New research confirms the link between perceived stress and psoriasis relapse

Innovative research has provided compelling evidence that perceived stress can directly lead to the recurrence of psoriatic skin lesions. The study, presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024is the first to scientifically validate this compound in vivo.

Psoriasis, a chronic skin condition that affects more than 6 million people in Europe, is characterized by rapid production of skin cells, leading to flaking and inflammation. Although it has long been suspected that stress plays a role in worsening psoriasis, this study provides compelling evidence for this link.

In the study, psoriatic lesions were induced in healthy human skin xenografts on Severe Combined Immunodeficiency (SCID)/beige mice (n=25) by the injection of autologous, in vitro IL-2-preactivated peripheral blood mononuclear cells.

After achieving remission of the lesion with topical dexamethasone, the mice were exposed to sonic (sound) or sham stress for 24 hours. The recurrence of psoriatic lesions was then monitored over the next 14 days.

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

Further analysis showed that sonic stress significantly increased the presence of immune cells in the skin and increased pro-inflammatory mediators such as CXCL10, IL-22, IL-15, IL-17A/F, IFN-γ and TNFα. In addition, biomarkers of neurogenic inflammation, such as nerve growth factor (NGF) and substance P (SP), were upregulated.

Sonic stress also led to increased levels of tryptase, indicating mast cell activation, and increased expression of NK-1R, the receptor for SP.

“Psychoemotional stress triggers the release of pro-inflammatory neuropeptides such as SP, which leads to neurogenic skin inflammation by activating immune cells, especially through degranulation of mast cells,” explains Professor Amos Gilhar, principal investigator of the Skin Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel.

“This is further enhanced by corticotropin-releasing hormone (CRH) and NGF, which increase inflammation and promote keratinocyte hyperproliferation, causing and aggravating psoriatic lesions in susceptible individuals.”

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

“Aprepitant shows promise as a potential therapy for stress-induced exacerbations of psoriasis,” noted Professor Gilhar, although 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 does not affect other mediators such as NGF and CRH. Combining NK-1R antagonists with other treatments may prove more effective.”

Reflecting on the wider implications of the study, Professor Gilhar adds: “In line with previous stress research in mice, our study using the ‘humanised’ psoriasis mouse model identifies SP/NK-1R signaling as a promising target for therapeutic intervention in stress – caused or aggravated psoriasis. It also points to additional candidate targets, including NGF, mast cell activation/degranulation, and CRH/CRH-R1 signaling.”

The study underlines the complex link between the nervous system and the immune response in psoriasis. “By recognizing how stress affects psoriasis, we can refine our treatment methods to better serve patients,” adds Professor Gilhar. “Looking ahead, our team plans to explore the clinical potential of NK-1R antagonists and delve deeper into the role of stress management in psoriasis care.”

Provided by the European Academy of Dermatology and Venereology