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BACKGROUND Medical therapy for strictures is limited and first-line treatment consists of endoscopic balloon dilatation, strictureplasty or surgical resection. Mycobacterium tuberculosis , Helicobacter pylori and Streptococcus can all cause stenosis, for which antibiotic treatment achieves stricture resolution. Mycobacterium avium ssp. paratuberculosis is a suspected causative agent in Crohn’s disease (CD). Thus, specialized antimicrobial treatment, in particular, anti-mycobacterial antibiotic therapy (AMAT) has been proposed as a potential treatment option. To our knowledge, the opening of CD strictures has not been recorded using any form of antibiotic therapy. We hypothesized that AMAT would resolve strictures in patients with CD. AIM To investigate the effect and outcomes of AMAT in a cohort of CD patients with an ileal stricture. METHODS A single center, retrospective, medical record case review was conducted on an observational cohort of patients with CD who had an ileal stricture on colonoscopy and were treated with AMAT. Forty patients meeting the inclusion criteria were identified from the internal medical database. Thirty (75%) patients had follow-up colonoscopy and clinical data available. The AMAT regimen was prescribed after the initial colonoscopy for a duration of at least six months until follow-up colonoscopy with the attending gastroenterologist. Patient demographics, symptoms, colonoscopy reports, inflammatory serum markers and concurrent medications were recorded at pre-treatment and follow-up between January 1995 and June 2018. RESULTS Of the patients that returned for follow-up after > 24 mo of AMAT, twenty (67%) had complete resolution (CR) of their ileal strictures, three (10%) had partial resolution and seven (23%) had no resolution. Irrespective of stricture outcome, 21 patients (70%) demonstrated clinical response to AMAT and there was a statistically significant reduction in inflammatory serum markers C-reactive protein ( P < 0.0001) and erythrocyte sedimentation rate ( P = 0.04) from pre-treatment to follow-up. It was observed that 11 (37%) patients experienced side effects, but no serious adverse effects were attributable to AMAT. At follow-up there were 26 (87%) patients on concomitant medication for CD and a statistically significant association between CR and AMAT with a concomitant immunomodulator ( P = 0.02). CONCLUSION This study demonstrated a high rate of stricture resolution (67%) similar to that seen in tuberculosis strictures (70%), suggesting a shared mycobacterial origin of strictures, and perhaps disease.

INTRODUCTION: Approximately one third of patients with Crohn’s disease (CD) will develop strictures within 10 years of diagnosis, commonly in the terminal ileum and ileocecal valve (ICV). Strictures often lead to abdominal pain, obstruction and are a risk factor for developing internal fistulae and cancer. Current treatment involves endoscopic balloon dilatation or strictureplasty. However, this may result in postoperative complications or recurrence. Recent evidence suggests that Mycobacterium avium ssp paratuberculosis may be a causative agent of CD and anti-mycobacterial antibiotic therapy (AMAT) has been shown to induce remission significantly better than placebo. The effects of AMAT on strictures has not been reported. AIM: To report the outcomes of AMAT in patients with CD and an ileal stricture/s. METHODS: This is a single centre retrospective (January 1995-December 2018) case review of patients diagnosed with CD, who had ileal stricture on colonoscopy and were treated with AMAT which comprised a combination of clarithromycin, rifabutin, and clofazimine, some with added ethambutol, ciprofloxacin, metronidazole or tinidazole. Symptoms, colonoscopy reports, biochemistry and concurrent medications were reviewed and recorded at pre-treatment and 6, 12, 18 and >24 months on treatment. RESULTS: Forty-three patients (24 male, 16-56 yrs) with an average age of 31 yrs, and 5 yrs (0-27 yrs) after diagnosis were included. At pre-treatment, 17 patients had stricturing of the ICV, 25 had stricturing of the ileum and one had stricturing in both the ileum and ICV. Of the patients who had follow up colonoscopy data (N = 32), after >24 months of AMAT, 22/32 patients (69%) had complete resolution and 2/32 patients had partial resolution of their strictures. Interestingly, after resolution of stricture on AMAT one patient ceased treatment. At 36 month follow up post cessation of AMAT the patient’s ileocecal stricture had returned. Further treatment with AMAT resulted in resolution of the stricture. CONCLUSION: AMAT for CD is effective in opening Crohn’s strictures avoiding the need for repeated dilatations or surgery. These observations suggest that stricturing in CD may be mediated by mycobacterial infection, as reported in tuberculosis strictures. To our knowledge, CD strictures have not previously been reported to open using medical therapy. Further prospective documentation is required to better define this positive effect of AMAT, including rate of resolution.

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