Clinical Review & Education
JAMA Clinical Guidelines Synopsis
Diagnosis and Management of Celiac Disease
Kerstin Austin, MD; Nimrod Deiss-Yehiely, MD; Jason T. Alexander, MD
2023 American College of Gastroenterology guidelines update on di-
GUIDELINE TITLE American College of Gastroenterology agnosis and management of celiac disease.
Guidelines Update: Diagnosis and Management of
Celiac Disease Characteristics of the Guideline Source
The guideline development group included content experts who
RELEASE DATE January 2023 generated key clinical questions and identified studies from the lit-
erature, as well as methodology experts who assessed level of evi-
PRIOR VERSION May 2013
dence using the GRADE framework and final recommendation
strength.1 All guideline authors were gastroenterologists. Litera-
DEVELOPER AND FUNDING SOURCE American College of
ture searches were conducted using the PICO (population, inter-
Gastroenterology
vention, comparison, and outcome) format, although no reporting
TARGET POPULATION Children and adults with celiac disease of the formal searches was provided (Table).
SELECTED RECOMMENDATIONS Evidence Base
• Screening for celiac disease in asymptomatic people in The strength of recommendations was expressed as strong or con-
the general population is not recommended (strong ditional. Quality of evidence was rated as high, moderate, low, or very
recommendation; low quality of evidence). low based on the likelihood that future research would have an im-
• Upper endoscopy with multiple (ⱖ4) duodenal biopsies portant impact on the effect estimates. There were a total of 11 rec-
is recommended for diagnostic confirmation in both ommendations; 6 were rated as strong (4 were based on moderate-
children and adults who have characteristic signs and quality and 2 on low-quality evidence).
symptoms of celiac disease (strong recommendation; Screening for celiac disease in the absence of characteristic
moderate quality of evidence). symptoms or signs is not recommended. Symptoms or laboratory
• In symptomatic children, a blood test with high-level tissue abnormalities that may prompt evaluation for celiac disease in-
transglutaminase antibody (tTG) IgA (>10 times the upper clude chronic diarrhea, abdominal pain, bloating, unexplained weight
limit of normal) and presence of endomysial antibody loss, and deficiencies of iron, vitamin B12, and fat-soluble vitamins.
(EMA) in a second blood sample are suggested for However, the sensitivity and specificity of gastrointestinal symp-
diagnosis of celiac disease. In symptomatic adults who are toms and abnormal laboratory findings for identification of celiac dis-
unwilling or unable to undergo upper endoscopy, high-level ease in adults vary widely. For example, diarrhea had a sensitivity
tTG IgA and presence of EMA can be used to establish of 0.27 to 0.86 and a specificity of 0.21 to 0.86 in a review of 6 co-
a diagnosis of likely celiac disease (conditional hort studies including 2265 adults who presented as outpatients with
recommendation; moderate quality of evidence). abdominal symptoms such as diarrhea, constipation, weight loss,
• A gluten-free diet is required (strong recommendation; abdominal pain, nausea, or flatulence.2
moderate quality of evidence) to achieve the treatment The diagnostic approach to celiac disease for adults incorpo-
goal of resolution of histologic mucosal lesions in adults rates serologic and histologic data. Blood tTG IgA assays are the
(conditional recommendation; low quality of evidence). first-line test for diagnosis of celiac disease in patients without IgA
Table. Guideline Ratinga
Summary of the Clinical Problem Standard Rating
Celiac disease is an immune-mediated response to gluten, a protein Establishing transparency Good
found in wheat, barley, and rye that affects approximately 1% of Management of conflict of interest in the guideline Good
development group
the US population. The hallmark of celiac disease is injury to the
Guideline development group composition Poor
small bowel mucosa that causes villous atrophy and results in
Clinical practice guideline–systematic review intersection Poor
malabsorption of micronutri-
Establishing evidence foundations and rating strength Fair
Multimedia
ents, fat-soluble vitamins, iron, for each of the guideline recommendations
vitamin B12, and folic acid. Com- Articulation of recommendations Good
mon signs and symptoms of External review Poor
CME at jamacmelookup.com
celiac disease include diarrhea, Updating Fair
abdominal bloating, abdominal discomfort, and constipation. Celiac
Implementation issues Fair
disease is also associated with extraintestinal manifestations such as
a
fatigue, weight loss, dermatitis herpetiformis, iron deficiency, and Cifu AS, Davis AM, Livingston EH. Introducing JAMA Clinical Guidelines
Synopsis. JAMA. 2014;312(12):1208-1209. doi:10.1001/jama.2014.12712
osteoporosis.1 This JAMA Clinical Guidelines Synopsis focuses on the
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Clinical Review & Education JAMA Clinical Guidelines Synopsis
deficiency. In a meta-analysis of 7 cohort and case-control studies with celiac disease. One prospective study (n = 381) found a 34%
(4500 patients; prevalence of celiac disease was 2%-13% in the co- rate of mucosal healing after 2 years of following a gluten-free diet.5
hort studies), tTG IgA had a sensitivity of 89% (95% CI, 82%-94%) Histologic recovery on endoscopy was documented in 1 study
and a specificity of 98% (95% CI, 95%-99%) compared with small among 96% (24/25) of children adherent to a gluten-free diet
bowel biopsy, provided that a patient was not following a gluten- after 2 years, although another study found that 19.4% (14/71) of pe-
free diet at the time of testing and that IgA deficiency was excluded.2 diatric patients had persistent enteropathy despite adherence to
When the titer of tTG IgA is less than 5-fold the upper limit of nor- a gluten-free diet for 1 year.6,7
mal, celiac disease is adequately ruled out (likelihood ratio, 0.11;
95% CI, 0.05-0.20) in patients with a low pretest probability of celiac Discussion
disease (ⱕ5%) and no IgA deficiency.2 If the pretest probability of This guideline provides an algorithm for diagnosing celiac disease
celiac disease is high (>5%), endoscopy with small bowel biopsy in children and adults. It does not discuss diagnosis and treatment
should be considered, even in the setting of normal tTG IgA, for both of nonceliac gluten sensitivity in individuals with symptomatic im-
children and adults. provement after gluten withdrawal, normal tTG, and normal small
Although the guideline recommends confirming celiac diagno- bowel histology. Although nonceliac gluten sensitivity is more com-
sis with histology in children with elevated tTG IgA, a biopsy-free ap- mon than celiac disease, no guidelines exist on the diagnosis and
proach for children with characteristic symptoms of celiac disease, management of this condition. The pathogenesis of nonceliac glu-
high tTG IgA, and positive EMA is suggested as an acceptable alter- ten sensitivity remains unclear and overlaps with several condi-
native. A 2017 multinational study of 707 patients younger than 19 tions, including functional dyspepsia, irritable bowel syndrome, and
years reported that the combination of tTG IgA (ⱖ10 times the up- eating disorders.
per limit of normal) with positive EMA and any symptom character-
istic of celiac disease had a sensitivity of 61.7% (95% CI, 57.8%- Benefits and Harms
65.5%) and a specificity of 98.4% (95% CI, 91.3%-100%) compared For individuals with celiac disease, adherence to a gluten-free diet
with biopsy.3 In another 2017 multicenter validation trial in chil- is associated with improved quality of life, decreased gastrointes-
dren aged 5 months to 18 years, a tTG IgA greater than 10 times the tinal symptoms, and improvement or resolution of iron deficiency
upper limit of normal identified patients with celiac disease with a anemia.8 Challenges with adherence to a strict gluten-free diet in-
sensitivity of 97.1% (95% CI, 95.8%-98.3%) and a specificity of 89.3% clude increased cost of gluten-free products compared with wheat-
(95% CI, 85.5%-92.1%).4 The biopsy-free approach has not been based products and constraints when eating outside the home.9
studied for symptomatic adults, so the guideline recommends using For patients with celiac disease, it is important to engage in
the combination of tTG IgA and EMA only in adults who are unwill- shared decision-making regarding the utility of repeating an upper
ing or unable to undergo endoscopy. endoscopy with biopsy to assess for small bowel healing. Endos-
A gluten-free diet is the only effective therapy for celiac dis- copy is typically a safe procedure; however, the risk of severe ad-
ease and is associated with decreased symptoms, improved qual- verse events (such as bleeding, infection, and perforation) is 1 in 200
ity of life, and decreased risk of complications such as malnutrition. to 1 in 10 000 procedures and is likely higher in older patients.10
For adults with celiac disease, a treatment goal of intestinal healing
is suggested. Most data showing benefit of this approach are from Areas in Need of Future Study or Ongoing Research
observational studies; prospective randomized trials are lacking. Investigation is needed on the frequency of biopsies and clinical man-
There is poor correlation among abdominal symptoms, tTG IgA se- agement of asymptomatic patients with celiac disease who have in-
rology, and mucosal healing, further emphasizing the need for up- flammation on small bowel biopsy but normal serologic findings and
per endoscopy with biopsy to confirm mucosal healing among adults no malabsorption.
ARTICLE INFORMATION Gastroenterol. 2023;118(1):59-76. doi:10.14309/ajg. 6. Wahab P, Meijer J, Mulder C. Histologic follow-up
Author Affiliations: Division of Gastroenterology 0000000000002075 of people with celiac disease on a gluten-free diet.
and Hepatology, University of Wisconsin, Madison, 2. van der Windt DA, Jellema P, Mulder CJ, et al. Am J Clin Pathol. 2002;118(3):459-463.
Wisconsin (Austin, Deiss-Yehiely); Department of Diagnostic testing for celiac disease among patients 7. Leonard MM, Weir DC, DeGroote M, et al. Value
Medicine, University of Chicago, Chicago, Illinois with abdominal symptoms. JAMA. 2010;303(17): of IgA tTG in predicting mucosal recovery in
(Alexander). 1738-1746. doi:10.1001/jama.2010.549 children with celiac disease on a gluten-free diet.
Corresponding Author: Kerstin Austin, MD, 3. Werkstetter KJ, Korponay-Szabó IR, Popp A, J Pediatr Gastroenterol Nutr. 2017;64(2):286-291.
Department of Gastroenterology and Hepatology, et al. Accuracy in diagnosis of celiac disease without doi:10.1097/MPG.0000000000001460
University of Wisconsin, 1685 Highland Ave, biopsies in clinical practice. Gastroenterology. 2017; 8. Berry N, Vaiphei K, Dhaka N, et al. Quality of life
Madison, WI 53705 ([email protected]). 153(4):924-935. doi:10.1053/j.gastro.2017.06.002 in celiac disease and the effect of gluten-free diet.
Section Editor: David L. Simel, MD, MHS, Associate 4. Wolf J, Petroff D, Richter T, et al. Validation of JGH Open. 2018;2(4):124-128. doi:10.1002/jgh3.
Editor. antibody-based strategies for diagnosis of pediatric 12056
Published Online: June 26, 2024. celiac disease without biopsy. Gastroenterology. 9. Theethira TG, Dennis M. Celiac disease and the
doi:10.1001/jama.2024.5883 2017;153(2):410-419. doi:10.1053/j.gastro.2017.04. gluten-free diet. Dig Dis. 2015;33(2):175-182. doi:10.
023 1159/000369504
Conflict of Interest Disclosures: None reported.
5. Rubio-Tapia A, Rahim MW, See JA, et al. Mucosal 10. Ben-Menachem T, Decker GA, Early DS, et al.
REFERENCES recovery and mortality in adults with celiac disease Adverse events of upper GI endoscopy. Gastrointest
after treatment with a gluten-free diet. Am J Endosc. 2012;76(4):707-718. doi:10.1016/j.gie.2012.
1. Rubio-Tapia A, Hill ID, Semrad C, et al. American Gastroenterol. 2010;105(6):1412-1420. doi:10.1038/ 03.252
College of Gastroenterology guidelines update: ajg.2010.10
diagnosis and management of celiac disease. Am J
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