Etiology of perianal Crohnʼs disease: Role of genetic, microbiological, and immunological factors

Tozer, P; Whelan, Kevin; Phillips, R. K. S.; Hart, Ailsa

doi:10.1002/ibd.21026

Cited by 52 publications

(29 citation statements)

References 76 publications

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“…The pathogenesis of perianal fistulae in CD is different from that of cryptoglandular ones. Usually, fistulae are believed to originate from either deep penetrating ulcers or anal gland infection/abscess [3]; however, other theories have been advocated in CD patients, involving microbiological, immunological, and genetic factors [4, 5]. These observations are in agreement with the higher rate of high, complex fistulae observed in CD patients with active rectal disease [6].…”

Section: Introductionmentioning

confidence: 76%

Surgical Treatment of Perianal Fistulizing Crohn’s Disease: From Lay-Open to Cell-Based Therapy—An Overview

Pellino

Selvaggi

2014

The Scientific World Journal

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Background. Perianal Crohn's disease (CD) can be challenging. Despite the high incidence of fistulizing CD, literature lacks clear guidelines. Several medical, surgical, and combined treatment modalities have been proposed, but evidences are scarce. Methods. We searched the literature to assess the facets of perianal CD, with particular focus on complex fistulae. Disease epidemiology, classification, diagnosis, activity scoring systems, and medical-surgical treatments were assessed. Results. Perianal fistulizing CD is common, frequently associated with upper gastrointestinal and colorectal CD. Complex fistulas often require repeated treatments. Continence is a major concern when dealing with repeated procedures. A prudent pathway is to resolve active sepsis and to limit damages, delaying a definitive treatment to the time when acute phase has been controlled. The improved diagnostic techniques allow better preoperative planning and are useful in monitoring the response to treatment. Besides newer devices, cell-based treatments are promising tools which have recently enriched the treatment portfolio. However, the need for proctectomy is still disturbingly high in CD patients with complex perianal fistulae. Conclusions. Perianal CD can impair quality of life and lead to need for proctectomy. A staged approach is reasonable. Treatment success can be improved by multimodal treatment and collaborative management by experienced gastroenterologists and surgeons.

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Section: Introductionmentioning

confidence: 76%

Surgical Treatment of Perianal Fistulizing Crohn’s Disease: From Lay-Open to Cell-Based Therapy—An Overview

Pellino

Selvaggi

2014

The Scientific World Journal

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“…23 The pharmacologic mechanism of AST-120 has been linked to the adsorption of proinflammatory molecules, such bacterial toxins, bile salts, and hydrogen sulfide that possess the potential of injuring the mucosal barrier. 14–16 A recent report from an open-label, uncontrolled U.S. study on the potential benefit of AST-120 in patients with pouchitis after ileal pouch–anal anastomosis would be in line with such mode of action.…”

Section: Discussionmentioning

confidence: 99%

AST-120 (Spherical Carbon Adsorbent) in the Treatment of Perianal Fistulae in Mild-to-Moderate Crohnʼs Disease

Reinisch¹,

Travis²,

Hanauer³

et al. 2014

Inflammatory Bowel Diseases

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Background AST-120 (spherical carbon adsorbent) was previously reported to be effective for perianal fistula healing in Japanese patients with mild-to-moderate Crohn’s disease. Methods To evaluate the efficacy and safety of AST-120 in a Western population, a phase 3, multicenter, randomized, double-blind, placebocontrolled, study (FHAST-1) was conducted in adult patients with at least 1 draining perianal fistula and a Crohn’s disease activity index <400. Patients received either AST-120 or matching placebo at a dose of 2 g 3 times daily for 8 weeks. The primary endpoint was the proportion of patients with treatment success, defined as a 50% reduction in the number of draining fistulae, at both weeks 4 and 8. A multivariate model was generated to assess covariates for treatment success among baseline variables. Results Two hundred forty-nine patients were randomized (AST-120; n = 122; placebo, n = 127). The proportions of patients achieving the primary endpoint were no different between treatment groups (13.9% versus 16.5%, P = 0.6). No differences in fistula response were noted at week 4 (23.0% versus 25.2%, P = 0.77) or week 8 (27.0 versus 34.6%, P = 0.22). Serum C-reactive protein concentrations >0.6 mg/dL and Crohn’s disease activity index scores >151 at baseline were associated with a reduced likelihood of treatment success (odds ratio, 0.40; confidence interval, 0.19–0.87; P = 0.02; and odds ratio, 0.45; confidence interval, 0.21–0.97; P = 0.04, respectively). Conclusions In this largest placebo-controlled trial to date to evaluate the impact of a therapeutic agent on perianal fistulae in Crohn’s disease, the efficacy of AST-120 could not be confirmed. An inverse relationship was observed between both inflammatory and clinical disease activity and fistula response.

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“…The cryptoglandular theory [7] may not be wholly applicable to the Crohn's setting in which anal ulceration may play a part [8]. As with luminal disease, an interplay of genetic predisposition, bacterial dysbiosis and host immune malfunction is implicated (reviewed in [9]) although recent work casts doubt on the relevance of bacteria in maintaining a fistula once formed [10]. The range of treatments available, their diversity and lack of efficacy speak to the poor understanding of fistula pathogenesis.…”

Section: Aetiologymentioning

confidence: 96%

Managing perianal Crohn’s fistula in the anti-TNFα era

et al. 2015

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Perianal fistulas in Crohn's disease are common and difficult to treat. Their aetiology is poorly understood. Assessment is clinical, endoscopic and radiological, and management is undertaken by a multidisciplinary team of gastroenterologists, surgeons and radiologists. Surgical drainage of the fistula tract system with the placement of loose setons precedes combined therapy with immunosuppressant and anti-TNFα agents in most patients. Proctitis should be rigorously eliminated where possible. Definitive surgical repair is sometimes possible and diversion or proctectomy are occasionally required. Combined medical and surgical management represents a promising avenue for the future.

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Etiology of perianal Crohnʼs disease: Role of genetic, microbiological, and immunological factors

Cited by 52 publications

References 76 publications

Surgical Treatment of Perianal Fistulizing Crohn’s Disease: From Lay-Open to Cell-Based Therapy—An Overview

Surgical Treatment of Perianal Fistulizing Crohn’s Disease: From Lay-Open to Cell-Based Therapy—An Overview

AST-120 (Spherical Carbon Adsorbent) in the Treatment of Perianal Fistulae in Mild-to-Moderate Crohnʼs Disease

Managing perianal Crohn’s fistula in the anti-TNFα era

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