Iron-deficiency anemia most commonly develops as a consequence of blood loss. This can happen due to a number of factors, including gastrointestinal malignancy or severe menstruation. Certain diseases that are more common in rheumatic patients also increase the risk of iron-deficiency anemia, like autoimmune gastritis, inflammatory bowel disease, celiac disease or Helicobacter pylori infection. Some drugs commonly used in rheumatic patients also put patients at increased risk of gastric bleeding, including non-steroidal anti-inflammatory drugs and glucocorticoids.1
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Explore This IssueDecember 2017
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Rheumatologists must also consider possible drug-induced anemias when evaluating their patients. Janus kinase inhibitors such as tofacitinib can dampen the effect of erythropoietin on cells, leading to a mild anemia. Immunosuppressant drugs such as methotrexate and azathioprine sometimes cause bone marrow failure and a megaloblastic anemia, and other drugs can cause aplastic anemia. Others such as non-steroidal anti-inflammatory drugs and proton pump inhibitors can also decrease erythropoiesis or erythrocyte half-life.1
Various disease-associated mechanisms can induce anemia, distinct from anemia of inflammation itself. Systemic lupus erythematosus (SLE) can induce anemia from hemolysis, aplasia, pure red cell aplasia, myelofibrosis or thrombotic microangiopathy.6 Secondary kidney complications, such as in SLE or systemic sclerosis, can also cause anemia due to reduced production of erythropoietin.
Vitamin deficiency also plays a role in some patients. Inadequate dietary intake of B12 or folic acid can cause a megaloblastic anemia. Folic acid deficiency can also occur as a result of methotrexate therapy given without adequate folic acid supplementation.1 Evidence also suggests that vitamin D plays a role in iron regulation, and that deficiency can contribute to anemia in patients with rheumatoid arthritis.7
If clinicians simply assume anemia is due to disease inflammation, they can miss other important medical conditions.
Pathophysiology of Anemia of Inflammation
In anemia of inflammation, the pathophysiology of the underlying disease also leads to anemia. This is why treating the underlying condition often adequately treats the anemia as well. Anemia of inflammation usually induces a mild to moderate anemia that is normochromic and normocytic on peripheral blood smear.5
In recent years, researchers have come to understand the important role of the iron-regulatory hormone hepcidin in anemia of inflammation. Abnormally high levels of hepcidin are thought to play a large role in triggering the condition. Hepcidin production is induced by increasing plasma and hepatic iron concentrations, as well as certain inflammatory cytokines.5
Molecularly, hepcidin targets the only known cellular iron exporter, ferroportin, which is expressed on cell membranes in tissues that deliver iron to plasma. When hepcidin binds ferroportin, it causes ferroportin endocytosis and its subsequent destruction. This results in proportional reduction of iron export to the plasma. Hepcidin regulates the iron delivery to plasma from the macrophages that recycle old erythrocytes. It also regulates the delivery of iron from the duodenal enterocytes absorbing dietary iron, as well as from hepatocytes participating in iron storage. Thus, high hepcidin limits the absorption, remobilization and recycling of iron, resulting in reduced levels of plasma iron.5