The frequency of microscopic and focal active colitis in patients with irritable bowel syndrome
© Ozdil et al; licensee BioMed Central Ltd. 2011
Received: 17 April 2011
Accepted: 31 August 2011
Published: 31 August 2011
Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. The frequency of microscopic colitis and focal active colitis in the colonic mucosa has been investigated in IBS patients.
Between June 2007 and September 2010, 378 patients (between 16 and 84 years) were recruited prospectively. Of these 378 patients, 226 patients were diagnosed with IBS using the Rome III criteria. 152 control patients were also enrolled who were undergoing colonoscopy for colorectal cancer screening or investigation of anemia. Histopathological abnormalities identified during colonoscopy were compared between the IBS and control groups.
The average age of the IBS group was 46.13 ± 14.16 years and and the average age of the control group was 57.01 ± 13.07 years. The prevalence of microscopic colitis (MC) in the diarrhea predominant and the mixed subgroup of IBS patients was 4.32% (7/162) whereas in all IBS patients, the prevalence was 3.09% (7/226). MC was not found in the 152 control cases, (p = 0.045). Lymphocytic colitis was seen in 7 IBS patients, with 1 case in the mixed group and 6 cases in the diarrhea group and there was a significant difference in the frequency of lymphocytic colitis between the IBS subgroups (p < 0.01). Focal active colitis was found in 6.6% (15/226) of the IBS patients and in none of the controls (p < 0.01), and there was no differences between IBS subtypes.
Microscopic colitis was more often found in the diarrhea predominant/mixed subgroups of IBS patients and in patients who were older women. In patients who are older woman with non-constipated IBS, it may be reasonable to perform a biopsy to screen for microscopic colitis. Focal active colitis was significantly increased in patients with IBS compared to controls.
Keywordsirritable bowel syndrome microscopic colitis focal active colitis
Irritable bowel syndrome (IBS) is a functional bowel disorder of unknown etiology without a curative treatment. In addition to abdominal discomfort and pain, relief from discomfort upon defecation and/or abdominal pain is associated with a change in the frequency of defecation and/or in the form of the feces . The prevalence of IBS varies in different populations. The prevalence of IBS in Turkey was found 7.4-19.1% with female percentage between 64% and 69% [2, 3]. Similar rates have been reported in the USA and Europe and range between 6.2% and 25% [4, 5]. Although the specific location and the pattern of symptoms varies among different functional gastrointestinal diseases, there are also many common characteristics . A small percentage of patients with IBS are referred to outpatient gastroenterology clinics.
In 1980, microscopic colitis (MC) was defined as having symptoms of watery diarrhea and specific histological characteristics when the colonic mucosa is macroscopically normal or near normal . Currently, MC is divided into two subtypes- collagenous colitis (CC) involving chronic mucosal inflammation and a wide subepithelial band and lymphocytic colitis (LC) involving chronic mucosal inflammation and no subepithelial band. In 1976, Lindstrom showed for the first time that collagen deposits accumulated as a wide subepithelial band in the rectum and colon in patients with persistent watery diarrhea of unknown cause . Some experts claim that LC is an early phase of CC [9–11]. In Europe, the annual incidence of CC is 0.6-2.3/100000 and the prevalence is 10-15.7/100000 whereas the annual incidence of LC is 3.1/100000 and the prevalence is 14.4/100000 [12–16]. MC and IBS have similar symptoms. MC not only leads to diarrhea but also causes constipation. Constipation may be short-term or chronic [17, 18].
Focal active colitis (FAC) is characterized by focal crypt damage caused by neutrophils and may be associated with infections, ischemia, Crohn's disease, partially-treated ulcerative colitis and IBS . It may consist of one focus that can be detected in a single biopsy, or multiple foci. Since focal inflammation is a feature of Crohn's disease, studies of FAC have examined whether it precedes the subsequent development or diagnosis of Crohn's disease. In two studies of adult patients with FAC, it was observed that very few developed Crohn's disease [19, 20]. However, in a group of pediatric patients with FAC, a higher proportion (27.6%) went on to develop Crohn's disease .
The purpose of this study was to determine histopathologically the frequency of underlying organic causes of IBS, including MC and FAC, in macroscopically normal colonic mucosa.
Between June 2007 and September 2010, 378 patients (between 16 and 84 years) were recruited into the study prospectively. Two hundred and twenty six of these patients were diagnosed with IBS using the Rome III criteria and had no alarm symptoms, no chronic disease history and had macroscopically normal colonoscopy/upper gastrointestinal system endoscopic findings. There were 152 control patients who had no history of chronic disease or drug use, who were undergoing colonoscopy for reasons not related to IBS (familial colorectal cancer screening or investigation of anemia) and who had macroscopically normal colonic mucosa.
Alarm features considered potentially relevant in the diagnosis of organic disease as opposed to Irritable Bowel Syndrome
Family history of colon cancer, inflammatory bowel disease, or celiac disease
Night-time symptoms (awakening the patient from sleep)
Signs of anemia
Biopsy specimens were sent to the pathology laboratory in 10% formol solution. All biopsy samples were evaluated by two pathologists who specialized in the gastrointestinal system. Paraffin blocks were cut into 5 μm thick sections and stained with hematoxylin-eosin (H&E) and Gomori's trichrome stain. A diagnosis of lymphocytic colitis required an increase in intraepithelial lymphocytes to more than 15 lymphocytes/100 epithelial cells, surface epithelial damage with increased lamina propria, plasma cells and absent or minimal crypt architectural disruption. For a diagnosis of collagenous colitis, an increase/irregularity in subepithelial collagen (> 10 μm) that typically trapped superficial capillaries was required as well as the other inflammatory changes seen in lymphocytic colitis . Focal active colitis is the term used to describe focal neutrophilic infiltration of colonic crypts. It may consist of one focus in a single biopsy, or multiple foci .
The study protocol was approved by our Institutional (Umraniye Training and Research Hospital) Research Ethics Committee and informed consent was obtained from each subject.
Statistical analysis was performed using NCSS (Number Cruncher Statistical System) 2007 & PASS (Power Analysis and Sample Size) 2008 Statistical Software (Utah, USA), SPSS version 11.0 and Microsoft Excel. Statistical comparisons of findings between the IBS and control groups were performed by χ2 or Fisher's exact test. Logistic regression was used to adjust for differences in age and gender between groups. A p < 0.05 was considered statistically significant.
Demographic and pathological data of IBS and control patients
IBS (n = 226)
Control (n = 152)
a Age; Mean ± SD
46.13 ± 14.16
57.01 ± 1.,07
b Gender (female, %)
b Lymphoscytic colitis
b Focal active colitis
Demographic and pathological data of IBS subgroups
IBS-C (n = 64)
IBS-M (n = 90)
IBS-D (n = 72)
α Age (Mean ± SD)
43.54 ± 13.17
47.53 ± 13.54
46.68 ± 15.57
b Gender (female,%)
β Lymphochytic colitis n (%)
β Focal active colitis n (%)
Demografic characteristics of patients with lymphocytic colitis and focal active colitis
(Mean age: 60.5)
Focal active colitis
(Mean age: 45.7)
Focal active colitis was found in 6.6% (15/226) of IBS patients and in none of the controls (p < 0.01). There was no significant difference among the incidence of focal active colitis according to IBS subtype (p > 0.05), although there was a higher incidence in the mixed group. Of the patients with FAC, 1.6% (1/64) were in the constipation predominant group, 11.1% (10/90) were in the alternate group and 5.6% (4/72) were in the diarrhea predominant group (Table 2).
IBS is a public health problem since it is widely seen and does not have a cure . Some experts claim that LC is a precursor to CC [9–11]. A previously published study evaluated 89 patients suspected to have IBS and 59 controls using flexible sigmoidoscopy and rectal biopsy. These authors reported that no IBS patients or controls had macroscopic or microscopic findings that resulted in a change in diagnosis. Specifically, the authors identified no patients or controls with microscopic colitis. But according to recently published a study by Kao et al. in which a total of 547 cases of MC were examined, MC had a higher occurrence in IBS than in controls (P < 0.001). Conditions such as celiac disease, IBS, and thyroid disease were found to be related to MC. Furthermore, neither an increased risk of colorectal cancer nor IBD was associated with MC . Chey et al. found that colonoscopy and colonic mucosal biopsies were able to identify an alternative diagnosis in 1.9% (9/466) of non-constipated IBS patients . Of these nine patients, seven had microscopic colitis, one had Crohn's disease, and one had ulcerative colitis. The overall prevalence of microscopic colitis was found to be 1.5% in a large cohort of non-constipated IBS patients. In a subgroup analysis of IBS patients over the age of 45, the prevalence of microscopic colitis was 2.3% (4/171). In our study we found that all subjects with microscopic colitis were at least 49 years old and microscopic colitis was seen in 4.32% (7/126) of non-constipated IBS patients and in 3.1% of all IBS patients (7/226). All MC patients were over 45 years old and the average age was 62 ± 8. Limsui et al. found that 56% of the 131 patients diagnosed with microscopic colitis fulfilled the Rome III criteria for IBS and that 33% had been diagnosed with IBS before receiving the diagnosis of microscopic colitis. Therefore, patients with suspected diarrhea-predominant IBS should undergo biopsies of the colon to investigate possible microscopic colitis if symptoms are not well controlled by anti-diarrheal therapy .
A retrospective study found that 11% (43/376) of patients with LC and 18% (30/171) of patients with CC had been diagnosed with IBS before receiving the diagnosis of MC . In two large studies of patients with MC, the mean age of diagnosis was found to be in the seventh decade [27, 29]. A recent review on this topic suggested that between 18% and 34% of patients with collagenous colitis may not be identified if only rectosigmoid biopsies are obtained .
IBS has 3 subtypes according to its clinical course (constipation predominant, diarrhea predominant and mixed). IBS can be differentiated from MC only by histopathological investigation. Symptoms of MC are often attributed to diarrhea predominant IBS . In view of this information, the present study explored if mucosal pathology, including MC, could be identified in IBS patients using microscopic evaluation, given that macroscopically, the colonic mucosa was normal.
Microscopic colitis is a rare disease [12–16]. However, Tuncer et al. reported that there is a 23.3% MC prevalence in IBS patients compared to a 5% prevalence in controls . According to a study by Olesen et al., MC was diagnosed in 10% of all Swedish patients (1018 patients) with non-bloody diarrhea referred for colonoscopy. In the subset of patients older than 70, the prevalence was almost 20% . Another study found that lymphocytic colitis was diagnosed in 199 cases. The female/male ratio was 2.4:1. The median age at diagnosis was 59 (range: 48-70) years. The most frequent symptoms were diarrhea (96%), abdominal pain (47%) and weight loss (41%). The symptom course was chronic intermittent in 30% of patients, chronic continuous in 7%, and single attack in 63%. MC patients may have constipation and there may be an association between MC and chronic constipation. Chronic constipation was found in 43.39% of MC patients in the study performed by Barta et al. [17, 26]. However, in our study, MC was not found in the constipation predominant IBS subgroup. According to the American College of Gastroenterology Task Force , "routine colonic imaging is not recommended in patients younger than 50 years of age with typical IBS symptoms and no alarm features. When colonoscopy is performed in patients with IBS-D, obtaining random biopsies should be considered to rule out microscopic colitis."
Focal active colitis is characterized by focal crypt damage caused by neutrophils and may be associated with infections, ischemia, Crohn's disease, partially-treated ulcerative colitis and IBS . There are reports that there is an association between focal active colitis and oral sodium phosphate ingestion [33–36]. Driman et al. indicated that evidence is emerging that sodium phosphate is a commonly used oral laxative agent, causes aphthoid ulcers and/or FAC in the colon and rectum. FAC was present in 11 of 316 patients (3.5%) who had biopsies but who were otherwise normal, as determined by endoscopic evaluation . In a follow-up study by Xin et al., which consisted of 29 patients who were diagnosed with focal active colitis, the disease duration ranged from 4 months to 7 years with a mean of 4.2 years. Eight patients (27.6%) developed Crohn's disease. Pediatric patients with focal active colitis have a much higher incidence of Crohn's disease than adults. Hence, it is important to document the presence of focal active colitis in pediatric patients . In this study we found that 6.6% of IBS patients had focal active colitis (15/226) and this ratio is higher than that reported in previous studies. It may be eligible take a routine biopsy in female patients and in patients over 50 years old.
We acknowledge the limitation of the study is the difference between the groups in terms of age and gender. The percentage of women with IBS is 55.3%. This percentage is close to the female:male ratio of previous studies from Turkey. The mean age of the control group was higher than the IBS patients. However, this situation was due to selection of asymptomatic patients screened for colorectal cancer and anemia.
Microscopic colitis can be identified in patients with diarrhea predominant IBS and in women of older age with IBS. It appears reasonable to test for microscopic colitis in those patients by performing a colonic biopsy. Focal active colitis was found to be more common than expected. Routine biopsy of normal colonic mucosa helps identify rare miscellaneous causes of colitis.
focal active colitis
irritable bowel syndrome
- Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müller-Lissner SA: Functional bowel disorders and functional abdominal pain. Gut. 1999, 45 (Suppl 2): II43-7.PubMedPubMed CentralGoogle Scholar
- Karaman N, Turkay C, Yonem O: Irritable bowel syndrome prevalence in city center of Sivas. Turk J Gastroenterology. 2003, 14 (2): 128-31.Google Scholar
- Celebi S, Acik Y, Deveci SE, Bahcecioglu IH, Ayar A, Demir A, Durukan P: Epidemiological features of irritable bowel syndrome in a Turkish urban society. Journal of gastroenterology and hepatology. 2004, 19 (7): 738-43. 10.1111/j.1440-1746.2004.03367.x.View ArticlePubMedGoogle Scholar
- Hungin AP, Whorwell PJ, Tack J, Mearin F: The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Alimentary pharmacology & therapeutics. 2003, 17 (5): 643-50. 10.1046/j.1365-2036.2003.01456.x.View ArticleGoogle Scholar
- Jones R: Investigating lower bowel symptoms in general practice. BMJ. 1992, 304 (6841): 1521-2. 10.1136/bmj.304.6841.1521.View ArticlePubMedPubMed CentralGoogle Scholar
- Talley NJ, Spiller R: Irritable bowel syndrome: a little understood organic bowel disease?. Lancet. 2002, 360 (9332): 555-64. 10.1016/S0140-6736(02)09712-X.View ArticlePubMedGoogle Scholar
- Read NW, Krejs GJ, Read MG, Santa Ana CA, Morawski SG, Fordtran JS: Chronic diarrhea of unknown origin. Gastroenterology. 1980, 78 (2): 264-71.PubMedGoogle Scholar
- Lindstrom CG: 'Collagenous colitis' with watery diarrhoea--a new entity?. Pathologia Europaea. 1976, 11 (1): 87-9.PubMedGoogle Scholar
- Bowling TE, Price AB, al-Adnani M, Fairclough PD, Menzies-Gow N, Silk DB: Interchange between collagenous and lymphocytic colitis in severe disease with autoimmune associations requiring colectomy: a case report. Gut. 1996, 38 (5): 788-91. 10.1136/gut.38.5.788.View ArticlePubMedPubMed CentralGoogle Scholar
- Jawhari A, Talbot IC: Microscopic, lymphocytic and collagenous colitis. Histopathology. 1996, 29 (2): 101-10. 10.1046/j.1365-2559.1996.d01-498.x.View ArticlePubMedGoogle Scholar
- Mosnier JF, Larvol L, Barge J, Dubois S, De La Bigne G, Hénin D, Cerf M: Lymphocytic and collagenous colitis: an immunohistochemical study. The American journal of gastroenterology. 1996, 91 (4): 709-13.PubMedGoogle Scholar
- Pardi DS, Smyrk TC, Tremaine WJ, Sandborn WJ: Microscopic colitis: a review. The American journal of gastroenterology. 2002, 97 (4): 794-802. 10.1111/j.1572-0241.2002.05595.x.View ArticlePubMedGoogle Scholar
- Fernández-Bañares F, Salas A, Forné M, Esteve M, Espinós J, Viver JM: Incidence of collagenous and lymphocytic colitis: a 5-year population-based study. The American journal of gastroenterology. 1999, 94 (2): 418-23.View ArticlePubMedGoogle Scholar
- Olesen M, Eriksson S, Bohr J, Järnerot G, Tysk C: Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998. Gut. 2004, 53 (3): 346-50. 10.1136/gut.2003.014431.View ArticlePubMedPubMed CentralGoogle Scholar
- Bohr J, Tysk C, Eriksson S, Järnerot G: Collagenous colitis in Orebro, Sweden, an epidemiological study 1984-1993. Gut. 1995, 37 (3): 394-7. 10.1136/gut.37.3.394.View ArticlePubMedPubMed CentralGoogle Scholar
- Olesen M, Eriksson S, Bohr J, Järnerot G, Tysk C: Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients. Gut. 2004, 53 (4): 536-41. 10.1136/gut.2003.023440.View ArticlePubMedPubMed CentralGoogle Scholar
- Barta Z, Mekkel G, Csípo I, Tóth L, Szakáll S, Szabó GG, Bakó G, Szegedi G, Zeher M: Microscopic colitis: a retrospective study of clinical presentation in 53 patients. World journal of gastroenterology: WJG. 2005, 11 (9): 1351-5.View ArticlePubMedPubMed CentralGoogle Scholar
- Leigh C, Elahmady A, Mitros FA, Metcalf A, al-Jurf A: Collagenous colitis associated with chronic constipation. The American journal of surgical pathology. 1993, 17 (1): 81-4. 10.1097/00000478-199301000-00010.View ArticlePubMedGoogle Scholar
- Greenson JK, Stern RA, Carpenter SL, Barnett JL: The clinical significance of focal active colitis. Human pathology. 1997, 28 (6): 729-33. 10.1016/S0046-8177(97)90183-0.View ArticlePubMedGoogle Scholar
- Volk EE, Shapiro BD, Easley KA, Goldblum JR: The clinical significance of a biopsy-based diagnosis of focal active colitis: a clinicopathologic study of 31 cases. Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 1998, 11 (8): 789-94.Google Scholar
- Brown PI, Greenson JK: The clinical significance of focal active colitis in pediatric patients. The American journal of surgical pathology. 2003, 27 (8): 1134-8. 10.1097/00000478-200308000-00011.View ArticlePubMedGoogle Scholar
- Saito YA, Locke GR, Talley NJ, Zinsmeister AR, Fett SL, Melton LJ: A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome. The American journal of gastroenterology. 2000, 95 (10): 2816-24. 10.1111/j.1572-0241.2000.03192.x.View ArticlePubMedGoogle Scholar
- Balboa A, Mearin F, Badía X, Benavent J, Caballero AM, Domínguez-Muñoz JE, Garrigues V, Piqué JM, Roset M, Cucala M, Figueras M: Impact of upper digestive symptoms in patients with irritable bowel syndrome. European journal of gastroenterology & hepatology. 2006, 18 (12): 1271-7. 10.1097/01.meg.0000243870.41207.2f.View ArticleGoogle Scholar
- Brandt LJ, Chey WD, Foxx-Orenstein AE, Schiller LR, Schoenfeld PS, Spiegel BM, Talley NJ, Quigley EM: An evidence-based position statement on the management of irritable bowel syndrome. American College of Gastroenterology Task Force on Irritable Bowel Syndrome. The American journal of gastroenterology. 104 (Suppl 1): S1-35.
- Olden KW: Diagnosis of irritable bowel syndrome. Gastroenterology. 2002, 122 (6): 1701-14. 10.1053/gast.2002.33741.View ArticlePubMedGoogle Scholar
- Hahn B, Watson M, Yan S, Gunput D, Heuijerjans J: Irritable bowel syndrome symptom patterns: frequency, duration, and severity. Digestive diseases and sciences. 1998, 43 (12): 2715-8. 10.1023/A:1026663613695.View ArticlePubMedGoogle Scholar
- Kao KT, Pedraza BA, McClune AC, Rios DA, Mao YQ, Zuch RH, Kanter MH, Wirio S, Conteas CN: Microscopic colitis: a large retrospective analysis from a health maintenance organization experience. World journal of gastroenterology: WJG. 2009, 15 (25): 3122-7. 10.3748/wjg.15.3122.View ArticlePubMedPubMed CentralGoogle Scholar
- Chey WD, Nojkov B, Rubenstein JH, Dobhan RR, Greenson JK, Cash BD: The yield of colonoscopy in patients with non-constipated irritable bowel syndrome: results from a prospective, controlled US trial. The American journal of gastroenterology. 2010, 105 (4): 859-65. 10.1038/ajg.2010.55.View ArticlePubMedPubMed CentralGoogle Scholar
- Limsui D, Pardi DS, Camilleri M, Loftus EV, Kammer PP, Tremaine WJ, Sandborn WJ: Symptomatic overlap between irritable bowel syndrome and microscopic colitis. Inflammatory bowel diseases. 2007, 13 (2): 175-81. 10.1002/ibd.20059.View ArticlePubMedGoogle Scholar
- Yantiss RK, Odze RD: Optimal approach to obtaining mucosal biopsies for assessment of inflammatory disorders of the gastrointestinal tract. The American journal of gastroenterology. 2009, 104 (3): 774-83. 10.1038/ajg.2008.108.View ArticlePubMedGoogle Scholar
- Loftus EV: Microscopic colitis: epidemiology and treatment. The American journal of gastroenterology. 2003, 98 (12 Suppl): S31-6.View ArticlePubMedGoogle Scholar
- Tunçer C, Cindoruk M, Dursun A, Karakan T: Prevalence of microscopic colitis in patients with symptoms suggesting irritable bowel syndrome. Acta gastro-enterologica Belgica. 2003, 66 (2): 133-6.PubMedGoogle Scholar
- Driman DK, Preiksaitis HK: Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution. Human pathology. 1998, 29 (9): 972-8. 10.1016/S0046-8177(98)90203-9.View ArticlePubMedGoogle Scholar
- Lee FD: Drug-related pathological lesions of the intestinal tract. Histopathology. 1994, 25 (4): 303-8. 10.1111/j.1365-2559.1994.tb01347.x.View ArticlePubMedGoogle Scholar
- Wong NA, Penman ID, Campbell S, Lessells AM: Microscopic focal cryptitis associated with sodium phosphate bowel preparation. Histopathology. 2000, 36 (5): 476-8.PubMedGoogle Scholar
- Zwas FR, Cirillo NW, el-Serag HB, Eisen RN: Colonic mucosal abnormalities associated with oral sodium phosphate solution. Gastrointestinal endoscopy. 1996, 43 (5): 463-6. 10.1016/S0016-5107(96)70286-9.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/11/96/prepub
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