Iron Deficiency Anemia Pruritus: A Review with Proposed Mechanisms of Action

Abstract

Chronic generalized pruritus without a primary skin lesion presents a dilemma for clinicians. A minority can be attributed to systemic diseases. Iron deficiency anemia (IDA) presents one such poorly defined cause. We comprehensively review the literature to support IDA pruritus as a valid etiology in the patient with chronic, generalized pruritus. Several studies and case reports describe the association of pruritus and IDA, and more importantly, resolution of the pruritus upon iron supplementation, strongly suggesting IDA as the primary etiology. Thus, we recommend obtaining a CBC and iron studies in all cases of chronic generalized pruritus without a primary lesion. Based on currently available evidence, we also present novel mechanisms of actions in which iron deficiency may precipitate pruritus that have not been proposed in the literature. Iron deficiency may precipitate pruritus at the level of the skin through decreased skin thickness, elasticity, or barrier function, thereby promoting xerosis. Iron deficiency may also cause neurologic pruritus from damage, compression, or irritation of nerves. The levels of known chemical mediators of itch, such as serotonin, opioids, and neurotrophins, are also affected by iron homeostasis. IDA pruritus likely manifests from a complex interplay of multiple proposed pathways.