Diagnostic Steps and Treatment Options for Celiac Disease
The diagnosis of celiac disease requires IgA tissue transglutaminase antibody (tTG-IgA) testing while the patient is on a gluten-containing diet, followed by intestinal biopsy for confirmation, and treatment consists of a strict lifelong gluten-free diet. 1
Diagnostic Algorithm
Initial Serologic Testing
- IgA tissue transglutaminase antibody (tTG-IgA) is the preferred initial screening test with high sensitivity (90-96%) and specificity (>95%) 2, 1
- Testing must be performed while the patient is on a gluten-containing diet (at least 10g daily for 6-8 weeks) to avoid false-negative results 1, 2
- Total IgA levels should be measured to rule out IgA deficiency, particularly in high-risk patients or when celiac disease is strongly suspected despite negative tTG-IgA 2, 1
- In IgA-deficient patients, IgG-based tests should be used (IgG deamidated gliadin peptide or IgG tTG) 2, 1
Confirmatory Testing
- Upper endoscopy with small intestinal biopsy remains the gold standard for diagnosis in adults 2, 1
- Multiple duodenal biopsies (at least 4-6 specimens) should be taken from the second part of the duodenum or beyond 2, 1
- Characteristic histologic findings include villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes 2, 1
- In adults with tTG-IgA >10x upper limit of normal plus positive endomysial antibody (EMA-IgA), the positive predictive value approaches 100%, though biopsy may still be performed for differential diagnosis 2, 1
Special Testing Considerations
- HLA-DQ2 and HLA-DQ8 testing has high negative predictive value (>99%) and is useful when celiac disease is strongly suspected despite negative serology 2, 1
- IgG isotype testing for tTG antibody is not specific in the absence of IgA deficiency 2, 1
- Lymphocytic infiltration of the intestinal epithelium without villous atrophy is not specific for celiac disease, and other causes should be considered 2
Treatment Approach
Gluten-Free Diet
- A strict, lifelong gluten-free diet is the only effective treatment for celiac disease 2, 1
- Patients should be referred to a dietitian experienced in celiac disease management 1, 3
- The diet requires elimination of wheat, barley, and rye 3, 4
- Improvement of symptoms after initiating a gluten-free diet has a low positive predictive value for celiac disease and should not be used for diagnosis without supportive evidence 2, 4
Monitoring Response to Treatment
- Follow-up serology should be performed at 6 and 12 months after diagnosis, and yearly thereafter 1, 4
- Negative serology after treatment does not guarantee intestinal mucosal healing 1, 4
- Persistently positive serology usually indicates ongoing intestinal damage and continued gluten exposure 1, 5
- Patients with persistent or relapsing symptoms should undergo repeat endoscopic biopsies to determine healing 1, 4
High-Risk Groups to Consider Testing
- First-degree relatives of patients with celiac disease 2, 1
- Patients with type 1 diabetes mellitus 2, 1
- Patients with unexplained iron deficiency anemia 2, 1
- Patients with premature osteoporosis 2, 1
- Patients with autoimmune thyroid disease 2, 1
- Patients with unexplained liver transaminase elevations 2, 1
- Patients with Down syndrome 2, 1
- Patients with unexplained infertility or recurrent miscarriage 2
Common Pitfalls in Diagnosis and Management
- Initiating a gluten-free diet before completing diagnostic testing can lead to false-negative results 1, 2
- Relying solely on serology without biopsy confirmation can lead to misdiagnosis 2, 1
- Antibodies directed against native gliadin are no longer recommended for primary detection 2, 6
- Seronegative celiac disease can occur and requires biopsy for diagnosis 1, 7
- Improvement of symptoms on a gluten-free diet alone is insufficient for diagnosis 2, 4
- Patients who have already started a gluten-free diet prior to diagnosis should resume a normal diet with gluten intake for 1-3 months before repeat testing 1, 7