Question

explain the role of stress in the development of psoriasis.

Answer 1

Solution

• The exact mechanism underlying the relationship between stress and psoriasis remains unclear. However, evidence has shown that the main physiological pathways involve the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary (SAM) axis, peripheral nervous system and immune‐mediated pathways.
• Psychological stress factors are processed in the hypothalamus to produce corticotrophin‐releasing hormone, which then result in the secretion of adrenocorticotrophic hormone and glucocorticoids.
• Regarding acute psychosocial stress, one study showed that cortisol level is increased significantly in patients with psoriasis compared with patients with rheumatoid arthritis and healthy controls.
• However, the repeated experimental stress resulted in an altered HPA axis with decreased cortisol levels in patients with psoriasis. Subjects who persistently experience higher levels of daily stress have been shown to have lower mean cortisol levels.
• These observations may not only suggest a difference between the acute and chronic stress, but also indicate an impaired glucocorticosteroid response to stressors in a subset of patients with psoriasis.
• The blunted HPA activity may result in upregulation of inflammatory cytokines,20 which could help explain the stress‐induced exacerbation of psoriasis.

• Studies have shown that both corticosterone and epinephrine (adrenaline) are important mediators in a short‐term stress‐induced immunoenhancement.
• It is observed an increase in SAM system activity in response to stress in patients with psoriasis compared with controls. The circulating epinephrine and norepinephrine (noradrenaline) levels were significantly increased by an experimental stressor.
• Evidence has shown that release of norepinephrine by sympathetic nerve termini during psychological stress exerts an adjuvant effect on DCs by promoting their enhanced migration to lymph nodes, resulting in increased T‐cell immune responses.
• In addition to eliciting the sympathetic response, stress also affects the peripheral nervous system in psoriasis by modulating the neuropeptides within the skin. Recent animal‐based studies have shown that key neuromodulators, including substance P (SP), calcitonin gene‐related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and nerve growth factor (NGF) can induce the exacerbation of psoriasis in a stress‐mediated manner.