Çölyak Hastası Çocuklarda Duodenal Histopatoloji ve Güçlü Pozitif Doku Transglutaminaz Antikorları Arasındaki İlişki

Yıl 2015, , 171 - 176, 01.12.2015

Güzide Doğan Semin Ayhan Bilge Yılmaz Yeliz Çağan Appak Pınar Erbay Dündar Talat Ecemiş Fatih Ünal , Erhun Kasırga

https://doi.org/10.4274/jcp.81994

Öz

Giriş: Çölyak hastalığında ÇH güçlü pozitif doku transglutaminaz antikor DTGA düzeylerinin ≥100 U/A hemen daima villöz atrofiye işaret ettiği gösterilmiştir. Bu çalışmanın amacı ≥100 U/A immünoglobulin Ig A tipi DTGA düzeylerinin ÇH tanısındaki yeterliliğini ortaya koymaktır. Gereç ve Yöntem: DTGA pozitifliği nedeniyle endoskopik duodenum biyopsisi yapılan 197 çocuk retrospektif olarak incelendi. IgA DTGA düzeylerinin pozitif değeri >18 U/A idi. Bu eşik değerinin 5 kat veya daha üzerindeki artışlar ≥100 U/A güçlü pozitiflik olarak kabul edildi. ÇH tanısı ESPGHAN ölçütlerine göre konuldu. Modifiye Marsh evre ≥2 ÇH için anlamlı kabul edildi. Bulgular: Olguların 129’u %65,5 kız, 68’i %34,5 erkekti. Duodenum histopatolojisi; olguların 1’inde %0,5 Marsh 0, 17’sinde %8,6 Marsh 2, 41’inde %20,8 Marsh 3a, 81’inde %41,1 Marsh 3b ve 57’sinde %28,9 Marsh 3c ile uyumluydu. Yüz doksan yedi olgunun 64’ünde %32,5 DTGA ≥100 U/ml idi. Güçlü DTGA pozitifliği saptanan olguların duodenum histolojisi 63’ünde Marsh 3 villöz atrofi ve birinde tip 1 diyabetli ve ÇH açısından asemptomatik Marsh 0 normal histoloji ile uyumluydu. DTGA ≥100 U/A olmasının Marsh 3c’nin varlığı için duyarlılığı %85,96 %95 CI: %74,2-%93,7 . Özgüllüğü %89,29 %95 CI: %82,9-%93,8 , pozitif tahmin değeri %76,56 %95 CI: %64,3-%86,2 ve negatif tahmin değeri %93,9 %95 CI: %88,4-%97,3 idi. Sonuç: Bu çalışma güçlü pozitif Ig A DTGA düzeylerinin ≥100 U/A neredeyse her zaman Marsh 3 duodenal histopatolojik değişikliklerle beraber olduğunu göstermiştir. Biyopsi yapılmadan ÇH tanısının konulması ÇH’ye eşlik eden bazı hastalıkların atlanmasına neden olabilir; fakat ileri tetkik edilmiş seçilmiş bazı olgularda çocuk gastroenteroloji uzmanları tarafından endoskopi yapılmadan da ÇH tanısı konulabilir.

Anahtar Kelimeler

Çölyak hastalığı, doku transglutaminaz antikoru, duodenum, histopatoloji

Relationship Between Duodenal Histopathology and Strong Positive Tissue Transglutaminase Antibodies in Children with Celiac Disease

Öz

Introduction: In celiac disease CD strong positive tissue transglutaminase antibody TTGA levels ≥100 U/A have been shown to almost always indicate villous atrophy. The aim of this study is to determine the sufficiency of ≥100 U/A Ig A type TTGA levels for diagnosis of CD. Materials and Methods: Results from duodenum biopsy performed due to positive TTGA in 197 children were retrospectively examined. IgA TTGA levels had a positive value of >18 U/A. Increases of 5 times or more than this threshold value ≥100 U/A are accepted as strong positivity. CD diagnosis was made according to ESPGHAN criteria. A modified Marsh stage ≥2 was accepted as significant for CD. Results: Of the cases, 129 were female 65.5% and 68 were male 34.5% . Duodenum histopathology was compatible with Marsh 0 for 1 case 0.5% , Marsh 2 for 17 cases 8.6% , Marsh 3a for 41 20.8% , Marsh 3b for 81 41.4% and Marsh 3c for 57 28.9% . The TTGA levels of 64 of the 197 cases 32.5% were ≥100 U/A. In cases with strong positivity for TTGA the duodenum histology was compatible with Marsh 3 villous atrophy for 63 and Marsh 0 normal histology for 1 case type 1 diabetic and asymptomatic for CD . For Marsh 3c TTGA levels ≥100 U/A had a sensitivity of 85.96% 95% CI: 74.2-93.7% , specificity of 89.29% 95% CI: 82.9-93.8% , positive predictive value of 76.56% 95% CI: 64.3-86.2% and negative predictive value of 93.9% 95% CI: 88.4- 97.3% . Conclusions: This study showed that positive IgA TTGA levels ≥100 U/A were almost always accompanied by Marsh 3 duodenal histopathological changes. Diagnosis of CD without biopsy may miss certain accompanying diseases, however in some cases with advanced examinations CD may be diagnosed by pediatric gastroenterology specialists without endoscopy.

Anahtar Kelimeler

Celiac disease, tissue transglutaminase antibody, duodenum, histopathology

Kaynakça

• 1. Green PH, Jabri B. Celiac disease. Annu Rev Med 2006;57:207- 21.
• 2. Alaedini A, Green PH. Narrative review: Celiac disease: Understanding a complex autoimmune disorder. Ann Intern Med 2005;142:289-98.
• 3. Ozgenc F, Aksu G, Aydogdu S, Akman S, Genel F, Kutukculer N, et al. Association between anti-endomysial antibody and total intestinal villous atrophy in children with coeliac disease. J Postgrad Med 2003;49:21-4.
• 4. Güleç SG, Urgancı N, Gül F, Emecen M, Erdem E. Çocuklarda çölyak hastalığının tanı ve takibinde doku transglutaminaz-IgA antikorunun yeri. Ş.E.E.A.H Tıp Bülteni 2011;45:119-23.
• 5. Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136-60.
• 6. Weir DC, Glickman JN, Roiff T, Valim C, Leichtner AM. Variability of histopathological changes in childhood celiac disease. Am J Gastroenterol 2010;105:207-12.
• 7. Perera DR, Weinstein WM, Rubin CE. Symposium on pathology of the gastrointestinal tract-Part II. Small intestinal biopsy. Hum Pathol 1975;6:157-217.
• 8. Rubin CE, Brandborg LL, Phelps PC, Taylor HC Jr. Studies of celiac disease. I. The apparent identical and specific nature of the duodenal and proximal jejunal lesion in celiac disease and idiopathic sprue. Gastroenterology 1960;38:28-49.
• 9. Shidrawi RG, Przemioslo R, Davies DR, Tighe MR, Ciclitira PJ. Pitfalls in diagnosing coeliac disease. J Clin Pathol 1994;47:693- 4.
• 10. Bonamico M, Mariani P, Thanasi E, Ferri M, Nenna R, Tiberti C, et al. Patchy villous atrophy of the duodenum in childhood celiac disease. J Pediatr Gastroenterol Nutr 2004;38:204-7.
• 11. Ravelli A, Bolognini S, Gambarotti M, Villanacci V. Variability of histologic lesions in relation to biopsy site in gluten-sensitive enteropathy. Am J Gastroenterol 2005;100:177-85.
• 12. Donaldson MR, Book LS, Leiferman KM, Zone JJ, Neuhausen SL. Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease. J Clin Gastroenterol 2008;42:256-60.
• 13. Hill ID, Dirks MH, Liptak GS, Colletti RB, Fasano A, Guandalini S, et al. Guideline for the diagnosis and treatment of celiac disease in children: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2005;40:1-19.
• 14. Tursi A, Brandimarte G, Giorgetti G, Gigliobianco A, Lombardi D, Gasbarrini G. Low prevalence of antigliadin and antiendomysium antibodies in subclinical/silent celiac disease. Am J Gastroenterol 2001;96:1507-10.
• 15. Hoffenberg EJ, Bao F, Eisenbarth GS, Uhlhorn C, Haas JE, Sokol RJ, et al. Transglutaminase antibodies in children with a genetic risk for celiac disease. J Pediatr 2000;137:356-60.
• 16. Fabiani E, Catassi C; International Working Group he serum IgA class anti-tissue transglutaminase antibodies in the diagnosis and follow up of coeliac disease. Results of an international multicentre study. International Working Group on Eu-tTG. Eur J Gastroenterol Hepatol 2001;13:659-65.
• 17. Hansson T, Dahlbohm I, Rogberg S, Dannaeus A, Hopfl P, Gut H, et al. Recombinant human tissue transglutaminase for diagnosis and follow up of childhood celiac disease. Pediatr Res 2002;51:700-5.
• 18. Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue antitransglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol 2003;36:219-21.
• 19. Scoglio R, Di Pasquale G, Pagano G, Lucanto MC, Magazzù G, Sferlazzas C. Is intestinal biopsy always needed for diagnosis of celiac disease? Am J Gastroenterol 2004;98:1325-31.
• 20. Diamanti A, Colistro F, Calce A, Devito R, Ferretti F, Minozzi A, et al. Clinical value of immunoglobulin A antitransglutaminase assay in the diagnosis of celiac disease. Pediatrics 2006;118:1696-700.
• 21. Donaldson MR, Firth SD, Wimpee H, Leiferman KM, Zone JJ, Horsley W, et al. Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease. Clin Gastroenterol Hepatol 2007;5:567-73.
• 22. Mubarak A, Wolters VM, Gmelig-Meyling FH, Ten Kate FJ, Houwen RH. Tissue transglutaminase levels above 100 U/mL and celiac disease: A prospective study. World J Gastroenterol 2012;18:4399-403.
• 23. Barker CC, Mitton C, Jevon G, Mock T. Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations? Pediatrics 2005;115:1341-6.
• 24. Alessio MG, Tonutti E, Brusca I, Radice A, Licini L, Sonzogni A, et al. Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease. J Pediatr Gastroenterol Nutr 2012;55:44-9.
• 25. Pellicano R, De Angelis C, Ribaldone DG, Fagoonee S, Astegiano M. 2013 update on celiac, disease and eosinophilic esophagitis. Nutrients 2013;5:3329-36.
• 26. Bizzaro N, Villalta D, Tonutti E, Doria A, Tampoia M, Bassetti D, et al. IgA and IgG tissue transglutaminase antibody prevalence and clinical significance in connective tissue disease, inflammatory bowel disease, and primary biliary cirrhosis. Dig Dis Sci 2003;48:2360-5.
• 27. Clemente MG, Musu MP, Frau F, Lucia C, De Virgiliis S. Antitissue transglutaminase antibodies outside celiac disease. J Pediatr Gastroenterol Nutr 2002;34:31-4.
• 28. Di Tola M, Sabbatella L, Anania MC, Viscido A, Caprilli R, Pica R, et al. Anti-tissue transglutaminase antibodies in inflammatory bowel disease: New evidence. Clin Chem Lab Med 2004;42:1092-7.
• 29. Carroccio A, Di Prima L, Falci C, Le Moli C, Soresi M, Montalto G, et al. Predictive value of serological tests in the diagnosis of celiac disease. Ann Ital Med Intern 2002;17:102-7.
• 30. Rashid M. Diagnosing celiac disease with a positive serological test and without an intestinal biopsy. Pediatrics 2005;116:1054-5.