Anemia of Chronic Disease

Also see Anemia: General Considerations.

Definition, Etiology, PathogenesisTop

Anemia of chronic disease (ACD) (also termed anemia of inflammation) is caused by decreased red blood cell (RBC) production due to an activated cellular immune response, increased production of proinflammatory cytokines, and hepcidin. It is the second or third most common cause of anemia after iron deficiency anemia and possibly thalassemia. Incidence increases with age and in patients with acute or chronic inflammatory conditions.

Causes: Acute or chronic infections, malignancy, autoimmune diseases (most frequently rheumatoid arthritis, systemic lupus erythematosus, and vasculitis syndromes), occult inflammatory conditions, selected drug therapies (eg, interferon).

Clinical Features and Natural History Top

ACD usually manifests within a few months of the development of the underlying condition. Clinical manifestations include signs and symptoms of the underlying condition as well as general symptoms of anemia.

DiagnosisTop

Diagnostic Tests

1. Complete blood count (CBC) (see Table 1 in Iron Deficiency Anemia, see Table 2 in Iron Deficiency Anemia), normal or low reticulocyte count, normal red cell distribution width.

2. Parameters of iron metabolism: see Table 1 in Iron Deficiency Anemia, see Table 2 in Iron Deficiency Anemia.

3. Other tests: Abnormalities caused by the underlying condition, frequently increased levels of the markers of inflammation. Endogenous erythropoietin levels do not correspond to the severity of anemia. Serum transferrin receptor (sTfR) is a protein that can be assayed in the blood in some centers. It generally should be normal in patients with ACD and increased in patients with iron deficiency anemia. Consider vitamin B12, thyroid-stimulating hormone (TSH), creatinine, and liver function testing.

Diagnostic Criteria

ACD is typically a normocytic and normochromic anemia. Other causes of anemia (particularly iron deficiency) should be excluded.

Differential Diagnosis

Iron deficiency anemia (see Table 1 in Iron Deficiency Anemia), other types of anemia (see Table 1 in Anemia: General Considerations).

Treatment Top

1. Treatment of the underlying condition.

2. Severe symptomatic anemia: Transfusion of packed red blood cells (PRBCs).

3. Patients with anemia in the course of anticancer chemotherapy and selected other patients with low serum erythropoietin levels: Consider the use of an erythropoiesis-stimulating agent (ESA): subcutaneous human recombinant erythropoietin alpha 40,000 IU once weekly, subcutaneous human recombinant erythropoietin beta 30,000 IU once weekly, or subcutaneous darbepoetin 500 microg every 3 weeks. Doses are titrated to increase hemoglobin to the lowest level sufficient to avoid PRBC transfusion. Contraindications and adverse effects: see Chronic Kidney Disease.

4. Absolute or relative iron deficiency may be observed in some patients with ACD and should be treated with oral or IV iron. Controversy exists regarding what ferritin and transferrin saturation level should be provided. In patients with underlying inflammation, maintain the level of transferrin saturated with iron >20%; ferritin levels may appear normal as a result of functional iron deficiency (iron-restricted erythropoiesis) and therefore may not be reflective of iron status. However, a low serum ferritin level is an absolute indication for iron therapy (see Iron Deficiency Anemia).