Implementing AHRQ Effective Health Care Reviews

Helping Clinicians Make Better Treatment Choices

Comparative Accuracy of Diagnostic Tests for Celiac Disease

 

Am Fam Physician. 2017 Jun 1;95(11):726-728.

Author disclosure: No relevant financial affiliations.

Key Clinical Issue

What is the best test for celiac disease in terms of sensitivity, specificity, and safety?

Evidence-Based Answer

Current evidence on the accuracy of tests used to diagnose celiac disease supports the excellent sensitivity and specificity of anti-tissue transglutaminase immunoglobulin A (tTG IgA) tests. The available evidence supports the current recommendation of the American College of Gastroenterology (ACG) to use tTG IgA as the first-line test for patients two years and older with suspected celiac disease. (Strength of Recommendation [SOR]: C, based on disease-oriented evidence.) Testing for deamidated gliadin peptide (DGP) IgA or IgG may be more accurate in children younger than two years. (SOR: C, based on disease-oriented evidence.) Human lymphocyte antigen (HLA) typing that reveals the absence of HLA-DQ2 and HLA-DQ8 essentially rules out celiac disease. (SOR: C, based on disease-oriented evidence.) Video capsule endoscopy and endoscopy with duodenal biopsy are invasive and associated with a small risk of adverse events. (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.)

eTable A describes tests currently used to diagnose celiac disease.

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eTable A.

Tests Currently Used to Diagnose Celiac Disease

TestDescriptionNotes

Anti-tTG IgA

tTG is an enzyme involved in the cross-linking of certain proteins.

This test is included in the algorithms of all recent guidelines. Other tests may be ordered for individuals who are IgA deficient.

EmA IgA

The endomysium is the thin layer of connective tissue covering individual muscle fibers. Endomysial antibodies develop when the intestinal lining is damaged.

Most patients with active celiac disease and many others with dermatitis herpetiformis have anti-EmA IgA. EmA is included in algorithms of recent diagnostic guidelines but is not as widely used in the United States as in other countries. EmA IgA is less useful in individuals with low IgA.

Anti-DGP IgA and IgG

Gliadins are one of the two main groups of proteins in gluten.

Elevated antibodies against DGP are often seen in patients who have celiac disease and are on a gluten-containing diet. This is a newer test that may give a positive result in some individuals with celiac disease who are anti-tTG negative, including children younger than two years.

HLA typing (HLA-DQ2 or HLA-DQ8)

Researchers hypothesize that HLA molecules present gluten antigens to T cells, which in turn induce tissue damage.

Approximately 95% of patients with celiac disease have the HLA-DQ2 heterodimer, and 5% have the HLA-DQ8 heterodimer. Lack of these heterodimers rules out celiac disease and genetic susceptibility for the disorder.

VCE

VCE involves the ingestion of a capsule containing a tiny camera.

This test is used in individuals (primarily adults) who want to avoid biopsy. It provides high-quality visual evidence of the scalloping, fissuring, and flattened folds associated with celiac disease. One limitation of VCE is that its accuracy depends on the expertise of the individual interpreting the images. Furthermore, the cost of VCE is often not covered by health insurance in the United States.

Endoscopy with duodenal biopsy

The histology of a duodenal biopsy is assessed according to the Modified Marsh Classification system (grades 0 to 3) or qualitatively.

Villous atrophy disclosed by biopsy plus clinical remission while on a gluten-free diet represents the internationally accepted diagnostic standard for celiac disease. The clinician should instruct the patient to stay on a gluten-containing diet before biopsy in most circumstances. Marsh grade 1 or grade 2 lesions—in the absence of clinical or serologic evidence—are nonspecific, and suggesting but not confirming celiac disease. Marsh grade 3 lesions are the classic celiac disease lesions and are characteristic but not diagnostic of celiac disease.


DGP = deamidated gliadin peptide; EmA = endomysial antibodies; HLA = human leukocyte antigen; IgA = immunoglobulin A; IgG = immunoglobulin G; tTG = tissue transglutaminase; VCE = video capsule endoscopy.

Adapted from the Agency for Healthcare Research and Quality, Effective Health Care Program. Diagnosis of celiac disease: current state of the evidence. Clinician research summary. Rockville, Md.: Agency for Healthcare Research and Quality; July 2016. https://www.effectivehealthcare.ahrq.gov/ehc/products/574/2259/celiac-disease-clinician-160720.pdf. Accessed February 8, 2017.

eTable A.

Tests Currently Used to Diagnose Celiac Disease

TestDescriptionNotes

Anti-tTG IgA

tTG is an enzyme involved in the cross-linking of certain proteins.

This test is included in the algorithms of all recent guidelines. Other tests may be ordered for individuals who are IgA deficient.

EmA IgA

The endomysium is the thin layer of connective tissue covering individual muscle fibers. Endomysial antibodies develop when the intestinal lining is damaged.

Most p

Address correspondence to Dean A. Seehusen, MD, at dseehusen@msn.com. Reprints are not available from the author.

Author disclosure: No relevant financial affiliations.

editor's note: AFP SOR ratings are different from the AHRQ Strength of Evidence (SOE) ratings.

 

The views expressed in this article are those of the authors and do not reflect the policy or position of the U.S. Army Medical Department, Department of the Army, Department of Defense, or the U.S. government.

REFERENCES

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3. Agency for Healthcare Research and Quality. Effective Healthcare Program. Diagnosis of celiac disease: current state of the evidence. Clinician research summary. Rockville, Md.: Agency for Healthcare Research and Quality; July 2016. https://www.effectivehealthcare.ahrq.gov/ehc/products/574/2259/celiac-disease-clinician-160720.pdf. Accessed February 8, 2017.

4. 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.

5. Bakker SF, Tushuizen ME, von Blomberg BM, Bontkes HJ, Mulder CJ, Simsek S. Screening for coeliac disease in adult patients with type 1 diabetes mellitus: myths, facts and controversy. Diabetol Metab Syndr. 2016;8:51.

The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health Care Program as part of its mission to produce evidence to improve health care and to make sure the evidence is understood and used. A key clinical question based on the AHRQ Effective Health Care Program systematic review of the literature is presented, followed by an evidence-based answer based upon the review. AHRQ's summary is accompanied by an interpretation by an AFP author that will help guide clinicians in making treatment decisions.

See the full review, clinician summary, and consumer summary.

This series is coordinated by Kenny Lin, MD, MPH, Associate Deputy Editor for AFP Online.

A collection of Implementing AHRQ Effective Health Care Reviews published in AFP is available at http://www.aafp.org/afp/ahrq.

 

 

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