Anemia of Chronic Disease: Pathophysiology, Diagnosis and Management

Anemia of chronic disease (ACD) is a condition linked to chronic immune activation secondary to a wide range of infectious, inflammatory, and autoimmune diseases. It is characterized by a state of iron-restricted erythropoiesis, in which prolonged activation of cytokines leads to retention of iron within the reticulo-endothelial system, driven primarily by hepcidin. Reduced iron availability contributes to a blunted response by erythropoietin and impaired erythropoiesis, in addition to a shortened red cell lifespan. In patients found to have anemia and evidence of chronic inflammation, parameters such as mean cell volume, iron studies, percentage of hypochromic red cells, reticulocyte hemoglobin content, and levels of ferritin, serum transferrin receptor, hepcidin, erythropoietin, and GDF15 are all used to build a picture of anemia of chronic disease. Following this, management normally utilizes erythropoietin-stimulating agents alongside parenteral iron supplementation when treatment of the underlying cause is not available. Newer therapies, such as hypoxia-inducible factor prolyl hydroxylase inhibitors and hepcidin inhibitors, also play a role, while cytokine targets, carbon dots, androgens, and other therapies are emerging as possible treatment routes. Despite its high prevalence, there remain few standardized methods of diagnosis or management in anemia of chronic disease. This narrative review explores long-standing and emerging practices in the diagnosis and management of this condition to ensure an up-to-date understanding.