- Pathophysiology/Etiology
- Anemia resulting from chronic inflammatory states (e.g., autoimmune diseases like RA, chronic infections like TB, malignancies, or chronic kidney disease).
- Key mediator: Hepcidin. An acute-phase reactant produced by the liver in response to inflammatory cytokines (esp. IL-6).
- Mechanism: ↑ Hepcidin → binds to and degrades ferroportin (iron exporter) on enterocytes and macrophages → ↓ intestinal iron absorption & ↓ iron release from macrophage stores (iron sequestration).
- This leads to functional iron deficiency: adequate total body iron stores, but iron is unavailable for erythropoiesis.
- Inflammatory cytokines also suppress erythropoietin (EPO) production and bone marrow response to EPO.
- Clinical Presentation
- Symptoms of anemia (fatigue, pallor, SOB) are often mild and may be overshadowed by the underlying chronic disease.
- Associated with chronic inflammatory conditions, infections, or cancer.
- Anemia is typically mild to moderate, with Hb rarely < 8 g/dL.
- Diagnosis
- CBC: Initially normocytic, normochromic anemia. Can become microcytic over time as iron-restricted erythropoiesis persists.
- Iron Studies (Classic Pattern):
- ↓ Serum Iron
- ↓ Total Iron-Binding Capacity (TIBC) / Transferrin
- ↑/Normal Serum Ferritin (an acute phase reactant, reflects high iron stores).
- ↓ Transferrin Saturation (% sat)
- Low reticulocyte count for the degree of anemia.
- Elevated inflammatory markers (e.g., CRP, ESR).
- DDx (Differential Diagnosis)
- Iron Deficiency Anemia (IDA): The key differential. Can also coexist with ACD.
- IDA vs. ACD: In IDA, TIBC is high and ferritin is low. In ACD, TIBC is low and ferritin is high/normal.
- A serum ferritin <100 ng/mL in an inflammatory state suggests concomitant IDA.
- Thalassemia: Microcytic anemia with normal/high iron studies; diagnosed via Hb electrophoresis.
- Sideroblastic Anemia: Can be microcytic; diagnosed by ring sideroblasts on bone marrow biopsy.
- Management/Treatment
- Primary goal: Treat the underlying chronic disease. This is the most effective long-term strategy.
- Iron supplementation is generally not effective and avoided unless true co-existing iron deficiency is confirmed, as the issue is iron utilization, not absolute deficiency.
- Erythropoiesis-stimulating agents (ESAs) (e.g., recombinant erythropoietin) may be used for anemia of CKD or chemotherapy-induced anemia.
- RBC transfusions for severe, symptomatic anemia (e.g., Hb < 7-8 g/dL or hemodynamic instability).
- Key Associations/Complications
- Associated Conditions: Rheumatoid arthritis (RA), SLE, inflammatory bowel disease (IBD), chronic kidney disease (CKD), chronic infections (TB, HIV), and malignancy.
- Buzzwords: “Anemia of inflammation,” high hepcidin, sequestered iron, low TIBC, high ferritin.