Celiac Panel Interpretation in the Context of Clinical Symptoms and Diagnostic Findings
A celiac panel should be interpreted by combining serologic test results with clinical symptoms and duodenal biopsy findings, with positive serology (particularly IgA-TTG and EMA) and villous atrophy on biopsy being diagnostic of celiac disease when the patient is on a gluten-containing diet. 1
Serologic Testing Components and Interpretation
Primary Serologic Tests
- IgA Tissue Transglutaminase (IgA-TTG): First-line test with high sensitivity (89%) and specificity (98%) 1, 2
- IgA Endomysial Antibodies (IgA-EMA): Excellent specificity (99%) and good sensitivity (90%) 2
- Total IgA level: Should be measured to rule out IgA deficiency 1
Secondary Tests
- IgG Tissue Transglutaminase (IgG-TTG): Use in IgA-deficient patients 1
- Deamidated Gliadin Peptide (DGP) IgA and IgG: Useful in IgA deficiency and in children under 2 years 1
Important: All serologic testing must be performed while the patient is on a gluten-containing diet to avoid false negatives 1
Diagnostic Algorithm Based on Serology and Biopsy
| Serology | Histology | Total IgA | HLA-DQ2/DQ8 | Interpretation |
|---|---|---|---|---|
| IgA-TTG/EMA positive | Villous atrophy | Normal | Not needed | Definite celiac disease |
| IgA-TTG/EMA positive | Increased IELs without villous atrophy | Normal | Positive | Probable celiac disease |
| IgA-TTG/EMA positive | Normal | Normal | Positive | Potential celiac disease |
| IgA-TTG/EMA negative | Villous atrophy | Normal | Positive | Unclear - Consider other causes of villous atrophy |
| IgA-TTG/EMA negative | Normal | Low/absent | Not needed | IgA deficient, not celiac |
| IgG-TTG/DGP positive | Villous atrophy | Low/absent | Positive | IgA deficient celiac disease |
Clinical Context for Interpretation
Symptoms to Correlate with Serology
- Classical symptoms: Diarrhea, steatorrhea, weight loss, abdominal pain, bloating
- Non-classical symptoms: Iron deficiency anemia, osteoporosis, abnormal liver function, dermatitis herpetiformis, neurological symptoms
- Note: Symptoms alone have poor sensitivity and specificity for diagnosis 2
Key Diagnostic Principles
- Confirm patient is on gluten-containing diet before testing 1
- Duodenal biopsy remains essential for adult diagnosis (≥1-2 biopsies from bulb and ≥4 from distal duodenum) 1
- Histologic findings should include villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis (≥25 IELs/100 enterocytes) 1
- HLA-DQ2/DQ8 testing is primarily useful to exclude celiac disease (>99% negative predictive value when both negative) 1
Interpreting Challenging Results
Seronegative Celiac Disease
- Consider when:
- Clinical symptoms suggestive of celiac disease
- Villous atrophy on biopsy
- HLA-DQ2/DQ8 positive
- Clinical and histologic response to gluten-free diet 1
Differential Diagnosis for Villous Atrophy with Negative Serology
- Common variable immunodeficiency
- Autoimmune enteropathy
- Tropical sprue
- Medication-induced enteropathy
- Small intestinal bacterial overgrowth
- Giardiasis
- H. pylori infection
- Crohn's disease
- Olmesartan use 1
Monitoring and Follow-up Interpretation
Assessing Response to Gluten-Free Diet
- Serologic tests typically normalize within 6-12 months on strict gluten-free diet
- Persistent positive serology suggests ongoing gluten exposure (40-50% of non-responsive cases) 1
- Consider testing for gluten immunogenic peptides in stool/urine to detect ongoing gluten ingestion 1
Refractory Celiac Disease Evaluation
When symptoms and villous atrophy persist despite strict gluten-free diet for ≥12 months:
- Type 1: Normal intraepithelial lymphocyte phenotype
- Type 2: Aberrant clonal T-cell population (requires flow cytometry and T-cell receptor gene rearrangement studies) 3
Common Pitfalls in Interpretation
- Testing while already on gluten-free diet: Can lead to false negatives 1
- Relying solely on symptoms: Poor predictors of disease 2
- Inadequate biopsy sampling: At least 4-6 samples needed for adequate sensitivity 1
- Ignoring IgA deficiency: Can cause false negative IgA-based tests 1
- Misinterpreting histology: Other conditions can mimic celiac histopathology 1
By systematically evaluating serologic tests in conjunction with clinical symptoms and biopsy findings, clinicians can accurately diagnose celiac disease and distinguish it from other conditions with similar presentations.