What is the recommended approach for a celiac disease workup?

Celiac Disease Workup

The recommended approach for celiac disease workup begins with serological testing using tissue transglutaminase IgA (tTG-IgA) antibodies along with total serum IgA level measurement, followed by duodenal biopsies if serology is positive. 1

Initial Serological Testing

Primary Testing

• Tissue transglutaminase IgA (tTG-IgA): First-line serological test with sensitivity of 90-96% in adults and 97.7% in children 1
• Total serum IgA level: Must be checked simultaneously to rule out IgA deficiency 1
• Patient preparation: Maintain regular gluten consumption (1-3 slices of gluten-containing bread daily) for at least 6 weeks prior to testing 1

Secondary/Confirmatory Testing

• IgA Endomysial Antibodies (EMA-IgA): Can be used as a confirmatory test with extremely high specificity (99.6% in adults) 1
• Deamidated Gliadin Peptide Antibodies (DGP): Particularly useful in certain scenarios 1
• For IgA deficiency: IgG-based testing (IgG tTG and IgG DGP) should be performed 1

Endoscopic Evaluation

Biopsy Protocol

• Number of specimens: At least 6 biopsy specimens 1
• Location: Both duodenal bulb and distal duodenum 1
• Diagnostic histological findings:
  • Villous atrophy
  • Crypt hyperplasia
  • Increased intraepithelial lymphocytes (≥25 IELs/100 enterocytes)
  • Increased lamina propria lymphocytes 1

Special Scenarios

Diagnostic Algorithm for Specific Populations

• IgA deficiency patients: IgG-based testing should be performed 1
• High-risk groups requiring testing:
  • Type 1 diabetes patients
  • First-degree relatives of celiac disease patients
  • Patients with other autoimmune disorders 1

Genetic Testing

• HLA-DQ2/DQ8 testing: Useful in specific scenarios:
  • Seronegative celiac disease
  • Patients with Down syndrome
  • Equivocal small-bowel histologic findings
  • Patients already on a gluten-free diet 1
  • Negative results virtually exclude celiac disease (>99% negative predictive value) 1

Monitoring After Diagnosis

Follow-up Testing

• Serological testing: At 6 and 12 months after diagnosis, then yearly 1
• Purpose: Monitor response to treatment and detect potential complications 1
• Note on monitoring limitations: Serum tTG IgA and EMA IgA have low sensitivity (<50%) for detecting persistent villous atrophy in patients on gluten-free diets 2

Common Pitfalls to Avoid

Diagnostic Errors

• Misinterpreting isolated intraepithelial lymphocytes: Increased IELs with normal villi should not be considered seronegative celiac disease 1
• Ignoring other causes of villous atrophy: Other conditions can cause similar histological findings:
  • Medications
  • Infections
  • Other immune-mediated disorders 1
• Relying solely on serology for monitoring: Tests for serum tTG IgA and EMA IgA have low sensitivity in detecting persistent villous atrophy in patients on gluten-free diets 2

Discordant Results

• Positive tTG-IgA/negative EMA-IgA: Patients with this pattern have a low probability of having celiac disease 3
  • Consider testing with multiple different anti-tTG IgA assays, as positivity on multiple platforms increases likelihood of true celiac disease 3

Evaluation of Non-responsive Celiac Disease

For Persistent Symptoms Despite Gluten-Free Diet

1. Confirm original diagnosis: Review prior diagnostic testing 4
2. Exclude ongoing gluten exposure:
   • Serologic testing
   • Dietitian review
   • Detection of immunogenic peptides in stool or urine 4
3. Repeat endoscopy with biopsies: To look for persistent villous atrophy 4
4. Consider alternative diagnoses if villous atrophy persists:
   • Common variable immunodeficiency
   • Autoimmune enteropathy
   • Tropical sprue
   • Medication-induced enteropathy 4

By following this structured approach to celiac disease workup, clinicians can ensure accurate diagnosis, appropriate monitoring, and improved outcomes for patients with this common autoimmune condition.