ACD

Key Points

Anemia is common in rheumatoid arthritis (RA) and may constitute an important clinical problem for many patients. The two primary types of anemia in patients with RA are acd and iron deficiency anemia. Erythropoietin therapy in combination with iron supplementation corrects anemia in most patients with RA, and may improve RA outcomes and quality of life. Erythropoietin is useful in facilitating autologous blood donation prior to elective surgery for patients with RA and in reducing transfusion requirements.

acd

Anemia is the most common extra-articular manifestation of RA, estimated to occur in 30% to 60% of patients.17-19 Patients with RA who are anemic have evidence of more severe disease, with more involved joints and higher levels of functional disability and pain.19-21

Although any type of anemia may be seen in patients with RA, the two primary types of anemia in RA appear to be iron deficiency anemia and acd. In their retrospective review of 225 patients with RA, Peeters and colleagues identified 64% as anemic. Of the group classified as anemic, 77% were found to have acd and 23% to have iron deficiency anemia.19

Differential diagnosis may be difficult, as serum iron levels are low in both types of anemia, and bone marrow staining for iron stores may be required. However, serum ferritin testing usually distinguishes between iron deficiency and acd. Patients with serum ferritin levels >50 µg/mL are likely to have acd, while those with a lower value of serum ferritin are likely to be iron deficient.22-24

The most common causes of iron deficiency anemia in RA are blood loss through menstrual bleeding and/or gastrointestinal bleeding secondary to nonsteroidal anti-inflammatory drugs. ACD is an “inflammatory anemia,” and its features in RA are similar to those seen in inflammatory bowel disease, HIV, aging, and cancer.

Impact of Inflammatory Cytokines

Development of acd in patients with RA appears to be related to inflammatory cytokines, which cause joint inflammation and interfere with normal red blood cell formation and destruction.25-28

Patients with RA make erythropoietin in response to the inflammatory anemia, as expected. However, the response is blunted in these patients, with both inadequate production of erythropoietin and inadequate bone marrow responses compared to people with similar levels of anemia and no inflammation. Animal studies suggest that increased

levels of the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-µ (TNF-µ) inhibit erythropoietin production and interfere with erythroid colony-forming units in the bone marrow.28,31,32

Iron Supplementation

Iron supplementation is of great importance in patients who have iron deficiency. Furthermore, iron deficiency may occur concomitantly with acd.28,35 Iron repletion is almost always required as an adjunctive treatment to erythropoietin therapy, as erythroid production is increased.36-39