Fistula Treatment: The Unresolved Challenge

In population-based studies, up to 50% of patients with Crohn's disease suffer from fistulas. Fistulas pose a considerable morbidity including permanent sphincter and perineal tissue destruction as well as professional and personal disabilities. Treatment options have progressed in recent years and fistula closure and fibrosis of the fistula track is achieved in some patients. Depending on severity of symptoms and fistula location, different medical and surgical therapies can be chosen. Internal fistulas such as ileoileal or ileocecal fistulas are either asymptomatic and do not require intervention or they are symptomatic and need surgery alone. They always carry a risk of abscess formation. Symptomatic perianal fistulizing disease can be treated with antibiotics (i.e. metronidazole and ciprofloxacin) for three months and/or immunosuppressant therapy (6-mercaptopurine or azathioprine). More complex cases require therapy with anti-TNF agents. Only few and preliminary data exist on cyclosporine A, tacrolimus or methotrexate in fistulizing Crohn's disease. Therefore, these therapies should mainly be used as second-line therapies. Surgery is reserved for the treatment of perianal sepsis in the presence of abscesses and refractory disease or complications of fistulas, or used in combination with pharmacological approaches. The surgical interventions in perianal disease consist of surgical drainage with or without seton placement, transient ileostomy, or in severe cases, proctectomy. The classification of fistulas in patients with Crohn's disease remains poorly defined and largely investigator dependent. The unresolved challenges in fistula treatment warrant randomized controlled trials for existing and future treatment strategies as well as a better classification system to compare available studies.