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Collagenous colitis shares histological and clinical similarities to lymphocytic colitis (microscopic colitis). Thus, both diseases will be discussed here. It is a clinicopathologic syndrome with watery diarrhea occurring in middle aged to older women (mean 59 yrs). Despite the symptoms, barium enema and colonoscopic examination is normal. The diagnosis rests with the pathologist.

Under the microscope, there is thickening of the subepithelial collagenous plate, increased to 10 microns or more. (Normal is 5 microns in thickness). There is a mild to moderate chronic inflammatory cell infiltrate expanding the lamina propria. There is significant infiltration of the overlying surface mucosa by underlying lymphocytes. Lymphocytic colitis differs only in lacking the thickened subepithelial collagenous plate.

Both diseases are associated with autoimmune diseases including celiac sprue, thyroid disease, and myasthenia gravis. Thus, an autoimmune etiology is strongly suspected.


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

Fernandez-Banares F, Salas A, Forne M, Esteve M, Espinos J, Viver JM.

Department of Gastroenterology, Hospital Universitari Mutua de Terrassa, Barcelona, Catalonia, Spain.

Am J Gastroenterol 1999 Feb;94(2):418-23 Abstract quote

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.



Synchronous occurrence of collagenous colitis and pseudomembranous colitis.

Vesoulis Z, Lozanski G, Loiudice T.

Akron City Hospital, OH 44304, USA

Can J Gastroenterol 2000 Apr;14(4):353-8 Abstract quote

Synchronous collagenous and pseudomembranous colitis has not been previously reported. A 73-year-old woman presented with chronic watery diarrhea and abdominal cramping of six weeks' duration. Biopsies of the colon revealed findings of collagenous colitis involving the endoscopically normal right colon, and superimposed collagenous and pseudomembranous colitis involving the rectosigmoid colon. Endoscopically, the left colon revealed discrete ulcerative plaques, and Clostridium difficile toxin A assay was positive. The patient partially responded to a three-week regimen of metronidazole, and symptoms resolved completely with subsequent steroid therapy.

At follow-up endoscopy four months later, colon biopsies demonstrated persistence of subepithelial collagen but no pseudomembranes. The patient remained asymptomatic during this interval. Collagenous colitis has been reported in association with other inflammatory bowel diseases, including lymphocytic colitis, sprue and idiopathic inflammatory bowel disease.

This unique association of collagenous colitis with an endotoxigenic inflammatory bowel disease is presented with a review of related disease features.



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

Ung KA, Gillberg R, Kilander A, Abrahamsson H.

Division of Gastroenterology, Department of Internal Medicine, Sahlgrenska University Hospital, S-413 45 Goteborg, Sweden.

Gut 2000 Feb;46(2):170-5 Abstract quote

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.

Long-term course in collagenous colitis and the impact of bile acid malabsorption and bile acid sequestrants on histopathology and clinical features.

Ung KA, Kilander A, Nilsson O, Abrahamsson H.

Division of Gastroenterology, Dept. of Internal Medicine, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden. .

Scand J Gastroenterol 2001 Jun;36(6):601-9 Abstract quote

BACKGROUND: Bile acid malabsorption is common in collagenous colitis, although long-term follow-up data on the impact of bile acids are limited. The aim was to study whether bile acid malabsorption is a permanent finding, with an impact on histopathology and clinical features in collagenous colitis.

METHODS: The objective was to reinvestigate 27 patients with collagenous colitis > or = 3 years after index investigation. The clinical course was evaluated by means of an interview, a review of the hospital records and registration of symptoms over a period of 7 days. The patients were invited to undergo a repeat colonoscopy and 75SeHCAT measurement. Initial and follow-up data and 75SeHCAT values from 29 controls were compared.

RESULTS: The median follow-up time was 4.2 (range 3-5.3) years. Twenty-two patients underwent a repeat 75SeHCAT test, 23 patients a colonoscopy and in 25 patients the clinical course could be evaluated. The 75SeHCAT values were abnormal in 32% at follow-up versus 44% at index, and the median retention value was 19% (range 2-69) versus 12% (range 0.5-41) (P = 0.024) although lower than in the control groups figure of 38% (range 8-91) (P < 0.005). Histopathology had improved independently of bile acid malabsorption, gender, smoking and autoimmune disease at follow-up. Four were normalized. Patients on bile acid binders had no significant change of histopathology. Four patients had recovered, seven displayed an intermittent course and 14 had continuous diarrhoea.

CONCLUSIONS: Collagenous colitis and bile acid malabsorption seem to be associated yet independent disorders. The histopathology improves during the long-term course although only a few patients resolve.


Evidence of local eosinophil activation and altered mucosal permeability in collagenous colitis.

Taha Y, Carlson M, Thorn M, Loof L, Raab Y.

Department of Internal Medicine, Clinical Chemistry and Surgery, University Hospital, Uppsala, Sweden.

Dig Dis Sci 2001 Apr;46(4):888-97 Abstract quote

The local release of the inflammatory mediators eosinophil cationic protein and myeloperoxidase and the permeability marker albumin was studied in collagenous colitis using a new technique for segmental perfusion of the rectum and descending colon.

Perfusion of both segments was successful in 19/25 (76%) of patients with collagenous colitis and controls with noninflammatory conditions. The concentration of myeloperoxidase was increased in the perfusion fluids from both segments in only one patient with collagenous colitis and in none of the controls. On the other hand, concentrations of eosinophil cationic protein and albumin in the perfusate from the rectum were significantly increased in collagenous colitis compared with controls, and similar trends were seen in the perfusates from the descending colon.

Furthermore, there was a significant correlation between the increased concentrations of eosinophil cationic protein and albumin, indicating a possible relation between eosinophil activation and disturbed mucosal permeability in collagenous colitis.


Extracellular matrix composition and gene expression in collagenous colitis.

Aigner T, Neureiter D, Muller S, Kuspert G, Belke J, Kirchner T.

Department of Pathology, University of Erlangen-Nurnberg, Erlangen, Germany.

Gastroenterology 1997 Jul;113(1):136-43 Abstract quote

BACKGROUND & AIMS: Collagenous colitis is a rare diarrheal disease of unknown pathophysiology that is histologically defined by subepithelial bandlike structures. The objective of this study was to elucidate the biochemical composition and the origin of the bandlike structures in collagenous colitis.

METHODS: Immunohistochemical and in situ hybridization analyses were performed on endoscopic specimens using specific antibodies and riboprobes for collagen types I, III, IV, and VI and for the glycoprotein tenascin.

RESULTS: In collagenous colitis, the mucosal matrix with the exception of the bands retained a normal architecture and extracellular matrix composition. The bands stained most prominently for type VI collagen and tenascin. Less abundant staining for both proteins was also found in the subepithelial matrix of the normal mucosa. In situ hybridization showed no significant increase in collagen type VI messenger RNA expression in cells around and entrapped in the bands in collagenous colitis compared with normal specimens.

CONCLUSIONS: The results support the suggestion that collagenous colitis is a localized alteration of the extracellular matrix, which involves the pericryptal-subepithelial myofibroblast sheath. The data suggest that reduced matrix degradation and not overactivation of matrix synthesis may be the reason for the subepithelial accumulation of matrix proteins.

Fibrogenesis and fibrolysis in collagenous colitis. Patterns of procollagen types I and IV, matrix-metalloproteinase-1 and -13, and TIMP-1 gene expression.

Gunther U, Schuppan D, Bauer M, Matthes H, Stallmach A, Schmitt-Graff A, Riecken EO, Herbst H.

Department of Gastroenterology, Institute of Pathology, University Hospital Benjamin Franklin, Berlin, Germany.

Am J Pathol 1999 Aug;155(2):493-503 Abstract quote

Collagenous colitis is characterized by the deposition of a superficial subepithelial collagenous layer, the pathogenesis of which is unknown. Because the excess matrix deposition is potentially reversible, a labile imbalance between fibrogenesis and fibrolysis may be suspected. Expression of procollagen alpha1(I) and alpha1(IV), matrix-metalloproteinase (MMP)-1 and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 genes was semiquantitated by in situ hybridization on serial biopsies of 12 patients with collagenous colitis and compared to controls.

Collagen types I, III, IV, and VI, tenascin, undulin/collagen XIV, and alpha-actin were localized by immunohistology. The superficial collagen layer stained strongly for collagen types I, III, and VI, and particularly for tenascin, but not for undulin. Elevated procollagen alpha1(I), procollagen alpha1(IV), and TIMP-1 transcript levels were found in alpha-actin-positive cells with linear distribution underneath the superficial collagenous layer, whereas MMP-1 RNA expression was variable and restricted to cell clusters. MMP-13 expression was undetectable.

The patterns of procollagen alpha1(I)- and alpha1(IV)-specific labeling, combined with an intense tenascin- but absent undulin-specific staining, indicate deposition of an immature interstitial matrix that may be susceptible to degradation. The restricted MMP-1 RNA expression, counteracted by increased TIMP-1 expression, suggests locally impaired fibrolysis as a relevant factor in the pathogenesis of collagenous colitis.


Non-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study.

Riddell RH, Tanaka M, Mazzoleni G.

Department of Pathology, McMaster University Medical Centre, Hamilton, Ontario, Canada.

Gut 1992 May;33(5):683-6 Abstract quote

The use of oral non-steroidal anti-inflammatory drugs (NSAIDs) in 31 patients with collagenous colitis and in 31 matched control patients with irritable bowel syndrome or colonic diverticular disease who had also undergone colonoscopy and biopsy was investigated.

The long term use (greater than 6 months) of NSAIDs was significantly commoner in the study group (19/31) than in the control group (4/31) (p less than 0.02), even assuming the most adverse drug history in six patients in whom this could not be established. In all patients with collagenous colitis taking NSAIDs, diarrhoea followed the use of these drugs, and by a mean (SD) of 5.5 (4.4) years (range 0.5 to 15 years).

In three patients with collagenous colitis, diarrhoea improved after withdrawing NSAIDs; rechallenge in one was followed by a recurrence of diarrhoea, which improved after withdrawing the drug again. It is suggested that NSAIDs may play an aetiological role in the diarrhoea and thickened collagen band in some patients with collagenous colitis.




Autoantibodies and immunoglobulins in collagenous colitis.

Bohr J, Tysk C, Yang P, Danielsson D, Jarnerot G.

Department of Medicine, Orebro Medical Centre Hospital, Sweden.

Gut 1996 Jul;39(1):73-6 Abstract quote

BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown. Autoimmunity has been suggested, but no serological findings have supported such a theory.

AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38 matched healthy controls was analysed for autoantibodies--that is, antinuclear antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and microsomal antigen, together with antibodies to endomysium, gliadin, and cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and complement factors C3 and C4 were also determined.

RESULTS: In patients with collagenous colitis the mean value of IgM was significantly increased 2.5 g/l (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p = 0.002). Antinuclear antibodies occurred in nine of 38 patients compared with three of 38 controls, this difference was not statistically significant (p = 0.11). The results of all other immunoglobulins, complement factors, and specific antibodies showed no statistical difference between patients and controls.

CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is found in this study, although the findings of a positive ANA-titre in some patients and an increased IgM level might give some support for this hypothesis.


Collagenous colitis: mucosal biopsies and association with fecal leukocytes.

Zins BJ, Tremaine WJ, Carpenter HA.

Division of Gastroenterology, Mayo Clinic Rochester, MN 55905, USA.

Mayo Clin Proc 1995 May;70(5):430-3 Abstract quote

OBJECTIVE: To determine the frequency of patchy colonic involvement, fecal leukocytosis, and association with celiac sprue in a large cohort of patients with collagenous colitis.

DESIGN: We conducted a retrospective review of the medical records of 172 consecutive Mayo Clinic patients in whom collagenous colitis had been diagnosed between 1982 and 1993.

METHODS: For each of the 172 patients, the medical record was reviewed to determine the frequency of (1) fecal leukocytosis; (2) characteristic histologic findings in the rectum and the sigmoid, descending, and ascending colon; and (3) small bowel biopsy findings consistent with celiac sprue.

RESULTS: The presence of fecal leukocytes was noted in 64 of 116 patients (55%) who had undergone assessment for fecal leukocytosis. On analysis of histologic findings, 113 of 123 rectal, 116 of 121 sigmoid, and 68 of 70 descending colon biopsy specimens were diagnostic of collagenous colitis. Small bowel biopsies were performed in 45 patients who did not have a history of small intestinal disease: 1 had celiac sprue and 44 had normal findings. Two other patients had previously diagnosed celiac sprue.

CONCLUSION: The finding of fecal leukocytes in 55% of patients with collagenous colitis confirms the inflammatory basis of this disease. Biopsy specimens obtained by flexible sigmoidoscopy seem sufficient to establish the diagnosis in most patients, and colonoscopic biopsy of the more proximal area of the colon is usually unnecessary. Celiac sprue infrequently accompanies collagenous colitis; thus, routine small bowel biopsy is not warranted.


Perinuclear antineutrophil cytoplasmic antibodies in collagenous or lymphocytic colitis with or without celiac disease.

Freeman HJ.

Department of Medicine (Gastroenterology), University of British Columbia, Vancouver.

Can J Gastroenterol 1997 Jul-Aug;11(5):417-20 Abstract quote

Microscopic forms of colitis, including lymphocytic and collagenous colitis, have been observed in both those with and without celiac disease. Although perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) occur in most patients with ulcerative colitis, investigations in microscopic, particularly lymphocytic, colitis are still needed.

In this study atypical p-ANCA was evaluated in 55 patients, including 27 with celiac disease alone, 13 with celiac disease and concomitant lymphocytic colitis, and 15 with microscopic forms of colitis, including lymphocytic and collagenous colitis. Nine patients (16.3%) had atypical p-ANCA, including six with celiac disease and three with a microscopic form of colitis alone. Although five of the six positive celiac disease patients had lymphocytic colitis, all three celiac disease patients with associated primary sclerosing cholangitis--a separate risk factor for a positive assay result--were serologically positive for atypical p-ANCA.

These results indicate for the first time that this serological marker may occur in histologically defined celiac disease with or without concomitant lymphocytic colitis. Furthermore, these results suggest that the pathogenesis of ulcerative colitis differs from that of lymphocytic colitis and further emphasizes the heterogeneous nature of these newly recognized types of colonic inflammatory mucosal disorders.



Collagenous colitis in symptomatic subjects without endoscopic morphologic evidence: case report.

Sumberaz A, Valentini M, Delehaye E, Gentile R, Testino G.

Department of Gastroenterology, San Martino Hospital, Genoa, Italy.

Panminerva Med 2001 Mar;43(1):53-5 Abstract quote

Collagenous colitis (CC) is a rare pathology and, even though various etiopathogenetic hypotheses have been put forward, the etiology and pathology are still not well defined. We report the case of a female patient suffering from chronic watery diarrhoea, positive for guaiac-based fecal occult blood test and morphologically negative to endoscopic investigation, but histologically classifiable as CC.

This case report suggests that the clinical history must lead towards the execution of a colonoscopy with bioptic samples done even on apparently normal mucosa. Furthermore, the clinic should always signal a suspect CC to the anatomopathologist in order to have a correct diagnosis.


Atypical forms of microscopic colitis: morphological features and review of the literature.

Chang F, Deere H, Vu C.

Department of Histopathology, St. Thomas' Hospital, Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.
Adv Anat Pathol. 2005 Jul;12(4):203-11. Abstract quote  

Microscopic colitis is defined as a syndrome of chronic watery diarrhea with a chronic inflammatory cell infiltrate in the colonic mucosa but without significant abnormalities at colonoscopy. It encompasses at least two histopathologic entities (ie, collagenous and lymphocytic colitis). The recognition and characterization of microscopic colitis has markedly changed the approach to the evaluation and management of chronic diarrhea.

The histologic features of collagenous and lymphocytic colitis are well known to most pathologists. By considering the clinical history and symptoms, the pathologist should be able to reach the correct diagnosis in most cases. However, the spectrum of morphologic changes associated with watery diarrhea syndrome appears to be broader than originally thought. Morphologic changes more often associated with chronic inflammatory bowel disease or even chronic ischemic or infectious colitis have been noted in patients with clinically established microscopic colitis.

The data presented in this article suggest that microscopic colitis is a heterogeneous entity, which includes both classic and "atypical" forms. Problems arise when cases do not fit the usual pattern or lack some of the findings that are expected. Pathologists should be aware of the presence of atypical forms of microscopic colitis.

Sequential clinical and histopathological changes in collagenous and lymphocytic colitis over time.

Shaz BH, Reddy SI, Ayata G, Brien T, Farraye FA, Antonioli DA, Odze RD, Wang HH.

Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Mod Pathol. 2004 Apr;17(4):395-401. Abstract qote

We conducted this retrospective study to evaluate the relationship between symptoms, histological findings, and treatment of collagenous (CC) and lymphocytic colitis (LC).

We identified 19 CC and 12 LC patients having multiple colonoscopic procedures with colonic biopsies during their course of illness. A detailed histological review of all biopsies was performed. Clinical history, including symptoms and medications, was obtained in 25 of the 31 patients and was correlated with their histological findings.

In all, 25% of the CC patients and 50% of the LC patients who had biopsies prior to their definitive diagnosis had the pathognomonic histological features on their prior biopsies to some extent (but were not recognized by the pathologists); however, these features were more pronounced on the biopsies from the procedure that established the diagnosis. Nonetheless, 10 of 12 such patients with clinical data available had symptoms and were being treated at the time of prior biopsies. Assessment of the relationship among histological, clinical and therapeutic data showed no association between symptoms or histological findings and treatment with any medication.

In summary, in this sample of CC and LC patients, symptoms often precede fully developed histological features. No change in symptoms or histological findings was found to be associated with medication.

Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.

Offner FA, Jao RV, Lewin KJ, Havelec L, Weinstein WM.

Department of Pathology, School of Medicine, University of Innsbruck, Austria.

Hum Pathol 1999 Apr;30(4):451-7 Abstract quote

In collagenous colitis, the literature is conflicting concerning where in the colon the lesions are most likely to be present and most severe. Conflicting data furthermore shed doubt on the sensitivity of the histological detection of the morphological abnormalities and the threshold criteria for diagnosis.

We addressed these questions in 56 patients with collagenous colitis. Two hundred ninety-one coded biopsy specimens were analyzed according to six standardized sites from cecum to rectum. Subepithelial collagen deposits were subjectively graded in hematoxylin and eosin (H&E) sections and quantitatively measured in trichrome-stained sections, respectively. Semiquantitative grading was also done for inflammatory changes of the lamina propria and abnormalities of the surface and crypt epithelium.

The transverse colon yielded the largest percentage of biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also had the largest percentage of biopsy specimens with inflammatory changes (98%). Biopsy specimens from both the rectosigmoid and the right colon (ascending and cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of specimens obtained from the rectosigmoid were diagnostic, and 18% of these were interpreted as normal. Subepithelial collagen deposits proved to be significantly thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm; range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had collagen deposits thicker than 10 microm. However, the subjective interpretation "diagnostic of collagenous colitis" proved to be most consistent with a threshold of 30 microm.

Our results indicate that biopsy specimens from at least as proximal as the transverse colon should be obtained to definitely rule out collagenous colitis. Furthermore, it is evident that in a given biopsy specimen, markedly abnormal subepithelial collagen deposition had to be present for an unequivocal histological diagnosis of collagenous colitis

Prevalence and Significance of Inflammatory Bowel Disease-Like Morphologic Features in Collagenous and Lymphocytic Colitis

Gamze Ayata, M.D.; Sarathehandra Ithamukkala, M.D.; Heidi Sapp, M.D.; Beth H. Shaz, M.D.; Tom P. Brien, M.D.; Helen H. Wang, M.D., Dr.Ph.; Donald A. Antonioli, M.D.; Francis A. Farraye, M.D., M.Sc.; Robert D. Odze, M.D., F.R.C.P.C.

Am J Surg Pathol 2002; 26(11):1414-1423 Abstract quote

Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by the presence of chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with CC also have a thickened subepithelial collagen layer.

We have noted, anecdotally, that biopsy specimens from some patients with CC or LC contain certain histologic features, such as Paneth cell metaplasia (PM), that are normally seen in inflammatory bowel disease (IBD), or other types of healed colitis, and thus may cause diagnostic difficulty.

Therefore, the purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with CC or LC. Five hundred thirty-one routinely processed hematoxylin and eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed CC (79 patients, male/female ratio: 14/65, mean age: 60 yr) or LC (71 patients, male/female ratio: 13/58, mean age: 55 yr) were evaluated in a blinded fashion for a variety of histologic features, including active crypt inflammation (cryptitis ± crypt abscess), surface ulceration, Paneth cell metaplasia, crypt architectural irregularity, number of intraepithelial lymphocytes, and thickness of the subepithelial collagen layer (CC only). The results were compared between CC and LC and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period.

Active crypt inflammation was a common finding in both groups, seen in 24 of 79 CC patients (30%) and 27 of 71 LC patients (38%). Surface ulceration was not seen in any of the LC biopsies but was present in 2 of 79 (2.5%) CC patients. Paneth cell metaplasia was frequent in both groups and significantly more common in CC compared with LC patients. Forty-four percent of CC patients, but only 9 of 63 (14%) of LC patients had Paneth cell metaplasia (p <0.001). Crypt architectural irregularity, although rare, was present in 6 of 79 patients with CC (7.6%) and 3 of 71 (4.2%) patients with LC. In patients with CC, the presence of Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (p <0.001) and a higher frequency of bowel movements (>3 bowel movements/day) (p = 0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (p = 0.04) and was present in the only two patients who had positive stool cultures (one each for Campylobacter jejuni and Salmonella). However, none of the other histologic findings correlated with any of the other clinical or endoscopic features, such as type of symptoms, stool consistency, type of medical treatment, associated autoimmune diseases or outcome (complete, partial, or no resolution) in either group of patients.

Pathologists should be aware that some histologic features normally associated with IBD such as crypt irregularity and neutrophilic cryptitis and crypt abscesses are not uncommon in patients with CC or LC and that the presence of one or more of these features should not necessarily be interpreted as evidence against either of these diagnoses.


Histopathological features of the terminal ileum in lymphocytic and collagenous colitis: a study of 32 cases and review of literature.

Padmanabhan V, Callas PW, Li SC, Trainer TD.

Departments of Pathology (VP, SCL, TDT) and Biostatistics (PWC), University of Vermont College of Medicine, Burlington, Vermont.

Mod Pathol 2003 Feb;16(2):115-9 Abstract quote

Biopsy specimens from the terminal ileum of 32 patients with the histopathological diagnosis of lymphocytic colitis or collagenous colitis and 11 control individuals were evaluated for the presence or absence of ileal mucosal abnormalities and for the number of intraepithelial lymphocytes, assessed by immunohistochemical stains for the pan T-cell marker, CD3.

We found that the mean CD3 counts in patients with lymphocytic/collagenous colitis were significantly higher than those in the control group. Seven of 14 patients with collagenous colitis and 14 of 18 patients with lymphocytic colitis revealed an increase in intraepithelial T lymphocytes when compared with the control group (P =.001).

Other notable changes included ileal villous atrophy in one case of lymphocytic colitis and in three cases of collagenous colitis and epithelial damage with thickened subepithelial collagen in two cases of collagenous colitis.

The Terminal Ileum Is Affected in Patients With Lymphocytic or Collagenous Colitis

Heidi Sapp, M.D., F.R.C.P.C.; Sarathehandra Ithamukkala, M.D.; Tom P. Brien, M.D.; Gamze Ayata, M.D.; Beth Shaz, M.D.; David M. Dorfman, M.D., Ph.D.; Helen H. Wang, M.D., Dr.Ph.; Donald A. Antonioli, M.D.; Francis A. Farraye, M.D., M.Sc.; Robert D. Odze, M.D., F.R.C.P.C.

Am J Surg Pathol 2002; 26(11):1484-1492 Abstract quote

Lymphocytic colitis (LC) and collagenous colitis (CC) are diseases characterized by the presence of marked intraepithelial lymphocytosis. Both of these disorders affect primarily the colon. However, involvement of the distal small intestine has not been systematically studied.

The purpose of this study was to evaluate the type and degree of intraepithelial lymphocytosis in the terminal ileum of patients with LC or CC. Terminal ileal mucosal biopsies from 22 patients with LC (male/female ratio 0.22, mean age 47 years) and 23 with CC (male/female ratio 0.43, mean age 54 years) were evaluated for the number of intraepithelial lymphocytes (IEL) per 100 epithelial cells (EC) both in the villi and crypts.

The results were compared with 30 patients with inflammatory bowel disease (16 with Crohn's disease [CD], 14 with ulcerative colitis [UC]) and 24 patients (male/female ratio 0.33, mean age 44 years) without colonic pathology as normal controls. None of the patients had celiac sprue. Paired terminal ileum and colonic mucosal biopsies from 6 patients with LC, 4 with CC, 5 with CD, 5 with UC, and 10 normal controls were also immunohistochemically stained with monoclonal antibodies to CD3, CD8, CD20, and a class II MHC antigen (LN3-HLA-DR). In the villi the IEL count/100 EC was 11.8 ± 1.8 in LC and 10.3 ± 1.9 in CC (p = 0.3).

These values were both significantly higher than in CD (2.8 ± 0.4, p <0.001), UC (3.1 ± 0.4, p <0.001), or normal controls (2.2 ± 0.2, p <0.001). In the crypts the IEL count was 3.8 ± 0.5 in LC and 3.2 ± 0.5 in CC (p = 0.3). These values were also significantly higher than in CD (2.3 ± 0.4, p = 0.02), UC (2.1 ± 0.3, p = 0.02), or normal controls (1.5 ± 0.2, p <0.001).

The presence of >5 IELs/100 EC in terminal ileum biopsies was highly specific for LC and CC (specificity 98%, sensitivity 73% and 56% for LC and CC, respectively). The IEL phenotype was similar in all groups of patients and in the ileum and colon of individual patients. Intraepithelial lymphocytes were CD3+, CD8+, CD20-, and LN3-HLA-DR-, indicative of a suppressor T-cell phenotype. Intraepithelial lymphocytosis occurs in the terminal ileum in patients with LC or CC and may be helpful in diagnosing these conditions and distinguishing LC or CC from CD or UC in diagnostically difficult cases.

The results suggest that the terminal ileum may be involved by a similar pathogenic process as the colon in LC and CC.


Increased eosinophil infiltration and degranulation in colonic tissue from patients with collagenous colitis.

Levy AM, Yamazaki K, Van Keulen VP, Burgart LJ, Sandborn WJ, Phillips SF, Kephart GM, Gleich GJ, Leiferman KM.

Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

Am J Gastroenterol 2001 May;96(5):1522-8 Abstract quote

OBJECTIVE: Eosinophils infiltrate the colonic mucosa of patients with collagenous colitis (CC), although the pathogenetic implications are unknown, including whether these eosinophils are activated and degranulate in situ. We examined eosinophil infiltration and degranulation in the intestines of patients with CC by immunofluorescence for eosinophil granule major basic protein (MBP).

METHODS: We used both conventional histology (hematoxylin and eosin) and indirect MBP immunofluorescence histochemistry on colon biopsy specimens from patients with CC (n = 21) and from healthy controls (n = 9). Scoring of histological features was performed on hematoxylin and eosin-stained sections on a 0 to 3 scale. Eosinophil infiltration and degranulation, as quantified by extracellular MBP staining, were scored in each specimen on a 0 to 4 scale.

RESULTS: The inflammatory infiltrate of the lamina propria, the thickness of the collagen band, the numbers of intraepithelial lymphocytes, and degree of epithelial cell damage were all significantly increased in patients with CC as compared to controls (p < 0.0001). Scores for both eosinophil infiltration and degranulation were also significantly higher in the CC group compared to controls (p < 0.0001). The degree of infiltrating eosinophils by hematoxylin and eosin was correlated with eosinophil infiltration and degranulation by MBP immunostaining; however, no other correlations were found between eosinophil infiltration or degranulation by immunofluorescence and any of the histological parameters measured in the CC group.

CONCLUSIONS: Eosinophil infiltration and degranulation are increased in the colonic mucosa of patients with CC compared to healthy controls. Eosinophils and their cytotoxic granule proteins could be involved in the pathogenesis of CC. Further studies will be necessary to elucidate the mechanisms of eosinophil activation in CC.


Pseudomembranous collagenous colitis.

Yuan S, Reyes V, Bronner MP.

Am J Surg Pathol. 2003 Oct;27(10):1375-9. Abstract quote  

SUMMARY: The classic clinical and histologic features of collagenous colitis are well characterized; however, the acute or neutrophilic inflammatory changes that may accompany this entity are less well established. In this report of 10 patients, we describe the first series of pseudomembranous collagenous colitis. Because superimposed Clostridium difficile infection was only demonstrated in one patient and no other causes of pseudomembranous colitis were evident in the remaining nine patients, we conclude that pseudomembranes are part of the spectrum of collagenous colitis itself.

This case series illustrates the importance of searching for collagenous colitis in the evaluation of pseudomembranous colitis. At the same time, superimposed infectious or ischemic etiologies need to be excluded clinically in any patient with superimposed pseudomembranes.

The existence of pseudomembranes in collagenous colitis also lends support to the hypothesis that toxin- and/or ischemia-mediated injury may be involved in the pathogenesis of collagenous colitis.



Tenascin: a sensitive and specific diagnostic marker of minimal collagenous colitis.

Muller S, Neureiter D, Stolte M, Verbeke C, Heuschmann P, Kirchner T, Aigner T.

Department of Pathology, University of Erlangen-Nurnberg, Germany.

Virchows Arch 2001 May;438(5):435-41 Abstract quote

Collagenous colitis is a rare cause of chronic watery diarrhea. In this condition, endoscopic findings are usually normal. Currently, the diagnosis relies on the histological presence of thick subepithelial bands of collagen deposits and an inflammatory infiltrate within the mucosa. However, these subepithelial bands may be developed only focally and may be too subtle to allow a definitive diagnosis upon routine hematoxylin and eosin (HE) and van Gieson's stainings.

Recently, we and others were able to show a prominent staining of tenascin and type-VI collagen in the subepithelial band-like structures. In this study, we tested the diagnostic value of tenascin staining and type-VI collagen immunolocalization for the identification of collagenous colitis and compared it with conventional histology and histochemical detection of collagens. The analysis was based on 434 biopsy specimens of collagenous colitis, other forms of colitis, and normal mucosa.

We were able to show that the immunohistochemical detection of increased amounts of tenascin, selectively in the subepithelial zone, is a specific test for collagenous colitis, with a sensitivity superior to conventional histological and histochemical detection, especially in minimal collagenous colitis (P<0.001).

Of note, tenascin staining also allows the diagnosis of collagenous colitis in biopsies obtained only from the rectum and sigmoid colon, thus avoiding the need for colonoscopic investigations. Tenascin immunostaining is a simple and safe tool to complement conventional histological diagnostics in clinically and histopathologically unclear cases of diarrhea.




Subepithelial collagen thickening in the colon: report on a series of 23 patients.

Loffeld RJ, Balk AT.

Department of Internal Medicine, Zaandam, The Netherlands.

Digestion 1998 Nov-Dec;59(6):715-8 Abstract quote

BACKGROUND: To investigate the prevalence of collagenous colitis in patients presenting with diarrhoea.

METHODS: Descriptive retrospective study in consecutive patients under study because of chronic diarrhoea. Results: In a 4.5-year period 23 consecutive patients had histological signs of thickening of the subepithelial collagen band in the colon. There was a female predominance: 19 women versus 4 men, mean age 60 years (range 33-83). The stool frequency was 1-13 stools daily. Indicanuria was present in 9 patients. The patients were divided into 3 groups: those with definite collagenous colitis (n = 11; thickness of the collagen band of more than 10 micrometer); those with indefinite collagenous colitis (n = 8; thickness between 3 and 10 micrometer), and those with a collagen band between 1 and 3 micrometer (n = 4).

During a mean follow-up of 20 months (range 13-36), 7 patients had waxing and waning episodes of diarrhoea, 11 showed spontaneous waning of complaints and a lower stool frequency. The 9 patients with indicanuria did well after a course of tetracyclin 250 mg t.i.d., but all cases relapsed during follow-up.

CONCLUSION: It is concluded that thickening of the collagen band and collagenous colitis are not as unusual as usually thought.


Amyloidosis of the rectum mimicking collagenous colitis.

Garcia-Gonzalez R, Fernandez FA, Garijo MF, Fernando Val-Bernal J.

Department of Anatomical Pathology, Marques de Valdecilla University Hospital, Medical Faculty, University of Cantabria, Santander, Spain.

Pathol Res Pract 1998;194(10):731-5 Abstract quote

Gastrointestinal involvement in cases of systemic amyloidosis is very common. In the colorectal mucosa, amyloid deposition is ordinarily seen around vessels or diffusely in the lamina propria.

We report two cases in men aged 69 and 29 years, whose rectal biopsies revealed prominent subepithelial amyloid deposits mimicking collagenous colitis. The amyloid deposits were composed of AA protein. A review of the literature has yielded only one previously reported case. Pathologists should be aware of this deposition pattern of amyloid to prevent misdiagnosis.

Our cases underline the importance of the routine use of histochemical stains for amyloid in all cases of colorectal biopsies showing histologic changes suggestive of collagenous colitis.


Focal lymphocytic colitis and collagenous colitis: patterns of Crohn's colitis?

Goldstein NS, Gyorfi T.

Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA.

Am J Surg Pathol 1999 Sep;23(9):1075-81 Abstract quote

The morphologic findings in mildly active colonic Crohn's disease (CD) include crypt disarray, patchy edema, and small lymphoid aggregates with neutrophils, sometimes associated with aphthous ulcers.

We describe four patients with CD whose colonic biopsies focally showed a lymphocytic colitis morphology, and one patient with CD whose biopsies showed a collagenous colitis morphology. The lymphocytic and collagenous colitis patterns of injury preceded the eventual clinical pathologic diagnosis of CD in four patients. Colonoscopic abnormalities were found in four patients. The lymphocytic colitis pattern was focal, involving some biopsy fragments, whereas other biopsy fragments were normal or had minimal nonspecific inflammation. In one patient, moderate numbers of neutrophils were admixed with the lymphoplasmacytic infiltrates. The presence of colonoscopic abnormalities, focal changes, and moderate admixed neutrophils could assist in the distinction from lymphocytic or collagenous colitis, both of which are colonoscopically normal, usually diffuse, and devoid of, or contain only a sparse number of, neutrophils.

A limited number of biopsy fragments may be incorrectly interpreted as lymphocytic or collagenous colitis. The temporal relationships suggest that these morphologic patterns precede typical active CD.


Colonic subepithelial collagenous thickening in diabetic patients.

Kandemir O, Utas C, Gonen O, Patiroglu TE, Ozbakir O, Kelestimur F, Yucesoy M.

Department of Pathology, Erciyes University, Kayseri, Turkey.

Dis Colon Rectum 1995 Oct;38(10):1097-100 Abstract quote

PURPOSE: This study was designed to investigate the effect of intestinal subepithelial collagenous thickening on diabetic diarrhea because one of the seven patients diagnosed with collagenous colitis was diabetic.

METHODS: Rectosigmoidoscopic rectal biopsies were taken from 50 diabetic patients (8 with and 42 without diarrhea), 20 nondiabetic patients with diarrhea, and 10 healthy patients. Histopathologic examinations and measurements of subepithelial collagen layers were performed on these biopsies.

RESULTS: In diabetic patients who had diarrhea, the subepithelial collagen layer (SCL) was thicker than it was in diabetics without diarrhea (P < 0.05). In diabetic groups, the SCL was thicker than it was in both nondiabetics with diarrhea and those without diarrhea (P < 0.05). There was no statistical difference between nondiabetics with diarrhea and those without (P > 0.05). There was no correlation between collagen thickness, age, and diabetes duration (P > 0.05).

CONCLUSIONS: It was concluded that there was a thickening of the colonic SCL in diabetic patients.


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

Baert F, Wouters K, D'Haens G, Hoang P, Naegels S, D'Heygere F, Holvoet J, Louis E, Devos M, Geboes K.

Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.

Gut 1999 Sep;45(3):375-81 Abstract quote

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.


Nonsteroidal anti-inflammatory drug-associated colitis with a histology of collagenous colitis.

Yagi K, Nakamura A, Sekine A, Watanabe H.

Dept. of Internal Medicine, Niigata Prefectural Yoshida Hospital, Nishikanbaragun, Japan.

Endoscopy 2001 Jul;33(7):629-32 Abstract quote

Here we report a case of nonsteroidal anti-inflammatory drug (NSAID)-associated colitis with a histology of collagenous colitis in a 77-year-old woman.

The patient had taken aspirin since 1993 after being diagnosed at another hospital, as having multiple cerebral infarctions. She began to suffer from intermittent diarrhea in April 1999. Serological examination showed hypoproteinemia, which indicated that she had protein-losing enteropathy. By July 1999, she had undergone colonoscopic examination four times. Biopsy specimens taken during the fourth colonoscopy revealed collagenous colitis. As the patient had been taking aspirin for 6 years, she was diagnosed as having NSAID-associated colitis with a histology of collagenous colitis. When she stopped taking aspirin, the diarrhea ceased. Three months later, the patient underwent a fifth colonoscopy. A histological examination of the biopsy specimen revealed that the collagen band had vanished. NSAID-associated colitis sometimes shows collagenous colitis histologically and is cured by withdrawing the drug.

It is important to differentiate NSAID-associated colitis, even if it shows a histology of collagenous colitis, from collagenous colitis as the two diseases differ in etiology and therapy.



Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients.

Bohr J, Tysk C, Eriksson S, Abrahamsson H, Jarnerot G.

Department of Medicine, Orebro Medical Center Hospital, Sweden.

Gut 1996 Dec;39(96):846-51Abstract quote

BACKGROUND: Data on collagenous colitis have been based on a limited number of patients. AIMS: To obtain more information on this disease from a register set up at Orebro Medical Center Hospital.

PATIENTS AND METHODS: Twenty five Swedish hospitals have contributed to this patient register, which comprises 163 histopathologically verified cases. Clinical data were retrospectively analysed.

RESULTS: Collagenous colitis followed a chronic intermittent course in most cases (85%) with a sudden onset in 42%. Symptoms were chronic watery diarrhoea, often nocturnal (27%), abdominal pain (41%), and weight loss (42%). Sixty six patients (40%) had one or more associated diseases. Routine laboratory data were mostly normal. The median age at diagnosis was 55 (range 16-86) years, but 25% of the patients were younger than 45 years. Seven patients died of unrelated diseases. The response rate for sulphasalazine was 59%, and 50% and 40% for mesalazine and olsalazine. Prednisolone was most effective with a response rate of 82%, but the required dose was often high and the effect was not sustained after withdrawal. Antibiotics were efficient in 63%. Cholestyramine and loperamide had response rates of 59% and 71% respectively.

CONCLUSIONS: Collagenous colitis follows a chronic continuous course. Symptoms can be socially disabling, but the disease does not seem to have a malignant potential. A plan for the treatment of a newly diagnosed patient with collagenous colitis is proposed.

Collagenous colitis: histopathology and clinical course.

Goff JS, Barnett JL, Pelke T, Appelman HD.

Department of Medicine, University of Michigan Hospitals, Ann Arbor, USA.

Am J Gastroenterol 1997 Jan;92(1):57-60 Abstract quote

OBJECTIVES: Collagenous colitis is a chronic diarrheal disease characterized by a normal or near-normal mucosa endoscopically and microscopic inflammation in the lamina propria, surface epithelial injury and a thick subepithelial collagen layer. The symptoms of collagenous colitis vary in duration and intensity, and long periods of remission have been described, but long-term follow-up data are limited. Our goal was to determine the natural clinical history of collagenous colitis and to determine whether there was a relationship between histopathologic changes and course of disease.

METHODS: Cases were identified at the University of Michigan Hospitals using surgical pathology records before 1992. All charts, including medical records from other hospitals, were reviewed, and a telephone interview was conducted with each locatable patient (pt). Biopsy specimens were reviewed by two pathologists for degree of collagen layer thickness, epithelial damage, and inflammation.

RESULTS: There were 31 patients (26 F, 5 M) with a mean age of 66 yr (range 33-83) and a mean duration of symptoms of 5.4 yr at the time of diagnosis. Of the 31 patients, 18 (56%) had some form of arthritis, and 22 (71%) were using NSAIDS regularly at the time of diagnosis. Follow-up interviews were conducted at least 2 yr after diagnosis (mean 3.5 yr, range 2-5 yr) with 27 of 31 patients (3 could not be located, 1 died). Two definable groups of patients were identified: (1) those with either spontaneous or treatment-related symptom resolution (63%), and (2) those with ongoing or intermittent symptoms requiring at least intermittent therapy (37%). There was no significant difference between the two groups with regard to sex, age, associated diseases, and use of medications. Patients with symptom resolution (mean duration 3.1 yr) had been treated with antidiarrheals (6), sulfasalazine (3), discontinuation of NSAIDS (3), reversal of jejunoilial bypass (1), or nothing (4). Those with ongoing symptoms experienced a wide range of symptom severity. Two required only antidiarrheals, but five required or failed steroids, azathioprine, or sandostatin. There was no significant difference in collagen thickness, epithelial damage, and inflammation between the two groups, but Paneth cell metaplasia was seen more often in those with ongoing symptoms. In 24 of 27 patients, diagnostic changes were present in left-sided biopsies.

CONCLUSIONS: In our cohort of patients, 63% had lasting resolution of symptoms after a mean 3.5 yr follow-up. There was a high incidence of arthritis and NSAID use in our population, but there was no relationship between these entities and clinical course or histology. Initial histology, except possibly for Paneth cell metaplasia, did not reliably predict severity or course of disease. Finally, although variable in clinical presentation, treatment-free remissions are common in collagenous colitis.

Collagenous colitis: a long-term follow-up study.

Bonderup OK, Folkersen BH, Gjersoe P, Teglbjaerg PS.

Department of Medical Gastroenterology, Aalborg Hospital, Denmark.

Eur J Gastroenterol Hepatol 1999 May;11(5):493-5 Abstract quote

OBJECTIVE: Collagenous colitis was first described in 1976. It is a rare disorder and the long-term course and prognosis of the disease are unknown. The aim of this study was to evaluate the course of the disease more than 5 years after the diagnosis.

DESIGN: A retrospective follow-up of patients with collagenous colitis diagnosed during the period 1979-1990.

METHODS: All examinations performed at the time of diagnosis were reviewed and the clinical courses of the patients were determined by evaluation of the medical records. At a follow-up visit in 1996 complete histories were obtained and conventional laboratory tests were performed.

RESULTS: Two men and 22 women aged 20-82 years with collagenous colitis were identified. At the time of diagnosis, extensive investigation did not reveal other gastrointestinal diseases. At the time of follow-up, six patients had died from diseases unrelated to collagenous colitis, 10 patients suffered from chronic or intermittent diarrhoea, and four patients had been without gastrointestinal symptoms for the last 2-10 years. None of the patients developed colorectal cancer or chronic inflammatory bowel disease. Four patients were lost to follow-up.

CONCLUSION: Collagenous colitis is a benign disease, most often with a chronic course. No association with other gastrointestinal diseases was found.

Short- and long-term follow-up of treatment for lymphocytic and collagenous colitis.

Bonner GF, Petras RE, Cheong DM, Grewal ID, Breno S, Ruderman WB.

Department of Gastroenterology, Cleveland Clinic Florida, Fort Lauderdale 33309, USA.

Inflamm Bowel Dis 2000 May;6(2):85-91 Abstract quote

Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies.

Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less.

Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids.

Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.


Cancer risk in collagenous colitis.

Chan JL, Tersmette AC, Offerhaus GJ, Gruber SB, Bayless TM, Giardiello FM.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Inflamm Bowel Dis 1999 Feb;5(1):40-3 Abstract quote

Collagenous colitis is a recently described form of chronic inflammatory bowel disease. Other inflammatory bowel disorders are associated with increased risk of colorectal and extracolonic malignancies, but this has not been evaluated in collagenous colitis.

Colorectal and extracolonic malignancies were identified in 117 patients with collagenous colitis from the Johns Hopkins Registry. The incidence rates of identified tumors, overall incidence rate of tumors, and overall mortality were then compared with general population through person year analysis with adjustment for population. No cases of colorectal cancer were found in collagenous colitis patients during a mean follow-up period of 7.0 years (range 2-12 years) after the diagnosis of colitis. Two patients developed colorectal cancer prior to the diagnosis of colitis, but no increase in life-time relative risk of colorectal cancer was found (relative risk 0.52; 95% confidence limits 0.05-1.5). An increased relative risk of lung cancer in women (relative risk 3.7; 95% confidence limits 1.0-9.6; p = 0.048) was noted. The relative risk of overall malignancy and overall mortality was not different than the general population.

In collagenous colitis patients the life-time relative risk of colorectal cancer and the relative risk after the diagnosis of colitis with a mean observation period of 7 years was not increased. An increase in relative risk of lung cancer in women with collagenous colitis argues for further investigation of the role of smoking and other factors in this disorder.


Spontaneous peritonitis from perforation of the colon in collagenous colitis.

Freeman HJ, James D, Mahoney CJ.

Department of Medicine (Gastroenterology), University of British Columbia Hospital, Vancouver, Canada.

Can J Gastroenterol 2001 Apr;15(4):265-7 Abstract quote

A 37-year-old woman presented with an acute abdomen following the onset of watery diarrhea.

Spontaneous peritonitis was detected, along with evidence of a focal sigmoid colon perforation. Subsequent postoperative colonoscopic studies revealed collagenous colitis with a focal, deep, nongranulomatous ulcer in the sigmoid colon. Although the literature suggests that collagenous colitis tends to have a relatively 'benign' clinical course characterized by chronic or episodic watery diarrhea.

Potentially serious and life- threatening complications may occur in this microscopic form of inflammatory bowel disease.


Progression of collagenous colitis to ulcerative colitis.

Pokorny CS, Kneale KL, Henderson CJ.

Liverpool Hospital, Sydney, Australia.

J Clin Gastroenterol 2001 May-Jun;32(5):435-8 Abstract quote

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.


Treatment responses in collagenous colitis.

Fiedler LM, George J, Sachar DB, Kornbluth AA, Janowitz HD, Harpaz N.

The Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine of the City University of New York, New York, USA.

Am J Gastroenterol 2001 Mar;96(3):818-21 Abstract quote

OBJECTIVE: In the nearly 20 yr since collagenous colitis was first recognized, the results of therapies have not been systematically described in substantial numbers of patients. We have therefore conducted a retrospective analysis of 26 patients treated in this institution during the years 1991-1994.

METHODS: Twenty-nine cases of collagenous colitis were obtained by review of biopsy specimens collected between 1991 and 1994 at The Mount Sinai Hospital. Each chart was reviewed for patient demographics, symptoms, coexisting conditions, specific therapies, and therapeutic outcomes. Additional data were obtained from telephone calls to patients when deemed necessary. Three patients were exeluded from the study because of lack of follow-up. Therapeutic outcomes were defined as follows: Complete Remission (CR): normalization of bowel function; Partial Remission (PR): 50% reduction in frequency of bowel movements; Failure: <50% reduction in frequency of bowel movements; or Relapse: return of symptoms after cessation of treatment. Median follow-up was 58 wk from time of diagnosis, with a range of 22-376 wk.

RESULTS: The 26 patients (25 women, one man) had a mean age of 62 yr (range, 22-85 yr) at diagnosis. Of 26 patients, 22 responded to some form of therapy and one had spontaneous remission. Six of the responders ultimately remained in CR with no therapy. Twelve are maintained on 5-aminosalicylic acid (5-ASA) and or antidiarrheals to control symptoms. An additional six required prednisone throughout the follow-up period to remain in CR or PR. Two patients failed all therapy.

CONCLUSION: Collagenous colitis is a treatable condition in most patients. We recommend initial therapy with antidiarrheals, followed by a trial of 5-ASA agent. A trial of 5-ASA in combination with prednisone should be attempted in patients refractory to 5-ASA alone, with subsequent attempts in the responders to taper prednisone and maintain remission with no therapy, if possible, or with 5-ASA and/or antidiarrheal agents if necessary.


Therapy of prednisone-refractory collagenous colitis with budesonide.

Lanyi B, Dries V, Dienes HP, Kruis W.

Abteilung fur Innere Medizin, Evangelisches Krankenhaus Kalk, Koln, Germany.

Int J Colorectal Dis 1999 Feb;14(1):58-61 Abstract quote

Collagenous colitis is a rare cause of chronic watery diarrhea. No effective standard treatment has yet been established. Based upon anecdotal reports some anti-inflammatory and symptomatic drugs seem to have some therapeutic efficacy. Prednisone is widely believed to be the most effective treatment.

Here we describe three female patients with histologically confirmed collagenous colitis refractory to therapy with prednisone. Each had received prednisone with a high starting bolus and lower dose maintenance therapy for their disease. However, definite clinical remission could not be achieved. After the administration of 3 x 3 mg/day controlled ileal release (CIR) capsules of budesonide the symptoms resolved immediately. The mean follow-up after beginning budesonide was 11 months (range 7-18). Two patients are still on budesonide. One had had a quick relapse of diarrhea after stopping her treatment. Budesonide therapy was therefore resumed. She has remained symptom-free on a lower daily dose of 2 x 3 mg/day budesonide. One patient has been in remission for more than 1 year after a 3-month course of budesonide. Budesonide is a topically acting steroid with rapid absorption, high receptor affinity, and low systemic bioavailability, thus causing almost no side effects. As yet only few case reports have been published on the use of budesonide for collagenous colitis.

We present here the first three cases of prednisone refractory collagenous colitis successfully treated with budesonide.

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