Clinical and radiological responses after infliximab treatment for perianal fistulizing Crohn's disease

OBJECTIVES: Infliximab is an effective therapy for fistulizing Crohn's disease of the perineum. We sought to determine whether the clinical improvement after infliximab is associated with radiological closure of fistula tracts. METHODS: Clinical responses and radiological imaging studies by transperineal ultrasound were evaluated in 35 patients with Crohn's disease perianal fistulas after treatment with infliximab 5 mg/kg up to 48 wk. Paired comparison of baseline and follow-up imaging studies at 8 wk and at 56 wk or discontinuation were assessed by an imaging score of perianal fistula severity, based on the Parks criteria. Complete clinical fistula closure and radiological healing were primary outcome measures. RESULTS: At 8 wk, after two infusions of infliximab at 0 and 2 wk, clinical fistula closure occurred in 49% of patients. The radiological score at 8 wk was higher for patients with clinical fistula closure than for patients with no clinical improvement (p= 0.023) and two patients showed complete radiological healing. At 56 wk, clinical fistula closure occurred in 46% patients. Clinical fistula scores correlated with radiological scores (R2= 0.52; p < 0.001) but were not associated with fistula complexity, number of fistulas, or number of collections at baseline imaging. The proportion of patients with marked radiological improvement increased from 14% at 8 wk to 43% at 56 wks (p= 0.015) and complete radiological healing occurred in 4 (11%) patients. CONCLUSIONS: For perianal fistulizing Crohn's disease, repeat dose infliximab improves clinical and radiological outcomes, although complete radiological healing occurs in a minority of patients.     

Treatment of perianal fistulizing Crohn's disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement

Perianal fistulas occur in approximately 30% of patients with Crohn's disease (CD). Infliximab, a chimeric monoclonal antibody targeting human tumor necrosis factor alpha (TNF), is approved for the treatment of fistulizing CD. Although the initial response to infliximab is dramatic, the median duration of fistula closure is approximately 3 months, and repeated infusions are often required. An exam under anesthesia (EUA) by a surgeon allows for complete inspection of the fistula as well as incision and drainage of an abscess and placement of a seton. Our aim was to compare the rate of perianal fistula healing, relapse rate, and time to relapse in patients with fistulizing CD treated with infliximab alone or as an adjunct to surgical EUA with seton placement. Thirty-two consecutive patients with perianal fistulizing CD who completed at least 3 infusions with infliximab (5 mg/kg at 0, 2, 6 weeks) between October 1999 and October 2001 were analyzed. All patients had at least 3 months of follow-up after the third dose of infliximab. Response was defined as complete closure and cessation of drainage from the fistula. Patients with CD and perianal fistulas who had an EUA prior to infliximab infusions had a better initial response (100% vs. 82.6%, p = 0.014), lower recurrence rate (44% vs. 79%, p = 0.001), and longer time to recurrence (13.5 months vs. 3.6 months, p = 0.0001) compared with patients receiving infliximab alone. In conclusion, patients with fistulizing CD treated with infliximab are more likely to maintain fistula closure if treatment is preceded by EUA and seton placement.     

Does Infliximab Infusion Impact Results of Operative Treatment for Crohn’s Perianal Fistulas?

PURPOSE: Infliximab is an effective treatment for active intestinal Crohn's disease; however, the efficacy of infliximab in perianal Crohn's disease is controversial. This study was designed to compare patients with Crohn's disease who underwent perianal fistula surgery with or without infliximab infusion. METHODS: A retrospective chart review of 226 consecutive patients with Crohn's disease who underwent operative treatment with or without infliximab (3-6 infusions of 5 mg/kg) from March 1991 through December 2005 was completed. Patients were classified as completely healed, minimally symptomatic (seton placement with minimal drainage and/or infliximab dependence), and failure (persistent or recurrent symptomatic fistula, diverting procedure, or proctectomy). RESULTS: A total of 226 patients underwent operative treatment alone (n = 147) or in combination with infliximab infusion (n = 79). Age, gender, and preoperative history of intestinal and perianal Crohn's disease were similar between groups. Mean follow-up was 30 (range, 6-216) months. Operative treatment consisted of seton drainage (n = 112), conventional fistulotomy (n = 92), fibrin glue injection (n = 14), advancement flap (n = 5), collagen plug insertion (n = 2), and transperineal repair (n = 1). Eighty-eight patients (60 percent) healed completely with operative treatment alone, and 47 patients (59 percent) healed after operative treatment in combination with infliximab (P = not significant). CONCLUSIONS: Operative treatment of perianal fistulas in patients with Crohn's disease resulted in complete healing in approximately 60 percent of patients. Preoperative infliximab infusion did not affect overall healing rates.     

Treatment of perianal fistulas in Crohn's disease by local injection of antibody to TNF-alpha accounts for a favourable clinical response in selected cases: a pilot study

OBJECTIVE: Intravenously administered infliximab, a monoclonal antibody directed against tumor necrosis factor-alpha, has been proven to be efficacious in the treatment of fistulas in patients with Crohn's disease. It has recently been suggested that local injections of infliximab might be beneficial as well. The aim of this study was to assess whether infliximab could play an effective role in the local treatment of perianal fistulas in Crohn's disease. MATERIAL AND METHODS: Local infliximab injections were administered to 11 patients suffering from Crohn's disease complicated by perianal disease. Eligible subjects included Crohn's disease patients with single or multiple draining fistulas, regardless of status of luminal disease at baseline. Patients, however, were excluded from the study if they had perianal or rectal complications, such as abscesses or proctitis or if they had previously been treated with infliximab. Twenty-milligram doses of infliximab were injected along the fistula tract and around both orifices at baseline and then every 4 weeks for up to 16 weeks or until complete cessation of drainage. No further doses were administered to patients who did not respond after three injections. Efficacy was measured in terms of response (a reduction in fistula drainage of 50% or more) and remission (complete cessation of fistula drainage for at least 4 weeks). Time to loss of response and health-related quality of life were also evaluated. RESULTS: Overall, 8/11 patients (72.7%) responded to the therapy and 4/11 (36.4%) reached remission, whereas 3/11 patients (27.2%) showed no response. Response or remission was very much dependent on the location of the fistulas, and time to loss of response was generally longer for patients who reached remission compared to patients in response. Changes in health-related quality of life, as assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ), also reflected response or remission, with more marked improvements associated with remission. After a mean 10.5 months' follow-up (range 7-18 months), 6/11 patients (54.5%) are in response and 4/11 patients (36.4%) are in remission. No adverse events have been observed in this cohort of patients. CONCLUSIONS: Local injections of infliximab along the fistula tract seem to be an effective and safe treatment of perianal fistulas in Crohn's disease. However, further controlled clinical investigations are warranted.     

Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn's disease

OBJECTIVES: Although the clinical efficacy of infliximab as measured by closure of fistulas in Crohn's disease has been demonstrated, its influence on the inflammatory changes in the fistula tracks is less clear. The aim of the present study was to assess the behavior of perianal fistulas before and after infliximab treatment. METHODS: Magnetic resonance imaging (MRI) and clinical evaluation were performed in a total of 18 patients before and after treatment with infliximab. An MRI-based score of perianal Crohn's disease severity was developed using both criteria of local extension of fistulas (complexity, supralavetoric extension, relation to the sphincters and of active inflammation (T2 hyperintensity, presence of cavities/abscesses, and rectal wall involvement). RESULTS: The MRI score was reliable in assessing the fistula tracks, with a good interobserver concordance (p < 0.001). Fistula tracks with signs of active inflammation were found in all 18 patients at baseline and collections in seven. After short-term infliximab treatment, active tracks persisted in eight of 11 patients who had clinically responded to infliximab. After long-term (46 wk) infliximab therapy, MRI signs of active track inflammation had resolved in three of six patients. CONCLUSIONS: We have developed an MRI-based score of perianal Crohn's disease severity to assess the anatomical evolution of Crohn's fistulas. Our study demonstrates that despite closure of draining external orifices after infliximab therapy, fistula tracks persist with varying degrees of residual inflammation, which may cause recurrent fistulas and pelvic abscesses. Whether complete fistula fibrosis occurs over time with repeated infliximab infusions needs further study.     

Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn’s disease with anal endosonographic monitoring: a single-centre experience

During infliximab treatment of perianal Crohn's disease (CD), the healing of the skin opening precedes fistula tract healing and this contributes to abscess formation and fistula recurrence. The aims of this study were to evaluate the efficacy of combined treatment with infliximab and setons for complex perianal fistulas in CD and to define the optimal time for seton removal by anal endosonography (AE). Nine consecutive patients with CD were studied. Perianal sepsis was eradicated when necessary and setons were placed before infliximab therapy. Setons were removed after AE evidence of fistulous tracts healing. Patients received a mean of 10+/-2.3 infliximab infusions. At week 6 all patients showed a reduction in mean CD activity index (p<0.005) and perianal disease activity index (p<0.0001). Complete fistula response was achieved in eight of nine patients. In six patients after a mean of 9.2 infusions, infliximab treatment was discontinued. Clinical and AE response persisted at 19.4+/-8.8 months (range 3-28 months) in five of these patients. One patient had fistula recurrence 20 weeks after infliximab discontinuation and responded rapidly to retreatment. At the time of this report, two patients were still on infliximab and in remission after a mean follow-up of 25+/-5 months. Combined therapy with infliximab and setons with AE monitoring of the response showed high efficacy in the management of patients with CD with complex perianal fistulas.     

Remicade does not abolish the need for surgery in fistulizing Crohn's disease

PURPOSE: Tumor necrosis factor antagonist therapy in the form of infliximab has been shown to promote significant healing in fistulizing Crohn's disease and therefore is often considered as a possible alternative to surgery. Our aim was to evaluate the role of infliximab in supplanting surgery for fistulizing Crohn's disease. METHODS: We performed a retrospective chart review of all adult patients who received infliximab for fistulizing Crohn's disease at one institution between September 1998 and October 2000. RESULTS: Twenty-six patients (14 male; mean age, 38 years; range, 19-80 years) received a mean of three (range, one to six) doses of infliximab (5 mg/kg) with the intent to cure fistulizing Crohn's disease. Nine patients (35 percent) had perianal, 6 (23 percent) enterocutaneous, 3 (12 percent) rectovaginal, 4 (15 percent) peristomal, and 4 (15 percent) intra-abdominal fistulas. Nineteen (73 percent) of the patients had had prior surgery for Crohn' s disease. Six patients (23 percent) had a complete response to infliximab with fistula closure, 12 (46 percent) had a partial response, and 8 (31 percent) had no response to infliximab. Fourteen (54 percent) patients still required surgery for their fistulizing Crohn's disease after infliximab therapy (10 bowel resections, 4 perianal procedures), whereas half (6/12) of the patients treated with infliximab who still had open fistulas after treatment declined surgical intervention. Five of six patients with fistula closure on infliximab had perianal or rectovaginal fistulas. None of the patients with either enterocutaneous or peristomal fistulas were healed with infliximab. CONCLUSIONS: Although it was associated with a 61 percent complete or partial response rate, infliximab therapy did not supplant the need for surgical intervention in the majority of our patients with fistulizing Crohn's disease. Seventy-three percent of the patients either required surgery or still had open fistulas after infliximab therapy. Infliximab was much more effective in treating perianal disease than abdominal enterocutaneous disease.     

Perianal Crohn's disease

PURPOSE: This study relates our experience with local surgical management of perianal Crohn's disease. METHOD: Of 1,735 patients with Crohn's disease seen between 1980 and 1990, records of 66 patients (3.8 percent) with symptomatic perianal Crohn's disease treated by local operations were retrospectively reviewed to study outcome of local surgical intervention. RESULTS: All patients had intestinal disease that was limited to the colon in 32 patients (48 percent), ileocolonic region in 22 patients (33 percent), and ileum in 12 patients (18 percent). Types of perianal disease encountered included perianal suppuration (57), anal fistula (47), anal fissure (21), anal stenosis (5), gluteal abscess (3), scrotal abscess (2), and anovaginal fistula (2). A total of 321 episodes of anal complications necessitated 256 local surgical interventions. Local anorectal operations performed included simple incision and drainage of abscess (57), fistulotomy (35), incision and drainage of complex anorectal abscesses and fistulas and insertion of seton (24), internal sphincterotomy (6), fissurectomy (1), and anal dilation (3). Of 24 patients with horseshoe abscesses and fistulas managed with insertion of a seton and 35 patients who underwent fistulotomy as a primary procedure or in conjunction with drainage of an abscess, none experienced fecal incontinence as a direct result of the operation. Thirteen patients required proctectomy to control perianal disease, and a similar number underwent total proctocolectomy for extensive intestinal disease. Forty patients (61 percent) continue to retain a functional anus. CONCLUSION: Patients with symptomatic low anal fistula involving minimum sphincter musculature can be treated safely with fistulotomy. In treatment of patients with horseshoe abscesses and high fistulas, aggressive local surgical intervention using a seton permits preservation of the sphincter and good postoperative function.Poster presentation at the meeting of the American Gastroenterological Association, Digestive Disease Week, San Diego, California, May 14 to 17, 1995.     

Combining infliximab with 6-mercaptopurine/azathioprine for fistula therapy in Crohn's disease

OBJECTIVES: Fistulas occur in about one third of patients with Crohn's disease and rarely heal spontaneously. Conventional medical and surgical therapy often fails. The anti-TNF-alpha antibody infliximab offers a novel therapeutic option. By this approach, closure of fistulas was reported in 45% of cases. However, after discontinuation of therapy, most fistulas recurred. Azathioprine and 6-mercaptopurine (6-MP) are effective drugs in Crohn's disease and lead to closure of fistulas in 30-40% of cases. Thus, the aim of this study was to evaluate the combination of infliximab with 6-mercaptopurine/azathioprine as therapy for fistulas in patients with Crohn's disease. METHODS: A total of 16 patients (mean age 37 yr) with Crohn's fistulas resistant to conventional measures were treated with a combination of three or four infusions of infliximab and long term 6-MP/azathioprine. In all, 13 patients had perianal fistulas, two had abdominal fistulas, and one patient had both perianal and recto-vaginal fistulas. Therapy success was defined as complete closure of fistulas for a minimum observation period of 6 months after fistula closure. RESULTS: In 12 (75%) of the 16 patients, we observed complete closure of the fistulas that persisted for >6 months (median follow-up 10 months, range 6-11 months). The median time to complete closure of fistulas was 14 days (range 2-36 days). In four patients, therapy success was not achieved. CONCLUSION: Our pilot study reveals that concomitant and long term 6-MP/azathioprine therapy could prolong the effect of an initial infliximab therapy on fistula closure in patients with Crohn's disease. These data prompt larger controlled trials.     

Combined seton placement,infliximab infusion,and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn's disease: a single center experience

PURPOSE: Infliximab (anti-TNF ) has been used for the treatment of fistulizing Crohns disease with variable efficacy. The aim of this study was to evaluate the efficacy of infliximab combined with selective seton drainage in the healing of fistulizing anorectal Crohns disease. METHODS: This was a retrospective chart review of all patients with fistulizing Crohns disease treated with infliximab between March 2000 and February 2002. RESULTS: Twenty-nine patients (12 male; mean age, 31 years) received a mean of 3 (range, 1–5) doses of infliximab 5 mg/kg. Twenty-one patients had perianal fistulas; eight had rectovaginal fistulas, four with combined rectovaginal/perianal fistula. Fourteen of 21 patients (67 percent) with perianal fistula had a complete response (mean follow-up, 9 months), 4 of the 14 relapsed (mean, 6 months), but all had a complete response to retreatment (mean, 9 months). A partial response occurred in four patients (19 percent), defined by decreased drainage (2 patients) or infliximab dependence (2 patients) requiring repeated dosing every six to eight weeks. Three patients (14 percent) had no response. Seton drainage was used before infusion in 13 perianal patients for perianal infection and 17 were treated with maintenance azathioprine or methotrexate. Of eight patients with rectovaginal fistula, complete response occurred in one, partial response in five, and no response in two. Two partial responders became infliximab dependent. A complete response was observed in one patient with isolated rectovaginal fistula, a partial response in five. No patient with a combined rectovaginal/perianal fistula had a complete response. Five rectovaginal fistula patients were taking maintenance immunosuppressive agents and two had seton drainage before infusion. CONCLUSIONS: Selective seton placement combined with infliximab infusion and maintenance immunosuppressives resulted in complete healing in 67 percent of Crohns patients with perianal fistula and partial healing in 19 percent. Relapse was successfully treated with repeat infusion. Concomitant rectovaginal fistula was a poor prognostic indicator for successful infliximab therapy.     

Emerging treatments for complex perianal fistula in Crohn＇s disease

Complex perianal fistulas have a negative impact on the quality of life of sufferers and should be treated. Correct diagnosis, characterization and classification of the fistulas are essential to optimize treatment. Nevertheless, in the case of patients whose fistulas are associated with Crohn＇s disease, complete closure is particularly difficult to achieve. Systemic medical treatments （antibiotics, thiopurines and other immunomodulatory agents, and, more recently, anti-tumor necrosis factor-α agents such as infliximab） have been tried with varying degrees of success. Combined medical （including infliximab） and less aggressive surgical therapy （drainage and seton placement） offer the best outcomes in complex Crohn＇s fistulas while more aggressive surgical procedures such as fistulotomy or fistulectomy may increase the risk of incontinence. This review will focus on emerging novel treatments for perianal disease in Crohn＇s patients. These include locally applied infliximab or tacrolimus, fistula plugs, instillation of fibrin glue and the use of adult expanded adipose-derived stem cell injection. More welldesigned controlled studies are required to confirm the effectiveness of these emerging treatments.     

A comparison of endoscopic ultrasound, magnetic resonance imaging, and exam under anesthesia for evaluation of Crohn's perianal fistulas.

BACKGROUND & AIMS: To determine accuracy of endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) for evaluation of Crohn's disease perianal fistulas. METHODS: Thirty-four patients with suspected Crohn's disease perianal fistulas were prospectively enrolled in a blinded study comparing EUS, MRI, and examination under anesthesia (EUA). Fistulas were classified according to Parks' criteria, and a consensus gold standard was determined for each patient. Acceptable accuracy was defined as agreement with the consensus gold standard for > or =85% of patients. RESULTS: Three patients did not undergo MRI; 1 did not undergo EUS or EUA; and consensus could not be reached for 1. Thirty-two patients had 39 fistulas (20 trans-sphincteric, 5 extra-sphincteric, 6 recto-vaginal, 8 others) and 13 abscesses. The accuracy of all 3 modalities was > or =85%: EUS 29 of 32 (91%, confidence interval [CI] 75%-98%), MRI 26 of 30 (87%, CI 69%-96%), and EUA 29 of 32 (91%, CI 75%-98%). Accuracy was 100% when any 2 tests were combined. CONCLUSIONS: EUS, MRI, and EUA are accurate tests for determining fistula anatomy in patients with perianal Crohn's disease. The optimal approach may be combining any 2 of the 3 methods.     

Topical tacrolimus in the treatment of perianal Crohn's disease: exploratory randomized controlled trial

BACKGROUND: The aim of this study is to evaluate the efficacy of topical tacrolimus in treating perianal Crohn's disease. METHODS: Nineteen patients, stratified into 7 with ulcerating, and 12 with fistulizing, perianal Crohn's disease were randomized to topical tacrolimus 1 mg/g (1 g ointment twice a day [bid]) or placebo for 12 weeks. Sixteen patients had been on, or were currently taking, azathioprine/6-MP, and 6 had received infliximab. The primary outcome in ulcerating disease was global improvement in perianal/anal lesions, as assessed by the attending physician; for fistulas, it was reduction of > or =50% of actively draining fistulas on 2 consecutive visits. Blood tacrolimus levels and adverse events were assessed. RESULTS: Three of 4 patients treated with topical tacrolimus for ulcerating disease improved compared with none of 3 in the placebo group. Complete healing was not achieved. In fistulizing disease, topical tacrolimus was not beneficial. Two tacrolimus-treated patients developed perianal abscesses, 1 after improvement in fistula drainage. Adverse events were otherwise infrequent and mild. Whole blood tacrolimus levels were detectable in only 2 patients and were low. CONCLUSIONS: These preliminary data suggest that topical tacrolimus is effective and safe in the treatment of perianal or anal ulcerating Crohn's disease. This therapy is unlikely to be beneficial in fistulizing perianal Crohn's disease, although a larger study is required to confirm this.     

Clinical course of perianal fistulas in Crohn's disease.

The clinical course of perianal fistulas and associated abscesses was evaluated prospectively in 90 patients with Crohn's disease. Fistula type, rectal disease, faecal diversion, and immunosuppression were examined as prognostic indicators for fistula healing and recurrence. Median follow up was 22 months. The outcome was evaluated with life table analysis. Prognostic factors were analysed by multiple regression. Inactivation was achieved in all patients. The risks of recurrent fistula activity were 48% at one year and 59% at two years. Fistulas were healed in 51% after two years but reopened in 44% within 18 months of healing. Faecal diversion and absence of rectal disease decreased recurrence rates (p = 0.019/0.04) and increased healing rates (p = 0.005/0.017). The outcome in patients with trans-sphincteric fistulas was better than that in those with ischiorectal fistulas but worse than in patients with subcutaneous fistulas (p = 0.015 for healing; p = 0.007 for recurrent fistula activity). After initial treatment about 20% of the patients were symptomatic and about 10% had painful events per six month period. Incontinence was rare and did not increase during the study period. Perianal fistulas and associated abscesses can be controlled safely by simple drainage of pus collections. Frequent reinfection and re-opening after healing of fistulas are characteristic. Fistula type, rectal disease, and stool contamination influence the clinical course. Only a few patients, however, have continuous symptoms from perianal fistulas.     

Long-term treatment of rectovaginal fistulas in Crohn's disease: response to infliximab in the ACCENT II Study.

BACKGROUND & AIMS: The ACCENT II study (A Crohn's Disease Clinical Trial Evaluating Infiximab in a New Long-term Treatment Regimen in Patients With Fistulizing Crohn's Disease) evaluated the efficacy and safety of infliximab maintenance treatment in patients with fistulizing Crohn's disease. This post hoc analysis was conducted to determine the efficacy and safety of infliximab therapy in women with rectovaginal fistulas. METHODS: All patients received 5 mg/kg infliximab intravenously at weeks 0, 2, and 6. Patients who achieved response at weeks 10 and 14 then were randomized as responders if they had at least 50% of baseline fistulas closed, or as nonresponders, to receive placebo or infliximab 5 mg/kg every 8 weeks through week 54. RESULTS: Of 282 patients in the ACCENT II study, 25 of 138 (18.1%) women had a total of 27 draining rectovaginal fistulas at baseline. After infusions of infliximab at weeks 0, 2, and 6, 60.7% (17 of 28) and 44.8% (13 of 29) of rectovaginal fistulas were closed at weeks 10 and 14, respectively. Among responders, 72.2% (13 of 18) of rectovaginal fistulas were no longer draining at week 14. The duration of rectovaginal fistula closure was longer in the infliximab 5-mg/kg maintenance group (median, 46 wk) than in the placebo group (33 wk). CONCLUSIONS: Infliximab is effective in short-term closure of rectovaginal fistulas and maintenance treatment was more effective than placebo in prolonging rectovaginal fistula closure.     

Perianal abscess in Crohn's disease

PURPOSE: Perianal disease is frequent in patients with Crohn's disease, and many of these patients will eventually have abscess formation. In a prospective follow-up study, we evaluated factors influencing the occurrence and recurrence of perianal abscesses. METHODS: Of 126 consecutive patients with perianal Crohn's disease seen regularly in an outpatient clinic, 61 (48.4 percent) had at least one perianal abscess (mean follow-up, 32±17 months). In all, 110 episodes of an abscess with 145 anatomically distinct abscesses were documented. RESULTS: The occurrence of first abscesses was dependent on the type of anal fistula (ischiorectal, 73 percent; transsphincteric, 50 percent; superficial, 25 percent;P < 0.02). Surgical therapy consisted of seton drainage (34 percent), mushroom catheter drainage (49 percent), or incision and drainage (29 percent) and led to inactivation in all patients. Cumulative two-year recurrence rates after the first and second abscess were 54 and 62 percent, respectively. Abscess recurrence was less frequent in patients with a stoma (13 vs. 60 percent in patients without stoma after two years) and in patients with superficial anal fistulas (0 vs. 55 percent/56 percent in patients with transsphincteric/ischiorectal fistulas). Only two abscesses recurred within one year after removal of seton drainage, whereas 13 abscesses recurred with the seton still in place. Neither intestinal nor rectal activity of Crohn's disease significantly influenced the occurrence of an abscess. During the study period, only two patients developed partial stool incontinence. CONCLUSION: Development of perianal abscesses in Crohn's disease depends on the fecal stream and the anatomic type of anal fistula. Seton and catheter drainage are safe and highly effective in treatment. Long-term use of setons to prevent recurrent abscesses is not supported by our data.     

Treatment of complex perianal fistulas with seton and infliximab in adolescents with Crohn's disease

Background and aimsTreatment of complex perianal fistulas associated with Crohn's disease is challenging. In adults, seton drainage combined with infliximab therapy has proven to be more effective than either one alone. Results following such treatment among pediatric patients have not been reported previously. The aim of this study was to describe outcomes after combined seton and infliximab treatment for complex perianal fistulas in adolescents with Crohn's disease.MethodsWe performed a retrospective medical record review of all consecutive Crohn's disease patients treated for perianal fistulas with seton drainage and infliximab between 2007 and 2013 (n = 13). A follow-up interview was conducted at median of two years.ResultsMedian age at fistula diagnosis was 14 years. Following seton placement in fistula tracks, infliximab induction was administered at weeks 0, 2, and 6 and maintenance therapy at 8-week intervals. Over 90% responded to seton drainage and infliximab induction. Final fistula response was obtained at median of 8 weeks, being complete in 77% and partial in 15%. Setons were kept in place for median of 8 months. Fistulas recurred in 23% over a year after the final response. At last follow-up, 85% still had a response and 70% were free from perianal symptoms. Most were still on anti-TNF-α therapy, but one third had switched to adalimumab. Patients' anorectal function was well preserved and overall satisfaction with the treatment was high.ConclusionsThe results suggest that combining seton drainage with infliximab therapy improves the perianal fistula response rates in pediatric patients.     

The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota

BACKGROUND & AIMS: Little is known about the cumulative incidence and natural history of fistulas in Crohn's disease in the community. METHODS: The medical records of all Olmsted County, Minnesota residents who were diagnosed with Crohn's disease from 1970 to 1993 and who developed a fistula were abstracted for clinical features and outcomes. Six patients denied research authorization. The cumulative incidence of fistula from time of diagnosis was estimated by using the Kaplan-Meier product-limit method. RESULTS: At least 1 fistula occurred in 59 patients (35%), including 33 patients (20%) who developed perianal fistulas. Twenty-six (46%) developed a fistula before or at the time of formal diagnosis. Assuming that the 9 patients with fistula before Crohn's disease diagnosis were instead simultaneous diagnoses, the cumulative risk of any fistula was 33% after 10 years and was 50% after 20 years (perianal, 21% after 10 years and 26% after 20 years). At least 1 recurrent fistula occurred in 20 patients (34%). Most fistulizing episodes (83%) required operations, most of which were minor. However, 11 perianal fistulizing episodes (23%) resulted in bowel resection. CONCLUSIONS: Fistulas in Crohn's disease were common in the community. In contrast to referral-based studies, only 34% of patients developed recurrent fistulas. Surgical treatment was frequently required.     

Infliximab: lack of efficacy on perforating complications in Crohn's disease

BACKGROUND: Infliximab (Remicade), a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), has emerged as promising therapeutic option in perianal fistulizing Crohn's disease (CD). However, little knowledge exists about its use for the treatment of internal fistulas in CD. We present our experience with infliximab in this situation. METHODS: Four patients with CD who had internal fistulas (Case 1: entero-enteral and entero-abdominal; Case 2: entero-enteral; Case 3: entero-enteral and parastomal; Case 4: entero-vesical) were treated with 3 infusions of infliximab (5 mg/kg body weight) with intervals of 2 and 4 weeks. In addition, 3 patients had strictures and 2 patients had perianal fistulas. RESULTS: After the three infusions of infliximab (5 mg/kg body weight), internal fistulas remained unchanged in all patients. The perianal fistulas present in 2 cases were healed. Administration of infliximab was safe and well tolerated in all cases. CONCLUSION: Treatment with 3 infusions of infliximab (5 mg/kg body weight) led to healing of only the perianal fistulas, whereas the internal fistulas were not influenced. We conclude that in these 4 cases, infliximab was well tolerated but not effective for the management of internal fistulas and was no alternative for surgery.     

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.