Spondyloarthritis affects up to 1.4 percent of the U.S. population — approximately 4,590,000 people, according to the American College of Rheumatology. More people are likely living with spondyloarthritis and don’t know it or haven’t been diagnosed. Axial spondyloarthritis is a chronic, inflammatory form of arthritis that primarily impacts the axial skeleton — the spine, hips, and rib cage. For women, axial spondyloarthritis is thought to be frequently underdiagnosed or misdiagnosed when compared to men.
Axial spondyloarthritis may be underrecognized in women because it historically has been thought of as a man’s illness. In the past, axial spondyloarthritis research has largely focused on men, contributing to the misperception that it rarely affects women. In recent years, more studies have included women in greater numbers. However, there’s not enough data yet to get concrete answers about the role of sex differences (sometimes referred to as gender differences) in axial spondylorarthritis.
It is helpful to understand some terms used to describe axial spondyloarthritis. Spondyloarthritis can manifest in different forms, including axial (affecting mainly the spine and hips) or peripheral (affecting mainly arms and legs).
Spondyloarthritis may also be described as “radiographic” or “nonradiographic”. In radiographic axial spondyloarthritis, damage to joints can be seen in X-rays. Radiographic axial spondyloarthritis, which is also called ankylosing spondylitis, is a severe form that primarily affects the sacroiliac joints where the spine meets the pelvis. In nonradiographic axial spondyloarthritis, joint damage is not yet visible in X-rays, although it may be visible on magnetic resonance imaging (MRI) scans.
Several studies that considered the differences between women and men with axial spondyloarthritis showed that women had different disease manifestations from men. Men with ankylosing spondylitis show higher scores on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and modified Stoke Ankylosing Spondylitis Spine Scores than women do. This suggests that men with axial spondyloarthritis show more radiographic damage and radiographic progression on X-rays.
Watch Emily Johnson, founder of the Arthritis Foodie community, discuss the difficulties in being diagnosed with arthritis.
The age of disease onset of axial spondyloarthritis does not differ between males and females. However, men and women tend to experience different symptoms and clinical characteristics of axial spondyloarthritis. Scientists believe this is likely due to biological differences in the genes, immune systems, and hormone levels in men and women.
There are genetic differences between men and women with axial spondyloarthritis. For instance, a gene known as HLA-B27 has been determined to be a risk factor for developing ankylosing spondylitis, a severe form of axial spondyloarthritis. HLA-B27 positivity occurs equally in men and women, but is more commonly found in men with ankylosing spondylitis than in women with the condition.
Another gene called ANKH is also being studied as a potential source of sex differences among people with axial spondyloarthritis.
Researchers believe sex hormones may activate various genes that influence a person’s immune response. The hormone estrogen is a complicated factor in several autoimmune diseases — protecting women against some autoimmune conditions and contributing to others. One study on mice suggested that estrogen may play an anti-inflammatory role in spondyloarthritis, but more research is needed before any conclusions can be drawn about the influence of sex hormones on axial spondyloarthritis in women.
Sex hormones are known to have specific effects on a person’s immune system. Research suggests that men with axial spondyloarthritis tend to have higher levels of tumor necrosis factor (TNF) alpha, C-reactive protein, and interleukin-17 compared with women.
The complex interaction between genes, sex hormones, and the immune system can moderate or aggravate different aspects of axial spondyloarthritis symptoms and disease progression. More research is needed to fully understand why and how these differences exist between men and women with axial spondyloarthritis.
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The most common symptoms of spondyloarthritis are inflammatory back pain, including sacroiliitis, and stiffness or limited movement. Spondyloarthritis can also impact other parts of the body or have systemic effects. Symptoms that affect areas of the body outside of the lumbar region (lower back) are called extra-articular manifestations (EAMs).
Research suggests that women experience more EAMs than men do. Specifically, women with axial spondyloarthritis are thought to be more likely than men to develop:
Nearly 40 percent of people with ankylosing spondylitis experience inflammation of the eyes. Acute anterior uveitis is thought to be more prevalent in males. However, a 2018 meta-analysis in Current Rheumatology Reports found approximately 28.5 percent of men with axial spondyloarthritis developed acute anterior uveitis compared to 33.3 percent of women, which indicates the rate of incidence may be similar between the sexes.
Spondyloarthritis may cause inflammation where the ligaments and tendons attach to bones, known as entheses. Inflammation of the entheses is known as enthesitis. Spondyloarthritis can affect entheses anywhere in your body, but it most commonly shows up at the back of the heel, near the Achilles tendon. Enthesitis is more common and tends to be more severe in women with axial spondyloarthritis than in men.
The inflammation that causes spondyloarthritis can also affect the gastrointestinal system. The Current Rheumatology Reports meta-analysis indicates that between 5 percent and 10 percent of people with axial spondyloarthritis also have IBD. Women with axial spondyloarthritis are more likely to experience IBD than men with axial spondyloarthritis.
The overactive autoimmune response that causes spondyloarthritis can trigger the development of psoriasis, an inflammatory skin condition. Approximately 10 percent of people with axial spondyloarthritis develop psoriasis, according to Current Rheumatology Reports. Some studies suggest that women with axial spondyloarthritis experience a higher rate of psoriasis compared to men.
The 2018 meta-analysis in Current Rheumatology Reports showed that women with axial spondyloarthritis reported a lower quality of life compared with men. Despite the fact that men with axial spondyloarthritis are considered to have a worse prognosis for disease progression, women are said to have a higher disease burden. This may be due to the fact that women often have to wait longer for a correct diagnosis. Women also show more disease activity and have less response to the TNF-alpha inhibitor (TNFi) treatments often used for axial spondyloarthritis.
Women with ankylosing spondylitis, a severe form of axial spondyloarthritis, often show higher scores than men on the BASDAI, a subjective measure of symptoms. Specifically, women report worse fatigue and back pain, and longer-lasting stiffness in the mornings.
Women often have longer waits for receiving an axial spondyloarthritis diagnosis compared to men. This may be because of the general underrecognition of the disease and its diagnostic criteria, especially in women. Women also tend to show less visible damage on X-rays and have a different clinical presentation from men.
Women experiencing longer diagnostic delays could also be the result of bias from health care professionals. There is a misperception that axial spondyloarthritis is largely a male disease, coupled with a lack of knowledge about how the disease manifests differently in men and women. Sex-based discrepancies in diagnostic delays are likely caused by a combination of these factors.
Lower Treatment Response and Fewer Options
TNF-alpha inhibitors are one class of treatments for spondyloarthritis. Multiple TNFi medications have been approved by the U.S. Food and Drug Administration (FDA) in recent years.
Although TNFi drugs offer many benefits to most people with axial spondyloarthritis, some studies point to important sex differences in their effectiveness. Women show lower response rates to treatment with certain TNFi medications. In other words, some treatments for axial spondyloarthritis may be less effective in women than in men.
Some newer biologic medications are available to treat ankylosing spondylitis and nonradiographic axial spondyloarthritis. Women, who are more likely to have a nonradiographic form of the condition, may have fewer treatment options for this reason.
Research presented at the American College of Rheumatology's 2018 annual meeting suggests significant sex differences in how axial spondyloarthritis affects the social aspects of quality of life, including work. This table illustrates some of the main differences.
|Social Impact of Axial Spondyloarthritis in Women vs. Men|
|Consequences of Axial Spondyloarthritis||Women||Men|
|Difficulty maintaining friendships||45%||25%|
|Often late to work||29%||12%|
|Forced to switch jobs||24%||15%|
Source: Ankylosing Spondylitis Is Probably Hurting Your Relationships and Ability to Work, But Too Few Patients Tell Their Doctors About It — CreakyJoints.
Axial spondyloarthritis is underdiagnosed in women, in part because of the difference in the way it presents and manifests. Knowing these differences can be your best tool in getting a prompt and accurate diagnosis, receiving the best follow-up health care for your condition, and advocating for your quality of life.
A rheumatologist experienced in diagnosing and treating axial spondyloarthritis is your best bet for an accurate diagnosis the first time.
For guidance on preparing for a conversation with your doctor, read When Your Doctor Won’t Listen: Tips for Women With Spondyloarthritis.
Support is crucial when you’re living with a chronic condition. MySpondylitisTeam, the social network for people with spondylitis, has your back. More than 85,000 members come together to ask questions, give advice, and share their experiences with others who understand life with spondylitis.
What sort of symptoms do you experience with spondyloarthritis? Comment below or share your thoughts on MySpondylitisTeam.