A point-of-care test for facing the burden of undiagnosed celiac disease in the Mediterranean area: a pragmatic design study

BACKGROUND: We aimed at assessing the factors that can influence results of the dissemination of an already validated, new generation commercial Point-of-Care Test (POCT) for detecting celiac disease (CD), in the Mediterranean area, when used in settings where it was designed to be administered, especially in countries with poor resources. METHODS: Pragmatic study design. Family pediatricians at their offices in Italy, nurses and pediatricians in Slovenia and Turkey at pediatricians', schools and university primary care centers looked for CD in 3,559 (1-14 yrs), 1,480 (14-23 yrs) and 771 (1-18 yrs) asymptomatic subjects, respectively. A new generation POCT detecting IgA-tissue antitransglutaminase antibodies and IgA deficiency in a finger-tip blood drop was used. Subjects who tested positive and those suspected of having CD were referred to a Celiac Centre to undergo further investigations in order to confirm CD diagnosis. POCT Positive Predictive Value (PPV) at tertiary care (with Negative Predictive Value) and in primary care settings, and POCT and CD rates per thousand in primary care were estimated. RESULTS: At tertiary care setting, PPV of the POCT and 95% CI were 89.5 (81.3-94.3) and 90 (56-98.5) with Negative Predictive Value 98.5 (94.2-99.6) and 98.7% (92-99.8) in children and adults, respectively. In primary care settings of different countries where POCT was performed by a different number of personnel, PPV ranged from 16 to 33% and the CD and POCT rates per thousand ranged from 4.77 to 1.3 and from 31.18 to 2.59, respectively. CONCLUSIONS: Interpretation of POCT results by different personnel may influence the performance of POC but dissemination of POCT is an urgent priority to be implemented among people of countries with limited resources, such as rural populations and school children

Celiac disease in the Mediterranean area.

International audienceBACKGROUND: The World Gastroenterology Organization recommends developing national guidelines for the diagnosis of Celiac Disease (CD): hence a profile of the diagnosis of CD in each country is required. We aim to describe a cross-sectional picture of the clinical features and diagnostic facilities in 16 countries of the Mediterranean basin. Since a new ESPGHAN diagnostic protocol was recently published, our secondary aim is to estimate how many cases in the same area could be identified without a small intestinal biopsy. METHODS: By a stratified cross-sectional retrospective study design, we examined clinical, histological and laboratory data from 749 consecutive unselected CD children diagnosed by national referral centers. RESULTS: The vast majority of cases were diagnosed before the age of 10 (median: 5 years), affected by diarrhea, weight loss and food refusal, as expected. Only 59 cases (7.8%) did not suffer of major complaints. Tissue transglutaminase (tTG) assay was available, but one-third of centers reported financial constraints in the regular purchase of the assay kits. 252 cases (33.6%) showed tTG values over 10 times the local normal limit. Endomysial antibodies and HLA typing were routinely available in only half of the centers. CD was mainly diagnosed from small intestinal biopsy, available in all centers. Based on these data, only 154/749 cases (20.5%) would have qualified for a diagnosis of CD without a small intestinal biopsy, according to the new ESPGHAN protocol. CONCLUSIONS: This cross-sectional study of CD in the Mediterranean referral centers offers a puzzling picture of the capacities to deal with the emerging epidemic of CD in the area, giving a substantive support to the World Gastroenterology Organization guidelines

Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: a multicenter study

An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases (VEO-IBD). The present study aimed at defining how next-generation sequencing (NGS) methods can be used to improve identification of known molecular diagnosis and adapt treatment.207 children were recruited in 45 Paediatric centres through an international collaborative network (ESPGHAN GENIUS working group) with a clinical presentation of severe VEO-IBD (n=185) or an anamnesis suggestive of a monogenic disorder (n=22). Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing (WES) of parents-child trios. Genetic findings were validated clinically and/or functionally.Molecular diagnosis was achieved in 66/207 children (32%): 61% with small bowel inflammation, 39% with colitis and perianal lesions and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations and identified large exonic copy number variations previously missed by WES.Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD

Corrigendum to: Diagnostic Yield of Next-Generation Sequencing in Very Early-Onset Inflammatory Bowel Diseases: A Multicenter Study

International audienc

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study

International audienceAn expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases (VEO-IBD). The present study aimed at defining how next-generation sequencing (NGS) methods can be used to improve identification of known molecular diagnosis and adapt treatment

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study

Background and Aims: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases {[}VEO-IBD]. The present study aimed at defining how next-generation sequencing {[}NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network {[}ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD {[}n = 185] or an anamnesis suggestive of a monogenic disorder {[}n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing {[}WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results: Molecular diagnosis was achieved in 66/207 children {[}32\%]: 61\% with small bowel inflammation, 39\% with colitis and perianal lesions, and 18\% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD