One of the major hurdles that has scuppered the sector’s awareness and management of Axial Spondyloarthritis (axSpA) is the long-entrenched perception that it’s male-specific. In fact, the role of gender in this chronic, inflammatory rheumatic disease might just surprise you. NIHR investigates why the disease’s impact has been discounted in the female population, and highlights the importance of more being done for women to ensure that they get the right diagnosis, at the right time, and receive the treatment they need.
Historically Axial Spondyloarthritis (axSpA) has been considered a disease that primarily affects men – however the emergence of new evidence is shifting our focus and opening up a new path for clinical consideration. In terms of this, it is now known that a significant proportion of women also suffer from axSpA. This prevalence is further fuelled by the discovery and concern that while diagnosis of axSpA has improved over the years, women still experience much longer diagnostic delay than men. As the burden is greater for women, increasing axSpA disease awareness will ultimately lead to better diagnosis and treatment for those affected by this condition.
axSpA: Facing the Facts
As the mission for a more axSpA-educated society marches on, the National Axial Spondyloarthritis Society’s website helps NIHR get to grips with the severity and symptoms of the condition we’re dealing with.
What is axSpA?
axSpA is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing severe pain, stiffness and fatigue. The disease typically starts in early adulthood, a critical period in terms of education and beginning a career path. One-in-200 of the adult population in the UK are impacted – that’s twice as many as multiple sclerosis and Parkinson’s disease.
What are the Symptoms?
The typical symptoms of axSpA include:
• Slow or gradual onset of back pain and stiffness over weeks or months, rather than hours or days
• Early-morning stiffness and pain, wearing off or reducing during the day with exercise
• Persistence for more than three months (as opposed to coming on in short attacks)
• Feeling better after exercise and worse after rest
• Weight loss, especially in the early stages
• Fatigue or tiredness
• Feeling feverish and experiencing night sweats
Although the painful form of inflammatory arthritis mainly affects the spine, it can also have an impact on other joints, tendons and ligaments. Other areas, such as the eyes and bowel, can sometimes be involved too:
• Inflammation occurs at the site where ligaments or tendons attach to the bone. This is known as enthesis
• The inflammation is followed by some wearing away of the bone at the site of the attachment. This is known as enthesopathy
• As the inflammation reduces, healing takes place and new bone develops
• Movement becomes restricted when bone replaces the elastic tissue of ligaments or tendons
• Repetition of this inflammatory process leads to further bone formation and the individual bones which make up your backbone (vertebrae) can fuse together
axSpA: The Female Focus
Explore the gender spectrum of axSpA – and why we must use it as a stepping stone for future change.
Instrumental to our treatment of axSpA and how we communicate it to patients must be the understanding that the condition is not troublesome for men alone – women have a greater, but different, burden to contend with. But why has the sector grappled with this realisation for so long – and what have been the drivers behind the misinformation regarding the female experience of the condition?
It used to be thought that three-times as many men as women had the disease, yet this was based on a diagnosis of the disease using x-ray. Men are more likely than women to experience changes to the bones and fusion, and thus they were being picked up using x-ray. Over time, however, a change in the sector’s approach to the condition occurred, contributed by the development of MRIs which could identify inflammation as women are more likely than men to experience inflammation rather than fusion.
To incorporate these changes in diagnostic techniques, the term axSpA was developed. This is an umbrella term and it includes:
• Ankylosing Spondylitis (AS) or radiographic axial spondyoarthritis – where changes to the sacroiliac joints or the spine can be seen on x-ray
• Non-radiographic axial spondyloarthritis (nr-axial SpA) – where x-ray changes are not present but inflammation is visible on MRI or you have symptoms
The prevalence of nr-axial SpA vs. AS is thought to be a ratio of one:one, while around seven-in-10 people with nr-axial SpA have visible inflammation in the sacroiliac joints or the spine when an MRI of the back is carried out.
Around three-in-10 may not have any inflammation visible on MRI despite symptoms of back pain. Some may never go on to develop visible inflammation on MRI – the reasons for this are still not well-understood, but may be due to the sensitivity of MRI.
Women with axSpA present differently to men and experience greater:
• Disease activity
• Widespread pain
• Peripheral involvement
• Functional impairment
Women and the Wider Impact of axSpA
From the under-the-surface mental health hindrance, to the limitations imposed upon their daily life pursuits, the less visible complications of axSpA can be incredibly debilitating for female sufferers. Many will experience severe fatigue, as well as a flare at some point which can make socialising, work and exercising problematic. The overwhelming feeling of not being able to be ‘normal’ when suffering from fatigue or in a flare also leads to the development of stress, anxiety and other related disorders.
The invisibility of the condition means that it is often difficult to communicate its impact to loved ones, leading to a profound effect on relationships – compounded by the findings that those with it are more likely to remain single or divorce than the general population, and women in particular are less likely to have children.
NIHR recaps some of the recent research on axSpA and how it’s offering enlightenment regarding the onset of the condition comparable between men and women.
Behind the Manifestations
In recent years, more and more studies have been homing in on the manifestations of axSpA and the underpinning factors. In particular, a key study presented at the 2016 American College of Rheumatology / Association of Reproductive Health Professionals Annual Meeting in Washington explored how gender and disease duration can help predict which axSpA patients will develop extra-articular manifestations, such as uveitis, or inflammation of the eye.
Gillian Fitzgerald, MD, Rheumatology Specialist Registrar at St. James’ Hospital in Dublin, and one of the authors of the study, explained that traditionally the condition was ‘thought to be a disease that almost exclusively affected men. However, more recently this has been shown not to be the case. Women can be affected almost as often as men. Therefore, we are very interested in looking at the gender differences in axSpA, and we specifically wanted to look at whether there are any differences between genders in the prevalence of these extra-articular manifestations.’
The researchers performed a standardised, detailed clinical assessment on 564 patients, and found that prevalence of uveitis is significantly higher in women (46.7 per cent vs. 32.3 percent), and that IBD prevalence is significantly higher in women (16.5 per cent vs. 7.7 per cent).
The data additionally demonstrated that being female and having axSpA disease for more than 10 years is predictive of uveitis, and being female, having an elevated CRP at baseline and peptic ulcer disease are predictive of IBD.
Behind the Burden
More recently, a 2018 review, ‘Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky’ by T Rusman, R F van Vollenhoven, and I van der Horst-Bruinsma, has provided evidence which helps dismantle the view that axSpA is a male-specific disease and demonstrates the complex burden for women in more detail.
Some of the findings reported include:
• The age of onset of AS does not differ between males and females, but females seem to have a relatively longer delay in diagnosis
• Despite the improvement in delay of diagnosis in women with axSpA, there is still a longer delay and more often misdiagnosis in women, which increase the disease burden in the female patient group
• Female axSpA patients showed a higher disease burden concerning disease activity and pain scores
• Females corresponded with a significantly lower quality of life
• Despite the fact that male axSpA patients have more radiographic damage compared to females, female patients have a higher disease burden due to a longer diagnostic delay, higher disease activity, and a lower efficacy of treatment