A 42-year-old man from Delhi with a 10-year history of celiac disease (on a gluten-free diet for 2 years) presents with progressive fatigue and dyspnea. His wife reports he has been eating wheat bread regularly for the past 6 months despite his diagnosis. Examination reveals glossitis and angular cheilitis. Laboratory findings: hemoglobin 8.5 g/dL, MCV 78 fL, serum B12 level 180 pg/mL (normal >200), serum folate 2.8 ng/mL (normal >5.4), serum ferritin 18 ng/mL, and reticulocyte count 0.8%. Peripheral blood smear shows hypersegmented neutrophils and microcytic RBCs. What is the primary mechanism of anemia in this patient?

Explanation

## Clinical Context: Celiac Disease Relapse This patient has **active celiac disease** (gluten re-exposure for 6 months) with intestinal villous atrophy causing **malabsorption of multiple micronutrients**. The anemia is multifactorial, not isolated iron or B12 deficiency. ## Laboratory Interpretation | Finding | Value | Significance | |---------|-------|---------------| | Hemoglobin | 8.5 g/dL | Moderate anemia | | MCV | 78 fL | **Microcytic** (not macrocytic) | | B12 | 180 pg/mL | Low-normal (borderline deficiency) | | Folate | 2.8 ng/mL | **Deficient** (<5.4) | | Ferritin | 18 ng/mL | **Depleted iron stores** | | Reticulocyte Count | 0.8% | Blunted response (inadequate) | | Hypersegmented Neutrophils | Present | Suggests B12/folate deficiency | | Microcytic RBCs | Present | Suggests iron deficiency | | Glossitis + Angular Cheilitis | Present | Signs of B12/folate deficiency | **Key Point:** The **microcytic MCV (78) is the critical clue** — pure B12 or folate deficiency alone would cause macrocytosis. The presence of BOTH microcytic and hypersegmented RBCs indicates **combined deficiency**. ## Pathophysiology of Malabsorption in Celiac Disease ```mermaid flowchart TD A[Gluten exposure in susceptible individual]:::outcome --> B[Intestinal villous atrophy]:::outcome B --> C[Reduced absorptive surface area]:::outcome C --> D1[Iron malabsorption<br/>Duodenum/Jejunum]:::action C --> D2[B12 malabsorption<br/>Terminal ileum]:::action C --> D3[Folate malabsorption<br/>Jejunum]:::action D1 --> E1[Iron deficiency anemia]:::outcome D2 --> E2[B12 deficiency<br/>Neurologic risk]:::outcome D3 --> E3[Folate deficiency]:::outcome E1 --> F[Combined deficiency anemia]:::urgent E2 --> F E3 --> F ``` ## Why This Is Combined Deficiency **High-Yield:** Celiac disease causes **pan-malabsorption** because villous atrophy affects the entire small intestine: 1. **Iron deficiency** (duodenum/proximal jejunum most affected) - Microcytic, hypochromic RBCs - Depleted ferritin (18 ng/mL) - Angular cheilitis, glossitis 2. **Folate deficiency** (jejunum) - Serum folate critically low (2.8) - Hypersegmented neutrophils - Glossitis, angular cheilitis 3. **B12 deficiency** (terminal ileum) - B12 borderline low (180) - Hypersegmented neutrophils - Risk of subacute combined degeneration if prolonged **Clinical Pearl:** The **microcytic MCV despite B12/folate deficiency** is a hallmark of combined deficiency — iron deficiency "wins" and lowers the MCV, masking the macrocytic tendency of B12/folate deficiency. This is why the blood smear is crucial (shows both microcytic AND hypersegmented RBCs). ## Management Implications **Warning:** Treating only B12 or folate without iron will fail. All three must be repleted: - Ferrous sulfate 200 mg daily - Cyanocobalamin 1000 µg IM monthly (or oral if compliance assured) - Folic acid 5 mg daily - **Strict gluten-free diet** (most important — allows mucosal healing) - Reassess at 4–6 weeks; expect Hb rise of 1–2 g/dL per month