Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management

Abstract

The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian‐rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night‐time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption. In addition, shift work, a circadian misalignment challenge, is associated with psoriasis. These features may be due to underlying circadian control of key effector elements known to be relevant in psoriasis such as cell cycle, proliferation, apoptosis and inflammation. Indeed, peripheral clock pathology may lead to hyperproliferation of keratinocytes in the basal layers, insufficient apoptosis of differentiating keratinocytes in psoriatic epidermis, dysregulation of skin‐resident and migratory immune cells and modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF‐A) in epidermal keratinocytes. Chronotherapeutic effects of topical steroids and topical vitamin D analogues have been reported, suggesting that knowledge of circadian phase may improve the efficacy, and therapeutic index of treatments for psoriasis. In this viewpoint essay, we review the current literature on circadian disruption in psoriasis. We explore the hypothesis that psoriasis is circadian‐driven. We also suggest that investigation of the circadian components specific to psoriasis and that the in vitro investigation of circadian regulation of psoriasis will contribute to the development of a novel chronotherapeutic treatment strategy for personalised psoriasis management. We also propose that circadian oscillations of VEGF‐A offer an opportunity to enhance the efficacy and tolerability of a novel anti‐VEGF‐A therapeutic approach, through the timed delivery of anti‐VEGF‐A drugs.

Psoriasis and exposome: Unveiling the inner and the external contributors of psoriasis disease

“…Sleep deprivation resulted in increased levels of proinflammatory cytokines, including IL-1β, IL-6, and IL-12, leading to an intensified inflammatory immune response. This suggests that circadian disruption might contribute to the development and progression of psoriasis [38,40].…”

Potential effects of shift work on skin autoimmune diseases

“…Glucocorticoids are potent antipruritic drugs, but are also known to inhibit pain pathways (460). Therefore, not only low beta-endorphin levels but also low cortisol levels could explain why symptoms of itch and pain are most pronounced at night, as it was demonstrated for itch in patients with psoriasis (211,461).…”

The Yin and Yang dualistic features of autophagy in thermal burn wound healing

“…28,61 Keratinocytes are non-immune cells involved in both angiogenesis (restoring the blood vessels and resuming circulation) and epithelialization (which means wound surface closure) modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF-A) in epidermal keratinocytes. 1,74,75 Keratinocytes represent the foundation of the epidermis. From all the skin cells, they are the most studied.…”