Skin stress

Skin stress is a broad physiological and pathological state rather than a single molecular target or receptor. It encompasses the skin's complex biological response to various external environmental factors, such as ultraviolet radiation, pollution, and blue light, as well as internal factors like psychological stress [2, 7, 8]. These stressors trigger the activation of a local cutaneous equivalent of the hypothalamic-pituitary-adrenal (HPA) axis, leading to the production of mediators like corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol directly within the skin [9, 13]. This response cascade results in oxidative stress, neurogenic inflammation, and the disruption of the skin barrier [10]. While "skin stress" itself is not a specific drug target, the pathways it activates—including the aryl hydrocarbon receptor (AhR) and various inflammatory cytokine pathways—are central to the pathogenesis of conditions such as psoriasis, atopic dermatitis, and photoaging [4, 11]. Therapeutic interventions generally focus on mitigating the consequences of skin stress through the use of antioxidants, anti-inflammatory agents like corticosteroids, and barrier-repairing compounds [12, 15].

Other names

Cutaneous stress responseSkin oxidative stressDermal stressNeuro-endocrine-immune skin responseEnvironmental skin stress

Pharmacological interventions do not target 'skin stress' directly but rather modulate the resulting pathways, such as through glucocorticoid receptor agonism to reduce inflammation, neutralization of reactive oxygen species by antioxidants, or activation of the aryl hydrocarbon receptor to enhance barrier function.