Description

• Otherwise known as anemia of chronic inflammation
• During chronic systemic infection, inflammation, or malignancy, the production of proinflammatory mediators causes inhibition of erythropoiesis as well as the imbalance in iron homeostasis (1).
• A normocytic, normochromic, hypoproliferative anemia and classically has low serum iron levels, decreased total iron-binding capacity (TIBC), and elevated ferritin levels (1)
• Anemia is typically mild to moderate with hemoglobin (Hgb) rarely <8 g/dL.

Epidemiology

Prevalence
Anemia of chronic disease (ACD) is the second most common anemia after iron-deficiency anemia (IDA). Worldwide, estimates suggest up to 40% of all anemias can be considered from ACD or with ACD as a contributing factor, affecting >1 billion individuals.

Etiology and Pathophysiology

• Production of red blood cells is decreased as a result of functional iron deficiency.
• Three major pathways are involved as a result of proinflammatory cytokines: iron restriction, inflammatory suppression of erythropoietin (EPO), and decreased erythrocyte survival (2).
• Iron overload and the proinflammatory cytokines IL-1, IL-6, and BMP6 increase the production of the iron-regulating hormone hepcidin (1).
  • Hepcidin binds to ferroportin causing internalization and degradation, preventing efflux of iron from stores in macrophages and hepatocytes.
  • Hepcidin decreases iron absorption by duodenal enterocytes.
  • Newer studies show hepcidin may directly block iron export and limit erythropoiesis (2).
• EPO production and the response to EPO by erythroid bone marrow is suppressed by proinflammatory cytokines such as IL-1, TNF-α, and IFN-γ (1).
• Inflammatory cytokines may also cause erythrophagocytosis and oxidative damage, reducing RBC survival.
• It is unclear if the severity of anemia corresponds to the severity of disease.

Risk Factors

Hepatic disease, renal disease, infections, autoimmune causes (see “Commonly Associated Conditions”)

General Prevention

Prevention of ACD involves timely identification and treatment of the underlying condition.

Commonly Associated Conditions

• Chronic inflammatory diseases
  • Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, temporal arteritis, inflammatory bowel disease (IBD)
• Cancer and hematologic malignancies
• Hepatic disease or failure
• Congestive heart failure or coronary artery disease
• Chronic kidney disease (CKD)
• Chronic obstructive lung disease
• Acute or chronic infections
  • Viral
    • HIV, HCV
  • Bacterial
    • Abscess, subacute bacterial endocarditis, tuberculosis, osteomyelitis
  • Fungal
  • Parasitic
• Malignancies
• Cytokine dysregulation (anemia of aging)
• Hypometabolic states
  • Protein malnutrition, thyroid disease, panhypopituitarism, diabetes mellitus, Addison disease