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Validation of new ESPGHAN diagnostic criteria for celiac disease
e294
Abstracts / Digestive and Liver Disease 45 (2013) e263–e311
PO33 VALIDATION OF NEW ESPGHAN DIAGNOSTIC CRITERIA FOR CELIAC DISEASE M. Proto 1 , P. Alvisi 2 , C. Barbera 3 , A. Campanozzi 4 , S. Cardile 5 , C. Romano 5 , R. Cozzali 6 , G. Castellucci 6 , M. Corvo 7 , W. Kleon 8 , G. Guariso 9 , M. Pescarin 9 , P. Kosova 10 , B. Malamisura 11 , P. Melli 12 , B. Parma 13 , L. Giancotti 14 , L. Pensabene 14 , S. Salvatore 15 , A. Tetro 16 , R. Auricchio 1
antibodies level greater than 10 times normal value) was greater than or equal to 4 (all requirements respected) in 98% of patients. Patients with different degree of villous atrophy had diagnostic score equal to or greater than 4 in 90.7% of cases. Only 2 out of 306 (0.84%) had a negative score in the presence of mucosal damage, while the 7.98% had positive score but absence of atrophy (potential CD patients). Conclusion: Our study confirm that patients fulfilling diagnostic score could avoid intestinal biopsy, even if there could be around 8% of potential CD in these group of patients prescribed a gluten-free diet not always necessary.
1
Department of Pediatrics, AOU Policlinico “Federico II”, Naples, Italy 2 Department of Pediatrics, Maggiore Hospital, Bologna, Italy 3 Department of Pediatrics, University of Turin “Alma Universitas Turinensis”, Turin, Italy 4 Department of Pediatrics, University of Foggia, Foggia, Italy 5 Department of Pediatric Medical and Surgical Sciences, AOU Policlinico “G.Martino”, Messina, Italy 6 Department of Pediatrics and Neonatology, San Giovanni Battista Hospital, Foligno, Italy 7 Department of Pediatrics, Macedonio Melloni Hospital, Milan, Italy 8 Department of Pediatrics, Lorenz Bohler Hospital, Bolzano, Italy 9 Department of Pediatrics “Salus Pueri”, University of Padova, Padova, Italy 10 Department of Pediatrics, PO San Paolo, Naples, Italy 11 Department of Pediatrics, AOU “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, Italy 12 Department of Pediatrics, AOU S.Maria Misericordia, Udine, Italy 13 Department of Pediatrics, AO Sant’Anna, Como, Italy 14 Department of Pediatrics, University of Catanzaro “Magna Graecia”, Catanzaro, Italy 15 Department of Pediatrics, F. Del Ponte Hospital, Varese, Italy 16 Department of Pediatrics, San Paolo Hospital, Bari, Italy Background: According with new ESPGHAN diagnostic criteria for celiac disease (CD) symptomatic patients with genetic predisposition (DQ2 and/or DQ8 positive) and high titer of CD serology (anti-transglutaminase antibodies, anti-TG2, above 10 times the reference value, and anti endomysial antibodies, EMA, positivity) could avoid duodenal biopsy. The purpose of this multicenter study is to validate these new diagnostic criteria. Methods: We collected data on 306 patients who underwent celiac disease diagnosis from January 2011 to November 2012 in 16 nationwide CD Centers. All patients underwent genetic, serology and histological analyses. Follow-up of 6 to 12 months were also performed to evaluate the effects of the gluten free diet. Data were collected using a specific form. Results: At time of diagnosis, 24.6% of patients were asymptomatic, 21.1% had a family history of CD, 10% of the cases had other related chronic diseases (thyroiditis, type 1 diabetes, dermatitis). Among symptomatic patients, 30.5% reported moderate recurrent abdominal pain, 12.1% diarrhea, 10.9% failure to thrive. Genetic analysis confirmed that the DQ2 haplotype is the most common haplotype (59.4%). The diagnostic score (including genetic predisposition, presence of symptoms, presence of EMA and anti-TG2
PO34 IMPACT OF MEASUREMENT OF INFLIXIMAB AND ANTI-INFLIXIMAB ANTIBODIES LEVELS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE S. Cardile, A. Costa, I. Loddo, G. Morabito, C. Pidone, C. Romano IBD Pediatric Unit, Pediatric Department, University of Messina, Messina, Italy Background: Infliximab (IFX), a chimeric monoclonal antibody directed against tumor necrosis factor (TNF), is approved for the induction and maintenance of remission in both Crohn’s disease (CD) and ulcerative colitis (UC). Clinical trials and case series have reported induction of remission in 40–60% of patients treated with this agent, with the majority continuing with maintenance therapy every 8 weeks. Despite its proven efficacy in maintenance of remission, a significant proportion of patients lose their clinical response over time despite maintenance treatment. This loss of response (LOR) occurs in up to 70% of patients treated with IFX. There are several mechanisms of LOR to IFX; however, immunogenicity to the antibody itself appears to be a commonly identified factor. ATIs (antibodies to infliximab) correlated to low serum IFX (s-IFX) concentrations and lack of clinical response in both CD and UC is a important clinical target. Multiple studies in IBD patients have linked the development of ATI with loss of treatment response, shorter duration of response, and infusion reactions. Conversely, others have shown no difference in clinical outcomes between ATIpositive or ATI-negative patients. The problem of immunogenicity of anti-TNF agents was not described in the pediatric IBD. Objectives: To study s-IFX and ATIs levels in pediatric patients with IBD. Materials and methods: s-IFX and ATI-s levels were measured in a total 30 blood samples of 15 pediatric IBD (CD, 10 and CU, 5) during the maintenance therapy. Values of s-IFX and sATI were correlated to serum markers of inflammation (c-reactive protein, CRP). The measurement was been done by an EnzymeLinked ImmunoSorbent Assay (ELISA). Sensitivity level for IFX was 0.4 g/ml. Cut-off level for ATI is equal to twice the Optical Density (OD) of the negative control. Trough levels of IFX and ATI were defined as the serum concentration immediately prior to an IFX infusion. Results: During maintenance therapy (5 mg/kg), the median sIFX levels were 5.5 g/ml (range −0.1/14.9). The s-IFX levels were similar in CU and CD (3.2 vs 2.5 g/ml, p: 0.6). ATI were positive in 2 patients (2.4 and 1.5 OD) with correlated low level of s-IFX (−0.3 and −0.1 g/ml). Shorter administration interval protocol was adopted in 2 patients with higher trough levels (p < 0.005). High level of CRP during maintenance therapy was associated with lower s-IFX (median 0.03 g/ml). There was no significative association between clinical score (PCDAI) and s-IFX/s-ATI levels. None of the patients had adverse IFX reactions.
Abstracts / Digestive and Liver Disease 45 (2013) e263–e311
PO33 VALIDATION OF NEW ESPGHAN DIAGNOSTIC CRITERIA FOR CELIAC DISEASE M. Proto 1 , P. Alvisi 2 , C. Barbera 3 , A. Campanozzi 4 , S. Cardile 5 , C. Romano 5 , R. Cozzali 6 , G. Castellucci 6 , M. Corvo 7 , W. Kleon 8 , G. Guariso 9 , M. Pescarin 9 , P. Kosova 10 , B. Malamisura 11 , P. Melli 12 , B. Parma 13 , L. Giancotti 14 , L. Pensabene 14 , S. Salvatore 15 , A. Tetro 16 , R. Auricchio 1
antibodies level greater than 10 times normal value) was greater than or equal to 4 (all requirements respected) in 98% of patients. Patients with different degree of villous atrophy had diagnostic score equal to or greater than 4 in 90.7% of cases. Only 2 out of 306 (0.84%) had a negative score in the presence of mucosal damage, while the 7.98% had positive score but absence of atrophy (potential CD patients). Conclusion: Our study confirm that patients fulfilling diagnostic score could avoid intestinal biopsy, even if there could be around 8% of potential CD in these group of patients prescribed a gluten-free diet not always necessary.
1
Department of Pediatrics, AOU Policlinico “Federico II”, Naples, Italy 2 Department of Pediatrics, Maggiore Hospital, Bologna, Italy 3 Department of Pediatrics, University of Turin “Alma Universitas Turinensis”, Turin, Italy 4 Department of Pediatrics, University of Foggia, Foggia, Italy 5 Department of Pediatric Medical and Surgical Sciences, AOU Policlinico “G.Martino”, Messina, Italy 6 Department of Pediatrics and Neonatology, San Giovanni Battista Hospital, Foligno, Italy 7 Department of Pediatrics, Macedonio Melloni Hospital, Milan, Italy 8 Department of Pediatrics, Lorenz Bohler Hospital, Bolzano, Italy 9 Department of Pediatrics “Salus Pueri”, University of Padova, Padova, Italy 10 Department of Pediatrics, PO San Paolo, Naples, Italy 11 Department of Pediatrics, AOU “San Giovanni di Dio e Ruggi D’Aragona”, Salerno, Italy 12 Department of Pediatrics, AOU S.Maria Misericordia, Udine, Italy 13 Department of Pediatrics, AO Sant’Anna, Como, Italy 14 Department of Pediatrics, University of Catanzaro “Magna Graecia”, Catanzaro, Italy 15 Department of Pediatrics, F. Del Ponte Hospital, Varese, Italy 16 Department of Pediatrics, San Paolo Hospital, Bari, Italy Background: According with new ESPGHAN diagnostic criteria for celiac disease (CD) symptomatic patients with genetic predisposition (DQ2 and/or DQ8 positive) and high titer of CD serology (anti-transglutaminase antibodies, anti-TG2, above 10 times the reference value, and anti endomysial antibodies, EMA, positivity) could avoid duodenal biopsy. The purpose of this multicenter study is to validate these new diagnostic criteria. Methods: We collected data on 306 patients who underwent celiac disease diagnosis from January 2011 to November 2012 in 16 nationwide CD Centers. All patients underwent genetic, serology and histological analyses. Follow-up of 6 to 12 months were also performed to evaluate the effects of the gluten free diet. Data were collected using a specific form. Results: At time of diagnosis, 24.6% of patients were asymptomatic, 21.1% had a family history of CD, 10% of the cases had other related chronic diseases (thyroiditis, type 1 diabetes, dermatitis). Among symptomatic patients, 30.5% reported moderate recurrent abdominal pain, 12.1% diarrhea, 10.9% failure to thrive. Genetic analysis confirmed that the DQ2 haplotype is the most common haplotype (59.4%). The diagnostic score (including genetic predisposition, presence of symptoms, presence of EMA and anti-TG2
PO34 IMPACT OF MEASUREMENT OF INFLIXIMAB AND ANTI-INFLIXIMAB ANTIBODIES LEVELS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE S. Cardile, A. Costa, I. Loddo, G. Morabito, C. Pidone, C. Romano IBD Pediatric Unit, Pediatric Department, University of Messina, Messina, Italy Background: Infliximab (IFX), a chimeric monoclonal antibody directed against tumor necrosis factor (TNF), is approved for the induction and maintenance of remission in both Crohn’s disease (CD) and ulcerative colitis (UC). Clinical trials and case series have reported induction of remission in 40–60% of patients treated with this agent, with the majority continuing with maintenance therapy every 8 weeks. Despite its proven efficacy in maintenance of remission, a significant proportion of patients lose their clinical response over time despite maintenance treatment. This loss of response (LOR) occurs in up to 70% of patients treated with IFX. There are several mechanisms of LOR to IFX; however, immunogenicity to the antibody itself appears to be a commonly identified factor. ATIs (antibodies to infliximab) correlated to low serum IFX (s-IFX) concentrations and lack of clinical response in both CD and UC is a important clinical target. Multiple studies in IBD patients have linked the development of ATI with loss of treatment response, shorter duration of response, and infusion reactions. Conversely, others have shown no difference in clinical outcomes between ATIpositive or ATI-negative patients. The problem of immunogenicity of anti-TNF agents was not described in the pediatric IBD. Objectives: To study s-IFX and ATIs levels in pediatric patients with IBD. Materials and methods: s-IFX and ATI-s levels were measured in a total 30 blood samples of 15 pediatric IBD (CD, 10 and CU, 5) during the maintenance therapy. Values of s-IFX and sATI were correlated to serum markers of inflammation (c-reactive protein, CRP). The measurement was been done by an EnzymeLinked ImmunoSorbent Assay (ELISA). Sensitivity level for IFX was 0.4 g/ml. Cut-off level for ATI is equal to twice the Optical Density (OD) of the negative control. Trough levels of IFX and ATI were defined as the serum concentration immediately prior to an IFX infusion. Results: During maintenance therapy (5 mg/kg), the median sIFX levels were 5.5 g/ml (range −0.1/14.9). The s-IFX levels were similar in CU and CD (3.2 vs 2.5 g/ml, p: 0.6). ATI were positive in 2 patients (2.4 and 1.5 OD) with correlated low level of s-IFX (−0.3 and −0.1 g/ml). Shorter administration interval protocol was adopted in 2 patients with higher trough levels (p < 0.005). High level of CRP during maintenance therapy was associated with lower s-IFX (median 0.03 g/ml). There was no significative association between clinical score (PCDAI) and s-IFX/s-ATI levels. None of the patients had adverse IFX reactions.