1.1. Anemia of Chronic Disease (ACD), or the anemia of inflammation, is a mild to moderate anemia accompanying infectious, inflammatory, or neoplastic disease that is characterized by abundant reticuloendothelial iron unavailable to bone marrow erythroid precursors.
2. Diagnosis
2.1. The diagnosis of ACD can be difficult, especially if it coexists with iron deficiency. Other contributing causes of anemia should be ruled out, including blood loss, malnutrition, folate or vitamin B12 deficiency, and hemolysis. Myelodysplastic syndrome frequently masquerades as ACD until it progresses, and the threshold for performing a bone marrow biopsy should be low, particularly for those in older age groups or in the absence of an obvious chronic disease. This was recently demonstrated in a study of anemia in patients with rheumatoid arthritis, a prototypical ACD. A large percentage (45%) of the anemic patients, however, were found to be iron deficient. Of these approximately 10% were found to have a malignant or premalignant lesion of the GI tract.14 Laboratory findings of ACD include a mild to moderate anemia with normocytic or slightly microcytic indices, reduced serum iron and TIBC (transferrin) levels, and increased ferritin level, reflecting the increase in iron stores (Table 4). Although the serum ferritin level is useful when there is no accompanying inflammation, it is influenced by acute phase responses. The soluble transferrin receptor (TFR) is present in human plasma and its concentration is determined by marrow erythroid activity and iron status. Its synthesis is induced by iron deprivation, so in iron-deficient states the level of TFR rises. The TFR concentration is not increased with infection or inflammation, providing a way of differentiating iron deficiency from ACD. Patients who have a combination of iron deficiency and an infectious, inflammatory, or malignant disorder may be more accurately diagnosed by the TFR-ferritin index (TFR concentration divided by the log of the ferritin concentration; see Table 4). This index has been found to be a useful tool in identifying iron deficiency in patients with rheumatoid arthritis.14 Theoretically, hepcidin levels should be elevated in ACD, and correlate with elevations in proinflammatory markers. Some but not all studies have demonstrated such a correlation.15–17 Further investigation will be required before we have a sensitive and specific marker for the diagnosis of chronic disease anemia.
