• 20 Mar 2018
  • 12 min
  • 20 Mar 2018
  • 12 min

Dr Andrew Boyden interviews Dr David Liew about the aetiology, pathophysiology and management of polymyalgia rheumatica. Read the full article in Australian Prescriber.


Welcome to the Australian Prescriber Podcast. Australian Prescriber, independent, peer reviewed and free.

I'm Dr Andrew Boyden, your host for this Australian Prescriber podcast about polymyalgia rheumatica. It's a pleasure to be speaking with Dr David Liew, consultant rheumatologist and clinical pharmacology fellow at Austin Health. Welcome David.

Thanks Andrew. It’s good to be here and it's very interesting to be on the other side of the microphone today.

That's great. Well, as the Australian Prescriber article outlines, polymyalgia rheumatica is the second most common autoimmune rheumatic disease after rheumatoid arthritis. Can you tell us a bit about its etiology and pathophysiology?

Well that's the thing. There's very little known about the pathophysiology and then that's part of the problem in trying to find effective treatments. Now we know of some of the cytokines and pathways involved with PMR, for example we know il-6 [interleukin-6] is involved with polymyalgia rheumatica, we certainly don't know how it starts or what triggers it. There may be a seasonal component but that's far from certain as well. And so for such a common condition, and we're talking 2.4% of women and 1.7% of men over their lifetime, there are still a lot of unanswered questions about what drives PMR and how it works and until we answer those it will be harder to target therapies as well as we'd like. But there's even been debate about the exact structures that are involved with PMR as well. Until relatively recently there have been people advocating that PMR was an arthritis and it certainly can evolve into an arthritis and there can be joint swelling and joint pain but really with the emergence of more complex imaging modalities such as MRI and nuclear medicine PET-CT studies in particular that we've been able to see, unlike an arthritis which involves the joint itself, PMR actually involves the structures around the joint, the periarticular structures. So we suddenly get a better understanding about what this is but the fact that it's not easy to pin down really goes a long way to explaining why the presentation of PMR can be a little bit more nebulous at times compared to a disease like rheumatoid arthritis.

Yes, and I suppose that really gets me on to the next question as, you know, plenty of uncertainties there and I think this probably relates to clinical presentations as well. Based on your experience is there such a thing as a typical first presentation or do we need to be attuned to a wide range of possible early presentations?

That's a great question Andrew and I think that it gets right to the heart of it. There's definitely a classical presentation of PMR but there are definitely a lot of patients with atypical presentations. The classical patients are the ones that are easy to diagnose. They’re the ones with prolonged early morning stiffness, with or without pain, involving the shoulders and the hips and sometimes the whole body. There's stiffness that's there before they even get out of bed and that usually lasts hours and, unlike the stiffness in say fibromyalgia which often gets worse with movement, classical polymyalgia rheumatica stiffness gets better with activity. PMR patients don't usually have extensive joint involvement. They usually have a high ESR and they'll often have an exquisite response to prednisolone – they often feel like Superman after a few days, and this is what we write in the textbooks and this is often what we tell medical students. But these rules are really the ones that are made to be broken. We know that PMR patients often have joint pain and joint swelling and this usually disappears with treatment, and this can happen relatively frequently in the hands and the posterior medial knee which are joints which people wouldn't usually associate with PMR. We know that up to 20% of patients will have a normally ESR and CRP at baseline and we know that a small proportion of patients won't respond immediately to the steroids and they can take up to two to three weeks. So it's not easy. Apart from age, and it's almost impossible to diagnose someone under the age of 50 with PMR, there are few definites in this disease but at the same time you don't want to diagnose someone who's actually got arthritis or myositis or an endocrinopathy or cancer, you don't want to diagnose those patients with polymyalgia rheumatic.

Absolutely and that makes the role of the differential diagnosis so important in the initial assessment. Can you just give us a bit of an outline of what you see is a critical baseline test and how they can help with these differential considerations?

It's true that to some extent what we're doing at the time of diagnosing polymyalgia rheumatica is not just outlining the disease activity markers but we are also trying to exclude other conditions because there's no one definitive test for polymyalgia rheumatica. Now we've put a table in the article in Australian Prescriber of some of those key differential diagnoses. I think that's worth looking at when one's trying to make a diagnosis of polymyalgia rheumatica but it's also one of the reasons why it's really often useful to involve a rheumatologist because while sometimes it's an easy diagnosis to make there are traps all over the place and there's real value in having the help of someone who sees a lot of this condition

Absolutely and just coming back to the testing, one of the differentials we’ll probably be considering is rheumatoid arthritis and I suppose within that baseline group of testing it's always going to be rheumatoid factor and anti-CCP.

Absolutely and while it's certainly possible to have polymyalgia rheumatica with a positive rheumatoid factor and anti-CCP, that'd certainly push your thinking towards rheumatoid arthritis, but once again not as straightforward a delineation as you might think.

I suppose one of the considerations is with a patient who comes in who might be quite disabled, the temptation to start prednisolone before a definitive diagnosis is given – what's your view about that in general practice?

Now that it's a bit of a difficult question to answer because I think different people have different viewpoints but my viewpoint on this is, if it's clear that this is polymyalgia rheumatica then there's no real reason to hold back on prednisone. We know that patients start to feel a lot better often quickly with prednisone and it would be cruel to wait for them to see a rheumatologist before starting steroids but, having said that, when it's unclear, their role is a little bit less certain, and while we can get some information from a trial of steroids it's not always as useful as you might think.

I suppose what you're saying is, even if an appointment is some time down the track, there's nothing that should stop the GP aiming to have a conversation with their local rheumatologist to maybe discuss the diagnosis and early treatment.

Oh absolutely.

Given the unpredictable course of the condition, what approach do you take in counselling patients to help them understand the condition?

There's no doubt that education is key in dealing with polymyalgia rheumatica. Firstly I think it's important to tell them what we're trying to do with treatment which is really to use a minimum dose to control the disease but to bring down the steroids as quickly as possible but not too quickly because sometimes going too fast is actually a step backward. The second thing is we need to be conscious about watching out for side-effects from steroids because we're really looking at the minimum of nearly a year of steroids and often much longer than that. And the third thing is it's crucial to ask about features of giant cell arteritis, not just at the time of diagnosis but for patients to be aware about what to look out for over the course of time. We know that patients with polymyalgia rheumatica can get giant cell arteritis with their disease and that occurs in about one in five patients and that's really not a diagnosis that we want to miss. It's important for patients to be aware of not just the cranial manifestations like sudden visual changes, headache in the temporal region or the occipital region, scalp tenderness and jaw claudication but they should also be aware of the extra cranial manifestations that can emerge like limb claudication and chest pain. They should also know what to do if those manifestations emerge.

Do you mind also expanding just a bit about prednisolone use in relation to what we really need to be monitoring?

Yes, this is really where the art of polymyalgia rheumatica comes about and I really summarise the overall approach to this in saying steroids are the kind of thing that you can't live with and can't live without. Now the first thing to say is that we should be trying to expose patients to the minimum possible amount of steroid. We know that steroids are needed. They're the only definitively accepted effective therapy at the moment and the standard I'd recommend from here is the British Society of Rheumatology protocol which starts with prednisone 15 mg for three weeks then drops to 12.5 mg for three weeks, 10 mg for three weeks and then drops by a milligram a day every four to six weeks. Now of course should there be a flare of disease, the dose needs to go back up again, but flares can be hard to delineate from musculoskeletal disease with all the general aches and pains that patients get when they get older and when steroids work away their muscles. This really does highlight the point that it's not easy for frontline clinicians to do this all by themselves. Treating polymyalgia rheumatica can be more complicated than you think, diagnosis can be difficult, determining disease activity can be difficult, optimal prednisolone weaning can be difficult, and knowing when to start a steroid-sparing agent can be difficult, and all these are reasons why it is useful often to involve a rheumatologist.

Can you just talk a little bit about the evidence for any role of methotrexate and other steroid-sparing medications?

If you're a little bit uncertain about what what the role of methotrexate is in polymyalgia rheumatica, you're not the only one. We know that there are some patients who just get stuck on a dose of prednisone. It's often between 5–10 mg and try as they might they can't seem to wean below it and that's a real problem because it's difficult to condemn these people to lifelong prednisolone and all the problems that it entails for the rest of their lives. We've put a table in the article of all the side effects that one might expect to see at those kinds of doses of corticosteroids that these patients are on. So we really do need something to substitute in for steroids for those patients who do keep on flaring. We would like to prove that methotrexate works in polymyalgia rheumatica and there's a real need to study that area but at the moment we do have some lower quality evidence to support it at present and certainly in my experience it does seem to work in some patients and it's the best of what we've got at the moment. Leflunomide is another drug which we used for rheumatoid arthritis and psoriatic arthritis and that's always been of interest in polymyalgia rheumatica as well, and certainly anecdotally that seems to have significant benefit as well. There's an il-6 inhibitor, tocilizumab, which has been used but really it's far from being proven in polymyalgia rheumatic and there'll be a lot of barriers to its use in PMR in the future.

In your experience do most patients eventually get over polymyalgia rheumatica without the need for any more steroids, or are they always potentially at risk of a flare?

Well first of all a lot of patients never get off prednisolone in the first place. Over half will have symptoms for more than two years and actually a substantial proportion will have symptoms for more than five years. Really what we need to be conscious about is that the therapy for patients with ongoing polymyalgia rheumatica isn't benign and that long-term steroids have long-term side effects.

Yes, and there’s a very helpful table as you mentioned before in the Australian Prescriber article that actually summarises the potential adverse effects and a lot of them well known but maybe some less well known.

That's part of the reason why we put this table in because there are a lot of side effects that can get easily forgotten, things like the cardiovascular risk associated with low to moderate dose corticosteroids often forgotten but really there's a whole range of potential side effects that can come about as a result of the term steroids.

In summary what would you say are real take-home messages for GPS in relation to the diagnosis and management?

PMR is not always straightforward. It can be difficult to pick and it can be difficult to treat optimally. We want to minimise the overall steroid exposure for our patients and part of that's about being conscientious about reducing prednisolone when we can but also not reducing it too quickly. And really though what we need, desperately need, are effective steroid-sparing agents, but in the meantime until that day don't be afraid to talk to a rheumatologist because often this is not a straightforward situation for anyone.

Thank you very much David.

Thanks for having me on.


The full article on polymyalgia rheumatica is available online at nps.org.au/australian-prescriber. The views of the hosts and their guests on the podcast are their own and may not represent Australian Prescriber or NPS MedicineWise. I'm Andrew Boyden and thank you once again for joining us on the Australian Prescriber Podcast.