Description

Anemia of chronic disease (ACD) is a normocytic, normochromic, hypoproliferative anemia associated with infectious, neoplastic, and inflammatory processes. The chronic immune activation accompanying these processes results in the production of inflammatory cytokines, which creates an anemic state by interfering with iron homeostasis and impairing erythropoiesis. ACD is the second most common type of anemia and is the most common anemia found in hospitalized patients (1).

Epidemiology

Incidence
Incidence of anemia in cancer: 30–90% (2)

Prevalence
The estimated reports of ACD prevalence for individual conditions vary widely in the literature.

Pathophysiology

Inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-6) released by cells of the immune system in the setting of malignant, autoimmune, or infectious disease are the major mediators of anemia in ACD. They exert their effects in 3 main ways:

• Disrupted iron homeostasis:
  • Chronic inflammation, infection, malignancy → ↑ IFN-γ, LPS, TNF-α → ↑ iron uptake by and ↓ iron release from reticuloendothelial system (RES) cells → ↓ iron availability for heme biosynthesis and RBC production in the bone marrow
  • Chronic inflammation, infection, malignancy → ↑ IL-6, LPS → ↑ hepatocyte production of hepcidin, a major negative iron regulator → ↓ iron absorption in duodenum and ↓ iron release from RES cells → ↓ iron availability for RBC production
• Impaired erythropoiesis:
  • ↑ IFN-γ, TNF-α, IL-1 → down regulation of erythropoietin (EPO) receptors on erythroid precursors, cytokine-induced apoptosis of erythroid precursors, ↓ hematopoietic growth factors in the marrow → impaired function, proliferation, and differentiation of erythroid cells → ↓ RBC production
  • ↑ IFN-γ, TNF-α, IL-1 → ↓ synthesis and diminished effect of EPO → ↓ RBC production
• RBC destruction:
  • ↑ TNF-α, IL-1 → ↑ phagocytosis of RBCs by RES cells → ↓ RBC half-life
  • ↑ IFN-γ, TNF-α, IL-1 → ↑ free radical formation → ↑ RBC destruction

Etiology

Inflammatory cytokines (e.g., TNF-α, IFN-γ, IL-6) released by cells of the immune system in the setting of infectious, inflammatory, or neoplastic diseases cause anemia by interfering with iron metabolism and RBC production.

Commonly Associated Conditions

• Autoimmune disease:
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Inflammatory bowel disease
  • Sarcoidosis
  • Vasculitis
• Infectious disease:
  • HIV and other viral infections
  • Chronic or subacute bacterial, fungal, parasitic infection
• Neoplastic disease:
  • Both solid and hematologic tumors
• Chronic kidney disease (CKD)
• Chronic rejection post solid-organ transplantation