A groundbreaking study has provided conclusive evidence linking stress to the recurrence of psoriasis, a chronic inflammatory skin condition that affects over 6 million people in Europe. The research, conducted by a team led by Professor Amos Gilhar, demonstrates that stress significantly contributes to the flare-up of psoriatic lesions, shedding light on the mechanisms behind this connection and suggesting new treatment options for patients.

The study involved inducing psoriatic lesions in human skin grafts transplanted onto mice. After achieving remission with the use of topical dexamethasone, the mice were exposed to either sonic (sound) or sham stress for 24 hours. The researchers then monitored the recurrence of psoriatic lesions over the following 14 days. Remarkably, every mouse exposed to sonic stress experienced a relapse of psoriatic lesions within two weeks, while those subjected to sham stress showed no such recurrence.

Further analysis revealed that stress caused significant changes in the skin, including increased thickness of the epidermis, elevated expression of keratin-16 (K16), and heightened keratinocyte proliferation. The skin samples also exhibited higher levels of anti-microbial peptides and activation of intraepidermal immune cells, all of which are hallmarks of psoriasis.

The study’s findings go beyond just observing physical changes. Researchers noted a surge in immune cell presence and proinflammatory mediators in the stressed skin samples. Additionally, stress led to an increase in neurogenic inflammation biomarkers, such as elevated tryptase levels, indicating mast cell activation. This response was associated with a rise in the expression of the neurokinin-1 receptor (NK-1R), which is known to bind to the stress-related neuropeptide substance P (SP).

Professor Gilhar explains that psychoemotional stress triggers the release of proinflammatory neuropeptides like SP, which in turn activate immune cells and cause neurogenic skin inflammation through mast cell degranulation. This inflammatory cascade is further amplified by other stress-related molecules, such as corticotropin-releasing hormone (CRH) and nerve growth factor (NGF), which exacerbate keratinocyte hyperproliferation and lead to the development and worsening of psoriatic lesions.

To explore potential treatment options, the research team tested the efficacy of aprepitant, an FDA-approved neurokinin-1 receptor antagonist commonly used to prevent chemotherapy-induced nausea and vomiting. The results were promising—aprepitant prevented stress-induced psoriasis relapse in 80% of the cases and normalized most inflammatory markers associated with the disease.

“Aprepitant shows great potential as a therapeutic option for managing stress-related exacerbations of psoriasis,” says Professor Gilhar. However, he emphasizes the need for caution, as the current findings are based on preclinical models. The drug targets only the SP-induced component of neurogenic inflammation and may not address other mediators like CRH and NGF, which are also involved in the process. He suggests that combining NK-1R antagonists with other treatments could be more effective in providing comprehensive relief for stress-induced psoriasis.

This study not only reinforces the importance of stress management for individuals with psoriasis but also opens new avenues for developing targeted therapies to prevent stress-related flare-ups. With further research, these findings could pave the way for better treatment options and improved quality of life for millions of people suffering from this chronic skin condition.