Autologous fibroblasts transplant after infliximab administration: a new approach in Crohn’s perianal fistulas?

Abstract

The transmural nature of the inflammatory process in Crohn’s Disease (CD) is the most important predisposing factor to the development of anal and perianal fistulae, which occur in 3–80% of patients affected with CD, a variation related to different defining criteria. Although several local and general treatments have been proposed, the management of perianal CD is still considered difficult and unsatisfactory, and the rate of recurrences remains really high. Azathioprine or 6-mercaptopurine, and in many cases, infliximab, have been proposed as alternative therapy to surgery for CD. Infliximab, a monoclonal antibody directed against tumor necrosis factor, has been found effective in the treatment of fistulizing CD. However reopening of apparently healed fistulas (treated only with infliximab infusion, without surgery) is frequent, and it has been related to the persistence of deep fistulas tracts, which could otherwise be detectable using anal endosonography. Novel approaches in healing of chronic wounds include the use of tissueengineered skin substitutes as human autologous fibroblasts; these cells have yet been successfully used for healing of diabetic or venous ulcers. In this preliminary report, the first procedure to manage CD perianal fistulas by combining fistulectomy with a transplantation of autologous fibroblasts seeded onto biocompatible HYAFF scaffolds (three-dimensional biodegradable scaffolds entirely composed of a benzylic ester of hyaluronic acid) is described. The patient was 61 years old, male, who was found affected with CD since 1996 and had undergone several medical approaches (steroid drugs, azathioprine, 6-mercaptopurine administration) with low clinical benefits; in 2001, he underwent surgical bowel resection for ileal multiple stenosis. In January 2004, a relapse of the disease with diarrhoea, perianal pain and fever occurred. Right kidney lithiasis, hepatic angioma and a diffuse thickening of the residual ileum were reported by ultrasonography and computed tomography (CT) exams. The inspection of the perianal region and an anal examination showed a trans-sphinteric fistula with a large abscess in the ischio-rectal fossa. The patient underwent drainage of the abscess and the loose-seton technique was applied; then the patient underwent a series of three infliximab administrations (5 mg/kg/die in a slow drip) at 1, 2, 6 weeks after surgery, followed by azathioprine administration (150 mg/ die) for 2 months. In October 2004, the patient was admitted to the autologous fibroblasts transplantation protocol. The patient was informed about the treatment and agreed to the implant of autologous S. Ascanelli . D. de Tullio . C. Gregorio . G. Azzena . S. Occhionorelli Department of Surgical, Anesthesiological, Radiological Sciences, Surgical Clinic Institute of the University of Ferrara, Ferrara, Italy