Intestinal blood loss as well as chronic inflammation are regarded as the most important mechanisms in the pathogenesis of anemia in Crohn's disease. In addition, cytokines such as interleukin-6 can suppress erythropoietin production. This study was performed to investigate the importance of iron status, inflammatory activity, and endogenous erythropoietin concentrations for the development of anemia in Crohn's disease. In 49 consecutive patients with Crohn's disease, hemoglobin, inflammatory activity (Crohn's disease activity index, C-reactive protein, α1-acid glycoprotein), iron status (serum iron, transferrin, transferrin saturation, ferritin), and serum erythropoietin levels were studied. Anemic (Hb<12.0 g/dl;N=16) vs nonanemic patients (Hb≥12 g/dl;N=33) showed reduced iron compartments (eg, ferritin 28.7±12.9 µg/liter vs 63.2±15.0 µg/liter, transferrin saturation 6.2±1.4% vs 11.5±1.3%,P<0.01) but no differences in inflammatory activity. An inverse correlation between erythropoietin and hemoglobin concentrations was found (r=-0.62;P<0.001), but the increase in erythropoietin levels was inadequate to the degree of anemia. There was no correlation between erythropoietin and interleukin-6 serum levels. Four of five anemic patients with hemoglobin below 10.5 g/dl and erythropoietin levels within the normal range were treated with parenteral iron (200 mg iron saccharate in 250 ml NaCl, weekly, intravenously). Two of them additionally received recombinant human erythropoietin (150 units/kg, 3× weekly, subcutaneously). After five weeks all patients had a marked increase in hemoglobin. However, the mean increase in erythropoietin-treated patients was 5.0 g/dl compared to 2.0 g/dl in the patients with iron therapy only. No side effects were seen. Our data demonstrate that inadequate erythropoietin production and iron deficiency are pathogenetic factors of anemia in Crohn's disease. The therapeutic management using recombinant human erythropoietin and parenteral iron is reasonable and effective.
Crohn's disease anemia erythropoietin iron interleukin-6