Long-term outcome of enterocutaneous fistula in patients with Crohn's disease treated with anti-TNF therapy: a cohort study from the GETAID.

OBJECTIVES: Although anti-tumor necrosis factor (TNF) therapy is the treatment of choice for perianal fistulizing Crohn's disease (CD), the efficacy and safety of anti-TNF therapy in enterocutaneous fistula (ECF) remains unclear. METHODS: Between January 2008 and December 2009, we retrospectively reviewed the outcomes of all CD patients with ECF (excluding perianal fistula) treated with anti-TNF therapy followed up in Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) centers. ECF closure and tolerance of anti-TNF therapy were studied using univariate and multivariate analyses. RESULTS: Forty-eight patients (twenty-six women; median age 34.6 (interquartile range=25.0-45.5) years) were included in this study. The median follow-up period was 3.0 (2.0-6.6) years. The fistula was located in the small bowel (n=38), duodenum (n=1), and colon (n=9). The fistula has been developed in ileocolonic anastomosis in 17 (35%) cases. Sixteen patients (33%) had complex fistulas with multiple tracts and eleven patients (23%) had a high ECF output (if wearing an ostomy bag). Complete ECF closure was achieved in 16 (33%) patients, of whom eight relapsed during the follow-up period. In multivariate analysis, complete ECF closure was associated with the absence of multiple ECF tracts and associated stenosis. An abdominal abscess developed in 15 (31%) patients. ECF resection was needed in 26 (54%) patients. One patient died after surgery owing to abdominal sepsis. CONCLUSIONS: In CD patients with ECF, anti-TNF therapy may be effective in up to one-third of patients, especially in the absence of stenosis and complex fistula. A careful selection of patients is mandatory to prevent treatment failure and improves the safety.

Alterations in the intestinal microbiome (dysbiosis) as a predictor of relapse after infliximab withdrawal in Crohn's disease.

BACKGROUND: Crohn's disease (CD)-associated dysbiosis could predispose patients to relapse. Gut microbiota composition of patients from the prospective cohort study designed to identify predictive factors of clinical relapse after infliximab discontinuation (STORI Study) was investigated to determine the impact of dysbiosis in CD relapse. METHODS: Fecal samples from 33 patients with CD in this cohort were collected at baseline, 2 months, 6 months, and at the end of the follow-up period (19 relapsers and 14 nonrelapsers). Healthy volunteers subjects (n = 29) were used as a control group. The fecal microbiota composition was assessed using quantitative PCR, and comparisons between the patient groups were made at different time points using the Wilcoxon test. The analysis of the time-to-relapse was performed according to the baseline median level of each bacterial signal. RESULTS: Dysbiosis was observed in patients with CD compared with healthy subjects, and it was characterized by low mean counts of Firmicutes (Clostridium coccoides [P = 0.0003], C. leptum [P < 0.0001], and Faecalibacterium prausnitzii [P = 0.003]). Lower rates of Firmicutes were seen in relapsers compared with nonrelapsers. Moreover, a low rate of F. prausnitzii (P = 0.014) and a low rate of Bacteroides (P = 0.030) predicted relapse independently from high C reactive protein level (P = 0.0001). CONCLUSIONS: In this work, we report that CD-associated dysbiosis, characterized by a decrease in Firmicutes, correlates with the time-to-relapse after infliximab withdrawal. A deficit in some bacterial groups or species, such as F. prausnitzii, may represent a predictive factor for relapse. Restoring normobiosis in CD could be a new goal for optimal CD management.

Portomesenteric vein thrombosis in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a high risk of deep venous thromboembolism. However, few data are available so far on portomesenteric vein thrombosis (PMVT). The aim of this study was to describe the characteristics of PMVT in patients with IBD. METHODS: A retrospective study was conducted at 13 GETAID (Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif) centers from January 1995 to June 2010. The following data were collected, using a standardized questionnaire: characteristics of IBD, disease status at the time of PMVT, PMVT characteristics and mode of discovery, concomitant prothrombotic disorders, anticoagulant therapy, and evolution of PMVT. RESULTS: Fifty cases (29 men and 21 women; median age, 41 years) were identified, including 14 patients with ulcerative colitis and 36 with Crohn's disease. Thirty-one patients (62%) presented with acute PMVT. Twenty-four patients had previously undergone surgical treatment, and IBD was active in 23 cases (77%) of acute thrombosis. The discovery of PMVT was fortuitous in 40% of our cases. Among the 43 patients screened for a prothrombotic disorder, abnormalities were observed in 17 patients (40%) (mainly hyperhomocysteinemia, n = 12). Forty-four patients (88%) were treated with anticoagulants. Recanalization of the vein was significantly more successful in patients with acute thrombosis (65% versus 37%, P = 0.05). CONCLUSIONS: PMVT can occur when IBD is inactive, and its diagnosis was fortuitous in 40% of our cases. Screening for prothrombotic disorders is essential because it is positive in more than one third of cases.

Pulmonary cryptococcosis in a patient with Crohn's disease treated with prednisone, azathioprine and adalimumab: exposure to chicken manure as a source of contamination.

BACKGROUND: Biotherapies targeting TNFα were proven to be effective in the most severe cases of Crohn's Disease, a chronic granulomatous inflammatory bowel disease that can involve any portion of the digestive tract. The tolerance of anti-TNFα therapy is usually good, although several infectious complications have been reported with these drugs. METHODS: We report a case of a Crohn's disease patient who developed pulmonary cryptococcosis following chicken manure exposition while he received adalimumab and azathioprine. CASE: A 54-year-old man, with history of severe Crohn's disease and ankylosing spondylitis, was admitted for diarrhea and abdominal pain under azathioprine treatment. In December 2010, he was treated with oral prednisone (1 mg/kg/day), but Crohn's disease relapsed when prednisone dose was lower than 30 mg/a day. The patient was then treated with adalimumab, but six weeks later he developed severe pulmonary cryptococcosis. The patient experienced a good outcome under antifungal therapy. We retrospectively found a high exposure to chicken manure in the last weeks. CONCLUSION: Cryptococcosis is an opportunistic infection that can occur under anti-TNFα therapy. The environmental exposure to Cryptococcus spp. (in particular in chicken manure) is a source of contamination. Avoiding exposition to bird manure should be a recommendation for patients who are living in rural areas.

Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped.

BACKGROUND & AIMS: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse. METHODS: We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model. RESULTS: After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% ± 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 × 10(9)/L, and levels of hemoglobin ≤145 g/L, C-reactive protein ≥5.0 mg/L, and fecal calprotectin ≥300 µg/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse. CONCLUSIONS: Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers.

Pregnancy outcome in patients with inflammatory bowel disease treated with thiopurines: cohort from the CESAME Study.

BACKGROUND AND AIMS: Few studies have been conducted addressing the safety of thiopurine treatment in pregnant women with inflammatory bowel disease (IBD). The aim of this study was to evaluate the pregnancy outcome of women with IBD who have been exposed to thiopurines. METHODS: 215 pregnancies in 204 women were registered and documented in the CESAME cohort between May 2004 and October 2007. Physicians documented the following information from the women: last menstrual date, delivery term, details of pregnancy outcome, prematurity, birth weight and height, congenital abnormalities, medication history during each trimester, smoking history and alcohol ingestion. Data were compared between three groups: women exposed to thiopurines (group A), women receiving a drug other than thiopurines (group B) and women not receiving any medication (group C). RESULTS: Mean age at pregnancy was 28.3 years. 75.7% of the women had Crohn's disease and 21.8% had ulcerative colitis, with a mean disease duration of 6.8 years at inclusion. Of the 215 pregnancies, there were 138 births (142 newborns), and the mean birth weight was 3135 g. There were 86 pregnancies in group A, 84 in group B and 45 in group C. Interrupted pregnancies occurred in 36% of patients enrolled in group A, 33% of patients enrolled in group B, and 40% of patients enrolled in group C; congenital abnormalities arose in 3.6% of group A cases and 7.1% of group B cases. No significant differences were found between the three groups in overall pregnancy outcome. CONCLUSIONS: The results obtained from this cohort indicate that thiopurine use during pregnancy is not associated with increased risks, including congenital abnormalities.

Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial.

BACKGROUND & AIMS: The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine (AZA) or 6-mercaptopurine (6-MP) in steroid-dependent Crohn's disease patients. METHODS: Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows: the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months, and the naive stratum consisted of patients not treated previously with AZA/6-MP. Patients were randomized to infliximab 5 mg/kg or placebo at weeks 0, 2, and 6. All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study. The primary end point was remission off steroids at week 24. RESULTS: Among the 113 enrolled patients (55 in the failure stratum), 57 were assigned to infliximab. At week 24, the success rate (intent-to-treat analysis) was higher in the infliximab group than in the placebo group (57% vs 29%; P = .003); at weeks 12 and 52, the corresponding rates were 75% vs 38% (P < .001) and 40% vs 22% (P = .04), respectively. In each stratum, the success rate was significantly higher in the infliximab group at weeks 12 and 24, and a trend was found at week 52. In the failure stratum, only 27% of the patients in the infliximab group were still in remission off steroids, compared with 52% in the naive stratum. Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group. CONCLUSIONS: Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn's disease patients.

Gastrointestinal quality of life before and after laparoscopic heller myotomy with partial posterior fundoplication.

OBJECTIVE: To assess the outcome of laparoscopic Heller myotomy for achalasia using a specific quality of life (QoL) instrument for gastrointestinal disorders. SUMMARY BACKGROUND DATA: Current therapies for achalasia do not restore normal esophageal motility but aim at palliating dysphagia. However, many other symptoms may persist that cannot be assessed objectively by currently available symptom scores. Although generic QoL instruments have shown improvement in QoL after myotomy, disease-specific QoL instruments may be more responsive to change and therefore more reliable for comparing outcomes of therapeutic options for achalasia. METHODS: The Gastrointestinal Quality of Life Index (GIQLI) was studied before and after laparoscopic Heller myotomy associated with posterior partial fundoplication. RESULTS: Starting in January 1991, 73 consecutive patients were operated on laparoscopically for various clinical stages of achalasia. Since 1996, 40 patients completed a GIQLI questionnaire both preoperatively and after a minimum postoperative follow-up of 1 year. Median preoperative GIQLI score was 84 (range 34-129) out of a theoretical maximum score of 144. At a median follow-up of 31 months (range 12-54), the score had significantly improved to 119 (range 77-143), close to the range for the normal French population. Not only items assessing gastrointestinal symptoms but also the domains of physical, social, and emotional function were significantly improved. The most marked improvements were achieved in patients with the lowest preoperative scores. CONCLUSIONS: The GIQLI allows us to objectify the impact of achalasia symptoms on health-related QoL. At medium-term follow-up, laparoscopic Heller myotomy, performed either as primary treatment or after endoscopic dilation, significantly improves most health-related QoL aspects. Short of randomized comparisons between the different therapeutic options available for achalasia, reported series could be made more comparable if validated QoL instruments specific for gastrointestinal disorders were used routinely for outcome evaluation.

Effect of acetazolamide on ocular hemodynamics in pseudotumor cerebri associated with inflammatory bowel disease.

PURPOSE: To describe the hemodynamic effect of oral acetazolamide administration on ocular perfusion in a patient with pseudotumor cerebri associated with Crohn disease. DESIGN: Interventional case report. METHODS: A 20-year-old woman with a 5-year history of Crohn disease presented with a 2-week history of headache and blurred vision in both eyes. Ophthalmologic examination was normal. Fluorescein angiography showed a profound delay in retinal and choroidal perfusion. Lumbar puncture showed an opening pressure of 320 mm water. Therapy was initiated with oral acetazolamide 750 mg per day. RESULTS: A subjective improvement of symptoms was noted over 4 days. Repeat fluorescein angiography showed resolution of the ocular perfusion deficit. No recurrent symptoms were noted 19 months after cessation of therapy. CONCLUSIONS: Crohn disease may present with pseudotumor cerebri and severe ocular perfusion deficits that are reversible with oral acetazolamide therapy.