One hundred years ago in Western society, Acute Rheumatic Fever(ARF) and Rheumatic Heart Disease (RHD) were common. Many sufferers were condemned to an early death with heart failure. Nowadays these diseases are all but unknown in most resource rich Western societies and interest in research has declined. But the disease is still common in the Third World and in marginalized groups in the West such as Remote Indigenous Communities. Indeed Australia has the highest rates in the world in Remote Northern Territory. We still use prophylaxis developed in the 1950s and treatment remains unchanged
The history of prophylaxis (1)
With the discovery of antibiotics in the 1920s and 1930s, and the linkage of Rheumatic Fever with the infection by Group B streptococcus, attention turned to antibiotic treatment. It was found that Sulphonamides reduced the incidence of recurrent attacks of Acute Rheumatic Fever and progressive valve damage.
When Penicillin was discovered in the 1940s it proved to be even more effective and less prone to side-effects than Sulphonamides. But all these regimes need frequent administration. A poorly soluble depot Penicillin preparation known as Benzathine Penicillin was developed in the 1950s and has remained the mainstay of prophylaxis for RHD ever since. It can be administered by injection every 3-4 weeks. While there has never been a controlled trial of this regime, there is good empirical evidence that it reduces ARF recurrences by two thirds. Group B Streptococcus has remained sensitive to it when many other bacteria have developed resistance. In recent years Benzathine Penicillin has been increasingly difficult to source as drug manufacturers turn to more lucrative drugs. Patients have become more resistant to painful intramuscular injections. In spite of Benzathine Penicillin’s success, there is clearly a need for a better prophylactic solution.
The History of Treatment
Treatment of an episode of Acute Rheumatic Fever remains symptomatic – analgesia for joint pain, antipyretics for fever and Valproate for Chorea. There is no current treatment to reduce the autoimmune mediated damage to heart valves. As far as I am aware there are no treatments under development. Any residual Streptococcal infection is treated with Benzathine Penicillin.
The History of Diagnosis
Acute Rheumatic Fever (ARF) has always been a clinical diagnosis and remains so today. There is no single source of truth – the diagnosis is made on the basis of major and minor criteria as devised by Jones (5). These criteria have been revised and relaxed over time to make them more sensitive. The corollary of this is that they have become less specific, particularly as the disease has become rarer. The “pretest probability” problem comes into play. In a low probability population (RHD is still relatively uncommon, even in Remote settings), a test or intervention with poor specificity will generate many false positives. The symptom/sign that generates most problems is joint involvement. Fever and arthralgia are common in various illnesses. Objective arthritis is less common, polyarthritis even less so. In the early days of the Jones Criteria, 2 major and one minor criterion were required for a diagnosis. This has now been relaxed to one major and two minor criteria. Moreover in the early Jones criteria, the only major criterion involving joints was polyarthritis – ie objective signs of arthritis (redness, warmth, effusion) in several joints. This is now relaxed to allow monoarthritis or even polyarthralgia (subjective pain in several joints) as a major criterion. In practice this means that a patient presenting with fever and arthralgia (common in viral illnesses), but without any other relevant signs can be labelled as ARF. Often the details of a clinical presentation are not recorded. In particular the results of examination of joints may not be available. Other major criteria such as carditis (Echo changes, new murmur, heart failure) and Chorea are more specific and predictive of ongoing RHD. In practice, the oft described eythema marginatum and subcutaneous nodules are rarely seen. Interestingly the finding of PR changes on ECG has never been regarded as a major criterion or evidence of carditis, though it appears to be specific in practice and is easy to perform at first assessment.
Incidence (2,4)
Rates of both ARF and RHD have been increasing in recent years. The reason for this is not clear – I have discussed the possibilities in a previous post
https://tjilpidoc.com/2024/06/13/rheumatic-heart-disease-a-new-epidemic/
In a paper from 2011, after a first ARF diagnosis, 61% developed RHD within 10 years. After RHD diagnosis, 27% developed heart failure within 5 years. So it is important to identify patients with ARF and prevent recurrences with prophylaxis.
There were 172 cases of surgery for RHD in indigenous patients in Australia and NZ in the period 2001- 2012 (3). On average this is less than 20 cases a year.
In 2023 in Queensland, Western Australia, South Australia and the Northern Territory, 97 people underwent surgical events for RHD (one event per person). Most of these (75 people, 77%) were First Nations people. (ref)
So clearly there has been an increase of RHD clients undergoing surgery – is this due to better access or is there a real increase in RHD?
The Northern Territory appears to have a dramatically higher incidence of ARF and RHD than other states with significant indigenous populations such as Queensland and WA. Again the reason for this is not clear – it seems intuitively unlikely that these indigenous populations are less prone to RHD.
Promotion of ARF diagnosis
There has been increased awareness of ARF and RHD in Remote communities in recent years with campaigns to educate health staff and promote the idea that ARF should be considered in patients presenting with fever and joint symptoms. While this is admirable, we know from a 2005 study that many patients entering hospital with a provisional diagnosis of ARF have an alternative at discharge. (6) Because of this promotion, ARF has become the “probability diagnosis” with this scenario in many places. Streptococcal titres have become a defacto criterion when in fact they are a poor positive discriminator of ARF. Diagnostic “precision” appears to have declined with alternatives not considered. Many of these patients do not not have an authoritative assessment by a senior clinician at the time – this is deferred to a later date. This is problematic because relevant clinical symptoms and signs resolve or the patient may not see the clinician at all. Once a provisional label of ARF/RHD is attached to the patient, it can be impossible to remove, even in doubtful cases.
What are the costs of misdiagnosis?
There is a significant imposition on the client with a diagnosis of ARF. They are subjected to monthly injections and periodic reviews for anything up to 10 years. The Health service also bears significant costs. Some of the differential diagnoses of ARF carry significant risk (eg osteomyelitis, septic arthritis, Slipped Capital Femoral Epiphysis). Clearly if these are not treated in a timely fashion there is a risk of long term disability or even death.
Outcomes from different presentations
Many cases of RHD are found when they are already established, presenting as heart failure, murmurs or on screening (eg “Deadly Heart Trek”). Those presenting with Chorea have a high correlation with later development of RHD. While the paper I have previously quoted suggested a high rate of RHD development in all cases of ARF, on my personal review of records those presenting with joint symptoms alone appeared to have a lower rate of development of documented RHD even after some years
Where to from here?
ARF/RHD remains a significant problem in Remote Australia and marginalized groups but treatment and assessment protocols have not changed in recent years. ARF remains a clinical diagnosis. There is a significant rate of misdiagnosis with associated costs and risks. If a single test to prove or disprove ARF could be developed, this would be an advance. There has never been a treatment to reduce the immune mediated harm of ARF. In the age of targeted antibodies, perhaps this issue could be revisited. A better prophylactic drug should also be sought.
In the meantime it should be policy that all new cases of ARF are assessed at the time by a Senior Clinician to avoid “mislabelling” as much as possible.
References
(1) Evolution Evidence and Effect of Secondary Prophylaxis for Rheumatic Fever
Wyber, Rosemary1,; Carapetis, Jonathan1,2
Journal of the Practice of Cardiovascular Sciences 1(1):p 9-14, Jan–Apr 2015. | DOI: 10.4103/2395-5414.157554
(2) Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia, 1997 to 2010
Joanna G Lawrence 1, Jonathan R Carapetis, Kalinda Griffiths, Keith Edwards, John R Condon
10.1161/CIRCULATIONAHA.113.001477
(3) A review of valve surgery for rheumatic heart disease in Australia
Elizabeth Anne Russell 1,2, Lavinia Tran 2, Robert A Baker 3, Jayme S Bennetts 3,4, Alex Brown 5,6, Christopher Michael Reid 2, Robert Tam 7, Warren Frederick Walsh 8, Graeme Paul Maguire 1,2,9,✉
BMC Cardiovasc Disord. 2014 Oct 2;14:134. doi: 10.1186/1471-2261-14-134
(4) Recent increases in incidence
(5) Rheumatic fever Identification, management and secondary prevention
Volume 41, Issue 1, January-February 2012
https://www.racgp.org.au/afp/2012/january-february/rheumatic-fever
(6) The challenge of acute rheumatic fever diagnosis in a high-incidence population: a prospective study and proposed guidelines for diagnosis in Australia’s Northern Territory
Anna Ralph 1, Susan Jacups, Kay McGough, Malcolm McDonald, Bart J Currie
Heart Lung Circ . 2006 Apr;15(2):113-8.
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