Like many topics in rheumatology, psoriatic arthritis (PsA) is complex. It is a heterogeneous chronic inflammatory immune-mediated disease, which manifests as musculoskeletal inflammation and psoriasis. It can also present with uveitis and inflammatory bowel disease. A review article in the International Journal of Molecular Sciences states that the pathogenesis of this condition is multifactorial, with genetics, environment, and the innate/adaptive immune system, as well as auto-inflammation, all playing a role.

Azuaga AB, Ramírez J, Cañete JD. Psoriatic arthritis: pathogenesis and targeted therapies. Int J Mol Sci. 2023;24(5):4901.

 

Estimates of the prevalence of PsA among patients with psoriasis also vary, but may be around 20%. There are also sex-based differences.

 

Peripheral arthritis

 

Researchers at the University of Toronto conducted a cross-sectional study of 345 men and 245 women with PsA and assessed the link between gender and disease activity, joint damage, quality of life, and disability.

Eder L, Thavaneswaran A, ChandranV, et al. Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis. Ann Rheumatic Dis. 2013;72:578–582.

 

 

They found that axial involvement occurred in 42.9% of men vs 31% of women (P = 0.003). Men had an increased chance of developing serious radiographic damage in the peripheral joints, based on the modified Steinbrocker score (mSS).

A cross-sectional study conducted in Turkey (360 men and 678 women) found that men with peripheral PsA were at higher risk of manifesting spondylitis.

Duruöz MT, Gezer HH, Nas K, et al. Gender-related differences in disease activity and clinical features in patients with peripheral psoriatic arthritis: A multi-center study. Joint Bone Spine. 2021;88(4):105177.

Other extra-articular manifestations were comparable between men and women. Women with peripheral PsA, however, exhibited decreased rates of remission and minimal disease activity (MDA), as well as increased levels of overall disease activity. 

 

The study authors concluded that female patients experience a more severe course of PsA, with higher levels of pain and fatigue, lower quality of life, and increased functional limitations. The predictors of MDA—which in this study were tender joint count, swollen joint count, Psoriasis Area and Severity Index (PASI) score, pain score on visual analog scale (VAS), and enthesitis—were similar between men and women.

The researchers speculated on the reasons for these differences. “While the etiology of the gender differences in PsA is unclear,” they wrote, “sex hormones, genetic mechanisms, and environmental components (trauma, obesity, smoking, and job-related) are probably the underlying factors.”

 

The influence of hormones

 

On the other hand, testosterone and progesterone have an anti-inflammatory effect and raise concentrations of IL-4, IL-5, and IL-10.

In one German study, researchers examined the relationship between serum levels of B-cell activating factor belonging to the TNF family (BAFF) and disease activity (DAS28) in 22 male and 31 female PsA patients.

Pongratz G, Straub RH, Schölmerich J, et al. Serum BAFF strongly correlates with PsA activity in male patients only--is there a role for sex hormones? Clin Exp Rheumatol. 2010;28(6):813–819.

 

 

They concluded that although a role for B cells in the pathogenesis of PsA has yet to be elucidated, BAFF levels were associated with disease activity in male patients. Moreover, serum testosterone levels in male patients negatively correlated with both disease activity and BAFF. They suggested that the BAFF/serum testosterone ratio could be used to predict disease activity in males with PsA.

 

Clinical implications

 

Sex differences in PsA may have clinical implications. 

The Turkish authors commented on the emergence of gender medicine, writing that “gender medicine is a new area because diseases differ between genders in diagnosis and treatment strategies. Gender differences in PsA with several manifestations are essential in terms of treatment, prognosis, and follow-up. The development of knowledge concerning gender differences represents a milestone in science, and now researchers are progressing to personalized medicine.”

They also attained minimal disease activity MDA less often than men. Treatment-emergent adverse events were generally similar across sexes.

Eder L, Gladman DD, Mease P, et al. Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension. RMD Open. 2023;9(1):e002718.

 

Publishing in Rheumatology, Danish researchers found that in 1,750 patients with PsA starting their first TNF inhibitor treatments, men had a more favorable baseline profile (ie, fewer comorbidities) and were more likely to attain 3- and 6-month treatment response.

Højgaard P, Ballegaard C, Cordtz R, et al. Gender differences in biologic treatment outcomes-a study of 1750 patients with psoriatic arthritis using Danish Health Care Registers. Rheumatology (Oxford). 2018;57(9):1651–1660.

Men also experienced longer TNF inhibitor persistence.

 

 

“Although we observed a poorer achievement of the minimal patient-reported disease activity response in females,” the researchers wrote, “we are not able to determine the extent to which psychological vs physiological factors contribute to this finding. Finally, lower compliance to biologic therapies in females vs males has been documented in [rheumatoid arthritis] and Crohn’s disease, and could also be an explanatory variable for the increased risk of TNFI failure among female patients with PsA.”