What is the best approach to diagnose celiac disease in a 30-year-old female patient with iron deficiency anemia and gastrointestinal symptoms, and negative autoimmune and tick panel results?

Celiac Disease Diagnosis in Iron Deficiency Anemia with GI Symptoms

Begin with celiac serology (tissue transglutaminase IgA antibody with total IgA level) immediately, and if positive, proceed to upper endoscopy with duodenal biopsies for histologic confirmation. 1

Diagnostic Algorithm for This Patient

Step 1: Celiac Serology First

• Order tissue transglutaminase IgA (TTG-IgA) with total IgA level as your initial test 2, 3, 4
• This strategy is cost-effective and diagnoses the majority of celiac disease cases with minimal harm 1
• Celiac disease accounts for 2-5% of iron deficiency anemia cases, even in asymptomatic patients, and your patient has the added risk factor of gastrointestinal symptoms 2, 5
• A ferritin <45 ng/mL should be confirmed to establish true iron deficiency 3, 4

Step 2: Interpretation and Next Steps

• If TTG-IgA is positive: Proceed directly to upper endoscopy with duodenal biopsies from multiple sites (at least 4-6 samples from the second and third portions of duodenum) for histologic confirmation 1, 6, 7
• If TTG-IgA is negative but clinical suspicion remains high: Consider that this patient has gastrointestinal symptoms AND iron deficiency anemia, which increases pre-test probability 1
• The AGA guidelines note that celiac disease should be reconsidered if iron deficiency persists despite adequate iron supplementation, even with initially negative serology 1

Step 3: Consider Bidirectional Endoscopy Regardless

Given this patient's presentation (30-year-old female with both GI symptoms AND iron deficiency anemia), you should strongly consider proceeding to bidirectional endoscopy even if celiac serology is negative. 2, 3

Here's why this matters:

• The AGA recommends bidirectional endoscopy for premenopausal women with iron deficiency anemia as a conditional recommendation 2, 3
• Your patient has the additional high-risk feature of gastrointestinal symptoms, which shifts the risk-benefit balance toward routine small bowel biopsies 1
• Upper endoscopy identifies bleeding sources in 30-50% of patients with iron deficiency anemia 2
• Dual pathology (lesions in both upper and lower GI tracts) occurs in 10-15% of cases 2

Step 4: What to Do During Upper Endoscopy

• Obtain duodenal biopsies routinely from the second and third portions of the duodenum, even if the mucosa appears normal 2, 6
• Take biopsies from multiple sites (at least 4-6 samples) to maximize diagnostic yield 6, 7
• If the duodenum appears abnormal visually, biopsies are mandatory regardless of serologic results 1

Important Clinical Caveats

Why Serology-First Makes Sense in Most Cases

• The strategy of serologic testing followed by biopsy only if positive is cost-saving compared to routine small bowel biopsies at endoscopy 1
• TTG-IgA has 90% sensitivity and when combined with other serologic markers approaches 100% sensitivity 5
• However, this cost-benefit analysis assumes celiac disease prevalence <5% in the population being tested 1

When to Go Straight to Endoscopy with Biopsies

Your patient may warrant direct endoscopy with biopsies based on shared decision-making because: 1

• She has gastrointestinal symptoms (not just isolated anemia) 1
• The combination of GI symptoms and iron deficiency anemia increases the pre-test probability of celiac disease 5, 8
• Screening studies show 1 in 44 anemic patients has celiac disease compared to 1 in 498 nonanemic controls 8
• Iron deficiency anemia is the most frequent presenting feature of celiac disease in adults 5, 8

Critical Pitfall to Avoid

• Do not rely on isolated TTG-IgG testing if TTG-IgA is negative—the utility is only 3% for diagnosing celiac disease 9
• Always check total IgA level with TTG-IgA, as IgA deficiency occurs in celiac disease and will cause false-negative TTG-IgA results 6, 9
• If IgA deficiency is present, you must proceed to biopsy or use IgG-based testing 6, 9

Follow-Up Considerations

• If initial serology is negative but iron deficiency persists despite adequate iron supplementation, reconsider celiac disease and proceed to endoscopy with biopsies 1
• Never accept upper GI findings (esophagitis, erosions, peptic ulcer) as the sole cause without completing colonoscopy, as dual pathology is common 2