Axial spondyloarthritis has historically been thought of as a male disease. This is especially true of ankylosing spondylitis, a severe type of spondyloarthritis in which new bone growth in the spine can cause vertebrae to fuse. In the past half-century, research has shown that axial spondyloarthritis does affect women. The difference in axial spondyloarthritis incidence between men and women is much lower than previously estimated, possibly as low as 1 woman to every 2.5 or 3 men.
The misperception that women are unlikely to develop axial spondyloarthritis is problematic because it results in underrecognition of the disease by doctors and in diagnostic delays that adversely affect women.
Axial spondyloarthritis is a type of inflammatory arthritis that primarily affects the spine and hips. It is an autoimmune disease that causes inflammation in the vertebrae and spinal ligaments. Inflammation can also occur in parts of the body besides the spine, known as peripheral inflammation. Peripheral inflammation can affect the joints, tendons, and ligaments in the shoulders, knees, ribs, ankles, and feet.
Over time, this inflammation in the joints and tissues can cause stiffness. In severe cases of axial spondyloarthritis, known as ankylosing spondylitis, new bone growth can occur and the vertebrae can fuse together. Fusion of the vertebrae leads to a rigid, inflexible spine which makes it difficult to bend.
Chronic back pain is a common issue. One study found as much as 80 percent of the U.K. population had back pain at some point in their lives. Chronic back pain from inflammation is less common. Axial spondyloarthritis causes inflammatory back pain, as opposed to mechanical back pain. Recognizing the distinct symptoms of axial spondyloarthritis can be difficult. It can be especially challenging in women because axial spondyloarthritis may be more likely to mirror other rheumatic and inflammatory conditions that also cause back pain.
Chronic back pain and stiffness, often worse in the morning, are the leading symptoms of axial spondyloarthritis. The pain is usually in the lower back where the spine and pelvis connect. Women more often experience pain in the neck than men. In addition to chronic back pain and stiffness, symptoms can include:
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Unfortunately, there is no single test or unique symptom that identifies axial spondyloarthritis. Doctors make an axial spondyloarthritis diagnosis based on the combined results from a physical exam, blood tests, imaging, and a person’s self-reported symptoms. Diagnosing axial spondyloarthritis is a clinical judgment call from a doctor.
Doctors consider the symptoms of inflammatory back pain along with other evidence of inflammation or damage to the sacroiliac joints, such as that found in imaging and lab tests. For instance, a blood test can detect the presence of HLA-B27, a genetic marker associated with ankylosing spondylitis. A positive HLA-B27 test may indicate that back pain is associated with ankylosing spondylitis.
When it comes to diagnosing axial spondyloarthritis, the hallmark symptom is sacroiliitis. Women with axial spondyloarthritis, however, tend to show less damage in imaging tests, such as magnetic resonance imaging (MRI) and X-rays.
Evidence of axial spondyloarthritis that is visible on X-rays is known as radiographic. This term is good to understand because doctors may refer to axial spondyloarthritis as being “radiographic” (visible on X-rays) or “nonradiographic” (not visible on X-rays). “Radiographic axial spondyloarthritis” is a newer term for ankylosing spondylitis.
Axial spondyloarthritis diagnostic criteria often fail to consider sex differences between men and women. Women’s symptoms often present in a different way from men’s. Methods used to diagnose axial spondyloarthritis may miss some symptoms that are more common in women.
Even with recent advancements and improvements, axial spondyloarthritis can be difficult to diagnose. Women with axial spondyloarthritis are significantly more likely to be misdiagnosed than men. A 2018 study in PLoS One found that one-third of males received a correct axial spondyloarthritis diagnosis after their first visit to a health care provider. Only one-tenth of women in the study were correctly diagnosed after one appointment.
Women with axial spondyloarthritis are more likely to be diagnosed with benign conditions, such as nonspecific chronic low-back pain or foot pain. Another common misdiagnosis is fibromyalgia, a chronic disorder that causes muscle pain and fatigue. Fibromyalgia and ankylosing spondylitis share other commonalities, making diagnosis more challenging. Having ankylosing spondylitis can also increase a woman’s risk of developing fibromyalgia.
After one or more misdiagnoses, a woman who finally receives a correct diagnosis of axial spondyloarthritis may have experienced more disease progression and lasting damage due to the delay.
Despite a general improvement in diagnosing axial spondyloarthritis, women continue to have a significantly longer delay in diagnosis than men do. A meta-analysis conducted in 2016, published in The Journal of Rheumatology, found an average delayed diagnosis of 8.8 years for women. Men in the same study experienced a diagnostic delay averaging 6.5 years.
Some physicians still rely on X-rays to detect sacroiliitis, a hallmark of axial spondyloarthritis. But traditional X-rays can only detect damage after seven to 10 years of unchecked disease progression.
MRI imaging is now considered the gold standard for diagnosing sacroiliitis. MRIs are better able to detect less severe damage earlier in the disease process than X-ray images. Women tend to have nonradiographic axial spondyloarthritis, showing no or less damage on X-rays than men’s spondyloarthritis. This makes relying too heavily on imaging to diagnose axial spondyloarthritis in women problematic.
Inflammation levels in the body may be detected by a blood test that measures a chemical called C-reactive protein (CRP). However, women with axial spondyloarthritis tend to have less measurable inflammation, or lower CRP levels, in their blood.
There is a dearth of studies designed to analyze the differences between men and women when it comes to spondyloarthritis. Dr. Vega Jovani of the University General Hospital of Alicante, Spain told The Rheumatologist, “There is a lack of sex-stratified results in most studies of diagnostic delay in spondyloarthritis, and influences of sex were rarely discussed.” This may contribute to the underrecognition and underdiagnosis of axial spondyloarthritis in women.
Gender bias also contributes to the underdiagnosis of axial spondyloarthritis in women. Although axial spondyloarthritis has been thought of as a man’s disease, research shows the prevalence of the disease is similar in men and women. Doctors also need to understand that women more frequently present with the symptoms of enthesitis (heel and tendon pain) and peripheral arthritis (arthritis in joints outside the spine and hips) compared with men.
As with other autoimmune disorders and inflammatory arthritis, axial spondyloarthritis requires early diagnosis and early treatment to stop or slow disease progression. This can help prevent joint deformity, disability, and associated health problems, such as cardiovascular disease.
A small percentage of people with inflammatory arthritis go into remission without proper treatment. Estimates suggest it’s as low as 5 percent. The vast majority will develop a chronic, progressive condition. Without early treatment, people with spondyloarthritis can suffer irreversible joint damage and associated health conditions, such as inflammatory bowel disease.
The mainstay treatments for spondyloarthritis are disease-modifying antirheumatic drugs (DMARDs), such as methotrexate and biologic tumor necrosis factor (TNF) inhibitors adalimumab (Humira), infliximab-dyyb (Inflectra), and golimumab (Simponi).
Starting treatment early can delay or even prevent irreversible spine curvature, limited mobility, and disability. Early treatment can reduce the amount of inflammatory damage done to the sacroiliac joints and may help lower the risk for developing associated conditions, such as atherosclerosis (hardening of the arteries).
In early inflammatory arthritis cases, there is a window of opportunity for treatment. It is thought that treating the condition in its earliest stages may help a person avoid irreversible joint erosion. The American College of Rheumatology conducted a meta-analysis of 14 clinical trials. The results of the study indicated that people who experienced a shorter disease duration before diagnosis were more likely to respond better to treatment and show decreased disease activity.
Evidence suggests that women with spondyloarthritis carry higher disease activity and levels of functional impairment than men do. Women, more than men, experience chronic pain of a generalized versus a focused nature. Women are also more likely to experience the peripheral pain symptoms and associated conditions of axial spondyloarthritis, such as inflammatory bowel disease.
According to a 2014 study in Arthritis Research & Therapy, women with ankylosing spondylitis are 80 percent more likely to experience depression than the general population, while men with ankylosing spondylitis experience depression at a rate 50 percent higher than men without the condition. Prompt diagnosis and earlier treatment can substantially improve quality of life.
Thanks to research and technological advancements, the diagnosis and classification of spondyloarthritis has improved. Overall, science has acknowledged the need for research inclusive of the biological sex differences in spondyloarthritis.
In the 1940s, scientists estimated that only 1 woman for every 9 to 10 men had ankylosing spondylitis. Today, researchers know women develop the condition more frequently than that.
Doctors now know that changes are visible earlier on MRI than in the radiographic activity shown in X-rays. Applying diagnostic criteria and tools through the lens of sex differences could help reduce the diagnostic delay, especially for women with spondyloarthritis.
With axial spondyloarthritis specifically, sex differences seem to play an important role. Researchers acknowledge the need to pay more attention to these differences when studying disease, as well as when diagnosing and treating people. However, more research is needed to fully inform how sex plays a role in spondyloarthritis.
Improved knowledge needs to be better translated into clinical practice. More education about sex differences among doctors who do not specialize in inflammatory and rheumatic disease is necessary. Better training for primary care physicians will empower them to consider axial spondyloarthritis as a diagnosis for more women who present with chronic back pain, hopefully leading to earlier diagnosis and treatment.
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