Results of a national survey on quality of life in inflammatory bowel diseases.

AIMS: Inflammatory bowel diseases (IBD) have a negative impact on patients' quality of life. The aims of this survey were to learn more about patients' concerns, and to compare their feelings with the beliefs of their close relations and physicians. PATIENTS AND METHODS: A specific questionnaire, including the RFIPC and the MFI-20, was used. Patients' answers were compared with those given by their close relations and attending physicians. RESULTS: This national survey included 2424 French patients. At the time of diagnosis, 73% of patients expressed having fears, but were also relieved to understand their symptoms. IBD was responsible for fatigue and weariness, and had a negative impact on daily, occupational, leisure, family and personal life. The main fears concerned unpredictable flare-ups followed by need for an ostomy bag and risk of surgery. The answers provided by close relations and physicians matched those of the patients, but physicians overestimated the patient's knowledge and underestimated disease impact. CONCLUSION: IBD has a deleterious effect on quality of life. Close relations of the patient realize the impact the disease has on the patients' life, but attending physicians still tend to minimize patients' symptoms.

Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprine.

BACKGROUND: There are few data on the incidence of benign infections (upper respiratory tract infections, herpes lesions and viral warts) during exposure to azathioprine. AIMS: To determine the incidence of benign infections in IBD out-patients receiving azathioprine (AZA+) and to look at the influence of leucocyte counts in the onset of these events. METHODS: A total of 230 patients were included in a prospective cohort and observed during 207 patient-years. Episodes of benign infections were collected and incidences of benign infections were compared between the AZA+ group and patients without AZA (AZA-). RESULTS: The incidence of upper respiratory tract infections in the cohort was 2.1 +/- 2.2 per observation-year. There was no difference between the AZA+ (n = 169) and AZA- (n = 61) groups (2.2 +/- 2.3 vs. 2.1 +/- 2.1, P = 0.77). The incidence of herpes flares was significantly increased in the AZA+ group compared to the AZA- group (1.0 +/- 2.6 vs. 0.2 +/- 0.8 per year, P = 0.04). Similarly, there were significantly more patients with appearance or worsening viral warts in the AZA+ group (17.2% (AZA+) vs. 3.3% (AZA-), P = 0.004). CONCLUSION: This study suggests that the incidence of herpes flares and the appearance or worsening of viral warts are increased in IBD patients receiving AZA.

A dose escalating, placebo controlled, double blind, single dose and multidose, safety and tolerability study of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease.

INTRODUCTION: This study was designed to evaluate the safety of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe Crohn's disease (CD). PATIENTS AND METHODS: Forty five patients with a CD activity index (CDAI) of 250-450 were randomised in a double blind, placebo controlled, dose escalating fashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo. By day 29, patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals. Primary objectives were safety and tolerability. Secondary outcomes included assessments of immunogenicity, clinical activity, and potential pharmacodynamic surrogates. RESULTS: Treatment was generally well tolerated. There were slightly more reports of chills, flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kg fontolizumab cohorts. Two serious adverse events rated as worsening of CD occurred under fontolizumab. Antibodies to fontolizumab were confirmed in one patient. No differences in clinical activity parameters were noted between any of the active treatment groups and placebo, with the placebo group having a particularly favourable outcome (60% response and 40% remission). By day 29, a more enhanced decrease in median Crohn's disease endoscopic index of severity (p = 0.02) and serum C reactive protein (p<0.001) was observed in the 4.0 mg/kg (n = 14) fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effects were observed by immunohistochemistry. CONCLUSIONS: Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD. A biological activity of fontolizumab is suggested.

[Impact of computed tomography (CT) and 18F-deoxyglucose positron emission tomography (FDG-PET) image fusion for conformal radiotherapy in esophageal carcinoma]. / Tomographie par émission de positons et fusion d'images de simulation virtuelle par tomodensitométrie. Impact sur la planification de la radiothérapie conformationnelle des cancers de l'oesophage.

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiation therapy (CRT) planning for patients with esophageal carcinoma. PATIENTS AND METHODS: Thirty-four patients with esophageal carcinoma were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. PET-images were coregistered using five fiducial markers. Target delineation was initially performed on CT images and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative CRT. The Gross Tumor Volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and was increased in 7 patients (20.5%). The GTV reduction was >or=25% in 4 patients due to reduction of the length of the esophageal tumor. The GTV increase was >or=25% with FDG-PET in 2 patients due to the detection of occult mediastinal lymph node involvement in one patient and an increased length of the esophageal tumor in the other patient. Modifications of the GTV affected the planning treatment volume (PTV) in 18 patients. Modifications of delineation of GTV and displacement of the isocenter of PTV by FDG-PET also affected the percentage of total lung volume receiving more than 20 Gy (VL20) in 25 patients (74%), with a dose reduction in 12 patients and a dose increase in 13 patients. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of patients with esophageal carcinoma related to modifications of GTV. The impact on treatment outcome remains to be demonstrated.

Impact of pregnancy on the clinical activity of Crohn's disease.

BACKGROUND: The impact of pregnancy on Crohn's disease activity has been poorly investigated. AIM: To determine the effect of pregnancy on Crohn's disease activity from the retrospective analysis of a cohort of women who had a regular clinical follow-up. METHODS: Seventy pregnancies occurring in 61 women were studied. The Harvey-Bradshaw index was determined during the four quarters preceding each pregnancy, the three quarters of pregnancy and the four quarters following delivery. RESULTS: The mean Harvey-Bradshaw index during pregnancy [0.68 (0.18), mean (S.E.M.)] was significantly lower than that of the year preceding pregnancy [0.98 (0.16), P = 0.03] and that of the year following delivery [1.10 (0.17), P = 0.04]. In non-smoking women (48 pregnancies), there was no significant change of Harvey-Bradshaw index between these intervals. Whereas in those who smoked (22 pregnancies), most of whom reduced tobacco consumption during pregnancy, the mean Harvey-Bradshaw index during pregnancy was significantly reduced compared with that of the year following delivery [0.58 (0.20) vs. 1.60 (0.33), P = 0.01]. The use of drugs was significantly lower during pregnancy. CONCLUSIONS: Crohn's disease activity is mildly but significantly lower during pregnancy. The reduction of tobacco consumption during pregnancy in smoking women may play an important role in this improvement.

Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery.

BACKGROUND/AIM: Immunosuppressants are now used much earlier in the course of Crohn's disease; however their effect on the natural history of the disease, especially on the need for surgery, is not known. The aim of this study was to assess the evolution of the need for surgery in Crohn's disease during the last 25 years. PATIENTS AND METHODS: The medical charts of 2573 patients were reviewed retrospectively. The use of immunosuppressants (azathioprine or methotrexate), the need for intestinal resection, and the occurrence of intestinal complications were assessed using Kaplan-Meier analysis in five consecutive cohorts of patients defined by the date of diagnosis of Crohn's disease (1978-82; 1983-87; 1988-92; 1993-97; 1998-2002). RESULTS: In 565 patients seen in the authors' unit within the first three months after diagnosis, characteristics of Crohn's disease at diagnosis did not differ from one cohort to another. The five year cumulative probability to receive immunosuppressants increased from 0 in the 1978-82 cohort to 0.13, 0.25, 0.25, and 0.56 in the 1983-87, 1988-92, 1993-97, and 1998-2002 cohorts, respectively (p<0.001). Concomitantly, the cumulative risk of intestinal resection remained unchanged (from 0.35 to 0.34 at five years; p=0.81). The cumulative risk of developing a stricturing or a penetrating intestinal complication remained also unchanged. Similar results were obtained in the 2008 patients seen during the same period who were referred to us more than three months after diagnosis. CONCLUSION: Although immunosuppressants have been used more frequently over the last 25 years, there was no significant decrease of the need for surgery, or of intestinal complications of Crohn's disease.

Reversal of abnormal collagen production in Crohn's disease intestinal biopsies treated with regenerating agents.

BACKGROUND: Crohn's disease (CD) is characterised by inflammation, muscle layer overgrowth, and collagenous fibrosis of the intestinal tract, with no effective therapy against collagen accumulation. AIMS: We quantified production of collagen in resection specimens from normal and CD patients and investigated the effect of regenerating agents (RGTAs) on collagen production. RGTAs are chemically substituted dextrans engineered to mimic the growth factor protecting effects of heparan sulphates. RGTAs have been shown to enhance tissue repair in various in vivo models and to modulate in vitro collagen phenotype differentially according to their structure. PATIENTS: We studied intestinal biopsies from two groups of CD patients: treated with glucocorticoids (CD-GC group: 10 patients) or not treated (CD group: seven patients), and from seven control patients. METHODS: After 24 hours of ex vivo incubation with (3H) proline, collagen I, III, and V were extracted by pepsin and quantitatively separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Biosynthesis of each collagen type was quantified on radiolabelled isolated collagen. RESULTS: Total intestinal collagen production in CD patients compared with controls was increased up to 3.5-fold overall (p<0.001). In particular, collagen III biosynthesis was enhanced by 6.2-fold (p<0.001) in CD patients. In the CD-GC group, collagen production abnormalities were less marked. RGTAs added to the incubation medium in the CD group decreased total collagen production by 50% and decreased collagen III synthesis by 76%. CONCLUSION: This finding offers a rationale for using RGTAs in the treatment of intestinal fibrosis in CD, thus opening up a potential new therapeutic field for this family of drugs.

Effects of appendicectomy on the course of ulcerative colitis.

BACKGROUND: Appendicectomy reduces the risk of having ulcerative colitis. However, its effect on the natural history of ulcerative colitis remains uncertain. AIM: To determine whether appendicectomy reduces the overall severity of ulcerative colitis. PATIENTS AND METHODS: Appendicectomy status and smoking habits were specified by direct interview in 638 patients seen consecutively between 1997 and 2000. Severity of ulcerative colitis was assessed by reviewing therapeutic needs from the onset of colitis. Additionally, the annual incidence of flare up was assessed prospectively between 1997 and 2000 in patients who had not been colectomised. RESULTS: The 10 year risk of colectomy was 16 (7)% in previously appendicectomised patients (n=49) compared with 33 (2)% in non-appendicectomised patients (n=589, p=0.05). Cox regression showed that previous appendicectomy and current smoking were independent factors protecting against colectomy (adjusted hazard ratio and 95% confidence intervals: 0.40 (0.20-0.78) and 0.60 (0.40-0.95), respectively). The respective proportions of appendicectomised and non-appendicectomised patients who required oral steroids and immunosuppressive therapy were not significantly different (67% v 70% and 27% v 19%, respectively). Between 1997 and 2000, ulcerative colitis was active for 48% of the time in appendicectomised patients (47 of 98 patient years) and for 62% of the time in non-appendicectomised patients (631 of 1024 patient years; p<0.01). CONCLUSION: Previous appendicectomy is associated with a less severe course of ulcerative colitis. The beneficial effect of appendicectomy on the risk of colectomy is additive to that of current smoking.

Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride.

BACKGROUND: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. AIM: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. METHODS: In this prospective, randomized, double-blind, parallel and placebo-controlled study, 94 patients with inflammatory bowel disease (lumbar spine T score below - 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dual-energy X-ray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. RESULTS: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 +/- 5.6% (n=29) and 3.2 +/- 3.8% (n=31) in the calcium-vitamin D-fluoride and calcium-vitamin D-placebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. CONCLUSIONS: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit.

Crohn's disease clinical course and severity in obese patients.

BACKGROUND AND AIMS: Obesity is unusual in Crohn's disease and the particularities of the disease in obese patients have not been studied. METHODS: 2065 patients were studied retrospectively. Obesity was defined by a BMI value >25.0 at disease onset and >30.0 at any time during the course of the disease. Disease characteristics, therapeutic needs, and year-by-year disease activity were determined in patients with and without obesity. RESULTS: 62 patients (3%) were obese. When compared with non-obese patients, obese patients did not show differences regarding sex, intestinal disease location, and disease behavior, but at diagnosis they were older (32 vs 28 years, P = 0.01) and a larger proportion had anoperineal disease (35 vs 24%, P = 0.03). When the 62 obese patients were paired for sex, location of disease at onset, date of birth, and date of diagnosis with 124 non-obese patients, the disease severity assessed by the importance of medical therapy and excisional surgery did not differ in the two groups but time to development of anoperineal abscess or fistula was shorter in obese patients, and obese patients were more prone to develop an active disease (OR 1.50, 95% CI 1.07-2.11) and to require hospitalization (OR 2.35, 95% CI 1.56-3.52) CONCLUSION: Obesity in Crohn's disease is associated with more frequent anoperineal complications and a more marked year-by-year disease activity, but does not alter significantly the long-term course of the disease.

Health-related quality of life in Crohn's disease: a prospective longitudinal study in 231 patients.

OBJECTIVE: The aim of this work was to assess the quality of life (QoL) of patients with Crohn's disease (CD) prospectively over 1 yr and to determine factors of influence. METHODS: A total of 231 CD patients were included. At month 0 (M0), M3, M6, M9, and M12, patients were given a validated QoL questionnaire (self-administered) to fill in and a clinical form referring to the period of 3 months before the visit. The QoL questionnaire was made up of the Short-Form-36 and the Rating Form of Inflammatory Bowel Disease Patients Concerns. The impact on QoL of the following factors was analyzed: age, gender, CD duration and localization, presence of extradigestive manifestations or concomitant disease, disease course, medical treatments, and surgery. We studied the correlations between QoL and disease activity assessed by both patients and investigators by a visual analog scale. RESULTS: At M0, all the scores of the Short-Form-36 were significantly lower than those of a standard population, nevertheless improving between M0 and M12. Patients' main worries were first "having an ostomy bag" followed by "uncertain nature of the disease," "energy level." and finally "having surgery." QoL was better correlated with assessment of disease course by the patient than by the investigator. Significant factors of impairment in QoL were female gender, tobacco, active CD, involvement of the colon, hospitalization, corticoid treatment, and surgery in the past 3 months. Conversely, intake of immunosuppressors improved QoL. CONCLUSION: Patients' QoL is impaired by CD and is underestimated by doctors. Tobacco, hospitalization, and use of corticoids have a negative impact on QoL. Conversely, the use of immunosuppressors is associated with a better QoL.

[Factors associated with hyperhomocysteinemia in Crohn's disease]. / Facteurs d'hyperhomocystéinémie au cours de la maladie de Crohn.

AIMS: The incidence of thromboembolic disease is increased in patients with inflammatory bowel disease. Hyperhomocysteinemia is one of the risk factors for thrombosis. The aims were: 1) to assess the prevalence of hyperhomocysteinemia in a large series of patients with Crohn's disease; 2) to search for clinical and biological factors associated with hyperhomocysteinemia. PATIENTS AND METHODS: One hundred seventy-one patients with Crohn's disease (64 males, 107 females), median age 31 years (range: 16-82), were studied. The median duration of the disease was 7 years. The concentrations of homocysteine, folate, cobalamin and C-reactive protein were measured in serum from blood sample of each patient. RESULTS: The mean concentration of seric homocysteine was 14.8 micromol/L (N: 4.4 - 12.4 micromol/L). Hyperhomocysteinemia was observed in 89 patients (52%). It was significantly associated with age, sex, smoking habit, serum cobalamin level and history of ileal surgical resection (P<0.05). In the group of operated patients, there was a statistically significant association between hyperhomocysteinemia and the length of small bowel resected. In multivariate analysis, sex and smoking were associated with hyperhomocysteinemia. CONCLUSION: More than half of the patients with Crohn's disease have hyperhomocysteinemia. This result stresses the need for preventing reversible factors associated with hyperhomocysteinemia, such as smoking and cobalamin deficiency, in order to lower the thrombotic risk of patients with Crohn's disease.

Chronic use of non-steroidal anti-inflammatory drugs does not alter colonic mucosa of patients without diarrhoea.

BACKGROUND: Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known. PATIENTS AND METHODS: Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry. RESULTS: Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients. CONCLUSION: These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis do not develop microscopic or inflammatory colitis.

Impact of cessation of smoking on the course of ulcerative colitis.

OBJECTIVES: The incidence and severity of ulcerative colitis (UC) are higher in nonsmokers than in smokers. The natural course of UC in smokers who stop smoking is not known. The aim of this study was to determine the impact of cessation of smoking on the course of UC among the cohort of patients regularly seen at our institution. METHODS: The severity of UC, as judged by the occurrence of flare-ups and the need for systemic steroids, immunosuppressive drugs and colectomy, was determined in 32 patients with UC who stopped smoking after the diagnosis of UC. We compared the period after cessation of smoking (7-yr mean follow-up) with the period between the onset of the disease and the cessation of smoking (9-yr mean duration). The course of UC in this group was compared with that of 32 nonsmokers and 32 continuing smokers matched for sex, age, and age at onset. RESULTS: In patients who quit, cessation of smoking was followed by an increase in the rate of years with active disease (p < 0.01), years with hospitalization (p < 0.05) and years with major medical therapy (oral steroids, intravenous steroids, and azathioprine, p < 0.01). After cessation of smoking, the rate of years with immunosuppressive therapy was significantly greater in ex-smokers and nonsmokers than in continuing smokers (p < 0.01). The risk of colectomy in ex-smokers after smoking cessation was similar to that of nonsmokers and continuing smokers. CONCLUSIONS: In smokers with UC who stop smoking, the severity of the disease increases after smoking cessation, with an increase in the disease activity and the need for hospital admission and major medical therapy. In addition, the need for azathioprine therapy becomes similar to that of nonsmokers.

Use of anti-tumour necrosis factor agents in inflammatory bowel disease. European guidelines for 2001-2003.

The introduction of novel anti-tumor necrosis factor (TNF) agents has not only led to impressive new therapeutic opportunities but also resulted in uncertainty regarding their optimal use and possible side effects. Guidelines are presented here for the use of anti-TNF agents in gastrointestinal disorders. Experts were chosen from different European countries by an algorithm to avoid bias. An expert consensus on guidelines was established using a two-stage procedure of systematic Medline and abstract search for evidence and a qualifying meeting to derive recommendations. Detailed guidelines were developed for the use and the future clinical development of anti-TNF agents in inflammatory bowel disease. Grading of available evidence and grading of recommendations were performed according to AHCPR guidelines. At present infliximab is the only registered agent for Crohn's disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines define the indications both in refractory and in fistulating disease for the readministration and before surgery. Guidelines for safety and for concomitant treatments are given. Prospects, potential clinical use, and future directions for the clinical development of other anti-TNF agents are detailed. Clinical use of anti-TNF agents will be influenced by a large number of clinical trials being concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an important long-term therapy for a proportion of patients with Crohn's disease. Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003.

Smoking cessation and the course of Crohn's disease: an intervention study.

BACKGROUND AND AIMS: To evaluate the benefit of smoking cessation in individuals with Crohn's disease, we performed an intervention study in a large cohort of smokers with the disease. METHODS: Repeated counseling to stop smoking, with easy access to a smoking cessation program, was given to 474 consecutive smokers with Crohn's disease. Patients who stopped smoking for more than 1 year (quitters) were included in a prospective follow-up study, which compared disease course and therapeutic needs with 2 control groups, continuing smokers and nonsmokers, paired for age, gender, disease location, and activity. RESULTS: There were 59 quitters (12%). Predictors of quitting were the physician, previous intestinal surgery, high socioeconomic status, and in women, oral contraceptive use. During a median follow-up of 29 months (1-54 months), the risk of flare-up in quitters did not differ from that in nonsmokers and was less than in continuing smokers (P < 0.001). Need for steroids and for introduction or reinforcement of immunosuppressive therapy, respectively, were similar in quitters and nonsmokers and increased in continuing smokers. The risk of surgery was not significantly different in the 3 groups. CONCLUSIONS: Patients with Crohn's disease who stop smoking for more than 1 year have a more benign disease course than if they had never smoked.

[Infliximab therapy for Crohn's disease anoperineal lesions]. / Traitement par anticorps anti-TNF alpha (infliximab, Remicade) des lésions anopérinéales de la maladie de Crohn.

AIM OF THE STUDY: To retrospectively evaluate the efficacy, the duration of response, and the tolerance of Remicade in anoperineal Crohn's disease. METHODS: Fifty patients with severe symptomatic and refractory anoperineal Crohn's lesions (38 fistulae and 29 cavitating ulcers and superficial fissures) were treated with 3 intravenous infusions of Remicade (5 mg/kg) at weeks 0, 2 and 6. Efficacy was assessed using Allan's functional score and proctologic examination at 8 weeks (W8) and 24 weeks (W24) after the first infusion. RESULTS: At W8, a response was noted for 71% (27/38) of fistulae and 79% (23/29) of ulcers and fissures. Healing rates were 39% and 49%, respectively. Efficacy of Remicade at W8 did not vary according to sex, number and type of fistulae and other treatments. At W24, 58% (15/26) of patients with fistulae and 63% (10/16) of patients with ulcers or fissures had a response. The response rate at W24 was higher in patients having anoperineal Crohn's lesions for less than one year: 77% vs 32% (P=0.004). Median Allan's score significantly decreased from 3.9 before treatment to 1.7 at W2 (P<0.001), 1.3 at W6 and 0.8 at W8. Median duration of response was 9.5 months (range: 0.5-12.5) after last infusion and was not influenced by associated treatments including immunomodulators. The relapse rate at 1 year was 64% for the responders followed at least one year (n=21). Minor adverse events occurred during 12% of all infusions. Eight patients had an infection, including one pneumonia. Eight patients developed a perineal abscess 16 weeks (range: 4-32) after the first infusion. CONCLUSION: Remicade is rapidly effective and well tolerated in anoperineal Crohn's lesions, but the high relapse rate stresses the need for long term therapeutic strategies in these patients.

Hepatocellular carcinoma and focal hepatic glycogenosis after prolonged azathioprine therapy.

A 22-year-old woman without predisposing liver disease developed focal hepatic glycogenosis and hepatocellular carcinoma after 6 years of azathioprine therapy for Crohn's disease. Hepatocellular carcinoma without cirrhosis has previously been described during immunosuppression, but this is the first report of disseminated focal hepatic glycogenosis after long-term azathioprine therapy.

Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy.

BACKGROUND & AIMS: Myelosuppression in patients with Crohn's disease (CD) treated with azathioprine has been attributed to low activity of thiopurine S-methyltransferase (TPMT). Allelic variants of the TPMT gene responsible for changes in the enzyme activity have been characterized. We investigated the distribution of mutant alleles associated with TPMT deficiency in patients with CD and myelosuppression during azathioprine/6-mercaptopurine therapy. METHODS: Forty-one patients with CD were included. They developed leukopenia or thrombocytopenia during azathioprine or 6-mercaptopurine treatment. Polymerase chain reaction-based methods were used to search for mutations associated with TPMT deficiency. RESULTS: Four patients (10%) had 2 mutant alleles associated with TPMT deficiency, 7 (17%) had 1 mutant allele, and 30 (73%) had no known TPMT mutation. The delay between administration of the drug and occurrence of bone marrow toxicity was less than 1.5 months in the 4 patients with 2 mutant alleles, and ranged from 1 to 18 months in patients with 1 mutant allele and from 0.5 to 87 months in patients with normal genotype. CONCLUSIONS: Twenty-seven percent of patients with CD and myelosuppression during azathioprine therapy had mutant alleles of the TPMT gene associated with enzyme deficiency. Myelosuppression is more often caused by other factors. Continued monitoring of blood cell counts remains mandatory in patients treated with azathioprine.

Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis.

BACKGROUND: Intensive intravenous treatment remains the first line therapy of severe, uncomplicated attacks of ulcerative colitis. AIM: To predict the failure of intensive intravenous treatment by combining clinical and laboratory parameters with endoscopy findings. METHODS: Retrospective study conducted in a tertiary care referral centre. Failure of intensive intravenous treatment was defined as colectomy before day 30, intravenous cyclosporin, or death. Predictive factors of outcome were assessed using univariate and multivariate prognostic analysis. RESULTS: Between January 1990 and May 1997, 85 consecutive patients were treated with intensive intravenous treatment for non-response to oral corticosteroids (n=59) and/or severe attack of ulcerative colitis (n=26). There were 41 successes and 44 failures (including 1 death, 13 cyclosporin and 30 colectomies before day 30). Multivariate prognostic analysis found that the presence of Truelove and Witts' criteria (P=0.018), an attack that had lasted more than 6 weeks (P=0.001), and severe endoscopic lesions (P=0.007) were associated with an increased risk of failure. Patients with severe endoscopic lesions and Truelove and Witts' criteria, or an attack of more than 6 weeks had a failure rate of 85-86%. CONCLUSION: Clinical, laboratory and endoscopic findings can predict the risk of failure of intensive intravenous treatment. A prospective study is required to confirm these results.