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Rheumatic Fever

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Rheumatic fever\: systemic in
Epidemiology\: rare in the developed world (\<1 in 100,000 in UK), common in developing nations, a
slightly more common in girls.
Pathophysiology\: develops 1-5 weeks post-strep infection (usually pharyngitis), caused by a hypersensitivity reaction (type
2) involving immune responses, leads to molecular mimicry and permanent valve damage.
Risk factors\:
Biological\: age (rare under 4), sex (more common in females), certain ethnicities, immune status, genetic susceptibility,
prior untreated strep infection, virulence of the organism.
Social\: low socioeconomic status, overcrowding, poor hygiene, climate.
Clinical features (Jones criteria)\: evidence of recent strep infection + two major or one major + two minor criteria\:
Major criteria\: polyarthritis (80%), carditis (50%), Sydenham’s chorea (10%), erythema marginatum (\<5%), subcutaneous
nodules.
Minor criteria\: polyarthralgia, prolonged PR interval, history of rheumatic fever, fever (>39°C), raised in
(CRP, ESR).
Di
Joint symptoms\: systemic-onset juvenile idiopathic arthritis, reactive arthritis, Henoch-Schönlein purpura.
Cardiac disease\: cardiomyopathy, Kawasaki disease, infective endocarditis.
Chorea\: Wilson’s disease, adverse drug reactions, Huntington’s disease.
Skin changes\: adverse drug reactions, Lyme disease/erythema migrans, erythema multiforme.
Investigations\:
Bedside\: ECG (prolonged PR interval), vital signs (fever).
Laboratory\: throat swabs, rapid strep antigen test, anti-streptococcal antibodies (ASO, anti-DNAse B), blood tests (FBC,
ESR, CRP, troponin, rheumatoid factor, anti-CCP).
Imaging\: chest X-ray (heart failure), Doppler echocardiogram (carditis).
Management\:
Acute management\:
Conservative\: bed rest until CRP normal for 2 weeks.
Medical\: penicillin (benzylpenicillin IV, penicillin V oral), aspirin (high-dose, monitor closely), corticosteroids (if severe
carditis), manage heart failure (ACE inhibitors, diuretics), diazepam or haloperidol for chorea.
Prophylaxis\: benzathine penicillin G IM every 4 weeks or daily oral penicillin, duration based on severity and presence of
carditis.
Complications\: chronic rheumatic heart disease (60% with carditis), valve disease (mitral regurgitation/stenosis most
common), heart failure, pericardial e
Prognosis\: relapses can occur with strep reinfection, OCP, pregnancy; most relapses within 5 years; long-term cardiac
monitoring needed; global mortality ~1.5%.
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Introduction

Rheumatic fever is a systemic in
S t r e p t o c o c c u s , but unlike the initial infection, rheumatic fever is not contagious.

Aetiology

Epidemiology

Rheumatic fever was fairly common in the UK up until the 1960s, but is, thankfully, now rare in the developed world, with
current UK incidence reported as less than 1 in 100,000.
1
This is largely due to major public health interventions, including the more widespread use of antibiotics and improved
public hygiene measures.
However, it remains prevalent in some developing nations and amongst certain ethnic groups in developed countries (such
as the indigenous people of Australia and New Zealand) and remains the number one cause of paediatric cardiac disease
globally.
2,3,4
Rheumatic fever typically a
than boys. It rarely presents for the
3,5,6
Rheumatic fever can return later in life if left untreated, and current NHS guidance recommends that all patients with a
sore throat who have previously had rheumatic fever seek medical advice promptly.
7

Pathophysiology

Rheumatic fever develops between one to
streptococci, otherwise known as S t r e p t o c o c c u s p y o g e n e s , a gram-positive organism.
8
Initial S t r e p t o c o c c u s p y o g e n e s infection typically manifests as pharyngitis (strep throat) but may also present as an
infection of the skin (i.e. cellulitis). 2
Rheumatic fever develops in susceptible hosts (roughly 2% of the population) due to a
hypersensitivity reaction against the bacteria, which involves both the humoral and cell-mediated immune responses
(type 2 hypersensitivity).
9,10
Similarities in the molecular makeup of the cell walls of streptococcal bacteria and human heart valve tissue may result in
the body’s antibodies erroneously attacking the host instead of the pathogen, leading to permanent damage to the valves.
This phenomenon is termed antigen mimicry.
5

Risk factors

A variety of biological and social factors are associated with an increased risk of developing rheumatic fever.
2,8,10,11

Biological risk factors

Age\: rare in children under 4 years.
Sex\: more common in females.
Ethnicity\: for example, there is a higher prevalence of rheumatic fever among indigenous groups in Australia and New
Zealand.
Immune status\: immunocompetent vs immunocompromised.
Genetic susceptibility\: as indicated by
Prior or untreated infection with Group A S t r e p t o c o c c u s .
Virulence of the infective organism.

Social risk factors

Low socioeconomic status\: due to poor access to healthcare and antibiotics.
Overcrowding and poor housing\: associated with poor hygiene and sanitation.
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Climate\: higher incidence over the winter months. In hot countries, streptococcal infection is more likely to present as a
skin infection versus pharyngitis.

Clinical features

The clinical features of rheumatic fever are outlined in the Jones criteria.
3,5
Jones criteria
In order to establish a diagnosis of rheumatic fever, there must be\:
Evidence of recent group A Streptococcus infection
Positive throat swab
Positive rapid streptococcal antigen test
Raised streptococcal antibody titre (ASO or DNAse B titres)
Recent episode of scarlet fever
plus either\:
two major criteria
or one major criterion and two minor criteria

Major criteria

Polyarthritis (80% of patients)
Multiple joints are a
usually a
The arthritis is described as a “
Carditis (50% of patients)
The heart consists of three layers (endocardium, myocardium and pericardium). In rheumatic fever, every layer of the heart
can be a
Damage to the endocardium leads to endocarditis, which can cause valvular dysfunction. Patients may present with
clinically signi
Myocardial in
complications.
Pericarditis may present clinically with a fairly benign pericardial rub or may lead to more serious complications such as
pericardial e
The most common valve a
In an attack of rheumatic fever, valve incompetence (i.e. regurgitation) is more likely to develop than valve stenosis. Valve
stenosis tends to develop as a feature of chronic disease many years later.
5
Sydenham’s chorea (10% of patients)
Sydenham’s chorea is a rare, and late-presenting sign of rheumatic fever, appearing around 2-6 months after the initial
streptococcal infection.
It consists of involuntary, semi-purposeful movements of the body which may be unilateral or bilateral. Occasionally the
chorea is preceded by emotional lability or behaviour which is out of character for the patient.
Sydenham’s chorea is also sometimes referred to as St Vitus’ dance.
Erythema marginatum (\<5% of patients)
Erythema marginatum is a rash found in rheumatic fever which may present early on in the disease process. However, it is a
rare sign and therefore should not be relied on as a means of diagnosis.
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Erythema marginatum is a pink macular rash predominantly a
expands outwards, leaving a pale centre and is described as a “geographical rash” because its borderlines resemble
those drawn on a map (
It is commonly confused with erythema migrans and erythema multiforme (see di
Figure 1.Erythema marginatum.
12
Subcutaneous nodules
Hard, mobile, pea-sized nodules, typically found on the extensor surfaces (e.g. back of the elbows) or the spine. They are
often painless and normally disappear within one month.
Subcutaneous nodules are a rare
13

Minor criteria

Polyarthralgia
Pain present in multiple joints. This is not included in the criteria if polyarthritis is already present.
Prolonged PR interval on ECG
This is only used as a criterion if there are no signs of pancarditis.
History of rheumatic fever
A previous history of rheumatic fever is a risk factor for subsequent
Fever
Typically, temperatures of more than 39 degrees centigrade.
Raised in
This includes markers such as CRP, ESR and leukocyte (white cell) count.

Di

The clinical presentation of rheumatic fever can be similar to several other conditions.
8
Joint symptoms
Systemic-onset juvenile idiopathic arthritis (JIA), also known as Still's disease
Reactive arthritis
Henoch-Schönlein purpura (HSP)
Cardiac disease
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Cardiomyopathy
Kawasaki disease
Infective endocarditis
Chorea
Wilson’s disease
Adverse drug reactions
Huntington’s disease (very rare in children)
Skin changes
Adverse drug reactions
Lyme disease/erythema migrans (
Erythema multiforme (
Figure 2. Erythema migrans. This rash is associated with lyme disease. Note the “bull’s eye” pattern, which, unlike erythema marginatum, has a
central red mark, surrounded by clear skin, which in turn is circumscribed by a ring of erythema.
14

Investigations

Several investigations may be used to assist in reaching the diagnosis of rheumatic fever.
5,8

Bedside investigations

Relevant bedside investigations include\:
ECG\: may show prolonged PR interval and tachycardia.
Vital signs\: fever may be present.

Laboratory investigations

Relevant laboratory investigations include\:
Throat swabs\: testing for cultures of group A S t r e p t o c o c c u s , although usually negative by the time the symptoms
appear.
Rapid streptococcal antigen test (RAST)\: may be performed before cultures if streptococcal infection is suspected.
Results are obtained quicker than for throat cultures but may be less accurate. 16
RAST tests can give false negatives, in
which case, cultures are then performed as well.
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Anti-streptococcal antibodies\: check for elevated antibody levels or a rise in levels. The sample should also be
repeated in 2 weeks. Levels tend to stay elevated for at least 6 months. The most common antibody tests used for
rheumatic fever are anti-streptolysin O (ASO) and anti-DNAse B.
Blood tests\: FBC (WCC may be raised), ESR and CRP, troponin (raised in myocarditis), rheumatoid factor and anti-CCP (to
exclude other diagnoses).

Imaging

Relevant imaging investigations include\:
Chest X-ray\: to rule out heart failure.
Doppler echocardiogram\: may be used to aid diagnosis of carditis in acute rheumatic fever.

Management

Acute attacks of rheumatic fever last on average for 3 months but can leave long-term complications if left untreated.
Management of rheumatic fever can be divided into acute management and prophylaxis.

Acute management

Conservative management
Rheumatic fever is one of the few conditions where bed rest is recommended as
feels well.
3,5,8
This is even more important in cases of suspected active myocarditis (indicated by abnormalities seen on the
echocardiogram and a raised ESR), where limitation of exercise is strongly advised.
3
Bed rest is recommended until the CRP has returned to the normal range (usually 0-5mg/L but refer to local guidelines) for
at least 2 weeks.
8
Medical management
Penicillin is the antibiotic of choice to kill any remaining streptococcal bacteria. A single stat dose of intravenous
benzylpenicillin is administered initially, followed by oral penicillin V (phenoxymethylpenicillin) for at least 10 days.
5
For patients who are allergic to penicillin, erythromycin or azithromycin can be given for 10 days instead.
5
To limit the in
levels. 3,5
Aspirin can be particularly toxic in children, initially causing a respiratory alkalosis (from hyperventilation), followed
by metabolic acidosis. Other complications include tinnitus and Reye’s syndrome.
8
If the in
on X-ray, complete heart block on ECG, evidence of heart failure), then corticosteroids are a useful alternative, and these
should be given quickly if any of the above are suspected.
3,5,8
Acute heart failure should be managed with expert advice and usually involves a combination of ACE inhibitors and
diuretics. 3
If
pericardiocentesis, may be necessary. 3 8
Mitral valve surgery may be warranted even in acute heart failure.
Joints with severe arthritis should be immobilised in the
5
While the chorea is often self-limiting, drugs such as diazepam or haloperidol may help to suppress the unpleasant
Diazepam is preferred over haloperidol as it is not associated with the extrapyramidal side-e
symptoms. 5,8
occur with haloperidol.

Prophylaxis

After the initial attack, the child should be followed up regularly and prophylactic treatment started to reduce the chance
of any future attacks. The current recommended
weeks as an intramuscular injection.
3,5,8
Alternatively, the patient can take oral penicillin instead of having the injections, but they must take these every day for the
duration of prophylaxis and this may make compliance di
3
As with acute attacks of rheumatic fever, for patients who are allergic to penicillin, erythromycin or azithromycin may be
used instead.
3
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How long prophylaxis treatment should be maintained for is open to debate, but current guidelines recommend that\:
5,8
If carditis is not a feature of the acute episode, and there is no evidence of valvular disease, then prophylaxis may be
given for only 5 years, or until age 21 (whichever is sooner).
If carditis is present during the acute episode but there is no valvular disease, then prophylaxis should be given for 10
years.
Where there is both carditis and persistent valvular disease, prophylaxis should be continued for life, or at least up to the
age of 40.

Complications

Without adequate treatment of the acute episode and prophylaxis, long-term complications can develop. The severity of
chronic disease is related to both the number and the severity of childhood attacks of rheumatic fever.
3
The majority of complications of rheumatic fever are related to the heart. 8,17
go on to develop chronic rheumatic heart disease.
5
60% of patients presenting acutely with carditis
If there have been multiple episodes of carditis with rheumatic fever during childhood, cardiac complications may arise as
early as the second decade (between ages 10-19). However, most cases of valvular disease manifest from early adult life
onwards.
3
Cardiac complications may be diverse and can include\:
Carditis (e.g. infective endocarditis)
Heart failure
Pericardial e
Valvular disease (especially the mitral valve)
Atrial
Pulmonary hypertension
Thromboembolic events, such as strokes (a consequence of atrial
Valvular disease
Acute episodes of rheumatic fever may lead to leaky, or regurgitant, valves. However, long-term, the valves may
become scarred, hardened and stenosed.
Mitral regurgitation is the most common valve lesion in rheumatic fever overall, whereas mitral stenosis is the most
common long-term cardiac complication, accounting for approximately 70% of chronic rheumatic valve disease.
Other valves may also be a
5
Most of the other features that appear during acute attacks of rheumatic fever, such as joint swelling and skin changes, are
thought to be transient, leaving no permanent damage after the
6
However, very occasionally, some individuals with rheumatic fever may develop refractory chorea, which may persist for
years and is resistant to standard treatment. In these patients, options such as plasmapheresis, whereby plasma is
removed from the blood and the cells are transfused back into the body with a plasma substitute, may be considered.
6,18

Prognosis

pill and pregnancy.
5
Further relapses can be triggered by re-infection with streptococcal bacteria, as well as the use of the oral contraceptive
Most relapses of acute rheumatic fever occur within 5 years of the initial episode, with each episode lasting around 3
months. 8 7
Recurrence is less likely after the age of 25.
Patients require long-term monitoring of cardiac function, especially those who initially present with myocarditis, as this
can result in permanent damage to the heart muscle.
8
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Chorea may disappear after the initial episode, it may relapse and remit for several years, or it may persist for many years
(although this is rare).
8
Mortality in developed nations is low but global mortality is around 1.5%.
8

References

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H e a l t h . 2019;16(4515)\: 1-39.
th
Lissauer T and Clayden G. I l l u s t r a t e d T e x t b o o k o f P a e d i a t r i c s . 4 ed. Edinburgh\: Mosby Elsevier; 2012. p. 321-322.
GBD 2017 Congenital Heart Disease Collaborators. Global, regional, and national burden of congenital heart disease 1990-
2017\: a systematic analysis for the Global Burden of Disease Study 2017. T h e L a n c e t C h i l d a n d A d o l e s c e n t H e a l t h . 2020;4\:
185-200.
th
Longmore M, Wilkinson IB, Baldwin A, Wallin E. O x f o r d H a n d b o o k o f C l i n i c a l m e d i c i n e . 9 ed. Oxford\: Oxford University
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and Middle-Income Countries. A m e r i c a n J o u r n a l o f E p i d e m i o l o g y a n d I n f e c t i o u s D i s e a s e . 2013;1(4)\: 34-40.
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Reviewer

Dr Will Sapwell
Registrar in Cardiology

Related notes

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Contents

Introduction
Aetiology
Risk factors
Clinical features
Di
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