The reported incidence of fistulae in patients with CD ranges from 17% to 50% . Fistulae may be ente-rocutaneous (more commonly perianal), easily recognisable; or internal, enteroenteric or between gut and other organs. Internal fistulae may be asymptomatic but may be more aggressive and require urgent surgery (temporary colostomy allows the patient to heal by bypassing the inflammatory tract).
In perianal disease, induction therapy with infliximab (5 mg/kg at 0, 2 and 6 weeks) is effective on fistula healing in more than 60% of patients [28, 35]. Concomitant conventional therapy (antibiotics and immunosuppressants) is useful since 3 months' treatment with antibiotic monotherapy (metronidazole and ciprofloxacin) showed 60-70% complete remission, improved quality of life and reduced disease recurrences [20,36,37]. Azathioprine monotherapy is effective as well, but its full action is evident after 2-3 months of therapy. Therefore, its use in fistulising (perforating) CD is limited, at least as initial treatment. In patients intolerant to azathioprine, methotrexate at dose of 25 mg intramuscularly weekly may be a possible alternative treatment .
In patients with perianal fistulae, first-line treatment with antibiotics is suggested. In case of relapse, antibiotics and immunosuppressant therapy (aza-thioprine or methotrexate) is effective. If fistulae persist, induction therapy with infliximab is recommended, followed by maintenance therapy with immunosuppressant or infliximab (every 8 weeks) [36, 39].
In our opinion, a more appropriate first-line treatment may include induction therapy with infliximab, followed in responders by a maintenance regimen with infliximab and introduction of immunosup-pressant drugs. In nonresponders or those intolerant to infliximab i.v., antibiotics, immunosuppressants and local injection of infliximab may be an alternative treatment . Internal fistulae are usually associated to a more aggressive subtype of CD and more difficult to treat conservatively . However, treatment with azathioprine and antibiotics or infliximab may be tried [42,43].
In some patients, clinical onset of CD occurs with subocclusive symptoms secondary to inflammatory strictures. In naive patients, infliximab probably induces rapid anti-inflammatory effects with symptomatic improvement, reducing the need for resec-tive surgery. There are no studies confirming this hypothesis but a top-down therapy has been recently proposed  and, probably, in the near future, this may be an appropriate initial treatment . However, concomitant therapy with immunomodulators increases the rate of clinical response and clinical remission, and smoking seems to be a negative predictor of response to infliximab therapy [45, 46]. Therefore, an initial therapeutic approach with steroids and immunosuppressants followed by infliximab is suggested, as well as smoking cessation.
On the contrary, infliximab is not indicated in the presence of a fibrotic stenosis [44,47]. Clinical (longstanding disease), laboratory data [inflammatory indexes, mainly C-reactive protein [48,49] and instru mental findings by magnetic resonance imaging (MRI) or fluorodeoxyglucose positron emission tomography (FDG-PET)] may help in discriminating an inflammatory or fibrotic process in the intestinal wall .
Finally, infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and significantly reducing hospitalisations, surgeries and procedures compared with placebo [50-55].
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