Sex differences in the association between plasma polyunsaturated fatty acids levels and moderate-to-severe plaque psoriasis severity: a cross-sectional and longitudinal study

Abstract

Background: Psoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles.

Methods: Plasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models.

Results: Males suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline.

Conclusions: Sex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.

Keywords: Polyunsaturated fatty acids; Psoriasis; Severity; Sex differences.

Fig. 1

Flowchart of the participants selection. PASI Psoriasis Area and Severity Index, BSA Body Surface Area, PGA Physician Global Assessment, PtGA patient global assessment, DLQI Dermatology Life Quality Index

Fig. 2

Predicted spline curves for the associations between the levels of total Omega-3 PUFAs, EPA and DHA (mol %) and PASI scores among male patients using RCS regression models. A Total Omega-3 PUFAs, B EPA, and C DHA in total males, males with BMI < 28 kg/m², and males with BMI < 23.99 kg/m², respectively. In the models, covariates including age, education, smoking history, and alcohol use history were adjusted. β β-Coefficient, BMI body mass index, CI confidence interval, DHA docosahexaenoic acid, EPA eicosapentaenoic acid, PASI Psoriasis Area and Severity Index, PUFAs polyunsaturated fatty acids

Fig. 3

Predicted spline curves for the associations between the levels of total Omega-3 PUFAs, EPA and DHA (mol %) and BSA scores among male patients using RCS regression models. A Total Omega-3 PUFAs, B EPA, and C DHA in total males, males with BMI < 28 kg/m², and males with BMI < 23.99 kg/m², respectively. In the models, covariates including age, education, smoking history, and alcohol use history were adjusted. β β-Coefficient, BMI body mass index, BSA Body Surface Area, CI confidence interval, DHA docosahexaenoic acid, EPA eicosapentaenoic acid, PUFAs, polyunsaturated fatty acids

Fig. 4

Difference of PASI scores or PASI response between male and female patients at week 12 (A–D). PASI Psoriasis Area and Severity Index