Iron deficiency and anemia in rheumatoid arthritis; pathophysiology, corticosteroid effects, and inflammatory mechanisms – a narrative review study

Abstract

Anemia is a common and clinically significant extra-articular complication of rheumatoid arthritis (RA), driven by multifactorial mechanisms including anemia of inflammation and coexisting iron deficiency anemia (IDA), which complicate diagnosis. Proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) promote hepcidin overproduction, leading to iron sequestration, reduced absorption, impaired erythropoiesis, and shortened erythrocyte survival, alongside suppressed erythropoietin (EPO) activity. Corticosteroids exert bidirectional effects, offering short-term improvement but potentially disrupting long-term hematopoiesis. Diagnosis is challenging due to inflammation-related elevations in ferritin, whereas soluble transferrin receptor (sTfR) provides greater accuracy. Targeting inflammation with disease-modifying antirheumatic drugs (DMARDs) and biologics, particularly tocilizumab (TCZ), effectively improves anemia. This narrative review synthesizes evidence from randomized controlled trials and cohort studies over the past decades, evaluating the pathophysiology, diagnostic challenges, corticosteroid interactions, and therapeutic approaches to anemia in RA to provide clinicians with a comprehensive, evidence-based framework for management.

Keywords: Rheumatoid arthritis, Anemia of chronic disease, Anemia of inflammation, Iron deficiency, Hepcidin, Ferroportin, Interleukin-6, Corticosteroids, Tocilizumab