Rheumatic fever and rheumatic heart disease: updates for clinical practice

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Rheumatic heart disease is a serious possible complication of infection with the common bacteria, group A streptococcus. You might've heard it called strep pyogenes or just plain old strep A. Globally, it is the most common cause of acquired childhood heart disease, and in Australia, it disproportionately affects our First Nations people.

Today on the Australian Prescriber Podcast, we are discussing the 2025 updated Australian guideline for the prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. Because this condition is largely preventable, we'll talk through the clinical practise points so that we can ensure we're providing excellent clinical care with a framework of cultural safety to priority populations.

I'm Dr Laura Beaton. I'm a GP in Melbourne, and I'm joined by Dr James Marangou, who's a consultant cardiologist at Royal Perth Hospital and undertaking a PhD at the Menzies School of Health Research at Charles Darwin University. James and his co-authors have summarised the 2025 guideline for Australian Prescriber into some really practise salient points that we'll share with you today. James, thank you so much, to you and your co-authors for this article and for taking the time to speak with me today.

Thanks for the opportunity, Laura. It's lovely to chat.

To start off with, can we have a quick immunology one-on-one refresher on how a seemingly mild skin or throat infection with strep A can lead to acute rheumatic fever, and in some instances, how that reaction can cause serious cardiac issues?

Yeah, absolutely. So as we know, strep A causes a constellation of infectious complications. In our setting, we're really interested in the superficial infections, that's the pharyngitis and impetigo. And then in a subset of people, they can get this non-infectious complication, which is immune-driven. It's traditionally been labelled as molecular mimicry, but essentially the thought is that there's cross-reaction between the strep A and then other organs in the body, which is resulting in rheumatic fever with that classical presentation of an arthritis particularly, but also other complications such as the cardiac involvement or occasionally, neurological involvement.

And what are the major risk factors for someone getting this molecular mimicry and this immune reaction to a group A strep, mild skin or a throat infection?

That's a really good question. So our understanding is that although there is a genetic predisposition, that doesn't differ between populations. And so that risk is there across everyone, but there's clearly the risk factors that we talk about from a primordial perspective which is driving the high group A strep exposure. And that early and consistent exposure to group A strep is really what we see then associated with the high rates of rheumatic fever.

In Australia, the ongoing impact of colonisation and that result on particularly, Aboriginal and Torres Strait Islander populations driving that socioeconomic disadvantage, inadequate housing, poor access to health, hygiene, infrastructure, those factors, we see associated with very high group A strep. And as a result, it's that population that's most affected by rheumatic fever and then subsequent rheumatic heart disease.

We know that those factors have existed previously, more globally. And as populations went through the industrial revolution and then the invention of penicillin as well, that's when we really saw a sharp decline in rheumatic fever globally. But unfortunately, it's now clustered particularly where those socioeconomic factors still persist.

Thanks for that context before we go into a lot of the clinical bedside details today, because when we think about prevention, sometimes we think about primary, but you mentioned primordial prevention. And a lot of this article, we are going to talk about treating strep A, treating rheumatic fever and preventing rheumatic heart disease, but it is a really good moment to reflect on the role we can play as advocates.

If we can advocate for improved housing, sanitation, and access to culturally appropriate healthcare, we could probably do a lot without picking up a stethoscope or a prescription pad. In your article, you talk about how determining whether the person in front of you is at high risk is actually imprecise.

What are the factors you recommend clinicians consider one-on-one with someone when thinking, 'Is this someone for whom it actually is important that I treat this group A strep or not?'

Yeah, absolutely. And this is a really important point. I completely agree with what you said. I think when we talk about rheumatic fever in Australia, we have to acknowledge that ongoing impact of colonisation and marginalisation for First Nations people in Australia. And we see that in other nations where rheumatic fever still exists in First Nations. We see it in Aotearoa, New Zealand and we see it in Canada, and that context can then guide how we approach risk.

In Australia, we see the highest burden of rheumatic fever and rheumatic heart disease in Aboriginal and Torres Strait Islander communities, particularly in central and northern Australia. But when we look at risk, we really need to be considering, what are the drivers of high group A strep?

So from a practical point of view, using the epidemiology and understanding where the highest cases are, so particularly remote communities in Northern Australia. But then also there's a nuance to it, appreciating if someone's coming from a setting where housing is inadequate, there may be overcrowding in that setting, a high burden of strep A infections in the family, for example, if there's siblings who've also had rheumatic fever and rheumatic heart disease, there's certainly association between siblings for increased risk.

So it's the broader epidemiological context and then narrowing that down for the person in front of you, to be able to really tailor that risk. What we know is when you have someone who is at high risk in front of you, then the treatment of group A strep infections is different to someone who's perhaps from the broader population who's at a lower overall risk for rheumatic fever.

And we'll talk about identification of those high-risk individuals and management throughout today. But before we get into that nitty-gritty detail, I wanted to ask you about the main new, or changed aspects of the 2025 updated national guidelines. What are the main salient points that might be different to previous recommendations?

Yeah, so we've really tried over the last few years to integrate more and more new evidence as it comes along. The 2025 guidelines are a integration over the last couple of years, of a few key new pieces of evidence. A few years ago, we had a randomised control trial that was published around the role of secondary antibiotic prophylaxis for preventing progression of early rheumatic heart disease.

So this was in individuals who didn't have a history of rheumatic fever, but they had an echocardiogram which demonstrated early RHD [rheumatic heart disease]. And the RCT [randomized controlled trial] data supported that treating those people with penicillin prevents progression of disease, whether or not there's a history of rheumatic fever.

But then there's some other key updates we have included. There's been a change in description of rheumatic heart disease over the last few years, from talking about borderline and early and definite RHD to a stage-based approach, which fits better with other international guidelines and how we approach diseases, and it's also got a clinical framework to it.

So being able to label someone with stage A through to stage D rheumatic heart disease links in with their risk of disease progression and their risk of clinical complications. And so that's been aligned with the 2023 World Heart Federation guidelines.

There's been some other updates around choices of therapy, so particularly antibiotic choices for primary prevention when considering treating group A strep, pharyngitis particularly. There's also been an adjustment to the guideline around where people with suspected rheumatic fever should be treated. And this is really useful for people who are working in remote Australian clinics where sometimes it can be very difficult to have patients transferred to a tertiary centre to have workups.

So we've given a guideline around who is safe to be treated in community. Whereas majority of cases, particularly children, should be transferred still to a tertiary centre. There is a subset of that group who could be managed closer to home, which is very useful logistically, when working in remote care.

Many of our listeners will be working nearby tertiary care, but many of them won't. So it's really helpful to have these clinically relevant points to go through today. So let's step back to that initial infection with group A strep. So those minor infections, which might be a sore throat or a skin infection.

We see these day-to-day in many people, but for populations who are at high risk, what are the differences in how we would manage someone who's at a high risk of rheumatic fever and heart disease for a sore throat or a skin infection?

So this is a really important point. I think for clinicians who aren't regularly working in rural or remote Australia and seeing rheumatic fever or seeing populations which are high risk of rheumatic fever regularly, the guideline is really useful to fall back on.

What we recommend in young people from a high-risk population is that any pharyngitis should be treated with antibiotics, which is different to if you're seeing someone in the city. And the reason for that is because of that higher risk of rheumatic fever, the aim is really to prevent that immune reaction.

So early detection of pharyngitis or skin sores and early administration of antibiotics is really key to preventing the development of rheumatic fever in those individuals. It's still important to have a diagnostic test if possible. So a throat swab should be collected before antibiotics are administered if possible, but it shouldn't prevent antibiotics being given in those individuals.

We know that intramuscular long-acting benzylpenicillin is recommended, but of course, if anyone has either given or received these injections, it's no walk in the park. You do mention some oral options that might be acceptable depending on circumstances, availability.

Yeah. So for the treatment of strep A pharyngitis, certainly intramuscular benzathine benzylpenicillin as a once-off dose is recommended, but there is definitely other oral options. And this is where it's really up to the clinician and the patient discussion and what the patient's going to be most comfortable with.

So certainly for pharyngitis, the other options would include oral phenoxymethylpenicillin, but other options as well, including cephalexin or amoxicillin, or if needed, azithromycin as well are all reasonable alternatives for treating group A pharyngitis.

Similarly, for impetigo, which can often have both group A strep, but also staphylococcus aureus, the recommendation is either, once again, benzathine IM [intramuscular] penicillin or co-trimoxazole as an oral option as well.

Thanks for reminding us all that. Of course, we are making our individualised risk assessment with the person in front of us, because even though I do work in the city, if someone has come with a previous or family history of rheumatic fever and they are living in crowded housing and don't have access to good sanitation, I treat that as high risk even if they are in a metropolitan area. It's really looking at that person right in front of you and their context.

Yes, definitely.

Before we move on to secondary prevention, which is managing rheumatic fever to try to reduce recurrence and progression of rheumatic heart disease, first we need to identify acute rheumatic fever, which of course can be a challenge. Could you speak to the diversity of the presentation of rheumatic fever?

Yes. A rheumatic fever is a difficult diagnosis to make. It's a purely clinical diagnosis. There's no diagnostic test yet for rheumatic fever. It's a clinical diagnosis based on a handful of symptoms and signs being evaluated in the person in front of you.

The most common presentation would be fever and a joint involvement, whether that's arthritis or arthralgia. Typically, multiple joints, typically large joints and migrating symptoms between joints is the most common presentation. The skin manifestations that we talk about are rare, but they're very specific. So if they are present, then that's very useful for confirming a diagnosis.

The cardiac manifestations, although a significant proportion of people will have cardiac involvement, the detection of that clinically can be very challenging, and that's where the role of early echocardiography is so important when working up someone for possible rheumatic fever. But the diagnosis is really that combination of a major criteria, classically cardiac involvement, arthritis and then the skin manifestations, so erythema marginatum or subcutaneous nodules, or Sydenham's chorea.

And Sydenham's chorea, which is the neurological manifestation of rheumatic fever, is unique in the sense that, that on its own is enough to diagnose someone with rheumatic fever, allowing that other less common causes are excluded. But it's a combination of major features as well as non-specific minor manifestations, which is fever and evidence of inflammation on blood tests, either elevated ESR [Erythrocyte Sedimentation Rate] or CRP [C-Reactive Protein], or conduction abnormalities on an ECG [electrocardiogram]. So a combination of the major and minor criteria is what we're using in the right context.

It's important that the pretest probability of an individual having rheumatic fever is taken into context when applying those criteria because they are so broad and most of them are non-specific.

For those of you who need to look this up, I would recommend having a look at table one in the Australian Prescriber article. These presentations nicely set out. Once we do identify rheumatic fever, what does management look like in the Australian context?

Similar to not having a diagnostic test, at this point in time, we also don't have any treatment that changes the trajectory of rheumatic fever. So the way we treat rheumatic fever now is all based around symptom control. What that means really, is symptoms for arthritis, analgesia, and anti-inflammatory treatment of arthritis, management of the cardiac complications. So particularly if they've got severe valve involvement, so they can have severe valvulitis, which can present with a heart failure syndrome. So managing that is the usual pathway for managing heart failure. All those treatments there are really around symptom control.

The other key aspect is eradication of strep A, so immediate prescription of long-acting benzathine benzylpenicillin, once again is important, but that doesn't change the trajectory of that index episode of rheumatic fever, but it's important for eradicating strep A and then reducing the risk of recurrent rheumatic fever over the preceding period of time.

You mentioned that part of this guideline talks about identifying those people for whom you need early cardiology input at a tertiary centre, and those who have a more mild presentation that's able to be managed in community on country, maybe with liaison with a cardiologist.

Can you talk us through when someone needs urgent cardiology input and transfer, and some of those cases where it would be more suitable to have community-based treatment with liaison with cardiology and access to echocardiography in a few weeks?

Yeah, absolutely. So this advice really came out of feedback from clinicians and health services, particularly in remote Australia. Traditionally, the Australian guideline has advocated that all patients with suspected rheumatic fever should be transferred to a tertiary centre where they can get complete assessment, workup, management.

One of the driving reasons for that was access to echocardiography because it is so crucial to clarify the diagnosis and also, determine prognosis based on severity of valve involvement. And so that really remains the default recommendation.

However, there is a subset group of people, who it may be reasonable to manage them in community. These individuals are typically lower risk, so clinically they appear stable, they appear relatively well. There's no obvious cardiac involvement based on a clinical assessment. They're older as well.

So certainly, any young people, so typically younger than teenage years should default be admitted to a tertiary centre for assessment. But that older teenage years, young adult group, who it may be more challenging to get them into a tertiary centre, who appear clinically well, who haven't gotten manifestations of significant heart disease, they've got no known history of rheumatic fever or rheumatic heart disease in the past.

And then crucially, those individuals need to be able to access echo within a short timeframe. So a couple-of-week period, they need to be able to access echocardiography and specialist review, and they're going to be engaging with their local clinic to be able to clarify diagnosis in a very short period of time.

And I imagine the use of virtual models of care and more local access to echocardiography, but video and telehealth calls with specialists, including liaison with on-the-ground clinicians might be very helpful.

Yeah, definitely. I think particularly in remote Australia, thinking creatively about how we can provide best practise to people closer to home is a really important part and very relevant to rheumatic heart disease.

Another point that was flagged in your article that I just wanted to ask you about was around these long-acting benzathine benzylpenicillin injections. They are no fun, but as we know, group A strep is luckily, quite sensitive to penicillin and it is probably the most effective treatment. What are the practical strategies you recommend to improve the tolerability and adherence to these?

Yeah. I mean, we've been using intramuscular penicillin for a very long time. And although there's work looking at alternatives such as subcutaneous administration with some really exciting research happening in that space, really the IM penicillin remains the mainstay.

What we've outlined in the Australian guidelines is a pyramid of support options that clinics and clinicians can provide their patients to assist particularly with the management of pain and anxiety. And so those can be simple strategies such as distraction, all the way up to using other pharmacological agents.

Often, lignocaine can be used in combination to try and reduce the immediate discomfort, but really the key is that the individual receiving the needles is able to determine how they would like to have their needles. So giving them autonomy, whether that's where they have their needles, is it at the clinic or is it at home? How they have their needles, whether that's lying down, sitting, standing. Where in the body they receive their needles. Giving that autonomy is really important to assist with maintaining the therapy.

And then in addition to that, that pyramid of options in regards to pain management and offering all of that to the individuals to be able to, again, engage them and feel that they've got autonomy and control over how they're receiving their treatment.

Thanks for including this and outlining that in the guideline. As practitioners, we perform lots of procedures which cause discomfort or pain, and those principles that you've just outlined there actually are really applicable to lots of different interventions.

Finally, this morning, I wanted to turn to the management of rheumatic heart disease, which is obviously the very complication we're trying to avoid. Could you talk through the key practise points that our listeners should consider, given that most of us aren't cardiologists, but we might be looking after people in the community for long-term follow-up? What are the things we need to be keeping an eye out for? How often do they need to see you? And what are the kinds of things we should be doing, opportunistically and routinely?

There's a couple of really useful resources in the guideline and they're in table format. So we've been talking about priority classification for rheumatic heart disease for a really long time, and those tables are a really good go-to resource for clinicians to check, 'Where does my patients sit in regards to risks, or risk of complications in their rheumatic heart disease? But also, how often should they be accessing cardiology, echocardiography, dental care? And importantly, how long do they need to be on benzathine penicillin for?'

The management of rheumatic heart disease itself is really around the severity of the valve dysfunction. So when we talk about RHD, we talk about that stage classification that I mentioned. Stage A is the earliest manifestations of rheumatic heart disease that we see in young people, so less than 20-year-olds. This is very minor valve changes, but they're a marker for very early RHD.

And then we go to stage B, which is mild valve dysfunction. And then once we get to stage C, this is more than mild. So this is prognostically significant disease, typically moderate or severe valve dysfunction or perhaps more than one valve involved. And stage C is really about identifying disease that's associated with risk of clinical complications.

Stage D is the same valve dysfunction, but the individuals had unfortunately, aclinical complications, whether that's a heart failure presentation or they've required valve surgery. They're classified as stage D. And each of those stages links into the priority table. And so based on that, there's recommendations of frequency of echocardiography, of cardiac follow-up.

The aim really, for when we're managing patients is to prevent progression of the valve dysfunction. So that's really around prevention of recurrences of rheumatic fever because we know that recurrences will drive worsening valve dysfunction. So in these individuals, there is that role for long-term antibiotic prophylaxis.

Also, other aspects of that care, so prevention of complications, so prevention of heart failure, so whether that's pharmacological agents that are needed to prevent progression of the valve disease, management of their heart failure if it's needed.

And then as a clinician, screening for those complications is really important. So we know atrial fibrillation is a common complication of rheumatic heart disease. So regular ECG and symptom screening is important for that. Similarly, heart failure is important to be screened for. And then additionally, to that is preventing overlaying complications. So individuals with rheumatic heart disease are certainly vulnerable to infective endocarditis.

And so, one of the key recommendations in the guidelines is about maintaining good dental care, but also the use of antibiotics for any procedures that are going to increase that risk of transient bacteraemia, so invasive dental procedures or other gastroenterological or urological procedures that are at risk of that. These individuals with rheumatic heart disease should have additional antibiotic prophylaxis on top of their long-term penicillin.

And if you are a clinician like me who sometimes gets asked, 'Does this procedure meet the threshold of being invasive enough to have a likely bacteraemia?' I will note that Therapeutic Guidelines has a really nice classification of dental and other procedures by invasiveness and whether or not this meets the criteria for needing antibiotics.

One of the things you also mentioned in your article is a point of care tool that's come out of the guidelines as well. What kind of things are in the clinical support app?

The app is an excellent in-your-pocket reference. It summarises both, the key diagnostic criteria for rheumatic fever, but it also summarises that priority table that I was talking about. So you can, in the palm of your hands see, 'Okay, when does my patient need to next see cardiology based on their priority, based on what the echocardiogram report says?'

All of that is in the app. It also provides information of duration, of secondary antibiotic prophylaxis, so that depends on the priority. It may be until the age of 21, but it may be until 35 or even longer for some individuals. So it's a quick go-to reference that summarises the key clinical points that are outlined in the overall 2025 guideline.

Thanks, James, for the conversation today. It is always great to speak through new guideline updates because this is your everyday practise. It is helpful to consider any new changes. And if this isn't a daily consideration for you, it actually is a really great refresher for when you really should have your clinical radar up and where to go for guidance.

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The views of the hosts and the guests on this podcast are their own and may not represent Australian Prescriber or Therapeutic Guidelines. James Marangou has received funding from the Australian government by the NHMRC [National Health and Medical Research Council] and MRFF [Medical Research Future Fund] for research and a fellowship relevant to rheumatic fever. He has also received research funding from The Heart Foundation.

James is a secretary of the Strep A Vaccine Global Consortium, SAVAC, echocardiography in Group A Strep Vaccine Trials Technical Advisory Working Group. He has received funding from SAVAC towards registration, accommodation, and travel for meeting attendances.

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