A. Marseglia

Investigation of Multiple Susceptibility Loci for Inflammatory Bowel Disease in an Italian Cohort of Patients

Background Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. Methods Eight SNPs were assessed in 1,070 Crohns disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. Results The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10−6). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10−5). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. Conclusions We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.

PP62 CELIAC DISEASE IN JUVENILE DERMATOMYOSITIS: A CASE REPORT

Introduction: Juvenile dermatomyositis (JDM) is a rare chronic autoimmune disease with onset during childhood. It is characterized by weakness in proximal muscles and pathognomonic skin rashes. Although the etiology remains unclear, it has been proposed that JDM is caused by a vasculopathy within the muscle tissue and multiple other organ systems of genetically susceptible individuals, possibly in response to environmental triggers. Celiac disease (CD) is a malabsorption syndrome resulting from a small-bowel enteropathy related to the intake of dietary gluten in susceptible individuals. Gluten is thought to cause both direct and immune-mediated toxicity. Clinical Case: We report a case of a six year and a six months old girl who was admitted to the hospital suffering from increasing muscle weakness and leg pain. She developed malaise, easy fatigability, fever with temperatures until to 38°C. The skin was pale and the physical examination revealed erythematous, desquamative lesions on the extensor surface of the fingers, especially the metacarpophalangeal and proximal interphalangeal and proximal interphalangeal joints (Gottron’s papules). She also had a heliotrope rash characterized by a violet eyelids erythema. Neurological examinations demonstrated moderate reduced strength in the proximal lower extremities. The laboratory investigations showed a marked elevation of creatine kinase (×5 and ×7 n.v.), a moderate elevation of aspartate aminotransferase and lactate dehydrogenase. The C-reactive protein was negative and the erythrocyte sedimentation rate was 33 mm in the first hour. In addition, several autoantibodies (rheumatoid factor, antinuclear antibodies, antimitochondrial antibodies, anti-DNA antibodies, antithyroid antibodies) was not detectable except for the antibodies against smooth muscle cells (++–). An electromyogram showed typical signs of myopathy. Chest X-ray, abdominal ultrasound, electrocardiogram and echocardiography showed no abnormalities. Her body weight was below the 3th percentile and was performed a celiac screening that revealed anti-endomysial (EMA) and anti-transglutaminase antibodies positive (TG × 3 n.v.). The patient underwent upper gastrointestinal endoscopy with a small-bowel biopsy that confirmed the suspicion of CD. Pathology revealed villous atrophy and moderate chronic inflammation in the lamina propria with an intraepithelial lymphocytosis. The patient’s human leucocyte antigen haplotype (HLA) study was positive for DR3 and DQ2 which have been shown to be associated with both JDM and CD. Both CD and JDM share common HLA associations, including most notable the DQA1*0501 allele. Conclusion: Our observation raises the question of an association between JDM and CD as part of a continuum, suggesting that CD disease may be included within the spectrum of the gastrointestinal manifestations of JDM. From a practical point of view, our data indicate that the diagnosis of CD should be suspected in JDM patients exhibiting malabsorption syndrome. Based on our findings, we further emphasize that an evaluation for CD, including EMA and TG antibodies should be considered in JDM patients presenting with unusual and unexplained gastrointestinal features. This could lead to the early management of such patients, resulting in decreased morbidity related to misdiagnosed CD.