V. Pannone

Mucosal NOD2 expression and NF-kappaB activation in pediatric Crohn's disease.

Background: Recent advances in the pathogenesis of Crohns disease (CD) have suggested that an aberrant innate immune response initiates the cascade of events leading to T‐cell activation and to disease development. NOD2 protein, which is mainly expressed by innate immunity cells, appears to play a key role against bacteria by triggering a host defense response through the activation of the transcriptor factor NF‐&kgr;B and a consequent proinflammatory cytokine production. The present study was aimed at investigating the expression and activity of NOD2, NF‐&kgr;B, and of 2 proinflammatory cytokines, TNF&agr; and IL‐1&bgr;, in mucosal biopsies of CD affected children compared to healthy controls. Methods: In all, 22 children with active CD and 10 matched controls were entered in the study. mRNA and protein expressions were detected using reverse‐transcriptase polymerase chain reaction (RT‐PCR) and Western blot; NF‐&kgr;B binding activity was assessed by electromobility gel shift assay (EMSA). Results: NOD2 and IL‐1&bgr; mRNAs were upregulated in CD children. Protein levels of NOD2, TNF&agr;, and nuclear NF‐&kgr;B, as well as the binding activity of NF‐&kgr;B to a consensus DNA sequence, were significantly increased in inflamed mucosa of patients as compared to controls. Moreover, NF‐&kgr;B activity was strongly upregulated in patients also when bound to the NOD2 promoter site. No difference was seen between patients and controls when NF‐&kgr;B binding activity was determined in the uninflamed tissue. Conclusions: This study suggests that altered mechanisms regulating NOD2 induction, NF‐&kgr;B activation and cytokine production may contribute to dysregulate the innate immune response underlying pediatric CD.

PA29 PRESUMPTIVE SAFETY FOR CELIAC PATIENTS OF WHEAT BAKED GOODS RENDERED GLUTEN-FREE DURING SOURDOUGH FERMENTATION

After several interviews, this teenager admitted participation to an unusual dietary party with three peers, 4 days before admission. They ate a “soup” formed by gravel, wheat flour and water, for slimming purposes. The soup recipe had been found on an unidentified web site. After the party, one of the friends underwent emergency appendectomy for appendix occlusion caused by a gravel stone, another had been admitted for acute abdominal pain followed by passage of gravel stones in the stool while the third eliminated the stones in the stools without any complaint. Discussion: This case-report highlights the risks related to improper use of uncontrolled information found on the internet. There is a rising and widespread use of the web among children and adolescents. Recent studies showed that adolescents disclose personal information and may display risky behaviour. Sylvia wanted to loose weight even though her BMI was normal (18.7 = 25th percentile for age and gender). Concerns about weight, body shape and dieting are common among adolescent girls and may represent risk factors for eating disorders. One’s body image perception is influenced by several factors, including personal, parental and friends’ judgement, sociocultural environment and media pressures, that are believed to encourage the development of an unrealistically thin ideal of body shape. Independent of age and BMI, parental and media influences on adolescents are predictive of becoming highly concerned with weight and a constant dieter. Abdominal ultrasound is usually the first-line (and often the only) imaging investigation performed in the diagnostic process of children with AAP, to exclude appendicitis or other surgical conditions (e.g. intussusception). Abdominal ultrasound has however limitations (e.g. presence of excessive intestinal gas and operator dependence) and does not always identify ingested foreign bodies. In this patient, the intestinal stones were indeed detected only by a standard abdominal x-ray. Conclusions: Acute or recurrent abdominal pain is a frequent complaint in adolescents, particularly of those experiencing emotional and socio-familial difficulties. A careful interview can help to identify risky behaviours that could be responsible for this distressing disorder. As suggested by this case-report, the use of junk information retrieved by uncontrolled internet sources should be investigated. The deliberate ingestion of foreign bodies is a possible cause of AAP in teenagers.

Atrioventricular block associated with Crohn's relapsing colitis in a 12‐year‐old child

To the Editor: Inflammatory bowel diseases (IBDs) are associated with extraintestinal manifestations. Many systems or organs, i.e., eye, skin, liver, bone, and joints are frequently involved in IBD, but cardiac involvement is considered rare. Myopericarditis, worsening of congestive heart failure, sinusal symptomatic bradycardia, and heart block have been described in IBD patients as side effects of infliximab (chimeric monoclonal antibody to tumor necrosis factor-a). Cardiac conduction disturbances associated with IBD, in the absence of infliximab treatment, have been described in only a few case reports regarding adult patients with ulcerative colitis. Cardiac conduction system disturbance in children with Crohn’s disease (CD), not treated with infliximab, have not been reported yet. We describe the case of a 12-year-old child with CD involving the terminal ileum. There was no past history of cardiac disease and no evidence of myocardial ischemia or recent viral infection. The patient was treated with nutritional therapy (Modulen) and with azathioprine, but he was not treated with any anti-TNFa drugs. CD had been in remission for 6 months when the child developed bloody diarrhea without any systemic symptoms. He was hospitalized for relapse of CD. Colonoscopy showed active pancolitis. Laboratory data showed hemoglobin 11.8 mg/dL, white cells 9340 (neutrophils 79.4%), erythrocyte sedimentation rate (ESR) (31 mm/h), and D-dimer (782 mg/dL). Serology for cytomegalovirus, Epstein–Barr virus, and Mantoux test were negative. Fecal exam was positive for Clostridium difficile and antiSaccharomyces cerevisiae antibodies (ASCA) were high (160; normal value < 14). ECG showed first-degree atrioventricular block which was absent in previous electrocardiogram (ECG) (Fig. 1) and it was confirmed by 24-hour ECG monitoring. To assess autonomic system balance, heart rate variability (HRV), by short computed ECG monitoring (10 minutes), was recorded. Low LF/HF ratio (0.36), which is a sign of increased parasympathetic tone, was shown. Treatment with intravenous methylprednisone for 2 days was started. After 48 hours the bloody diarrhea cleared. Subsequently, oral therapy was carried out for several weeks. The azathioprine therapy was later replaced with methotrexate 20 mg/week intramuscularly, salazopyrin 2 cp 3 times a day, and folic acid. Metronidazole for C. difficile infection was also administered. On 3-month follow-up both outpatient review of bowel habits and colonoscopy were normal. Hematochemical parameters returned to normal range (hemoglobin 12.4 mg/dL, white cell 5000, ESR 8 mm/h). The LF/HF ratio returned to normal values (1.48). Monitoring ECG for 5 hours confirmed the persistence of atrioventricular block (PR mean 0.21 sec; normal value for age: 0.09–0.18 sec). To today, atrioventricular block is still present. We describe the case of a child with first-degree atrioventricular block associated with CD. This heart block, absent in previous ECG, appeared during the relapse of colitis and did not disappear at termination of relapse and is still present after 12 months. The excess of vagal activity, observed during relapse of disease, seems not have been implicated in the origin of atrioventricular block because of its persistence after vagal reequilibrium. Atrioventricular block in CD has been associated with infliximab therapy, but our patient had not been treated with this drug. Azathioprine and aminosalycilates seem to play a role in the etiology of pericarditis, but not in cardiac conduction disturbances. In conclusion, in our case both autonomic imbalance and drug therapy do not seem to be implicated in atrioventricular block, so it might be that the inflammatory state of relapsing colitis has caused damage to the cardiac conduction system cells. Microvascular endothelial dysfunction has been found in IBD patients. We speculate that some ischemic microdamage in the cardiac conduction system of our FIGURE 1. ECG recorded in Lead II before (A) and during (B) relapse of CD. ECG in B shows atrioventricular block.