Thiopurines, a previously unrecognised cause for fatigue in patients with inflammatory bowel disease.

BACKGROUND: Active inflammatory bowel disease, anaemia, iron deficiency and depression, alone or in combination, are known contributing factors of fatigue in inflammatory bowel disease. However, in some patients, fatigue cannot be attributed to known causes. Thiopurines are not a recognized cause. AIM: To describe the clinical scenario of a series of patients where thiopurines were the likely cause of fatigue. METHOD: The clinical scenario of 5 patients was examined with specific reference to the temporal association of thiopurine therapy with fatigue, the effect of its withdrawal and rechallenge, and drug specificity. RESULTS: The onset of severe fatigue was related to the introduction of azathioprine or 6-mercaptopurine, rapid relief was experienced on its withdrawal in all patients, and fatigue rapidly occurred on rechallenge. The speed of onset was rapid in two patients and in the context of gradual withdrawal of moderate steroid dose, but recurred rapidly on rechallenge when not on steroids. CONCLUSIONS: Marked fatigue is a previously unrecognized adverse effect of thiopurines. It does not appear to be drug-specific. Its onset might be masked by concurrent steroid therapy.

A single center experience of methotrexate in the treatment of Crohn's disease and ulcerative colitis: a case for subcutaneous administration.

BACKGROUND AND AIM: Methotrexate (MTX) is used as a second-line immuno-modulator in patients with inflammatory bowel disease when purine analogs are not tolerated or lack efficacy. High-level evidence indicates efficacy for intramuscular administration in Crohn's disease, but there are few reports of experience with subcutaneous delivery. This study aimed to evaluate the response to and tolerance of MTX where subcutaneous administration was the preferred option. METHOD: The records of all patients treated with MTX were evaluated with regard to the dose, duration, response, and tolerance to MTX. Remission was defined as improvement in symptoms with no corticosteroid requirement for 3 months or ability to wean off steroids. RESULTS: MTX was initiated in 45 patients with Crohn's disease and 23 ulcerative colitis (median age, 46 years; range, 20-80 years; 54% men) because of intolerance (69%) or resistance (31%) to purine analogues. MTX was initiated in 74% of patients in doses of 25 mg (33) or 20 mg (17), administered by subcutaneous self-injection in 90% of subjects. Remission was achieved in 24 of 45 (53%) with Crohn's disease and 11 of 23 (48%) with ulcerative colitis. An additional four (9%) patients with Crohn's disease and three patients (13%) with ulcerative colitis demonstrated symptomatic improvement and/or ability to decrease corticosteroid dose. While nine patients ceased therapy and nine successfully reduced their doses due to intolerance, three of four patients had no adverse effects. Subcutaneous delivery was well accepted. CONCLUSIONS: Subcutaneously administered MTX exhibits apparent efficacy, acceptance, tolerance, and safety in patients with Crohn's disease or ulcerative colitis who are steroid-dependent and where purine analogs have been ineffective or intolerable.

5-Aminosalicylic acid (mesalazine) use in Crohn's disease: a survey of the opinions and practice of Australian gastroenterologists.

BACKGROUND: The use of 5-aminosalicylate (5-ASA) drugs in Crohn's disease (CD) is controversial, with their continuing apparent widespread use despite high-level evidence indicating marginal benefit at best and international guidelines recommending limited indications. METHODS: In order to understand how clinicians translate the evidence base into clinical practice, we surveyed a cross-section of Australian gastroenterologists to determine opinions and prescribing patterns of 5-ASA drugs in CD. RESULTS: In all, 42% of 285 gastroenterologists who were sent a questionnaire by e-mail responded. Five (4%) never use 5-ASA drugs in CD. The drugs are most commonly prescribed for patients with colonic (96%) or ileocolonic (92%) disease location, inflammatory disease behavior (80%), and mild disease activity (97%). The majority (64%) use a dose of 1-3 g/day, but only 6% use over 4.5 g/day. Less than one-half use 5-ASA drugs as maintenance following surgical resection, but most use it for inducing remission alone (70%) or in combination with other drugs (90%), and continue its use for maintenance. Side effects are thought to be infrequent (62%) or rare (20%) and few common side effects are believed to be serious. Respondents estimated that over 90% of patients were nonadherent to prescribed 5-ASA regimens at least 50% of the time. While 84% believed that 5-ASA drugs were effective in CD, only 58% believed that they were cost-effective. CONCLUSIONS: In Australia 5-ASA drugs are extensively prescribed for CD at relatively low doses without expectation of patient adherence. Current evidence and guidelines has had little apparent impact on clinical practice. The cost implications are considerable.

Endoscopic balloon dilatation of intestinal strictures in Crohn's disease: safe alternative to surgery.

BACKGROUND AND AIM: Endoscopic balloon dilatation (EBD), a non-surgical treatment option for intestinal strictures in Crohn's disease, appears to be applied infrequently, possibly due to the perceived risk of perforation and early recurrence. This study aimed to determine the outcomes of EBD by a single endoscopist using a defined technique. METHODS: The records of all patients with Crohn's disease in whom EBD was attempted over a 12-year period were examined to determine the rate of technical success, complications and outcome. A stricture was defined as that which prevented passage of the 14 mm diameter colonoscope. Technical success was defined as the ability to traverse the stricture postdilatation. Patients were selected on the colonoscopic appearance of the stricture and dilatation was performed using through-the-endoscope balloons. Antibiotics were given during and for 7 days postdilatation. RESULTS: EBD was attempted on 83 strictures (31 anastomotic and 52 primary) in 37 patients (15 males) and was successful in 75 (90%) of 31 patients. A single dilatation only was required in 21 patients who had a median follow-up of 20 months (range 6-122 months). Recurrent symptomatic stricture requiring dilatation (eight patients) or surgery (two patients) occurred 8 (1-112) months after the initial dilatation. The only complication occurred in one patient where an intra-abdominal fistula and abscess were probably related to the dilatation. CONCLUSION: EBD of intestinal strictures associated with Crohn's disease has a low complication rate and leads to prolonged clinical benefit. It should be considered as a real alternative to surgery.