What is the diagnosis and management for a patient with elevated TTG antibody IgA and gliadin antibody IgA?

Celiac Disease Diagnosis Based on Serology Results

The serologic profile with elevated TTG antibody IgA >250, gliadin antibody IgA >250, gliadin antibody IgG 126.4, normal IgA level of 98, and low TTG antibody IgG <1 is highly diagnostic for celiac disease and requires immediate referral to a gastroenterologist for intestinal biopsy confirmation and initiation of a gluten-free diet.

Interpretation of Serologic Results

• The markedly elevated TTG antibody IgA (>250) is the most sensitive and specific serologic marker for celiac disease, with sensitivity of 90-96% and specificity >95% 1
• Normal total IgA level (98) confirms that the elevated IgA-based antibody tests are valid and not falsely negative due to IgA deficiency 2
• The combination of elevated TTG antibody IgA and gliadin antibody IgA (both >250) significantly increases the likelihood of celiac disease 3
• TTG antibody IgA levels >10 times the upper limit of normal (as seen in this case) correlate strongly with the degree of intestinal damage 2
• The elevated gliadin antibody IgG (126.4) with normal IgA levels provides additional supportive evidence for celiac disease 4
• Low TTG antibody IgG (<1) is not concerning in the setting of normal IgA levels, as IgG-based tests are primarily useful in IgA-deficient patients 2

Diagnostic Algorithm

1. Confirm diagnosis with intestinal biopsy:

   • The American Gastroenterological Association recommends small bowel biopsy as the gold standard for establishing celiac disease diagnosis 5
   • Multiple biopsy specimens (ideally 6) should be obtained from the second part of the duodenum or beyond 5

2. Consider biopsy-free diagnosis in select cases:

   • Recent guidelines suggest that in some cases with TTG-IgA ≥10× upper limit of normal (as in this case), positive EMA-IgA, and positive HLA typing, biopsy might be avoided 1
   • However, this approach is more commonly accepted in pediatric populations 3

3. Maintain gluten-containing diet:

   • Testing and biopsy must be performed while the patient is on a gluten-containing diet to avoid false negative results 5, 1
   • Initiating a gluten-free diet before completing diagnostic evaluation can lead to inconclusive results 5

Management Approach

• Referral to gastroenterology: Patients with confirmed elevated TTG antibodies should be referred to a gastroenterologist for consultation and intestinal biopsy 2
• Gluten-free diet: After confirmation of diagnosis, patients should follow a strict gluten-free diet to prevent nutritional, metabolic, and oncologic consequences of celiac disease 2
• Nutritional consultation: Consultation with a registered dietitian experienced in managing celiac disease is essential 5
• Monitor for complications: Patients should be evaluated for common complications including malabsorption, nutritional deficiencies, and associated autoimmune conditions 2

Clinical Manifestations to Evaluate

• Gastrointestinal symptoms: diarrhea, abdominal pain, bloating, weight loss 2
• Extra-intestinal manifestations: fatigue, irritability, inability to concentrate, growth failure (in children) 2
• Nutritional deficiencies: iron deficiency anemia, osteoporosis, vitamin deficiencies 1
• Associated conditions: type 1 diabetes, autoimmune thyroid disease 1

Common Pitfalls to Avoid

• Initiating a gluten-free diet before completing diagnostic evaluation 5
• Relying solely on serology without biopsy confirmation, which can lead to misdiagnosis 5
• Failing to consider other causes of villous atrophy if clinical picture is atypical 5
• Inadequate biopsy sampling (fewer than 4-6 specimens) may lead to missed diagnosis 5