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.     

Abdominoperineal resection for severe perianal Crohn's disease

Despite the high incidence of involvement of the perianal region in Crohn's disease, excisional surgery seldom is required for perianal disease alone. Nine patients are presented who had severe perianal Crohn's disease, which eventually required abdominoperineal excision of the anorectum. In all nine patients, it was secondary manifestations of anal Crohn's disease that precipitated proctectomy, such as high fistulas, strictures, and rectovaginal fistulas. These secondary phenomena, especially fistulas caused by cavitating ulceration, become self-perpetuating by the mechanical effect of feces being forced into the tract. During the same period, 17 patients required rectal excision by abdominoperineal resection, where perianal disease was incidental to severe colorectal disease. There is a tendency for excessive delay before advising surgery for severe perianal disease. An attempt should be made to identify patients with a poor prognosis to avoid unnecessarily prolonged morbidity. Assessment of the exact nature of the anal lesion and assessment of Crohn's disease activity are important in making this decision.     

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.     

Computer-assisted evaluation of perianal fistula activity by means of anal ultrasound in patients with Crohn's disease

OBJECTIVES: Assessment of the activity of perianal fistulas may be of clinical relevance in patients with Crohn's disease. Fistula activity is currently evaluated by means of magnetic resonance imaging; anal ultrasound can also be used, but its diagnostic performance in this setting remains to be defined. Our aims were to evaluate the agreement between clinical examination, magnetic resonance imaging, and anal ultrasound in assessing perianal fistula activity, and to apply computerized analysis to improve the assessment of ultrasound images. METHODS: Thirty-one consecutive patients with Crohn's perianal fistulas underwent clinical examination, and magnetic resonance and anal ultrasound imaging. Active fistulas were defined as the presence of active drainage or signs of local inflammation on clinical examination, and the definition was confirmed by surgical examination. Activity was assessed on the basis of T2 hyperintensity on magnetic resonance imaging and the degree of hypoechogenicity on anal ultrasound; the anal ultrasound images were also analyzed using dedicated computer image-analysis software. RESULTS: Twenty-five patients had an active fistula at clinical examination. The agreement between clinical examination and magnetic resonance imaging was good (k-value = 0.739), whereas that with anal ultrasound was only fair (k-value = 0.266-0.294); computer-assisted analysis of the anal ultrasound images improved the agreement from fair to good (k-value = 0.608-0.670). CONCLUSIONS: Anal ultrasound can be used to assess fistula track activity in patients with Crohn's disease. The diagnostic performance of the technique can be improved to values comparable with those of magnetic resonance imaging by using a computer-assisted evaluation of the anal ultrasound images.     

Experience with perirectal fistulas in patients with Crohn's disease

The experience of the senior author has been reviewed in dealing with perianal fistulas in patients with Crohn's disease. Early surgical therapy was advocated, the theory being, that perianal fistulas start as intersphincteric fistulas. This fistula is easily controlled surgically by fistulotomy with partial internal anal sphincterotomy. Delay in surgical treatment, especially in Crohn's patients, results in more complicated fistulas that may require colostomy or proctectomy. The presence of Crohn's disease did not affect the healing of fistulotomy. In our series fistulotomy was the treatment of choice in patients with 26 fistulas; 18 of 19 went on to full healing. We conclude that early fistulotomy, before an intersphincteric fistula has time to blossom fistulotomy, before an intersphincteric fistula has time to blossom into a more difficult management problem, is the treatment of choice in patients with Crohn's disease who have perianal fistulas Read at the XIIth, Biennial Congress of the International Society of University Colon and Rectal Surgeons, Glasgow, Scotland, July 10 to 14, 1988. Work performed at the Orlando Regional Medical Center, Orlando, Florida.     

Endoscopic sonography of the anorectum in inflammatory rectal diseases]

213 patients, classified in 3 groups, were examined in a prospective trial using endorectal ultrasound. 80 patients (group A) had no anorectal disease, the endorectal ultrasound showed normal structures of the anorectum and the perirectal tissue. 80 patients (group B) suffered from Crohn's disease, 30 of them had no clinical signs, the rest of this group (50 patients) felt pain in the anal/perianal region. 83 patients (group C) had perianal abscesses or fistulas, Crohn's disease could be excluded. In all 64 perianal fistulas and 66 perianal abscesses were diagnosed. The results of the rectal-proctological examination were compared with endorectal ultrasound. 100% of the perianal abscesses could be recognized using endosonography. The digital-proctological examination revealed only 57% of perianal abscesses and 48% of perianal fistulas; the supralevatory abscesses couldn't be detected proctologically at all. By endorectal ultrasonography we obtained useful informations about localization and extension of the inflammatory process. From a therapeutic and prognostic view the endorectal ultrasound is a simple, practicable and useful method to investigate perianal and anorectal diseases.     

Endosonographic evidence of persistence of Crohn's disease-associated fistulas after infliximab treatment, irrespective of clinical response.

PURPOSE: Infliximab has been reported to improve fistulizing Crohn's disease. Moreover, prompt healing of mucosal ulcers has been described. Whether fistulas disappear or remainders of fistulas persist is unknown. This study documents fistulous tracts before and after infliximab therapy by means of hydrogen peroxide-enhanced endosonography METHODS: Eight patients with perianal, vaginal, or perineal fistulas were treated with a triplet of infliximab 5 mg/kg infusions. At baseline, and at Week 4 after the last infusion, fistulas were documented by local inspection, digital examination, and hydrogen peroxide-enhanced anal or vaginal endosonography. RESULTS: Patients with vaginal or perineal fistulas did not respond clinically to therapy, whereas patients with perianal fistulas improved considerably. However, in all patents remainders of fistulous tracts were demonstrated by endosonographic techniques. CONCLUSIONS: Short-term treatment of Crohn's disease-associated fistulas with infliximab does not induce disappearance of fistulous tracts, irrespective of therapeutic response.     

Factors related to frequency,type, and outcome of anal fistulas in Crohn's disease

PURPOSE: Relation of clinical factors to frequency, type, and, in particular, outcome of anal fistulas in Crohn's disease was studied. METHODS: One hundred twelve patients seen in this hospital between January 1972 and June 1993 who suffered from Crohn's disease were included in the study. Those 35 (31 percent) with anal fistulas were reexamined or interviewed and asked about their perianal symptoms and anal control. RESULTS: Rectal involvement of Crohn's disease was associated with an increased incidence of anal fistula (49 vs. 17 percent;P <0.01), especially high ones (82 vs. 17 percent;P <0.01). Ten of 18 patients with low fistulas underwent fistulotomy; all 10 fistulas healed, but slowly (mean healing time, 7.5 months), and 4 of them recurred. Of eight low fistulas managed by drainage alone, four healed. Finally, 11 of 18 patients with low fistulas had their fistulas healed. Fourteen of 17 patients with high fistulas were primarily treated by drainage and 3 by local surgery. Finally, only three patients had healed fistulas—two after simple drainage and one after local surgery, and seven patients had to undergo proctectomy. Only two patients with low fistulas required proctectomy. Eight patients (33 percent) of those 24 with fistulas in whom anal continence could be assessed, 5 with local surgery and 3 with drainage alone, reported minor defects in anal control. CONCLUSIONS: Fistulotomy is a justifiable option with satisfactory results for low symptomatic anal fistulas associated with Crohn's disease, although healing may be delayed and some fistulas will recur. Outcome of high fistulas is less satisfactory, and proctectomy is ultimately required in a number of patients; therefore, for high fistulas a conservative approach is primarily recommended.     

Carcinoma arising in anorectal fistulas of Crohn's disease

PURPOSE: Anorectal fistulas are commonly associated with Crohn's disease. Carcinoma arising in an anal fistula in the absence of Crohn's disease occurs rarely. Carcinoma arising in an anorectal fistula of Crohn's disease is likewise rare and is the subject of this article. METHODS: We have seen eight cases in seven patients. Four of these were squamous carcinoma and three were adenocarcinoma. Details of these seven patients are presented. RESULTS: Two deaths in the four patients with squamous carcinoma and one in the two patients with adenocarcinoma with adequate follow-up suggest a poorer prognosis in both types of malignancy than when these lesions occur without Crohn's disease. CONCLUSION: Carcinoma does arise in the midst of the anorectal fistulas and abscesses of Crohn's disease. Carcinoma arising in a Crohn's disease fistula can be very difficult to diagnose. Examination may be limited by pain, stricture, or induration of the perianal and perineal tissues. Examination under anesthesia can also overlook the lesion. Diagnostic examination under anesthesia yields increases with biopsies or curettage of the fistulous tracts.     

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.     

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.     

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.     

Multidisciplinary and evidence-based management of fistulizing perianal Crohn's disease

Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial toimprove outcomes.     

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.     

Imaging of perianal Crohn''s disease

Perianal fistulas and abscesses are common complications of Crohn's disease, affecting up to 50% of patients during their disease course. Accurate diagnosis and classification of perianal disease is crucial before and during treatment to plan an adequate approach for each patient and to avoid irreversible functional consequences. Although examination under anaesthesia has been considered the gold standard for diagnosis and classification of Crohn's disease perianal fistulas, taken alone it does not have perfect accuracy, stressing the need for concomitant or alternative, non-invasive, methods of evaluation. In this context, imaging modalities assessed for diagnosis, classification and monitoring of Crohn's disease perianal fistulas include pelvic magnetic resonance imaging, anorectal endoscopic ultrasonography, transcutaneous perianal ultrasound, fistulography and computed tomography. In particular, magnetic resonance imaging and endoscopic ultrasonography findings have shown the best accuracy, and the ability to influence therapeutic management of these patients. For transcutaneous perianal ultrasound too, good preliminary data have been reported. This paper reviews the available data on imaging methods for the management of perianal Crohn's disease.     

Antimicrobial peptides in chronic anal fistula epithelium

OBJECTIVE: Anal fistulas are the result of chronic infection of an intersphincteric gland. Despite the passage through mesenchymal tissue, fistulas seldom lead to systemic infection. Antimicrobial peptides are secreted by a variety of epithelia, belonging to the innate immune system and are potential factors contributing to infection control. The aim of this study was to investigate whether epithelium is present in the fistulas and what the origin might be. MATERIAL AND METHODS: Forty-seven chronic anal fistulas from patients, excluding Crohn's disease, were compared with healthy rectal and perianal control tissue. Expression of antimicrobial peptide mRNA was analysed by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Tissue was further studied by cytokine and cytokeratin staining. RESULTS: Chronic anal fistulas express high levels of hBD-2 and hBD-3 and the newly identified antimicrobial peptides RNase7 and psoriasin compared to rectal mucosa from control patients. Perianal skin has almost identical levels of RNase7 and psoriasin expression to those in fistulas. IL-1b and IL-8 were the only cytokines detectable in fistulas. Fistulas are lined with squamous epithelium that expresses identical cytokeratines as skin. CONCLUSIONS: Epithelialization and local production of antimicrobial peptides in anal fistulas serve as defence mechanisms to prevent local and systemic infection by microbes from faeces passing through the fistula tract.     

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 in the treatment of Crohn''s disease: Predictors of response in an Italian multicentric open study

BACKGROUND: Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. AIMS.: To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. PATIENTS AND METHODS: Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI)>220-400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endpoints of the study were clinical response and clinical remission for luminal refractory and fistulising disease. We evaluated at univariable and multivariable analysis the following variables: number of infusions, sex, age at diagnosis, smoking habit, site of disease, previous surgery, extraintestinal manifestations and concomitant therapies, and type of fistulas. RESULTS: Patients with luminal refractory disease: 322 patients (84.1%) had a clinical response and 228 (59.5%) reached clinical remission. Patients with fistulising disease: 187 patients (72%) had a reduction of 50% of the number of fistulas and in 107 (41%) a total closure of fistulas was observed. For luminal disease, single infusion (OR 0.49, 95% CI 0.28-0.86) and previous surgery (OR 0.53, 95% CI 0.30-0.93) predicted a worse response for fistulising disease. Other fistulas responded worse than perianal fistulas (OR 0.57, 95% CI 0.303-1.097). CONCLUSION: In Crohn's disease infliximab is effective in luminal refractory and in fistulising disease. A single infusion and previous surgery predicted a worse response in luminal disease whereas perianal fistulas predicted a better response than other type of fistulas.     

Crohn disease associated with Turner's syndrome (a possible physiopathological mechanism)

We describe a patient with Turner's syndrome who has developed chronic diarrhea, anal fissures, rectovaginal and perianal fistulas. Radiological study of the ileum and rectal mucosa biopsy have confirmed the diagnosis of Crohn's disease. Like the majority of patients previously described with similar pathological association, the intestinal disease in our patient starts at the time wherein the pubertal pituitary crisis happens. The lack of gonadal counter-regulation following the pubertal pituitary crisis leads to an hormonal imbalance with elevated FSH and LH levels. We suppose that this hormonal imbalance can activate immunopathogenic mechanisms related to Crohn's disease.     

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.