Objectives: The ESPGHAN 2012 coeliac disease (CD) diagnostic guidelines aimed to guide physicians in accurately diagnosing CD and permit omission of duodenal biopsies in selected cases. Here, an updated and expanded evidence-based guideline is presented. Methods: Literature databases and other sources of information were searched for studies that could inform on 10 formulated questions on symptoms, serology, human leukocyte antigen genetics, and histopathology. Eligible articles were assessed using QUADAS2. GRADE provided a basis for statements and recommendations. Results: Various symptoms are suggested for case finding, with limited contribution to diagnostic accuracy. If CD is suspected, measurement of total serum IgA and IgA-antibodies against transglutaminase 2 (TGA-IgA) is superior to other combinations. We recommend against deamidated gliadin peptide antibodies (DGP-IgG/IgA) for initial testing. Only if total IgA is low/undetectable, an IgG-based test is indicated. Patients with positive results should be referred to a paediatric gastroenterologist/specialist. If TGA-IgA is ≥10 times the upper limit of normal (10× ULN) and the family agrees, the no-biopsy diagnosis may be applied, provided endomysial antibodies (EMA-IgA) will test positive in a second blood sample. Human leukocyte antigen DQ2-/DQ8 determination and symptoms are not obligatory criteria. In children with positive TGA-IgA <10× ULN at least 4 biopsies from the distal duodenum and at least 1 from the bulb should be taken. Discordant results between TGA-IgA and histopathology may require re-evaluation of biopsies. Patients with no/mild histological changes (Marsh 0/I) but confirmed autoimmunity (TGA-IgA/EMA-IgA+) should be followed closely. Conclusions: CD diagnosis can be accurately established with or without duodenal biopsies if given recommendations are followed.

Complementary blood investigations are relevant at the time of diagnosis of CD but have little diagnostic yield during follow-up visits once the patient is placed on a gluten-free diet. Thus, we recommend that these variables only be assessed on indication, such as fatigue or abnormal growth.

NTR3759 [Netherlands Trial Registry].

Trialregister.nl: NTR3688.

There is a need for consensus on the recommendations for follow-up of children and adolescents with celiac disease. Objectives: To gather the current evidence and to offer recommendations for follow-up and management. Methods: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. Results: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. Conclusions: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.

Celiac disease (CD) is known to be more prevalent in first-degree relatives of patients. In this retrospective cohort study of 609 relatives between 1994 and 2016, we investigated the effect of sex, HLA type, and age at time of index celiac diagnosis. Pearson's chi-square test and Kaplan-Meier survival analysis were used as statistical analyses. CD screening was carried out for 427 relatives (70%), resulting in a prevalence of 15%. HLA typing in 335 relatives showed HLA-DQ2/DQ8 positivity in 87.5%. In 63% of children and all parents, celiac disease was diagnosed at first screening. It was diagnosed significantly more often in females, HLA-DQ2 homozygosity, and children (all p < 0.05). In children aged 0-1 year at time of index diagnosis, celiac disease was diagnosed after consecutive screening in 58%, after 3.9 ± 2.5 (max 10) years (p < 0.001).Conclusion: Future screening policies for relatives of celiac patients should include retesting, especially in HLA-positive relatives younger than 10 years of age. In addition, one-time celiac-specific antibody testing alone could be sufficient to rule out the disease in adolescent siblings and parents of newly diagnosed celiac patients. What is Known: • Celiac disease is more prevalent in first-degree relatives of celiac patients (risk 3-12%). • HLA-DQ2 homozygous sisters/daughters are at highest risk (25%). What is New: • If younger than 10 years of age, repeated testing is necessary in HLA-DQ2/DQ8-positive first-degree relatives when celiac disease is diagnosed in a family. • One-time celiac-specific antibody testing alone could be sufficient to rule out the disease in adolescent siblings and parents of newly diagnosed celiac patients.

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surrounding the SCD itself regarding the mechanism of action, its long-term efficacy, best populations for its effective use, and the possibility of narrowing the restrictions.Despite these obvious limitations and the questions raised, lessons can be learned from both the authors' efforts and their findings. In many ways, the lessons can be grouped under the broad umbrella of caution, both for physicians and the families who opt for sustained dietary therapy instead of medication. First, the SCD is very restrictive and young patients often find it difficult to perpetuate; hence, the patients and families often modify their adherence (to say it kindly). They often start the diet on their own and, as seen in this study, they follow their own dictates as they chose what foods they want to add back and when. Second, the patients and their families are often presumptive about how well they are doing. Significant signs of malnutrition and lack of weight gain may be ignored, especially when laboratory measures are falsely reassuring. Our own experience suggests that the patients, particularly those on the diet, underreport their symptoms and overreport their adherence so as not to disappoint their parents, at least in the beginning. As these young patients tire of dietary restrictions, those strategies may reverse as they try to persuade their families to let them ''cheat'' and consume normally restricted foods.Lastly, to use a Southern homily, our surrogate markers ''ain't all they're cracked up to be.'' As clinicians, we have become devoted to laboratory tests and their numbers to explore less observable conditions or to confirm our impressions. In following pediatric patients with inflammatory bowel disease, we even incorporate hemoglobins, albumins, and sedimentation rates into the Pediatric Crohn's Disease Activity Index as evidence of the degree of activity, to imperfect effect (4,5). We do know that these markers and the CRPs are not always reliable. The CRP, with a halflife of 19 hours, is considered the most reliable and hence, the most widely used. But single nucleotide polymorphisms in the gene affect hepatocyte production in 20% to 30% of patients with active CD (6,7). Thus, they are useful when they are interpretable for the individual patient and for their aggregate, in studies. The problem is knowing when they are not (which is one of the reasons why results in some studies or their post-hoc analyses are stratified by CRP results) (8). Fortunately, Wabbeh et al all but ignored the biomarkers and again demonstrated how unreliable surrogates, and patient/family-reported symptoms can be (while they also instructed us on how unreliable a modified diet can be). Calprotectins were more useful in the present study, primarily by using a low threshold (>50 mg/g) to enhance detection (whereas other studies use considerably higher levels (3,9) and commercial laboratories report values to be abnormal at 120-150 mg/g) (10,11).The sad truth here is that the same situation may exist with medication use and nutritional t...