What is the next step after a positive Tissue Transglutaminase (TTG) test?

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Last updated: February 17, 2025 • View editorial policy

From the Guidelines

Following a positive tissue transglutaminase (tTG) result, indicative of celiac disease, the next step involves referral for intestinal biopsy to confirm the diagnosis, as recommended by the National Institute for Health and Care Excellence guidelines 1.

Diagnosis Confirmation

  • The biopsy is essential to assess the degree of intestinal damage and to rule out other potential causes of symptoms, as some conditions may mimic celiac disease, such as immune disorders, autoimmune diseases, and infections 2.
  • In some cases, particularly in children, a biopsy-avoidance strategy may be considered if the tTG levels are significantly elevated and other criteria are met, such as positive endomysial antibodies (EMA) and HLA-DQ2 or HLA-DQ8 positivity 1, 2.

Management

  • If the biopsy confirms celiac disease, the patient should be advised to initiate a strict gluten-free diet, avoiding all foods containing wheat, barley, and rye, for a minimum of 6-12 months to allow for intestinal mucosal healing 3, 4.
  • Additionally, supplementation with ferrous sulfate (65 mg orally, twice daily) and folate (1 mg orally, daily) may be recommended for a period of 6-12 months to address potential iron and folate deficiencies.
  • It is essential to note that reduction or avoidance of gluten prior to diagnostic testing should be discouraged, as it may reduce the sensitivity of both serology and biopsy testing 4.
  • Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of celiac disease but may be useful in ruling out the condition in seronegative patients with histologic changes or in patients with a historic diagnosis of celiac disease 4.

From the Research

Next Steps After a Positive Tissue Transglutaminase (TTG) Test

  • A positive TTG test is a strong indicator of celiac disease, and the next step is typically to confirm the diagnosis through an intestinal biopsy 5.
  • The biopsy is used to assess the degree of mucosal damage and to confirm the presence of villous atrophy, which is a characteristic feature of celiac disease 5, 6.
  • In some cases, a duodenal biopsy may not be necessary if the patient has a high titer of anti-TTG antibodies and is symptomatic, as the positive predictive value of the test is nearly 100% 5.
  • After confirmation of the diagnosis, the patient should be advised to follow a strict gluten-free diet, which is the only currently available treatment for celiac disease 7, 8.
  • Regular follow-up appointments and monitoring of the patient's symptoms and serology tests, including TTG antibodies, are necessary to assess the effectiveness of the treatment and to detect any potential complications 6, 8.

Importance of TTG Test in Celiac Disease Diagnosis

  • The TTG test is a sensitive and specific marker for celiac disease, with a high positive predictive value 5, 8.
  • The test can be used to diagnose celiac disease in patients with symptoms and to monitor their response to treatment 8.
  • However, the test is not 100% sensitive or specific, and a negative result does not rule out the possibility of celiac disease 8.
  • Therefore, a combination of clinical evaluation, serology tests, and intestinal biopsy is often necessary to confirm the diagnosis of celiac disease 5, 6, 8.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.