Efrat Broide

Effects of current cigarette smoking on clinical course of Crohn's disease and ulcerative colitis.

Cigarette smoking worsens Crohns disease (CD) but ameliorates ulcerative colitis (UC). In Israel, where there is no epidemiological association of smoking with CD, we examined the effects of current smoking on the course of CD and UC. Patients at nine public hospitals completed a questionnaire detailing their smoking history, disease course and treatments; subjects altering their smoking habit after the onset of disease were excluded. Sixty-four smokers and 144 nonsmokers had CD, and 34 smokers and 158 nonsmokers had UC. No differences were found between CD smokers and nonsmokers for hospitalizations, operations, and requirement for corticosteroid and immunosuppressive treatment. By contrast, UC smokers had less extensive disease than nonsmokers (P < 0.02) and fewer hospitalizations (P = 0.01) and operations (P = 0.025). Our results agree with a minority of studies showing no adverse effect of smoking on the course of CD, and confirm the protective effect of smoking in UC.

Lack of association between smoking and Crohn's disease but the usual association with ulcerative colitis in Jewish patients in Israel: a multicenter study

OBJECTIVE:The association between smoking and inflammatory bowel disease (IBD) is well established, but data in Jewish patients in Israel were discrepant. The aim of this study was to examine the smoking habits of Jewish IBD patients in Israel in a large scale, multicenter study.METHODS:Patients with established IBD aged 18–70 yr were interviewed in relation to smoking and other habits. Two controls (one clinic and one neighborhood control matched by age, sex, community group, and education) were sought for each subject.RESULTS:A total of 534 patients (273 ulcerative colitis [UC], and 261 Crohns disease [CD]), along with 478 clinic controls and 430 neighborhood controls, were interviewed. There was no significant difference in the smoking habits between CD patients and their controls. Of patients with CD, 24.5% were current smokers, as compared to 19.9% of clinic controls and 25.2% of neighborhood controls (NS).The odds ratio for CD in current smokers was 1.30 (95% confidence interval 0.85–1.99) versus clinic controls, and 0.96 (0.63–1.46) versus neighborhood controls. There were also no significant differences in the proportion of ex-smokers between the groups. Only12.9% of UC patients were current smokers versus 21.9. % Clinic controls, and 26.4% community controls (p < 0.005). The proportions of ex-smokers were higher in UC patients 29.7%versus 25.9%, and 19.5% in their respective controls (p < 0.001vs community controls). No significant differences were found in the proportions of never-smokers between IBD patients and controls. All the above trends were similar in four different parts of the country. The proportion of current smokers in UC decreased with the extent of disease (19.7% in proctitis, 13.6% in left-sided, and 4.5% in total colitis) (p < 0.05). Patients with UC were more likely to be light smokers(1–10 cigarettes/day), whereas patients with CD were more likely to be moderate smokers (11–20 cigarettes/day) in comparison to their controls.CONCLUSIONS:The lack of association between smoking and CD has now been established in Jewish patients in Israel. The association was found in UC. The stronger genetic tendency in CD may contribute to this discrepancy.

Long-term outcome of tumor necrosis factor alpha antagonist's treatment in pediatric Crohn's disease

BACKGROUND Anti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD. METHODS The long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short- and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed. RESULTS 120 patients [101 crohns disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2-90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p<0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p<0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p<0.001). The cumulative probability of losing response to anti-TNFα treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders had a significantly lower weight and BMI Z-scores at initiation of anti-TNFα treatment in compared to non-responders (p=0.04 and 0.02 respectively). CONCLUSIONS Our long term cohort supports the current evidence on the effectiveness and safety of anti-TNFα treatment in children with IBD. Response to treatment was interestingly associated with lower weight and BMI.

A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease

Objectives Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease. Methods A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease. Results Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P < 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P < 0.01). Conclusions Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.

A controlled double blind multicenter study of the effectiveness of 5-aminosalicylic acid in patients with Crohn's disease in remission.

We evaluated the efficacy of an oral formulation of 5-amino-salicylic acid in lowering the relapse rate after remission of Crohns disease. Included were 59 patients who had proven Crohns disease of at least 1 years duration, and who had been in continuous remission for at least 6 months, while taking only 5-aminosalicylic acid or no therapy at all. Remission was defined as a Harvey Bradshaw index score (Softley-Clamp modification) of < 4. Patients were given coded mesalzaine 250 mg or placebo tablets (2 x 2 day). They were seen at 0, 1, and 2 months, and then every 2 months until the end of the study. Trial endpoints were 1 year of follow-up, or clinical relapse results. After randomization, 31 patients were included in the placebo arm, and 28 in the treatment arm. There were no significant differences between the two groups at entry. Ten patients were withdrawn from the trial because of noncompliance, loss of follow-up, or headache. There were more clinical relapses in the placebo arm (15 patients, 55%) than in the treatment arm (6 patients, 27%) (p < 0.05). Mesalazine had a significant advantage over placebo (p < 0.05) only in the subgroups of patients with ileal Crohns disease and in those older than 30 years. We conclude that mesalazine has a moderate but significant benefit in preventing relapse in Crohns disease in remission; this occurred only in patients with small-bowel involvement or in those older than 30 years.

Serum transferrin receptor in children and adolescents with inflammatory bowel disease

Abstract Iron studies are difficult to interpret in patients with chronic inflammatory states such as inflammatory bowel disease (IBD). Serum transferrin receptor (TfR) has been reported to be a reliable tool for the diagnosis of iron deficiency in adults. Our aim was to evaluate the role of serum TfR in diagnosing iron deficiency in children and adolescents with IBD. A total of 63 consecutive patients with IBD, aged 9 to 22 years (median 15 years), were tested for serum haemoglobin level, mean corpuscular volume (MCV), and serum iron, transferrin, ferritin and serum TfR levels. Those found to be anaemic were compared with seven age-matched subjects with iron deficiency anaemia (IDA) and 24 age-matched children without signs of anaemia or inflammation. Of the 63 patients with IBD, 26 had anaemia. Based on ferritin levels and MCV indices, anaemia was classified as IDA in 11 patients and as anaemia of chronic disease (ACD) in 15 patients. Mean serum TfR level in normal controls was 3.5 mg/l (range 1.2–8.2 mg/l). Mean (±SD) serum TfR levels were significantly lower in the IBD patients with ACD (5.3 ± 2.3 mg/l) than in the IBD patients with IDA (8.2 ± 3.1 mg/l) (P < 0.05). Serum TfR levels above 5 mg/l identified 10/11 IBD patients with IDA. The calculated TfR/ferritin ratio was 84 (range 17–367) for controls and 133 (range 6.4–1840) for IBD patients. A cut-off level of 350 (91% sensitivity, 100% specificity, 100% positive predictive value, 98% negative predictive value) was established for the diagnosis of IDA in IBD. Conclusion The results suggest that serum transferrin receptor is a useful parameter for the diagnosis of iron deficiency in inflammatory bowel disease, in particular, the transferrin receptor/ferritin ratio with a cut-off level ≥350.

Appendectomy is more frequent but not a risk factor in Crohn's disease while being protective in ulcerative colitis: a comparison of surgical procedures in inflammatory bowel disease.

OBJECTIVE:Appendectomy was shown to be protective in patients with ulcerative colitis (UC). There are fewer data in Crohns disease (CD). Other operations were less studied. The aim of this study was to investigate the prevalence of appendectomy, cholecystectomy, and tonsillectomy, including their timing, in patients with inflammatory bowel disease in comparison to controls.METHODS:Two hundred seventy-one patients with UC and 260 with CD, 475 clinic controls, and 428 community controls were interviewed.RESULTS:Appendectomy was found in 5.5% patients with UC, in 11% of clinic controls (p < 0.05), and 7.7% of community controls (p = not significant). The differences were more significant for appendectomy before onset of disease. Appendectomy was performed in 19.2% of patients with CD, in 10.9% of clinic controls, and in 10.1% of community controls (p < 0.01). However, there were no significant differences when only appendectomy before onset of disease was considered. Cholecystectomy was found in 1.5% of patients with UC, in 6.1% of clinic controls (p < 0.01), and in 4.5% of community controls (p = not significant). The difference remained significant when confined to operations performed before disease onset. No such difference was found in patients with CD. No significant difference was found in the prevalence of tonsillectomy between patients and controls.CONCLUSIONS:Appendectomy is protective in UC; it is more frequent, but not a risk factor in CD. The role of cholecystectomy should be investigated further.

Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine analogues.

Background: Immunomodulatory drugs play a major role in maintaining remission and steroid sparing in children with Crohn disease. Although thiopurine agents are commonly used, unresponsiveness or intolerance to these drugs is common. The efficacy of methotrexate in maintenance of remission has been shown in adult Crohn disease; however, pediatric data are limited. Our goal was to evaluate the efficacy and safety of methotrexate in induction and maintenance of clinical remission in children with active Crohn disease who failed thiopurine treatment. Patients and Methods: In a retrospective multicenter study, efficacy of methotrexate in inducing and maintaining remission or response was assessed by Harvey-Bradshaw activity index, paediatric Crohn disease activity index and steroid use, in 25 children with Crohn disease, refractory or intolerant to thiopurine analogues. Results: Crohn disease was diagnosed at a mean age of 11.1 ± 3.1 years and methotrexate was initiated at age 14.5 ± 3.1 years. The median methotrexate dose was 12.5 mg/m2. Remission was achieved in 16 patients (64%), and response in 6 patients (24%). Out of 18 patients treated for longer than 6 months, 83% were in remission or response after 12 months of treatment. The mean duration of remission and response was 10.8 ± 8.8 months. Steroid withdrawal was possible in 12/16 patients (75%) receiving steroids at methotrexate introduction. Adverse effects were observed in 6 patients (24%) including nausea and vomiting in 3, elevation of liver enzymes in 2 and pancreatitis in 1 patient. Conclusions: Methotrexate is beneficial in maintaining remission and steroid-sparing treatment in children with Crohn disease following failure of thiopurine therapy.

Prevalence of celiac antibodies in children with neurologic disorders

Neurologic complications are a recognized but unusual manifestation of celiac disease (CD) in adults and children. The use of antigliadin and antiendomysial antibodies in screening has revealed the frequency of CD among symptom-free individuals to be high. Recently, a high frequency (57%) of antigliadin antibodies was demonstrated in adult patients with neurologic dysfunctions of unknown cause. We investigated the yield of screening for CD in children with common neurologic disorders. One hundred sixty-seven children, 1-16 years of age, were included in the study: 41 with migraine headaches, 39 with attention-deficit disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were evident in 22 children (13%) in the study group compared with three children (9%) in the control group. However, in all children, negative IgA and endomysial antibodies were observed; thus duodenal biopsies were not performed. Contrary to studies performed in adults, these results did not demonstrate any relationship between common neurologic disorders without a specific diagnosis during childhood and CD. Thus screening for CD does not need to be routinely included in the diagnostic evaluation of children with these disorders.

Superoxide dismutase activity in children with chronic liver diseases

BACKGROUND/AIMS Liver disease in infancy has multiple etiologies. As reactive oxygen intermediates are involved in several types of tissue damage, we have investigated whether different forms of liver disease in infancy are associated with increased free radical generation, using an indirect approach in which superoxide dismutase (a free radical scavenger) activity is determined in the liver tissue. METHODS A total of 48 liver biopsies performed at diagnosis were evaluated retrospectively. Nine infants had biliary atresia, eight Alagille syndrome, seven alantitrypsin deficiency and 12 cryptogenic hepatitis. As controls we studied 12 biopsies with normal histology obtained from seven children with portal vein thrombosis and five children who underwent biopsy for management reason but had no liver disease. Superoxide dismutase activity in liver biopsy specimens was measured using the cytochrome C method by spectrophotometry and expressed as U SOD/mg protein. RESULTS Superoxide dismutase activity was significantly increased in biliary atresia (1.25 +/- 0.56 U SOD/mg protein, p<0.0001) and Alagille syndrome (1.31 +/- 0.56 U SOD/mg protein, p<0.0001) as compared with al-antitrypsin deficiency (0.75 +/- 0.3 U SOD/mg protein), neonatal hepatitis (0.72 +/- 0.37 U. SOD/mg protein) and normal controls (0.4 +/- 0.7 U. SOD/mg protein). The highest level of SOD activity was found, however, in control children with portal vein thrombosis (2.09 +/- 0.96 U SOD/mg protein; p<0.0001 as compared to the other groups). CONCLUSION Superoxide dismutase, a key enzyme in free radical protection, is increased significantly in the liver tissue of infants with cholestatic liver disease due to bile duct damage and in children with portal vein thrombosis, suggesting that products of free radical reactions are involved in the pathogenesis of these disorders.