Juha Taavela1, Alina Popp1,2, Ilma Rita Korponay-Szabo3, Adina Ene4, Martine Vornanen5, Päivi Saavalainen6, Marja-Leena Lähdeaho1, Tarja Ruuska1, Kaija Laurila1, Alexandru Parvan7, Ioana Anca2, Kalle Kurppa1, Markku Mäki1. 1. Tampere Centre for Child Health Research, School of Medicine, University of Tampere and Tampere University Hospital, Tampere, Finland. 2. University of Medicine and Pharmacy "Carol Davila" and Institute for Mother and Child Care, Bucharest, Romania. 3. Celiac Disease Center, Heim Palm Children's Hospital, Budapest and Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. 4. Department of Pathology, Institute for Mother and Child Care, Bucharest, Romania. 5. Department of Pathology, University of Tampere and Tampere University Hospital, Tampere, Finland. 6. Research Programs Unit, Immunobiology, and Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland. 7. University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
Abstract
OBJECTIVES: Several recent celiac disease guidelines recommend the acquisition of duodenal bulb biopsies for diagnostics. This is in conflict with previously reported evidence and routine practice from the 1960s onward. We reopened the issue in a prospective multicenter study and used morphometric variables in evaluating the usefulness of bulb biopsies in children. We further sought to establish whether deposits of IgA targeting bulb transglutaminase 2 (TG2) could be of diagnostic help. METHODS: Diagnoses of celiac disease were based on clinic and distal duodenal histopathology statements. Centralized reading of villous height (VH) to crypt depth (CrD) ratios and IgA deposits was performed on anatomical duodenal bulb specimens. All children participating also underwent routine investigations for other diseases. RESULTS: Twenty-two children had celiac disease, and another 22 served as non-celiac disease controls. The quality of the anatomical bulb specimens was unsatisfactory for reliable morphometric measurements in 20 out of 44 (45%) patients even after recuttings. All celiac disease patients had VH:CrD<2.0 (mean 0.2) but also 10 out of 13 (77%) non-celiac control patients had an injured bulb mucosal lining (mean 1.3) even up to false-positive "flat lesion". Bulb IgA deposits were able to separate celiac disease from disease controls. CONCLUSIONS: Morphological injury is common in the anatomical bulb even without celiac disease, increasing the risk of false-positive diagnoses. Premature conclusions might have been drawn on current care guidelines as to celiac disease diagnosis based solely on anatomical bulb specimens. Bulb mucosal IgA targeting TG2 in poor quality biopsy specimens is a powerful clinical tool in finding celiac disease patients.
OBJECTIVES: Several recent celiac disease guidelines recommend the acquisition of duodenal bulb biopsies for diagnostics. This is in conflict with previously reported evidence and routine practice from the 1960s onward. We reopened the issue in a prospective multicenter study and used morphometric variables in evaluating the usefulness of bulb biopsies in children. We further sought to establish whether deposits of IgA targeting bulb transglutaminase 2 (TG2) could be of diagnostic help. METHODS: Diagnoses of celiac disease were based on clinic and distal duodenal histopathology statements. Centralized reading of villous height (VH) to crypt depth (CrD) ratios and IgA deposits was performed on anatomical duodenal bulb specimens. All children participating also underwent routine investigations for other diseases. RESULTS: Twenty-two children had celiac disease, and another 22 served as non-celiac disease controls. The quality of the anatomical bulb specimens was unsatisfactory for reliable morphometric measurements in 20 out of 44 (45%) patients even after recuttings. All celiac disease patients had VH:CrD<2.0 (mean 0.2) but also 10 out of 13 (77%) non-celiac control patients had an injured bulb mucosal lining (mean 1.3) even up to false-positive "flat lesion". Bulb IgA deposits were able to separate celiac disease from disease controls. CONCLUSIONS:Morphological injury is common in the anatomical bulb even without celiac disease, increasing the risk of false-positive diagnoses. Premature conclusions might have been drawn on current care guidelines as to celiac disease diagnosis based solely on anatomical bulb specimens. Bulb mucosal IgA targeting TG2 in poor quality biopsy specimens is a powerful clinical tool in finding celiac disease patients.
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