Population-based screening for celiac disease reveals that the majority of patients are undiagnosed and improve on a gluten-free diet
Jan-Magnus Kvamme, Sveinung Sørbye, Jon Florholmen, Trond S Halstensen, Jan-Magnus Kvamme, Sveinung Sørbye, Jon Florholmen, Trond S Halstensen
Abstract
The impact of a gluten-free diet (GFD) on screen-detected celiac disease (CD) is currently ambiguous. We aimed to identify the population-based prevalence of undiagnosed adult CD and examine the impact of a GFD on screen-detected CD. In total, 12,981 adults participated in a population-based health study in Tromsø, Norway. Participants with increased levels of anti-tissue transglutaminase-2 IgA or anti-deamidated gliadin peptide IgG were invited to undergo gastroduodenoscopy with both histological and immunohistochemical examination of small-bowel biopsies. The prevalence of previously diagnosed CD was 0.37%. Additionally, the prevalence of previously undiagnosed CD was 1.10%. Thus, 1.47% of the population had CD, of whom 75% were previously undiagnosed. A GFD resulted in significant improvements in overall gastrointestinal symptoms, diarrhea, and health-related quality of life, with reduced abdominal discomfort (76%) and improved levels of energy (58%). The large majority of patients with adult CD were undiagnosed and benefited from a GFD with reduced gastrointestinal symptoms and improved health-related quality of life. In clinical practice, there should be a low threshold for CD testing even in the absence of abdominal complaints because most adult patients appear to consider their symptoms a part of their normal state and therefore remain untested and undiagnosed.Trial registration: Clinical Trials. Gov Identifier: NCT01695681.
Conflict of interest statement
Trond S. Halstensen has served as speaker, consultant, and head of the scientific board of the Norwegian Celiac Disease association. He has also served as a speaker for Phadia. Jan-Magnus Kvamme has served as a speaker for the Norwegian Celiac Disease association. Jon Florholmen and Sveinung W Sørbye declare no personal interests.
© 2022. The Author(s).
Figures
References
- Green PHR, Cellier C. Celiac disease. N. Engl. J. Med. 2007;357:1731–1743. doi: 10.1056/NEJMra071600.
- Fuchs V, et al. Factors associated with long diagnostic delay in celiac disease. Scand. J. Gastroenterol. 2014;49:1304–1310. doi: 10.3109/00365521.2014.923502.
- Singh P, et al. Global prevalence of celiac disease: Systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 2018;16:823–836.e2. doi: 10.1016/j.cgh.2017.06.037.
- Vilppula A, et al. Increasing prevalence and high incidence of celiac disease in elderly people: A population-based study. BMC Gastroenterol. 2009;9:1–5. doi: 10.1186/1471-230X-9-49.
- Fluge G, Dybdahl JH, Ek J, Løvik A, Røhme R. Guidelines for diagnosis and follow-up of patients with celiac disease. Tidsskr Nor Lægeforen. 1997;117:672–674.
- Diez-Sampedro, A., Olenick, M., Maltseva, T. & Flowers, M. A gluten-free diet, not an appropriate choice without a medical diagnosis. J. Nutr. Metab.2019 (2019).
- Halstensen TS, Scott H, Brandtzaeg P. Intraepithelial T cells of the TCRγ/δ CD8− and Vδ1/Jδ1 phenotypes are increased in coeliac disease. Scand. J. Immunol. 1989;30:665–672. doi: 10.1111/j.1365-3083.1989.tb02474.x.
- Popp A, et al. A new intraepithelial γδ T-lymphocyte marker for celiac disease classification in formalin-fixed paraffin-embedded (FFPE) duodenal biopsies. Dig. Dis. Sci. 2021;66:3352–3358. doi: 10.1007/s10620-020-06680-x.
- Salmi TT, et al. Endomysial antibody-negative coeliac disease: Clinical characteristics and intestinal autoantibody deposits. Gut. 2006;55:1746–1753. doi: 10.1136/gut.2005.071514.
- Viljamaa M, et al. Is coeliac disease screening in risk groups justified? A fourteen-year follow-up with special focus on compliance and quality of life. Aliment. Pharmacol. Ther. 2005;22:317–324. doi: 10.1111/j.1365-2036.2005.02574.x.
- Mustalahti K, Collin P, Sievänen H, Salmi J, Mäki M. Osteopenia in patients with clinically silent coeliac disease warrants screening. Lancet. 1999;354:744–745. doi: 10.1016/S0140-6736(99)01990-X.
- Kurppa K, et al. Benefits of a gluten-free diet for asymptomatic patients with serologic markers of celiac disease. Gastroenterology. 2014;147:610–617. doi: 10.1053/j.gastro.2014.05.003.
- Vermeersch P, et al. Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease. Clin. Chim. Acta. 2010;411:931–935. doi: 10.1016/j.cca.2010.02.060.
- Ress K, et al. High prevalence of coeliac disease: Need for increasing awareness among physicians. Dig. Liver Dis. 2007;39:136–139. doi: 10.1016/j.dld.2006.07.012.
- Lindberg, M., Garmo Hov, G., Hardang, I. & Bjørke Monsen, A.-L. National User Handbook in Medical Biochemistry.
- Ludvigsson JF, et al. Outcome measures in coeliac disease trials: The Tampere recommendations. Gut. 2018;67:1410–1424. doi: 10.1136/gutjnl-2017-314853.
- Oxentenko AS, Murray JA. Celiac disease: Ten things that every gastroenterologist should know. Clin. Gastroenterol. Hepatol. 2015;13:1396–1404. doi: 10.1016/j.cgh.2014.07.024.
- Koskinen O, et al. Usefulness of small-bowel mucosal transglutaminase-2 specific autoantibody deposits in the diagnosis and follow-up of celiac disease. J. Clin. Gastroenterol. 2009;44:483–488. doi: 10.1097/MCG.0b013e3181b64557.
- Dickson BC, Streutker CJ, Chetty R. Coeliac disease: An update for pathologists. J. Clin. Pathol. 2006;59:1008–1061. doi: 10.1136/jcp.2005.035345.
- Hayat M, Cairns A, Dixon MF, O’Mahony S. Quantitation of intraepithelial lymphocytes in human duodenum: What is normal? J. Clin. Pathol. 2002;55:393–395. doi: 10.1136/jcp.55.5.393.
- Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG clinical guidelines: Diagnosis and management of celiac disease. Am. J. Gastroenterol. 2013;108:656–676. doi: 10.1038/ajg.2013.79.
- Rostami K, et al. ROC-king onwards: Intraepithelial lymphocyte counts, distribution and role in coeliac disease mucosal interpretation. Gut. 2017;66:2080–2086. doi: 10.1136/gutjnl-2017-314297.
- Spencer J, Isaacson PG, MacDonald TT, Thomas AJ, Walker-Smith JA. Gamma/delta T cells and the diagnosis of coeliac disease. Clin. Exp. Immunol. 2008;85:109–113. doi: 10.1111/j.1365-2249.1991.tb05690.x.
- Ludvigsson JF, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62:43–52. doi: 10.1136/gutjnl-2011-301346.
- Kurppa K, Collin P, Maaki M, Kaukinen K. Celiac disease and health-related quality of life. Expert Rev. Gastroenterol. Hepatol. 2011;5:83–90. doi: 10.1586/egh.10.81.
- Olafsson S, Hatlebakk JG, Berstad A. Patients with endoscopic gastritis and/or duodenitis improve markedly following eradication of Helicobacter pylori, although less so than patients with ulcers. Scand. J. Gastroenterol. 2002;37:1386–1394. doi: 10.1080/003655202762671251.
- Svedlund J, Sjödin I, Dotevall G. GSRS—A clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig. Dis. Sci. 1988;33:129–134. doi: 10.1007/BF01535722.
- Helvik AS, Jacobsen G, Hallberg LR. Psychological well-being of adults with acquired hearing impairment. Disabil. Rehabil. 2006;28:535–545. doi: 10.1080/09638280500215891.
- Dupuy, H. The Psychological General Well-Being (PGWB) index. in Assessment of Quality of Life in Clinical Trials of Cardiovascular Therapies 170–183 (Le Jacq Publishing, 1984).
- Husby S, 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. doi: 10.1097/MPG.0b013e31821a23d0.
- Caio G, et al. Celiac disease: A comprehensive current review. BMC Med. 2019;17:1–20. doi: 10.1186/s12916-019-1380-z.
- Mustalahti K, et al. The prevalence of celiac disease in Europe: Results of a centralized, international mass screening project. Ann. Med. 2010;42:587–595. doi: 10.3109/07853890.2010.505931.
- Nachman F, et al. Quality of life in celiac disease patients: Prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. Dig. Liver Dis. 2009;41:15–25. doi: 10.1016/j.dld.2008.05.011.
- Nachman F, et al. Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance. Dig. Liver Dis. 2010;42:685–691. doi: 10.1016/j.dld.2010.03.004.
- Lebwohl B, Rubio-Tapia A. Epidemiology, presentation, and diagnosis of celiac disease. Gastroenterology. 2021;160:63–75. doi: 10.1053/j.gastro.2020.06.098.
- Hujoel IA, et al. Natural history and clinical detection of undiagnosed coeliac disease in a North American community. Aliment. Pharmacol. Ther. 2018;47:1358–1366. doi: 10.1111/apt.14625.
- Kårhus LL, et al. Symptoms and biomarkers associated with undiagnosed celiac seropositivity. BMC Gastroenterol. 2021;21:90. doi: 10.1186/s12876-021-01667-y.
- Katz KD, et al. Screening for celiac disease in a North American population: Sequential serology and gastrointestinal symptoms. Am. J. Gastroenterol. 2011;106:133–139.
- van der Windt DAWM, Jellema P, Mulder CJ, Kneepkens CMF, van der Horst HE. Diagnostic testing for celiac disease among patients with abdominal symptoms. JAMA. 2010;303:1738–1746. doi: 10.1001/jama.2010.549.
- Mariné M, et al. Impact of mass screening for gluten-sensitive enteropathy in working population. World J. Gastroenterol. 2009;15:1331–1338. doi: 10.3748/wjg.15.1331.
- Ludvigsson JF, et al. Screening for celiac disease in the general population and in high-risk groups. United Eur. Gastroenterol. J. 2015;3:106–120. doi: 10.1177/2050640614561668.
- Stull DE, Leidy NK, Parasuraman B, Chassany O. Optimal recall periods for patient-reported outcomes: Challenges and potential solutions. Curr. Med. Res. Opin. 2009;25:929–942. doi: 10.1185/03007990902774765.
- Freeman HJ. Dietary compliance in celiac disease. World J. Gastroenterol. 2017;23:2635–2639. doi: 10.3748/wjg.v23.i15.2635.
- Kurppa K, et al. Factors associated with dietary adherence in celiac disease: A nationwide study. Digestion. 2012;86:309–314. doi: 10.1159/000341416.
- Ivarsson A, et al. High prevalence of undiagnosed coeliac disease in adults: A Swedish population-based study. J. Intern. Med. 1999;245:63–68. doi: 10.1046/j.1365-2796.1999.00403.x.
- Choung RS, et al. Prevalence and morbidity of undiagnosed celiac disease from a community-based study. Gastroenterology. 2017;152:830–839. doi: 10.1053/j.gastro.2016.11.043.
- Gould MJ, Brill H, Marcon MA, Munn NJ, Walsh CM. In screening for celiac disease, deamidated gliadin rarely predicts disease when tissue transglutaminase is normal. J. Pediatr. Gastroenterol. Nutr. 2019;68:20–25. doi: 10.1097/MPG.0000000000002109.
- Sollid LM. The roles of MHC class II genes and post-translational modification in celiac disease. Immunogenetics. 2017;69:605–616. doi: 10.1007/s00251-017-0985-7.
- Lande A, et al. HLA -A, -C, -B, -DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in 4514 healthy Norwegians. Hum. Immunol. 2018;79:527–529. doi: 10.1016/j.humimm.2018.04.012.
- Husby S, Murray JA, Katzka DA. AGA clinical practice update on diagnosis and monitoring of celiac disease—Changing utility of serology and histologic measures: Expert review. Gastroenterology. 2019;156:885–889. doi: 10.1053/j.gastro.2018.12.010.
- Biesiekierski JR, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: A double-blind randomized placebo-controlled trial. Am. J. Gastroenterol. 2011;106:508–514. doi: 10.1038/ajg.2010.487.
- Laurikka P, et al. Gastrointestinal symptoms in celiac disease patients on a long-term gluten-free diet. Nutrients. 2016;8:429. doi: 10.3390/nu8070429.
- Hære P, et al. Long-term mucosal recovery and healing in celiac disease is the rule—Not the exception. Scand. J. Gastroenterol. 2016;51:1439–1446. doi: 10.1080/00365521.2016.1218540.
- Chou R, et al. Screening for celiac disease: Evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2017;317:1258–1268. doi: 10.1001/jama.2016.10395.
- Popp, A., Kivelä, L., Fuchs, V. & Kurppa, K. Diagnosing celiac disease: Towards wide-scale screening and serology-based criteria? Gastroenterol. Res. Pract.2019 (2019).
- Kivelä L, et al. Long-term health and treatment outcomes in adult coeliac disease patients diagnosed by screening in childhood. United Eur. Gastroenterol. J. 2018;6:1022–1031. doi: 10.1177/2050640618778386.
- Paavola A, et al. Gastrointestinal symptoms and quality of life in screen-detected celiac disease. Dig. Liver Dis. 2012;44:814–818. doi: 10.1016/j.dld.2012.04.019.
Source: PubMed