Cardiovascular Disorders

Rheumatic Heart Disease

What is rheumatic heart disease?

Rheumatic heart disease is a condition in which permanent damage to heart valves is caused by
rheumatic fever. The heart valve is damaged by a disease process that generally begins with a
strep throat caused by bacteria called Streptococcus, and may eventually cause rheumatic
fever.

Who is at risk for rheumatic fever?

Rheumatic fever is uncommon in the US, except in children who have had strep infections that
were untreated or inadequately treated. Children ages 5 to 15, particularly if they experience
frequent strep throat infections, are most at risk for developing rheumatic fever.

Why is rheumatic fever a concern?

Rheumatic fever, an inflammatory disease, can affect many connective tissues, especially in the
heart, joints, skin, or brain. The infection often causes heart damage, particularly scarring of the
heart valves, forcing the heart to work harder to pump blood. The damage may resolve on its
own, or it may be permanent, eventually causing congestive heart failure (a condition in which
the heart cannot pump out all of the blood that enters it, which leads to an accumulation of blood
in the vessels leading to the heart and fluid in the body tissues).

What are the symptoms of rheumatic fever?

The symptoms of rheumatic fever usually start about one to five weeks after your child has been
infected with Streptococcus bacteria. The following are the most common symptoms of
rheumatic fever. However, each child may experience symptoms differently. Symptoms may
include:
 joint inflammation - including swelling, tenderness, and redness over multiple joints. The
joints affected are usually the larger joints in the knees or ankles. The inflammation
"moves" from one joint to another over several days.

 small nodules or hard, round bumps under the skin

 a change in your child's neuromuscular movements (this is usually noted by a change in

your child's handwriting and may also include jerky movements)

 rash (a pink rash with odd edges that is usually seen on the trunk of the body or arms
and legs)

 fever

 weight loss

 fatigue

 stomach pains
 The symptoms of rheumatic fever may resemble other conditions or medical problems. Always
consult your child's physician for a diagnosis.

Treatment for rheumatic heart disease:

Specific treatment for rheumatic heart disease will be determined by your child's physician
based on:
 your child's overall health and medical history
 extent of the disease
 your child's tolerance for specific medications, procedures, or therapies
 expectations for the course of the disease
 your opinion or preference

The best treatment for rheumatic heart disease is prevention. Antibiotics can usually treat strep
throat (a Streptococcus bacterial infection) and stop acute rheumatic fever from developing.
Antibiotic therapy has sharply reduced the incidence and mortality rate of rheumatic fever and
rheumatic heart disease.

Children who have previously contracted rheumatic fever are often given continuous (daily or
monthly) antibiotic treatments to prevent future attacks of rheumatic fever and lower the risk of
heart damage.

If inflammation of the heart has developed, children may be placed on bed rest. Medications are
given to reduce the inflammation, as well as antibiotics to treat the Streptococcus infection.
Other medications may be necessary to handle congestive heart failure.

If heart valve damage occurs, surgical repair or replacement of the valve may be considered.

Background: Rheumatic heart disease is the most serious complication of rheumatic fever. Acute
rheumatic fever follows 0.3% of cases of group A beta-hemolytic streptococcal pharyngitis in
children. As many as 39% of patients with acute rheumatic fever may develop varying degrees of
pancarditis with associated valve insufficiency, heart failure, pericarditis, and even death. With
chronic rheumatic heart disease, patients develop valve stenosis with varying degrees of
regurgitation, atrial dilation, arrhythmias, and ventricular dysfunction. Chronic rheumatic heart
disease remains the leading cause of mitral valve stenosis and valve replacement in adults in the
United States.

Acute rheumatic fever and rheumatic heart disease are thought to result from an autoimmune
response, but the exact pathogenesis remains unclear. While rheumatic heart disease was the
leading cause of death 100 years ago in people aged 5-20 years in the United States, incidence of
this disease has decreased in developed countries, and the mortality rate has dropped to just
above 0% since the 1960s. Worldwide, rheumatic heart disease remains a major health problem.
Chronic rheumatic heart disease is estimated to exist in 5-30 million children and young adults;
90,000 patients die from this disease each year. The mortality rate from this disease remains 1-
10%.

Pathophysiology: Rheumatic fever develops in children and adolescents following pharyngitis

with group A beta-hemolytic Streptococcus (ie, Streptococcus pyogenes). The organisms attach to
the epithelial cells of the upper respiratory tract and produce a battery of enzymes allowing them to
damage and invade human tissues. After an incubation period of 2-4 days, the invading organisms
elicit an acute inflammatory response with 3-5 days of sore throat, fever, malaise, headache, and
an elevated leukocyte count.

In 0.3-3% of cases, infection leads to rheumatic fever several weeks after the sore throat has
resolved. Only infections of the pharynx initiate or reactivate rheumatic fever. The organism
spreads by direct contact with oral or respiratory secretions, and spread is enhanced by crowded
living conditions. Patients remain infected for weeks after symptomatic resolution of pharyngitis and
may serve as a reservoir for infecting others. Penicillin treatment shortens the clinical course of
streptococcal pharyngitis and, more importantly, prevents the major sequelae.

Group A Streptococcus is a gram-positive coccus that frequently colonizes the skin and
oropharynx. This organism may cause suppurative disease, such as pharyngitis, impetigo, cellulitis,
myositis, pneumonia, and puerperal sepsis. It also may be associated with nonsuppurative
disease, such as rheumatic fever and acute poststreptococcal glomerulonephritis. Group A
streptococci elaborate the cytolytic toxins streptolysins S and O. Of these, streptolysin O induces
persistently high antibody titers that provide a useful marker of group A streptococcal infection and
its nonsuppurative complications. Group A Streptococcus, as identified using the Lancefield
classification, has a group A carbohydrate antigen in the cell wall that is composed of a branched
polymer of L-rhamnose and N-acetyl-D-glucosamine in a 2:1 ratio.

Group A streptococci may be subserotyped by surface proteins on the cell wall of the organism.
The presence of the M protein is the most important virulence factor for group A streptococcal
infection in humans. More than 90 M serotypes have been identified, some of which have a long
terminal antigenic domain (epitopes) similar to antigens in various components of the human heart.
Rheumatogenic strains often are encapsulated mucoid strains rich in M proteins and resistant to
phagocytosis. These strains are strongly immunogenic, and anti–M antibodies against the
streptococcal infection may cross react with heart tissue. Streptococcal antigens that are
structurally similar to those in the heart include hyaluronate in the bacterial capsule, cell wall
polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share
epitopes with the sarcolemma and smooth muscle.

Acute rheumatic heart disease often produces a pancarditis characterized by endocarditis,

myocarditis, and pericarditis. Endocarditis is manifested as valve insufficiency. The mitral valve is
most commonly and severely affected (65-70% of patients), and the aortic valve is second in
frequency (25%). The tricuspid valve is deformed in only 10% of patients and almost always is
associated with mitral and aortic lesions. The pulmonary valve is rarely affected. Severe valve
insufficiency during the acute phase may result in congestive heart failure and even death (1% of
patients). Whether myocardial dysfunction during acute rheumatic fever is related primarily to
myocarditis or is secondary to congestive heart failure from severe valve insufficiency is not known.
Pericarditis, when present, rarely affects cardiac function or results in constrictive pericarditis.

Chronic manifestations due to residual and progressive valve deformity occur in 9-39% of adults
with previous rheumatic heart disease. Fusion of the valve apparatus resulting in stenosis or a
combination of stenosis and insufficiency develops 2-10 years after an episode of acute rheumatic
fever, and recurrent episodes may cause progressive damage to the valves. Fusion occurs at the
level of the valve commissures, cusps, chordal attachments, or any combination of these.
Rheumatic heart disease is responsible for 99% of mitral valve stenosis in adults in the United
States. Associated atrial fibrillation or left atrial thrombus formation from chronic mitral valve
involvement and atrial enlargement may be observed.

Frequency:

 In the US: At this time, rheumatic fever is uncommon among children in the United States.
Incidence of rheumatic fever and rheumatic heart disease has decreased in the United
States and other industrialized countries in the past 80 years. Prevalence of rheumatic heart
disease in the United States now is less than 0.05 per 1000 population, with rare regional
outbreaks reported in Tennessee in the 1960s and in Utah, Ohio, and Pennsylvania in the
1980s. In the early 1900s, incidence was reportedly 5-10 cases per 1000 population.
Decreased incidence of rheumatic fever has been attributed to the introduction of penicillin
or a change in the virulence of the Streptococcus.

 Internationally: In contrast to trends in the United States, the incidence of rheumatic fever
and rheumatic heart disease has not decreased in developing countries. Retrospective
studies reveal developing countries to have the highest figures for cardiac involvement and
recurrence rates of rheumatic fever. Estimations worldwide are that 5-30 million children and
young adults have chronic rheumatic heart disease, and 90,000 patients die from this
disease each year.

Mortality/Morbidity: Rheumatic heart disease is the major cause of morbidity from rheumatic fever
and the major cause of mitral insufficiency and stenosis in the United States and the world.
Variables that correlate with severity of valve disease include the number of previous attacks of
rheumatic fever, the length of time between the onset of disease and start of therapy, and sex.
(The disease is more severe in females than in males.) Insufficiency from acute rheumatic valve
disease resolves in 60-80% of patients who adhere to antibiotic prophylaxis.

Race: Native Hawaiian and Maori (both of Polynesian descent) have a higher incidence of
rheumatic fever, 13.4 per 100,000 hospitalized children per year, even with antibiotic prophylaxis of
streptococcal pharyngitis. Otherwise, race (when controlled for socioeconomic variables) has not
been documented to influence disease incidence.

Sex: Rheumatic fever occurs in equal numbers in males and females, but the prognosis is worse
for females than for males.

Age: Rheumatic fever is principally a disease of childhood, with a median age of 10 years,
although it also occurs in adults (20% of cases).

CLINICAL Section 3 of 10
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History: A diagnosis of rheumatic heart disease is made after confirming antecedent rheumatic
fever. The modified Jones criteria (revised in 1992) provide guidelines for the diagnosis of
rheumatic fever.

 The Jones criteria require the presence of 2 major or 1 major and 2 minor criteria for the
diagnosis of rheumatic fever.

o The major diagnostic criteria include carditis, polyarthritis, chorea, subcutaneous

nodules, and erythema marginatum.

o The minor diagnostic criteria include fever, arthralgia, prolonged PR interval on the
electrocardiogram, elevated acute phase reactants (increased erythrocyte
sedimentation rate [ESR]), presence of C-reactive protein, and leukocytosis.

 Additional evidence of previous group A streptococcal pharyngitis is required to diagnose

rheumatic fever. One of the following must be present:

o Positive throat culture or rapid streptococcal antigen test

o Elevated or rising streptococcal antibody titer

o History of previous rheumatic fever or rheumatic heart disease

 These criteria are not absolute; the diagnosis of rheumatic fever can be made in a patient
with chorea alone if the patient has had documented group A streptococcal pharyngitis.

 After a diagnosis of rheumatic fever is made, symptoms consistent with heart failure, such
as difficulty breathing, exercise intolerance, and a rapid heart rate out of proportion to fever,
may be indications of carditis and rheumatic heart disease.

Physical: Physical findings in a patient with rheumatic heart disease include cardiac and
noncardiac manifestations of acute rheumatic fever. Some patients develop cardiac manifestations
of chronic rheumatic heart disease.

 Cardiac manifestations of acute rheumatic fever

o Pancarditis is the most serious and second most common complication of rheumatic
fever (50%). In advanced cases, patients may complain of dyspnea, mild-to-moderate
chest discomfort, pleuritic chest pain, edema, cough, or orthopnea.
o On physical examination, carditis is most commonly detected by a new murmur and
tachycardia out of proportion to fever. New or changing murmurs are considered
necessary for a diagnosis of rheumatic valvulitis.
o Some cardiologists have proposed that echo-Doppler evidence of mitral insufficiency,
particularly in association with aortic insufficiency, may be sufficient for a diagnosis of
carditis (even in the absence of accompanying auscultatory findings); however, given
 the sensitivity of modern Doppler devices, this remains controversial.
o Other cardiac manifestations include congestive heart failure and pericarditis.
o Patients in whom the diagnosis of acute rheumatic fever is made should be examined
frequently because of the progressive nature of the disease.

 New or changing murmurs: The murmurs of acute rheumatic fever are typically from valve
insufficiency. The following murmurs are most commonly observed during acute rheumatic
fever:

o Apical pansystolic murmur is a high-pitched, blowing-quality murmur of mitral

regurgitation that radiates to the left axilla. The murmur is unaffected by respiration or
position. Intensity varies but is grade 2/6 or greater. The mitral insufficiency is related
to dysfunction of the valve, chordae, and papillary muscles.
o Apical diastolic murmur (also known as a Carey-Coombs murmur) is heard with
active carditis and accompanies severe mitral insufficiency. It is related to relative
mitral stenosis, as the large volume of regurgitant flow recrosses the mitral valve
during ventricular filling. It is heard best with the bell of the stethoscope, while the
patient is in the left lateral position and the breath held in expiration. This murmur is
low pitched, rumbling, and resembles the roll of a distant drum.
o Basal diastolic murmur is an early diastolic murmur of aortic regurgitation and is high-
pitched, blowing, decrescendo, and heard best along the right upper sternal border
after deep expiration while the patient is leaning forward.

 Congestive heart failure

o Heart failure may develop secondary to severe valve insufficiency or myocarditis.
o The physical findings associated with heart failure include tachypnea, orthopnea,
jugular venous distention, rales, hepatomegaly, a gallop rhythm, and peripheral
swelling and edema.

 Pericarditis

o A pericardial friction rub indicates that pericarditis is present.

o Increased cardiac dullness to percussion and muffled heart sounds are consistent
with pericardial effusion.

o A paradoxical pulse (drop in systolic blood pressure with inspiration) with decreased
systemic pressure and perfusion and evidence of diastolic indentation of the right
ventricle on echocardiogram reflect impending pericardial tamponade. In this clinical
emergency, pericardial effusion should be treated by pericardiocentesis.

 Common noncardiac (and diagnostic) manifestations of acute rheumatic fever include

polyarthritis, chorea, erythema marginatum, and subcutaneous nodules. Other clinical,
noncardiac manifestations include abdominal pain, arthralgias, epistaxis, fever, and
rheumatic pneumonia.
o Polyarthritis is the most common symptom and frequently is the earliest manifestation
of acute rheumatic fever (70-75%). Characteristically, the arthritis begins in the large
joints of the lower extremities (knees and ankles) and migrates to other large joints in
the lower or upper extremities (elbows and wrists). Affected joints are painful,
swollen, warm, erythematous, and limited in their range of motion. The pain is out of
proportion to clinical findings. The arthritis reaches maximum severity in 12-24 hours,
persists for 2-6 days (rarely more than 3 wk) at each site, and responds rapidly to
aspirin. Aspirin improves symptoms in affected joints and prevents further migration
of the arthritis. Polyarthritis is more common and more severe in teenagers and
young adults than in younger children.

o Sydenham chorea occurs in 10-30% of patients with rheumatic fever. Patients

present with difficulty writing, involuntary grimacing, purposeless (choreiform)
movements of the arms and legs, speech impairment, generalized weakness, and
emotional lability. Physical findings include hyperextended joints, hypotonia,
diminished deep tendon reflexes, tongue fasciculations ("bag of worms"), and a "milk
sign" or relapsing grip demonstrated by alternate increases and decreases in tension
when the patient grips the examiner's hand.
o In the absence of a family history of Huntington chorea, the diagnosis of acute
rheumatic fever is almost certain. There is a long latency period (1-6 mo) between
streptococcal pharyngitis and the onset of chorea; a history of an antecedent sore
throat frequently is not obtained. Patients with chorea often do not demonstrate other
Jones criteria. Chorea is slightly more common in females than males. It also is
known as rheumatic chorea, Sydenham chorea, chorea minor, and St Vitus dance.
Daily handwriting samples can be used as an indicator of progression or resolution of
disease. Complete resolution of the symptoms typically occurs with improvement in 1-
2 weeks and full recovery in 2-3 months. Cases have been reported, however, in
which symptoms wax and wane for several years.

o Pediatric autoimmune neuropsychiatric disorders associated with streptococcal

infections (PANDAS) may be associated with chorea. Children have been identified in
whom group A streptococcal infection appears to have triggered a relapsing-remitting
symptom complex characterized by obsessive-compulsive disorder and/or a tic
disorder and neurologic abnormalities, such as cognitive defects and motoric
hyperactivity. The symptoms are prepubertal in onset and may include emotional
lability, separation anxiety, and oppositional behaviors. Streptococcal infection has
been proposed to trigger the formation of antibodies that cross-react with the basal
ganglia of genetically susceptible hosts in a manner similar to the proposed
mechanism for Sydenham chorea, thus causing the symptom complex.

o Erythema marginatum, also known as erythema annulare, is a characteristic rash that

occurs in 5-13% of patients with acute rheumatic fever. It begins as 1-3 cm in
diameter, pink-to-red nonpruritic macules or papules located on the trunk and
proximal limbs but never on the face. The lesions spread outward to form a
serpiginous ring with erythematous raised margins and central clearing. The rash
may fade and reappear within hours and is exacerbated by heat. Thus, if the lesions
 are not well visualized, they can be accentuated by the application of warm towels, a
hot bath, or the use of tangential lighting. The rash occurs early in the course of the
disease and remains long past the resolution of other symptoms. Erythema
marginatum also has been reported in association with sepsis, drug reactions, and
glomerulonephritis.

o Subcutaneous nodules currently are an infrequent manifestation of rheumatic fever.

The frequency has declined over the past several years to 0-8% of patients with
rheumatic fever. When present, the nodules appear over the extensor surfaces of the
elbows, knees, ankles, knuckles, and on the scalp and spinous processes of the
lumbar and thoracic vertebrae where they are attached to the tendon sheath. They
are firm, nontender, and free from attachments to the overlying skin and range in size
from a few mm to 1-2 cm. They vary in number from one to dozens (mean 3-4).
Histologically, they contain areas resembling the Aschoff bodies seen in the heart.
Subcutaneous nodules generally occur several weeks into the disease and resolve
within a month. They are associated strongly with severe rheumatic carditis, and, in
the absence of carditis, the diagnosis of subcutaneous nodules should be questioned.

o Other clinical noncardiac manifestations: Abdominal pain usually occurs at the onset
of acute rheumatic fever. This pain resembles abdominal pain from other conditions
with acute microvascular mesenteric inflammation and may mimic acute appendicitis.
Patients may complain of arthralgias on presentation.
o In the history, it is important to determine if the patient has taken aspirin or
nonsteroidal anti-inflammatory drugs (NSAIDs) because these may suppress the full
manifestations of the disease. Epistaxis may be associated with severe protracted
rheumatic carditis. Fevers above 39°C with no characteristic pattern are present
initially in almost every case of acute rheumatic fever. Fever may be low-grade in
children with mild carditis or absent in patients with pure chorea. It decreases without
antipyretic therapy in about 1 week, but low-grade fevers persist for 2-3 weeks.
Patients with rheumatic pneumonia present with the same signs as patients with
infectious pneumonia. Rheumatic pneumonia should be differentiated from
respiratory distress related to congestive heart failure.

 Cardiac manifestations of chronic rheumatic heart disease: Valve deformities,

thromboembolism, cardiac hemolytic anemia, and atrial arrhythmias are the most common
cardiac manifestations of chronic rheumatic heart disease.

o Valve deformities
 Mitral stenosis occurs in 25% of patients with chronic rheumatic heart disease
and in association with mitral insufficiency in another 40%. Progressive
fibrosis, ie, thickening and calcification of the valve, takes place over time,
resulting in enlargement of the left atrium and formation of mural thrombi in
that chamber. The stenotic valve is funnel-shaped, with a "fish mouth"
resemblance. On auscultation, S1 is initially accentuated but becomes reduced
as the leaflets thicken. P2 becomes accentuated, and the splitting of S2
decreases as pulmonary hypertension develops. An opening snap of the mitral
 valve often is heard at the apex, where a diastolic filling murmur also is heard.
 Aortic stenosis from chronic rheumatic heart disease typically is associated
with aortic insufficiency. The valve commissures and cusps become adherent
and fused, and the valve orifice becomes small with a round or triangular
shape. On auscultation, S2 may be single because the aortic leaflets are
immobile and do not produce an aortic closure sound. The systolic and
diastolic murmurs of aortic valve stenosis and insufficiency are heard best at
the base of the heart.
 Thromboembolism occurs as a complication of mitral stenosis. It is more likely
to occur when the left atrium is dilated, cardiac output is decreased, and the
patient is in atrial fibrillation. The frequency of this complication has decreased
with the use of anticoagulation and the development of surgical repair for the
valve abnormality.

o Cardiac hemolytic anemia is related to disruption of the red blood cells by a deformed
valve. Increased destruction and replacement of platelets also may occur.

o Atrial arrhythmias typically are related to a chronically enlarged left atrium (from a
mitral valve abnormality). Successful cardioversion of atrial fibrillation to sinus rhythm
is more likely to be successful if the left atrium is not markedly enlarged, the mitral
stenosis is mild, and the patient has been in atrial fibrillation for less than 6 months.
Patients should be anticoagulated before cardioversion to decrease the risk of
systemic embolization.

Causes: Rheumatic fever is thought to result from an autoimmune response, but the exact
pathogenesis remains unclear. Rheumatic fever only develops in children and adolescents
following group A beta-hemolytic streptococcal pharyngitis, and only infections of the pharynx
initiate or reactivate rheumatic fever. At least some rheumatogenic strains of group A
Streptococcus have antigenic domains similar to antigens in components of the human heart. That
anti–M antibodies against the streptococci may cross react with heart tissue causing the
pancarditis observed in rheumatic fever has been proposed. Streptococcal antigens that
structurally are similar to those in the heart include hyaluronate in the bacterial capsule, cell wall
polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share
epitopes with the sarcolemma and smooth muscle.

DIFFERENTIALS Section 4 of 10
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Aortic Stenosis, Valvar

Aortic Valve Insufficiency
Aortic Valve, Bicuspid
Appendicitis
Arthritis, Septic
Cardiac Tumors
Cardiomyopathy, Dilated
Carnitine Deficiency
Coccidioidomycosis
Endocarditis, Bacterial
Heart Failure, Congestive
Histoplasmosis
Human Immunodeficiency Virus Infection
Kawasaki Disease
Mitral Stenosis, Congenital
Mitral Valve Insufficiency
Mitral Valve Prolapse
Myocarditis, Viral
Pericardial Effusion, Malignant
Pericarditis, Bacterial
Pericarditis, Viral
Sarcoidosis
Systemic Lupus Erythematosus
Transient Synovitis

Other Problems to be Considered:

Glomerulonephritis

WORKUP Section 5 o
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Lab Studies:

 Throat culture: Throat cultures for group A beta hemolytic Streptococcus usually are negative by the time sym
fever or rheumatic heart disease appear. Attempts should be made to isolate the organism before the initiatio
therapy to help confirm a diagnosis of streptococcal pharyngitis and to allow typing of the organism if it is isola

 Rapid antigen detection test: This test allows rapid detection of group A streptococcal antigen and allows the
streptococcal pharyngitis and the initiation of antibiotic therapy while the patient is still in the physician's office
antigen detection test has a specificity of greater than 95% but a sensitivity of only 60-90%, a throat culture sh
conjunction with this test.

 Antistreptococcal antibodies: The clinical features of rheumatic fever begin at the time antistreptococcal antib
their peak. Thus, antistreptococcal antibody testing is useful for confirming previous group A streptococcal inf
level of antistreptococcal antibodies is useful particularly in patients that present with chorea as the only diagn
Sensitivity for recent infections can be improved by testing for several antibodies. Antibody titers should be ch
intervals in order to detect a rising titer.

o The most common extracellular antistreptococcal antibodies tested include antistreptolysin O (ASO), a
 deoxyribonuclease (DNAse) B, antihyaluronidase, antistreptokinase, antistreptococcal esterase, and a
tests for cellular components of group A streptococcal antigens include antistreptococcal polysaccharid
antibody, and anti–M protein antibody.

o In general, the ratio of antibodies to extracellular streptococcal antigens rises during the first month afte
plateaus for 3-6 months before returning to normal levels after 6-12 months. When the ASO titer peaks
onset of rheumatic fever), the sensitivity of this test is 80-85%. The anti-DNAse B has a slightly higher
detecting rheumatic fever or acute glomerulonephritis. Antihyaluronidase results are frequently abnorm
patients with a normal level of ASO titer and may rise earlier and persist longer than elevated ASO tite
fever.

 Acute phase reactants: The C-reactive protein and erythrocyte sedimentation rate are elevated in rheumatic f
inflammatory nature of the disease. Both tests have a high sensitivity but low specificity for rheumatic fever. T
monitor the resolution of inflammation, detect relapse when weaning aspirin, or identify the recurrence of dise

 Heart reactive antibodies: Tropomyosin is elevated in acute rheumatic fever.

 Rapid detection test for D8/17: This immunofluorescence technique for identifying the B cell marker D8/17 is p
patients with rheumatic fever. It may be useful for identifying patients who are at risk for developing rheumatic

Imaging Studies:

 Chest roentgenogram: Cardiomegaly, pulmonary congestion, and other findings consistent with heart failure m
chest x-ray. When the patient has fever and respiratory distress, the chest x-ray helps differentiate heart failur
pneumonia.

 Doppler-echocardiogram: In acute rheumatic heart disease, Doppler-echocardiography identifies and quantita

insufficiency and ventricular dysfunction.

o With mild carditis, Doppler evidence of mitral regurgitation may be present during the acute phase of d
in weeks to months. In contrast, patients with moderate-to-severe carditis have persistent mitral and/or

o The most important echocardiographic features of mitral regurgitation from acute rheumatic valvulitis a
elongation of the chordae to the anterior leaflet, and a posterolaterally directed mitral regurgitation jet.

o During acute rheumatic fever, the left ventricle is frequently dilated in association with a normal or incre
shortening. Thus, some cardiologists believe that valve insufficiency (from endocarditis), rather than m
(from myocarditis), is the dominant cause of heart failure in acute rheumatic fever.

o In chronic rheumatic heart disease, echocardiography may be used to track the progression of valve s
help determine the time for surgical intervention. The leaflets of affected valves become diffusely thicke
the commissures and chordae tendineae. Increased echodensity of the mitral valve may signify calcific

 Heart catheterization: In acute rheumatic heart disease, this procedure is not indicated. With chronic disease,
catheterization has been performed to evaluate mitral and aortic valve disease and to balloon stenotic mitral v
 o Postcatheterization precautions include hemorrhage, pain, nausea and vomiting, and arterial or venou
thrombosis or spasm.

o Complications may include mitral insufficiency after balloon dilation of the mitral valve, tachyarrhythmia
and vascular occlusion.

Other Tests:

 Electrocardiogram

o Sinus tachycardia most frequently accompanies acute rheumatic heart disease. Alternatively, some ch
bradycardia from increased vagal tone. No correlation exists between bradycardia and the severity of t

o First-degree atrioventricular (AV) block (prolongation of the PR interval) is observed in some patients w
disease. This abnormality may be related to localized myocardial inflammation involving the AV node o
involving the AV nodal artery. First-degree AV block is a nonspecific finding and should not be used as
diagnosis of rheumatic heart disease. Its presence does not correlate with the development of chronic
disease.

o Second-degree (intermittent) and third-degree (complete) AV block with progression to ventricular stan
described. Heart block in the setting of rheumatic fever, however, typically resolves with the rest of the

o When acute rheumatic fever is associated with pericarditis, ST segment elevation may be present and
lead II, III, aVF, and V4-V6.

o Patients with rheumatic heart disease also may develop atrial flutter, multifocal atrial tachycardia, or at
chronic mitral valve disease and atrial dilation.

Histologic Findings: Pathologic examination of the insufficient valves may show verrucous lesions at the line of clo
(perivascular foci of eosinophilic collagen surrounded by lymphocytes, plasma cells, and macrophages) are found in
perivascular regions of the myocardium, and endocardium. The Aschoff bodies assume a granulomatous appearanc
fibrinoid focus and eventually are replaced by nodules of scar tissue. Anitschkow cells are plump macrophages with
the pericardium, fibrinous and serofibrinous exudates may produce an appearance of “bread and butter” pericarditis
TREATMENT Section 6 o
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical Care: Medical therapy is directed toward eliminating the group A streptococcal pharyngitis (if still present),
inflammation from the autoimmune response, and providing supportive treatment for congestive heart failure. Oral p
the drug of choice for treatment of group A streptococcal pharyngitis. When oral penicillin is not feasible or dependab
intramuscular benzathine penicillin G is therapeutic. For patients who are allergic to penicillin, administer erythromyc
generation cephalosporin. Other options include clarithromycin for 10 days, azithromycin for 5 days, or a narrow-spe
generation) cephalosporin for 10 days. As many as 15% of penicillin-allergic patients also are allergic to cephalospo
and sulfonamides should not be used to treat group A streptococcal pharyngitis.

 For recurrent group A streptococcal pharyngitis, a second 10-day course of the same antibiotic can be repeat
 include narrow-spectrum cephalosporins, amoxicillin-clavulanate, dicloxacillin, erythromycin, or other macrolid

 In general, antimicrobial therapy is not indicated for pharyngeal carriers of group A Streptococcus. Exceptions
following:
o Outbreaks of rheumatic fever or poststreptococcal glomerulonephritis
o Family history of rheumatic fever
o Outbreaks of group A streptococcal pharyngitis in a closed community
o When considering tonsillectomy for chronic group A streptococcal carriage
o Multiple episodes of documented group A streptococcal pharyngitis within a family despite appropriate
o Following group A streptococcal toxic shock syndrome or necrotizing fasciitis in a household contact

Carriage is difficult to eradicate with conventional penicillin therapy. Thus, oral clindamycin (20 mg/kg/d in 3 d
days) is recommended.

 Treatment of the acute inflammatory manifestations of acute rheumatic fever consists of administering salicyla
Aspirin in anti-inflammatory doses effectively reduces all manifestations of the disease except chorea, and the
is dramatic. In fact, if rapid improvement is not seen after 24-36 hours of therapy, the diagnosis of rheumatic f
questioned.
o Attempts are made to obtain aspirin blood levels at 20-25 mg/dL, but, due to variable GI absorption of
levels may be difficult to achieve during the inflammatory phase. Aspirin is maintained at anti-inflamma
signs and symptoms of acute rheumatic fever are resolved or subsiding (6-8 wk) and the acute phase
returned to normal levels.
o Anti-inflammatory doses of aspirin may be associated with abnormal liver function tests and GI toxicity
necessary to adjust the aspirin dosage. When discontinuing therapy, aspirin should be withdrawn grad
while monitoring the acute phase reactants for evidence of rebound.

 If moderate-to-severe carditis is indicated by cardiomegaly, congestive heart failure, or third-degree heart blo
should be added to salicylate therapy. Prednisone should be continued for 2-6 weeks, depending on the seve
and tapered during the last week of therapy. Adverse effects can be minimized by discontinuing prednisone th
weeks and maintaining salicylates for an additional 2-4 weeks. Additional treatment for patients with acute rhe
congestive heart failure should include digoxin, diuretics, supplemental oxygen, bed rest, and sodium and flui

Digoxin should be initiated only after checking electrolyte values and correcting abnormal findings in serum p
total loading dose is 20-30 mcg/kg orally with 50% of the dose given initially, followed by 25% of the dose 8 a
initial dose. Maintenance doses typically are 8-10 mcg/kg/d orally in 2 divided doses. For older children and a
loading dose is 1.25-1.5 mg orally, and the maintenance dose is 0.25-0.5 mg/d orally. Therapeutic digoxin lev
trough levels of 1.5-2 ng/mL. The diuretics most commonly used in conjunction with digoxin for children with c
failure include furosemide and spironolactone, both at doses of 1-2 mg/kg/dose twice per day.

 Surgery is indicated to decrease valve insufficiency when heart failure persists or worsens during the acute p
aggressive medical therapy.

 Preventive and prophylactic therapy is indicated after rheumatic fever and rheumatic heart disease to prevent
valves. The initial course of antibiotics given to eradicate the streptococcal infection also serves as the first co
An injection of 0.6-1.2 million units of benzathine penicillin G intramuscularly every 4 weeks is the recommend
secondary prevention for most patients in the United States. The same dosage should be given for 3 weeks in
 rheumatic fever is endemic, in patients with residual carditis, and in high-risk patients.
o While oral penicillin prophylaxis also is effective, data from the World Health Organization suggest that
for group A streptococcal pharyngitis is lower when penicillin is administered parentally.
o The duration of antibiotic prophylaxis is controversial. Antibiotic prophylaxis should be continued indefi
high risk (eg, health care workers, teachers, daycare workers) for recurrent group A streptococcal infec
prophylaxis should be continued indefinitely because recurrent group A streptococcal infection and rhe
possible at any age. The American Heart Association, however, currently recommends that rheumatic
without carditis receive prophylactic antibiotics for 5 years, or until aged 21 years, whichever is longer.
o Patients with rheumatic fever and carditis but no valve disease should receive prophylactic antibiotics f
into adulthood, whichever is longer. Finally, patients with rheumatic fever and carditis and valve diseas
antibiotics at least 10 years or until aged 40 years. Patients with rheumatic heart disease require antibi
before certain surgical and dental procedures to prevent bacterial endocarditis. Patients who have had
without valve disease do not need prophylaxis for prevention of endocarditis. Penicillin should not be u
of endocarditis in patients who are receiving secondary rheumatic fever prophylaxis because of relative
penicillin. The recommended alternative for these patients is erythromycin.

Surgical Care: When heart failure persists or worsens after aggressive medical therapy for acute rheumatic heart d
decrease valve insufficiency may be life-saving.

 Forty percent of patients with acute rheumatic fever subsequently develop mitral stenosis as adults.

 In patients with critical stenosis, mitral valvulotomy, percutaneous balloon valvuloplasty, or mitral valve replac
indicated.

 Due to high rates of recurrent symptoms after annuloplasty or other repair procedures, valve replacement app
preferred surgical option.

Diet: The diet should be nutritious and without restrictions except in the patient with congestive heart failure, whose
intake should be restricted. Potassium supplementation may be necessary because of the mineralocorticoid effect o
the diuretics (if used).

Activity: Initially, patients should be placed on bed rest followed by a period of indoor activity before being permitted
Full activity should not be allowed until the acute phase reactants have returned to normal levels.

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 MEDICATION Section 7 o
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Medical therapy is directed at eliminating the group A streptococcal pharyngitis (if still present), suppressing inflamm
autoimmune response, and providing supportive treatment for congestive heart failure. The treatment and preventio
streptococcal pharyngitis outlined here is based on the current recommendations of the Committee on Infectious Dis
Academy of Pediatrics). See the eMedicine article Pharyngitis.

Penicillin V is the drug of choice for treatment of group A streptococcal pharyngitis. Ampicillin or amoxicillin may be u
penicillin V but have no microbiologic advantage. Tetracyclines and sulfonamides should not be used to treat group
pharyngitis. For recurrent group A streptococcal pharyngitis, a second 10-day course of the same antibiotic can be r
drugs include narrow-spectrum cephalosporins, amoxicillin-clavulanate, dicloxacillin, erythromycin, or other macrolid
as 15% of patients allergic to penicillin also are allergic to cephalosporins.

Drug Category: Antibiotics -- Antibiotics are used for the initial treatment of group A streptococcal pharyngitis to prevent
rheumatic fever (primary prophylaxis), for recurrent streptococcal pharyngitis, and for continuous therapy to prevent recurrent r
rheumatic heart disease (secondary prophylaxis).

Drug Name Penicillin VK (Beepen-VK, Betapen-VK, Pen-Vee K) -- DOC for

treatment of group A streptococcal pharyngitis. Inhibits the
 biosynthesis of cell wall mucopeptide. Bactericidal against sensitive
organisms when adequate concentrations are reached, and most
effective during the stage of active multiplication. Inadequate
concentrations may produce only bacteriostatic effects.
Adult Dose 500 mg PO bid/tid for 10 d
Children: 250 mg (400,000 U) PO bid/tid for 10 d
Pediatric Dose
Adolescents: Administer as in adults
Contraindications Documented hypersensitivity
Probenecid may increase effectiveness by decreasing clearance;
Interactions tetracyclines are bacteriostatic, causing a decrease in the effectiveness
of penicillins when administered concurrently
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in renal impairment; administer 1 h ac or 2 h pc
Penicillin, benzathine (Bicillin L-A) and procaine (Wycillin) -- Used
when oral administration of penicillin is not feasible or dependable.
Discomfort of IM injection may be minimized if the penicillin G is
brought to room temperature before injection or if a combination of
benzathine penicillin G and procaine penicillin G (Bicillin CR) is used.
Drug Name Initial course of antibiotics given to eradicate the streptococcal infection
also serves as the first course of prophylaxis. Benzathine penicillin G
IM q4wk is recommended for secondary prevention for most United
States patients. The same dosage should be used q3wk in areas
where rheumatic fever is endemic, in patients with residual carditis,
and in patients with high risk.
1.2 million U of benzathine penicillin G or a combination of 900,000 U
of benzathine penicillin G with 300,000 U of procaine penicillin G single
Adult Dose dose IM to eradicate streptococcal infection; for secondary prevention
of rheumatic fever, administer the above dose q3wk (high-risk areas or
patients) or q4wk (most areas in United States)
<27 kg: 600,000 U of benzathine penicillin G single dose IM to
eradicate the streptococcal infection; for secondary prevention of
Pediatric Dose rheumatic fever, administer the above dose q3wk (high-risk areas or
patients) or q4wk (most areas in United States)
>27 kg: Administer as in adults
Contraindications Documented hypersensitivity
Increases risk of bleeding when administered concurrently with
warfarin; ethacrynic acid, aspirin, indomethacin, and furosemide may
Interactions
compete with penicillin G for renal tubular secretion increasing
penicillin serum concentrations
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Never use IV route to administer penicillin G procaine; perform cultures
 after treatment to confirm streptococci eradication
Erythromycin estolate (Ilosone) or ethyl succinate (E.E.S, EryPed) --
Used to treat patients allergic to penicillin. Inhibits bacterial growth,
Drug Name
possibly by blocking dissociation of peptidyl tRNA from ribosomes
causing RNA-dependent protein synthesis to arrest.
Adult Dose 1 g/d PO divided bid/qid for 10 d
Pediatric Dose 20-40 mg/kg/d PO divided bid/qid for 10 d
Contraindications Documented hypersensitivity; hepatic impairment
Coadministration may increase toxicity of theophylline, digoxin,
carbamazepine, and cyclosporine; may potentiate anticoagulant effects
Interactions
of warfarin; coadministration with lovastatin and simvastatin, increases
risk of rhabdomyolysis
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Caution in liver disease; estolate formulation may cause cholestatic
jaundice; GI adverse effects are common (give doses pc); discontinue
use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Category: Anti-inflammatory agents -- The manifestations of acute rheumatic fever (including carditis) typically
therapy with anti-inflammatory agents. Aspirin, in anti-inflammatory doses, is the drug of choice. Prednisone is added when the
worsening carditis and heart failure.

Aspirin (Anacin, Ascriptin, Bayer Aspirin) -- Also called acetylsalicylic

acid. Inhibits prostaglandin synthesis, which prevents formation of
Drug Name platelet-aggregating thromboxane A2. Start immediately after the
diagnosis of rheumatic fever has been made. Initiation of therapy may
mask manifestations of the disease.
4-8 g/d PO in 4-6 divided doses; maintain salicylate serum levels in a
Adult Dose 20-25 mcg/dL range until all symptoms resolve and the acute phase
reactants return to normal values
80-100 mg/kg/d PO in 4-6 divided doses; maintain salicylate serum
Pediatric Dose levels in a 20-25 mcg/dL range until all symptoms resolve and the
acute phase reactants return to normal values
Documented hypersensitivity; liver damage, hypoprothrombinemia,
vitamin K deficiency, bleeding disorders, asthma; because of
Contraindications
association of aspirin with Reye syndrome, do not use in children (<16
y) with flu
Interactions Effects may decrease with antacids and urinary alkalinizers;
corticosteroids decrease salicylate serum levels; additive
hypoprothrombinemic effects and increased bleeding time may occur
with coadministration of anticoagulants; may antagonize uricosuric
effects of probenecid and increase toxicity of phenytoin and valproic
 acid; doses >2 g/d may potentiate glucose lowering effect of
sulfonylurea drugs
Pregnancy C - Safety for use during pregnancy has not been established.
Pregnancy category D in third trimester; risk of salicylate intoxication
and poisoning; watch for hyperventilation with prolonged expiratory
Precautions phase with respiratory alkalosis and metabolic acidosis; risk of tinnitus,
hepatic dysfunction, GI discomfort, and ulceration; taken during
pregnancy increases the risk of pulmonary hypertension in the neonate
Prednisone (Deltasone, Orasone) -- May decrease inflammation by
reversing increased capillary permeability and suppressing PMN
activity.
If moderate to severe carditis is indicated by cardiomegaly, congestive
heart failure, or third-degree heart block, 2 mg/kg/d PO should be used
Drug Name
in addition to, or in lieu of, salicylate therapy. Prednisone should be
continued for 2-4 wk, depending on the severity of the carditis, and
tapered during the last week of therapy. Adverse effects can be
minimized by discontinuing prednisone therapy after 2 wk and adding
or maintaining salicylates for an additional 2-4 wk.
Adult Dose 2 mg/kg/d PO for 2-4 wk
Pediatric Dose Administer as in adults
Documented hypersensitivity; viral infection, peptic ulcer disease,
Contraindications hepatic dysfunction, connective tissue infections, and fungal or
tubercular skin infections; GI ulceration or bleeding
Coadministration with estrogens may decrease prednisone clearance;
concurrent use with digoxin may cause digitalis toxicity secondary to
Interactions hypokalemia; phenobarbital, phenytoin, and rifampin may increase
metabolism of glucocorticoids (consider increasing maintenance dose);
monitor for hypokalemia with coadministration of diuretics
Pregnancy B - Usually safe but benefits must outweigh the risks.
Abrupt discontinuation of glucocorticoids may cause adrenal crisis;
hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease,
Precautions
hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis,
growth suppression, and infections may occur with glucocorticoid use
FOLLOW-UP Section 8 o
Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography

Further Outpatient Care:

 Patients usually show significant improvement after initiation of anti-inflammatory therapy. They should not be
full activities, however, until all clinical symptoms have abated and laboratory values have returned to normal

 The importance of prophylaxis against recurrent streptococcal pharyngitis and rheumatic fever should be emp
 patient. Each recurrent episode of rheumatic carditis produces further valve damage and increases the likelih
replacement will be required. Patients should remain on antibiotic prophylaxis at least until their early twenties
believe that lifelong prophylaxis is appropriate.

 Patients should be examined regularly to detect signs of mitral stenosis, pulmonary hypertension, arrhythmias
heart failure.

Deterrence/Prevention:

 Primary prevention of rheumatic fever consists of diagnosis and treatment of group A beta-hemolytic streptoc

Complications:

 Potential complications include heart failure from valve insufficiency (acute rheumatic carditis) or stenosis (ch
carditis). Associated cardiac complications include atrial arrhythmias, pulmonary edema, recurrent pulmonary
endocarditis, intracardiac thrombus formation, and systemic emboli.

Prognosis:

 Manifestations of acute rheumatic fever resolve over a period of 12 weeks in 80% of patients and may extend
weeks in the remaining patients.

 Rheumatic fever was the leading cause of death in people aged 5-20 years in the United States 100 years ag
mortality rate was 8-30% from carditis and valvulitis but decreased to a 1-year mortality rate of 4% by the 193

 Following the development of antibiotics, the mortality rate decreased to almost 0% by the 1960s in the Unite
has remained 1-10% in developing countries. The development of penicillin also has affected the likelihood o
valvular disease after an episode of acute rheumatic fever. Before penicillin, 60-70% of patients developed va
compared to 9-39% of patients since penicillin was developed.

 In patients who develop murmurs from valve insufficiency from acute rheumatic fever, numerous factors, inclu
the initial carditis, the presence or absence of recurrences, and the amount of time since the episode of rheum
likelihood that valve abnormalities and the murmur will disappear. The type of treatment and the promptness
is initiated does not affect the likelihood of disappearance of the murmur. In general, the incidence of residual
disease at 10 years is 34% in patients without recurrences but 60% in patients with recurrent rheumatic fever
the murmur, when it occurs, happens within 5 years in 50% of patients. Thus, significant numbers of patients
resolution of valve abnormalities even 5-10 years after their episode of rheumatic fever. The importance of pr
of rheumatic fever is evident.