Complete resolution of enterocolic fistulas with infliximab.

Fistulas are a frequent and serious complication of Crohn's disease. Most of the literature has been focused on perianal fistulas, which are by far the most frequent. The effectiveness of treatment with infliximab in fistulizing Crohn's disease was demonstrated in the ACCENT II trial. In that study, however, all patients had external fistulas, and the majority of those were perianal fistulas. The response to fistula treatment in other locations was not evaluated.

Risk factors for metabolic bone disease in Crohn's disease patients.

BACKGROUND: The aim was to evaluate the presence of metabolic bone disease (MBD) in patients with Crohn's disease (CD) and to identify potential etiologic factors. METHODS: The case-control study included 99 patients with CD and 56 controls with a similar age and gender distribution. Both groups had dual-energy x-ray absorptionmetry and a nutritional evaluation. Single nucleotide polymorphisms at the IL1, TNF-α, LTα, and IL-6 genes were analyzed in patients only. Statistical analysis was performed using SPSS software. RESULTS: The prevalence of MBD was significantly higher in patients (P = 0.006). CD patients with osteoporosis were older (P < 0.005), small bowel involvement and surgical resections were more frequent (P < 0.005), they more often exhibited a penetrating or stricturing phenotype (P < 0.05), duration of disease over 15 years (P < 0.005), and body mass index (BMI) under 18.5 kg/m(2) (P < 0.01) were more often found. No association was found with steroid use. Patients with a Z-score < -2.0 more frequently had chronic active disease (P < 0.05). With regard to diet, low vitamin K intake was more frequent (P = 0.03) and intake of total, monounsaturated, and polyunsaturated fat was higher in patients with Z-score < -2.0 (P < 0.05). With respect to genetics, carriage of the polymorphic allele for LTα252 A/G was associated with a higher risk of osteoporosis (P = 0.02). Regression analysis showed that age over 40 years, chronic active disease, and previous colonic resections were independently associated with the risk of developing MBD. CONCLUSIONS: The prevalence of MBD was significantly higher in CD patients. Besides the usual risk factors, we observed that factors related to chronic active and long-lasting disease increased the risk of MBD.

Fat intake interacts with polymorphisms of Caspase9, FasLigand and PPARgamma apoptotic genes in modulating Crohn's disease activity.

BACKGROUND & AIMS: Crohn's disease (CD) is a multifactorial disease where resistance to apoptosis is one major defect. Also, dietary fat intake has been shown to modulate disease activity. We aimed to explore the interaction between four single nucleotide polymorphisms (SNPs) in apoptotic genes and dietary fat intake in modulating disease activity in CD patients. METHODS: Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques were used to analyze Caspase9+93C/T, FasLigand-843C/T, Peroxisome Proliferator-Activated Receptor gamma+161C/T and Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNPs in 99 patients with CD and 116 healthy controls. Interactions between SNPs and fat intake in modulating disease activity were analyzed using regression analysis. RESULTS: None of the polymorphisms analyzed influenced disease susceptibility and/or activity, but a high intake of total, saturated and monounsaturated fats and a higher ratio of n-6/n-3 polyunsaturated fatty acids(PUFA), was associated with a more active phenotype (p < 0.05). We observed that the detrimental effect of a high intake of total and trans fat was more marked in wild type carriers of the Caspase9+93C/T polymorphism [O.R(95%CI) 4.64(1.27-16.89) and O.R(95%CI) 4.84(1.34-17.50)]. In the Peroxisome Proliferator-Activated Receptor gamma Pro12Ala SNP, we also observed that a high intake of saturated and monounsaturated fat was associated to a more active disease in wild type carriers [OR(95%CI) 4.21(1.33-13.26) and 4.37(1.52-12.51)]. Finally, a high intake of n-6 PUFA was associated with a more active disease in wild type carriers for the FasLigand-843C/T polymorphism [O.R(95%CI) 5.15(1.07-24.74)]. CONCLUSIONS: To our knowledge, this is the first study to disclose a synergism between fat intake and SNPs in apoptotic genes in modulating disease activity in CD patients.

Fatty acids, IL6, and TNFalpha polymorphisms: an example of nutrigenetics in Crohn's disease.

OBJECTIVES: The aim of this work was to study the interaction between genetic polymorphisms (single-nucleotide polymorphisms, SNPs) of pro- and anti-inflammatory cytokines and fat intake on the risk of developing Crohn's disease (CD) or modifying disease activity. METHODS: Seven SNPs in interleukin 1 (IL1), tumor necrosis factor alpha (TNFalpha), lymphotoxin alpha (LTalpha), and IL6 genes were analyzed in 116 controls and 99 patients with CD. The type of fat intake was evaluated, and the interaction between SNPs and dietary fat in modulating disease activity was analyzed. RESULTS: Individuals who were homozygous for the IL6-174G/C polymorphism had a six-fold higher risk for CD (odds ratio (OR)=6.1; 95% confidence interval (95% CI)=1.9-19.4), whereas the TT genotype on the TNFalpha-857C/T polymorphism was associated with more active disease (OR=10.4; 95% CI=1.1-94.1). A high intake of total, saturated, and monounsaturated fats, as well as a higher ratio of n-6/n-3 polyunsaturated fatty acid (PUFA), was associated with a more active phenotype (P<0.05). Furthermore, there was an interaction between dietary fat intake and SNPs, with a high intake of saturated and monounsaturated fats being associated with active disease, mainly in patients carrying the variant alleles of the 857 TNFalpha polymorphism (OR=6.0, 95% CI=1.4-26.2; OR=5.17; 95% CI=1.4-19.2, respectively) and the 174 IL6 polymorphism (OR=2.95; 95% CI=1.0-9.1; OR=3.21; 95% CI=1.0-10.4, respectively). Finally, low intake of n-3 PUFA and high n-6/n-3 PUFA ratio in patients with the TNFalpha 857 polymorphism were associated with higher disease activity (OR=3.6; 95% CI=1.0-13.0; OR=5.92; 95% CI=1.3-26.5, respectively). CONCLUSIONS: These results show that different types of fat may interact with cytokine genotype, modulating disease activity.

Crohn's disease in a southern European country: Montreal classification and clinical activity.

BACKGROUND: Given the heterogeneous nature of Crohn's disease (CD), our aim was to apply the Montreal Classification to a large cohort of Portuguese patients with CD in order to identify potential predictive regarding the need for medical and/or surgical treatment. METHODS: A cross-sectional study was used based on data from an on-line registry of patients with CD. RESULTS: Of the 1692 patients with 5 or more years of disease, 747 (44%) were male and 945 (56%) female. On multivariate analysis the A2 group was an independent risk factor of the need for steroids (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3) and the A1 and A2 groups for immunosuppressants (OR 2.2; CI 1.2-3.8; OR 1.4; CI 1.0-2.0, respectively). An L3+L3(4) and L(4) location were risk factors for immunosuppression (OR 1.9; CI 1.5-2.4), whereas an L1 location was significantly associated with the need for abdominal surgery (P < 0.001). After 20 years of disease, less than 10% of patients persisted without steroids, immunosuppression, or surgery. The Montreal Classification allowed us to identify different groups of disease severity: A1 were more immunosuppressed without surgery, most of A2 patients were submitted to surgery, and 52% of L1+L1(4) patients were operated without immunosuppressants. CONCLUSIONS: Stratifying patients according to the Montreal Classification may prove useful in identifying different phenotypes with different therapies and severity. Most of our patients have severe disease.

A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: a case-control study.

OBJECTIVES: Evaluate the nutritional status of patients with inactive or mildly active Crohn's disease (CD), and identify possible causes for potential deficiencies. METHODS: A total of 78 CD patients and 80 healthy controls were evaluated in respect of nutritional status, dietary intake, and life styles factors. RESULTS: These 73/78 CD patients were on immunomodulating therapies. Mean body mass index (BMI) was lower in patients as compared to controls (P= 0.006) but 32% of CD patients and 33.8% of controls had a BMI > 25, whereas 8% and 23.8% in each group, respectively, were obese (BMI > 30Kg/m(2)). Fat free mass was significantly decreased in both genders (P < 0.05) whereas fat mass was decreased only in males (P= 0.01). Energy intake was significantly lower in CD patients (P < 0.0001) and we observed significantly lower adjusted mean daily intakes of carbohydrates, monounsaturated fat, fiber, calcium, and vitamins C, D, E, and K (P < 0.05). 29% of patients had excluded grains from their usual diet, 28% milk, 18% vegetables, and 11% fruits. Milk exclusion resulted in a significantly lower consumption of calcium and vitamin K (P < 0.001) and the exclusion of vegetables was associated to a lower consumption of vitamins C and E (P < 0.05). Physical activity was significantly lower in CD patients (P= 0.01) and this lack of physical activity was inversely correlated with increased fat mass percentage (r=-0.315, P= 0.001). CONCLUSIONS: Results showed that the most prevalent form of malnutrition in CD patients was an excess of body weight, which was concomitant with an inadequate dietary intake, namely micronutrients, clearly related to dietary exclusion of certain foods.

NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype-phenotype analysis in Danish and Portuguese patients and controls.

BACKGROUND: A North-South gradient in Crohn's disease (CD) implying a higher incidence in northern Europe compared to southern Europe has been established. AIMS: To investigate whether there is a difference between Denmark and Portugal in the frequency of CARD15 mutations in CD patients compared to a healthy background population and to compare genotype-phenotype relations in the two countries. METHODS: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. RESULTS: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates in Danish patients were significantly different (p=0.02) compared with Danish controls, no difference (p=0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p=0.03) using the Mantel-Haenszel test. No difference in evolution of phenotypes and the CARD15 status in CD was found during follow-up between the two matched populations. Ileal disease correlated to high occurrence of CARD15. CONCLUSION: No North-South gradient regarding occurrence of CARD15 was revealed. Although a trend towards more mutations in the Portuguese controls was seen, a relationship between CD and CARD15 mutations was observed in both countries.