Rheumatic Fever

Etiology
• Considerable evidence supports the link between antecedent
GAS pharyngitis and acute rheumatic fever (RF) and rheumatic
heart disease .
• As many as two thirds of patients with an acute episode of
RF have history of an upper respiratory tract infection
several weeks before, and the peak age and seasonal
incidence of acute RF closely parallel that of GAS pharyngitis.
• Patients with acute RF almost always have serologic
evidence of a recent GAS infection. Their antibody titers are
usually considerably higher than those seen in patients with
uncomplicated GAS infections. Outbreaks of GAS pharyngitis in
closed communities, such as boarding schools or military
bases, may be followed by outbreaks of acute RF.
• Antimicrobial therapy that eliminates GAS from the pharynx
also prevents initial episodes of acute RF, and long-term,
continuous antibiotic prophylaxis that prevents GAS pharyngitis
also prevents recurrences of acute RF.
• Not all serotypes of GAS can cause rheumatic fever. When
some GAS strains (e.g., M type 4) caused acute pharyngitis in
a very susceptible rheumatic population, there were no
recurrences of RF.
• In contrast, episodes of pharyngitis caused by other serotypes
in the same population led to frequent recurrences of acute RF,
suggesting that the latter organisms were rheumatogenic.
• The concept of rheumatogenicity is further supported by the
observation that although serotypes of GAS frequently
associated with skin infection can be isolated also from the
upper respiratory tract, they rarely cause recurrences of RF in
individuals with a previous history of RF or first episodes of RF.
• In addition, certain serotypes of GAS (M types 1, 3, 5, 6, 18, 29)
are more frequently isolated from patients with acute RF than
are other serotypes.
Epidemiology
• The annual incidence of acute rheumatic fever in some
developing countries exceeds 50 per 100,000 children, and
very high rates are also seen in ethnic minority populations
within Australia and New Zealand.
• Worldwide, rheumatic heart disease remains the most
common form of acquired heart disease in all age-
groups, accounting for up to 50% of all cardiovascular
disease and 50% of all cardiac admissions in many
developing countries.
• Striking differences in the incidence of acute RF and
rheumatic heart disease among different ethnic groups are
often evident within the same country; these differences are
partially related to differences in socioeconomic status, and
there is a genetic basis for increased susceptibility.
• In the United States at the beginning of the 20th century,
acute RF was a leading cause of death among children and
adolescents, with annual incidence rates of 100-200 per
100,000 population.
• In addition, rheumatic heart disease was a leading cause of
heart disease among adults <40 yr old.
• At that time, as many as 25% of pediatric hospital beds in the
United States were occupied by patients with acute RF or its
complications.
• By the 1940s, the annual incidence of acute RF had
decreased to 50 per 100,000 population, and over the next 4
decades, the decline in incidence accelerated rapidly.
• By the early 1980s, the annual incidence in some areas of the
United States was as low as 0.5 per 100,000 population.
• This sharp decline in the incidence of acute RF has been
observed in other industrialized countries as well.
• The explanation for this dramatic decline in the incidence of
acute RF and rheumatic heart disease in the United States
and other industrialized countries is not clear but is likely
related in large part to a decline in circulating rheumatogenic
strains causing acute pharyngitis .
• Historically, acute RF was associated with poverty and
overcrowding, particularly in urban areas.
• Much of the decline in the incidence of acute RF in
industrialized countries during the preantibiotic era was
probably the result of improved living conditions.
• Of the various manifestations of poverty, crowding , which
facilitates spread of GAS infections, is most closely associated
with the incidence of acute RF.
• The decline in incidence of acute RF in industrialized countries
over the past 4 decades is also attributable to the greater
availability of medical care and to the widespread use of
antibiotics.
• Antibiotic therapy of GAS pharyngitis is important in
preventing initial attacks and, particularly, recurrences of the
disease.
• In addition, the decline in the United States is attributed to a
shift in the prevalent strains of GAS causing pharyngitis from
mostly rheumatogenic to nonrheumatogenic.
• A dramatic outbreak of acute RF in the Salt Lake City, UT,
area began in early 1985, and 198 cases were reported by the
end of 1989. Other outbreaks were reported between 1984
and 1988 in Columbus and Akron, OH; Pittsburgh, PA;
Nashville and Memphis, TN; New York, NY; Kansas City, MO;
Dallas, TX; and among Navy recruits in California and Army
recruits in Missouri.
• In virtually all areas of the United States, rates have declined
substantially.
• Certain rheumatogenic serotypes (types 1, 3, 5, 6, and 18)
that were isolated less often during the 1970s and early
1980s dramatically reappeared during rheumatic fever
outbreaks, and their appearance in selected communities
was probably a major factor.
• GAS that are associated with rheumatogenicity often form
highly mucoid colonies on throat culture plates.
• In addition to the specific characteristics of the infecting
strain of GAS, the risk of developing acute RF also depends
on various host factors.
• The incidence of both initial attacks and recurrences of acute
RF peaks in children 5-15 yr old, the age of greatest risk
for GAS pharyngitis.
• Patients who have had an attack of acute RF tend to have
recurrences, and the clinical features of the recurrences tend
to mimic those of the initial attack.
• In addition, there appears to be a genetic predisposition to
acute RF.
• Studies in twins show a higher concordance rate of acute RF
in monozygotic than in dizygotic twin pairs.
Pathogenesis
• The cytotoxicity theory suggests that a GAS toxin is involved
in the pathogenesis of acute rheumatic fever and rheumatic
heart disease.
• GAS produces a number of enzymes that are cytotoxic for
mammalian cardiac cells, such as streptolysin O, which has a
direct cytotoxic effect on mammalian cells in tissue culture.
• Most proponents of the cytotoxicity theory have focused on this
enzyme. However, a major problem with the cytotoxicity
hypothesis is its inability to explain the substantial latent
period (usually 10-21 days) between GAS pharyngitis and
onset of acute RF.
• An immune-mediated pathogenesis for acute RF and
rheumatic heart disease has been suggested by its clinical
similarity to other illnesses with an immunopathogenesis and
by the latent period between the GAS infection and acute RF.
• The antigenicity of several GAS cellular and extracellular
epitopes and their immunologic cross-reactivity with cardiac
antigenic epitopes also lends support to the hypothesis of
molecular mimicry.
• Common epitopes are shared between certain GAS
components (e.g., M protein, cell membrane, group A cell wall
carbohydrate, capsular hyaluronate) and specific mammalian
tissues (e.g., heart valve, sarcolemma, brain, joint).
• For example, certain rheumatogenic M proteins (M1, M5, M6,
and M19) share epitopes with human myocardial proteins such
as tropomyosin and myosin.
• Additionally, the involvement of GAS superantigens such as
pyrogenic exotoxins in the pathogenesis of acute RF has
been proposed.
• Another proposed pathogenetic hypothesis is that the binding
of an M-protein N-terminal domain to a region of collagen type
IV leads to an antibody response to the collagen , resulting in
ground substance inflammation, especially in subendothelial
areas such as cardiac valves and myocardium.
Clinical Manifestations and Diagnosis
• Because no clinical or laboratory finding is
pathognomonic for acute rheumatic fever, T. Duckett Jones
proposed guidelines in 1944 to aid in diagnosis and to limit
overdiagnosis.
• The Jones Criteria, as revised in 2015 by the American Heart
Association (AHA), are intended for diagnosis of the initial
attack of acute RF and recurrent attacks (Table 210.2 ).
• There are 5 major and 4 minor criteria and a requirement of
evidence of recent GAS infection.
• The 2015 revision includes separate criteria for Low-Risk
populations (defined as those with incidence ≤2 per 100,000
school-age children per year or all-age rheumatic heart
disease prevalence of ≤1 per 1,000 population) and Moderate/
High-Risk populations (defined as those with higher incidence
or prevalence rates).
• Virtually all of the United States, Canada, and Western Europe
are Low-Risk, whereas Moderate/High-Risk populations
include Maoris in New Zealand, aborigines in Australia, Pacific
Islanders, and most developing countries.

• Diagnosis of a first attack or recurrent attack of acute RF can

be established when a patient fulfills 2 major or 1 major and 2
minor criteria and has evidence of preceding GAS infection.

• Diagnosis of recurrent acute RF can also be made only in the

Moderate/High-Risk population by presence of 3 minor
criteria with evidence of preceding GAS infection.
• In the 2015 Jones Criteria revision, a major change from
previous versions expands the definition of the major criterion
carditis to include subclinical evidence (e.g., in the absence
of a murmur, echocardiographic evidence of mitral
regurgitation [MR] meeting specific criteria to distinguish
physiologic from pathologic MR) (see Table 465.1 ).
• Areas in which the Jones Criteria differ in Low-Risk from
Moderate/High- Risk populations relate to the major criterion
of arthritis and the minor criteria of arthralgia, definition of
fever, and of elevated inflammatory markers (see Table 210.2
and text below).
• These changes are designed to make it easier to fulfill the
Jones Criteria in patients from Moderate/High-Risk
populations.
• Even with strict application of the criteria, overdiagnosis as
well as underdiagnosis of acute RF may occur.

• The diagnosis of acute RF can be made without strict

adherence to the Jones Criteria in 3 circumstances:
1. When chorea occurs as the only major manifestation of acute
RF
2. When indolent carditis is the only manifestation in patients
who first come to medical attention only months after the
apparent onset of acute RF
3. In a limited number of patients with recurrence of acute RF in
particularly high-risk populations.
The 5 Major Criteria

1. Migratory Polyarthritis
• Arthritis occurs in approximately 75% of patients with
acute rheumatic fever and 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 classically hot, red, swollen, and
exquisitely tender, with even the friction of bedclothes being
uncomfortable.
• The pain can precede and can appear to be disproportionate
to the objective findings.
• The joint involvement is characteristically migratory in
nature; that is, a severely inflamed joint can become normal
within 1-3 days without treatment, even as 1 or more other
large joints become involved.
• Severe arthritis can persist for several weeks in untreated
patients.
• Monoarticular arthritis is unusual unless anti inflammatory
therapy is initiated prematurely, aborting the progression of
the migratory polyarthritis.
• If a child with fever and arthritis is suspected to have acute
RF, it is frequently useful to withhold salicylates and observe
for migratory progression.
• A dramatic response to even low doses of salicylates is
another characteristic feature of the arthritis, and the
absence of such a response should suggest an alternative
diagnosis.
• Rheumatic arthritis is almost never deforming.
• Synovial fluid in acute RF usually has 10,000-100,000 white
blood cells/μL with a predominance of neutrophils, protein
level of approximately 4 g/dL, normal glucose level, and
forms a good mucin clot.
• Frequently, arthritis is the earliest manifestation of acute RF
and may correlate temporally with peak antistreptococcal
antibody titers.
• There is often an inverse relationship between the severity
of arthritis and the severity of cardiac involvement.

• In Moderate/High-Risk populations only, monoarthritis in the

absence of prior inflammatory therapies, or even
polyarthralgia without frank objective signs of arthritis, can
fulfill this major criterion. Before polyarthralgia should be
considered a major criterion in the Moderate/High-Risk
population, other potential causes should be excluded.
2. Carditis
• A major change in the 2015 revision of the Jones Criteria is the
acceptance of subclinical carditis (defined as without a
murmur of valvulitis but with echocardiographic evidence
of valvulitis) or clinical carditis (with a valvulitis murmur) as
fulfilling the major criterion of carditis in all populations.
• The echocardiographic features of subclinical carditis must
meet those included in Table 465.1 , to distinguish pathologic
from physiologic degrees of valve regurgitation.
• Subclinical (i.e. only echocardiographic) evidence of
pathologic mitral regurgitation requires that a jet is seen
in at least two views, the jet length is ≥2 cm in at least 1
view, peak jet velocity is >3 meters/second, and the peak
systolic jet is in at least 1 envelope.
• Subclinical pathologic evidence of aortic regurgitation is
similar except that the jet length is ≥1 cm in at least 1 view.
• Carditis and resultant chronic rheumatic heart disease are the
most serious manifestations of acute RF and account for
essentially all the associated morbidity and mortality.
• Rheumatic carditis is characterized by pancarditis , with
active inflammation of myocardium, pericardium, and
endocardium (see Chapter 465 ).
• Cardiac involvement during acute RF varies in severity from
fulminant, potentially fatal exudative pancarditis to mild,
transient cardiac involvement.
• Endocarditis (valvulitis) is a universal finding in rheumatic
carditis, whereas the presence of pericarditis or myocarditis
is variable.
• Myocarditis and/or pericarditis without clinical evidence of
endocarditis almost never is rheumatic carditis; alternate
etiologies (especially viral) need to be sought.
• Most rheumatic heart disease is isolated mitral valvular
disease or combined aortic and mitral valvular disease.
• Isolated aortic or right-sided valvular involvement is quite
uncommon.
• Serious and long-term illness is related entirely to the
severity of valvular heart disease as a consequence of a
single attack or recurrent attacks of acute RF.

• Valvular insufficiency is characteristic of both acute and

convalescent stages of acute RF, whereas mitral and/or
aortic valvular stenosis usually appears years or even
decades after the acute illness. However, in developing
countries, where acute RF often occurs at a younger age,
mitral stenosis and aortic stenosis may develop sooner
after acute RF than in developed countries and can occur
in young children.

• 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 heart failure with hepatomegaly and
peripheral and pulmonary edema.

• Echocardiographic findings include

- pericardial effusion
- decreased ventricular contractility
- aortic and/or mitral regurgitation
• Mitral regurgitation is characterized typically by a high-
pitched apical holosystolic murmur radiating to the
axilla. In patients with significant MR, this may be
associated with an apical mid-diastolic murmur of
relative mitral stenosis.

• Aortic insufficiency is characterized by a high-pitched

decrescendo diastolic murmur at the left sternal
border.

• Carditis occurs in approximately 50–60% of all cases of

acute RF. Recurrent attacks of acute RF in patients who had
carditis with their initial attack are associated with high rates
of carditis with increasing severity of cardiac disease.

• The major consequence of acute rheumatic carditis is

chronic, progressive valvular disease, particularly valvular
stenosis, which can require valve replacement.
3. Chorea
• Sydenham chorea occurs in approximately 10–15% of
patients with acute RF and usually presents as an isolated,
frequently subtle, movement disorder.
• Emotional lability, incoordination, poor school
performance, uncontrollable movements, and facial
grimacing are characteristic, all exacerbated by stress and
disappearing with sleep.
• Chorea occasionally is unilateral (hemichorea).
• The latent period from acute GAS infection to chorea is
usually substantially longer than for arthritis or carditis and
can be months.
• Onset can be insidious, with symptoms being present for
several months before recognition.
• Clinical maneuvers to elicit features of chorea include
1. Demonstration of milkmaid's grip (irregular contractions and
relaxations of the muscles of the fingers while squeezing the
examiner's fingers)
2. Spooning and pronation of the hands when the patient's arms
are extended
3. Wormian darting movements of the tongue on protrusion
4. Examination of handwriting to evaluate fine motor
movements.

• Diagnosis is based on clinical findings with supportive

evidence of GAS antibodies.
• However, in the usual patient with a long latent period from
the inciting streptococcal infection to onset of chorea,
antibody levels have often declined to normal.
• Although the acute illness is distressing, chorea rarely if ever
leads to permanent neurologic sequelae.
4. Erythema Marginatum
• Erythema marginatum is a rare (approximately 1% of
patients with acute RF) but characteristic rash of acute
RF.
• It consists of erythematous, serpiginous, macular
lesions with pale centers that are not pruritic (Fig.
210.2 ).
• It occurs primarily on the trunk and extremities, but not on
the face, and it can be accentuated by warming the skin.

5. Subcutaneous Nodules
• Subcutaneous nodules are a rare (≤1% of patients with
acute RF) finding and consist of firm nodules
approximately 0.5-1 cm in diameter along the extensor
surfaces of tendons near bony prominences.
• There is a correlation between the presence of these
nodules and significant rheumatic heart disease.
Minor Criteria
• These are more nonspecific than major criteria, and the 2015
revised Jones Criteria have included some changes from
previous criteria.

• The 1st of the 2 clinical minor criteria involve joint

manifestations (only if arthritis is not used as a major
criterion) and is defined as polyarthralgia in Low-Risk
populations and monoarthralgia in Moderate/High-Risk
populations.
• The 2nd clinical minor manifestation is fever, defined as at
least 38.5°C in Low-Risk populations and at least 38.0°C in
Moderate/High-Risk populations.

• The 2 laboratory minor criteria are:

1. elevated acute-phase reactants, defined as erythrocyte
sedimentation rate (ESR) at least 60 mm/hr and/or C-
reactive protein (CRP) at least 3.0 mg/dL (30 mg/L) in Low-
Risk populations, and ESR at least 30 mm/hr and/or CRP at
least 3.0 mg/dL (30 mg/L) in Moderate/High-Risk
populations
2. prolonged P-R interval on ECG (unless carditis is a major
criterion). However, a prolonged P-R interval alone does not
constitute evidence of carditis or predict long-term cardiac
sequelae.
Recent Group A Streptococcus Infection
• An absolute requirement for the diagnosis of acute RF is
supporting evidence of a recent GAS infection.
• Acute RF typically develops 10-21 days after an acute
episode of GAS pharyngitis at a time when clinical findings of
pharyngitis are no longer present and when only 10–20% of
patients still harbor GAS in the throat.
• One third of patients with acute RF have no history of an
antecedent pharyngitis. Therefore, evidence of an antecedent
GAS infection is usually based on elevated or rising serum
antistreptococcal antibody titers.
• A slide agglutination test (Streptozyme) purports to detect
antibodies against 5 different GAS antigens. Although this test
is rapid, relatively simple to perform, and widely available, it is
less standardized and less reproducible than other tests and is
not recommended as a diagnostic test for evidence of an
antecedent GAS infection.
• If only a single antibody is measured (usually anti–
streptolysin O), only 80–85% of patients with acute RF have
an elevated titer; however, 95– 100% have an elevation if 3
different antibodies (anti–streptolysin O, anti– DNase B,
antihyaluronidase) are measured.
• Therefore, when acute RF is suspected clinically, multiple
antibody tests should be performed. Except for chorea, the
clinical findings of acute RF generally coincide with peak
antistreptococcal antibody responses.
• Most patients with chorea have elevation of antibodies to at
least 1 GAS antigen. However, in patients with a long latent
period from the inciting GAS infection, antibody levels may
have declined to within the normal range.
• The diagnosis of acute RF should not be made in those
patients with elevated or increasing streptococcal antibody
titers who do not fulfill the Jones Criteria.
Differential Diagnosis
• The differential diagnosis of rheumatic fever includes many
infectious as well as noninfectious illnesses (Table 210.3 ).
• When children present with arthritis, a collagen vascular
disease must be considered.
• Juvenile idiopathic arthritis (JIA) must be distinguished from
acute RF. Children with JIA tend to be younger and usually
have less joint pain relative to their other clinical findings than
those with acute RF. Spiking fevers, nonmigratory arthritis,
lymphadenopathy, and splenomegaly are more suggestive of
JIA than acute RF. The response to salicylate therapy is also
much less dramatic with JIA than with acute RF.
• Systemic lupus erythematosus (SLE) can usually be
distinguished from acute RF by antinuclear antibodies in SLE.
• Other causes of arthritis such as pyogenic arthritis,
malignancies, serum sickness, Lyme disease, sickle cell
disease, and reactive arthritis related to gastrointestinal
infections (e.g., Shigella, Salmonella, Yersinia ) should also be
considered.
• Poststreptococcal reactive arthritis is discussed earlier (see
Chapter 210).
• When carditis is the sole major manifestation of suspected
acute RF, viral myocarditis, viral pericarditis, Kawasaki
disease, and infective endocarditis should also be considered.
Patients with infective endocarditis may present with both joint
and cardiac manifestations. These patients can usually be
distinguished from patients with acute RF by blood cultures
and the presence of extracardiac findings (e.g., hematuria,
splenomegaly, splinter hemorrhages). When chorea is the sole
major manifestation of suspected acute RF, Huntington chorea,
Wilson disease, SLE, and various encephalitides should also
be considered.
Treatment
• All patients with acute rheumatic fever should be placed on
bed rest and monitored closely for evidence of carditis.
They can be allowed to ambulate when the signs of acute
inflammation have improved. However, patients with carditis
require longer periods of bed rest.

Antibiotic Therapy
• Once the diagnosis of acute RF has been established and
regardless of the throat culture results, the patient should
receive 10 days of orally administered penicillin or
amoxicillin or a single intramuscular injection of benzathine
penicillin to ensure eradication of GAS from the upper
respiratory tract.
• If penicillin allergic, 10 days of erythromycin, 5 days of
azithromycin, or 10 days of clindamycin is indicated.
• After this initial course of antibiotic therapy, long- term
antibiotic prophylaxis for secondary prevention should be
instituted (see later).

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 acute RF.
• Premature treatment with one of these agents may interfere
with the development of the characteristic migratory
polyarthritis and thus obscure the diagnosis of acute RF.
• Acetaminophen can be used to control pain and fever while
the patient is being observed for more definite signs of acute
RF or for evidence of another disease.
•
• Patients with typical migratory polyarthritis and those with
carditis without cardiomegaly or congestive heart failure
should be treated with oral [Link] usual dose of
aspirin is 50-70 mg/kg/day in 4 divided doses orally (PO) for
3-5 days, followed by 50 mg/kg/day in 4 divided doses PO for
2-3 wk and half that dose for another 2-4 wk.
• Determination of the serum salicylate level is not necessary
unless the arthritis does not respond or signs of salicylate
toxicity (tinnitus, hyperventilation) develop. There is no
evidence that NSAIDs are more effective than salicylates.

• Patients with carditis and more than minimal cardiomegaly

and/or congestive heart failure should receive
corticosteroids. The usual dose of prednisone is 2 mg/kg/day
in 4 divided doses for 2-3 wk, followed by half the dose for 2-3
wk and then tapering of the dose by 5 mg/24 hr every 2-3
days.
• When prednisone is being tapered, aspirin should be
started at 50 mg/kg/day in 4 divided doses for 6 wk to
prevent rebound of inflammation.

• Supportive therapies for patients with moderate to severe

carditis include digoxin, fluid and salt restriction, diuretics, and
[Link] cardiac toxicity of digoxin is enhanced with
myocarditis.

• Termination of the antiinflammatory therapy may be followed

by the reappearance of clinical manifestations or of elevation
in ESR and CRP (rebound).

• It may be prudent to increase salicylates or corticosteroids

until near-normalization of inflammatory markers is achieved.
Sydenham Chorea
• Because chorea often occurs as an isolated manifestation after
the resolution of the acute phase of the disease,
antiinflammatory agents are usually not indicated.
• Sedatives may be helpful early in the course of chorea;
phenobarbital (16-32 mg every 6-8 hr PO) is the drug of
choice. If phenobarbital is ineffective, haloperidol (0.01-0.03
mg/kg/24 hr divided twice daily PO) or chlorpromazine (0.5
mg/kg every 4-6 hr PO) should be initiated.
• Some patients may benefit from a few-week course of
corticosteroids.

Complications
• The arthritis and chorea of acute RF resolve completely without
sequelae. Therefore, the long-term sequelae of RF are
essentially limited to the heart (see Chapter 465 ).
• The AHA has published updated recommendations regarding
the use of prophylactic antibiotics to prevent infective
endocarditis (see Chapter 464 ).
• The AHA recommendations no longer suggest routine
endocarditis prophylaxis for patients with rheumatic heart
disease who are undergoing dental or other procedures.
However, the maintenance of optimal oral healthcare
remains an important component of an overall healthcare
program. For the relatively few patients with rheumatic heart
disease in whom infective endocarditis prophylaxis remains
recommended, such as those with a prosthetic valve or
prosthetic material used in valve repair, the current AHA
recommendations should be followed (see Chapter 464 ).
These recommendations advise using an agent other than a
penicillin to prevent infective endocarditis in those receiving
penicillin prophylaxis for RF because oral α-hemolytic
streptococci are likely to have developed resistance to
penicillin.
Prognosis
• The prognosis for patients with acute rheumatic fever
depends on the clinical manifestations present at the initial
episode, the severity of the initial episode, and the presence
of recurrences.
• Approximately 50–70% of patients with carditis during the
initial episode of acute RF recover with no residual heart
disease; the more severe the initial cardiac involvement, the
greater the risk for residual heart disease.
• Patients without carditis during the initial episode are less
likely to have carditis with recurrent attacks, but there is a
stepwise increase in cardiac involvement as the number of
episodes increases.
• In contrast, patients with carditis during the initial episode
are very likely to have carditis with recurrences, and the risk
for permanent heart damage increases with each recurrence.
Patients who have had acute RF are susceptible to
recurrent attacks following reinfection of the upper respiratory
tract with GAS, with approximately 50% risk with each GAS
pharyngitis. Therefore, these patients require long-term
continuous chemoprophylaxis.
• Before antibiotic prophylaxis was available, 75% of patients
who had an initial episode of acute RF had 1 or more
recurrences in their lifetime.
• These recurrences were a major source of morbidity and
mortality.
• The risk of recurrence is highest in the 1st 5 yr after the
initial episode and decreases with time.
• Approximately 20% of patients who present with “pure” chorea
who are not given secondary prophylaxis develop rheumatic
heart disease within 20 yr. Therefore, patients with chorea,
even in the absence of other manifestations of RF, require
long-term antibiotic prophylaxis (see Table 210.4 ).
Prevention
• Prevention of both initial and recurrent episodes of acute
rheumatic fever depends on controlling GAS infections of
the upper respiratory tract.

• Prevention of initial attacks (primary prevention) depends

on identification and eradication of GAS causing acute
pharyngitis. A New Zealand study in a population with very
high rates of acute RF showed that a school-based GAS
pharyngitis screening and management program using oral
amoxicillin substantially decreased pharyngeal GAS
prevalence and rates of acute RF.

• Individuals who have already suffered an attack of acute RF

are particularly susceptible to recurrences of RF with any
subsequent GAS upper respiratory tract infection, whether or
not they are symptomatic. Therefore, these patients should
receive continuous antibiotic prophylaxis to prevent
recurrences (secondary prevention).

Primary Prevention
• Appropriate antibiotic therapy instituted before the 9th day of
symptoms of acute GAS pharyngitis is highly effective in
preventing first attacks of acute RF.
• However, approximately 30% of patients with acute RF do
not recall a preceding episode of pharyngitis and did not
seek therapy.
Secondary Prevention
• Secondary prevention is directed at preventing acute GAS
pharyngitis in patients at substantial risk of recurrent acute RF.
• Secondary prevention requires continuous antibiotic prophylaxis,
which should begin as soon as the diagnosis of acute RF has
been made and immediately after a full course of antibiotic
therapy has been completed.
• Because patients who have had carditis with their initial
episode of acute RF are at higher risk for having carditis with
recurrences and for sustaining additional cardiac damage, they
should receive long-term antibiotic prophylaxis well into
adulthood and perhaps for life (Tables 210.4 and 210.5 ).
• Patients who did not have carditis with their initial episode of
acute RF have a relatively low risk for carditis with recurrences.
• Antibiotic prophylaxis should continue in these patients until the
patient reaches 21 yr of age or until 5 yr have elapsed since the
last rheumatic fever attack, whichever is longer.
• The decision to discontinue prophylactic antibiotics should be
made only after careful consideration of potential risks and
benefits and of epidemiologic factors such as the risk for
exposure to GAS infections.
• The regimen of choice for secondary prevention is a single
intramuscular injection of benzathine penicillin G (600,000
IU for children weighing ≤60 lb and 1.2 million IU for those
>60 lb) every 4 wk (Table 210.4 ).
• In certain high- risk patients, and in certain areas of the world
where the incidence of rheumatic fever is particularly high, use of
benzathine penicillin G every 3 wk may be necessary because
serum concentrations of penicillin may decrease to marginally
effective levels after 3 wk.