What is the most likely diagnosis for a young adult patient with chronic diarrhea, intermittent abdominal pain, macrocytic anemia (low Mean Corpuscular Volume (MCV)), low vitamin B12, and severely low folic acid levels, without a history of gastrointestinal (GI) bleeding?

Diagnosis: Celiac Disease

The most likely diagnosis is (A) Celiac disease, based on the combination of chronic diarrhea, macrocytic anemia with severely low folate and low vitamin B12, thrombocytosis, and absence of GI bleeding in a young adult. 1

Key Diagnostic Features Supporting Celiac Disease

Laboratory Pattern Analysis

• Macrocytic anemia (MCV 100 fL) with dual vitamin deficiency is characteristic of small bowel malabsorption, particularly celiac disease 1, 2
• Severely low folate (0.099 pmol/L, reference >0.1) is a sensitive indicator of proximal small bowel enteropathy, as folate is absorbed in the duodenum and proximal jejunum 3, 2
• Low vitamin B12 (0.074 nmol/L) combined with low folate strongly suggests diffuse small bowel involvement affecting both proximal (folate) and distal (B12) absorption sites 3, 2
• Thrombocytosis (540 × 10⁹/L) is a reactive finding commonly seen in celiac disease due to chronic inflammation and iron deficiency, even when anemia is macrocytic 3, 1
• Pallor without jaundice indicates chronic anemia from malabsorption rather than hemolysis 2

Clinical Presentation Alignment

• Chronic diarrhea is present in 43-85% of newly diagnosed celiac disease patients 1
• Celiac disease prevalence in patients with chronic diarrhea ranges from 3-10% in secondary care settings 1
• Small bowel biopsies reveal celiac disease in 2-3% of patients presenting with iron deficiency anemia, though this patient has macrocytic anemia suggesting more advanced malabsorption 1

Why Other Diagnoses Are Less Likely

Crohn's Disease (B) - Less Likely

• Crohn's disease typically causes vitamin B12 deficiency when the distal ileum is involved or resected, but isolated B12 deficiency without predominant folate deficiency would be expected 3
• Folate deficiency in Crohn's disease is less severe and usually secondary to medications (methotrexate) or reduced intake, not primary malabsorption 3
• The absence of bloody diarrhea, fever, or signs of obstruction/perforation makes inflammatory bowel disease less likely 3
• Crohn's disease would more typically present with focal or patchy inflammation, skip lesions, and potentially granulomas on biopsy 3

Ulcerative Colitis (C) - Unlikely

• Ulcerative colitis affects the colon, not the small bowel, where folate and B12 are absorbed 3
• Macrocytic anemia with dual vitamin deficiency indicates small bowel pathology, which UC does not cause 3
• UC typically presents with bloody diarrhea, which this patient lacks 3

Whipple's Disease (D) - Rare and Less Likely

• Whipple's disease is extremely rare and typically presents with additional features including joint inflammation, sun-exposed skin changes, and PAS-positive macrophages in lamina propria 3
• While it can cause malabsorption with vitamin deficiencies, the absence of systemic features (arthritis, neurologic symptoms, fever) makes this diagnosis unlikely 3

Recommended Diagnostic Approach

Immediate Serological Testing

• Tissue transglutaminase antibody (TTG IgA) with total IgA level is the recommended first-line test 1, 2
• If IgA deficient (occurs in 2.6% of celiac patients), obtain IgG-based tests (IgG TTG or IgG EMA) to avoid false-negative results 1, 2
• Endomysial antibody (EMA) has combined sensitivity and specificity over 90% 1

Endoscopic Confirmation

• Upper GI endoscopy with duodenal biopsies should be performed even if antibodies are negative, as 2-3% of patients with iron deficiency anemia have celiac disease despite negative serology 1
• Multiple biopsies from the second portion of the duodenum (minimum of 4-6 biopsies) are required for adequate sensitivity 3, 1

Baseline Malabsorption Screen

• Complete metabolic panel, liver function tests, calcium, ferritin, ESR, and CRP should be obtained 2
• Iron studies are essential even with macrocytic anemia, as mixed deficiency is common 3, 2
• Vitamin D (25-hydroxyvitamin D) should be checked, as deficiency occurs in 16-95% of patients with malabsorption 2

Critical Pitfalls to Avoid

• Do not start a gluten-free diet before completing diagnostic testing, as this will reduce the accuracy of both serologic and histologic results 3
• Do not overlook IgA deficiency when testing for celiac disease, as selective IgA deficiency occurs in 2.6% of celiac patients and causes false-negative IgA-based antibody tests 1, 2
• Do not assume normal ferritin excludes iron deficiency in the presence of inflammation—ferritin up to 100 μg/L may still indicate iron deficiency when transferrin saturation is <20% 3, 2
• Do not rely solely on vitamin levels to exclude celiac disease—the diagnosis requires histologic confirmation regardless of laboratory findings 1