What is the diagnostic approach for gluten intolerance?

Diagnosing Gluten Intolerance

The definitive diagnosis of gluten intolerance requires serological testing followed by duodenal biopsy while the patient is on a gluten-containing diet, with tissue transglutaminase IgA (tTG-IgA) being the primary initial screening test. 1

Diagnostic Algorithm for Gluten Intolerance

Step 1: Serological Testing

• Primary test: Tissue transglutaminase IgA (tTG-IgA)

  • Sensitivity: 90-96% in adults, 97.7% in children 1
  • Specificity: 87.4% in adults, 70.2% in children 1
  • Threshold: 15-20 U/mL 1

• Always check total serum IgA levels simultaneously to rule out IgA deficiency, which can cause false-negative results 1

• If IgA deficient:

  • Order IgG-based tests: IgG Deamidated Gliadin Peptide (IgG-DGP) or IgG tissue transglutaminase (IgG-tTG) 1
  • Note: IgG tTG alone has low diagnostic utility (3%) in non-IgA deficient patients 1

• Confirmatory serological test: IgA Endomysial Antibodies (EMA-IgA)

  • Sensitivity: 88% in adults, 94.5% in children 1
  • Specificity: 99.6% in adults, 93.8% in children 1
  • When a strongly positive tTG-IgA (>10x upper limit) is combined with positive EMA-IgA, the positive predictive value approaches 100% 2

Step 2: Endoscopy and Biopsy

• Upper endoscopy with multiple duodenal biopsies is required for definitive diagnosis 1
• Collect at least 6 biopsy specimens from both the duodenal bulb and distal duodenum 1
• Diagnostic histological findings:
  • Villous atrophy
  • Crypt hyperplasia
  • Increased intraepithelial lymphocytes (≥25 IELs/100 enterocytes)
  • Increased lamina propria lymphocytes 2, 1

Step 3: Genetic Testing (in specific scenarios)

• HLA-DQ2/DQ8 testing is not first-line but useful in:
  • Patients with Down syndrome
  • Equivocal small-bowel histological findings
  • Patients already on a gluten-free diet
  • Note: Negative HLA-DQ2/DQ8 virtually excludes celiac disease 1

Critical Considerations for Accurate Diagnosis

Pre-testing Requirements

• Maintain regular gluten consumption for at least 6 weeks prior to testing
• Consume 1-3 slices of gluten-containing bread daily before testing 1
• Premature gluten restriction can reduce lesion severity and lead to false-negative results 1

Diagnostic Pitfalls to Avoid

1. Inadequate biopsy sampling (less than 6 samples from different duodenal locations) can lead to missed diagnoses 1
2. Testing after starting a gluten-free diet significantly reduces test sensitivity 3
3. Relying solely on symptom improvement with gluten restriction is insufficient for diagnosis 1
4. Using antigliadin antibodies alone is no longer recommended for diagnosing classical celiac disease 4

Special Populations Requiring Screening

• Type 1 diabetes patients (5.4% prevalence of positive tTG-IgA) 1
• First-degree relatives of celiac disease patients 1
• Patients with other autoimmune disorders 1

Monitoring After Diagnosis

• Implement strict gluten-free diet under dietitian guidance 1
• Monitor tTG-IgA levels at 6 and 12 months after diagnosis, then yearly 1
• Persistently elevated levels suggest ongoing gluten exposure or poor diet adherence 1

Distinguishing Between Gluten-Related Disorders

• Celiac disease: Immune-mediated enteropathy with specific genetic genotype (HLA-DQ2/DQ8) and autoantibodies 5
• Non-celiac gluten sensitivity: Intestinal and/or extraintestinal symptoms related to gluten ingestion without celiac disease or wheat allergy; lacks validated biomarkers 5
• Wheat allergy: IgE-mediated immune response to wheat proteins 6

Remember that celiac disease is a systemic disorder that can present with gastrointestinal symptoms, extraintestinal manifestations, or both 5. Early diagnosis and treatment are crucial for preventing complications such as growth failure in children and unpredictable blood glucose levels in diabetic patients 1.