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Is an intestinal biopsy necessary when the blood work suggests celiac disease?

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EVIDENCE-BASED ANSWER:

It depends on the antibody levels in the blood work. Symptomatic patients with serologic levels of immunoglobulin A anti-tissue transglutaminase (IgA anti-tTG) or immunoglobulin G anti-deamidated gliadin peptide antibody (IgG anti-DGP) greater than 10 times the upper limits of normal—especially if they also are positive for endomysial antibodies (EMA) and human leukocyte antigen DQ2 (HLA-DQ2 or HLA-DQ8)—may not need an intestinal biopsy to confirm the diagnosis of celiac disease (strength of recommendation [SOR]: B, inconsistent or limited-quality cohort studies).

Patients with antibody levels lower than 10 times the upper limits of normal or who are asymptomatic most likely need an intestinal biopsy to confirm the diagnosis (SOR: B, inconsistent or limited-quality cohort studies).


 

References

EVIDENCE SUMMARY

A 2013 Belgian prospective study of 104 non-IgA–deficient adults and children diagnosed with celiac disease and 537 adults and children without celiac disease evaluated the accuracy of 4 manufacturers’ serologic tests for IgA anti-tTG.1 All patients underwent serologic testing followed by a diagnostic biopsy. A Marsh type 3 or greater lesion on duodenal biopsy was considered diagnostic for celiac disease.

Anti-tTG levels greater than 10 times the manufacturer-recommended level for a positive test (cut-off) were associated with a likelihood ratio of 111 to 294 (depending on the manufacturer) of positive biopsy. Post-test probabilities were calculated based on various pretest probabilities using an anti-tTG level of greater than 10 times the cut-off (TABLE1).

Investigators also obtained IgG anti-DGP levels from 2 of the manufacturers.1 Likelihood ratios increased along with antibody levels. Ratios of 80 and 400, depending on the manufacturer, were found at IgG anti-DGP levels 10-fold greater than the cut-off. Pre- and post-test probabilities weren’t calculated.

Post-test probability of celiac disease in patients with an elevated anti-tissue transglutaminase antibody level image

Positive predictive value rises with antibody levels

A 2013 retrospective study evaluated the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition’s recommendation to forego intestinal biopsy in non-IgA–deficient, symptomatic children and adolescents with positive IgA anti-tTG levels greater than 10 times the cut-off value, positive EMA, and positive HLA-DQ2 or HLA-DQ8.2

Overall, 153 symptomatic patients referred to the gastroenterology unit met these criteria. The age range was 9 months to 14.6 years (mean 4 years). All but 3 of the patients had Marsh 2 or greater lesions with biopsy-confirmed diagnoses of celiac disease. The remaining 3 developed biopsy-positive celiac disease on follow-up. The positive predictive value of combined serologic testing in this small selected patient population was 100%.

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