Diagnostics

• Celiac disease is an underdiagnosed condition that requires a high index of suspicion.

• Diagnosis is based on serology (initial testing) and EGD with duodenal biopsy (confirmation).

  • A gluten-free diet can cause negative test results.

  • HLA-based testing and/or a gluten challenge are options for patients not consuming gluten.

• Common indications for testing include:

  • Symptoms of malabsorption (e.g., steatorrhea)

  • First-degree relatives with celiac disease [6]

  • Iron deficiency anemia unresponsive to treatment

• IgA tissue transglutaminase antibody (tTG IgA): initial test, crucial part of celiac disease serology

  • Widely available test with high specificity (≥ 96%) [5]

  • Risk of false negatives (e.g., in IgA deficiency, gluten-free diet)

• Total IgA

  • Indicated for all patients because of the high prevalence of IgA deficiency in patients with celiac disease (approx. 2–3%) [3]

  • If patients have low IgA, perform further IgG-based testing.

• Deamidated gliadin peptide

  • IgG-based testing: indicated in IgA deficiency or discordant biopsy and serology

    • IgG-tissue transglutaminase (tTG IgG)

    • IgG deamidated gliadin peptide (DGP IgG)

  • IgA-based testing: IgA deamidated gliadin peptide (DGP IgA)

• HLA testing: second-line testing after unclear initial evaluation

  • Assesses for haplotypes HLA-DQ2 and HLA-DQ8

  • Indications include:

    • Uncertain diagnosis (e.g., disparity between serology and histopathology)

    • Gluten-free diet prior to diagnosis

    • Patients with Down syndrome

• Anti-endomysial antibody (EMA): Potential second-line confirmatory test (high-specificity)

• EGD with small intestine biopsy (confirmatory test)

  • Indications: positive serology or high clinical suspicion despite negative serology

  • At least five duodenal biopsies should be taken (with ≥ 1 from the duodenal bulb).

  • Histological findings: typically ranked by severity according to the Marsh classification

    • Intraepithelial lymphocytic infiltration

    • Crypt hyperplasia

    • Villous atrophy

• Video capsule endoscopy: if EGD is declined or as follow-up if symptoms persist despite treatment

False-negative serology and histopathology results are possible if patients are already adhering to a gluten-free diet.

• Gluten challenge: may be indicated if patients are already adhering to a gluten-free diet [5]

• Nutrient deficiency screening (individualize): indicated in confirmed celiac disease [14][15]

• Tests for malabsorption: not routinely indicated (low sensitivity and specificity)

  • D-xylose absorption test: low urine d-xylose levels (The passive absorption of d-xylose in the proximal small intestine is impaired by the mucosal defect and bacterial overgrowth.)

  • Fat malabsorption: quantitative stool fat assays or qualitativel

Repeat laboratory studies after 3–6 months and 12 months, then annually