Predictive value of infliximab trough levels in maintenance therapy for 5-year sustained clinical remission in patients with inflammatory bowel disease.

BACKGROUND: Despite long-term use of infliximab (IFX) in IBD treatment, its optimized use is unclear due to its complicated pharmacokinetics/dynamics. Hence, the predictive value of IFX trough levels (TL) is important in treatment management. METHODS: We performed a prospective, cross-sectional, observational study with 74 IBD patients treated with IFX (mean 9.1 years, SD ± 3). TL was measured during maintenance therapy, in which maintenance of remission was followed for 5 years. RESULTS:  TL > 3 µg/ml during maintenance therapy was a significant predictor of clinical remission in 5 years in UC patients (82 % vs 62 %, p 3 µg/ml during maintenance therapy in a cohort of IBD patients (p = 0.05). Deviations in percentage of remission and fraction of relapses in TL categories were insignificant in a cohort of CD patients (85 % vs 74 %, p > 0.05). CONCLUSIONS:  TL > 3 µg/ml during maintenance therapy is a strong predictor of sustained clinical remission for 5 years in UC patients. The use of combination therapy with AZA, due to its significant association with high TL, may have a practical benefit in achieving better clinical outcomes in UC patients (Tab. 2, Fig. 10, Ref. 20).

Real-world observational cohort study of treatment patterns and safety outcomes of infliximab biosimilar CT-P13 for the treatment of inflammatory bowel disease (CONNECT-IBD).

BACKGROUND: The objective of this non-interventional, observational prospective cohort study (CONNECT-IBD) was to assess the use of CT-P13 (Inflectra®) in the treatment of patients with Crohn's disease (CD) and ulcerative colitis (UC) in the context of treatment with reference infliximab (IFX; Remicade®). METHODS: Patients (recruited April 2015 to October 2018) at 150 sites across 13 European countries were followed for up to 2 years. Primary outcomes were safety, population characteristics, and drug utilization patterns. Secondary outcomes included clinical assessment of disease activity. Data were analyzed descriptively. RESULTS: Overall, 2543 patients (CD, n = 1676; UC, n = 867) were included. In the CT-P13 cohort (n = 1522), median disease duration was 63 (0-579) months and 30% of patients were IFX naïve; median duration of prior IFX treatment was 5 months. During the observation period, median duration of drug exposure was 14 (0-28) months. 41% of patients reported 912 all-causality treatment-emergent adverse events (TEAEs); 24% experienced treatment-related TEAEs. Most TEAEs were of mild-to-moderate severity. Treatment-emergent serious adverse events were reported by 17% of patients. CONCLUSION: Safety information for CT-P13 in this large study was consistent with the known safety profile for IFX and did not alter the established benefit-risk profile of CT-P13.

Nuclear and Mitochondrial Circulating Cell-Free DNA Is Increased in Patients With Inflammatory Bowel Disease in Clinical Remission.

Background: The role of cell-free DNA (cfDNA) in the pathogenesis of inflammatory bowel disease (IBD) has been recently suggested. The aim of this study was to analyze circulating cfDNA and deoxyribonuclease (DNase) activity in IBD patients in clinical remission. Materials and Methods: Plasma and serum were obtained from 72 patients with Crohn's disease and 28 patients with ulcerative colitis. Total cfDNA, nuclear DNA (ncDNA), mitochondrial DNA (mtDNA) and DNase activity were measured. Results: IBD patients showed higher levels of both ncDNA and mtDNA compared to healthy controls. Concentration of ncDNA was higher in males compared to females, including patients and healthy controls. However, unlike males higher amount of ncDNA was found in female IBD patients compared to healthy controls. DNase activity was significantly lower in male IBD patients compared with healthy controls. In addition, there was a negative correlation between DNase activity and ncDNA levels in male IBD patients. Conclusions: Herein we present increased amount of circulating ncDNA and mtDNA in IBD patients in clinical remission. Thus, unlike total cfDNA, circulating ncDNA and mtDNA might not represent the optimal biomarkers of disease activity. This is also the first report on sex difference in circulating ncDNA levels, possibly associated with lower DNase activity in males.

Seasonal changes of circulating 25-hydroxyvitamin D correlate with the lower gut microbiome composition in inflammatory bowel disease patients.

Higher probability of the development of Crohn's disease (CD) and ulcerative colitis (UC) as a possible consequence of the north-south gradient has been recently suggested. Living far north or south of the equator is manifested in fluctuation of vitamin D (vitD) levels depending on the season in both healthy and affected individuals. In the present study we investigate the possible link between the seasonal serum vitD level to the microbial composition of the lower gut of Inflammatory Bowel disease (IBD) patients using 16S rRNA sequencing. Decrease of serum vitD level in winter/spring season in a cohort of 35 UC patients and 39 CD patients was confirmed. Low gut microbiota composition of patients with IBD correlated with the serum level of 25(OH)D that directly coupled to seasonal variability of the sunshine in the central European countries. It is supposed to be related to increased abundance of Actinobacteria and Proteobacteria in UC and Actinobacteria, Fusobacteria, Firmicutes and Bacteroidetes in CD. In summer/autumn period, we observed a reduction in abundance of bacterial genera typical for inflammation like Eggerthella lenta, Fusobacterium spp., Bacteroides spp., Collinsella aerofaciens, Helicobacter spp., Rhodococcus spp., Faecalibacterium prausnitzii; and increased abundance of Pediococcus spp. and Clostridium spp. and of Escherichia/Shigella spp.

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.

Decrease of trabecular bone score reflects severity of Crohn's disease: results of a case-control study.

OBJECTIVES: Osteoporosis and osteopaenia are known chronic complications of inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect measurement of bone microarchitecture, independent of bone mineral density (BMD). PATIENTS AND METHODS: The study was designed as a case-control study with the aim to assess and compare bone quantity and quality in patients with Crohn's disease (CD). We purposefully excluded postmenopausal women and patients on long-term corticosteroid therapy. RESULTS: The cohort consisted of 50 CD patients and 25 healthy controls who matched in age, sex, weight, or vitamin D status. There was no significant difference between CD patients versus controls in the mean lumbar BMD of 0.982±0.119 versus 0.989±0.12 g/cm and the mean TBS score of 1.37±0.12 versus 1.38±0.12. We observed significantly lower TBS, but not lumbar BMD, in CD patients with stricturing (B2, 1.36±0.08) or penetrating (B3, 1.32±0.11) disease compared with those with luminal disease (B1, 1.42±0.11; P=0.003 and <0.0001, respectively). We also observed lower mean±SD TBS in patients on versus not on anti-tumour necrosis factor-α therapy: 1.341±0.138 versus 1.396±0.099, respectively. However, the difference between these groups failed to reach statistical significance (P=0.11). No similar finding was seen comparing lumbar BMD in these groups. CONCLUSION: For the first time, it was observed that TBS, but not BMD, correlates with the severity of CD. Our results therefore suggest that TBS can potentially help to identify high fracture risk CD patients better than BMD alone.

Drug-induced liver injury in inflammatory bowel disease: 1-year prospective observational study.

AIM: To analyze 1-year liver injury burden in inflammatory bowel disease (IBD) patients. METHODS: During a 6-mo inclusion period, consecutive IBD cases having a control visit at IBD center were included. Basic demographics, IBD phenotype and IBD treatment were recorded on entry. Aminotransferase (AT) activities of ALT, AST, ALP and gamma-glutamyl transpeptidase (GGT) were measured at baseline, 3 mo prior to study entry and prospectively every 3 mo for 1 year. Liver injury patterns were predefined as: Grade 1 in ALT 1-3 × upper limit of normal (ULN), grade 2 in ALT > 3 × ULN, hepatocellular injury in ALT > 2 × ULN, cholestatic injury in simultaneous GGT and ALP elevation > ULN. Persisting injury was reported when AT elevations were found on > 1 measurement. Risk factors for the patterns of liver injury were identified among demographic parameters, disease phenotype and IBD treatment in univariate and multivariate analysis. Finally, implications for the change in IBD management were evaluated in cases with persisting hepatocellular or cholestatic injury. RESULTS: Two hundred and fifty-one patients were included having 917 ALT and 895 ALP and GGT measurements. Over one year, grade 1 injury was found in 66 (26.3%), grade 2 in 5 (2%) and hepatocellular injury in 16 patients (6.4%). Persisting hepatocellular injury was found in 4 cases. Cholestasis appeared in 11 cases (4.4%) and persisted throughout the entire study period in 1 case. In multivariate analysis, hepatocellular injury was associated with BMI (OR = 1.13, 1.02-1.26), liver steatosis (OR = 10.61, 2.22-50.7), IBD duration (1.07, 1.00-1.15) and solo infliximab (OR = 4.57, 1.33-15.7). Cholestatic liver injury was associated with prior intestinal resection (OR = 32.7, 3.18-335), higher CRP (OR = 1.04, 1.00-1.08) and solo azathioprine (OR = 10.27, 1.46-72.3). In one case with transient hepatocellular injury azathioprine dose was decreased. In 4 cases with persisting hepatocellular injury, fatty liver or alcohol were most likely causes and IBD treatment was pursued without change. In the case with persisting cholestatic injury, no signs of portal hypertension were identified and treatment with infliximab continued. CONCLUSION: Liver injury was frequent, mostly transient and rarely changed management. Infliximab or azathioprine were confirmed as its risk factors indicating the need for regular AT monitoring.

[Hemosuccus pancreaticus - rare complication of chronic pancreatitis]. / Hemosuccus pancreaticus - raritná komplikácia chronickej pankreatitídy.

Hemosuccus pancreaticus is a rare cause of upper digestive tract bleeding, it is hemorrhage to the pancreatic duct. A case report is about 56-years old man who was repeatedly hospitalized and suffered from melena and enterorrhagia during 3 years. Imaging studies did not clearly identified etiology of bleeding or source of hemorrhage was wrong identified. Finally, hemosuccus pancreaticus from collaterals of pseudoaneurysm after embolization was suspected because of repeating hemorrhage and embolization of a gastroduodenal artery in history. The interventional procedure was made in a the proximal part of the gastroduodenal artery with a good clinical response. This disease causes severe diagnostic and therapeutic problems, the unrecognized one can be fatal.Key words: enterorrhagia - hemosuccus pancreaticus - chronic pancreatitis - melena.

[Hepatic transit times and liver elasticity compared with meld in predicting a 1 year adverse clinical outcome of a clinically diagnosed cirrhosis]. / Význam merania obehových casov a elasticity pecene v porovnaní s MELD pri odhade jednorocného rizika nepriaznivého priebehu klinicky diagnostikovanej cirhózy.

INTRODUCTION AND OBJECTIVES: Hepatic transit times measured by the contrast enhanced ultrasonography and liver elasticity were found to predict a clinically significant portal hypertension. However, these modalities we not yet sufficiently evaluated in predicting adverse clinical outcome in patients with clinically diagnosed cirrhosis (D´Amico stages > 1), having a clinically significant portal hypertension. The aim of our study was to assess the predictive power of the liver transit times and the liver elasticity on an adverse clinical outcome of clinically diagnosed cirrhosis compared with the MELD score. METHODS: The study group included 48 consecutive outpatients with cirrhosis in the 2., 3. and 4. DAmico stages. Patients with stage 4 could have jaundice, patients with other complications of portal hypertension were excluded. Transit times were measured from the time of intravenous administration of contrast agent (Sonovue) to a signal appearance in a hepatic vein (hepatic vein arrival time, HVAT) or time difference between the contrast signal in the hepatic artery and hepatic vein (hepatic transit time, HTT) in seconds. Elasticity was measured using the transient elastography (Fibroscan). The transit times and elasticity were measured at baseline and patients were followed for up for 1 year. Adverse outcome of cirrhosis was defined as the appearance of clinically apparent ascites and/or hospitalization for liver disease and/or death within 1 year. RESULTS: The mean age was 61 years, with female/male ratio 23/25. At baseline, the median Child-Pugh score was 5 (IQR 5.0-6.0), MELD 9.5 (IQR 7.6 to 12.1), median HVAT was 22 s (IQR 19-25) and HTT 6 (IQR 5-9). HTT and HVAT negatively correlated with Child-Pugh (-0.351 and -0.441, p = 0.002) and MELD (-0.479 and -0.388, p = 0.006) scores. The adverse outcome at 1-year was observed in 11 cases (22.9 %), including 6 deaths and 5 hospitalizations. Median HVAT in those with/without the adverse outcome was 20 seconds (IQR 19.3-23.5) compared with 22 s (IQR 19-26, p = 0.32). Cases with adverse outcome had significantly higher MELD (12.9 vs 8.5), Child-Pugh score (7.0 vs 5.0) and the liver elasticity (52.5 vs 21.5 kPa) (p < 0.05). The AUROC of the HVAT, liver elasticity and MELD for the prediction of the adverse outcome was 0.60 (95% CI 0.414 to 0.785), 0.767 (0.56 to 0.98) and 0.813 (0.66 to 0.97). Unlike HVAT, the liver elasticity > 35.3 kPa increased the risk of the adverse outcome 10.3-times and MELD score > 11 points 8.5-times. CONCLUSION: In patients with clinically diagnosed cirrhosis having a clinically significant portal hypertension hepatic transit times do not predict the 1-year adverse clinical outcome. However, the liver elasticity > 35.3 kPa appears clinically useful with a prognostic value comparable with MELD. KEY WORDS: clinically diagnosed cirrhosis - hepatic transit times - liver elasticity - MELD - portal hypertension.

[Fecal microbiota transplantation]. / Fekálna mikrobiálna terapia.

Fecal microbiota transplantation (FMT) is a therapeutic method, in which the fecal microflora from healthy donors is transmitted to the patient to restore the healthy microbial composition of the gut. In the recent years, there is a growing interest in the therapeutic potential of FMT in various diseases. The standard FMT protocols do not exist. Procedures of FMT vary in several aspects such as donor selection, preparation of fecal material, preparation of the recipient and administration way. FMT appears to be the most successful in the treatment of recurrent Clostridium difficile infection (CDI), randomized controlled studies reported 90 % success rate. There is a limited evidence for FMT as a treatment of ulcerative colitis. FMT has been also studied as treatment of diseases with impaired gut microbiota, such as cardiovascular, autoimmune and metabolic diseases. Many unanswered questions with regard to FMT remain and further research is needed.

Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much?

BACKGROUND: The north­south geographical gradient of inflammatory bowel disease (IBD) prevalence, its epidemiology, the genetic association of vitamin D receptor polymorphisms, and results in animal models suggest that vitamin D plays an important role in the pathogenesis of IBD. AIMS: The purpose of this review was to critically appraise the effectiveness and safety of vitamin D therapy in patients with IBD. METHODS: MEDLINE, Scopus and Google Scholar were searched from inception to May 20, 2014 using the terms 'Crohn's disease', 'ulcerative colitis' and 'vitamin D'. Results: Vitamin D deficiency is common in patients with IBD. Limited clinical data suggest an association between low vitamin D concentration and increased disease activity in both ulcerative colitis (UC) and Crohn's disease (CD). To date, only two small open label trials and one randomized controlled trial have shown a positive effect of vitamin D supplementation on disease activity in patients with CD; no effect has been shown for UC. An optimal vitamin D supplementation protocol for patients with IBD remains undetermined, but targeting serum 25-hydroxy vitamin D [25(OH)D] levels between 30 and 50 ng/mL appears safe and may have benefits for IBD disease activity. Depending on baseline vitamin D serum concentration, ileal involvement in CD, body mass index, and perhaps smoking status, daily vitamin D doses between 1800­10,000 international units/day are probably necessary. CONCLUSION: Increasing preclinical and clinical evidence suggests a role for vitamin D deficiency in the development and severity of IBD. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation.

Biological therapy in inflammatory bowel diseases: access in Central and Eastern Europe.

Biological drugs opened up new horizons in the management of inflammatory bowel diseases (IBD). This study focuses on access to biological therapy in IBD patients across 9 selected Central and Eastern European (CEE) countries, namely Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovakia. Literature data on the epidemiology and disease burden of IBD in CEE countries was systematically reviewed. Moreover, we provide an estimation on prevalence of IBD as well as biological treatment rates. In all countries with the exception of Romania, lower biological treatment rates were observed in ulcerative colitis (UC) compared to Crohn's disease despite the higher prevalence of UC. Great heterogeneity (up to 96-fold) was found in access to biologicals across the CEE countries. Poland, Bulgaria, Romania and the Baltic States are lagging behind Hungary, Slovakia and the Czech Republic in their access to biologicals. Variations of reimbursement policy may be one of the factors explaining the differences to a certain extent in Bulgaria, Latvia, Lithuania, and Poland, but association with other possible determinants (differences in prevalence and incidence, price of biologicals, total expenditure on health, geographical access, and cost-effectiveness results) was not proven. We assume, nevertheless, that health deterioration linked to IBD might be valued differently against other systemic inflammatory conditions in distinct countries and which may contribute to the immense diversity in the utilization of biological drugs for IBD. In conclusion, access to biologicals varies widely among CEE countries and this difference cannot be explained by epidemiological factors, drug prices or total health expenditure. Changes in reimbursement policy could contribute to better access to biologicals in some countries.

[Hormonal changes in inflammatory bowel disease]. / Hormonálne zmeny pri chronických zápalových chorobách creva.

Inflammatory bowel disease is often accompanied by extraintestinal manifestations due to a common autoimmune etiopathogenesis, chronic systemic inflammation, frequent nutrition deficits, and the treatment. Endocrine system changes belong to manifestations too. Interaction is mutual, Crohn's disease and ulcerative colitis cause functional and morphological changes of endocrine tissues. On the other hand the endocrine disorders negatively influence the course of bowel disease. In the article we analyze correlation of IBD with gonadal hormone production and fertility, with adrenal function, with the function and morphology of the thyroid, with growth hormone production and growth disorders in children, and with bone mineral density reduction. This topic is not studied enough and needs more analysis and clarification.

[Hormonal changes in inflammatory bowel disease]. / Hormonálne zmeny pri chronických zápalových chorobách creva.

UNLABELLED: Inflammatory bowel disease is often accompanied by extraintestinal manifestations due to a common autoimmune etiopathogenesis, chronic systemic inflammation, frequent nutrition deficits, and the treatment. Endocrine system changes belong to manifestations too. Interaction is mutual, Crohn´s disease and ulcerative colitis cause functional and morphological changes of endocrine tissues. On the other hand the endocrine disorders negatively influence the course of bowel disease. In the article we analyze correlation of IBD with gonadal hormone production and fertility, with adrenal function, with the function and morphology of the thyroid, with growth hormone production and growth disorders in children, and with bone mineral density reduction. This topic is not studied enough and needs more analysis and clarification. KEY WORDS: Crohn´s disease - endocrine system - inflammatory bowel disease - ulcerative colitis.

Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases.

AIM: To investigate the effect of vitamin D (VD) concentrations and VD supplementation on health related quality of life in inflammatory bowel disease (IBD) patients. METHODS: A cohort of 220 IBD patients including 141 Crohn's disease (CD) and 79 ulcerative colitis (UC) patients was followed-up at a tertiary IBD center. A subgroup of the cohort (n = 26) took VD supplements for > 3 mo. Health related quality of life was assessed using the short IBD questionnaire (sIBDQ). VD serum concentration and sIBDQ score were assessed between August and October 2012 (summer/autumn period) and between February and April 2013 (winter/spring period). The mean VD serum concentration and its correlation with disease activity of CD were determined for each season separately. In a subgroup of patients, the effects of VD supplementation on winter VD serum concentration, change in VD serum concentration from summer to winter, and winter sIBDQ score were analyzed. RESULTS: During the summer/autumn and the winter/spring period, 28% and 42% of IBD patients were VD-deficient (< 20 ng/mL), respectively. In the winter/spring period, there was a significant correlation between sIBDQ score and VD serum concentration in UC patients (r = 0.35, P = 0.02), with a trend towards significance in CD patients (r = 0.17, P = 0.06). In the winter/spring period, VD-insufficient patients (< 30 ng/mL) had a significantly lower mean sIBDQ score than VD-sufficient patients; this was true of both UC (48.3 ± 2.3 vs 56.7 ± 3.4, P = 0.04) and CD (55.7 ± 1.25 vs 60.8 ± 2.14, P = 0.04) patients. In all analyzed scenarios (UC/CD, the summer/autumn period and the winter/spring period), health related quality of life was the highest in patients with VD serum concentrations of 50-59 ng/mL. Supplementation with a median of 800 IU/d VD day did not influence VD serum concentration or the sIBDQ score. CONCLUSION: VD serum concentration correlated with health related quality of life in UC and CD patients during the winter/spring period.

Combination therapy with an immunomodulator and anti-TNFα agent improves bone mineral density in IBD patients.

OBJECTIVE: There is a high prevalence of low bone mineral density (BMD) among patients with inflammatory bowel disease (IBD) although there is a lack of clinical data on the impact of IBD specific medications and recommended vitamin D (VD) and calcium (Ca) supplements on it. DESIGN: The cohort consisted of 150 IBD patients. The average change in BMD at the lumbar spine per year (∆BMDL/year) was calculated and the impact of clinical characteristics, medications and VD and Ca supplements was analysed. RESULTS: The prevalence of osteopenia was 69/150 (46%) and osteoporosis was identified in 15/150 (10%) patients at baseline. The presence of osteoporosis was associated with the disease duration OR=1.07 per year of disease duration (95% CI=1.01-1.14), p=0.03. The average ∆BMDL/year was 0.010 g/cm(2)/year. Among patients with no IS the ∆BMDL/year was -0.001±0.010 g/cm(2)/year, with AZA -0.001±0.013 g/cm(2)/year, with anti-TNFα 0.003±0.006 g/cm(2)/year and with COMBO 0.027±0.004 g/cm(2)/year; p<0.05 COMBO vs any other subgroup. ∆BMDL/year among patients treated with CS was -0.031±0.012 g/cm(2)/year versus CS free patients 0.013±0.004 g/cm(2)/year; p<0.001. There was no effect of VD/Ca supplementation on BMDL. CONCLUSIONS: The prevalence of low BMD was 55%. Duration of disease was the only independent predictor of low BMD. The BMDL was reduced by high cumulative dose of CS and improved by combined anti-TNFα/AZA therapy. The supplementation with recommended doses of VD and Ca had no effect on BMDL.

Biosimilars in the therapy of inflammatory bowel diseases.

A biosimilar is a copy of an approved biological medicine whose patent protections have expired. Biosimilars of antibodies to tumour necrosis factor α (TNFα) are becoming important in the treatment of inflammatory bowel diseases (IBD). The first one introduced commercially is an infliximab biosimilar. The aim of this study was to provide an overview of anti-TNFα biosimilars. The literature on biosimilars of monoclonal anti-TNFα antibodies was reviewed, including their manufacture and approval pathways, concerns about efficacy, safety, immunogenicity, extrapolation, switching and labelling. Previous experience with biosimilars of epoetin and other growth factors was also reviewed. The infliximab biosimilar CT-P13 was the first biosimilar monoclonal antibody registered for the treatment of IBD. The major advantage of biosimilars is the reduced cost of therapy. Concerns have arisen, however, about the efficacy and safety of CT-P13 in IBD, the extrapolation of results from rheumatologic trials to IBD and the free interchangeability of CT-P13 with infliximab. Experience with simple peptide biosimilars, such as epoetins and growth factors, has generally been positive, with these biosimilars having similar efficacy and safety as the original products, although immunogenicity remains a major concern. Upcoming postregistration studies will address concerns on biosimilars in IBD, including their efficacy, safety, immunogenicity, switching and interchangeability. Biosimilars active against the same epitopes, but with improved pharmacokinetic properties that enhance their efficacy and/or safety, may be the next stage in the development of biosimilars. Anti-TNFα biosimilars represent promising new treatment options for patients with IBD. However, data on their efficacy and safety in IBD are needed.

Delayed hypersensitivity reaction after initial dose of infliximab: a case report.

We report here an unusual case of delayed hypersensitivity reaction in a young woman with ulcerative colitis after the first administration of infliximab (IFX). The patient developed severe serum-sickness-like reaction, and her anti-IFX antibody titer increased rapidly after a single infusion of IFX. The possible reason for the delayed hypersensitivity reaction to a single IFX exposure might be the presensitization of the patient by murine antigens as she had been keeping mice and hamsters as pets for several years.

Smoking, breastfeeding, physical inactivity, contact with animals, and size of the family influence the risk of inflammatory bowel disease: A Slovak case-control study.

BACKGROUND: The aetiology of inflammatory bowel disease (IBD) is not known but is likely to involve a combination of genetic predisposition and environmental risk factors. Smoking has been associated consistently with a higher risk of Crohn's disease (CD), while appendectomy and smoking appear to diminish the risk of ulcerative colitis (UC). The roles of other environmental factors are unclear. The aim of the present study was to evaluate the association of CD and UC with several environmental risk factors. METHODS: This case-control study included 338 patients (190 CD, 148 UC) and 355 controls. All subjects completed a detailed questionnaire regarding breastfeeding duration, history of helminthic infections, allergic diseases, appendectomy, household size, housing type, contact with specific domestic animals, physical activity, and smoking. Associations between risk factors and CD and UC were investigated by univariate and multivariate analysis. RESULTS: On multivariate analysis, CD associated with smoking at diagnosis (odds ratio, OR, 3.7, 95% CI 2.2-6.2; p < 0.001), being breastfed for <6 months (OR 2.7, 95% CI 1.7-4.4; p < 0.001), and less than two childhood sporting activities weekly (OR 2.7, 95% CI 1.5-5.0; p < 0.001) and inversely associated with frequent contact with cats in childhood (OR 0.6, 95% CI 0.4-0.9; p < 0.03). UC associated with less than two sporting weekly activities in childhood (OR 2.0, 95% CI 1.1-3.5, p = 0.02), fewer household members in childhood (OR 0.8, 95% CI 0.7-0.98, p = 0.03), and being breastfed for <6 months (OR 1.7, 95% CI 1.02-2.8, p = 0.04). A composite environmental risk index for CD revealed that 47 and 14% of the controls and patients with CD had no risk factors, respectively, and that 14 and 38% of the controls and patients with CD had at least two risk factors, respectively. CONCLUSION: CD and UC associated with infrequent childhood sports activities and short breastfeeding. Furthermore, CD associated with smoking and infrequent contact with animals in childhood. UC associated with a smaller family size in childhood.