Diagnostic criteria put out by medical organizations are supposed to help make diagnoses more straightforward for doctors and patients by defining what the disease is. They should make it easier to study the disease and easier to decide treatment. But what about when those criteria are based on biased assumptions? Research for spondyloarthritis has a history of discrimination affecting women and people of color, and decisions continue to be made from that research. Doctors and researchers need to consider this when making recommendations and designing studies today.
Spondyloarthritis (SpA) is a group of autoinflammatory diseases that mostly feature arthritis of the spine which can lead to spinal fusion. The most well-known of these is ankylosing spondylitis, and others include psoriatic arthritis and arthritis with inflammatory bowel disease. Common symptoms of these conditions are low back pain, tendonitis, and arthritis of other large joints (hips, knees, shoulders). Morning stiffness and fatigue are also common, and pain often gets better with activity and worse with rest. It’s not a rare disease, but it’s so underdiagnosed that people treat it like one.
SpA has a notoriously long diagnostic delay, often seven to 11 years from onset of symptoms. This is partly because joint damage from the disease isn’t visible on X-rays right away. That’s why the most recent Assessment of Spondyloarthritis International Society (ASAS) criteria were created: they include a type of SpA called “non-radiographic,” which can diagnose someone with SpA before there’s extensive damage to their body. The requirements? That they have at least two of the listed symptoms of SpA and a gene called HLA-B27.
SpA has long been associated with the gene HLA-B27, a protein found on the surface of white blood cells. HLA-B27 is commonly cited as being found in up to 95% of (white) people with AS. The importance placed on HLA-B27 could be a problem for women and people of color, though, and I don’t see this being addressed.
Studies have found that people of color with SpA have lower rates of HLA-B27, as do women of all ethnicities. The starkest difference affects African Americans: only about half of African Americans with SpA have HLA-B27. Being female and not having HLA-B27 are both associated with longer diagnostic delays and less successful treatment, which could help explain why women and people of color with SpA face more active disease and more disability than men and whites, respectively.
This has to be talked about. Why is HLA-B27 still considered so important when it’s really most prevalent in white men? Women and people of color already face disturbing gaps in healthcare quality, and diagnostic criteria shouldn’t make it easier for this to continue by delaying diagnosis and creating barriers to research participation.
Early diagnosis is extremely important for effective treatment. It’s true that doctors don’t sit with the ASAS criteria out in front of them when they diagnose a patient, but the criteria still perpetuate the high regard given to HLA-B27 for diagnosis. Doctors might know that it’s not present in all cases, but the fact is, it’s currently very hard to be diagnosed without it: multiple doctors were on the cusp of diagnosing me, only to stop when they found out I didn’t have the gene. My mom was “lucky” enough to have clear damage visible on MRI so that she could be diagnosed, but no one should be lucky to have physical damage to their body.
Diagnostic criteria also affect research. Clinical studies are important to the approval of any drug or treatment, and it’s crucial to know how these drugs work for all people. If ASAS criteria are used to determine who qualifies for a study, it could mean that fewer women and people of color are included.
Not that this is anything new. For decades, SpA was thought to be a predominantly male disease because the symptoms were defined based on men’s experiences, which led to fewer women being diagnosed and participating in studies. And while there isn’t an SpA-specific reason that people of color were excluded from studies, there’s a general history of people of color being underrepresented in research. It’s no wonder that the current state-of-the-art SpA treatments are less effective for women and people without HLA-B27.
We need to increase the number of patients without HLA-B27 in trials, not make it harder for them to participate. Diagnostic criteria with such serious bias need to be reconsidered. For example, criteria that are based on family history or that allow for other known (but less prevalent) genetic markers could acknowledge the important role genetics play while avoiding harmful restrictions.
SpA can’t be the only condition affected by this unconscious reliance on unintentionally biased data, but it’s the one I’m most familiar with. In this case, it’s true; the studies strongly associate HLA-B27 with SpA. But why? Who participated in these studies? Is there an alternative that can be used? Medicine in the past was touched by discrimination, so reliance on historical givens isn’t necessarily accurate. Doctors and scientists need to think critically about this and make decisions that are best for all people.