Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific preventive care services for patients without obvious related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
Celiac disease is a multisystem autoimmune disorder in genetically predisposed adults and children that is triggered by dietary gluten. Ingestion of gluten by persons with celiac disease causes immune-mediated inflammatory damage to the small intestine, which can cause gastrointestinal and nongastrointestinal illness. The clinical presentation, severity of symptoms, and natural history of the disease varies and includes asymptomatic (or "silent") celiac disease.
In studies of US populations, the estimated prevalence of celiac disease among adults ranges from 0.40% to 0.95%.1 Prevalence is higher than average among non-Hispanic whites, persons with a family history of celiac disease, and persons with other autoimmune conditions.2
The USPSTF found inadequate evidence regarding the accuracy of screening tests for celiac disease in asymptomatic populations.
Benefits of Early Detection and Intervention or Treatment
The USPSTF found inadequate evidence on the effectiveness of screening for celiac disease in asymptomatic adults, adolescents, and children with regard to morbidity, mortality, or quality of life. The USPSTF also found inadequate evidence on the effectiveness of targeted screening in persons who are at increased risk for celiac disease (eg, persons with family history or other risk factors).
The USPSTF found inadequate evidence on the effectiveness of treatment of screen-detected, asymptomatic celiac disease to improve morbidity, mortality, or quality of life compared with no treatment or treatment initiated after clinical diagnosis.
Harms of Early Detection and Intervention or Treatment
The USPSTF found inadequate evidence on the harms of screening for or treatment of celiac disease.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. Evidence is lacking, and the balance of benefits and harms cannot be determined.
Patient Population Under Consideration
This recommendation applies to adults, adolescents, and children who do not have signs or symptoms of celiac disease.
Suggestions for Practice Regarding the I Statement
Potential Preventable Burden
Classic celiac disease is associated with symptoms of malabsorption, including diarrhea, abdominal pain, and weight loss. It may also manifest as nonspecific, nongastrointestinal symptoms, including anemia, osteoporosis, chronic fatigue, peripheral neuropathy or ataxia, and short stature.2 Data from the United States suggest that some patients may have symptoms for years before being diagnosed.4 Evidence also suggests that celiac disease is associated with excess mortality, intestinal adenocarcinoma, and lymphoma; however, evidence is insufficient as to whether silent, or asymptomatic, disease has the same risk as symptomatic disease.2,5-7
In 3 US-based studies, the prevalence of laboratory-confirmed celiac disease ranged from 0.40% to 0.95% among adults.1 Some variations in prevalence can be attributed in part to the method used to confirm diagnosis.2 For example, some population-based studies on prevalence rely on serologic testing without histologic confirmation, which may result in false-positive diagnoses and overestimate prevalence. However, in a systematic review of 38 studies from North America and Western Europe, prevalence of celiac disease was similar among studies that included biopsy confirmation (0.15% to 1.90%) and among studies that did not include biopsy confirmation (0.15% to 2.70%).1
Celiac disease affects children, adolescents, and adults. Seroconversion to antibodies associated with celiac disease may occur at any time, and disease progression can take months or years, if it occurs at all. Data suggest that the average age at diagnosis is now in the fourth to sixth decade of life.8,9 Data are limited on the proportion of persons with silent celiac disease (positive histology findings but no symptoms) or potential celiac disease (positive serology findings but mild or no intestinal damage on biopsy) who later develop symptomatic celiac disease. Three long-term studies of US adults with follow-up ranging from 10 to 45 years reported rates of progression from positive serology findings to clinical diagnosis of celiac disease of 0% to 15%.10-12
Persons at increased risk for celiac disease include those who have a positive family history (eg, a first- or second-degree relative), with an estimated prevalence of 5% to 20%,13 and persons with other autoimmune diseases (eg, type 1 diabetes mellitus, inflammatory luminal gastrointestinal disorders, Down syndrome, Turner syndrome, IgA deficiency, and IgA nephropathy).14 Several specialty societies recommend screening in these populations.15-17 Reported prevalence among racial/ethnic minorities is lower than among non-Hispanic whites.2,5
Potential harms of screening for celiac disease in asymptomatic populations include false-positive, inconclusive, or unnecessary serologic test results and biopsies, with possible anxiety or complications from testing. Based on estimated likelihood ratios in the general population,2 the positive predictive value of serologic testing for celiac disease is 12% to 40%, assuming a prevalence of approximately 1%. In a higher-risk population, the positive predictive value is 40% to 80%, depending on the serologic test used and whether the assumed prevalence is 5% or 10%. Some patients with positive serology findings who do not undergo histologic confirmation may make efforts to avoid dietary gluten, which can increase costs and burdens and may result in limitations on quality of life. Limited evidence from 5 long-term follow-up studies (3 studies of patients with positive serology findings; 2 studies of children with biopsy confirmation) has shown that some persons who are diagnosed with celiac disease may never develop symptoms or complications; thus, overdiagnosis is also a potential concern.10-12,18,19
Reliable data on the frequency of screening for celiac disease in asymptomatic persons in clinical practice are not available.20 It is not known how many patients with positive serology findings without biopsy confirmation are treated with a gluten-free diet.
Screening for celiac disease is typically not performed in average-risk persons.2 The standard method of diagnosing celiac disease in symptomatic persons older than 2 years is the tissue transglutaminase (tTG) IgA test, followed by intestinal biopsy for histologic confirmation.2
Treatment and Interventions
Treatment of celiac disease is lifelong adherence to a gluten-free diet, which reverses disease manifestations in a majority of patients.2
Additional Approaches to Prevention
The National Institute of Diabetes and Digestive and Kidney Diseases provides current, comprehensive, science-based information about the symptoms, diagnosis, and treatment of celiac disease.21
Research Needs and Gaps
Studies that randomly assign participants to screening vs no screening and evaluate clinical outcomes are lacking. However, screening studies that target populations at increased risk for celiac disease are likely to be more informative than trials that target the general population, because of the higher prevalence of disease, and should be given higher priority. More information is needed about the accuracy of serologic testing in asymptomatic persons, particularly those with disease risk factors.
Treatment studies in screen-detected, asymptomatic persons are also needed to understand the effects of adherence to a gluten-free diet (compared with no dietary intervention), as well as the effects of immediate vs delayed dietary changes (ie, at the time of screen-detected diagnosis vs when symptoms develop). Ideally, studies would report both short-term effects on symptoms and quality of life and long-term outcomes (eg, osteoporotic fractures, cancer, and mortality). As for screening, treatment studies focused on asymptomatic persons at high risk for celiac disease who screen positive would be helpful for developing guidance for this population and may be faster and more efficient to complete than other study designs. More research is needed to better understand the natural history of positive serology in patients without histologic changes or with histologic confirmation but no symptoms. Also, treatment studies should report results stratified according to baseline histologic findings, given current uncertainty about the natural history of celiac disease in persons with mild histologic abnormalities.
Burden of Disease
Celiac disease is caused by an immune response in persons who are genetically susceptible to dietary gluten, a protein complex found in wheat, rye, and barley. Ingestion of gluten by persons with celiac disease causes immune-mediated inflammatory damage to the small intestine mucosa, resulting in malabsorption of nutrients.
Celiac disease can have several different presentations. Classic celiac disease is associated with diarrhea, abdominal pain, and weight loss. However, celiac disease is also associated with nongastrointestinal, nonspecific manifestations of disease such as anemia, osteoporosis, chronic fatigue, peripheral neuropathy or ataxia, aphthous stomatitis, dermatitis herpetiformis, infertility, recurrent fetal loss, or short stature.3 Children may also experience pubertal delay and dental enamel defects.22 For patients with subclinical disease, symptoms may be mild and not recognized until after initiation of a gluten-free diet. Patients with silent, or asymptomatic, celiac disease have been diagnosed by serologic testing and intestinal biopsy but do not have the typical signs or symptoms of celiac disease. Patients with potential celiac disease have positive serology findings and mild or no intestinal damage on biopsy; they may or may not have symptoms. The natural history of silent and potential celiac disease is not well understood, and it is not clear if they represent progressive stages of celiac disease or distinct subtypes.2
Data on the prevalence of silent celiac disease in the United States, as well as the proportion of these individuals who later develop symptomatic celiac disease, are limited.2 Reported prevalence of celiac disease in the literature varies due to the different racial/ethnic populations studied and the method used to confirm diagnosis.2 In a systematic review of 38 studies from North America and Western Europe, prevalence was similar among studies that included biopsy confirmation (0.15% to 1.90%) and among studies that did not (0.15% to 2.70%).1 In the 3 US-based studies, prevalence among adults ranged from 0.40% to 0.95%.1
Scope of Review
The USPSTF reviewed the evidence on the accuracy of screening in asymptomatic adults, adolescents, and children; the potential benefits and harms of screening vs not screening, as well as targeted vs universal screening; and the benefits and harms of treatment of screen-detected celiac disease. For questions regarding the benefits and harms of screening and treatment, outcomes of interest included morbidity, mortality, and quality of life. The USPSTF also reviewed contextual information on the prevalence of celiac disease among patients without evident symptoms and the natural history of subclinical or silent celiac disease.2 The USPSTF did not review the evidence on nonceliac gluten sensitivity because this condition is defined based on the presence of symptoms rather than diagnostic tests, and it is not thought to lead to the health complications associated with celiac disease.23
Accuracy of Screening Tests
A recent good-quality systematic review on the accuracy of diagnostic tests for celiac disease, which included studies enrolling both persons with symptoms and those whose symptom status was not described, found high strength of evidence that the tTG IgA test has high (>90%) sensitivity and specificity and endomysial antibody (EMA) IgA tests have high specificity, based on consistent results from prior systematic reviews and new studies.24 This systematic review included only 2 studies reporting diagnostic accuracy in asymptomatic persons at higher risk for celiac disease, due to other autoimmune disorders or family history, and no studies in asymptomatic persons at average risk. These 2 cross-sectional studies, which were both conducted outside the United States, found lower sensitivity and specificity for the tTG and EMA IgA tests (sensitivity, 57% to 71%; specificity, 83% to 98%), compared with studies that did not restrict enrollment to asymptomatic patients. One study was conducted in Iraq among patients with type 1 diabetes mellitus, no symptoms of celiac disease, and no family history of celiac disease or thyroid disorders. Sensitivity was 71% for both the tTG and EMA IgA tests and specificity was 93% for the tTG test and 96% for the EMA IgA test.25 The second study was conducted in the Czech Republic among children and adolescents at higher risk for celiac disease due to family history or a diagnosis of type 1 diabetes mellitus. Among asymptomatic patients, specificity and sensitivity of detecting antitransglutaminase levels of more than 10 times the upper limit of normal and a positive EMA IgA test result in patients with a Marsh histologic classification of stage 2 or 3 were 67% and 83%, respectively. Among first-degree relatives of patients with celiac disease (n=32), specificity was 70% and sensitivity was 81%. Among patients with type 1 diabetes mellitus (n=40), specificity was 64% and sensitivity was 93%.26
Effectiveness of Early Detection or Treatment
The USPSTF found no trials or controlled observational studies on the benefits of screening vs not screening or targeted vs universal screening in asymptomatic populations.
The USPSTF found no studies on the benefits of treatment of screen-detected celiac disease compared with treatment initiated after clinical diagnosis. The USPSTF found 1 small fair-quality trial on the benefits of treatment of screen-detected, asymptomatic adults compared with no treatment.27 This study (n=40) reported that after 1 year, a gluten-free diet was associated with improvements in histopathologic findings and small improvements in 3 of 5 gastrointestinal symptoms that were statistically but not clinically significant (<1 point on a 7-point scale). While there was also improvement in anxiety, no other measures of health-related quality of life showed improvements, and social functioning was worse in the group being treated with a gluten-free diet. After 2 years, more than 90% of participants in the intervention group reported adherence to the gluten-free diet, but there were no differences between the 2 groups in serology or subjective perception of health as measured by the visual analog scale.
Potential Harms of Screening or Treatment
The USPSTF found no trials or controlled observational studies on the harms of screening for celiac disease in asymptomatic populations. Potential harms of screening include false-positive, inconclusive, or unnecessary serologic test results and biopsies, with possible anxiety or complications from testing. However, the USPSTF found no studies on these harms. A subset of patients with biopsy-confirmed celiac disease may never develop symptoms; therefore, overdiagnosis is also a potential concern.2
One small fair-quality trial of treatment with a gluten-free diet27 reported no withdrawals due to major symptoms or complications. The USPSTF found no other studies on the harms of treatment with a gluten-free vs nongluten-free diet in persons with screen-detected celiac disease.
Estimate of Magnitude of Net Benefit
The USPSTF found inadequate evidence on the accuracy of screening for celiac disease in asymptomatic populations. The USPSTF found inadequate evidence on the potential benefits and harms of screening vs not screening, as well as targeted vs universal screening in asymptomatic populations. The USPSTF found inadequate evidence on the potential benefits and harms of treatment of screen-detected celiac disease compared with no treatment or treatment after clinical diagnosis. Therefore, the USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons.
Response to Public Comment
A draft version of this recommendation statement was posted for public comment on the USPSTF Web site from May 3 to May 30, 2016. Many comments described patients’ personal experience of a delayed diagnosis because of atypical or nonspecific symptoms. In response, the USPSTF expanded the "Suggestions for Practice" section to call attention to the prevalence of nonclassical symptoms, including anemia and osteoporosis, and delayed diagnosis. Another frequently raised concern was the higher risk among relatives of patients with celiac disease and patients with other autoimmune diseases. The USPSTF revised the "Research Needs and Gaps" section to emphasize the importance of developing evidence to guide clinical practice for this population.
The American Academy of Family Physicians has concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons.28 The American College of Gastroenterology recommends that asymptomatic persons with a first-degree relative who has a confirmed diagnosis of celiac disease be considered for testing. Patients with type 1 diabetes mellitus should be tested for celiac disease if there are any digestive symptoms, signs, or laboratory evidence suggestive of celiac disease.15
The National Institute for Health and Care Excellence recommends offering serologic testing to persons with a first-degree relative with celiac disease or persons with type 1 diabetes mellitus or autoimmune thyroid disease on diagnosis. Serologic testing for celiac disease should be considered for persons with any of the following: metabolic bone disorder (reduced bone mineral density or osteomalacia), unexplained neurologic symptoms (particularly peripheral neuropathy or ataxia), unexplained subfertility or recurrent miscarriage, persistently elevated liver enzymes with unknown cause, dental enamel defects, Down syndrome, or Turner syndrome.16
The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends testing for celiac disease in asymptomatic children who have conditions associated with celiac disease (type 1 diabetes mellitus, autoimmune thyroiditis, Down syndrome, Turner syndrome, Williams syndrome, or selective IgA deficiency) or a first-degree relative with celiac disease. It recommends testing these children beginning around age 3 years, provided they have had an adequate gluten-containing diet for at least 1 year prior. It also recommends that asymptomatic, at-risk children with negative serology findings be considered for repeat testing.17
The US Preventive Services Task Force (USPSTF) members include the following individuals: Kirsten Bibbins-Domingo, PhD, MD, MAS (University of California, San Francisco); David C. Grossman, MD, MPH (Group Health Research Institute, Seattle, Washington); Susan J. Curry, PhD (University of Iowa, Iowa City); Michael J. Barry, MD (Harvard Medical School, Boston, Massachusetts); Karina W. Davidson, PhD, MASc (Columbia University, New York, New York); Chyke A. Doubeni, MD, MPH (University of Pennsylvania, Philadelphia); Mark Ebell, MD, MS (University of Georgia, Athens); John W. Epling Jr, MD, MSEd (Virginia Tech Carilion School of Medicine, Roanoke); Jessica Herzstein, MD, MPH (Independent consultant, Washington, DC); Alex R. Kemper, MD, MPH, MS (Duke University, Durham, North Carolina); Alex H. Krist, MD, MPH (Fairfax Family Practice Residency, Fairfax, Virginia, and Virginia Commonwealth University, Richmond); Ann E. Kurth, PhD, RN, MSN, MPH (Yale University, New Haven, Connecticut); C. Seth Landefeld, MD (University of Alabama at Birmingham); Carol M. Mangione, MD, MSPH (University of California, Los Angeles); Maureen G. Phipps, MD, MPH (Brown University, Providence, Rhode Island); Michael Silverstein, MD, MPH (Boston University, Boston, Massachusetts); Melissa A. Simon, MD, MPH (Northwestern University, Evanston, Illinois); Chien-Wen Tseng, MD, MPH, MSEE (University of Hawaii, Manoa).
Source: This article first appeared in JAMA on March 28, 2017.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Authors followed the policy regarding conflicts of interest described at http://www.uspreventiveservicestaskforce.org/Page/Name/conflict-of-interest-disclosures. All members of the USPSTF receive travel reimbursement and an honorarium for participating in USPSTF meetings.
Funding/Support: The USPSTF is an independent, voluntary body. The US Congress mandates that the Agency for Healthcare Research and Quality (AHRQ) support the operations of the USPSTF.
Disclaimer: Recommendations made by the USPSTF are independent of the US government. They should not be construed as an official position of AHRQ or the US Department of Health and Human Services.
Copyright Notice: USPSTF recommendations are based on a rigorous review of existing peer-reviewed evidence and are intended to help primary care clinicians and patients decide together whether a preventive service is right for a patient's needs. To encourage widespread discussion, consideration, adoption, and implementation of USPSTF recommendations, AHRQ permits members of the public to reproduce, redistribute, publicly display, and incorporate USPSTF work into other materials provided that it is reproduced without any changes tothe work of portions thereof, except as permitted as fair use under the US Copyright Act.
AHRQ and the U.S. Department of Health and Human Services cannot endorse, or appear to endorse, derivative or excerpted materials, and they cannot be held liable for the content or use of adapted products that are incorporated on other Web sites. Any adaptations of these electronic documents and resources must include a disclaimer to this effect. Advertising or implied endorsement for any commercial products or services is strictly prohibited.
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- Chou R, Blazina I, Bougatsos C, Mackey K, Grusing S, Selph S. Screening for Celiac Disease: Systematic Review for the US Preventive Services Task Force. Evidence Synthesis No. 144. AHRQ Publication No. 14-05215-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2017.
- Green PH, Cellier C. Celiac disease. N Engl J Med. 2007;357(17):1731-43.
- Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H, Neugut AI; Green PH. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol. 2001;96(1):126-31.
- Chou R, Bougatsos C, Blazina I, Mackey K, Grusing S, Selph S. Screening for celiac disease: evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. doi:10.1001/jama.2016.10395.
- Tursi A, Elisei W, Giorgetti GM, Brandimarte G, Aiello F. Complications in celiac disease under gluten-free diet. Dig Dis Sci. 2009;54(10):2175-82.
- Tio M, Cox MR, Eslick GD. Meta-analysis: coeliac disease and the risk of all-cause mortality, any malignancy and lymphoid malignancy. Ailment Pharmacol Ther. 2012;35(5):540-51.
- 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-e14.
- 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.
- Rubio-Tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology. 2009;137(1):88-93.
- 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):530-8.
- Godfrey JD, Brantner TL, Brinjikji W, et al. Morbidity and mortality among older individuals with undiagnosed celiac disease. Gastroenterology. 2010;139(3):763-9.
- Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med. 2003;163(3):286-92.
- Murray JA. Celiac disease in patients with an affected member, type 1 diabetes, iron-deficiency, or osteoporosis? Gastroenterology. 2005;128(4)(suppl 1):S52-S56.
- 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):656-76.
- Richey R, Howdle P, Shaw E, Stokes T; Guideline Development Group. Recognition and assessment of coeliac disease in children and adults: summary of NICE guidance. BMJ. 2009;338:b1684.
- Hill ID, Dirks MH, Liptak GS, et al; North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. 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):1-19.
- Mäki M, Mustalahti K, Kokkonen J, et al. Prevalence of celiac disease among children in Finland. N Engl J Med. 2003;348(25):2517-24.
- van Koppen EJ, Schweizer JJ, Csizmadia CG, et al. Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study. Pediatrics. 2009;123(4):e582-e588.
- Fasano A, Catassi C. Clinical practice: celiac disease. N Engl J Med. 2012;367(25):2419-26.
- National Institute of Diabetes and Digestive and Kidney Diseases. Celiac disease. https://www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease. Accessed January 24, 2017.
- Fasano A. Clinical presentation of celiac disease in the pediatric population. Gastroenterology. 2005;128(4)(suppl 1):S68-S73.
- Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62(1):43-52.
- Maglione MA, Okunogbe A, Ewing B, et al. Diagnosis of Celiac Disease. AHRQ Publication No. 15(16)-EHC032-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
- Mansour AA, Najeeb AA. Coeliac disease in Iraqi type 1 diabetic patients. Arab J Gastroenterol. 2011;12(2):103-5.
- 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. 2014;173:497-502.
- 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.e1.
- American Academy of Family Physicians. Clinical preventive services recommendations. http://www.aafp.org/patient-care/browse/type.tag-clinical-preventive-services-recommendations.html. Accessed January 24, 2017.