Diagnosis of Coeliac Disease in Children Younger Than 2 Years Zrinjka Mis ˇ ak, Iva Hojsak, Oleg Jadres ˇ in, Alemka Jaklin Kekez, Slaven Abdovic´, and Sanja Kolacˇek ABSTRACT Background and Aim: To diagnose coeliac disease (CD) in children younger than 2 years, the old ESPGHAN criteria based on 3 small bowel biopsies were recommended until recently. The aim of the present study was to investigate the applicability of only 1 small intestinal biopsy plus positive serology for the diagnosis of CD in children younger than 2 years. Methods: A prospective cohort study included 81 patients younger than 2 years with symptoms suggestive of CD, who all completed the diagnostic procedure based on 3 small bowel biopsies. According to the finding of the third biopsy, patients were divided into group A—CD confirmed (N ¼ 44), and group B—CD not confirmed, after the gluten challenge (N ¼ 37). Results: At the time of the first biopsy, total villous atrophy (Marsh IIIc) was found more often in group A than in group B (77% vs 27%, P < 0.01). Also, all of the studied antibodies were more frequently positive in group A than in group B (P < 0.01 for all of the tested antibodies). Positive anti-endomysial antibodies and Marsh IIIc finding were the best discriminators between the group A and the group B and considerably contributed to the prediction of CD. Conclusions: The second and the third biopsies (before and after the gluten challenge) may also be avoided when diagnosing CD in children younger than 2 years provided that the child, at the time of presentation, has positive anti-endomysial antibodies and Marsh IIIc on the small bowel biopsy. A gluten challenge should be still considered in all other children younger than 2 years. Key Words: children, coeliac disease, diagnostic criteria (JPGN 2013;56: 201–205) C oeliac disease (CD) is an immune-mediated systemic dis- order elicited by gluten and related prolamines in genetically susceptible individuals. It is characterised by the presence of a variable combination of gluten-dependent clinical manifestations, CD-specific antibodies, human leukocyte antigen (HLA)-DQ2 or -DQ8 haplotypes and enteropathy (1). The ingestion of gluten, a constituent of wheat, barley, and rye, in these susceptible indi- viduals causes morphologic changes in small intestinal mucosa characterised by villous atrophy, leading ultimately to malabsorp- tion (2,3). Population studies have shown that CD is affecting 0.5% to 1% of general population, although the majority of affected individuals are still undiagnosed (4). Early diagnosis and strict gluten-free diet (GFD) act protectively against complications and decrease mortality rates in patients with CD, and therefore, making a definitive diagnosis of CD is of great importance (5,6). The first diagnostic criteria for CD in children were proposed by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) in 1969. According to these original criteria, the diagnosis of CD was made upon the sequence of 3 biopsies if there were structurally abnormal jejunal mucosa when taking a diet containing gluten; clear improvement of villous structure when taking a GFD; deterioration of the mucosa during the gluten challenge (7). This sequence of small bowel biopsies was meant to help differentiate CD from other transient causes of abnormal small intestinal mucosa. In 1990, ESPGHAN revised the original diagnostic criteria to omit the second and the third biopsies for children younger than 2 years at the time of the first biopsy. According to these, the diagnosis of CD is based on the typical histological finding of hyperplastic villous atrophy while the patient is eating adequate amounts of gluten; and un- equivocal and full clinical remission after withdrawal of gluten from the diet (8); however, the gluten challenge was still recom- mended: when there were doubts about the initial diagnosis (eg, initial biopsy not performed, the biopsy specimen inadequate or uncharacteristic, lack of clinical response on GFD) (8,9). Also, in children younger than 2 years at presentation (as they can have enteropathy because of other causes such as cow’s-milk–sensitive enteropathy, postenteritic syndrome, and giardiasis), a gluten challenge was advised, preceded, and followed by a small bowel biopsy (8,10); however, the new, just recently published, ESPGHAN guidelines for the diagnosis of CD state that in the presence of high antibody levels the diagnosis of CD may be based on a combination of symptoms, antibodies, and HLA, thus omitting the duodenal biopsy. The diagnosis is confirmed by an antibody decline and preferably a clinical response to a GFD, whereas gluten challenge and repetitive biopsies are only necessary in selected, unclear cases (1). Conversely, children younger than 2 years represent a diag- nostic problem and original protocol based on 3 biopsies is long- lasting, invasive, and particularly demanding for the patients and health care system in general. In Croatia, unlike the most western countries, a considerable proportion of paediatric patients with CD still presents with classic symptoms before the age of 2 years (11). That provided us with the opportunity to investigate the applica- bility of just 1 small intestinal biopsy and positive serology for the diagnosis of CD in children younger than 2 years and that was the aim of the present study. METHODS This is a prospective cohort study carried out at the Children’s Hospital Zagreb. All of the consecutive patients younger Received March 6, 2012; accepted August 14, 2012. From the Referral Centre for Paediatric Gastroenterology and Nutrition, Children’s Hospital Zagreb, Zagreb, Croatia. Address correspondence and reprint requests to Zrinjka Mis ˇ ak, MD, PhD, Referral Centre for Paediatric Gastroenterology and Nutrition, Chil- dren’s Hospital Zagreb, University Hospital Centre ‘‘Sisters of Mercy,’’ Klaic ´eva 16, Zagreb, Croatia (e-mail: zrinjka.misak@gmail.com). The authors report no conflicts of interest. Copyright # 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition DOI: 10.1097/MPG.0b013e3182716861 ORIGINAL ARTICLE:GASTROENTEROLOGY JPGN  Volume 56, Number 2, February 2013 201