What is the recommended approach for a celiac disease (CD) workup?

Recommended Approach for Celiac Disease Workup

The recommended approach for celiac disease (CD) workup begins with IgA tissue transglutaminase antibody (tTG-IgA) as the primary serological test, followed by intestinal biopsy for confirmation if serology is positive, all while the patient maintains a gluten-containing diet. 1

Initial Serological Testing

• Primary test: IgA tissue transglutaminase antibody (tTG-IgA)

  • Sensitivity: 97.7% in children
  • Specificity: 70.2% in children 1

• IgA level measurement: Should be performed simultaneously with tTG-IgA to rule out IgA deficiency (present in 2-3% of celiac patients) 1

• For IgA-deficient patients: Use IgG-based tests

  • IgG tissue transglutaminase (tTG-IgG)
  • IgG deamidated gliadin peptides (DGP-IgG) 1

• Confirmatory test: IgA endomysial antibody (EMA-IgA) for positive tTG-IgA results

  • Sensitivity: 94.5% in children
  • Specificity: 93.8% in children 1
  • Positive predictive value: 85% (compared to 45% for tTG-IgA alone) 2

Important Considerations for Testing

• Maintain gluten-containing diet: Testing must be performed while the patient is consuming gluten

  • If already on gluten-free diet: Gluten challenge with three slices of wheat bread daily for 1-3 months before testing 1

• Avoid inappropriate tests: The following should NOT be used for CD diagnosis:

  • Stool studies
  • Small-bowel follow-through
  • Intestinal permeability testing
  • D-xylose testing
  • Salivary testing
  • Skin testing 1

Intestinal Biopsy

• Gold standard: Endoscopic duodenal biopsy remains the definitive diagnostic test 3, 1

• Biopsy protocol: At least 6 specimens should be obtained

  • 4 oriented biopsies from second part of duodenum
  • 2 oriented biopsies from duodenal bulb 3
  • Multiple biopsies are essential due to patchy distribution of intestinal damage 1

• Histological findings: Look for

  • Villous atrophy
  • Crypt hyperplasia
  • Intraepithelial lymphocytosis (≥25 IELs per 100 enterocytes) 1

Biopsy-Sparing Approach

• In children and adolescents with high tTG-IgA levels, repeated serological testing may render gastroscopy with biopsy unnecessary 3
• This approach is not recommended for adults 1

Genetic Testing

• HLA-DQ2/DQ8 testing: Has high negative predictive value (>99%)
• Useful in specific scenarios:
  • Patients with negative serology but strong clinical suspicion
  • Patients already on gluten-free diet without prior testing
  • Patients with equivocal biopsy results 1

High-Risk Groups for Screening

• First-degree relatives of CD patients (7.5% risk)
• Patients with:
  • Type 1 diabetes
  • Autoimmune thyroid disease
  • Down syndrome
  • Turner syndrome
  • Unexplained iron deficiency anemia 1

Follow-Up After Diagnosis

• Serological monitoring: Anti-TG2 antibodies at 6 months, 12 months, and annually thereafter 1
• Dietetic evaluation: To assess adherence to gluten-free diet and nutritional balance 3
• Clinical assessment: Annual evaluation for symptom resolution, nutritional status, and weight management 1
• Nutritional deficiency testing: Iron, folate, vitamin B12, vitamin D 1
• Bone mineral density: DXA scan to evaluate BMD, especially in cases of prolonged malabsorption 3

Management of Non-Responsive CD

• For persistent symptoms despite adherence to gluten-free diet:
  • Confirm original diagnosis
  • Evaluate dietary adherence (dietetic review and serology)
  • Consider gluten immunogenic peptide (GIP) testing in urine or stool 3
  • Consider follow-up biopsy 1
  • Evaluate for complications such as refractory CD 3

By following this structured approach to celiac disease workup, clinicians can achieve accurate diagnosis and implement appropriate management strategies to improve patient outcomes and quality of life.