Oral tacrolimus for steroid-dependent and steroid-resistant ulcerative colitis in children.

PURPOSE: To evaluate tacrolimus in 3 situations: for the induction of remission in children with severe steroid-resistant ulcerative colitis (UC); for steroid sparing in children with steroid-dependent UC in whom treatment with other immunosuppressants fails; and for the maintenance of remission in children with steroid-dependent and steroid-resistant UC. PATIENTS AND METHODS: We retrospectively evaluated 18 consecutive patients (13 with pancolitis) who were treated with oral tacrolimus at our institution from May 1999 to October 2005. Nine patients had steroid-resistant UC and 9 patients were steroid-dependent. We started patients initially on tacrolimus 0.2 mg/kg divided twice daily, with a goal plasma trough level of 10 to 15 ng/mL for the first 2 weeks, and then titrated doses to achieve plasma levels between 7 and 12 ng/mL after induction. RESULTS: Of the 18 patients in this study, 17 showed a positive response to tacrolimus therapy (ie, cessation of diarrhea and other symptoms) and 5 showed a prolonged response to tacrolimus. The mean time from initiation of tacrolimus therapy until response was 8.5 days. The mean duration of response was 260 days. Eleven of 18 patients required colectomy, including all of the patients with steroid-resistant UC, but only 2 of 9 who were steroid-dependent. The mean time from initiation of tacrolimus until colectomy was 392 days. CONCLUSIONS: It is possible that tacrolimus may benefit selected patients with steroid-dependent UC, including those who are intolerant of 6-mercaptopurine or azathioprine. Conversely, patients with steroid-resistant UC are unlikely to sustain a prolonged clinical response to tacrolimus and seem to require colectomy eventually. Careful considerations of risk versus benefit, as well as close monitoring for adverse effects, are essential in all patients.

High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn's disease: a pilot study.

In Crohn's disease, antibiotics are used with variable efficacy, suggesting that some patients are more likely to respond. The aim of this study was to determine whether Crohn's patients with predominant serum antibody reactivity toward bacterial antigens OmpC and/or I2 were more likely to achieve remission with antibiotics. Patients with ileal or ileal with right-sided colonic Crohn's disease were studied in a double-blind trial of budesonide alone or budesonide plus metronidazole and ciprofloxacin. In the budesonide plus metronidazole and ciprofloxacin group, patients with OmpC/I2 predominant profiles had the highest remission rate, whereas the group with no antibody predominant profiles had the lowest rate. In the budesonide group, patients with the OmpC/I2 predominant profile had the lowest remission rate, and the no-antibody group rate was higher. Although not statistically significant, these results support further testing to determine whether predominant serum reactivity to certain bacterial antigens may be a marker for efficacious use of antibiotics.

High incidence of anergy in inflammatory bowel disease patients limits the usefulness of PPD screening before infliximab therapy.

BACKGROUND & AIMS: Reports of tuberculosis (TB) in patients administered infliximab prompted the Food and Drug Administration to recommend that all patients being considered for this therapy be evaluated for the risk for latent TB infection by means of a tuberculin skin test (TST). The aim of this study is to evaluate the utility of a TST as an adequate screen for TB exposure in patients with inflammatory bowel disease (IBD). METHODS: Eighty-two consecutive patients with IBD (Crohn's disease, 70 patients; ulcerative colitis, 4 patients; indeterminate colitis, 8 patients) seen at Cedars-Sinai Medical Center IBD Center (Los Angeles, CA) being treated with or considered for infliximab therapy underwent a standard intradermal purified protein derivative (PPD) TST before or between infusions of infliximab. One or more control antigens (Candida, tetanus, and/or mumps) were concurrently placed on 69 of these patients. Skin tests were read for induration at 48-72 hours after placement, and results were recorded. RESULTS: None of 82 patients had a positive PPD TST result. Overall, 71% of patients (49 of 69 patients) with controls placed failed to react to any antigen. Eighty-three percent of patients (40 of 48 patients) who were administered corticosteroids and/or immunosuppressive medications, not including infliximab, for at least 1 month were anergic compared with 43% of patients (9 of 21 patients; P < 0.002) who were not administered those medications. CONCLUSIONS: Given the high prevalence of anergy, a negative TST result in patients with IBD administered infliximab is an unreliable indicator for TB exposure. Evaluation for TB risks should include not only a TST, but also a detailed history of travel, TB exposures, and such symptoms as chronic cough and weight loss, and a chest radiograph should be considered.

Initial experience with wireless capsule enteroscopy in the diagnosis and management of inflammatory bowel disease.

BACKGROUND AND AIMS: Wireless capsule enteroscopy (WCE) offers the potential to directly visualize the entire small bowel and identify superficial lesions not detected by traditional endoscopy and radiography. The aim of this study is to assess the clinical utility of WCE in the evaluation of patients with known or suspected inflammatory bowel disease (IBD). METHODS: Fifty patients with ongoing symptoms underwent Given M2A endoscopic capsule examinations. Indications included: (1) evaluation for small-bowel involvement in patients with IBD with isolated colitis (n = 22), (2) determination of the extent of small-bowel disease in patients with Crohn's disease (CD; n = 20), and (3) workup of suspected IBD (n = 8). Outcome measures were classified as diagnostic when multiple ulcerations were present, suspicious when

Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease.

BACKGROUND & AIMS: Crohn's disease patients can be characterized by antibody responses against Crohn's disease-related bacterial sequence, Escherichia coli outer membrane porin C, Saccharomyces cerevisiae (oligomannan), and neutrophil nuclear antigens. Our aim was to determine whether expression of antibodies against Crohn's disease-related bacterial sequence and Escherichia coli outer membrane porin C is associated with distinct phenotypic manifestations. METHODS: Sera from 303 patients were tested for antibodies to the Crohn's disease-related bacterial sequence (I2), anti-Escherichia coli outer membrane porin C, anti-Saccharomyces cerevisiae, and perinuclear antineutrophil cytoplasmic antibodies and for 3 Crohn's disease-associated variants of the NOD2 gene (R702W, G908R, and 1007fs) and compared with clinical data. RESULTS: Patients expressing I2 were more likely to have fibrostenosing Crohn's disease (64.4% vs. 40.7%; P < 0.001) and to require small bowel surgery (62.2% vs. 37.4%; P < 0.001). Patients with anti-Escherichia coli outer membrane porin C were more likely to have internal perforating disease (50.0% vs. 30.7%; P = 0.001) and to require small bowel surgery (61.4% vs. 44.2%; P = 0.003). Anti-Crohn's disease-related bacterial sequence was independently associated with fibrostenosis (P = 0.027) and small bowel surgery (P = 0.01), whereas anti-Escherichia coli outer membrane porin C was independently associated with internal perforations (P < 0.006). Patients positive for I2, anti-Escherichia coli outer membrane porin C, and anti-Saccharomyces cerevisiae were the most likely to have undergone small bowel surgery (72.0%; odds ratio, 8.6; P < 0.001) compared with patients without reactivity (23.0%). When the presence and magnitude of antibody responses were considered, 90% of patients with small bowel disease who required surgery had high levels of I2, Escherichia coli outer membrane porin C, and oligomannan antibodies, compared with only 18.2% with low-titer responses (P < 0.001). CONCLUSIONS: I2 and anti-Escherichia coli outer membrane porin C are associated with Crohn's disease phenotypes, and patients with the highest level of serum reactivity toward an increasing number of microbiota have the greatest frequency of strictures, internal perforations, and small bowel surgery.