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Q and A - antibiotics special

Published on 24 July 2012
Dr Philip HelliwellIn a change to our regular Q & A format, Dr Philip Helliwell looks at possible links between infection and arthritis, following a number of letters on this controversial subject.

We have had a number of readers report that their arthritis improves when taking a course of antibiotics. This short article discusses this phenomenon and offers some possible explanations.

Q) What is the evidence that infection causes arthritis?


A) Some forms of arthritis are definitely associated with infection. Septic arthritis is due to bacteria entering the joint and causing inflammation and damage. It is rare but when it occurs it is one of the few emergencies in rheumatological medicine. The joint is swollen, hot and very painful. Untreated, septic arthritis can cause severe damage and generalised illness, and even death. When it occurs, hospitalisation and intravenous antibiotics are necessary.

Reactive arthritis can occur following an infection. Infections can include severe stomach upsets, usually due to a bacterium called campylobacter, and venereal disease including chlamydia, but many other bacteria and viruses can be triggers. There is evidence that reactive arthritis occurs more often in susceptible people, in particular people who carry the HLA-B27 gene (also found in ankylosing spondylitis).

The difference between reactive and septic arthritis is the fact that it is not possible to find any infection in the joint in reactive arthritis – the infection triggers an inflammatory response in the joint. As to other types of arthritis, such as rheumatoid arthritis and osteoarthritis, there is very little evidence that infection is relevant. This hasn’t stopped people working on that assumption – there was once a fashion to remove the teeth and tonsils in rheumatoid arthritis and there are still websites that link these common forms of arthritis to infection.

Perhaps the most compelling evidence is that the best treatments we have for rheumatoid arthritis (TNF inhibitors and rituximab) are both powerful immune suppressing drugs, and if infection were playing a major role in this disease it would surely become a lot worse with these treatments, rather than improve.

Q) Do antibiotics work for arthritis?

A) If septic arthritis is diagnosed antibiotics are life savers, so there is no question about that. It would also seem logical to give antibiotics in reactive arthritis but the evidence for benefit in such cases is not entirely supportive. This may be because the ‘reaction’ has already taken place. Of course, if the infection is on-going it makes sense to treat it but this may not influence the course of the arthritis. A research study involving many centres in Europe found no apparent benefit of a course of antibiotics in reactive arthritis. However, the patients enrolled were a ‘mixed bag’ and may have had arthritis following a number of different infections. In contrast a research study in the southern US found definite improvement in people with recent onset post-chlamydial reactive arthritis. So, there may be some benefit when the arthritis has a definite and treatable trigger and when it has just started.

TabletQ) Do antibiotics work in the absence of infection?

A) Why may antibiotics work for arthritis if not related to their ability to treat infections? Well there are certain antibiotics that have other actions in addition to their ability to kill organisms. Minocycline, in particular, has beneficial effects on both the enzymes that can cause damage to joint tissues and the cells that cause inflammation. This effect can be shown in the laboratory and there have been several successful clinical trials in rheumatoid arthritis. However, I think it is fair to say that the effect of minocycline is not usually very marked, in comparison to methotrexate for example. No other antibiotics have been found to have such a definite clinical benefit as far as I know. It is also worth noting that minocycline and related drugs can also cause a lupus-like syndrome – I have seen several cases in my practice. The good news is that it usually resolves when the drug is stopped.

Q) Where does this leave all those people who find their arthritis improves when they take antibiotics?

A) Everyone is different. And we don’t know all there is to know. Be assured that if there are enough ‘signals’, any benefit of antibiotics will be investigated further in clinical trials. But remember, only twins are identical (those who share the same egg of course) and in some people there may just be a reason that antibiotics work for them. Maybe, for example, the ‘normal’ bugs in the gut are triggering a long-term reaction in the joints (this theory has long been held for rheumatoid arthritis and may well be true for ankylosing spondylitis). When you take a course of antibiotics the normal flora (your usual gut bacteria) are decimated, along with the bugs causing the infection. This may be why some, but not all, people improve temporarily on antibiotics. However, the answer is not long-term antibiotics! Why? Because bacteria have a clever way of adapting and changing and developing resistance to antibiotics, and so would grow back quickly enough (an alternative is that other, not so nice, bugs take over and can be harmful themselves – ever heard of clostridium difficle infection?). Other ways of permanently altering gut flora have been tried, particularly in ankylosing spondylitis, but without much success at the present time. 

For people with osteoarthritis who improve on antibiotics there just isn’t a simple explanation. The tetracycline group of drugs mentioned above can inhibit the harmful enzymes found in an osteoarthritic joint but the effect is likely to be mild and more of a slow onset long-term effect than a short-term benefit, and quite unassociated with their ability to kill bacteria. A website (www.theroadback.org) devoted to rejuvenating the link between arthritis and infection may, while keeping largely to evidence from trials, mislead in the implications for patients and their treatment, particularly for diseases such as scleroderma and psoriatic arthritis, for which there is no ‘hard’ evidence whatsoever. Physicians contributing to this website are clearly convinced of the benefit of tetracyclines and use them every day in their practice, but it would seem foolhardy to do this to the exclusion of other drugs with proven benefit in preventing damage and progression of the disease.

Conclusion

I hope this answers some of the questions sent in. I have tried to be fair to those who still strongly advocate that infection is the cause of arthritis and maybe, in years to come, we may discover some truth in this. If that is the case, I doubt antibiotics will be the answer – maybe some form of immune tolerance induction, such as vaccination, or maybe manipulation of the ways our bodies ‘see’ infection. We’ll see.

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