Innovative research has provided compelling evidence that perceived stress can directly trigger a relapse of psoriatic skin lesions. The study, presented today at the EADV Congress 2024, is the first to scientifically confirm this connection in vivo.
Psoriasis, a chronic skin disease that affects over 6 million people in Europe, is characterized by rapid production of skin cells, leading to scaling and inflammation. While it has long been suspected that stress plays a role in worsening psoriasis, this research provides conclusive evidence of this connection.
In the study, psoriatic lesions were induced in healthy human skin xenografts on mice (n=25) by injection of autologous, in vitro IL-2-preactivated peripheral blood mononuclear cells. After remission of the lesions was achieved with topical dexamethasone, mice were exposed to either sound or sham exposure for 24 hours. Recurrence of the psoriatic lesions was then monitored over the following 14 days.
Remarkably, acoustic exposure resulted in relapse of psoriatic lesions within 14 days in all human skin xenografts. This was accompanied by significant changes in psoriasis-related skin phenomena, including an increase in epidermal thickness, K16 expression, keratinocyte proliferation, antimicrobial peptide expression, and immune activation of intraepidermal cells.
Further analysis revealed that acoustic stress significantly increased the presence of immune cells in the skin and led to an increase in pro-inflammatory mediators. In addition, biomarkers of neurogenic inflammation were upregulated. Sonic stress also resulted in increased tryptase levels, indicating mast cell activation, and increased expression of NK-1R, the substance P (SP) receptor.
“Psychoemotional stress triggers the release of pro-inflammatory neuropeptides such as SP, which leads to neurogenic skin inflammation by activating immune cells, particularly through mast cell degranulation,” explains Professor Amos Gilhar, the study leader. “This is further compounded by corticotropin-releasing hormone (CRH) and NGF, which increase inflammation and promote hyperproliferation of keratinocytes, triggering and aggravating the psoriatic lesions in susceptible individuals.
The research team also tested the effectiveness of aprepitant, an FDA-approved neurokinin-1 receptor (NK1-R) anti-emetic antagonist, in preventing stress-related psoriasis flare-ups. Aprepitant prevented relapse in 80% of cases and normalized most inflammatory markers.
“Aprepitant is a promising agent for the treatment of stress-related psoriasis exacerbations,” said Professor Gilhar, who cautioned against its off-label use and the need for further safety data. “Aprepitant selectively targets the SP-induced component of neurogenic inflammation, but has no effect on other mediators such as NGF and CRH. Combining NK-1R antagonists with other treatments may prove more effective.
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