A 48-year-old Indian woman with a 10-year history of strict vegetarian diet presents with megaloblastic anemia. A 55-year-old man with chronic atrophic gastritis and intrinsic factor antibodies also has megaloblastic anemia. Which laboratory finding best distinguishes dietary B12 deficiency from pernicious anemia?

## Distinguishing Dietary B12 Deficiency from Pernicious Anemia **Key Point:** Both dietary B12 deficiency and pernicious anemia (autoimmune B12 deficiency) present with megaloblastic anemia and low B12 levels, but the **Schilling test** definitively differentiates them by identifying the mechanism of deficiency: inadequate intake vs. impaired absorption. ### Comparison Table | Feature | Dietary B12 Deficiency | Pernicious Anemia | | --- | --- | --- | | **Cause** | Inadequate dietary intake | Autoimmune destruction of parietal cells | | **Intrinsic factor antibodies** | Absent | Present | | **Parietal cell antibodies** | Absent | Present (60%) | | **Serum B12** | Low | Low | | **Methylmalonic acid** | Elevated | Elevated | | **Homocysteine** | Elevated | Elevated | | **Schilling test (stage 1)** | Normal absorption (corrected by IF) | Abnormal absorption | | **Schilling test (stage 2)** | Normal | Corrected by intrinsic factor | | **Gastric parietal cell atrophy** | Absent | Present | | **Achlorhydria** | Absent | Present | ### Why Schilling Test Is the Gold Standard? 1. **Mechanism identification:** Stage 1 (B12 alone) shows whether absorption is impaired. Stage 2 (B12 + intrinsic factor) determines if the defect is IF-related. 2. **In dietary deficiency:** Schilling stage 1 is **normal** (absorption is intact); stage 2 is also normal. The problem is intake, not absorption. 3. **In pernicious anemia:** Schilling stage 1 is **abnormal** (impaired absorption); stage 2 is **corrected by IF**, proving the defect is lack of intrinsic factor. 4. **Clinical Pearl:** The Schilling test is the only investigation that directly assesses the mechanism of B12 malabsorption and is diagnostic for pernicious anemia. **High-Yield:** Schilling test stage 2 correction = pernicious anemia (IF deficiency). No correction = other causes of malabsorption (ileal disease, pancreatic insufficiency). **Mnemonic:** **SCHILLING-IF** — Schilling test with intrinsic factor correction confirms pernicious anemia.