Understanding Gender Differences in IMIDs: Insights into Spondyloarthritis and Rheumatoid Arthritis

Feb 126 min read

Immune-Mediated Inflammatory Diseases (IMIDs)

IMIDs are a group of conditions characterized by an abnormal immune response, leading to inflammation that can affect various parts of the body (Ortega et al., 2022). These diseases are diverse, including conditions like rheumatoid arthritis, psoriasis, inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis), and multiple sclerosis. While the specific causes of IMIDs are not fully understood, they are believed to result from a combination of genetic and environmental factors that trigger an inappropriate immune response. This response leads to chronic inflammation, which is the hallmark of these conditions.

If you're navigating the complex world of Immune-Mediated Inflammatory Diseases (IMIDs), understanding how these conditions differ between genders can be crucial. Recent studies shed light on these differences, particularly in Spondyloarthritis and Rheumatoid Arthritis.

Spondyloarthritis: A Tougher Battle for Women?

Spondyloarthritis, a type of arthritis affecting the spine, shows significant gender disparities. Research indicates that women with this condition might experience more severe symptoms (Rusman et al., 2018). The increased severity in women displays in various ways, including higher levels of pain and fatigue, more functional limitation (mean Functional Limitation Index ± SD: 21.2 ± 16.0 vs. 19.1 ± 16.7)(Garrido-Cumbrera et al., 2022), and potentially greater impact on overall physical function and quality of life.

In recent scientific developments, it has become increasingly clear that autoimmune diseases disproportionately impact women compared to men. Groundbreaking research has revealed that the expression of Xist, a long non-coding RNA crucial for X chromosome inactivation in females, may play a significant role in predisposing women to autoimmune diseases (Dou et al., 2024). This is further supported by studies showing that male mice when engineered to express Xist, develop autoimmune symptoms akin to those observed in females.

Additionally, evidence suggests that maternal autoimmune diseases could elevate the risk of certain cancers in offspring, highlighting the genetic and environmental intricacies of these conditions. Additionally, women with autoimmune diseases face unique challenges during pregnancy, including higher risks of complications, underscoring the need for specialized care and management strategies (Autoimmune Disease and Pregnancy | RheumNow, n.d.; Orimoloye et al., 2024).

Moreover, the disease progression in women with spondyloarthritis tends to differ from that in men, specifically in the pattern of symptoms, response to treatment, and the overall trajectory of the disease (Rusman et al., 2018). For example, women respond differently to certain medications compared to men, and their disease may follow a distinct course, necessitating a more tailored approach to management and treatment. This can impact diagnosis and treatment effectiveness, highlighting the need for gender-specific approaches in managing the disease. Without proper and prompt treatment SpA, especially axSpA, leads to irreversible joint damage which causes higher healthcare costs, work disability, physical comorbidity, psychological comorbidity, and decreased life quality (Al Rayes et al., 2023).

Rheumatoid Arthritis: Long-term Outcomes and Gender

When it comes to Rheumatoid Arthritis, another common IMID, the long-term outcomes can also vary by gender. Women often have distinct experiences compared to men. These differences aren't just in symptoms and severity but also in how the disease progresses over time. For women with RA, the risks can be multifaceted. They might experience more severe symptoms, which can lead to a greater impact on their quality of life. These symptoms include not only the traditional joint pain and swelling associated with RA but also general fatigue and a higher overall disease burden (Krasselt & Baerwald, 2019).

Women with rheumatoid arthritis (RA) face increased risks during pregnancy, both in terms of adverse maternal and fetal outcomes. A comprehensive systematic review and meta-analysis, which included over 50 million participants, highlighted that pregnant women with RA have a significantly higher risk of complications (Huang et al., 2023). These complications include cesarean section, pre-eclampsia, gestational hypertension, and spontaneous abortion. Additionally, the study noted an increased risk of adverse fetal outcomes such as preterm birth, being small for gestational age, low birth weight, congenital anomalies, and stillbirth. This emphasizes the necessity for close monitoring of RA patients before and during pregnancy.

In addition to the symptomatic and treatment-related challenges, women with RA are also at a higher risk for developing certain comorbidities. Osteoporosis, a condition characterized by weakened bones and increased fracture risk, is more prevalent in women with RA, partly due to inflammation and the use of certain RA medications like corticosteroids (Baker et al., 2022; Raterman et al., 2020). Furthermore, women with RA have an elevated risk of cardiovascular diseases, which can be exacerbated by the chronic inflammation associated with RA (Sparks et al., 2016).

Research into the role of dopamine in RA pathogenesis has revealed interesting gender-specific aspects (Wieber et al., 2022). Dopamine receptor 1 expressing B cells have been identified to exert a proinflammatory role, particularly in female RA patients, suggesting that women might have a distinct immunological response in RA compared to men.

Why This Matters for Patients

The McKinsey report delves into the gender disparity in health, particularly emphasizing the impact of conditions like RA (Ellingrud et al., n.d.). It highlights the "disability weight" for moderate RA at 0.3017, illustrating the significant quality-of-life reduction for those affected, potentially leading individuals to trade years of life to avoid prolonged suffering. This insight, combined with the report's focus on the broader women's health gap, which could add $1 trillion annually to the global economy by 2040, underscores the economic and health urgency. Women, often spending more time in poor health than men, face reduced societal presence and productivity. Addressing these disparities through targeted healthcare interventions and research can promise enhanced outcomes for women and substantial economic benefits, demonstrating why this gender disparity matters significantly for patients.