We need to leave behind prejudiced science

Diagnostic criteria put out by medical organizations are supposed to help make diagnosis 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

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 (AS), and some others are psoriatic arthritis and arthritis with inflammatory bowel disease.

(Some 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. If this sounds like you, talk to a doctor! Somewhere around 1% of the population have SpA, but it’s incredibly underdiagnosed.)

SpA has a notoriously long diagnostic delay, often 7-11 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 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 as well as a gene called HLA-B27.

The numbers

SpA has long been associated with the gene HLA-B27, a protein found on the surface of white blood cells. HLA-B27 is often 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 women with SpA have lower rates of HLA-B27 (somewhere around 80%) along with longer diagnostic delays and less successful treatment. People of color also have lower rates of HLA-B27, with the starkest difference affecting African Americans: only around 50% of African Americans with SpA have HLA-B27! Not having HLA-B27 is also associated with less successful treatment outcomes. Women and people of color already face disturbing gaps in healthcare quality, and diagnostic criteria should not make it easier for this to continue.

What it means for diagnosis

Earlier diagnosis is extremely important for effective treatment. It’s true that doctors don’t sit there 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 can be very hard to be diagnosed without it. And the difference between 95% (1 in 20 won’t have HLA-B27) and 80% (1 in 5 won’t have HLA-B27) and 50% (1 in 2 won’t have HLA-B27) is huge for the mindset doctors have when evaluating a patient.

This has to be talked about. Why is HLA-B27 still considered so important when it’s really most prevalent in white men? Multiple doctors were on the cusp of diagnosing me, only to stop when they found out I didn’t have it. 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.

What it means for research

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 members of the population. If ASAS criteria are used to determine who qualifies for a study, it could mean that fewer women and people of color will be included.

Not that this is anything new: for decades, SpA was thought to be a man’s disease, with women having “atypical” SpA because their symptoms were different (as a result, the male-to-female ratio for the disease was thought to be 9:1 when we now find it to be 1-3:1).⁹ This led to women not being included in studies of the disease, which is perhaps why treatments don’t work as well for women. Today, women with SpA face more active disease and more disability than men.¹

Similarly, African Americans have been historically underrepresented in medical research studies. African Americans with SpA have also been found to have more severe disease and face more disability than white patients, as have Latinos with SpA. This especially makes sense considering that current treatments are less effective for 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 in autoimmune disease while avoiding harmful restrictions.

SpA can’t be the only condition affected by this unconscious reliance on unintentionally biased data, although 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.

-Bri

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