Reactive arthritis
Reproduced from Issue 109 of Arthritis Today
Professor Hill Gaston
Professor Hill Gaston, University of Cambridge, explains one of the lesser-known forms of arthritis.
At first sight you wouldn't think there was any connection between painful, swollen joints and an unfortunate encounter with a dodgy curry, one of Edwina Currie's Salmonella-infected eggs, or a milk bottle whose top has been pecked by the birds.
However, there may be important clues about arthritis to be gained by looking at the connection, because there certainly is one. We're all increasingly aware of the dangers of food poisoning, with bacteria such as Salmonella not infrequent intruders into food we eat. There are several similar bugs to look out for: Campylobacter is carried by magpies, so as a simple rule of thumb avoid milk pecked by big birds (magpies) and worry less about those pecked by little ones (blue tits don't carry Campylobacter).
Whilst food poisoning has little to recommend it, for the vast majority of people it's a short-lived episode which resolves with no long-term problems. However, for an unfortunate few, the end of the food poisoning is the beginning of an episode of joint inflammation which is likely to last several months, and in an even unluckier few, persist indefinitely. This is called reactive arthritis because the arthritis is seen as some kind of reaction to the infection.
Now although reactive arthritis isn't one of the commonest kinds of arthritis we see, there are some very good reasons why it's worth studying. Firstly, unlike most kinds of arthritis it has a very definite beginning; a fit, healthy and often young person without any arthritis has an encounter with a known bug, and after that rapidly develops obvious arthritis. Contrast this with rheumatoid arthritis. Here the onset is usually rather slow, and we currently have no idea about the events which lead up to the arthritis.
Secondly,
reactive arthritis is part of a larger family of arthritic conditions
which together are almost as common as rheumatoid arthritis. These
include ankylosing spondylitis, psoriatic arthritis, which some
people develop if they also have the skin condition psoriasis, and
inflammatory bowel disease – diseases such as ulcerative colitis
and Crohn's disease.
We know some of the genes which are important in determining who gets ankylosing spondylitis also affect whether some people are liable to get reactive arthritis. These include the well-known tissue type, HLA-B27, which is present in virtually all ankylosing spondylitis patients. HLA-B27 positive reactive patients have more severe disease and it lasts longer. So, studying reactive arthritis might reveal ways in which HLA-B27 causes this outcome, or help us find other genes which influence severity – or perhaps even genes which allow the arthritis to settle quickly in some people.
What do we know so far about how reactive arthritis comes about? The first thing we know is that the arthritis is tied up with the way in which our immune system deals with infections such as Salmonella. Our laboratory has been studying immune cells (lymphocytes) from reactive joints for some years, and we can find many cells which react to the infection which started the arthritis.
We can grow these cells in the lab, clone them, and work out in detail what they're doing. Recently, we've shown that the cells in the joint are already making some of the chemicals which drive inflammation – the same chemicals which we can get normal lymphocytes to make if we stimulate them with bacteria. This suggests they are already turned on in the joint.
What would turn on the lymphocyte in the joint? For some time this was a bit of a mystery because we thought that the food poisoning bacteria were only in the gut and never got near the joint. After all, when we drain fluid from a swollen, inflamed joint and try to cultivate the bacteria, we are always unsuccessful. However, new techniques including some very sensitive ones, now tell us that pieces of bacteria certainly do get to the joints, and probably some live bacteria as well, although they are not be very happy there – hence the difficulty in growing them from joint fluid.
Very recently we showed for the first time that one of the food poisoning bacteria can get into the joint as a live organism. Prior to this it was known that another reactive arthritis-causing bacterium, Chlamydia, could live in the joint, and some of the proteins Chlamydia makes in the joint are good at stimulating the lymphocytes we find in the joint. So, it seems quite likely that the reactive arthritis is due to the body's immune response to bacteria, or pieces of bacteria, which get to the joint.
Where do we go from here? Well, obviously having lymphocytes which react to food poisoning bacteria is generally a good thing, and necessary to get rid of infection. The only problem in reactive arthritis is that lymphocytes act in the joint and thereby stir up inflammation – swelling, pain and stiffness. We need to find out whether bacteria get to the joint in everyone who gets food poisoning, but don't usually cause inflammation, or can be cleared out of the joint before they cause trouble.
Alternatively, the reactive arthritis patients may make a poor job of dealing with infection in the gut, so that bacteria hang around for much longer and have a chance to get to the joint. Or again, it's possible the arthritis patients are especially sensitive ("allergic") to the bacteria. All these possibilities need to be investigated further.
We also need to think about whether the other members of this family of arthritic conditions have a similar cause. We don't know of any infection which sparks off ankylosing spondylitis, but there is gut inflammation in some of these patients, and also in patients with Crohn's disease. There might easily be bacteria which we haven't yet identified involved in these diseases, or maybe some of the bacteria which we all normally carry in our intestine are enough to trigger arthritic conditions in susceptible people.
A final plea – if you're unlucky enough to organise a party where all the guests come down with food poisoning – get in touch! Your guests may never forgive you, but studying who gets arthritis and who doesn't might well advance rheumatology research.
