DOVECOT COLLEGE OF HEALTH SCIENCES

• Paediatrics and Child Health

• ACUTE RHEUMATIC FEVER (ARF)

• Dr. Mukape Mukape

- UNZA ([Link], MBChB, MSc in Progress)
- ZIDIS (Diplomatic Practice and Public Relations)
- Senior Resident Medical Officer (SRMO) at Ministry of
Health, Zambia
- Staff Development Fellow (SDF), SOM, UNZA.
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 Introduction
• One starts with group A beta–haemolytic STREPTOCOCCAL
PHARYNGITIS (sore throat) which leads to ACUTE
RHEUMATIC FEVER (ARF) in susceptible children
• This then leads to RHEUMATIC HEART DISEASE (RHD) later in
life making heart valves susceptible to micro-organisms
• This leads to INFECTIVE ENDOCARDITIS (IE)
• Hence, adequate treatment of streptococcal pharyngitis in
children is very vital
• Treat with:
a. Natural penicillins (DOC):
- Oral Pen V for 10 days
- IM single dose of Benzathine Penicillin G
b. Macrolides: Erythromycin
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 Acute Rheumatic Fever (ARF)

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 Acute Rheumatic Fever (ARF)
• Is an acute, immunologically mediated (Type 2
hypersensitivity reaction) multisystem
inflammatory disease that occurs a few weeks
after an episode of group A β-haemolytic
streptococcal pharyngitis
• It can also rarely occur with streptococcal
infections at other sites (e.g., skin)
• Acute rheumatic heart disease (RHD) is the
cardiac manifestation of ARF and is associated with
inflammation of the valves, myocardium, or
pericardium (pan-carditis)
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 Acute Rheumatic Fever (ARF)
• ARF appears most often in children aged 5 to 15 yrs
(school going children)
• But about 20% of first attacks occur in adults
• Typically, the symptoms occur 2-4 weeks after an
episode of streptococcal pharyngitis at a time
when:
1. Clinical findings of pharyngitis are no longer
present and
2. When only 10–20% of the throat culture or rapid
streptococcal antigen test results are positive

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 Aetiology of ARF
• There is considerable evidence to support the link
between group A beta haemolytic streptococcus
(GAS) URTI and ARF and RHD
• ⅔ of the patients with an acute episode of
rheumatic fever have a history of an URTI several
weeks before
• The peak age and seasonal incidence of ARF
closely parallel those of GAS infections

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 Aetiology of ARF
• Patients with ARF almost always have serologic
evidence (antibody titres) of a recent GAS
infection
• Although cultures for streptococci are negative by
the time clinical illness begins, antibodies to one
or more streptococcal antigens (streptolysin O or
DNAase) can be detected in most patients
• Antimicrobial therapy that eliminates GAS from
the pharynx also prevents initial episodes of ARF
• Long-term, continuous prophylaxis that prevents
GAS pharyngitis also prevents recurrences of ARF
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 Aetiology of ARF
• Not all of the serotypes of GAS can cause ARF
• When some strains (M type 4) were present in a
very susceptible rheumatic population, no
recurrences of ARF occurred
• In contrast, episodes of pharyngitis with other
serotypes prevalent in the same population were
associated with frequent recurrences
• Certain serotypes of GAS (M types 1, 3, 5, 6, 18,
24) are more frequently isolated from patients
with ARF than are other serotypes
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 Epidemiology
• ARF and hence, RHD is a disease of the poor (low
socio-economic status)
• Mostly, found in developing areas of the world
with annual incidence of ARF as high as
282/100,000 population
• Worldwide, RHD remains the most common form
of acquired heart disease in all age groups
• Accounts for as much as 50% of all cardiovascular
disease and as much as 50% of all cardiac
admissions in many developing countries
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 Pathogenesis
• The pathogenic link between a GAS infection of
the URT and an attack of ARF is still not clear
• Several theories of the pathogenesis of ARF and
RHD have been proposed, but only 2 are seriously
considered:
1. Cytotoxicity theory
2. Immunologic theory (Type II hypersensitivity)

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 The Cytotoxicity Theory
• Suggests that a GAS toxin may be involved in the
pathogenesis of ARF and RHD
• GAS produces several enzymes that are cytotoxic
for mammalian cardiac cells, such as streptolysin O
• This enzyme has a direct cytotoxic effect on
mammalian cells in tissue culture
• Most of the proponents of the cytotoxicity theory
have focused on this enzyme
• However, the theory is unable to explain the latent
period between GAS pharyngitis and the onset of
ARF
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 The Immunological Theory
• Is able to explain the latent period between the GAS
infection and the ARF
• Suggests that some GAS components share common
antigenic determinants (epitopes) with some
mammalian tissues
• The antibodies against the GAS components after
being formed binds not only to the GAS components
but also to the mammalian tissues having similar
epitopes
• This is called immunologic cross reactivity (molecular
mimicry)
• Hence, instead of the antibodies destroying only the
bacteria, they also damage specific tissues in the body
having similar epitopes to the bacteria components
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 The Immunological Theory
• Components of GAS that share epitopes with some
mammalian tissues include:
- M protein
- Protoplast membrane
- Cell wall group A carbohydrate
- Capsular hyaluronate
• The specific mammalian tissues sharing common epitopes
with the above bacteria components are:
1. Heart
2. Brain
3. Joints
4. Skin
• For example, certain M proteins (M1, M5, M6, and M19)
share epitopes with human tropomyosin and myosin
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 Clinical Manifestations and Diagnosis
• Because no clinical or lab finding is pathognomonic
for ARF , T. Duckett Jones in 1944 proposed
guidelines to aid in diagnosis and to limit over-
diagnosis
• The Jones criteria, as revised in 1992 by the
American Heart Association are intended only for
the diagnosis of the INITIAL ATTACK of ARF and
NOT for recurrences
• There are 5 major and 4 minor criteria and an
absolute requirement for evidence (microbiologic
or serologic) of recent GAS infection
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 Clinical Manifestations and Diagnosis
• The diagnosis of ARF can be established by the
Jones criteria when a patient meets the absolute
requirement for evidence (microbiologic or
serologic) of recent GAS infection and fulfils:

A. 2 major criteria or
B. 1 major and 2 minor criteria

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 Clinical Manifestations and Diagnosis
• There are 3 circumstances in which the diagnosis
of ARF can be made without strict adherence to
the Jones criteria:
1. Sydenham Chorea
2. Carditis
3. Recurrence:

• Although most patients with recurrences of ARF

fulfil the Jones criteria, some may not

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 The Jones Criteria
• Major criteria • Minor criteria
1. Progressive migratory 2 clinical:
polyarthritis of the large 1. Fever of > 38⁰C
Joints 2. Arthralgia in the absence of
2. Carditis (Heart) polyarthritis
3. Sydenham Chorea (Brain)
4. Erythema marginatum of 2 laboratory:
the Skin 1. Elevated blood levels of
5. Subcutaneous nodules acute-phase reactants e.g.
under the Skin CRP, ESR
2. Prolonged PR interval on
ECG (1st degree heart block)
in the absence of carditis
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 Major Manifestations
Progressive Migratory Polyarthritis (PMP)
• Occurs in about 75% of patients with ARF
• Typically involves larger joints, particularly the knees, ankles,
wrists, and elbows
• Involvement of the spine, small joints of the hands and feet,
or hips is uncommon
• Rheumatic joints are generally hot, red, swollen, non-
suppurative and exquisitely tender; even the friction of
bedclothes is uncomfortable
• Characteristically migratory in nature
• Treatment: salicylates (Aspirin)
- There is a dramatic response to salicylates which is another
characteristic feature of the arthritis, and the absence of such
a response should suggest an alternative diagnosis
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 Carditis
• Carditis and resultant chronic RHD are the most
serious manifestations of ARF and account for
essentially all of the associated morbidity and
mortality
• Rheumatic carditis is characterized by pancarditis,
with active inflammation of:
- Endocardium
- Myocardium
- Pericardium
• Endocarditis (valvulitis), which manifests by 1 or
more cardiac murmurs, is a universal finding in
rheumatic carditis
• The presence of pericarditis or myocarditis is variable
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 Carditis
• Myocarditis and/or pericarditis without evidence of
endocarditis is rarely due to RHD
• Valves of the left side of the heart are the commonly
affected
• The common valve involved is the mitral valve (70%)
• Next is aortic and then tricuspid. Pulmonary valve is
very rarely involved
• Serious and long-term illness is related entirely to
valvular heart disease as a consequence of a single
attack or recurrent attacks of ARF
• Valvular insufficiency is characteristic of both acute
and convalescent stages of ARF
• Valvular stenosis usually appears several years or
even decades after the acute illness
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 Carditis
• Acute rheumatic carditis usually presents as
tachycardia and cardiac murmurs, with or without
evidence of myocardial or pericardial involvement
• Moderate to severe rheumatic carditis can result in
cardiomegaly and CCF with hepatomegaly and
peripheral and pulmonary edema
• Echocardiographic findings include pericardial
effusion, decreased ventricular contractility, and
mitral and/or aortic regurgitation
• Echocardiographic demonstration of valvular
regurgitation without accompanying auscultatory
evidence does not satisfy the Jones criteria for
carditis
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 Carditis
• Carditis occurs in about 50–60% of all cases of ARF
• Recurrent attacks of acute rheumatic fever in
patients who had carditis with the initial attack are
associated with high rates of carditis
• The major consequence of acute rheumatic carditis
is chronic, progressive valvular disease,
particularly valvular stenosis
• This can require valve replacement and
predispose to infective endocarditis (IE)

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 Histopathology of Carditis
• Aschoff bodies within the heart muscle are
pathognomonic for ARF
• Consist of a central zone of degenerating,
hypereosinophilic extracellular matrix infiltrated by
lymphocytes (primarily T cells), occasional plasma
cells, and plump activated macrophages called
Anitschkow cells
• Anitschkow cells have abundant cytoplasm and
central nuclei with chromatin arrayed in a slender,
wavy ribbon
• Hence, called caterpillar cells
• Aschoff bodies can be found in any of the three layers
of the heart-pericardium, myocardium, or
endocardium (including valves)-so-called pancarditis
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 Sydenham Chorea
• Historically called Saint Vitus Dance

• Is a disorder characterized by rapid involuntary

purposeless (uncoordinated) jerking movements
primarily affecting the face, hands and feet

• Emotional lability, incoordination, poor school

performance, uncontrollable movements, and
facial grimacing, exacerbated by stress and
disappearing with sleep, are characteristic
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 Sydenham Chorea
• Occurs in about 10–15% of patients with ARF
• Usually presents as an isolated, frequently
subtle, neurologic behaviour disorder
• Chorea occasionally is unilateral
• The latent period from acute GAS infection to
chorea is usually longer than for arthritis or
carditis and can be months
• Onset can be insidious, with symptoms being
present for several months before recognition

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 Sydenham Chorea
• Clinical manoeuvres to elicit features of sydenham
chorea include:
1. Demonstration of milkmaid's grip (irregular
contractions and relaxation of the muscles of the
hands while squeezing the examiner's fingers, as if
milking from a breast)
2. Wormian darting movements of the tongue upon
protrusion
3. Handwriting examination to evaluate fine motor
movements
4. Spooning and pronation of the hands when the
patient's arms are extended

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 Erythema Marginatum of the Skin
• Is a rare: <3% of patients with ARF
• Is a characteristic rash of ARF
• Consists of maculoerythematous, serpiginous,
lesions with pale centres that are not pruritic
• Occurs primarily on the trunk and extremities,
but not on the face, and it can be accentuated by
warming the skin

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 Erythema Marginatum of the Skin

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 Subcutaneous Nodules

• Rare: ≤1% of patients with ARF

• Consist of firm nodules approximately 1 cm in
diameter along the extensor surfaces of tendons
near bony prominences
• There is a correlation between the presence of
these nodules and significant RHD

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 Differential Diagnosis
• Arthritis • Carditis
- Rheumatoid arthritis (RA) - Viral myocarditis
- Reactive arthritis (e.g. - Viral pericarditis
Shingella, Salmonella, - Infective endocarditis (IE)
Yersinia) - Kawasaki disease
- Serum sickness - Congenital heart disease
- Sickle cell disease (SCD) (CHD)
- Malignancy - Mitral valve prolapse
- Systemic lupus
erythromatosus (SLE)
- Lyme disease (Borreria
burgdorferi)
- Gonoccocal infection
(Neisseria gonorrhaeae)

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 Differential Diagnosis
• Chorea
- Huntington chorea
- Wilson disease
- SLE
- Cerebral palsy (CP)
- Tics
- Hyperactivity

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 Management
• Prevention
• Investigations:
- Aim to establish the Jones criteria (throat swabs
or blood for MCS, serology, ECG)
- Others: CXR, Echo, routine lab tests
• Treatment
- Medical: non-pharmacologic/pharmacological
- Surgical

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 Treatment
• Bed rest and monitor closely for evidence of carditis
• To ambulate as soon as the signs of acute inflammation
have subsided
• Patients with carditis require longer periods of bed rest
Antibiotic Therapy
• Once diagnosed of ARF, regardless of the throat culture
results, the patient should receive 10 days of PO pen V or
erythromycin, or a single IV injection of benzathine
penicillin
• This is done to eradicate GAS from the URT
• After this initial course of antibiotic therapy, the patient
should be started on long-term antibiotic prophylaxis

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 Treatment
Anti-Inflammatory Therapy
• Anti-inflammatory agents (e.g., salicylates,
corticosteroids) should be withheld if arthralgia or
atypical arthritis is the only clinical manifestation of
presumed ARF
• Premature treatment may interfere with the
development of the characteristic migratory
polyarthritis
• This can obscure the diagnosis of ARF
• Paracetamol can be used to control pain and fever
while the patient is being observed for more
definite signs of ARF or for evidence of another
disease

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 Treatment
• Typical migratory polyarthritis: oral salicylates
- Aspirin: 100 mg/kg/day in 4 divided doses PO for 3–5
days, followed by 75 mg/kg/day in 4 divided doses PO
for 4 wk
• Carditis and cardiomegaly or congestive heart failure:
corticosteroids and anti-heart failure drugs
- Prednisone: 2 mg/kg/day in 4 divided doses for 2–3
wk followed by a tapering of the dose that reduces
the dose by 5 mg/24 hr every 2–3 days
- At the beginning of the tapering of the prednisone
dose, aspirin should be started at 75 mg/kg/day in 4
divided doses for 6 wk
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 Treatment
• Supportive therapies for patients with moderate
to severe carditis include:
- Digoxin
- Fluid and salt restriction
- Diuretics
- Oxygen

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 Sydenham Chorea
• Sedatives may be helpful early in the course of
chorea
• Phenobarbital is the drug of choice: 16–32 mg
every 6–8 hr PO
• Haloperidol: 0.01–0.03 mg/kg/24 hr divided bid
PO
• Chlorpromazine: 0.5 mg/kg every 4–6 hr PO

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 Prognosis
• Depends on:
1. Clinical manifestations present at the time of the initial
episode
2. Severity of the initial episode
3. Presence of recurrences
• 70% of the patients with carditis during the initial episode
of ARF recover with no residual heart disease
• The more severe the initial cardiac involvement, the greater
the risk for residual heart disease
• Patients who have had ARF are susceptible to recurrent
attacks following reinfection of the URT with GAS
• Therefore, these patients require long-term continuous
chemoprophylaxis
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 Prevention
• Prevention of both initial and recurrent episodes of
ARF depends on controlling GAS infections of the
URT
• There are 4 types of prevention:
1. Primordial prevention
2. Primary prevention
3. Secondary prevention
4. Tertiary prevention

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 Primordial Prevention
- Aims to stop the development of risk factors
for ARF/RHD in a population
- This means preventing the acquisition of GAS
infection and thus preventing GAS pharyngitis
- This can be achieved via implementing actions
and measures that target environmental,
economic, social and behavioural conditions,
and cultural patterns of living that are known to
increase the risk of GAS infection

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 Primary Prevention
• Means prevention of initial attacks of ARF after
the patient has acquired GAS pharyngitis
• Appropriate antibiotic therapy instituted before
the 9th day of symptoms of acute GAS
pharyngitis is highly effective in preventing 1st
attacks of ARF from that episode
• However, about ⅓ of patients with ARF do not
recall a preceding episode of pharyngitis

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 Secondary Prevention
• Means prevention of GAS pharyngitis recurrences
after first attack of ARF
• Requires continuous antibiotic prophylaxis
• This should begin as soon as the diagnosis of ARF has
been made and immediately after a full course of
antibiotic therapy has been completed
• Patients who have had carditis should receive
antibiotic prophylaxis well into adulthood and
perhaps for life
• This is because with they are at a relatively high risk
for recurrences with carditis and for sustaining
additional cardiac damage
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 Tertiary prevention
- Means treatment options for patients diagnosed
with RHD
- The goal is to reduce symptoms of the disease,
reduce disability and ultimately prevent
premature death
- Once damaged, the preventive measures have
palliative rather than curative effect
- Depending on the degree of damage, tertiary
prevention may include:
1. Surgical repair/replacement of the valves
2. Drug therapy
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Chemoprophylaxis for Recurrence of ARF

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 Duration of Prophylaxis for People Who Have Had Acute Rheumatic Fever:
Recommendations of the American Heart Association

• Rheumatic fever without carditis:

- 5 yr or until 21 yr of age, whichever is longer
• Rheumatic fever with carditis but without
residual heart disease (no valvular disease):
- 10 yr or well into adulthood, whichever is longer
• Rheumatic fever with carditis and residual heart
disease (persistent valvular disease):
- More than 10 yrs since last episode and at least
until 40 yr of age; sometimes lifelong prophylaxis

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 Thanks

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