Low-grade systemic inflammation is associated with risk of psoriasis in a general population study of more than 100 000 individuals

Background Biomarkers of low-grade systemic inflammation have been reported to be higher in patients with psoriasis than in healthy controls. However, it is unknown whether this low-grade systemic inflammation contributes to the development of psoriasis or is merely a consequence. Objectives To investigate whether low-grade systemic inflammation, measured as systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) or C-reactive protein (CRP), is an independent risk factor for psoriasis. Methods We used data from the Copenhagen General Population Study, a prospective cohort study of the Danish general population where individuals aged 20-100 years were enrolled between 2003 and 2015. Upon enrolment in the study, all individuals underwent a physical examination, completed an extensive self-reported questionnaire regarding lifestyle, and provided blood samples, from which SII, NLR and CRP were measured. Psoriasis was identified using International Classification of Diseases codes with individual linkage to the Danish National Patient Registry. Associations between SII, NLR and CRP and psoriasis were estimated using hazard ratios from Cox proportional hazard regression models. Analyses were adjusted for potential confounders including sex, age, smoking, alcohol consumption, physical activity, educational level, hypertension, dyslipidaemia and obesity. Results We included 105 418 individuals with a median age of 58 years, 55% of whom were women. The risk of receiving a diagnosis of psoriasis increased with increasing levels of SII, NLR and CRP. In individuals with high levels (> 90th percentile) of SII, NLR and CRP, the multivariable adjusted hazard ratios were 1.78 [95% confidence interval (CI) 1.41-2.24], 1.56 (95% CI 1.22-1.99) and 2.83 (95% CI 2.27-3.51), respectively, compared with individuals with low levels. Results were similar but slightly attenuated when we used topical calcipotriol (alone or in combination with corticosteroids) for mild psoriasis. Conclusions We found that low-grade systemic inflammation, as measured by SII, NLR and CRP, was an independent risk factor for psoriasis, especially moderate-to-severe disease. These findings support the hypothesis that low-grade systemic inflammation may contribute to the pathogenesis of psoriasis rather than simply being a consequence of the disease.