What is the best approach to diagnose and manage gluten sensitivity?

Diagnosis and Management of Gluten Sensitivity

The best approach to diagnose gluten sensitivity is to first rule out celiac disease through serologic testing (IgA tissue transglutaminase antibody) while the patient is on a gluten-containing diet, followed by duodenal biopsies if serology is positive, and then consider non-celiac gluten sensitivity only after celiac disease has been excluded. 1, 2

Diagnostic Algorithm for Gluten-Related Disorders

Step 1: Initial Serologic Testing (Patient Must Be on Gluten-Containing Diet)

• Primary test: IgA tissue transglutaminase antibody (tTG-IgA) 1, 2
• Check total serum IgA if tTG-IgA is negative but suspicion remains high 1, 2
• If IgA deficiency is present, order IgG-based tests:
  • IgG deamidated gliadin peptide (IgG-DGP) antibodies
  • IgG tissue transglutaminase (IgG-tTG) 2

Step 2: Endoscopic Evaluation

• Multiple duodenal biopsies are essential (at least 6 specimens) 1
  • 1-2 from duodenal bulb
  • At least 4 from distal duodenum 1
• Histologic findings in celiac disease:
  • Villous atrophy
  • Crypt lengthening
  • Increased intraepithelial lymphocytes 1

Step 3: HLA Testing (in Select Cases)

• HLA-DQ2/DQ8 testing has high negative predictive value (>99%) 1, 2
• 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

Step 4: Gluten Challenge (if needed)

• For patients already on gluten-free diet without prior diagnosis:
  • Resume normal diet with three slices of wheat bread daily for 1-3 months 1
  • Then repeat serologic testing 1

Diagnosing Non-Celiac Gluten Sensitivity (NCGS)

NCGS should only be considered after celiac disease and wheat allergy have been ruled out 1, 3, 4. The diagnosis requires:

1. Negative celiac serology and normal duodenal biopsies while on gluten-containing diet 3, 4
2. Improvement of symptoms on gluten-free diet
3. Recurrence of symptoms with gluten challenge 5, 6

Important caveat: Studies show only about 7% of patients self-reporting gluten-related symptoms actually have NCGS 5. Most patients (86%) reporting gluten sensitivity have neither celiac disease nor NCGS 5.

Management Approach

For Confirmed Celiac Disease:

• Strict, lifelong gluten-free diet 1, 2
• Follow-up serology at 6 months, 12 months, and annually thereafter 2
• Referral to dietitian with expertise in celiac disease 2
• Evaluation for nutritional deficiencies (iron, folate, vitamin B12, vitamin D) 2
• Endoscopic follow-up for patients with persistent symptoms despite adherence to gluten-free diet 1

For Non-Celiac Gluten Sensitivity:

• Gluten-free diet with periodic reassessment of gluten tolerance 6
• Unlike celiac disease, NCGS may be transient 6

Common Pitfalls to Avoid

1. Starting gluten-free diet before testing: This reduces sensitivity of both serology and biopsy 1, 2
2. Inadequate biopsy sampling: Celiac disease can present with patchy intestinal lesions 1
3. Relying solely on symptoms: Symptoms alone cannot differentiate celiac disease from NCGS 1, 4
4. Missing IgA deficiency: In IgA-deficient patients, standard tTG-IgA will be falsely negative 1, 2
5. Overdiagnosis of NCGS: Most self-reported gluten sensitivity is not true NCGS 5

By following this systematic approach, clinicians can accurately diagnose and appropriately manage patients with suspected gluten-related disorders, improving morbidity, mortality, and quality of life outcomes.