Fistula is one of the most common and unpleasant complications ofCrohn’s disease. A female patient with Crohn’s disease presentingan enterovesical fistula was treated with infliximab infusion 5m/kg,achieving complete resolution of the lesion. The dose infusion wasrepeated once more 10 weeks later. The patient remainsasymptomatic one year after the initial infusion

Flávio Steinwurz

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22*Study performed at Hospital Israelita Albert Einstein.1 Gastroenterologista do Hospital Israelita Albert Einstein. Fellow do American College of Gastroenterology. Presidente da ABCD - Associação Brasileira de Colite Ulcerativa e Doença de Crohn.Correspondence to: Flavio Steinwurz - Av. Albert Einstein 627 - sala 1009 - São Paulo - SP - Brasil - e-mail: steinwu@attglobal.netRecebido para publicação em 10/12/2002 – Aceito em 18/6/2003CASE REPORTClosure of enterovesical fistula in Crohn’s disease with infliximab:Case reportFechamento de fístula enterovesical por doença de Crohn com o uso de infliximab: Relato de caso*Flávio Steinwurz1ABSTRACTFistula is one of the most common and unpleasant complications ofCrohn’s disease. A female patient with Crohn’s disease presentingan enterovesical fistula was treated with infliximab infusion 5m/kg,achieving complete resolution of the lesion. The dose infusion wasrepeated once more 10 weeks later. The patient remainsasymptomatic one year after the initial infusion.Keywords: Crohn disease/drug therapy; Bladder fistula/drug therapy;Antibodies, monoclonal/therapeutic useRESUMOA doença de Crohn tem nas fístulas uma de suas mais freqüentes edesagradáveis complicações. Uma paciente com Doença de Crohnapresentando uma fístula enterovesical foi tratada com infusão deinfliximab, na dose de 5 mg/kg, e obteve completa resolução doproblema. A dose foi repetida apenas mais uma vez, após 10 semanas.A paciente continua sem sintomas, após 1 ano da aplicação inicial.Descritores: Doença de Crohn/quimioterapia; Fístula vesical/quimioterapia; Anticorpos monoclonais/uso terapêuticoINTRODUCTIONCrohn’s disease is a chronic inflammatory disease that may affectany part of the digestive tract. One of its major complications ispossible fistula formation. The most frequent fistulas are external- perianal or on the abdominal wall. Internal fistulas can beenterovaginal, enterovesical, or enteroenteric, and occur in 5-10%of the patients affected by Crohn´s disease(1).Treating fistulas is not an easy task in most cases. To date, theonly drugs that have shown to be effective to close part of theselesions are immunosuppressors and infliximab. Infliximab is achimeric monoclonal antibody to tumor necrosis factor alpha(anti-TNF)(1-4).Infliximab contains 75% human and 25% murine elements. Itneutralizes the biological activity of tumor necrosis factor alpha(TNF) for presenting high binding affinity to TNF. Thereforeinfliximab prevents TNF from binding to its receptors, resulting indecreased production of proinflammatory cytokines and migrationof leukocytes through the endothelium, thus reducing inflammation.The mechanism of action of infliximab on fistulas is still uncertainbut it would be partially related to achieving remission.This study reports the case of a female patient with anenterovesical fistula due to Crohn´s disease and treated withinfliximab.CASE REPORTM.M.F.O.Z., 39 years old, female, married, dentist, suffering fromCrohn’s disease for 5 years. She has presented a flare-up for oneyear, characterized by diarrhea, abdominal pain and nausea. Sixmonths ago, the patient had recurrent urinary tract infections.Clinical investigation showed that these infections were due to anenterovesical fistula. The following diagnostic studies wereperformed to draw this conclusion:• Abdominal ultrasound (including the urinary tract): thickeningof the lateral wall of the bladder (figs. 1 and 2);• Computerized tomography: presence of mass on the lateralwall of the bladder; thickening of the terminal ileum.• Cystoscopy: visualization of fistula opening on the bladder.• Colonoscopy: partial stenosis of the ileocecal valve withcobblestone lesions, and scar retraction in transverse colon.At that time the patient was continuously taking corticoids andantibiotics. Infliximab was chosen to check possible closure of thefistula and remission of persisting flare-up symptoms. The patientwas hospitalized under day clinic regimen at Albert Einstein JewishHospital, and was infused infliximab 5 mg/kg, according to specificguidelines regarding appropriate material and length ofadministration.The symptoms significantly improved, and after one monthboth antibiotic and corticoid were discontinued. The patient didnot present any complaints or recurrence of infection. Laboratoryexams carried out 15 days later showed normalization ofinflammatory activity tests (ESR and CRP), normal urine analysisand sterile urine culture. A new abdominal ultrasound scan wasperformed (fig. 3), including the urinary tract, and the exam wasabsolutely normal with no residual image of the previouslyeinstein 2003; 1:22-323Figure 2. Ultrasound showing progression of the fistula on the vesical wall. Figure 1. Ultrasound image showing the enterovesical fistula before treatment.observed thickening, which represented the fistula. Despite theresults, it was decided that it would be convenient to administeranother dose of infliximab 10 weeks after the first infusion.One year after discontinuation of the drugs, the patient is stillasymptomatic and with normal exam results.DISCUSSIONCrohn’s disease may affect any part of the digestive tract, andpresent intestinal and extraintestinal complications. Undoubtedly,fistulas are one of the most frequent complications of the diseaseand cause much trouble to patients. External fistulas, such asenterocutaneous fistulas, are the most common; however internalfistulas are more difficult to be diagnosed, and their therapeuticcontrol is less evident.Few therapeutic options have proved to be effective to treatthese complications.For many years medical therapy was restricted to use ofimmunosuppressors, which demonstrated good results in severalstudies described in the literature(1-2,4-5). More recently, infliximabshowed significant results in treatment of fistulas, bringing newperspectives for patients(3-4). There are few reports on enterovesicalfistulas, and even less regarding their treatment(5).Some authors believe that fistulas healed with infliximab mayrequire surgery in the long run(6). For this reason, this treatmentremains empirical and common sense should be applied to eachcase. Treatment with infliximab was proposed to this patient, whoimmediately accepted it. The fistula was completely healed verysoon. Thirty days after the first infusion of infliximab the patientdiscontinued all drugs, and no longer presented recurrent urinarytract infection or flare-ups. A second infusion of infliximab wasadministered, and the patient has been in full remission ofsymptoms for a year, with no recurrence of fistula, showingsustained healing of the lesion.Despite few reports in the literature and very restrictedexperience, the use of infliximab in treatment of enterovesicalfistulas in Crohn’s disease seems to be valid.Figure 3. Ultrasound performed after infusion of iInfliximab, showing lesionson bladder wall have disappeared.REFERENCES1. Levy C,Tremaine WJ. Management of internal fistulas in Crohn’s disease.Inflamm Bowel Dis 2002;8:106-11.2. korelitz BI, Present DH. Favorable response of 6-mercaptopurine on fistula ofCrohn’s disease. Dig Dis Sci 1985;30:58-62.3. Present DH, Mayer L, van Deventer SVH, Rutgeerts P, Hanauer SB, De WoodyTK et al. cA2 Study Group. Anti TNF alpha chimeric antibody (cA2) is effectivein the treatment of the fistula of Crohn’s disease. Am J Gastroenterol1997;92:1746-52.4. Steinwurz F. Estudo evolutivo de fístulas na Doença de Crohn. Arq Gastroenterol1999;36:207-9.5. Wheeler SC, Marion JF, Present DH. Medical therapy, not surgery, is theappropriate first line treatment for Crohn´s enterovesical fistula. Am JGastroenterol 1998;114:A1113.6. Poritz LS, Rowe WA, Koltun WA. Remicade does not abolish the need of surgeryin fistulizing Crohn´s disease. Dis Colon Rectum 2002;45:771-5.einstein 2003; 1:22-3Closure of enterovesical fistula In Crohn’s

Closure of enterovesical fistula in Crohn’s disease with infliximab: case report

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