# Iron Deficiency in Immune-Mediated Inflammatory Skin Diseases: A Missing Link Between Systemic Inflammation, Immunometabolism, and Disease Burden

## TL;DR

This paper explores how iron deficiency contributes to inflammatory skin diseases by linking it to systemic inflammation and immune metabolism.

## Contribution

It introduces the concept of an 'iron-skin axis' and highlights iron's role in immune and skin cell metabolism.

## Key findings

- Chronic inflammation causes functional iron deficiency through IL-6–hepcidin pathways.
- Iron deficiency disrupts mitochondrial activity and increases oxidative stress in immune and skin cells.
- Skin cells, especially keratinocytes, actively regulate iron pathways, linking skin health to systemic iron metabolism.

## Abstract

Iron deficiency (ID) has emerged as a pivotal yet underrecognized factor in the pathogenesis of immune-mediated inflammatory skin diseases (IMISDs) such as psoriasis, atopic dermatitis, and hidradenitis suppurativa. Beyond its classical role in erythropoiesis, iron acts as a key modulator of immune cell activity, redox balance, and overall metabolic homeostasis. This review synthesises the latest evidence on the intricate relationship between systemic inflammation, disturbances of iron metabolism, and immunometabolic imbalances that underline the pathogenesis of IMISDs. Findings indicate that chronic inflammation drives functional iron deficiency through IL-6–hepcidin-mediated sequestration of iron, resulting in reduced bioavailability and altered mitochondrial activity in immune and epithelial cells. This imbalance is associated with excessive and chronically enhanced oxidative and inflammatory responses of these cells, further advancing inflammation, anaemia of chronic disease, and disturbances of tissue repair. Moreover, emerging evidence supports an “iron-skin axis,” and suggests that skin cells, particularly epidermal keratinocytes, are actively involved in the regulation of iron pathways. Collectively, these insights position iron homeostasis as a missing link between systemic inflammation, immunometabolic imbalance, and disease burden in IMISDs.