Screening for Celiac Disease: Evidence Report and Systematic Review for the US Preventive Services Task Force | Gastroenterology | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Dubé  C, Rostom  A, Sy  R,  et al.  The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review.  Gastroenterology. 2005;128(4)(suppl 1):S57-S67.PubMedGoogle ScholarCrossref
Rubio-Tapia  A, Ludvigsson  JF, Brantner  TL, Murray  JA, Everhart  JE.  The prevalence of celiac disease in the United States.  Am J Gastroenterol. 2012;107(10):1538-1544.PubMedGoogle ScholarCrossref
Hill  I, Fasano  A, Schwartz  R, Counts  D, Glock  M, Horvath  K.  The prevalence of celiac disease in at-risk groups of children in the United States.  J Pediatr. 2000;136(1):86-90.PubMedGoogle ScholarCrossref
Tai  V, Crowe  M, O’Keefe  S.  Celiac disease in older people.  J Am Geriatr Soc. 2000;48(12):1690-1696.PubMedGoogle ScholarCrossref
Rampertab  SD, Pooran  N, Brar  P, Singh  P, Green  PH.  Trends in the presentation of celiac disease.  Am J Med. 2006;119(4):355.e9-355.e14.PubMedGoogle ScholarCrossref
Green  PH.  The many faces of celiac disease: clinical presentation of celiac disease in the adult population.  Gastroenterology. 2005;128(4)(suppl 1):S74-S78.PubMedGoogle ScholarCrossref
Crowe  SE.  In the clinic: celiac disease.  Ann Intern Med. 2011;154(9):ITC5-ITC1.PubMedGoogle ScholarCrossref
Green  PH, Cellier  C.  Celiac disease.  N Engl J Med. 2007;357(17):1731-1743.PubMedGoogle ScholarCrossref
Tio  M, Cox  MR, Eslick  GD.  Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy.  Aliment Pharmacol Ther. 2012;35(5):540-551.PubMedGoogle ScholarCrossref
Godfrey  JD, Brantner  TL, Brinjikji  W,  et al.  Morbidity and mortality among older individuals with undiagnosed celiac disease.  Gastroenterology. 2010;139(3):763-769.PubMedGoogle ScholarCrossref
Rubio-Tapia  A, Kyle  RA, Kaplan  EL,  et al.  Increased prevalence and mortality in undiagnosed celiac disease.  Gastroenterology. 2009;137(1):88-93.PubMedGoogle ScholarCrossref
Catassi  C, Kryszak  D, Bhatti  B,  et al.  Natural history of celiac disease autoimmunity in a USA cohort followed since 1974.  Ann Med. 2010;42(7):530-538.PubMedGoogle ScholarCrossref
Chou  R, Blazina  I, Bougatsos  C, Mackey  K, Grusing  S, Selph  S.  Screening for Celiac Disease: A Systematic Review for the US Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
US Preventive Services Task Force.  US Preventive Services Task Force Procedure Manual. Rockville, MD: US Preventive Services Task Force; 2015.
Rubio-Tapia  A, Hill  ID, Kelly  CP, Calderwood  AH, Murray  JA; American College of Gastroenterology.  ACG clinical guidelines: diagnosis and management of celiac disease.  Am J Gastroenterol. 2013;108(5):656-676.PubMedGoogle ScholarCrossref
US Preventive Services Task Force.  US Preventive Services Task Force Procedure Manual. Rockville, MD: Agency for Healthcare Research and Quality; 2015.
Maglione  M, Okunogbe  A, Ewing  B,  et al; Southern California Evidence-based Practice Center.  Diagnosis of Celiac Disease. Rockville, MD: Agency for Healthcare Research and Quality; 2016. Comparative Effectiveness Review 162.
Basso  D, Guariso  G, Bozzato  D,  et al.  New screening tests enrich anti-transglutaminase results and support a highly sensitive two-test based strategy for celiac disease diagnosis.  Clin Chim Acta. 2011;412(17-18):1662-1667.PubMedGoogle ScholarCrossref
Nevoral  J, Kotalova  R, Hradsky  O,  et al.  Symptom positivity is essential for omitting biopsy in children with suspected celiac disease according to the new ESPGHAN guidelines.  Eur J Pediatr. 2013;173:497-502.PubMedGoogle ScholarCrossref
Olen  O, Gudjónsdóttir  AH, Browaldh  L,  et al.  Antibodies against deamidated gliadin peptides and tissue transglutaminase for diagnosis of pediatric celiac disease.  J Pediatr Gastroenterol Nutr. 2012;55(6):695-700.PubMedGoogle ScholarCrossref
Dahlbom  I, Korponay-Szabó  IR, Kovács  JB, Szalai  Z, Mäki  M, Hansson  T.  Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase.  J Pediatr Gastroenterol Nutr. 2010;50(2):140-146.PubMedGoogle ScholarCrossref
Mansour  AA, Najeeb  AA.  Coeliac disease in Iraqi type 1 diabetic patients.  Arab J Gastroenterol. 2011;12(2):103-105.PubMedGoogle ScholarCrossref
Mozo  L, Gómez  J, Escanlar  E, Bousoño  C, Gutiérrez  C.  Diagnostic value of anti-deamidated gliadin peptide IgG antibodies for celiac disease in children and IgA-deficient patients.  J Pediatr Gastroenterol Nutr. 2012;55(1):50-55.PubMedGoogle ScholarCrossref
Sakly  W, Mankaï  A, Ghdess  A, Achour  A, Thabet  Y, Ghedira  I.  Performance of anti-deamidated gliadin peptides antibodies in celiac disease diagnosis.  Clin Res Hepatol Gastroenterol. 2012;36(6):598-603.PubMedGoogle ScholarCrossref
Van Meensel  B, Hiele  M, Hoffman  I,  et al.  Diagnostic accuracy of ten second-generation (human) tissue transglutaminase antibody assays in celiac disease.  Clin Chem. 2004;50(11):2125-2135.PubMedGoogle ScholarCrossref
Vermeersch  P, Geboes  K, Mariën  G, Hoffman  I, Hiele  M, Bossuyt  X.  Serological diagnosis of celiac disease: comparative analysis of different strategies.  Clin Chim Acta. 2012;413(21-22):1761-1767.PubMedGoogle ScholarCrossref
DeGaetani  M, Tennyson  CA, Lebwohl  B,  et al.  Villous atrophy and negative celiac serology: a diagnostic and therapeutic dilemma.  Am J Gastroenterol. 2013;108(5):647-653.PubMedGoogle ScholarCrossref
Barada  K, Habib  RH, Malli  A,  et al.  Prediction of celiac disease at endoscopy.  Endoscopy. 2014;46(2):110-119.PubMedGoogle ScholarCrossref
Çekın  AH, Çekın  Y, Sezer  C.  Celiac disease prevalence in patients with iron deficiency anemia.  Turk J Gastroenterol. 2012;23(5):490-495.PubMedGoogle ScholarCrossref
Emami  MH, Karimi  S, Kouhestani  S.  Is routine duodenal biopsy necessary for the detection of celiac disease in patients presenting with iron deficiency anemia?  Int J Prev Med. 2012;3(4):273-277.PubMedGoogle Scholar
Dutta  AK, Chacko  A, Avinash  B.  Suboptimal performance of IgG anti-tissue transglutaminase in the diagnosis of celiac disease in a tropical country.  Dig Dis Sci. 2010;55(3):698-702.PubMedGoogle ScholarCrossref
Sugai  E, Hwang  HJ, Vázquez  H,  et al.  New serology assays can detect gluten sensitivity among enteropathy patients seronegative for anti-tissue transglutaminase.  Clin Chem. 2010;56(4):661-665.PubMedGoogle ScholarCrossref
Dahle  C, Hagman  A, Ignatova  S, Ström  M.  Antibodies against deamidated gliadin peptides identify adult coeliac disease patients negative for antibodies against endomysium and tissue transglutaminase.  Aliment Pharmacol Ther. 2010;32(2):254-260.PubMedGoogle ScholarCrossref
Harrison  E, Li  K-K, Petchey  M, Nwokolo  C, Loft  D, Arasaradnam  RP.  Selective measurement of anti-tTG antibodies in coeliac disease and IgA deficiency: an alternative pathway.  Postgrad Med J. 2013;89(1047):4-7.PubMedGoogle ScholarCrossref
Kaukinen  K, Collin  P, Mykkänen  AH, Partanen  J, Mäki  M, Salmi  J.  Celiac disease and autoimmune endocrinologic disorders.  Dig Dis Sci. 1999;44(7):1428-1433.PubMedGoogle ScholarCrossref
Srinivas  M, Basumani  P, Podmore  G, Shrimpton  A, Bardhan  KD.  Utility of testing patients, on presentation, for serologic features of celiac disease.  Clin Gastroenterol Hepatol. 2014;12(6):946-952.PubMedGoogle ScholarCrossref
Swallow  K, Wild  G, Sargur  R,  et al.  Quality not quantity for transglutaminase antibody 2: the performance of an endomysial and tissue transglutaminase test in screening coeliac disease remains stable over time.  Clin Exp Immunol. 2013;171(1):100-106.PubMedGoogle ScholarCrossref
Vermeersch  P, Coenen  D, Geboes  K, Mariën  G, Hiele  M, Bossuyt  X.  Use of likelihood ratios improves clinical interpretation of IgA anti-tTG antibody testing for celiac disease.  Clin Chim Acta. 2010;411(1-2):13-17.PubMedGoogle ScholarCrossref
Vermeersch  P, Geboes  K, Mariën  G, Hoffman  I, Hiele  M, Bossuyt  X.  Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease.  Clin Chim Acta. 2010;411(13-14):931-935.PubMedGoogle ScholarCrossref
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(4):280-285.PubMedGoogle ScholarCrossref
Kurppa  K, Paavola  A, Collin  P,  et al.  Benefits of a gluten-free diet for asymptomatic patients with serologic markers of celiac disease.  Gastroenterology. 2014;147(3):610-617.PubMedGoogle ScholarCrossref
Leffler  D. A prospective trial of celiac disease screening [NCT01902368]. Accessed August 25, 2015.
Johnston  SD, Rodgers  C, Watson  RG.  Quality of life in screen-detected and typical coeliac disease and the effect of excluding dietary gluten.  Eur J Gastroenterol Hepatol. 2004;16(12):1281-1286.PubMedGoogle ScholarCrossref
Ukkola  A, Mäki  M, Kurppa  K,  et al.  Diet improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease.  Clin Gastroenterol Hepatol. 2011;9(2):118-123.PubMedGoogle ScholarCrossref
Vilppula  A, Kaukinen  K, Luostarinen  L,  et al.  Clinical benefit of gluten-free diet in screen-detected older celiac disease patients.  BMC Gastroenterol. 2011;11:136.PubMedGoogle ScholarCrossref
Lähdeaho  M-L. A phase 2a, double-blind, placebo controlled study of the efficacy, safety and tolerability of 6-weeks treatment with ALV003 in patients with well-controlled celiac disease [NCT00959114]. Accessed August 25, 2015.
Rasmussen  H. A double-blind, placebo-controlled study to evaluate the efficacy and safety of different doses of larazotide acetate for the treatment of celiac disease [NCT01396213]. Accessed August 25, 2015.
Leon  F. A phase IIb, randomized, double-blind, placebo controlled, dose ranging, multicenter study to determine the safety, tolerance, and efficacy of AT-1001 in celiac disease subjects during a gluten challenge [NCT00492960]. Accessed August 25, 2015.
Makharia  G. Effect of addition of short course of prednisolone to gluten free diet and gluten free diet alone in the recovery of clinical, histological and immunological features in naive adult patients with celiac disease [NCT01045837]. Accessed August 25, 2015.
Mahmud  FH, De Melo  EN, Noordin  K,  et al.  The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) protocol: a randomised controlled study to evaluate treatment of asymptomatic coeliac disease in type 1 diabetes.  BMJ Open. 2015;5(5):e008097.PubMedGoogle ScholarCrossref
US Preventive Services Task Force
Evidence Report
March 28, 2017

Screening for Celiac Disease: Evidence Report and Systematic Review for the US Preventive Services Task Force

Author Affiliations
  • 1The Pacific Northwest Evidence-based Practice Center, Departments of Medicine and Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland
  • 2The Pacific Northwest Evidence-based Practice Center, Oregon Health & Science University, Portland
  • 3Division of General Internal Medicine and Geriatrics, Oregon Health & Science University, Portland
  • 4The Pacific Northwest Evidence-based Practice Center, Departments of Family Medicine and Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland
JAMA. 2017;317(12):1258-1268. doi:10.1001/jama.2016.10395

Importance  Silent or subclinical celiac disease may result in potentially avoidable adverse health consequences.

Objective  To review the evidence on benefits and harms of screening for celiac disease in asymptomatic adults, adolescents, and children 3 years and older for the US Preventive Services Task Force.

Data Sources  Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews, searched to June 14, 2016.

Study Selection  Randomized clinical trials and cohort or case-control studies on clinical benefits and harms of screening vs no screening for celiac disease or treatment vs no treatment for screen-detected celiac disease; studies on diagnostic accuracy of serologic tests for celiac disease.

Data Extraction and Synthesis  One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria.

Main Outcomes and Measures  Cancer incidence, gastrointestinal outcomes, psychological outcomes, child growth outcomes, health outcomes resulting from nutritional deficiencies, quality of life, mortality, and harms of screening. No meta-analytic pooling was done.

Results  One systematic review and 3 primary studies met inclusion criteria. No trials of screening for celiac disease were identified. One recent, good-quality systematic review of 56 original studies and 12 previous systematic reviews (sample sizes of primary studies ranging from 62 to more than 12 000 participants) found IgA tissue transglutaminase was associated with high accuracy (sensitivity and specificity both >90%) for diagnosing celiac disease. IgA endomysial antibodies tests were associated with high specificity. Only 2 studies of serologic tests for celiac disease involving 62 and 158 patients were conducted in asymptomatic populations and reported lower sensitivity (57% and 71%). One fair-quality, small (n = 40) Finnish treatment trial of asymptomatic adults with screen-detected celiac disease based on positive serologic findings found initiation of a gluten-free diet associated with small improvement in gastrointestinal symptoms compared with no gluten-free diet (difference less than 1 point on a scale of 1 to 7) at 1 year, with no differences on most measures of quality of life. No withdrawals due to adverse events occurred during the trial; no other harms were reported. No studies were identified that addressed the other outcomes.

Conclusions and Relevance  Although some evidence was found regarding diagnostic accuracy of tests for celiac disease, little or no evidence was identified to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals. More research is needed to understand the effectiveness of screening and treatment for celiac disease, accuracy of screening tests in asymptomatic persons, and optimal screening strategies.