In Psoriatic Arthritis, Men Are from Mars, Women Are from Venus

By Linda Rath | Nov. 9, 2024

Evidence increasingly suggests that women and men diagnosed with psoriatic arthritis (PsA) differ significantly in almost all aspects of the disease, including diagnosis, symptoms, pain and response to biologic drugs. The reasons for these differences aren’t clear, and until recently, not many studies have looked at them. So Laura Coates, PhD, a clinician-scientist at the University of Oxford, and Lihi Eder, MD, a rheumatologist-scientist at Women’s College Hospital in Toronto, Canada, and others are investigating and calling attention to sex- and gender-based disparities. They spoke at the American College of Rheumatology’s 2024 conference about how biological and sociocultural differences affect outcomes of PsA patients. 

Some of the differences they discussed included:

Time to diagnosis. Although women seek care more often than men, they are generally diagnosed later. It commonly takes two to three years for them to get a diagnosis after first seeing a primary care physician or rheumatologist for joint pain. During that time, they have many more imaging tests, but most are X-rays, which don’t pick up early signs of PsA. According to Dr. Eder, unconscious biases in the medical community may also play a role, “with studies showing that men and women are treated differently when it comes to ordering advanced diagnostic tests, potentially resulting in delays.” Other factors may contribute, too, including co-existing osteoarthritis (OA), which can cause similar symptoms, as well as depression, obesity and fibromyalgia, which are all more common in women.

Symptoms. Most women who have PsA have polyarticular arthritis, which affects five or more joints, usually in the arms and legs. Men tend to have pain and inflammation in the spine and sacroiliac joints, where the spine connects to the pelvis (axial PsA). 

Other patterns that don’t change over time and have been consistently seen in real-world data going back at least a decade include:

• Women have more tender and sometimes swollen joints; men have more severe psoriasis and slightly higher C-reactive protein (CRP), a measure of inflammation.
• Women are more likely to have inflammation where ligaments and tendons attach to bone (enthesitis); men are more likely to have swelling in their fingers and toes (dactylitis). Enthesitis and dactylitis both indicate severe disease but may be hard to detect with X-rays, making ultrasound and MRI better imaging options.
• Women have a lower rate of disease progression and joint erosion over time. This finding isn’t universal, but the general consensus is that men with PsA have more joint damage. Still, women have higher disease activity by most measures.
• Women fare worse than men on all quality-of-life measures, including sleep, fatigue, anxiety, depression, coping mechanisms and embarrassment. Coates emphasized that “PsA has a massive impact on women’s mental health, including anxiety and depression,” whereas the effect is less on men.
• More than half of women have different perceptions of their disease activity than doctors do. This tends to occur in many other diseases, too. Men and women also define remission differently; despite experiencing more pain, women are more tolerant of higher disease activity than men are. 
• Probably most important, women experience more pain with PsA than men and seem to have a lower tolerance for pain overall. Dr. Eder said both biological and sociocultural factors contribute to these differences, noting that even women who don’t have arthritis tend to experience pain more intensely than men do. Researchers are trying to understand how these various factors come into play. One theory is that higher testosterone levels may cause men to process pain differently. There may also be differences in the number and location of opioid receptors — naturally occurring protein molecules that can block the transmission of pain signals to the brain. And there are differing social expectations for women and men; in most cultures, men are more likely to ignore pain and women more likely to report it.

Response to treatment

Coates doesn’t think there is a single explanation for gender differences in PsA, and Dr. Eder doesn’t think one-size-fits-all is the right approach to treatment. In cardiology, she noted, it’s well known that blood pressure is influenced by sex and gender. “To assume that what works for men works for women is just not true,” she said.

This is particularly obvious in the way men and women respond to common biologic medications. In both observational and randomized controlled trials, the drugs are less effective in women and cause worse side effects, so women stop taking them sooner.

According to Dr. Eder, there are probably many reasons for varying drug responses, including “differences in immune profiles, pain perception, the way the body interacts with medications and the development of more anti-drug antibodies.” Dr. Eder has shown in rodent studies that common PsA medications may not be targeting active pathways in women.

Still, she said, it’s hard to draw conclusions due to a lack of research, and harder still to explain why JAK inhibitors like tofacitinib (Xeljanz) are the only class of psoriasis drugs that have similar outcomes in both women and men. JAK inhibitors are not considered a first-line or even second-line medication for PsA, and she suggested that methotrexate might make more sense for women, though there is so far little evidence to support that.