Can ESPGHAN criteria be applied in the diagnosis of Celiac disease in children in Turkey?: Single-Center Experience

Abstract

Objective

To investigate the applicability of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria for celiac disease in pediatric patients in our country.

Methods

This study included patients aged 1–18 years who have high tissue transglutaminase IgA antibody levels. The cut-off tissue transglutaminase IgA antibody value was expressed as times the upper limit of normality. Endomysial antibody IgA was analyzed with monkey liver tissue and the titer of the antibodies was measured. Based on the modified Marsh–Oberhuber classification, patients classified as stage III were considered to have celiac disease.

Results

Of the 416 patients, 290 (69.7%) patients were diagnosed with celiac disease. The sensitivity, specificity, positive predictive value, and negative predictive value of tissue transglutaminase IgA antibody≥10 upper limit of normality alone in the diagnosis of celiac disease were 86.5, 74.6, 88.7, and 70.7%, respectively. The tissue transglutaminase IgA antibody titer was revealed to be a significant predictor of discriminating celiac diseases from non-celiac diseases at a cut-off value of x10ULN (area under the curve=0.822, p<0.05, and 95%, confidence interval: 0.772–0.873) with a sensitivity and specificity of 86.5% and 74.6%, respectively. The sensitivity and specificity of tissue transglutaminase IgA antibody≥10ULN and endomysial antibody IgA positivity were 79.1 and 64.3%, respectively.

Conclusions

Although European Society for Pediatric Gastroenterology, Hepatology, and Nutrition posits that most of pediatric patients with celiac disease can be diagnosed without endoscopy, it seems highly difficult to apply these criteria in our country.

Zusammenfassung

Ziel dieser Studie war es, die Anwendbarkeit der ESPGHAN-Diagnosekriterien für ZK bei pädiatrischen Patienten in unserem Land zu bewerten. In diese retrospektive Studie wurden Patienten im Alter von 1 bis 18 Jahren mit erhöhten Anti-tTG-IgA-Werten eingeschlossen. Die Anti-tTG-IgA-Titer wurden als Vielfaches des oberen Normwertes (xULN) angegeben. EMA-IgA wurde mittels indirekter Immunfluoreszenztechnik (IFA) unter Verwendung von Affenlebergewebe bestimmt. Die histopathologische Auswertung erfolgte nach der modifizierten Marsh-Oberhuber-Klassifikation, wobei Stadium III als diagnostisch für Zöliakie gewertet wurde.Von insgesamt 416 eingeschlossenen Patienten wurden 290 (69,7 %) mit ZK diagnostiziert. Die Sensitivität, Spezifität, der positive prädiktive Wert (PPV) und der negative prädiktive Wert (NPV) von Anti-tTG-IgA ≥10×ULN allein betrugen 86,5 %, 74,6 %, 88,7 % bzw. 70,7 %. Der Anti-tTG-IgA-Titer stellte bei einem Schwellenwert von ≥10×ULN einen signifikanten Prädiktor zur Unterscheidung zwischen ZK- und Nicht-ZK-Patienten dar (AUC = 0,822; 95 %-KI: 0,772–0,873; p < 0,05). Die Kombination aus Anti-tTG-IgA ≥10×ULN und EMA-IgA-Positivität ergab eine Sensitivität von 79,1 % und eine Spezifität von 64,3 %.Auch wenn die ESPGHAN-Leitlinien eine endoskopiefreie Diagnosestellung bei den meisten Kindern mit Zöliakie vorsehen, gestaltet sich die praktische Anwendung dieser Kriterien in unserem Land als herausfordernd.

Keywords

Celiac disease - ESPGHAN criteria - Turkey - pediatric

Schlüsselwörter

Zöliakie - ESPGHAN-Kriterien - Türkei - Pädiatrie

Publication History

Received: 27 March 2025

Accepted after revision: 17 September 2025

Article published online:
22 October 2025

• References

• 1 Husby S, Koletzko S, Korponay-Szabo IR. et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54: 136-160
• 2 Husby S, Koletzko S, Korponay-Szabo IR. et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease. J Pediatr Gastroenterol Nutr 2020; 70: 141-156
• 3 Fahey L, Hoffenberg E, Leonard MM. et al. Letter to the Editor in Response to ACG Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol 2023; 118 (11) 2094-2095
• 4 Hill ID, Fasano A, Guandalini S. et al. NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. J Pediatr Gastroenterol Nutr 2016; 63 (01) 156-65
• 5 Rubio-Tapia A, Hill ID, Semrad C. et al. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol 2023; 118 (01) 59-76
• 6 Graham K, Gidrewicz D, Turner JM. et al. Review and Critical Appraisal of Clinical Practice Guidelines of Modalities Used in the Diagnosis of Celiac Disease. J Can Assoc Gastroenterol 2023; 6 (03) 106-115
• 7 Oberhuber G, Granditsch G, Vogelsang H.. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol 1999; 11 (10) 1185-94
• 8 Werkstetter KJ, Korponay-Szabó IR, Popp A. et al. Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice. Gastroenterology 2017; 153 (04) 924-935
• 9 Sheppard AL, Elwenspoek MMC, Scott LJ. et al. Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease. Aliment Pharmacol Ther 2022; 55 (05) 514-527
• 10 Pachisia AV, Kumari A, Mehta S. et al. Validation of no-biopsy pathway for the diagnosis of celiac disease in Asian adults: a multicenter retrospective study. J Gastroenterol Hepatol 2024; 39 (03) 489-495
• 11 Baykan AR, Cerrah S, Ciftel S. et al. A No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: Can It Be Real?. Cureus 2022; 14 (07) e26521
• 12 Kımıloğlu E, Karagülle A, Keçeciler M. et al. Clinical, Laboratory, and Histopathological Evaluation of 493 Patients Who Underwent Endoscopic Biopsy with a Presumptive Diagnosis of Celiac Disease: Association with Autoimmune Diseases. Turk J Gastroenterol 2023; 34 (07) 681-690
• 13 Sengul OK, Akkelle BS, Ay P. et al. Evaluation of mucosal status in the follow-up of pediatric patients with celiac disease: the role of serology. Eur J Pediatr 2022; 181 (09) 3283-3289
• 14 Özekinci BB, Aydın E, Şen FS. et al. Is it possible to diagnose Celiac Disease without biopsy? Six years of single center experience. Paper presented at: 59th Turkish Pediatric Congress, May 22–26, 2024 https://www.turkpediatri2024.org/assets/files/bildiri-kitabi.pdf [accessed July 10, 2024]
• 15 Ozbey G, Hanafiah A.. Epidemiology, Diagnosis, and Risk Factors of Helicobacter pylori Infection in Children. Euroasian J Hepatogastroenterol 2017; 7 (01) 34-39
• 16 Kırkoyun Uysal H, Akgül O, Purisa S. et al. Twenty-five years of intestinal parasite prevalence in İstanbul University, İstanbul Faculty of Medicine: a retrospective study. Turkiye Parazitol Derg 2014; 38 (02) 97-101
• 17 Zanini B, Magni A, Caselani F. et al. High tissue-transglutaminase antibody level predicts small intestinal villous atrophy in adult patients at high risk of celiac disease. Dig Liver Dis 2012; 44 (04) 280-5
• 18 Girard C, De Percin A, Morin C. et al. Accuracy of Serological Screening for the Diagnosis of Celiac Disease in Type 1 Diabetes Children. Medicina (Kaunas) 2023; 59 (07) 1321
• 19 Sugai E, Moreno ML, Hwang HJ. et al. Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable?. World J Gastroenterol 2010; 16 (25) 3144-52
• 20 Singh P, Singh AD, Ahuja V. et al. Who to screen and how to screen for celiac disease. World J Gastroenterol 2022; 28 (32) 4493-4507