Ancient skeleton with RA may suggest ‘we’ve been dealing with these diseases forever’

Archaeologists in Egypt recently discovered evidence of an ancient case of rheumatoid arthritis, potentially filling in the timeline of humanity’s relationship with autoimmune disease.

The skeleton was excavated in 2018 from an ancient cemetery in what is now Aswan, in southern Egypt, and determined to be that of a woman aged 25 to 30 years who lived between 1750 BCE and 1550 BCE. Macroscopic examination revealed bilateral, erosive periarticular lesions with smooth borders on multiple hand and foot joints. A differential diagnosis, limited by a lack of X-ray imagery and other facts of the passage of time, suggested the woman most likely suffered from the condition we now know as RA, Madeleine Mant, PhD, of the University of Toronto Mississauga, and colleagues wrote in a study published in January in the International Journal of Paleopathology.

The discovery joins a growing number of possible prehistoric RA cases, many of which remain controversial.

“Understanding the history of autoimmunity in general is really fascinating and something that I don't think we have a very good grasp on,” Adam J. Brown, MD, a rheumatologist at the Cleveland Clinic and host of the podcast Healio Rheuminations, told Healio. He added that this skeleton could be a clue that “these diseases are probably just in our genes somewhere — that we’ve been dealing with these diseases forever.”

Healio sat down with Brown to learn more about what this latest finding could mean for the history of RA — and what this ancient woman’s life may have been like.

Healio: What do you think about the methodology of diagnosing RA in this skeleton?

Brown: There have been talks about other diseases, like diagnosing a skeleton with ankylosing spondylitis from the skeletal remains, but I think it sort of got disproven and is actually just the natural progress of what happens to bones over time. So there’s always that question of what happens to bones over thousands of years. Is it just chipped away and how bones disintegrate?

For this particular skeleton, it’s multiple joints, not just one or two, and they’re all in the pattern that we could potentially see in rheumatoid arthritis. So, I wouldn’t say “absolutely not” to it. I think it’s very possible.

Also, the erosions in rheumatoid arthritis are somewhat unique. The article goes on to talk about why they’re probably not psoriatic arthritis or gout, for instance. First of all, gout is pretty easy; they think the skeletal remains are from a young woman, so gout, especially back then, would be extremely rare in a very young person. So that’d be unlikely. The pattern of joint erosions is more consistent with rheumatoid arthritis than psoriatic arthritis, although that could be difficult to say for sure.

Healio: What would it have been like to live in ancient Egypt with RA?

Brown: It would be unbelievably difficult, I imagine. I think living with untreated rheumatoid arthritis now is extremely difficult, and we have modern conveniences of people driving you in cars and taking aspirin and ibuprofen, and getting a nice hot pool or something to calm the joints down. However, back then they didn't have access to any of that. I’m not sure what people would do if they couldn't walk, if the hips were too severely arthritic, their knees too severely arthritic. What capabilities did they have to kind of push people around — in carts?

Not only is mobility an issue, but also just the pain — everyday severe pain with movement, severe swelling of joints, severe stiffness. And then if you had a job, which was very common back in the day, having to do pretty significant manual labor, it would have been practically impossible over time to do these things. You’d have to question, what was the social help situation there? Where, if someone’s severely disabled, are they not required to work? Does the family take over to do all their tasks for them? That’s a whole bunch of big question marks. And I think it's hard now, let alone what it must have been like a thousand years ago. I can't imagine how difficult that would have been.

Healio: What treatment or management options might have been available?

Brown: It probably would have been putting warm towels around somebody, but again, heating water back then was hard. All these things would be very, very hard. It probably would have involved some sort of what we think of now as a mystical solution, like some sort of salve or beeswax that that I don't know anything about. However, every culture had their own ways of healing, which they probably would have tried to apply with mixed results, I'm sure.

As we can see, from this patient’s erosions, if they’re truly rheumatoid, whatever it was probably didn't work too well. This patient was probably in severe pain and disability.

Healio: How should we be thinking about genetic vs. environmental causes of RA in light of this finding?

Brown: I did a podcast series on this called “The Environment and Autoimmunity.” It starts with allergies, like sinusitis and rhinitis and allergic rhinitis, and how there’s basically no description of allergic rhinitis until the Industrial Revolution, and then all of the sudden everyone has allergies. The question is whether or not allergies come from some sort of changes in our environment. Allergy has a pretty clear indication that there probably is an association, but autoimmunity is a little bit tougher, because there have been decent descriptions that patients probably suffered from this.

The problem is using our modern terms to know for sure what they were referring to back in the day. Gout, again, is easy. Patient has severe toe swelling and pain, they couldn't walk and they couldn't put a blanket on it. People describe that pretty well from hundreds of years ago. However, rheumatoid is a little bit more subtle I think, and it’s harder to make heads or tails if we had it back in the day.

There is this theory that there’s probably no rheumatoid until very recently, because now lots of people have rheumatoid. It’s still less than 1% of the population, so it’s not common, and, similar to allergies, it’s probably something from our environment, according to this theory. There may be truth to that. The data’s kind of all over the place on how true it is.

I give a talk in the podcast about a good example of this in northwest Russia, near the border of Finland. Finland has mostly moderate amenities and health care and sanitation, and it’s fairly wealthy. And then the town right next to it is in northwest Russia, and that area is impoverished. However, it has very similar genetics compared with the people in Finland, and it has one-one-hundredth the risks for autoimmunity in that area. There’s something about this that’s probably compelling. There’s something in our environment that we don’t quite understand.

There’s even data on migration. If someone is coming from an area with very low rates of autoimmunity and they move to Europe or England, for example, they actually have a much higher rate of developing autoimmunity once they’ve moved, but the move has to happen before the age of 15 years. So, I think there is definitely something about the environment. However, I think that there’s probably higher rates of autoimmunity now, and I think the environment is involved, but that’s probably just a piece of the puzzle. I’m not totally surprised by there being evidence of this disease being around forever — for all of mankind, as we say.

References:

Mant M, et al. Int J Paleopathol. 2024;doi:10.1016/j.ijpp.2023.12.003.