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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 1  |  Page : 15-19
Microscopic colitis in patients presenting with chronic diarrhea


1 Department of Pathology, Moti Lal Nehru Medical College, Allahabad, India
2 Department of Gastroenterology, Moti Lal Nehru Medical College, Allahabad, India

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Date of Web Publication19-Jan-2010
 

   Abstract 

Aim: To investigate the prevalence of microscopic colitis among patients presenting with chronic watery diarrhea. Material and Methods: Colonic biopsies from 400 patients presenting with chronic watery diarrhea and other symptoms pertaining to lower gastrointestinal tract were studied. After a detailed clinical history and thorough physical examination full length colonoscopy was done using flexible colonoscope. Colonic biopsies were taken from abnormal and normal areas. Three to five micron thick sections were cut and stained with hematoxylin and eosin and Masson's trichrome stain to highlight sub epithelial collagen. Results: Fifteen out of 400 (3.7%) colonic biopsies from patients presenting with chronic diarrhea had evidence of microscopic colitis. Five out of fifteen biopsies (33%) were diagnosed as collagenous colitis, 10 biopsies (67%) had evidence of lymphocytic colitis; 14/400(3.5%) histologically normal biopsies were taken as controls to compare various demographic and risk factors. Ten out of 15 patients (67%) were clinically diagnosed as irritable bowel syndrome. In the remaining five an infective etiology was suspected. On colonoscopy12/15 (80%) had no abnormality and 3/15 (20%) had mild hyperemia. Conclusion: A possibility of microscopic colitis should be considered while examining colonoscopic biopsy of a patient with chronic watery diarrhea and normal colonoscopy to avoid the misdiagnosis that may affect the treatment of patients

Keywords: Collagenous colitis, Lymphocytic colitis, Microscopic colitis, Watery diarrhea

How to cite this article:
Misra V, Misra S P, Dwivedi M, Singh PA, Agarwal V. Microscopic colitis in patients presenting with chronic diarrhea. Indian J Pathol Microbiol 2010;53:15-9

How to cite this URL:
Misra V, Misra S P, Dwivedi M, Singh PA, Agarwal V. Microscopic colitis in patients presenting with chronic diarrhea. Indian J Pathol Microbiol [serial online] 2010 [cited 2014 Nov 24];53:15-9. Available from: http://www.ijpmonline.org/text.asp?2010/53/1/15/59176



   Introduction Top


Microscopic colitis is an umbrella term used to describe two less common forms of inflammatory bowel diseases i.e. lymphocytic colitis and collagenous colitis. The term was coined originally by Read et al. in 1980 [1] who found mild increase in inflammatory cells in rectal or colonic biopsies of patients with chronic watery diarrhea but normal sigmoidoscopy. It is usually seen in elderly patients (fifth or sixth decade). Common presentation is watery diarrhea without blood. Radiology and colonoscopy is normal. Nocturnal diarrhea helps in its differentiation from irritable bowel syndrome. [2] Colonoscopic biopsies have definite histological changes in the form of thickened sub epithelial collagen (collagenous colitis) [3] or increased intraepithelial lymphocytes with focal denudation of mucosa (lymphocytic colitis). [4] Workers have different opinions on whether these are two distinct entities or they are the part of the spectrum of one disease. [5],[6],[7]

It accounts for approximately 10% of patients presenting with chronic diarrhea. [6] Prevalence of lymphocytic and collagenous colitis in North America (64 and 36/100,000) has been documented to be much higher than Europe (15.7 and14.4/100,000). [7],[8]

As there are very few well documented studies from India [9],[10] the present study was done to find out the prevalence of microscopic colitis among patients presenting with chronic watery diarrhea.


   Material and Methods Top


The study included colonic biopsies of 400 patients presenting with chronic watery diarrhea and other symptoms pertaining to lower gastrointestinal tract viz. pain abdomen, feeling of incomplete evacuation and weight loss. Patients with blood and mucous in stools were not included in the study.

After looking into the detailed clinical history of patients, especially for dietary habits, active smoking and drug intake, physical examination was done. A thorough full length colonoscopy using flexible colonoscope (Olympus, Japan) was done and multiple colonic biopsies were taken from abnormal and normal areas. Three to five micron thick sections were cut and stained with hematoxylin and eosin and Masson's trichrome stain to highlight sub epithelial collagen.

Morphometry

Thickness of sub epithelial collagen was measured and the Leitz optical micrometer was used to count the number of intraepithelial lymphocytes.

Diagnostic criteria for collagenous and lymphocytic colitis were as follows:

Collagenous colitis

  • Presence of diffuse or patchy thickened (greater than10µ) sub epithelial collagen layer
  • Flattening and detachment of epithelial layer
  • Increased intraepithelial lymphocytes (IELs) but less than 20/100 epithelial cells
  • Mild inflammation in lamina propria
Lymphocytic Colitis



  • Increased intraepithelial lymphocytes greater than 20/100 epithelial cells
  • Mild predominantly mononuclear inflammatory infiltrate in lamina propria
  • Damage to surface epithelium
  • Sub epithelial collagen normal
Demographic features, risk factors, symptoms and histological features in patients with collagenous colitis and lymphocytic colitis were compared with controls (patients with normal colonoscopy and histology).

Statistics: Chi square test with and without Yates' correction was used to find any significance. P less than or equal to 0.05 were taken as critical level of significance.


   Results Top


Fifteen out of 400 (3.7%) colonic biopsies from patients presenting with chronic diarrhea had evidence of microscopic colitis. Fourteen (3.5%) cases having normal colonoscopy with normal histology were taken as controls. Five out of these fifteen biopsies (33%) were diagnosed as collagenous colitis on biopsy, rest of the 10 biopsies (67%) had evidence of lymphocytic colitis. Ten out of 15 patients (67%) were clinically diagnosed as irritable bowel syndrome; in five an infective etiology was suspected. On colonoscopy12/15 (80%) had no abnormality and 3/15 (20%) had mild hyperemia.

Collagenous Colitis

Mean (SD) age of the patients was 52.4(8.3) years. M: F ratio was 1:4. All patients presented with chronic watery diarrhea with mild abdominal pain. Mean (SD) duration of illness was 3.2 (2.5) months. Three (75%) had more than five stools / day, 2/5(40%) had a history of active smoking and 1/5(20%) each had h/o non steroidal anti inflammatory drugs (NSAID) and proton pump inhibitors (PPI) intake. Two (40%) patients had joint pain. Colonoscopy was normal in four patients. One patient had mild hyperemia.

On histopathological examination a continuous or patchy layer (two cases) of thickened sub epithelial collagen (thickness over 10m) was present beneath the basement membrane. [Figure 1] A and B The presence of increased sub epithelial collagen was highlighted by Masson's trichrome stain. [Figure 2]. Epithelial detachment was present in places with mild increase (5-10/100 epithelial cells) in IELs and mononuclear inflammatory cells in lamina propria. [Table 1] and [Table 2]

Lymphocytic Colitis

Ten cases had evidence of lymphocytic colitis. Mean (SD) age of presentation was 55(5.6). Male: female ratio was 1:1.25. Most common symptom was pain abdomen and diarrhea (100%). Three patients (30%) complained of incomplete evacuation also. Mean (SD) duration of Illness was 2.5(2.8) months and four (40%) had more than five stools /day. 2/10(20%) had history of smoking. 2/10(20%), 1/10(10%) and 2/10(20%) had history of Aspirin, NSAID and PPI intake respectively. Colonoscopy was normal in 80% (8/10). In two (20%) patients mild hyperemia was present.

On histopathology the main abnormality was increase in number of IELs (20 - 35 IEL /100 epithelial cells) on surface and crypt epithelial lining. Mean (SD) IELs at 29.2 (5.1) were higher than the normal (five to six / 100 epithelial cells). Mononuclear inflammatory cells in lamina propria were not significantly increased. Focal areas of epithelial injury and detachment were also seen [Figure 3].

None of the biopsies showed significant neutrophil infiltration, loss of goblet cells, crypt abscess, crypt distortion, marked lymphocytic infiltrate in lamina propria, lymphoid aggregates/ follicles /granuloma and fibrosis of lamina propria. [Table 1] and [Table 2]

Controls

Mean (SD) age was 44.2(5.2). M: F ratio was 1:1.8. Most common presentation was pain abdomen (100%) and gaseous distention (50%). Two (14.3%) had a history of smoking. None of them had any history of drug intake. Mean (SD) duration of symptoms was 2.1(1.2) months and only two patients had a frequency of more than five stools/ day. Colonoscopy and histology was normal in all the subjects [Table 1] and [Table 2].


   Discussion Top


Microscopic colitis is a relatively new term used to describe the histopathological changes in elderly patients with chronic watery diarrhea of unknown etiology with normal imaging and colonoscopic findings.

Prevalence of microscopic colitis was found to be 3.7% in this study. A gradual increase in the incidence of microscopic colitis in last decade has been reported in an epidemiological study from USA. [7] They observed an incidence of 0.8, 2.6, 10.3 and 19.1 (per 100000 population) in the years 1985-89, 1990-93, 1994-97 and 1998-2001 respectively. [7] This was probably due to increased awareness of this entity and its diagnostic features.

Smoking was more commonly associated with collagenous colitis than lymphocytic colitis. However, the difference was not statistically significant probably due to smaller number of cases. Baert et al. found a statistically significant association of smoking with collagenous colitis. [11] History of aspirin and NSAID intake was more in collagenous colitis than lymphocyte colitis whereas PPI intake was seen in equal percentage of patients in the two groups. No statistically significant difference was observed.

In this study there was a female preponderance in patients with collagenous colitis and most of the patients presented with chronic watery diarrhea without significant radiological and colonoscopic abnormalities similar to earlier reports. [2],[12],[13] All patients had characteristic histology with patchy or continuous thickened collagen band of more than 10 micron in thickness that was well in accordance with earlier reports. [2],[12] Lazenby et al.[4] observed that other qualitative abnormalities in the form of entrapment of superficial capillaries and an irregular lower edge of the basement membrane are sufficient to make a diagnosis of collagenous colitis in the absence of significantly thickened collagen band. Two such cases have been noted in this study too.

Lymphocytic colitis was also observed in elderly patients but without a female preponderance as observed earlier. [2],[13] Radiological and colonoscopic findings were normal and the most significant abnormality was an increase in the number of IELs in surface and crypt epithelium. [14] Lymphocytes in lamina propria were not significantly increased similar to earlier reports. [2],[4]

Sixty seven per cent (10/15) patients with evidence of microscopic colitis on histology were clinically diagnosed as patients of irritable bowel syndrome (IBS) and had normal colonoscopy. The findings were similar to earlier reports, where microscopic colitis was the predominant histological abnormality observed in biopsies from patients with IBS or undergoing routine colonoscopy. [15],[16],[17] Limsui observed that there is symptomatic overlap between IBS and microscopic colitis and therefore patients with diarrhea predominant IBS should be routinely biopsied even when colonoscopy is normal. [18] In an earlier study from North India 7.1% of patients presenting with chronic diarrhea had microscopic (lymphocytic) colitis. [9] None of the patients in their study had collagenous colitis. [9] A lower prevalence of microscopic colitis in present study may be attributed to stringent criteria used for histopathological identification of these entities.

In some of the recent reports microscopic colitis has been divided into five sub types: Collagenous colitis (CC), lymphocytic colitis (LC), minimal change colitis (MCC), microscopic colitis not otherwise specified (MC-NOS) and MC with giant cell. [10],[18],[19],[20] Essential criteria for MCC include crypt abnormalities like cryptitis, abscess and dystrophy along with a collagen layer and IEL less than 10µ and less than 20/100 epithelial cells respectively. Similarly for MC-NOS the important criteria is an increase in the inflammatory infiltrate (lymphocytes, Eosinophils and plasma cells) in lamina propria. In present study only two main groups were considered as MCC, MC-NOS and MC with giant cell may sometimes overlap with early features of inflammatory bowel diseases. There are reports where patients initially diagnosed as MC progressed to crohn's disease or ulcerative colitis later on. [21],[22],[23],[24]

This study is different from earlier reports from India [9],[10] as it highlights the incidence of two main histological variants of microscopic colitis without going into details of minor variants and showing chances of missing this entity by an unaware pathologist as it clinically has overlapping features with the irritable bowel syndrome.

The main differential diagnosis considered was acute self limiting colitis (ASLC), ulcerative colitis (UC) and Crohn's disease. These were differentiated according to various differentiating features as described by Lazenby [Table 3]. [4]

There are differences of opinion among workers on whether the two entities are part of same spectrum or different diseases. On comparison it was observed that despite having similar clinical presentation incidence of lymphocytic colitis is three times more common than collagenous colitis and has no female preponderance as seen in collagenous colitis. Furthermore, clinical resolution with optimum treatment is higher in lymphocytic colitis than collagenous colitis. Histological features further help in differentiating them. Both the entities have similar HLA abnormalities (HLADQ2) and identical treatment.

To conclude, the possibility of microscopic colitis should be considered while examining colonoscopic biopsy of a patient with chronic watery diarrhea and normal colonoscopy to avoid any misdiagnosis that may affect the treatment and prognosis of the patients.

 
   References Top

1.Read NW, Krejs GJ, Read MG, Santa An a CA, Morawski SG, Fordtran JS. Chronic diarrhoea of unknown origin. Gastroenterology 1980;78:264-71.  Back to cited text no. 1      
2.Tagkalidis P, Bhathal P, Gibson P. Microscopic colitis. J Gastroenterol Hepatol 2002;17:236-48.  Back to cited text no. 2      
3.Lindström CG. "Collagenous colitis" with watery diarrhoea - a new entity? Pathol Eur 1976;11:87-9.  Back to cited text no. 3      
4.Lazenby AJ, Yardley JH, Giardiello FM, Jessurun J, Bayless TM. Lymphocytic (microscopic) colitis: a comparative histopathologic study with particular reference of collagenous colitis. Hum Pathol 1989;20:18-28.  Back to cited text no. 4      
5.Jessurun J, Yardley JH, Lee EL, Vendrell DD, Schiller LR, Fordtran JS. Microscopic and collagenous colitis: different names for the same condition? Gastroenterology 1986;91:1583-84.  Back to cited text no. 5      
6.Levison DA, Lazenby AJ, Yardley JH. Microscopic colitis cases revisited. Gastroenterology 1993;105;1594-96.   Back to cited text no. 6      
7.Bogomoletz WV, Flejou JF. Microscopic colitis - A trans atalantic unifying concept. Gastroenterology 1994;106:1727-9.  Back to cited text no. 7      
8.Shah RJ, Fenoglio-Preiser C, Bleau BL, Giannella RA. Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhoea. Am J Gastroenterol 2001;96:1091-5.  Back to cited text no. 8      
9.Pardi DS, Loftus EV Jr, Smyrk TC, Kammer PP, Tremaine WJ, Schleck CD, et al The epidemiology of microscopic colitis: a population based study in Olmsted County, Minnesota. Gut 2006;56:504-8.  Back to cited text no. 9      
10.Agnarsdottir M, Gunnlaugsson O, Orvar KB, Cariglia N, Birgisson S, Bjornsson S, et al Collagenous and Lymphocytic colitis in Iceland. Dig Dis Sci 2002; 47:1122-28.  Back to cited text no. 10      
11.Garg PK, Singh J, Dhali GK, Mathur M, Sharma MP. Microscopic colitis is a cause of large bowel diarrhea in Northern India. J Clin Gastroenterol 1996;22:11-15.  Back to cited text no. 11      
12.Falodia S, Makharia GK, Sateesh J, Deo Vaishali, Tevatia MS, Datta Gupta S. Spectrum of microscopic colitis in a tertiary care centre in India. Tropical Gastroenterology 2007;28:121-25.  Back to cited text no. 12      
13.Baert F, Wouters K, Haens GD, Hoang P, Naegels S, Heygere HD et al. Lymphocytic colitis: a distinct clinical entity? A clinicopathologicalconfrontation of lymphocytic and collagenous colitis. GUT 1999;45:375-81.  Back to cited text no. 13      
14.Fernández-Bañares F, Salas A, Esteve M, Espinós J, Forné M, Viver JM. Collagenous and lymphocytic colitis. Evaluation of clinical and histological features, response to treatment, and long-term follow-up. Am J Gastroenterol 2003;98:340-7.   Back to cited text no. 14      
15.Giardiello FM, Lazenby AJ, Bayless TM. The new colitidis. collegenous, lymphocytic and diversion colitis. Gastroenterol Clin North Am 1995;24:717-29.  Back to cited text no. 15      
16.Liszka £, Woszczyk D, Pajak J. Histopathological diagnosis of microscopic colitis. J Gastroenterol Hepatol 2006;21:792-7.   Back to cited text no. 16      
17.Gineston JL, Sevestre H, Descombes P, Viot J, Sevenet F, Davion T, et al Biopsies of the endoscopically normal rectum and colon: a necessity. Incidence of collagenous colitis and microscopic colitis. Gastroenterol Clin Biol 1989;13:360-3.  Back to cited text no. 17      
18.Fine KD, Seidel RH, Do K. the prevalence, anatomic distribution and diagnosis of colonic causes of chronic diarrhea. Gastrointest Endosc 2000;51:318-26.  Back to cited text no. 18      
19.da Silva JG, De Brito T, Cintra Damião AO, Laudanna AA, Sipahi AM. Histologic study of colonic mucosa in patients with chronic diarrhea and normal colonoscopic findings. J Clin Gastroenterol 2006;40:44-8.  Back to cited text no. 19      
20.Limsui D, Pardi DS, Camilleri M, Loftus EV Jr, Kammer PP, Tremaine WJ, et al Symptomatic overlap between irritable bowel syndrome and microscopic colitis. Inflamm Bowel Dis 2006;13:175-81.   Back to cited text no. 20      
21.Warren BF, Edwards CM, Travis SP. Microscopic colitis: classification and terminology. Histopathology 2002;40:374-76.  Back to cited text no. 21      
22.Geboes K, Villanacci V. Terminology for the diagnosis of colitis. J Clin Pathol 2005;58:1133-4.  Back to cited text no. 22      
23.O'Beirne JP, Ireland A. Progression of collagenous colitis to crohn's disease. Eur J Gastroenterol Hepatol 2005;17:573-5.  Back to cited text no. 23      
24.Pokorny CS, Kneale KL, Henderson CJ. Progression of collagenous colitis to ulcerative colitis. J Clin Gastroenterol 2001;32:435-8.  Back to cited text no. 24      

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Correspondence Address:
Vatsala Misra
Department of Pathology, M.L.N.Medical College, Allahabad - 211 001
India
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DOI: 10.4103/0377-4929.59176

PMID: 20090215

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]

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