What Causes Ankylosing Spondylitis? 4 Risk Factors for This Type of Spinal Arthritis

Ankylosing spondylitis (AS) is a rare condition defined by inflammation in the joints and tissues of the spine, which can lead to spinal stiffness. When AS is severe, the small bones in the spinal column can actually fuse together, says the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

What sets off this inflammatory process? Experts don't know for sure, although there's reason to suspect that your genes may be involved.

What causes ankylosing spondylitis?

A review article published by the US National Library of Medicine (NLM) points to an association between ankylosing spondylitis and a protein called HLA-B27, which is found on the surface of infection-fighting white blood cells. More specifically, a mutation in a gene called HLA-B produces this protein, which can elevate your risk of AS, according to the Cleveland Clinic.

So, while the exact cause of AS is unknown, a few clues have surfaced.

"We know it's an inflammatory process. There is some genetic predisposition to it, especially as a link to the HLA-B27 marker," explains Nick Shamie, MD, chief of orthopedic spine surgery and professor of orthopedic surgery and neurosurgery at UCLA School of Medicine.

But, as Dr. Shamie tells Health, "we don't know if there are environmental factors that affect you to be more predisposed to this, nor we do we know if there's anything we can do to prevent it from happening."

Meantime, scientists continue to look for other clues. One hypothesis is that changes to the gut microbiome may trigger an immune response that leads to ankylosing spondylitis, particularly in patients with HLA-B27. But researchers are still trying to understand if this is true and for how many patients, notes the Spondylitis Association of America (SAA).

What are the risk factors for ankylosing spondylitis?

While anyone can develop AS, certain things can boost your risk, and they include:

A positive HLA-B27 test

If your doctor suspects ankylosing spondylitis, you will likely have an HLA-B27 blood test. Per the NLM, the presence of this protein suggests that you are at greater risk of developing AS.

Still, most people who test positive for the protein don't become ill.

"We don't have a good idea of why certain patients develop it and certain patients don't," says Anand Veeravagu, MD, assistant professor of neurosurgery and director of minimally invasive neurospine surgery at Stanford Medicine. Lots of people are positive for HLA-B27 and never develop ankylosing spondylitis, and the opposite is also true: "There are many patients who don't have HLA-B27 gene positivity that still have a diagnosis of ankylosing spondylitis," Dr. Veeravagu tells Health.

According to the SAA, the association between AS and this blood marker varies greatly by race and ethnicity. While 95% of white people with AS test positive for HLA-B27, only 50% of Black people with AS are HLA-B27-positive.

Meantime, scientists have started identifying other genes that may play a role in ankylosing spondylitis. There are now at least 60, including ERAP 1, IL-12, IL-17, and IL-23, says the SAA. It's likely that many genes are involved in causing the condition rather than a single one.

Family history

How much does family history influence your risk of developing AS? Studies offer varying estimates, as a 2021 review article in Frontiers in Genetics points out. But the consensus seems to be that having a first-degree relative (a parent, sibling, or child) with ankylosing spondylitis means you're more likely to develop this chronic disease.

Again, just because you have a family member with AS doesn't mean you will develop it. It's likely that multiple genetic and environmental factors play a role in determining one's risk, says NLM.

Age

Symptoms of ankylosing spondylitis usually begin between the ages of 17 and 45, notes the Cleveland Clinic.

"It's known to peak in the second and third decade of life," Dr. Shamie says. "The 20s and 30s [are] when you first start seeing signs and symptoms of it."

But that's not always the case. The SAA notes that anyone can develop AS, even children and older adults.

Having another inflammatory condition

People with Crohn's disease, ulcerative colitis, or psoriasis may be more likely to develop ankylosing spondylitis, say NIAMS. These conditions has long been associated with AS, but the exact relationship is unclear. The National Axial Spondyloarthritis Society (NASS) lists these conditions among the complications and comorbidities of AS.

Is sex a risk factor for ankylosing spondylitis?

Experts used to think that ankylosing spondylitis mostly affected men, that it was predominantly a male disease. It's not hard to understand why: men are more apt to develop joint changes that are visible on X-ray, explains NASS. Women, though, are more likely to experience inflammation than bone fusion. So, until MRI became more widely used, women's symptoms often slipped through the cracks.

It remains true that males are diagnosed more often than females. Women accounted for 47% of AS patients in 2016, according to an analysis funded by pharmaceutical giant Eli Lilly and Company, which was published in BMJ Rheumatology in 2019.

However, that doesn't make AS a male disease. A 2020 review in Rheumatology finds that the burden of disease is similar for males and females. Separately, an analysis of gender differences published in 2018 in Current Rheumatology Reports finds that women with AS face delays in diagnosis, less effective treatment, and greater disease activity than men.

What can trigger an ankylosing spondylitis flare-up?

As with other inflammatory conditions, ankylosing spondylitis symptoms can wax and wane over time, meaning that it's not usual for people with AS to have episodes of worsening symptoms followed by periods during which symptoms subside, says the SAA.

So what triggers these flare-ups? That's not well understood, notes the SAA. The factors involved may vary from one person to the next, but the possibilities may include:

Overactivity

Depending on where in the body your ankylosing spondylitis symptoms are most severe, activities that overwork those areas can sometimes lead to a flare in pain and require rest and additional help from your doctor, Dr. Veeravagu says.

Physical therapy can be an important part of managing ankylosing spondylitis, as it both strengthens the muscles that must support the joints most affected, and can also teach you new movement patterns that aggravate those joints less, he says.

Stress

"Any kind of pain can be triggered by environmental stressors, and that includes psychological stressors like depression, increased anxiety, [and] family stressors," Dr. Veeravagu says. These kinds of stressors can make pain medication and other anti-pain therapy less effective, too, he says, so it's important for patients and doctors to work together to manage outside stress.

"Getting proper sleep, taking care of yourself, and eating right can all lower your stress level," says Dr. Shamie.

Weather

Where you live might have an impact on your condition. "In general, cold weather tends to be something that a lot of ankylosing spondylitis patients indicate makes them feel a little worse," says Dr. Veeravagu. But that's not always the case, and every patient reacts a bit differently. "It's very subjective," he says.

Smoking

Smokers, particularly men who smoke, tend to have more severe disease than those who don't, notes the Arthritis Foundation. And NASS points out that smoking can worsen AS symptoms, while quitting smoking may result in improvements in symptoms and overall quality of life. And, of course, quitting smoking is a bonus for your health in general.