Ulcerative Colitis: Plevy SE

Long MD, Plevy SE. · Department of Medicine, Division of Gastroenterology and Hepatology, Multidisciplinary Inflammatory Bowel Disease Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. · Clin Gastroenterol Hepatol. · Pubmed #19306946 No free full text.

This publication has no abstract.

Meier CB, Hegazi RA, Aisenberg J, Legnani PE, Nilubol N, Cobrin GM, Duerr RH, Gorfine SR, Bauer JJ, Sachar DB, Plevy SE. · Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA. · Inflamm Bowel Dis. · Pubmed #16239841 No free full text.

Abstract: BACKGROUND: Pouchitis is a frequent complication after ileal pouch-anal anastamosis (IPAA) for ulcerative colitis (UC). The aim of this study was to determine whether genetic polymorphisms in the innate immune receptors toll-like receptor (TLR)4 and caspase activation and recruitment domain family member 15 (CARD15) genes are associated with pouchitis. METHODS: From a retrospectively ascertained cohort of patients with UC 5 to 12 years after IPAA (n = 101), subjects were classified into 3 groups: no pouchitis (n = 52); 1 to 2 episodes per year (n = 11), and more than 2 episodes per year (n = 38). Single nucleotide polymorphisms in the tlr4 gene (D299G, T399I) were determined by a real-time polymerase chain reaction-based fluorogenic probe technique; and card15 polymorphisms (L1007fsinsC, R702W, G908R) were determined by pyrosequencing. RESULTS: Pouchitis affected 49% (49/101) of the study population. No correlation between pouchitis and the presence of TLR4 polymorphisms was found. The percentage of patients who harbored CARD15 mutations was significantly higher in patients with pouchitis than in patients without pouchitis (18% versus 8%; P < 0.05); 24% of pouchitis patients with more than 2 episodes per year harbored CARD15 mutations (P < 0.01 compared with the no pouchitis group). The CARD15 insertion mutation L1007fsinsC was present in 14% of patients with pouchitis and in 0% without pouchitis (P < 0.05). All patients who carried L1007fsinsC developed more than 2 episodes per year. CONCLUSIONS: CARD15 polymorphisms are seen in greater frequency in patients with pouchitis after IPAA for UC. These findings, if borne out in prospective analyses, suggest that CARD15 mutations, particularly L1007fsinsC, may predispose to the development of pouchitis after IPAA for UC.

Aisenberg J, Legnani PE, Nilubol N, Cobrin GM, Ellozy SH, Hegazi RA, Yager J, Bodian C, Gorfine SR, Bauer JJ, Plevy SE, Sachar DB. · Department of Gastroenterology, Mount Sinai Medical Center, New York, USA. · Am J Gastroenterol. · Pubmed #15056081 No free full text.

Abstract: OBJECTIVE: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for ulcerative colitis. This study aims to analyze the frequency and characteristics of pouchitis in long-term follow-up in a large population, and to determine whether a significant association exists between five immunogenetic markers and pouchitis. METHODS: From a population of over 500 ulcerative colitis patients who had undergone ileal pouch-anal anastamosis 5-12 yr earlier, 102 subjects participated in the study. Using clinical data obtained from interviews and chart reviews, patients were classified into three groups: no pouchitis; 1-2 episodes per year; and >2 episodes per year. Coded sera from the patients were analyzed for ulcerative colitis-associated perinuclear antineutrophil cytoplasmic antibodies and Crohn's disease-associated anti-saccharomyces cerevesiae antibodies. Interleukin-1 receptor antagonist, tumor necrosis factor (TNF), and lymphotoxin beta (lymphotoxin) polymorphisms were also analyzed. RESULTS: Pouchitis affected 49% of the study population. Antineutrophil cytoplasmic antibodies, anti-saccharomyces cerevesiae antibodies, and lymphotoxin-beta polymorphisms were not associated with pouchitis. Carriage of interleukin-1 receptor antagonist allele 2 was significantly greater among those without pouchitis than those with pouchitis. Patients without pouchitis had a significantly greater carriage rate of TNF allele 2. CONCLUSIONS: Perinuclear antineutrophil cytoplasmic antibodies and anti-saccharomyces cerevesiae antibodies are not correlated with pouchitis, but interleukin-1 receptor antagonist and TNF may play a role in its development. Further evaluation of these markers in pouchitis will require larger populations, long-term prospective observation, and studies that correlate polymorphisms with specific immunologic functions.

Rowe FA, Walker JH, Karp LC, Vasiliauskas EA, Plevy SE, Targan SR. · Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. · Am J Gastroenterol. · Pubmed #10950049 No free full text.

Abstract: OBJECTIVE: Cyclosporin-A (CSA) has been demonstrated to be effective for treatment of severe, steroid-resistant ulcerative colitis (UC). Use of CSA has been limited, however, because of low 1-yr response rates and the potential for complications. The aim of this study is to define clinical and laboratory factors predictive of response in severe, steroid-resistant UC. METHODS: A retrospective review of 36 cases of severe, steroid-resistant UC treated with CSA was performed. Intravenous (i.v.) CSA was administered at an initial dose of 2.5 mg/kg, and oral (p.o.) CSA was given as twice the i.v. dose. Clinical response was recorded and logistic regression analysis was performed on clinical and laboratory factors for prediction of response to CSA. RESULTS: Of 36 patients, 25 responded to i.v. CSA and were switched to p.o. CSA. Of the 25, 13 required colectomy by 9 months. The other 12 patients had a sustained response to CSA and avoided colectomy at 9 months. Overall, 24 of 36 patients treated with CSA required colectomy by 9 months. A high percentage of band neutrophils (bands) on admission was found to be a significant predictor of response to CSA. CONCLUSIONS: Bands on admission are predictive of response to CSA and ultimately, the requirement for surgery in steroid-resistant UC.

Facklis K, Plevy SE, Vasiliauskas EA, Kam L, Taylor K, Targan SR, Fleshner PR. · Division of Colon and Rectal Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Dis Colon Rectum. · Pubmed #10344681 No free full text.

Abstract: PURPOSE: Genetic markers have been used to define subgroups of patients within the broad categories of Crohn's disease and ulcerative colitis that may differ in clinical course and response to medical therapy. The tumor necrosis factor microsatellite haplotype a2blc2d4e1 has been found previously to be present in 24 percent of patients with Crohn's disease and only 5 percent of patients with ulcerative colitis. This study examined associations between this microsatellite haplotype and the postoperative clinical course of patients with ulcerative colitis undergoing ileal pouch-anal anastomosis. METHODS: As part of a large, controlled, prospective study to correlate genetic markers with clinical phenotypes, tumor necrosis factor microsatellite alleles at five loci (a, b, c, d, and e) were determined from genomic DNA by polymerase chain reaction in 32 patients with a clinical and histopathologic diagnosis of ulcerative colitis who underwent ileal pouch-anal anastomosis for medically unresponsive disease. All patients with ileal pouch-anal anastomosis were also studied prospectively for pouch-specific complications. RESULTS: The tumor necrosis factor haplotype a2blc2d4e1 was present in 11 patients. Median follow-up was 19 months. Thirteen patients had a pouch-specific complication (12 pouchitis and 1 pouch-perineal fistula). Six of 11 patients (55 percent) with the haplotype had a pouch-specific complication compared with 7 of the 21 patients (33 percent) who did not possess this haplotype (P = 0.22). Median time from surgery to pouch-specific complication was eight months. Patients with the haplotype had a median time to pouch-specific complication of three months, whereas patients without the haplotype had a median time of 11 months (P = 0.04). In addition, 36 percent of patients with the haplotype had chronic pouch complications vs. only 10 percent of patients without the haplotype (P = 0.05). CONCLUSION: The Crohn's disease-associated tumor necrosis factor haplotype a2blc2d4e1 may define a subgroup of medically unresponsive patients with ulcerative colitis who are predisposed to a higher incidence of pouch-specific complications after ileal pouch-anal anastomosis.