Anemia of chronic disease, increasingly referred to as "anemia of inflammation", is a form of anemia seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy. New discoveries suggest that the syndrome is likely primarily the result of the body's production of hepcidin, a master regulator of human iron metabolism.
Before the recent discovery of hepcidin and its function in iron metabolism, anemia of chronic disease was seen as the result of a complex web of inflammatory changes. Over the last few years, however, many investigators have come to feel that hepcidin is the central actor in producing anemia of chronic inflammation. Hepcidin offers an attractive Occam's Razor (parsimonious) explanation for the condition, and more recent descriptions of human iron metabolism and hepcidin function reflect this view.
Nonetheless, in addition to effects of iron sequestration, inflammatory cytokines promote the production of white blood cells. Bone marrow produces both red blood cells and white blood cells from the same precursor stem cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This effect may be an important additional cause for the decreased erythropoiesis and red blood cell production seen in anemia of inflammation, even when erythropoietin levels are normal, and even aside from the effects of hepcidin.
In the short term, the overall effect of these changes is likely positive: it allows the body to keep more iron away from bacterial pathogens in the body, while producing more immune cells to fight off infection. Bacteria, like most life forms, depend on iron to live and multiply. However, if inflammation continues, the effect of locking up iron stores is to reduce the ability of the bone marrow to produce red blood cells. These cells require iron for their massive amounts of hemoglobin which allow them to transport oxygen.
Because anemia of chronic disease can be the result of non-bacterial causes of inflammation, future research is likely to investigate whether hepcidin antagonists might be able to treat this problem.
Anemia of chronic disease as it is now understood is to at least some degree separate from the anemia seen in renal failure in which anemia results from poor production of erythropoietin, or the anemia caused by some drugs (like AZT, used to treat HIV infection) that have the side effect of inhibiting erythropoiesis. In other words, not all anemia seen in people with chronic disease should be diagnosed as anemia of chronic disease. On the other hand, both of these examples show the complexity of this diagnosis: HIV infection itself can produce anemia of chronic disease, and renal failure can lead to inflammatory changes that also can produce anemia of chronic disease.
While no single test is always reliable to distinguish the two causes of disease, there are sometimes some suggestive data:
If the importance of hepcidin in this condition is borne out, tests to measure hepcidin or cellular expression of ferroportin may one day be useful, but neither are available as validated clinical assays.
Examination of the bone marrow to look for the absence or presence of iron, or a trial of iron supplementation (pure iron deficiency anemia should improve markedly in response to iron, while anemia of chronic disease will not) can provide more definitive diagnoses.
The ideal treatment for anemia of chronic disease is to treat the chronic disease successfully. Barring that, many patients with anemia of chronic disease simply live with the effects of the anemia as part of enduring the limits placed on them by other aspects of their underlying medical conditions. In more severe cases, transfusions or several versions of commercially-produced erythropoietin can be helpful in some circumstances; both approaches are costly.
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