EADV Congress 2024: New research confirms link between perceived stress and psoriasis relapse

Innovative research has provided compelling evidence that perceived stress can directly trigger the relapse of psoriatic skin lesions. The study, presented today at the EADV Congress 2024, is the first to scientifically validate this connection in vivo.

AMSTERDAM, Sept. 26, 2024 /PRNewswire/ — Psoriasis, a chronic skin condition affecting over 6 million people in Europe, is characterised by rapid skin cell production, leading to scaling and inflammation. While it has long been suspected that stress plays a role in exacerbating psoriasis, this research offers conclusive evidence of this link.

In the study, psoriatic lesions were induced in healthy human skin xenografts on mice (n=25) through the injection of autologous, in vitro IL-2-preactivated peripheral blood mononuclear cells. After achieving lesion remission with topical dexamethasone, the mice were exposed to either sonic (sound) or sham stress for 24 hours. The recurrence of psoriatic lesions was then tracked over the following 14 days.

Remarkably, sonic stress led to a relapse of psoriatic lesions in all human skin xenografts within 14 days. This was accompanied by significant changes in psoriasis-related skin phenomena, including increased epidermal thickness, K16 expression, keratinocyte proliferation, anti-microbial peptide expression, and immune activation of intraepidermal cells.

Further analysis showed that sonic stress significantly increased immune cell presence in the skin and elevated proinflammatory mediators. Additionally, neurogenic inflammation biomarkers were upregulated. Sonic stress also led to elevated levels of tryptase, indicating mast cell activation, and increased expression of NK-1R, the receptor for substance P (SP).

“Psychoemotional stress triggers the release of proinflammatory neuropeptides like SP, leading to neurogenic skin inflammation by activating immune cells, particularly through mast cell degranulation,” explains Professor Amos Gilhar, lead researcher of the study. “This is further amplified by corticotropin-releasing hormone (CRH) and NGF, which heighten inflammation and promote keratinocyte hyperproliferation, thereby triggering and worsening psoriatic lesions in susceptible individuals.”

The research team also tested the efficacy of aprepitant, an FDA-approved anti-emetic neurokinin-1 receptor (NK1-R) antagonist, in preventing stress-induced psoriasis relapse. Aprepitant prevented relapse in 80% of cases and normalised most inflammatory markers.

“Aprepitant shows great promise as a potential therapy for stress-induced psoriasis exacerbations,” Professor Gilhar remarks, though he cautioned about its off-label use and the need for further safety data. “Aprepitant selectively targets the SP-induced component of neurogenic inflammation but doesn’t impact other mediators like NGF and CRH. Combining NK-1R antagonists with other treatments may prove more effective.”

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