A 58-year-old Indian vegetarian man presents with progressive dyspnea and paresthesias. Laboratory findings show macrocytic anemia with hypersegmented neutrophils and a serum B12 level of 85 pg/mL (normal >200). What is the most common cause of megaloblastic anemia in this patient?

Explanation

## Most Common Cause of Megaloblastic Anemia Globally **Key Point:** Vitamin B12 deficiency is the most common cause of megaloblastic anemia worldwide, and pernicious anemia (autoimmune gastritis with anti-intrinsic factor antibodies) is the most common cause of B12 deficiency in developed countries. In India, dietary B12 deficiency is also prevalent in vegetarians. **High-Yield:** The clinical presentation of progressive dyspnea (anemia) + paresthesias (B12 neuropathy) + macrocytic anemia + hypersegmented neutrophils + low serum B12 is pathognomonic for B12 deficiency. ## Comparison of Megaloblastic Anemia Causes | Cause | Mechanism | Prevalence | Key Feature | |-------|-----------|-----------|-------------| | **B12 deficiency (pernicious anemia)** | Autoimmune gastritis → ↓ intrinsic factor | Most common globally | Neurologic symptoms (paresthesias, ataxia) | | Folate deficiency | Dietary inadequacy, malabsorption, drugs | Common in developing countries | No neurologic symptoms; pregnancy-related | | Methotrexate | Inhibits dihydrofolate reductase | Iatrogenic; less common | Reversible; associated with chemotherapy | | Nitrous oxide | Inactivates B12 cofactor | Rare; abuse-related | Acute presentation; reversible if caught early | **Clinical Pearl:** B12 deficiency causes both megaloblastic anemia AND subacute combined degeneration (SCD) of the spinal cord, presenting with paresthesias, ataxia, and loss of vibration/proprioception. Folate deficiency causes anemia alone without neurologic manifestations. **Mnemonic: B12 NEURO** — B12 deficiency → Neuropathy, Encephalopathy, Unsteadiness, Reflexes (hyperactive), Optic atrophy, Orthostatic hypotension ## Why B12 Deficiency Is Most Common 1. **Pernicious anemia** accounts for ~60% of B12-deficient megaloblastic anemia in Western populations 2. **Dietary B12 deficiency** is prevalent in vegetarians and vegans (no animal products) 3. **Malabsorption** (post-gastrectomy, Crohn's disease, tropical sprue) is common in developing countries 4. Folate deficiency, while common, is less frequent as a sole cause of megaloblastic anemia in clinical practice **Warning:** Do not confuse folate deficiency (common in pregnancy, alcoholism, malnutrition) with B12 deficiency. Folate deficiency does NOT cause neurologic symptoms; B12 deficiency does.