What are the diagnostic tests for celiac disease (CD)?

From the Guidelines

The diagnostic workup for celiac disease should begin with serologic testing, including tissue transglutaminase IgA antibody (tTG-IgA) and total serum IgA, while the patient is on a gluten-containing diet, as recommended by the most recent and highest quality study 1. The tTG-IgA test is highly sensitive and specific for celiac disease, while total IgA helps identify IgA deficiency which could lead to false negative results.

• If IgA deficiency is present, deamidated gliadin peptide IgG (DGP-IgG) or tTG-IgG should be ordered instead, as suggested by 1 and 1.
• Positive serologic tests should be followed by an upper endoscopy with multiple duodenal biopsies (at least 4-6 samples) to confirm the diagnosis, as stated in 1.
• Biopsies should show characteristic villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes.
• Genetic testing for HLA-DQ2 and HLA-DQ8 can be helpful in certain situations, particularly to rule out celiac disease in ambiguous cases, as nearly all celiac patients carry at least one of these haplotypes, as mentioned in 1. It's crucial that patients maintain a normal gluten-containing diet (equivalent to at least 2-4 slices of bread daily) for 6-8 weeks before testing to avoid false negative results, as emphasized by 1. After diagnosis, patients should be evaluated for nutritional deficiencies including iron, folate, vitamin B12, vitamin D, and zinc, as malabsorption is common in celiac disease, which affects approximately 1% of the population and causes intestinal damage through an immune-mediated reaction to gluten proteins, as discussed in 1. Key points to consider in the diagnostic workup of celiac disease include:
• The importance of serologic testing while the patient is on a gluten-containing diet
• The need for upper endoscopy with multiple duodenal biopsies to confirm the diagnosis
• The role of genetic testing in certain situations
• The importance of evaluating for nutritional deficiencies after diagnosis.

From the Research

Diagnostic Tests for Celiac Disease

The diagnostic tests for celiac disease (CD) include:

• Serologic tests, such as tissue transglutaminase immunoglobulin antibody and endomysial immunoglobulin antibody, which are the most sensitive and specific tests for identifying individuals who need to undergo an intestinal biopsy 2
• Intestinal biopsy, which is the gold standard for the diagnosis of celiac disease, showing villous atrophy 2, 3, 4
• Duodenal mucosal biopsies, which should be performed on a gluten-containing diet 3
• Immunoglobulin A tissue transglutaminase serologic testing, which is the recommended initial screening for all age groups 4
• Esophagogastroduodenoscopy with small bowel biopsy, which is recommended to confirm the diagnosis in most patients, including those with a negative serologic test for whom clinical suspicion of celiac disease persists 4

Serologic Tests

The serologic tests used to diagnose celiac disease include:

• IgA class anti-endomysial and anti-tissue transglutaminase antibodies, which correlate well with histological findings in negative patients and in those with high levels of antibodies 5
• Tissue transglutaminase IgA assay, which has a high specificity (0.83) but low sensitivity (0.50) in detecting persistent villous atrophy 6
• Endomysial IgA assay, which has a high specificity (0.91) but low sensitivity (0.45) in detecting persistent villous atrophy 6

Biopsy and Histological Findings

The biopsy and histological findings used to diagnose celiac disease include:

• Villous atrophy, which is the hallmark of celiac disease 2, 3, 4
• Increased number of intra-epithelial lymphocytes in the duodenal biopsy, which can be detected in patients with positive serological tests 5
• Partial or total villous atrophy, which can be detected with high levels of antibodies 5