What Is the Current Approach to Diagnosing Celiac Disease?

Answer in brief: In adults, celiac disease is usually diagnosed by compatible serology obtained while the patient is eating gluten and confirmed with upper endoscopy and multiple duodenal biopsies. Tissue transglutaminase IgA is the usual first-line test, accompanied by assessment for IgA deficiency. HLA-DQ2/DQ8 testing is most useful to exclude celiac disease when the diagnosis is uncertain, not as a routine screening test.

Do not start with a gluten-free diet

Testing becomes less sensitive after gluten withdrawal. If celiac disease is suspected, obtain diagnostic studies while the patient is consuming gluten whenever possible. Patients who already stopped gluten may need specialist-directed HLA testing and, in selected cases, a gluten challenge.

Use the right serology

IgA tissue transglutaminase is the standard first-line serologic test for most patients. Measure total IgA or otherwise account for IgA deficiency; in IgA-deficient patients use appropriate IgG-based testing such as deamidated gliadin peptide or tTG IgG.

Biopsy remains important in adults

At endoscopy obtain multiple biopsies from the duodenum, including the bulb and distal duodenum, because mucosal abnormalities can be patchy. Pathology should report villous architecture, crypt hyperplasia and intraepithelial lymphocytes in context.

Consider the pretest probability

Celiac testing is appropriate in chronic diarrhea, weight loss, iron-deficiency anemia, unexplained nutrient deficiencies, dermatitis herpetiformis and selected associated autoimmune/familial settings. A weakly positive antibody in a low-risk patient carries different meaning from strongly positive serology in a patient with classic malabsorption.

Use HLA strategically

Absence of HLA-DQ2/DQ8 makes celiac disease very unlikely and can be valuable when serology and biopsy conflict or when a patient is already gluten free. A positive HLA result is common and does not establish the diagnosis.

What trainees should remember

Diagnose celiac disease before treating it: test while gluten is being eaten, account for IgA deficiency, obtain adequate duodenal biopsies in adults, and use HLA mainly to rule disease out in uncertain cases.

Frequently asked questions

Can celiac disease be diagnosed from symptoms alone?

No. Symptoms are nonspecific and objective diagnostic testing is needed.

Is a positive HLA-DQ2 result diagnostic?

No. Many healthy people carry DQ2 or DQ8; their main value is the high negative predictive value when both are absent.

References and further reading

1. Thomson ABR. Practice Review in Gastroenterology. CAPstone Academic Publishers; 2014.

2. Thomson ABR. First Principles of Gastroenterology and Hepatology in Adults and Children, 7th ed. CAPstone Academic Publishers; 2013.

3. Rubio-Tapia A, et al. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2023.