suggested that increased vagal tone promoted the peptide's release.     

Gender differences in the response of colitis to smoking.

BACKGROUND AND AIMS: The aim of this study was to examine in parallel the effect of smoking on ulcerative colitis and Crohn's colitis and assess the effect of gender on the response of colitis to smoking. METHODS: Medical charts of 1784 adult consecutive patients (978 patients, ulcerative colitis; 118 patients, indeterminate colitis; and 688 patients, Crohn's colitis), whose smoking habits were specified by direct interview, were reviewed. RESULTS: The proportion of ever smokers was 42% in ulcerative colitis, 43% in indeterminate colitis, and 61% in Crohn's colitis. Smoking cessation preceded the onset of colitis in 279 patients with ulcerative colitis or indeterminate colitis (61%) and only 52 patients (12%) with Crohn's colitis. In ulcerative colitis and indeterminate colitis, current smoking delayed mean age at disease onset in men (from 32 to 41 yr; P < 0.001), but not women (from 33 to 33 yr), and decreased the need for immunosuppressants in men (10-yr cumulative risk, 26% +/- 4% in nonsmokers vs. 8% +/- 4% in smokers; P < 0.01), but not significantly in women. Conversely, in Crohn's colitis, current smoking hastened disease onset in women (from 35 to 29 yr; P < 0.001), but not men (from 32 to 31 yr), and increased the need for immunosuppressants in women (10-yr cumulative risk, 48% +/- 5% in nonsmokers vs. 58% +/- 4% in smokers; P < 0.01), but not men. CONCLUSIONS: The dual effects of smoking in colitis, beneficial in ulcerative colitis and harmful in Crohn's colitis, are modulated importantly by gender, with women having more disadvantage than men.     

Indeterminate colitis

Uncertainty persists concerning the long-term results of ileal pouch-anal anastomosis performed for indeterminate colitis. PURPOSE: This study was designed to compare functional outcomes of ileal pouch-anal anastomosis in patients with typical chronic ulcerative colitis and indeterminate colitis. METHOD: Seventy-one ileoanal pouch patients were identified with a diagnosis of indeterminate colitis. Mean follow-up was 56 months. Outcomes were compared with 1,232 chronic ulcerative colitis patients after ileal pouchanal anastomosis. Mean follow-up was 60 months. RESULTS: (mean±SD) There was no difference in the frequency of daily bowel movements (indeterminate colitis, 7±3,vs.chronic ulcerative colitis, 7±2). Daytime and nighttime incontinence rates were likewise similar. Prevalence of pouchitis was identical (33 percent). However, failure rate was higher in the indeterminate colitis group (indeterminate colitis, 19 percent,vs. chronic ulcerative colitis, 8 percent; (P =0.03)). CONCLUSIONS: At a mean of nearly five years after surgery, failure appears to occur more frequently in patients with indeterminate colitis than in patients with chronic ulcerative colitis. However, the great majority of indeterminate colitis patients (>80 percent) have long-term functional results identical to those of patients with chronic ulcerative colitis.     

Can quinolones cause hemorrhagic colitis of late onset?

PURPOSE: This study was undertaken to demonstrate that quinolones may cause acute colitis resembling penicillin-induced hemorrhagic colitis. METHODS: We reviewed the medical records of patients with acute colitis in our institutes. Twenty-eight patients with acute hemorrhagic colitis in which no pathogenic microorganisms were identified were the subjects of this study. Pseudomembranous colitis caused by Clostridium difficile was excluded. Ulcerative colitis, Crohn's disease, and radiation proctocolitis were also excluded. RESULTS: Among these patients, 25 had a history of recent administration of penicillin derivatives. The remaining three patients had never been given any penicillin derivatives, but had ingested quinolones approximately four weeks before the developing colitis had been identified. Klebsiella oxytoca was also isolated in these three patients. CONCLUSIONS: Quinolones may cause acute hemorrhagic colitis. The time interval from antibiotic ingestion to onset of the condition may be much longer in quinolones than in penicillin derivatives.