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• W2126861738 abstract "Chronic diarrhea continues to be a diagnostic challenge for gastroenterologists, largely because of the vast number of conditions included in its differential diagnosis. While the clinical history remains an indispensable part of sorting through the differential diagnosis, testing of various kinds is essential for making a specific diagnosis.1Fine K.D. Schiller L.R. AGA technical review on the evaluation and management of chronic diarrhea.Gastroenterology. 1999; 116: 1464-1486Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar, 2Schiller L.R. Chronic diarrhea.Gastroenterology. 2004; 127: 287-293Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar One of the most useful techniques is visualization of the colonic mucosa endoscopically with biopsy of the mucosa to look for histologic evidence of disease. In this issue of Gastrointestinal Endoscopy, Harewood et al.3Harewood G.C. Olson J.S. Mattek N.C. Holub J.L. Lieberman D.A. Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic database.Gastrointest Endosc. 2005; 61: 371-375Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar review the practice of physicians contributing to the Clinical Outcome Research Initiative (CORI) database in obtaining colonic biopsy specimens in patients with chronic diarrhea who do not have gross findings with colonoscopy. Across the board, about 80% of patients, in a variety of settings, had colonic biopsy specimens made when there was chronic diarrhea with no gross findings at colonoscopy. Is that too many or too few? To answer that question, we must consider what diseases we are looking for with biopsies in patients with chronic diarrhea who have normal gross appearances in the colon. The most common of these is microscopic colitis. This syndrome, which includes lymphocytic colitis and collagenous colitis as subtypes, has been recognized as a leading cause of chronic watery diarrhea.4Fernandez-Banares F. Salas A. Esteve M. Espinos J. Forne M. Viver J.M. Collagenous and lymphocytic colitis. Evaluation of clinical and histological features, response to treatment, and long-term follow-up.Am J Gastroenterol. 2003; 98: 340-347Crossref PubMed Google Scholar, 5Pardi D.S. Microscopic colitis.Mayo Clin Proc. 2003; 78: 614-616Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 6Schiller L.R. Diagnosis and management of microscopic colitis syndrome.J Clin Gastroenterol. 2004; 38: S27-S30Crossref PubMed Scopus (26) Google Scholar, 7Olesen M. Eriksson S. Bohr J. Jarnerot G. Tysk C. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998.Gut. 2004; 53: 346-350Crossref PubMed Scopus (267) Google Scholar, 8Muller M. Willen R. Stotzer P.O. Colonoscopy and SeHCAT for investigation of chronic diarrhea.Digestion. 2004; 69: 211-218Crossref PubMed Scopus (18) Google Scholar Much has been learned about this condition in the nearly 30 years since collagenous colitis was first described. The histopathology has been described in great detail, including a paucicellular form that does not have as dramatic findings as the classical forms.9Goldstein N.S. Bhanot P. Paucicellular and asymptomatic lymphocytic colitis: expanding the clinicopathologic spectrum of lymphocytic colitis.Am J Clin Pathol. 2004; 122: 405-411Crossref PubMed Google Scholar We now recognize that microscopic colitis may occur as a side effect of treatment with drugs, including proton pump inhibitors and nonsteroidal anti-inflammatory drugs.10Thomson R.D. Lestina L.S. Bensen S.P. Toor A. Maheshwari Y. Ratcliffe N.R. Lansoprazole-associated microscopic colitis: a case series.Am J Gastroenterol. 2002; 97: 2908-2913PubMed Google Scholar, 11Yagi K. Nakamura A. Sekine A. Watanabe H. Nonsteroidal anti-inflammatory drug-associated colitis with a histology of collagenous colitis.Endoscopy. 2001; 33: 629-632Crossref PubMed Scopus (44) Google Scholar Effective treatments have been defined.2Schiller L.R. Chronic diarrhea.Gastroenterology. 2004; 127: 287-293Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 4Fernandez-Banares F. Salas A. Esteve M. Espinos J. Forne M. Viver J.M. Collagenous and lymphocytic colitis. Evaluation of clinical and histological features, response to treatment, and long-term follow-up.Am J Gastroenterol. 2003; 98: 340-347Crossref PubMed Google Scholar, 5Pardi D.S. Microscopic colitis.Mayo Clin Proc. 2003; 78: 614-616Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar, 6Schiller L.R. Diagnosis and management of microscopic colitis syndrome.J Clin Gastroenterol. 2004; 38: S27-S30Crossref PubMed Scopus (26) Google Scholar, 12Miehlke S. Heymer P. Bethke B. Bastlein E. Meier E. Bartram H.P. et al.Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial.Gastroenterology. 2002; 123: 978-984Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar Other conditions that might produce histologic abnormalities without gross changes in the mucosa include the occasional case of Crohn's disease; colonic ischemia; celiac disease; vasculitis; and rare conditions, such as amyloidosis or mast-cell disease. There is no single clinical criterion (such as stool output) that can be used instead of mucosal biopsy to distinguish microscopic colitis or any of these other conditions from irritable bowel syndrome with diarrhea. Microscopic colitis is the most common diagnosis to be made histologically in patients with chronic diarrhea who have normal mucosa on gross inspection. Two recent surveys from Sweden suggest that 10% to 15% of all patients evaluated for chronic diarrhea with colonoscopy have microscopic colitis,7Olesen M. Eriksson S. Bohr J. Jarnerot G. Tysk C. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998.Gut. 2004; 53: 346-350Crossref PubMed Scopus (267) Google Scholar, 8Muller M. Willen R. Stotzer P.O. Colonoscopy and SeHCAT for investigation of chronic diarrhea.Digestion. 2004; 69: 211-218Crossref PubMed Scopus (18) Google Scholar and one of these suggested that the annual incidence is similar to that of Crohn's disease.7Olesen M. Eriksson S. Bohr J. Jarnerot G. Tysk C. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998.Gut. 2004; 53: 346-350Crossref PubMed Scopus (267) Google Scholar There would seem to be no question that patients with chronic diarrhea who are subjected to colonoscopy and who have normal gross findings should have the colon biopsied to look for microscopic colitis. This has been the general consensus of experts in the field.1Fine K.D. Schiller L.R. AGA technical review on the evaluation and management of chronic diarrhea.Gastroenterology. 1999; 116: 1464-1486Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar, 13Bernstein C.N. Riddell R.H. Colonoscopy plus biopsy in the inflammatory bowel disorders.Gastrointest Endosc Clin N Am. 2000; 10: 755-774PubMed Google Scholar, 14Shah R.J. Fenoglio-Preiser C. Bleau B.L. Giannella R.A. Usefulness of colonoscopy with biopsy in the evaluation of patients with chronic diarrhea.Am J Gastroenterol. 2001; 96: 1091-1095Crossref PubMed Google Scholar, 15Yusoff I.F. Ormonde D.G. Hoffman N.E. Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea.J Gastroenterol Hepatol. 2002; 17: 276-280Crossref PubMed Scopus (66) Google Scholar Thus, the answer to the question posed before is that all patients undergoing colonoscopy for the evaluation of chronic diarrhea should have biopsy specimens made and that too few patients in the CORI study were biopsied.Which patients with chronic diarrhea should undergo colonoscopy, and how should the biopsies be obtained? Which patients with chronic diarrhea should undergo colonoscopy, and how should the biopsies be obtained? This begs two other questions that are important to answer: which patients with chronic diarrhea should have colonoscopy, and how should the biopsy specimens be obtained? In 1999, Kenneth Fine and I reviewed the evaluation of chronic diarrhea for the American Gastroenterological Association and formulated the recommendation that the first endoscopic test in patients with chronic watery diarrhea should be flexible sigmoidoscopy with biopsies, not colonoscopy with biopsies.1Fine K.D. Schiller L.R. AGA technical review on the evaluation and management of chronic diarrhea.Gastroenterology. 1999; 116: 1464-1486Abstract Full Text Full Text PDF PubMed Scopus (281) Google Scholar This was based on the concept that most diseases producing watery diarrhea (as opposed to diarrhea with “inflammatory” characteristics, such as blood or pus) involved the colon diffusely and that biopsy specimens from the left colon were as likely to be positive as those from the right colon. Certainly this is true for microscopic colitis if sufficient numbers of biopsy specimens are taken from the left colon.16Lee E. Schiller L.R. Fordtran J.S. Quantification of colonic lamina propria cells by means of a morphometric point-counting method.Gastroenterology. 1988; 94: 409-418PubMed Google Scholar, 17Lee E. Schiller L.R. Vendrell D. Santa Ana C.A. Fordtran J.S. Subepithelial collagen table thickness in colon specimens from patients with microscopic colitis and collagenous colitis.Gastroenterology. 1992; 103: 1790-1796PubMed Google Scholar Fewer than 10% of patients with microscopic colitis would be missed by obtaining biopsy specimens only from the left colon. Many other conditions that cause diarrhea and gross changes in the colonic mucosa, such as ulcerative colitis, also would be likely to be encountered during sigmoidoscopy. This concept then was tested prospectively in a study by Fine et al.18Fine K.D. Seidel R.H. Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea.Gastrointest Endosc. 2000; 51: 318-326Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar; a correct histologic diagnosis could have been reached in 99.7% of patients presenting with chronic diarrhea with distal colonic biopsies only.18Fine K.D. Seidel R.H. Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea.Gastrointest Endosc. 2000; 51: 318-326Abstract Full Text Full Text PDF PubMed Scopus (141) Google Scholar Thus, flexible sigmoidoscopy (a procedure now infrequently done by gastroenterologists) would be adequate for diagnosis in most cases. Nevertheless, as shown in the study by Harewood et al.,3Harewood G.C. Olson J.S. Mattek N.C. Holub J.L. Lieberman D.A. Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic database.Gastrointest Endosc. 2005; 61: 371-375Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar colonoscopy still is being done by many gastroenterologists to evaluate chronic diarrhea. I believe that this is because of the concept that “something” might be missed in the right colon or the ileum if a complete colonoscopy with ileoscopy is not done. Certainly, this is a risk if other diagnostic testing (such as radiographic tests) does not complement the sigmoidoscopic examination in appropriate patients. Also, older patients and those with blood or pus in the stool should have a complete colon examination, because the possibility of colonic or ileal pathology is much greater in those situations. There, however, are many young patients with “chronic diarrhea” who have irritable bowel syndrome with diarrhea and who do not need to have colonoscopy. The clinical challenge is to sort these patients. This can be done by applying a criteria-based diagnosis that emphasizes the concurrence of abdominal pain with altered bowel habit19Adeniji O.A. Barnett C.B. Di Palma J.A. Durability of the diagnosis of irritable bowel syndrome based on clinical criteria.Dig Dis Sci. 2004; 49: 572-574Crossref PubMed Scopus (30) Google Scholar and by excluding patients with intermittent diarrhea (as opposed to those with continuous diarrhea) from consideration for colonoscopy. If colonoscopy is done in patients with chronic diarrhea, the terminal ileum should be visualized to look for gross evidence of infection or inflammation. Normal-appearing ileal mucosa need not be biopsied, because, unlike the colon—random biopsy of normal-appearing ileal mucosa does not have a very high yield.15Yusoff I.F. Ormonde D.G. Hoffman N.E. Routine colonic mucosal biopsy and ileoscopy increases diagnostic yield in patients undergoing colonoscopy for diarrhea.J Gastroenterol Hepatol. 2002; 17: 276-280Crossref PubMed Scopus (66) Google Scholar The other issue is how to obtain biopsy specimens from the colon. I believe that the key to a proper histologic diagnosis is to provide the pathologist with a large number of biopsy specimens. Although a formal study has not been completed, I think that at least 12 specimens should be obtained from the left colon (and the right colon, if examined) to give the pathologist a good chance of making a diagnosis. It is not necessary to place biopsy specimens from different regions of the suprarectal colon in separate containers, because the mucosa is similar throughout that part of the colon.17Lee E. Schiller L.R. Vendrell D. Santa Ana C.A. Fordtran J.S. Subepithelial collagen table thickness in colon specimens from patients with microscopic colitis and collagenous colitis.Gastroenterology. 1992; 103: 1790-1796PubMed Google Scholar (Biopsy specimens of the rectal mucosa ordinarily have a slightly thicker submucosal collagen table than other regions of the colon17Lee E. Schiller L.R. Vendrell D. Santa Ana C.A. Fordtran J.S. Subepithelial collagen table thickness in colon specimens from patients with microscopic colitis and collagenous colitis.Gastroenterology. 1992; 103: 1790-1796PubMed Google Scholar and should be segregated from other biopsy specimens.) Much of the regional variability of histology reported previously could be because of inadequate sampling. Use of the proper colon preparation also may be important. Hypertonic preparations may produce histologic artifacts on biopsy specimens that can mimic some of the changes of microscopic colitis.20Pockros P.J. Foroozan P. Golytely lavage versus a standard colonoscopy preparation. Effect on normal colonic mucosal histology.Gastroenterology. 1985; 88: 545-548PubMed Google Scholar Use of an isotonic preparation solution may minimize histologic artifacts that can confuse the pathologist.21Schmelzer M. Schiller L.R. Meyer R. Rugari S.M. Case P. Safety and effectiveness of large-volume enema solutions.Appl Nurs Res. 2004; 17: 265-274PubMed Scopus (43) Google Scholar When faced with a patient with chronic watery diarrhea who does not have irritable bowel syndrome by clinical criteria, biopsy specimens should be obtained from the colon. Sigmoidoscopy could be used in young patients without blood or pus in their stools and colonoscopy in older patients or those with alarm findings that would mandate a complete colon examination. Enough biopsy specimens should be obtained to give the pathologist a reasonable chance of making the right diagnosis. Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic databaseGastrointestinal EndoscopyVol. 61Issue 3PreviewThe colonic biopsy is the only reliable method for identification of microscopic colitis in patients with chronic diarrhea and normal endoscopic findings. Full-Text PDF" @default.
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