Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic, autoimmune disease for which there is no known cure. It is a common disorder and affects more than 2.1 million Americans.

Because it is a systemic condition, it affects more than joints. Like other inflammatory conditions, RA causes anemia. The anemia is not the result of bleeding (although some patients treated with non-steroidal anti-inflammatory drugs can develop gastrointestinal bleeding), or deficiency of vitamin B12, folate, or iron.

This type of anemia is called the anemia of chronic disease (ACD).

Patients with RA who develop anemia are more likely to have more severe joint disease, worse quality of life indicators, and more severe disease.

As mentioned earlier, while m some patients with RA can develop an iron deficiency anemia as a result of non-steroidal anti-inflammatory drug therapy and subsequent gastrointestinal blood loss, most anemia (60%) associated with RA is due to ACD.

While it is difficult sometimes to differentiate iron deficiency anemia from ACD, there are laboratory characteristics that separate them. The key differentiating feature is that iron deficiency anemia is due to an absolute lack of iron. ACD is not due to iron deficiency- there's plenty of iron available; ACD is due to an inability to unlock the iron that is available.

Another complicating problem is that some patients with RA have both types of anemia.

ACD is due to systemic inflammation. The severity of ACD can be predicted by the amount of elevation of laboratory markers of inflammation such as the erythrocyte sedimentation rate ("sed rate") and the C- reactive protein (CRP).

In RA, many chemical mediators of inflammations, called cytokines, are overproduced. These cytokines inhibit the ability of iron stores to be used.

These inflammatory cytokines affect the production of red blood cells at different levels.

One inflammatory cytokine, interleukin-6 (IL-6) adversely affects iron utilization by causing increased production of hepcidin. Hepcidin is an inflammatory protein that prevents release of iron from cells called macrophages. It also reduces absorption of iron from the small intestine.

Other cytokines such as interferon-y and tumor necrosis factor (TNF) block the production of erythropoietin, a hormone that is critically needed for the production of red blood cells. In addition, TNF and interleukin-1 (IL-1) prevent the maturation of red blood cells.

The net effect is a marked reduction of iron available to make red cells.

Studies on anemia in rheumatoid arthritis have produced interesting data. Patients with ACD have more severe disease. If patients have a good response to RA treatment, the anemia improves at the same time. Some data exists that treatment of the ACD will also help improve the symptoms of RA.

The association of inflammatory mediators with the development of ACD indicates that anemia should be monitored during the course of therapy in patients with RA.

Newer biologic agents such as tocilizumab which block the effects of interleukin-6 may help with the resolution of ACD. Preliminary pilot data has shown that blockade of IL-6 in RA patients helps improve quality of life and improves fatigue coincident with the resolution of anemia.