Saudi Journal of Gastroenterology
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Year : 2006  |  Volume : 12  |  Issue : 3  |  Page : 142-145
Diagnosis and management of microscopic colitis


Division of Gastroenterology, Department of Medicine, Riyadh Military Hospital, Riyadh, Saudi Arabia

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   Abstract 

Microscopic colitis (MC) in both of its forms, collagenous and lymphocytic colitis, is considered now an important cause of diarrhea in middle aged and elderly patients. In this entity, endoscopic and radiological examinations are normal while specific histological findings are seen on colonic biopsy. Once the diagnosis of MC is confirmed, a stepwise approach with medical therapy is suggested. Ruling out other causes of chronic diarrhea should be the initial step. Once the diagnosis of MC is confirmed, a stepwise treatment algorithm is suggested. In this review, I will introduce the entity of MC and describe the stepwise approach to diagnosis and management by reviewing the available evidence. The literature was reviewed regarding both collagenous colitis and lymphocystic colitits focusing on clinical trails. This was then critically examined and an approach to the diagnosis and management of microscopic colitis was suggested.

Keywords: Microscopic colitis, collagenous colitis, lymphocytic colitis

How to cite this article:
Al Malki A. Diagnosis and management of microscopic colitis. Saudi J Gastroenterol 2006;12:142-5

How to cite this URL:
Al Malki A. Diagnosis and management of microscopic colitis. Saudi J Gastroenterol [serial online] 2006 [cited 2019 Aug 21];12:142-5. Available from: http://www.saudijgastro.com/text.asp?2006/12/3/142/29756


Microscopic colitis (MC) is an inflammatory condition of the colon in which the colonic mucosa appears normal endoscopically and radiologically, while histological examination of the colonic mucosa reveals specific histopathologic features. This entity of inflammatory bowel disease is composed of two separate but related diseases - collagenous colitis (CC) and lymphocytic colitis (LC). The two entities are similar in their presentation and natural history but differ in their histological appearances. In both the conditions, there is inflammation in the lamina propria of the colonic mucosa, with increased intraepithelial lymphocytes. Specifically in CC and not in LC, there is, in addition, marked thickening of the sub-epithelial collagen layer, which is the hallmark of this disease [Figure - 1]. This disease entity has attracted a lot of attention recently as an important and relatively common cause of chronic diarrhea.[1],[2] The initial description of MC was first published in 1976 and since that time, it has been increasingly recognized as a relatively common cause of chronic diarrhea.


   Epidemiology Top


Although initially thought to be rare, more recent estimates have suggested that the yearly incidence of MC may be around 5.8/100,000 and the prevalence about 10-15.7/100,000 in Europe[3] while it may be as high as 15/100,000 in elderly females, which is similar to the incidence of ulcerative colitis.[4] The incidence of lymphocytic colitis has been estimated to be around 3.1/100,000 and the prevalence 14.4/100,000. One retrospective study from three tertiary care centers in Canada found 94 cases of CC from 1990-1997.[5] Moreover, there is a recent report demonstrating increase in the annual incidence of MC to an equal incidence of Crohn's disease.[6] A female-to-male ratio of 2.4:1 was noticed in most studies. The reason for the increased recognition of MC in recent years is likely due to the increased awareness of its existence, and thus gastroenterologists routinely perform biopsy in patients with endoscopically normal-appearing colons. This has been shown in two studies published in Gastrointestinal Endoscopy, showing 5 years apart, which demonstrated increase of biopsy of normal colonic mucosa - increasing from 15% in 2000 to 78% in 2005.[7],[8]

Unfortunately the data regarding MC from the Arab world is scant, but a recent report from Tunisia showed MC in 29% of the 150 patients who had normal colonoscopy and biopsies as part of their work-up for chronic diarrhea.[9]

MC typically presents in the sixth to seventh decade of life, but it has been reported in all ages.


   Clinical features Top


The most frequent symptoms are diarrhea (96%). Between 3 and 20 bowel movements can occur per day, often accompanied by abdominal cramping and nocturnal bowel movements. Abdominal pain occurs in around 47% and weight loss in 41%. The course of the disease is chronic intermittent in 30% of patients, chronic continuous in 7% and a single attack in 63%.[10],[11]

Arthralgias and various other autoimmune-like conditions appear to also be associated with MC and may be seen in as many as 40% of the patients. The most common association to date is that of celiac disease. It has been estimated that approximately one-third of celiac disease patients have histological changes that may be compatible with microscopic colitis. CC should particularly be looked for in celiac disease patients who are not responsive to gluten-free diet.[12] An entity named collagenous sprue has also been described, where changes similar to colonic CC are seen in the stomach or small bowel. Drugs are considered to be an important cause in at least 10% of patients having typical clinical and histological findings of MC, and the list of drugs incriminated is expanding [Table - 1].

To date there is no clear evidence that MC is an inherited disease; however, several families have been described in which first-degree family members were diagnosed with MC.[13]


   Histopathology Top


Intraepithelial lymphocytosis (IEL), with greater than 20 lymphocytes per 100 epithelial cells, is pathognomonic of the diagnosis of LC though lesser numbers of IEL may be present in some patients with LC. The second typical feature of MC is infiltration of the lamina propria with lymphocytes and plasma cells along with loss of integrity of superficial epithelium. For CC, in addition to the above-mentioned features, there is presence of diffuse noncontinuous thickening of a sub-epithelial collagen layer under the basement membrane of more than 10 mm (range 7-80 mm). Thickness varies by location in the colon, and bands often are widest in proximal segments and absent in the rectum.[14] A number of atypical features have been described in the literature, including but not limited to presence of crypt abscesses, granulomas, goblet cell depletion and giant cells.[15]


   Diagnosis Top


A detailed history should be the first step in evaluating a patient suspected of having MC. This should include the duration of diarrhea and a description of the stool characteristics. In MC, the diarrhea is often chronic, intermittent and usually watery, although steatorrhea has rarely been described. Significant bloody diarrhea is not compatible with MC. Other gastrointestinal symptoms that may suggest celiac disease or inflammatory bowel disease should be asked about. Possible associated autoimmune diseases should also be looked for. Drug history is an essential part of the diagnostic work-up for patients suspected of having MC.

Other causes of chronic diarrhea should be ruled out first, including infections and inflammation-related causes. For this reason, stool cultures should be taken, and stool should be examined for ova and parasites. Fecal leukocytosis is seen in up to 50% of patients with CC.[16] In general, radiological investigations including barium studies are not useful in these patients but may be required originally to rule out other causes, especially in an older patient. Although sigmoidoscopy is generally accepted as the first endoscopic procedure in these patients because of the pancolonic nature of the disease, if biopsies from the sigmoid colon are not revealing and the clinical suspicion remains high, then a full colonoscopy is warranted, given the studies showing a possible miss rate as high as 40% with sigmoidoscopy alone.


   Treatment Top


Many different agents have been tried in patients with MC. Due to the poorly understood pathophysiology of this disorder, the therapeutic interventions have been multiple, with variable degrees of success. A stepwise approach to these patients has been suggested by many authors.[1],[11]

General measures should be carried out first. The patient's volume status and general condition should be assessed. Volume repletion and corrections of possible aggravating factors (including caffeine, dairy products, dietary supplements and artificial sweeteners) should be the initial step in management. Medications that may aggravate symptoms or even contribute to pathogenesis, such as nonsteroidal antiinflammatory drugs (NSAIDs), should be stopped if possible. It seems reasonable to suggest stopping NSAIDs if possible in MC patients and assessing the response.[1]

  1. Nonspecific antidiarrheal therapy: No prospective or randomized studies were identified. Results of two large retrospective studies are included in [Table - 2]. Given the relative safety of these agents and the possibility of spontaneous remission, many groups have suggested that these agents should be the first-line therapy for MC.[11]
  2. Mesalamine or sulfasalazine: No prospective or randomized studies have been done. Results of the two large retrospective studies are summarized in [Table - 2].
  3. Bismuth subsalicylate: A prospective open-labeled study has been published examining the use of eight chewable 262 mg bismuth subsalicylate tablets per day for 8 weeks in patients with microscopic colitis (7 of whom with CC).[17] In this study, of the 12 patients who completed the trial, 11 patients had resolution of diarrhea and a reduction in fecal weight after an average duration of 2 weeks. In 9 patients the histological changes resolved. After a follow-up period of 7-28 months, 9 patients remained well, 2 required re-treatment and 1 had continuance diarrhea. The same group later reported the results of a randomized study in which 14 patients with microscopic colitis were included (9 with CC). Seven patients were randomized to bismuth (same dose as above) and 7 to placebo. The patients were then crossed over, and post-treatment sigmoidoscopy and biopsy were performed. Overall, the treatment was effective in 12 of the 13 patients who completed the trial, with 9 patients achieving long-term remission. No significant side effects or toxicities were reported. Based on the above encouraging results, bismuth is suggested as a second-line therapy after antidiarrheals for patients with CC.[18]
  4. Corticosteroids: No prospective or randomized studies have been done. Patients refractory to the above therapies should be treated with a short course of steroids. Most patients will have a positive response to therapy, but the relapse rate is high.[17]
  5. Budesonide: In a recent systematic review, a total of 94 patients enrolled in three randomized trials studying budesonide (9 mg daily for 6 to 8 weeks) were reviewed. The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients.[18] These results are very encouraging; therefore, budesonide should also be considered as a second-line therapy in patients who do not respond to simple antidiarrheal therapy.
  6. Bile acid binders: A recent study by Ung et al. found that 44% of patients with CC had an abnormal Se-momocholic acid taurine test (SeHCAT test), suggesting some element of bile acid malabsorption.[21] They then treated all the patients (normal and abnormal SeHCAT tests) with open-labeled cholestyramine at a dose of 4 g per day or colestipol at a dose of 5 g per day as bile acid binders. This was followed by a rapid, marked or complete improvement in 78% of patients. Rapid improvement occurred in 92% of the patients who had an abnormal SeHCAT test, indicating bile acid malabsorption, and in 67% of patients with normal test. In their large series, Bohr et al. report a 59% response rate to cholestyramine.
  7. Immune modulatory therapy: Recently, Pardi et al. reported retrospective analyses of all the patients treated at the Mayo Clinic for microscopic colitis with Azathioprine and 6-Mercaptopurine.[22] Nine patients with microscopic colitis were identified, 6 of whom had CC. Patients were either refractory to steroids or dependent on steroids. Four of the eight patients who were on steroids had resolution of diarrhea and withdrawal of steroids. The other patients were able to taper or discontinue steroids successfully but had mild residual diarrhea. Severe diarrhea persisted in one patient, requiring an ileostomy. In another study, methotrexate treatment for concomitant rheumatoid arthritis has been associated with a positive clinical response in two patients.[21]



   Conclusion Top


Microscopic colitis in both of its forms, collagenous and lymphocytic, is a relatively common and significant cause of diarrhea in middle-aged and elderly patients. Other causes of chronic diarrhea must be ruled out and then sigmoidoscopy performed for colonic biopsies. Once the diagnosis of MC is confirmed and other associated disease states ruled out, a stepwise approach with medical therapy is suggested.

 
   References Top

1.Pardi DS, Smyrk TC, Tremaine WJ, Sandborn WJ. Microscopic colitis: A review. Am J Gastroenterol 2002;97:794-802.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Bohr J, Olesen M, Tysk C, Jarnerot G. Collagenous and lymphocytic colitis: A clinical and histopathological review. Can J Gastroenterol 2000;14:943-7.  Back to cited text no. 2  [PUBMED]  
3.Fernandez-Banares F, Salas A, Forne M, Esteve M, Espinos J, Viver JM. Incidence of collagenous and lymphocytic colitis: A 5-year population-based study. Am J Gastroenterol 1999;94:418-23.  Back to cited text no. 3  [PUBMED]  
4.Bohr J, Tysk C, Eriksson S, Jarnerot G. Collagenous colitis in Orebro, Sweden, an epidemiological study 1984-1993. Gut 1995;37:394-7.  Back to cited text no. 4  [PUBMED]  
5.Abdo A, Raboud J, Freeman HJ, Zetler P, Tilley J, Chaun H, et al . Clinical and histological predictors of response to medical therapy in collagenous colitis. Am J Gastroenterol 2002;97:1164-8.  Back to cited text no. 5    
6.Olesen M, Eriksson S, Bohr J, Jδrnerot G, Tysk C. Microscopic colitis: A common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut 2004;53:346-50.  Back to cited text no. 6    
7.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. 7  [PUBMED]  [FULLTEXT]
8.Harewood GC, Olson JS, Mattek NC, Holub JL, Lieberman DA. Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: Results from a national endoscopic database. Gastrointest Endosc 2005;61:371-5.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Essid M, Kallel S, Ben Brahim E, Chatti S, Azzouz MM. Prevalence of the microscopic colitis to the course of the chronic diarrhea: About 150 cases. Tunis Med 2005;83:284-7.  Back to cited text no. 9  [PUBMED]  
10.Olesen M, Eriksson S, Bohr J, Ja¨rnerot G, Tysk C. Lymphocytic colitis: A retrospective clinical study of 199 Swedish patients. Gut 2004;53:536-41.   Back to cited text no. 10    
11.Bohr J, Tysk C, Eriksson S, Abrahamsson H, Jarnerot G. Collagenous colitis: A retrospective study of clinical presentation and treatment in 163 patients. Gut 1996;39:846-51.  Back to cited text no. 11  [PUBMED]  
12.Fine KD, Meyer RL, Lee EL. The prevalence and causes of chronic diarrhea in patients with celiac sprue treated with a gluten-free diet. Gastroenterology 1997;112:1830-8.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Abdo AA, Zetler PJ, Halparin LS. Familial microscopic colitis. Can J Gastroenterol 2001;15:341-3.  Back to cited text no. 13  [PUBMED]  
14.Lazenby AJ, Yardley JH, Giardiello FM, Jessurun J, Bayless 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. 14  [PUBMED]  
15.Chang F, Deere H, Vu C. Atypical forms of microscopic colitis: Morphological features and review of the literature. Adv Anat Pathol 2005;12:203-11.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]
16.Fine KD, Lee EL. Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis. Gastroenterology 1998;114:29-36.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Fernandez-Banares F, Salas A, Esteve M, Espinos J, Forne 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. 17    
18.Nielsen OH, Schaffalitzky de Muckadell OB. Treatment of collagenous colitis. An analysis of a systematic Cochrane review. Ugeskr Laeger 2003;165:3154-6.  Back to cited text no. 18    
19.Halaby IA, Rantis PC, Vernava AM 3rd, Longo WE. Collagenous colitis: Pathogenesis and management. Dis Col Rectum 1996;39:573-8.   Back to cited text no. 19  [PUBMED]  
20.Zins BJ, Tremaine WJ, Carpenter HA. Collagenous colitis: Mucosal biopsies and association with fecal leukocytes. Mayo Clin Proc 1995;70:430-3.   Back to cited text no. 20  [PUBMED]  
21.Ung KA, Kilander A, Nilsson O, Abrahamsson H. Long-term course in collagenous colitis and the impact of bile acid malabsorption and bile acid sequestrants on histopathology and clinical features. Scand J Gastroenterol 2001;36:601-9.  Back to cited text no. 21  [PUBMED]  
22.Pardi DS, Loftus EV Jr, Tremaine WJ, Sandborn WJ. Treatment of refractory microscopic colitis with azathioprine and 6-mercaptopurine. Gastroenterology 2001;120:1483-4.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]

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Correspondence Address:
Ahmad Al Malki
Division of Gastroenterology, Department of Medicine, Riyadh Military Hospital, Riyadh
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-3767.29756

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This article has been cited by
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[Pubmed] | [DOI]
2 Improving the detection rate of microscopic colitis by introducing a colonoscopy quality-assurance programme
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