Researchers say they have confirmed what has long been suspected – that perceived stress can directly trigger the relapse of psoriatic skin lesions.
New research has confirmed a link between perceived stress and psoriasis relapse – a connection long suspected but never scientifically tested.
The study, presented last week at the European Academy of Dermatology and Venereology (EADV) Congress 2024, was the first to scientifically validate this connection in vivo, said the researchers.
While it has long been suspected that stress plays a role in exacerbating psoriasis, they said their research offered conclusive evidence of this link.
In the study, psoriatic lesions were induced in healthy human skin xenografts on Severe Combined Immunodeficiency (SCID)/beige 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. Sonic stress led to a relapse of psoriatic lesions in all human skin xenografts within the follow-up period. 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 like CXCL10, IL-22, IL-15, IL-17A/F, IFN-γ and TNFα.
Additionally, neurogenic inflammation biomarkers, such as nerve growth factor (NGF) and substance P (SP), were upregulated. Sonic stress also led to elevated levels of tryptase, indicating mast cell activation, and increased expression of NK-1R, the receptor for SP.
“Psycho-emotional stress triggers the release of proinflammatory neuropeptides like SP, leading to neurogenic skin inflammation by activating immune cells, particularly through mast cell degranulation,” said Professor Amos Gilhar, lead researcher from the Skin Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
“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 researchers also tested the efficacy of aprepitant, an FDA-approved anti-emetic 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,” said Professor Gilhar.
However, 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,” he said.
“Combining NK-1R antagonists with other treatments may prove more effective.”
Professor Gilhar said in line with previous stress research in mice, the study using the ‘humanised’ psoriasis mouse model identified SP/NK-1R signalling as a promising target for therapeutic intervention in stress-triggered or aggravated psoriasis.
“It also points to additional candidate targets, including NGF, mast cell activation/degranulation, and CRH/CRH-R1 signalling,” he said.
He said the study underscored the complex link between the nervous system and the immune response in psoriasis.
“Recognising how stress influences psoriasis allows us to refine our treatment approaches to better serve patients,” said Professor Gilhar.
“Looking ahead, our team plans to explore the clinical potential of NK-1R antagonists and to delve deeper into the role of stress management in psoriasis care.”
