Diagnosis of Celiac Disease: Intestinal Biopsy is Required
The correct answer is B: Intestinal biopsy is required to confirm the diagnosis of celiac disease. 1
Diagnostic Algorithm for Celiac Disease
Initial Serological Testing
IgA tissue transglutaminase (TTG-IgA) is the preferred initial screening test for patients over 2 years old, with sensitivity of 90.7% and specificity of 87.4%. 1, 2
Total IgA levels must be measured simultaneously to identify selective IgA deficiency, which occurs in 1-3% of celiac patients and causes false-negative results on IgA-based tests. 1, 2, 3
In children under 2 years, combine TTG-IgA with deamidated gliadin peptide IgG and IgA to improve sensitivity. 1, 2
Confirmatory Biopsy is Mandatory
A diagnosis of celiac disease requires demonstration of histologic changes through upper endoscopy with small bowel biopsy—this is a critical component of evaluation. 1
Obtain at least 6 duodenal biopsies: 1-2 from the duodenal bulb and minimum of 4 from the distal duodenum or beyond. 1, 2
Biopsies must show characteristic findings: villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. 1, 2
Confirmation requires a combination of medical history, physical examination, serology, and histologic analysis—not serology alone. 1
Why the Other Options Are Incorrect
Option A is Wrong: Diagnostic Tests ARE Available
Multiple validated diagnostic tests exist for celiac disease, including serological markers (TTG-IgA, endomysial antibodies, deamidated gliadin peptides) and histological evaluation. 1, 4
Option C is Wrong: Serology Alone Cannot Confirm Diagnosis
Positive serology is not sufficient for diagnosis without biopsy confirmation in most adult patients. 1
The exception: In children with TTG-IgA >10 times upper normal limit AND positive endomysial antibodies in a second sample, biopsy may be avoided. 1, 2
In adults, even with very high TTG-IgA levels (>10x upper limit) combined with positive endomysial antibodies, endoscopy should still be performed for differential diagnosis purposes. 1
Option D is Wrong: Clinical Response Has Very Low Predictive Value
Improvement on a gluten-free diet or symptom exacerbation with gluten reintroduction has very low positive predictive value for celiac disease and should NOT be used for diagnosis without other supportive evidence. 1
Celiac disease overlaps with multiple gastrointestinal conditions including irritable bowel syndrome, lactose intolerance, microscopic colitis, and non-celiac gluten sensitivity. 1
Symptoms alone cannot differentiate celiac disease from these other disorders. 1
Critical Pitfalls to Avoid
Pre-Test Requirements
All testing (serology and biopsy) must be performed while the patient is consuming gluten—at least 10g daily (approximately 3 slices of wheat bread) for 6-8 weeks. 1, 3
Reduction or avoidance of gluten before testing significantly reduces sensitivity of both serology and biopsy. 1, 3
When to Consider Additional Testing
HLA-DQ2/DQ8 genetic testing has limited diagnostic role but high negative predictive value (>99% when both absent) for ruling out celiac disease in seronegative patients with villous atrophy. 1, 2
Use genetic testing when: serology and histology are discordant, patient already started gluten-free diet before diagnosis, or equivocal histologic findings exist. 1, 2