What are the steps for testing and managing gluten intolerance?

Testing and Managing Gluten Intolerance

The gold standard for diagnosing celiac disease requires a combination of serological testing (primarily IgA tissue transglutaminase antibody) and intestinal biopsy, with testing performed while the patient is on a gluten-containing diet. 1

Diagnostic Approach for Gluten-Related Disorders

Initial Serological Testing

1. Primary Test: IgA tissue transglutaminase antibody (tTG-IgA)

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

2. Total IgA level measurement

   • Essential to rule out IgA deficiency (affects 2-3% of celiac patients)
   • For IgA-deficient patients, use IgG-tTG or IgG deaminated gliadin peptides (DGP) 2, 1

3. Confirmatory Tests (if tTG-IgA is positive):

   • IgA endomysial antibody (EMA-IgA)
   • Sensitivity: 94.5% in children
   • Specificity: 93.8% in children 1
   • EMA testing significantly improves diagnostic accuracy (positive predictive value of 85% vs 45% for tTG alone) 3

4. IgA against deamidated gliadin peptide (DGP-IgA) 2

Important Testing Considerations

• Testing must be performed while on a gluten-containing diet
• If already on gluten-free diet, a gluten challenge with three slices of wheat bread daily for 1-3 months before testing is recommended 1
• Do NOT use: stool studies, small-bowel follow-through, intestinal permeability testing, D-xylose testing, salivary testing, or skin testing 1

Endoscopic Evaluation and Biopsy

1. Multiple biopsies (at least 6 specimens) are essential due to patchy distribution of intestinal damage 1
2. Histological findings to look for:
   • Villous atrophy
   • Crypt hyperplasia
   • Intraepithelial lymphocytosis (≥25 IELs per 100 enterocytes) 1

Genetic Testing

• HLA-DQ2/DQ8 testing has high negative predictive value (>99%)
• Useful in:
  • Patients with negative serology but strong clinical suspicion
  • Patients already on gluten-free diet without prior testing
  • Patients with equivocal biopsy results 1
• Negative results can effectively rule out celiac disease in seronegative patients 2

Differential Diagnosis

Seronegative Enteropathy

• Review medication history (especially angiotensin II receptor blockers like olmesartan)
• Consider travel history to identify potential causes of villous atrophy
• Review histologic findings with experienced GI pathologists 2

Non-Celiac Gluten Sensitivity (NCGS)

• Consider after celiac disease has been ruled out
• Diagnosis requires:
  • Negative celiac serology
  • Normal duodenal biopsies while on gluten-containing diet
  • Improvement of symptoms on gluten-free diet
  • Recurrence of symptoms with gluten challenge 1, 4

Management Approach

For Confirmed Celiac Disease

1. Strict, lifelong gluten-free diet

   • Complete elimination of wheat, rye, and barley
   • Careful attention to hidden sources of gluten 1

2. Expert Support

   • Referral to a dietitian with expertise in celiac disease
   • Patient education and support groups 1

3. Monitoring

   • Serological monitoring with anti-TG2 antibodies at 6,12 months, and annually thereafter
   • Clinical assessment including evaluation for symptom resolution, nutritional status, and weight management
   • Evaluation for nutritional deficiencies (iron, folate, vitamin B12, vitamin D) 1

For Seronegative Celiac Disease

1. Follow-up endoscopic evaluation after 1-3 years on a gluten-free diet to assess improvement in villous atrophy
2. Confirm diagnosis based on clinical and histologic markers of improvement on the gluten-free diet 2

For Persistent Symptoms Despite Treatment

• For patients with identified cause of enteropathy: treat accordingly
• For patients with persistent symptoms despite adherence to gluten-free diet and no identified etiology: consider budesonide treatment 2
• Consider refractory celiac disease if symptoms and villous atrophy persist despite strict gluten-free diet 1

Common Pitfalls and Caveats

1. False negatives in serological testing

   • IgA deficiency can lead to false-negative tTG-IgA results
   • Serological tests have low sensitivity (below 50%) for detecting persistent villous atrophy in patients already on gluten-free diets 5

2. Inadequate biopsy sampling

   • Patchy distribution of intestinal damage can lead to false negatives with insufficient sampling
   • Multiple biopsies (at least 6) are essential 1

3. Testing while on gluten-free diet

   • Can lead to false-negative results
   • Proper gluten challenge is necessary before testing 1

4. Monitoring limitations

   • Negative serology does not guarantee intestinal healing
   • Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure 1

5. Misdiagnosis of NCGS

   • NCGS should only be considered after celiac disease has been ruled out
   • Requires standardized double-blind, placebo-controlled gluten challenge for definitive diagnosis 4