Indeterminate Colitis

INDETERMINATE COLITIS • • • • • Term first described by Price in 1978 to patients in whom it was impossible to distinguish between Ulcerative Colitis (UC) and Crohn’s Disease (CD) Originally temporary until final pathology could establish a diagnosis, nowadays used after endoscopic, histologic and radiologic criteria fail to discriminate UC or CD of the colon. Thought to be a third entity by a group Incidence: 2-16% of all IBD. Ratio M:F is 1 Do patients with initial diagnosis of IC express the features of UC or CD? o Moum et al. prospective study with 50% of IC reclassified as UC (2/3) and CD (1/3) after 1-2 years. o Wells et al. 16/46 patients after surgery were left with diagnosis of IC, followed for 10 years 12/16 maintained diagnosis of IC, 3 UC and 1 CD. Pathologic features • Fulminant UC with fissures, transmural inflammation and rectal sparing • Insufficient clinical, radiological and pathologic info to establish UC or CD • Failure to accept “hard” criteria, such as, transmural inflammation, granulomas, deep fissuring ulceration, ileal involvement or segmental disease as representative of CD • Failure to recognize unusual variants of UC: CD-like patchiness, with relative rectal sparing, right sided involvement of patients with left sided UC • Other forms, such as, pseudomembranous, ischemic and infectious colitis may simulate IBD • Inter-observer variability Serologic Markers • Perinuclear antineutrophil cytoplasmic antibodies (pANCA) are found in 60-80% of patients with UC and a subgroup of UC-like CD (diffuse left side colitis like rectal bleeding, urgency, mucus discharge) • Antibodies against cell wall oligomannosidic epitopes of Saccaromyces cerevisiae (ASCA) appear in approx. 60% of CD patients • 97 patients - prospective study. ASCA+/pANCA- (sensitivity 66.7%, specificity 77.8) is predictive of CD in 80% and ASCA-/pANCA+ (sensitivity 77.8%, specificity 66.7) is predictive of UC or UC-like CD in all patients but cannot differentiate between them. • Retrospective multicenter study: specificity to distinguish between UC and CD 92-98% and sensitivity 44-57% • Do ASCA-/pANCA- patints represent a yet-undefined clinicoserological subgroup? 144 Diagnostic criteria (Matsui et al., follow-up 6years, n=735, with 23 patients as IC) • UC: at least 3 o History of diarrhea or blood or pus in the stool o macroscopic appearance on endoscopy or mucosal inflammation affecting the rectum in continuity with some or all the colon o microscopic features in the biopsy specimen compatible with UC o No suspicion of CD on SB radiography, ileocolonoscopy or biopsy. • CD: one or more o Intestinal longitudinal ulcer or deformity induced by ulcer or cobblestone pattern o Intestinal small aphtous ulceration arranged in a longitudinal fashion for at least 3 months plus noncaseating granulomas (NCG) o Multiple small aphtous ulcerations in both the uppers and lower digestive tract, not necessarily with longitudinal arrangement for at least 3 months plus NCG IC: 3 clinical patterns according to clinical course and final diagnosis: o UC changing to CD with UC-like presentation preceding definite CD (34.8%) o CD changing to UC with CD-like presentation preceding definite UC (21.8%) o UC or CD with coexisting UC and CD-like presentations (43.4%) • Medical treatment • No randomized studies • Approach to medical treatment has more to do with anatomic distribution of dz. And severity of relapse • 5-ASA suppositories and/or topical steroid for proctitis or proctosigmoiditis • 5-ASA or sulfasalazine for moderate for moderate actively dz. • Oral steroids for moderate-severe disease (not helpful in maintaining a remission in colonic disease) • For cases of steroid-refractory or steroid-dependent disease: the use of 6-MP or azathioprine may be necessary to maintain a long-term remission. Remicade for steroid dependent steroid refractory cases in conjunction with 6-MP/azathioprine. Surgical treatment • Does this patient with IC have or has had in the past perianal disease? If so, IPAA not recommended due to complications. However, UC patients may present it, with anastomotic leak or postoperative perianal complication rate increased but IPAA is still an option. • Mayo Clinic experience: wait for frozen pathology of the abdominal colon and proceed with IPAA if UC or IC, if unequivocal CD then complete proctocolectomy and perform Brooke ileostomy • IPAA success rate over 20 years in IC 73-85% compared to definitive UC rate of 89% • Complications (n=1519, 1437 UC and 82 IC over 10 years) o Pelvic sepsis 17% IC vs. 7% UC o Pouch fistula 31% vs. 9% o Pouch failure 27% vs. 11% 145 References • Joossens et al. The Value of Serologic Markers in Indeterminate Colitis: A Prospective Follow-up study. Gastroenterology 2002. • Plevy, S. Do Serological Markers and Cytokines Determine the Indeterminate?. J. Clin. Gastroenterol. May/June 2004. • Wolff, B. Is Ileoanal the Proper Operation for Indeterminate Colitis: The Case For. IBD Sep 2002. • Shoetz, D. Jr. Is Ileoanal the Proper Operation for Indeterminate Colitis: The Case Against. IBD Sep 2002. • Burakoff, R. Indeterminate Colitis: Clinical Spectrum of Disease. J. Clin. Gastroenterol. May/June 2004 • Rudolph, W. et al. Indeterminate Colitis: The Real Story. Dis Colon Rectum, Nov 2002. • Matsui, T. et al. Clinical Features and Pattern of Indeterminate Colitis: Crohn’s Disease with Ulcerative Colitis-like Clinical Presentation. J Gastroenterol 2003. • Odze, R. Pathology of Indeterminate Colitis. J Clin Gastroenterol May/June 2004 Luciano Fiszer, M.D. August 19, 2004 146