A 38-year-old woman from rural Maharashtra presents with a 3-month history of progressive fatigue, dyspnea on exertion, and recurrent oral ulcers. On examination, she is pale with mild hepatosplenomegaly. Laboratory investigations reveal: Hb 7.2 g/dL, WBC 2800/μL, platelets 45,000/μL. Peripheral blood smear shows hypersegmented neutrophils and macro-ovalocytes. Serum vitamin B12 is 180 pg/mL (normal >200), and serum folate is 2.1 ng/mL (normal >5.4). Intrinsic factor antibodies are negative. Which is the most likely etiology of her pancytopenia?

Explanation

## Clinical Diagnosis: Tropical Sprue ### Key Clinical Features **Key Point:** Tropical sprue is an acquired malabsorptive disorder endemic to tropical regions (India, Caribbean, Southeast Asia) causing simultaneous B12 and folate deficiency. ### Diagnostic Reasoning | Feature | Tropical Sprue | Pernicious Anemia | Dietary Folate Deficiency | |---------|---|---|---| | **B12 level** | Low (malabsorption) | Low (intrinsic factor loss) | Normal | | **Folate level** | Low (malabsorption) | Normal or high | Low | | **IF antibodies** | Negative | Positive | Negative | | **Geographic risk** | Tropical endemic areas | Any region | Any region | | **Diarrhea/steatorrhea** | Common | Rare | Rare | | **Both B12 & folate low** | Yes | No | No | **High-Yield:** The simultaneous depression of both B12 and folate with negative intrinsic factor antibodies in a patient from an endemic tropical region is pathognomonic for tropical sprue. ### Pathophysiology 1. Chronic infection/inflammation of small intestine (exact etiology unclear; possibly bacterial overgrowth or persistent infection) 2. Damage to intestinal mucosa → impaired absorption of both B12 and folate 3. Results in megaloblastic anemia + pancytopenia (bone marrow suppression from dual deficiency) 4. Often associated with glossitis, diarrhea, and weight loss **Clinical Pearl:** Unlike pernicious anemia (which spares folate absorption), tropical sprue damages the entire intestinal mucosa, affecting absorption of multiple nutrients including both B12 and folate. ### Why This Patient? - Rural Maharashtra (tropical endemic region) ✓ - Both B12 AND folate low ✓ - Negative IF antibodies (rules out autoimmune pernicious anemia) ✓ - Hypersegmented neutrophils and macro-ovalocytes (megaloblastic pattern) ✓ - Oral ulcers and hepatosplenomegaly (systemic manifestations of tropical sprue) ✓ **Mnemonic:** **TROPICAL** — **T**ropical region, **R**educed both B12 and **F**olate, **O**ral ulcers, **P**ancytopenia, **I**ntrinsic factor antibodies negative, **C**hronic malabsorption, **A**cquired disorder, **L**ow hemoglobin.