Hormone hepcidin identified as potential trigger for psoriasis

Scientists may have uncovered the root cause of psoriasis, a chronic and sometimes debilitating skin disease that affects 2-3% of the global population. The condition is characterized by red, scaly patches that impact the quality of a patient's life and can sometimes be life-threatening.

Those most likely to benefit from such a treatment are patients with pustular psoriasis (PP) – a particularly severe and treatment-resistant form of the disease that can affect a patient's nails and joints as well as skin.

We need skin iron – but not too much

Iron is an essential trace metal, not just for transporting oxygen through the body's circulatory system but also for maintaining healthy skin: it's involved in many essential cellular functions, including wound healing, collagen production and immune function. However, iron overload in the skin can be harmful, amplifying the damaging effects of UV sunlight and causing hyperproliferative chronic diseases (where cells grow and multiply more than normal), including psoriasis.

Studies going back 50 years have reported high iron concentrations in the skin cells of psoriatic patients, however the cause of this excess and its significance to the condition have remained unclear until now.

Hepcidin is responsible for controlling how much iron is absorbed from food and later released into the body. In healthy individuals, it's produced exclusively in the liver, however the new study has found that in people with psoriasis, the hormone is also generated in the skin.

Exposure to hepcidin triggers iron overload

In the new study, mice (which have many genetic and physiological similarities to humans) developed a rodent form of psoriasis after being exposed to high levels of skin-produced hepcidin.

This over-abundance of the hormone caused the animals' skin cells to retain far more iron than was required. In turn, this excess iron triggered both a hyperproliferation of skin cells and an abnormally high concentration of inflammation-inducing neutrophils (a type of immune system cell) in the topmost layer of skin.

These two outcomes – an overproduction of skin cells and an abundance of neutrophils – are main features of human psoriasis.

Psoriasis runs in families though experts believe 'environmental' factors such as weight, infections and smoking are also triggers.

A disease with no cure

Currently there is no cure for psoriasis, though treatments that include topical creams, light therapy and oral drugs can help keep symptoms under control for patients with some forms of the condition. Recent treatments have focused on targeting the immune pathways that contribute to psoriasis developing.

Dr Pourzand believes a drug targeting hepcidin has the potential to dramatically improve treatment options for all psoriasis patients.

She said: "Our data strongly suggests hepcidin would be a good target for skin psoriasis treatment. A drug that can control this hormone could be used to treat flare-ups and keep patients in remission to prevent recurrence.

Dr William Tillett, a senior lecturer at the University of Bath and a consultant rheumatologist specializing in the diagnosis and treatment of psoriatic arthritis, said: "This research from Dr Pourzand and colleagues is an exciting step forward for people living with psoriasis and for the clinical teams treating them.

"We don't know exactly why people develop psoriasis but the identification of hepcidin as an important factor in the development of the disease opens doors not only to potential new treatments but also to the possibility of preventing the disease developing in people at high risk. Existing drugs – called biologics – can be highly effective but they are costly and rationed in the UK. Furthermore, these drugs don't work for everyone and they can stop working after a while, so a new approach to treatment would be very welcome."

He added: "However, developing drugs is notoriously time consuming and costly, so a new treatment won't be available immediately and it's important for patients to manage expectations."

Source:

University of Bath

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