Dual zeitgeber axes in psoriasis: a chronobiological framework for immune jet lag.

Psoriasis is a chronic inflammatory skin disease jointly shaped by genetic susceptibility and environmental factors, with the IL-23/Th17 axis representing a central immune pathway (). While biologic agents targeting the IL-23/Th17 axis substantially improve short-term lesion control and reshape the therapeutic landscape (), real-world evidence shows that a considerable proportion of patients, during long-term follow-up, still experience loss of efficacy, reduced drug retention, and recurrent disease fluctuations (, ). This clinical reality, characterized by limited durability of therapeutic response and marked inter-individual variability, suggests that inflammatory intensity alone may not fully explain the complex and dynamic course of psoriasis, and that time-dependent regulatory dimensions warrant consideration within the current disease framework. A large body of clinical and epidemiological evidence further indicates that psoriasis exhibits consistent temporal dynamic patterns. During seasonal transitions, disease activity consistently shows a pattern of exacerbation in winter and alleviation in summer (–). At the circadian level, symptom exacerbation is often concentrated from the evening to nighttime, forming a relatively stable circadian phenotype, accompanied by increased nocturnal pruritus and disruption of sleep architecture (, ). These patterns are quantitatively assessed using objective measures, making them more readily observable (). Epidemiological studies further suggest an association between circadian disruption and psoriasis. An analysis based on data from the National Health and Nutrition Examination Survey (NHANES) found that circadian syndrome, a composite construct incorporating insufficient sleep, depression, obesity, and hypertension, had greater predictive value for psoriasis than the traditional metabolic syndrome model. These findings suggest that circadian disruption may represent a systemic risk context relevant to psoriasis (). Together, these time-related clinical and epidemiological observations suggest that psoriasis is not shaped solely by whether inflammatory pathways are activated, but may also involve dysregulated temporal organization of immune responses.