Saudi Journal of Gastroenterology
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CASE REPORT Table of Contents   
Year : 1999  |  Volume : 5  |  Issue : 1  |  Page : 36-39
Collagenous colitis : A case report with study of the neuroendocrine markers

1 Department of Histopathology, Central Laboratory and Blood Bank, Riyadh, Saudi Arabia
2 Department of Pathology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
3 Department of Medicine, College of Medicine, Riyadh, Saudi Arabia

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Date of Submission25-Mar-1998
Date of Acceptance30-May-1998

How to cite this article:
Baez-Giangreco A, Afzal M, Antonious J, Laajam MA, Zargar SA. Collagenous colitis : A case report with study of the neuroendocrine markers. Saudi J Gastroenterol 1999;5:36-9

How to cite this URL:
Baez-Giangreco A, Afzal M, Antonious J, Laajam MA, Zargar SA. Collagenous colitis : A case report with study of the neuroendocrine markers. Saudi J Gastroenterol [serial online] 1999 [cited 2022 Jan 27];5:36-9. Available from:

Collagenous colitis (CC) is a recently described clinico-pathologic entity characterized by intractable chronic watery diarrhea, crampy abdominal pain, normal or near normal colonoscopic examination and histologically by a thickened subepithelial collagenous band associated with chronic inflammatory reaction and increased intraepithelial lymphocytic infiltrate in the colonic biopsies. Its pathogenesis remains nclear. We report a rare case of collagenous colitis in which immunohistochemical studies revealed marked deviations from normal in the endocrine elements of the colonic bowel. To our knowledge this is the first report of such a study in collagenous colitis.

   Case Report Top

A 68 years old Syrian woman complaining for eight months history of recurrent episodes of watery diarrhea, associated with colicky abdominal pain. The diarrhea was intermittent or continuous for several months with remissions and relapses. There was no significant loss of weight or dehydration. The diarrhea was mainly watery in appearance but occasionally associated with mucus material. There was no clinical history of use of drugs, medication or joint pain. Family history was negative. Physical examination was unremarkable.

Laboratory investigation showed Hb, WBC 8,500 ul (Neutrophils 70%, Lymphocytes 25%, Monocytes 3% and Eosinophils 2%). Multiple fecal analyses were negative for parasites. Bacteriologic cultures of the feces were negative. Blood biochemical analyses also were within normal limits. Endoscopic examination showed mildly congested colonic mucosa. Biopsies from different parts of colon and rectum were taken.

   Histopathologic Findings Top

Microscopically the seven fragments of the colonic mucosa revealed intact crypt architecture with mild to moderate nonspecific chronic inflammation. The overlying epithelium revealed mild lymphocytic infiltration. No significant esinophilic or neutrophilic infiltration was noted. Some fragments showed the presence of thick collagenous band like material beneath the surface epithelium leading to thickened basement membrane [Figure - 1]. The basement membrane measured 12 um in thickness on the Masson Trichrome stained slides [Figure - 2]. It stained positive with PAS but negative with Congo Red (Amyloid stain). This histopathological picture was compatible with a diagnosis of CC.

Immunohistochemistry studies were performed using Dako kits with antibodies against serotonin, gastrin, vasoactive intestinal polypeptide, somatostatin and neurofilaments protein. The Avidin-Biotin Peroxidase Complex method was used. Slides of normal areas of colon from patients with colonic carcinoma were used as control. The result are listed in [Table - 1].

In summary the distribution of the endocrine cells is erratic in collagenous colitis and varies from one area to another. Decreased expression of markers were seen in Gastrin and VIP. The amount of Neurofilament protein were not decreased but the distribution in the stromal tissue was irregular and clumped in groups of cells rather than diffuse. Increased staining was observed with serotonin markers [Figure - 3]. The number of staining cells was about twice as observed in the normal control [Figure - 4]. These cells were mainly found beneath the region showing thick collagenous deposition in the basal membrane. Staining with somatostatin antibodies was reduced in the epithelial cells but showed normal density in some areas of the stromal cells.

Our patient responded to treatment with Sulphasalizine. It was not possible to repeat the endoscopic histopathological studies during remission as the patient left the country.

   Discussion Top

The first case of "collagenous colitis" was reported in detail in 1976 by Lindstrom, who coined the original term [1] .

Collagenous colitis is a clinicopathologic entity characterized by chronic watery diarrhea and irregular colonic subepithelial collagenous band-like deposit associated with increase of inflammatory cells in the lamina propria and lymphocytic infiltration of the overlying epithelium.

Collagenous colitis shows a striking predominance for women (90% of all patients), particularly in their fifth decade, although cases also have been reported in men and the disease has affected all age groups (age range, 19 to 86 years old). A pediatric case in a five-year-old boy was recently recorded [2] .

Patients typically present with intractable chronic watery diarrhea as in our case. Sporadic cases of collagenous colitis have been reported with chronic constipation [3] . The diarrhea is intermittent or continuous, often lasting for months or years, with remissions and relapses, which may occur spontaneously or with treatment. The watery stools seldom contain mucus or blood. Colicky abdominal pain is another common symptom. Nausea and vomiting are unusual. Patients rarely show significant weight loss or dehydration. Routine bacteriology, biochemistry, and hematology usually fail to disclose any major abnormalities. This is the first case of collagenous colitis in arabs.

Conventional or double-contrast radiology tend to be unhelpful. At endoscopy, the colorectal mucosa appears within normal limits or, rarely, shows mild and non-specific changes such as congestion,edema, pallor or slight friability of colonic mucosa[ 4] . There are none of the typical clinical features of inflammatory bowel disease. The consistent characteristic in collagenous colitis is the thick collagenous band like deposition in the subepithelial basal cell membrane and increased lymphocytic infiltration in the surface epithelium as observed in our case. These changes are most frequently found in more proximal segment of the colon and less frequently distally. The collagenous thickening is patchy and may be missed even on two or three biopsies. Original reports set the threshold for the upper limit of thickness of normal subepithelial basement membrane of colorectal mucosa in adults to about 7 um and have advised caution in making a diagnosis of collagenous colitis if the basement membrane thickness is less than 10 um [3],[5] . However recent reports have given more emphasis to the collagenous character of the subepithelial deposition rather to the thickness. Both, the chollagenous character of the deposition as well as the thickeness of more than 10 um were present in our case. The cause of collagenous colitis remains unknown. It is not clear whether the chronic watery diarrhea is the cause or the result of the collagenous deposition. It does not seem directly related to inflammatory bowel disease, as many patients with long standing history of collagenous colitis, have not developed clinical or histological evidence of inflammatory bowel disease. And in most of the accepted forms of inflammatory bowel disease the colorectal mucosa has not shown a subepithelial collagen deposit similar to that found in collagenous colitis [2],[6],[7] . The triggering factor may cause not only mucosal injury but also dysfunction of the pericryptal myofibroblats resulting in reduced cell turnover, a prolonged phase of cell maturity, and more than normal collagen production [6],[8],[9] .

Studies of VIP and Subst. P [10] show significant decrease of VIP and increase of Subst. P in ulcerative colitis correlated to the severity of the colonic inflammation. In our case, also there is decrease of the VIP marker, probably due to the inflammatory reaction.

The distribution of endocrine cells is erratic also with somatostatin and neurofilament protein being found mostly in patches within the lamina propria.

In view of the observation that the collagen in CC has been known to disappear, and is therefore inconstant, it is suggested that the same is true of somatostatin and neurofilament protein.

Interesting finding was the marked increase of the serotonin marked cells mainly in areas with thick collageneous deposition. Since serotonin appears to be involved in the stimulation of intestinal cell physiology, such as stimulation of fibroblasts adhesions and multiplication in tissue culture, decreased cholagenase production, as well as a role in the pathogenesis of cholera, further investigation to define its role in collagenous colitis should be done [11],[12],[13] . We do not have a clear picture of the distribution of serotonin because only biopsies were available for study. This point is not resolved in the literature. Since neuropeptides form a part of the brain-gut axis which may regulate gastrointestinal functions, including immune regulation, the finding of marked deviation from normal in the neuroendocrine elements studies in this case of collagen colitis deserve further evaluation.

   References Top

1.Lindstrom CG. "Collagenous colitis" with watery diarrhea A new entity? Pathol. Fur 1976;11:87-9.  Back to cited text no. 1    
2.Gremse DA, Boundreaux CW, mancy EA. Collagenous Colitis in Children. Gastroenterology 1993;104:906-9.  Back to cited text no. 2    
3.Leigh C, Elahmady A, Mitros FA. Metcalf A, AL Jurf A. Collagenous colitis associated with Chronic constipation. Am. J. Surg. Pathol. 1993;17:81-4.  Back to cited text no. 3    
4.Jessurun J, Yardley JH, Giardello FM, et al. Chronic colitis with thickening of the subepithelial collagen layer (collagenous colitis).Histopathologic finding in 15 patients. Hum Pathol. 1987;18:839-48.  Back to cited text no. 4    
5.Mazundar S, Das KM. Immunocytochemical localization of vasoactive intestinal peptide and substance P in the colon from normal subjects and patients with inflammatory bowel disease. Am. J. of Gastroent. 1992;87:176-81.  Back to cited text no. 5    
6.Giardellon FM, Bayless TM, Jessurun J, Hamilton SR. Yardley JH. Collagenous colitis;Physiollogic and histopathologic studies in seven patients. Ann Intern Med. 1987;106:46-9.  Back to cited text no. 6    
7.Breen EG, Farren C, Connoly CE, McCarthy CF. Collagenous colitis and celiac disease. Gut 1987;28:364.  Back to cited text no. 7    
8.Bogomoletz WV. Collagenous colitis. A clinicopathological review. Surg. Dig. Dis. 1983;1:19-25.  Back to cited text no. 8    
9.Lazenby AJ, Yardley JH, Giardiello FM, Jwssurun 3l, Baless TM. Lymphocytic ("microscopic") colitis. A comparative histopathologic study with particular reference to collagenous colitis. Hum. Pathol. 1989;20:18-28.  Back to cited text no. 9    
10.Koch TR, Camcy JA. W. Go VL. Distribution and Quantitation of Gut Neuropeptides in Normal Intestine and Inflammatory Bowel Disease. Dig. Dis. & Sc. 1987;32:369-76.  Back to cited text no. 10    
11.Gedevanishvili MD, Tsutsunava- LE, Malazoniia NA. Serotonin independently stimulates fibroblasts adhesion and multiplication in culture. Tsitologiia; 1982;24:224-6.  Back to cited text no. 11    
12.Warter J, Schirardin H, Warier A. Probable inhibition of a bacterial collagenase by serotonin. C-R-Seances-Soc-Biol­Fil. 1982;176.288-95.  Back to cited text no. 12    
13.Peterson JW, Lu Y, Duncan S, Cantu J, Chopra AK. Interaction of intestinal mediators in the mode of action of cholera toxin. J. Med. Microb. 1994;41:3-9.  Back to cited text no. 13    

Correspondence Address:
Atilio Baez-Giangreco
P.O. Box 60179, Riyadh 11545
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 19864759

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]

  [Table - 1]


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