IBD Watch®
Timely Information for Practicing Physicians
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NOVEMBER 2003 ULCERATIVE COLITIS (UC) High-dose vs. low-dose cyclosporine. Intravenous (i.v.) cyclosporine 4 mg/kg has previously been shown to be effective in the treatment of severe UC flare-ups. Gert Van Assche and colleagues in Belgium now report the results of a single-center, double-blind trial in which 73 patients with severe UC were randomized to receive either 4 mg/kg (high dose) or 2 mg/kg (low dose) of cyclosporine as acute treatment. Mean cyclosporine blood levels were 237 ± 33 ng/mL in the low-dose group and 332 ± 43 ng/mL in the high-dose group. Assessment at Day 8 showed that the response rates were 85.7% and 84.2% for the low- and high-dose groups, respectively. In addition, short-term colectomy rates were higher in the high-dose group (13.1% vs. 8.6%). There was also a trend toward a higher incidence of hypertension in the high-dose compared to the low-dose cyclosporine group (23.7% vs. 8.6%, p<0.08). These data indicate that therapy with 4 mg/kg of i.v. cyclosporine has no additional clinical benefit over 2 mg/kg of i.v. cyclosporine in the acute treatment of severe UC. (Van Assche G, et al. Gastroenterology 2003;125:1025-1031) CROHN'S DISEASE (CD) Defining contributions of gene mutations, age at onset, and tobacco use. Steven Brant and others conducted a retrospective multicenter record analysis of 275 patients with CD to assess risk factors for disease outcomes. They observed that NOD2 mutations, age at onset of CD, and smoking were important predictive factors of the clinical course of CD in these patients. The risk for the development of ileal disease was found to be increased in CD patients with two NOD2 mutations (Odds Ratio 10.1), a smoking history at diagnosis (Odds Ratio 2.25 per pack per day), and a younger age at diagnosis (Odds Ratio 0.97 per each increased year). Ileal disease (Odds Ratio 4.8) and the presence of one or two NOD2 mutations (Odds Ratio 1.9 and 3.5, respectively) were identified as independent risk factors for stricturing or non-perianal fistulizing disease. Ileal disease, onset at a younger age, and smoking at diagnosis were risk factors for early surgery. (Brant SR, et al. Inflamm Bowel Dis 2003;9:281-289) CD after allogeneic stem cell transplantation. S A Sonwalkar and coworkers at the University of Leeds (Leeds, UK) report a case of fulminant CD that occurred following non-myeloablative allogeneic stem cell transplantation for Hodgkin's Disease. The donor and recipient had several haplotype mismatches in HLA class III genes at the IBD3 locus and the donor had a polymorphism of the 5' UTR region of NOD2/CARD15 that has been associated with CD. The authors suggest that adoptive transfer of CD by hematopoietic cells may have occurred and that there may be a need to screen stem cell donors for markers of inflammatory bowel diseases. (Sonwalkar SA, et al. Gut 2003;52:1518-1521) INFLAMMATORY BOWEL DISEASE (IBD) Oral iron therapy in IBD. Although iron deficiency is common in IBD, it has been suggested that oral iron is poorly tolerated by IBD patients and may exacerbate disease activity. To investigate further the effects of iron therapy in patients with IBD, Anupama De Silva and coworkers performed a retrospective case record review that included 53 patients with IBD who had received oral iron and 24 non-IBD control patients with iron deficiency treated with oral iron. They found documentation of iron deficiency to be lacking in the records of many of the patients. Intolerance to iron therapy was reported in 25% and 17% of the IBD and non-IBD patients and iron therapy was associated with an increase in inflammatory markers in only 2 of the IBD patients. Iron repletion was achieved at least as frequently in IBD patients as in non-IBD patients (59% and 45%, respectively). These findings demonstrate that IBD patients tolerated iron therapy as well as non-IBD patients. (De Silva AD, et al. Inflamm Bowel Dis 2003;9:316-320) Indeterminant Colitis. The diagnosis of indeterminant colitis is currently applied to all cases of chronic inflammatory bowel disease confined to the colon that do not fulfill the diagnostic criteria for UC or CD. In the September issue of Inflammatory Bowel Disease, Karl Geboes and Gert De Hertogh suggest that indeterminant colitis has become a clinicopathologic diagnosis in of itself. They argue that indeterminant colitis patients have different clinical characteristics than those of patients with UC and CD and serologic markers that are strongly linked with UC and CD, such as perinuclear antineutrophil cytoplasmic antibody and anti-Saccharomyces cerevisiae, are negative in indeterminant colitis. Thus, the authors encourage the initiation of studies to investigate whether or not indeterminant colitis should be considered as a separate disease entity. (Geboes K and De Hertogh G. Inflamm Bowel Dis 2003;9:324-331) |
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