Abstract: Anemia in Early Rheumatoid Arthritis Is Associated with Interleukin 6-Mediated Bone Marrow Suppression, But Has No Effect on Disease Course or Mortality

Anemia in Early Rheumatoid Arthritis Is Associated with Interleukin 6-Mediated Bone Marrow Suppression, But Has No Effect on Disease Course or Mortality

CATHRIN NIKOLAISEN, YNGVE FIGENSCHAU, and JOHANNES C. NOSSENT

ABSTRACT.

Objective. Anemia of chronic disease (ACD) is the most common extraarticular manifestation of rheumatoid arthritis (RA), but there is limited information on the cause and consequences of ACD. We investigated the prevalence, relation with proinflammatory cytokines, and effect on disease outcome of ACD in patients with RA.

Methods. The presence of anemia was analyzed in a cohort of 111 consecutive patients with early RA. Anemia was related to markers of erythropoiesis and inflammation [clinically and by levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin 1ß (IL-1ß), IL-2, IL-6, IL-8, and tumor necrosis factor-a]. The frequency of various disease outcomes during the mean followup of 74 months was compared between ACD and nonanemic patients.

Results. ACD was present in 25% during the first year of disease. ACD was associated with higher CRP (45 vs 22 g/l; p = 0.04) and ESR levels (54 vs 33 mm/h; p = 0.002). Hemoglobin levels were inversely correlated with serum erythropoietin (p = 0.003) in univariate analysis, but in multivariate analysis only ESR (p = 0.005) and IL-6 (p = 0.056) remained as independent predictors of hemoglobin levels. Presence of ACD was not associated with later development of disease manifestations or mortality.

Conclusion. While ACD affected 25% of patients with RA early in the disease course, this had no influence on disease outcome including mortality during the following 6 years. The association between IL-6 and ACD suggests that IL-6-mediated bone marrow suppression is the main mechanism for development of ACD in RA. (First Release Feb 1 2008; J Rheumatol 2008;35:380-6)

Key Indexing Terms:

ANEMIA
RHEUMATOID ARTHRITIS
INTERLEUKINS
OUTCOME
CHRONIC DISEASE

From the Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø; and the Departments of Medical Biochemistry and Rheumatology, University Hospital North Norway, Tromsø, Norway.

Supported by Norwegian Society for Rheumatology Helse Nord (project SFP-96-04).

C. Nikolaisen, MD, Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø; Y. Figenschau, MD, PhD, Department of Medical Biochemistry; J.C. Nossent, MD, PhD, Professor of Medicine, Department of Rheumatology, University Hospital North Norway.

Address reprint requests to Dr. C. Nikolaisen, Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway. E-mail: cathrin.nikolaisen@unn.no

Accepted for publication October 24, 2007.