Script – Paediatric Diagnosis of ARF
SLIDE 1
Welcome to Rheumatic Heart Disease Australia’s Health Provider Education series.
Educational resources developed for clinicians by clinicians.
Rheumatic Heart Disease Australia is an initiative of Baker IDI, James Cook University, and
Menzies School of Health Research and is supported by the Commonwealth Department of
Health and Ageing.
This module will discuss the paediatric diagnosis of acute rheumatic fever with a focus on the
Australian perspective.
SLIDE 2
This presentation was developed with the assistance of Alan Ruben, and Ben Reeves, who are
both based in Cairns in far northern Queensland, Australia. Both specialists have a longstanding
interest in acute rheumatic fever and rheumatic heart disease, and remote health care delivery.
Alan is a paediatrician and public health physician who has worked in Aboriginal Health for
over 20 years. He has also spent a significant amount of time in the Pacific, working with
WHO, UNICEF and AusAID.
Ben is a paediatric cardiologist, providing outreach paediatric cardiology services to Cape York
and the Torres Strait Islands. His interest in rheumatic heart disease began in Fiji, where he
worked for two years as a general paediatrician before completing his paediatric cardiology
training at the Mater Children’s hospital in Brisbane.
SLIDE 3
The learning objectives of this presentation are to provide an understanding of the sequence of
events leading to acute rheumatic fever and subsequently rheumatic heart disease.
You will learn how to recognize those most at risk for acute rheumatic fever and rheumatic
heart disease, and gain an understanding of the Jones criteria used for diagnosis.
The recommended investigations and current treatment guidelines will be outlined.
SLIDE 4
The take home messages include that the incidence of acute rheumatic fever and rheumatic
heart disease in Australian Aboriginal and Torres Strait Islander peoples is amongst the highest
recorded in the world.
Acute rheumatic fever predominantly affects children from disadvantaged populations aged
between 5 to 15 years.
A high index of suspicion is needed for those at greatest risk of disease, which means people
living in high incidence populations.
Rheumatic fever diagnosis demands that clinical criteria be met, and that relevant investigation
results are compatible.
Because the diagnosis can be complex, inpatient admission is often required.
SLIDE 5
Before proceeding further, it is worthwhile defining the terms and abbreviations that will used
during this presentation.
AR is used for aortic regurgitation. This is when there is a backward flow of blood from the
aorta into the left ventricle, because the aortic valve does not close properly.
Acute rheumatic fever is often termed ARF. This is a complication of Group A streptococcal
infection, a common bacteria found in the throat and on the skin. In susceptible individuals, and
particularly children, immune mimicry results in inappropriate cross reactivity between
streptococcal and patient tissue antigens associated with joints, skin, brain and, most
importantly here, the heart.
BPG, or benzathine penicillin G, remains the most effective antibiotic for both the prevention
and management of GAS pharyngitis and ARF.
CRP is C-reactive protein, an acute phase protein produced by the liver during an inflammatory
reaction.
The erythrocyte sedimentation rate, or ESR, is the rate at which red blood cells settle. It is a
non-specific measure of inflammation.
Group A beta haemolytic streptococcus, otherwise known as ‘G’ ‘A’ ‘S’ or GAS, causes
approximately twenty to forty per cent of symptomatic pharyngitis or sore throat. GAS-related
pharyngitis is thought to be the major driver of ARF.
Mitral regurgitation, or MR, occurs when blood leaks back from the left ventricle into the left
atrium due to incomplete closure of the mitral valve
Rheumatic heart disease, or RHD, is the chronic sequelae of recurrent episodes of ARF.
Recurrent carditis with valve inflammation leads to scarring, distortion and eventual valve
dysfunction.
SLIDE 6
For those who would like more information regarding the prevention, diagnosis and
management of ARF and RHD, this can be found in the Australian Guidelines. These guidelines
were substantially updated and revised in 2012, and are available at the RHD Australia website.
SLIDE 7
There is also a Quick Reference Guide which can be a useful tool for busy clinicians,
population health staff and managers.
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Further education modules are available at the RHD Australia Health Provider Education
website.
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Let’s commence by highlighting a few basic facts regarding acute rheumatic fever.
Approximately 3 to 6% of any population is susceptible to ARF, with the incidence and
prevalence in females greater than in males.
ARF and rheumatic heart disease can run in families, and although specific genetic markers
have been identified, there is no racial predisposition to disease.
Thus the higher incidence of ARF in Aboriginal and Torres Strait Islander people is not due to
an inherently higher susceptibility to ARF but rather a greater exposure to GAS infection.
SLIDE 10
So what in particular ought we be concerned about in the Australian setting? Australian rates
are amongst the highest recorded in the world, with ARF most frequently occurring in remote
and disadvantaged areas and populations.
Because ARF has largely disappeared in Australian urban areas, Australian health care
providers are often unfamiliar with the diagnosis, treatment and management of this condition.
SLIDE 11
If Aboriginal and Torres Strait Islander people are not inherently more susceptible to ARF, then
what is driving this greater burden of disease?
th
Improved living standards resulted in reduced transmission of GAS in the early 20 century,
and almost the disappearance of ARF and RHD in the high income and industrialised world. It
is a different story in low and middle income nations, where exposure to GAS infection remains
high, and surveillance, diagnosis, secondary prophylaxis and treatment remain under resourced.
A greater risk of ARF is associated with overcrowding, poor sanitation, and other conditions
that may easily result in the rapid transmission or multiple exposures to GAS.
For more information on the primary and primordial prevention of ARF and RHD, please refer
to the module in this health provider education series.
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So what might be some of the underlying social and environmental determinants driving greater
exposure to GAS?
History has taught us that ARF has a clear link with poverty, household overcrowding, poor
sanitation, housing quality and appropriateness, and educational disadvantage.
Almost half of Aboriginal and Torres Strait Islander households earn an income in the bottom
quarter of the national average. The average weekly household income for Aboriginal and
Torres Strait Islander peoples is only 62% that of non-Indigenous Australians.
Remoteness is also another driving of disadvantage. This reflects the distance people have to
travel to obtain services. 68% of Aboriginal and Torres Strait Islander peoples live outside
major cities, with 43% in regional areas, 9% in remote, and 15% in very remote areas.
The combination of economic disadvantage and remoteness in turn translates to environmental
disadvantage with housing quality and household overcrowding being more common for
Aboriginal and Torres Strait Islander people. Australian communities at greatest risk of this
inter-related nexus of remoteness, poverty and environmental disadvantage include those in
remote northern and Central Australia, extending from the Torres Strait adjacent to Papua New
Guinea through to the desert regions of southern WA.
SLIDE 13
So how does ARF develop? This flowchart provides a graphic depiction of the disease process.
Pharyngitis caused by GAS infection results in an exaggerated immune response in susceptible
individuals, causing any or all of the symptoms listed here, chorea, carditis, arthritis and fever.
Recognition and diagnosis of ARF can reduce progression to RHD through the use of
prophylactic antibiotics which prevent further episodes of ARF.
A high level of suspicion in target populations will facilitate early diagnosis and
commencement of prophylaxis.
There is clear evidence that prophylaxis with benzathine penicillin reduces GAS infections,
prevents recurrent attacks of ARF, and progressive RHD.
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How does ARF progress to rheumatic heart disease?
Repeated episodes of ARF and recurrent heart inflammation eventually result in scarring and
permanent damage to heart valves.
These damaged heart valves do not function properly, and can eventually lead to stroke, heart
infection, called endocarditis, and heart failure.
ARF and RHD are a preventable cause of disability and early death, and are associated with an
increased need for surgical heart and other interventions.
SLIDE 15
So how do we accurately diagnose acute rheumatic fever?
ARF diagnosis is based on the modified Jones criteria, seen here as presented in the Australian
guideline for the prevention, diagnosis and management of acute rheumatic fever and rheumatic
heart disease. These criteria have been modified and are slightly different in high risk and low
risk populations, with the changes in high risk populations being made to increase sensitivity
and avoid under-diagnosis.
They rely on looking for and confirming a combination of major and minor criteria. The
diagnosis of an initial episode of ARF requires two major manifestations, or one major and two
minor manifestations, with evidence of recent GAS infection.
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As a confirmed diagnosis of both initial and recurrent ARF requires evidence of recent GAS
infection, let’s look at how that is confirmed. Remember in all cases of ARF, except those
associated with chorea, evidence of recent GAS infection is essential.
Evidence can be demonstrated by a positive throat swab OR serological or antibody evidence of
exposure to GAS based on a raised ASOT or anti-DNAse.
If serology is negative AND ARF continues to be suspected, and if an alternate diagnosis is not
made, serology should be repeated after two weeks, because an increase in titer can be delayed.
Since antibodies directed at GAS are produced as a delayed hypersensitivity reaction, there is
no normal value, and the presence of these antibodies only indicates an exposure to GAS. Many
people exposed to GAS remain asymptomatic, so the mere presence of positive GAS serology
does not in itself indicate ARF.
Once evidence of recent GAS infection is confirmed, diagnosis of an initial episode of ARF
relies on also having 2 major criteria or 1 major and 2 minor criteria, with no other probable
diagnosis.
It is worthwhile to note the latest Australian guidelines have included additional categories and
requirements for recurrent ARF and probable ARF.
SLIDE 17
This chart from the Australian Guidelines summarises and describes the major manifestations
required for the diagnosis of ARF in a high risk population.
They are arthritis, polyarthralgia, Sydenham’s Chorea, carditis, subcutaneous nodules and
erythema marginatum. As we progress through this module, a more detailed description will be
provided for each of these major manifestations.
SLIDE 18
Let’s look at high risk groups, and start with polyarthritis, aseptic mono-arthritis and
polyarthralgia.
SLIDE 19
Arthritis and arthralgia are the most common presentations of ARF in children.
Classically, the arthritis is a polyarthritis, usually affecting peripheral large joints, with joints in
the lower limbs affected more frequently than the upper limbs. The polyarthritis is often
extremely painful, with movement avoided and passive movement not tolerated. Sometimes,
other significant signs of inflammation are absent.
Usually asymmetrical and migratory, resolution in one joint is often followed by reappearance
in another shortly afterwards. When this happens in an adjacent joint, the arthritis appears to be
migrating. Sometimes however the arthritis is additive.
The arthritis is usually of limited duration, two days to 3 weeks, although it can occasionally
last longer.
Treatment with aspirin or other non-steroidal anti-inflammatory drugs results in dramatic
improvement, sometimes with relief of symptoms occurring overnight, and definitely within 2
to 3 days. This rapid response can assist with diagnosis.
If anti-inflammatory treatment is ceased, arthritis may recur, generally within one to 2 months
of the original episode.
SLIDE 20
In high risk populations, a monoarthritis can be considered as a major manifestation of ARF, as
it is often associated with carditis.
One important point to remember is that aseptic monoarthritis should always be investigated
and followed up as possible ARF even if preemptive antibiotic treatment is given.
Collaboration between physicians and orthopaedic surgeons is valuable in this setting.
SLIDE 21
Polyarthralgia can be less dramatic than the classical polyarthritis and monoarthritis seen in
ARF. In high risk populations the modified Australian Jones criteria for ARF classify this as a
major manifestation whilst in other populations in remains a minor manifestation of ARF.
The differentiation of arthralgia from arthritis is clinical and is based on painful joints without
clinical signs such as effusions and heat, along with no history of morning stiffness.
SLIDE 22
Let’s now describe the second major manifestation, carditis.
Carditis can involve all the layers of the heart. If the pericardium is affected, pericardial
effusions can result.
Heart function and conduction will be impacted if the myocardium is involved.
The classic valvular lesions seen ARF are caused when the endocardium is involved, with the
most common being mitral regurgitation or MR and then aortic regurgitation or AR.
The right sided heart valves, the tricuspid and pulmonary valves are rarely involved.
It is important to remember that subclinical carditis, that is heart valve inflammation
demonstrated on echocardiography without an associated murmur, is now classified as a major
criterion in the diagnosis of ARF in high risk populations
SLIDE 23
So what are the recommended investigations if carditis is suspected?
Echocardiography is key.
It can distinguish innocent murmurs and detect subclinical carditis. However it is often difficult
to access echo services, especially in remote areas with high incidence of ARF and this is one
reason why cases of suspected ARF should be admitted to hospital.
Determining valvular disease can be difficult and often requires follow-up echocardiogram
examination, as initial findings may be normal with changes only appearing after 2 to 6 weeks.
Carditis does not always occur in ARF and incidence varies between 30 to 80%.
Because the changes of carditis can be delayed, it is important that all patients with suspected
ARF have follow-up echocardiography.
Remember a normal echocardiogram does not exclude a diagnosis of ARF.
SLIDE 24
Let’s discuss the management of acute ARF-related carditis.
The key here is admission to hospital, with close observations and investigation, and
consideration of bed rest along with diuretics and ACE inhibitors if heart failure develops.
Steroids may be considered in myocarditis with heart failure but usually heart failure in this
setting is due to valve dysfunction.
SLIDE 25
We will move on to discuss the next major manifestation, Sydenham's chorea.
This is a disease characterized by rapid, uncoordinated jerking movements affecting primarily
the face, feet and hands. Sydenham's chorea results from childhood infection with GAS and is
reported to occur in 20-30% of patients with ARF. The disease is usually latent, occurring up to
6 months after the acute infection, but may occasionally be the presenting symptom of acute
rheumatic fever. Sydenham's Chorea is more common in females than males and most patients
are younger than 18 years of age. Adult onset of Sydenham's Chorea is comparatively rare and
most of the adult cases are associated with exacerbation of chorea following childhood
Sydenham's Chorea.
Sydenham's chorea is characterized by the acute onset (sometimes a few hours) of neurologic
symptoms, classically chorea, usually affecting all limbs. Other neurologic symptoms include
behavior change, dysarthria, gait disturbance, loss of fine and gross motor control with resultant
deterioration of handwriting, headache, slowed cognition, facial grimacing, fidgetiness and
hypotonia. Also, there may be tongue fasciculations ("bag of worms"), and a "milk maids sign",
which is a relapsing grip demonstrated by alternate increases and decreases in tension, as if
hand milking.
Emotional changes, such as easy crying or inappropriate laughing, may precede the
development of chorea and, in some cases, deteriorating school performance can be the initial
concern.
The hypotonia may be severe and the extremities may appear paralysed. The cranial nerves are
not involved, but speech often is abnormal and is described as "jerky" with sudden changes in
pitch and loudness.
SLIDE 26
Erythema marginatum is the next major manifestation, and an example of the rash can be seen
here. The rash is difficult to see on dark skin, and will blanch under pressure. This is a rare
finding, reported in less than 2% of Aboriginal and Torres Strait Islander patients with ARF. It
is an erythematous rash with a pale centre and a darker margin. It has a circular pattern and
predominantly occurs on trunk and extremities, and is neither itchy nor painful.
SLIDE 27
The final major manifestation that needs description is subcutaneous nodules.
Subcutaneous nodules are also rare but highly specific for ARF and strongly associated with
carditis. The nodules are round, firm, and freely mobile, with a diameter of half to 2 cm. They
occur predominantly over pressure areas including the extensor surface of joints, in particular
the elbows, knees and ankles. They can also occur over the head and posterior spinal processes.
SLIDE 28
Let’s now discuss the minor manifestations for ARF diagnosis. In high-risk groups these are
monoarthralgia, or joint pain, fever, raised inflammatory markers and ECG evidence of heart
block.
SLIDE 29
Fever can be both documented and greater than 38 degrees Celsius, or a reliable history of fever
if anti-inflammatory therapy has been given, or in the absence of a documented fever. It is
important that the temperature is measured and recorded at the time of initial presentation.
SLIDE 30
Inflammatory markers are non-specific indicators for ARF.
Nonetheless ESR and CRP elevations are considered minor manifestations, with the criteria
requiring that either of these be 30 or greater.
The CRP tends to rise and fall more quickly than ESR., so that performing both can be useful.
CRP is often easier to perform in a remote setting.
SLIDE 31
An ECG should always be performed when ARF is suspected. A prolonged PR interval is the
nd
most common manifestation, although 2 degree and complete heart block can also occur.
The normal PR interval for a 3 to 12 year old is 0.16 of a second, and for 12 to 16 year old is
0.18 of a second.
If the PR interval is prolonged, repeat the ECG after 1 to 2 months. The changes are more likely
to be related to ARF if the ECG returns to normal, and this therefore increases the probability of
diagnosis.
SLIDE 32
Investigations are important both to confirm a diagnosis of ARF and for diagnosis of other
conditions which may be mistaken for ARF
Throat swab, antistreptococcal serology (ASOT and antiDNAse), white cell count, differential,
ESR, CRP, ECG and echocardiogram are always necessary.
If heart failure is suspected a chest x-ray may be useful both to confirm pulmonary oedema and
to rule out other causes of shortness of breath, including pneumonia.
If infective endocarditis or septic arthritis is considered a possibility , multiple sets of blood
cultures should be taken prior to the commencement of antibiotics.
Any patient from a high risk population presenting with an acute monoarthritis should be
considered to have possible septic arthritis, and a joint aspirate should be performed. In children
this may be a difficult and expert advice will assist with this decision.
SLIDE 33
Let’s now consider the differential diagnosis of ARF.
This chart from the Australian guidelines outlines the differential diagnosis of the three most
common major manifestations of acute rheumatic fever, polyarthritis with fever, carditis and
chorea. Some of the diseases listed are extremely rare, and some, such as Lyme disease, do not
occur in Australia.
There are only a few important conditions which need to be considered in most patients
presenting with possible ARF. These include septic arthritis and infective endocarditis, both of
which have high levels of associated morbidity if missed.
Gout and pseuodogout usually occur in older adults and leukaemia and lymphoma presenting
with polyarthritis and fever is very uncommon. Conditions such as disseminated gonococcal
infection however, are not uncommon especially in sexually active adolescents.
SLIDE 34
So what are the key diagnostic points?
ARF can be difficult to diagnose, as there are multiple, and sometimes repeated tests
recommended for confirmation. A high index of suspicion is needed in high risk populations to
avoid possible missed diagnosis.
Specialist paediatrician input can be helpful if you suspect ARF.
Consider the possibility of ARF in any child from a high risk population presenting with
arthritis, especially if more than 5 years of age.
Keep in mind that monoarthritis is a common presentation of ARF in Aboriginal and Torres
Strait Islander populations.
Remember that simple falls rarely cause joint effusions.
And finally admission to hospital is recommended for all initial presentations, in order to
confirm diagnosis, assess severity of disease and develop a treatment plan.
SLIDE 35
Unfortunately a definite diagnosis of ARF cannot be made in all cases even though no alternate
diagnosis is reached.
In this case a diagnosis of probable ARF should be considered.
The Australian guidelines provide a reference flowchart for the management and follow up of
probable ARF and subdivides this group into Uncertain and Highly Suspected groups. It should
be noted that secondary prophylaxis is recommended for both these groups.
A diagnosis of probable ARF can be made when a patient has a clinical presentation
compatible with ARF but falls short of meeting the diagnostic criteria by either one major or
one minor manifestation, or in the absence of definitive GAS serology. In this case close
follow-up is essential both to determine a definite episode of ARF, and to ensure that another
condition is not being missed.
The Australian guidelines have also made the criteria for diagnosing a recurrent episode of ARF
more sensitive by allowing this diagnosis to be made even if no major and only three minor
criteria are met.
SLIDE 36
We will now conclude by recapping the principles of diagnosis and management of ARF in
children and adolescents.
Any effective treatment first requires diagnosis, and then commencement of secondary
prophylaxis.
Remember that a diagnosis of probable ARF also warrant prophylaxis and close follow-up.
Hospitalisation is generally necessary for a number of reasons. First to complete the
recommended tests and investigations, second to access specialist opinion and review, and third
to arrange and coordinate an appropriate treatment plan.
Early specialist input is helpful to ensure alternate diagnoses are considered and to facilitate
ongoing follow-up and management.
Bed rest and aspirin or NSAIDs may be required.
Initial and follow up echocardiography, is important.
Medical management with ACE inhibitors and diuretics may be needed in the setting of heart
failure and severe myocarditis may benefit with commencement of steroids.
Finally chorea will often settle spontaneously but if troublesome should prompt specialist input.
SLIDE 37
As we conclude, it’s useful to cover the basic principles of secondary prevention. For more
information on secondary prevention please see the appropriate module in this health provider
education series.
Secondary prevention first requires the diagnosis of acute rheumatic fever and/or rheumatic
heart disease.
Once the diagnosis has been made, the person must be given long term antimicrobial or
antibiotic prophylaxis to prevent recurrent episodes of acute rheumatic fever, and associated
valve inflammation which can progress to rheumatic heart disease.
There are significant challenges in the delivery of antimicrobial prophylaxis, and successful
delivery requires a register based secondary prevention program, effective recall systems, and a
functioning primary health care service.
SLIDE 38
In closing, let’s revisit our take home messages:
Remember the incidence of acute rheumatic fever and rheumatic heart disease in Australian
Aboriginal and Torres Strait Islander peoples is amongst the highest recorded in the world.
Acute rheumatic fever predominantly affects children from disadvantaged populations between
5 to 15 years of age.
A high index of suspicion is needed for those at greatest risk of disease, which means people
living in high incidence populations.
Rheumatic fever diagnosis demands that clinical criteria be met, and that relevant investigation
results are compatible.
Because the diagnosis can be complex, inpatient admission is often required.
SLIDE 39
If you would like to know more about ARF and RHD please refer to the new Australian
guidelines. Further education modules are available at the RHD Australia Health Provider
Education website.
SLIDE 40
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SLIDE 41
Finally for those of you who would like to test your knowledge regarding the information
presented in this module, please go to the Brief Self-Assessment Quiz at the link provided on
this website.