Pediatric Rheumatic Heart Disease 

Updated: Jun 12, 2019
Author: Thomas K Chin, MD; Chief Editor: Syamasundar Rao Patnana, MD 

Overview

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 mitral 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. Although 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 occur in 5-30 million children and young adults; 90,000 individuals die from this disease each year. The mortality rate from this disease remains 1-10%. A comprehensive resource provided by the World Health Organization (WHO) addresses the diagnosis and treatment.[1]

Pathophysiology

Rheumatic fever develops in some 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 have been shown to initiate or reactivate rheumatic fever. However, epidemiological associations in certain populations have led to speculation that group A Streptococcus impetigo could predispose to or cause rheumatic fever as well.[2] However, such a concept is contrary to earlier views advocated by well-respected authorities.[3] 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, is effective in decreasing the incidence of major sequelae such as rheumatic fever.

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 120 M protein serotypes or M protein genotypes have been identified[4] some of which have a long terminal antigenic domain (ie, epitopes) similar to antigens in various components of the human heart.

Rheumatogenic strains are often 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 components of heart tissue (ie, sarcolemmal membranes, valve glycoproteins). Currently, emm typing is felt to be more discriminating than M typing.[4]

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 is almost always 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 primarily related 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.

Etiology

Rheumatic fever is thought to result from an inflammatory autoimmune response. Rheumatic fever only develops in children and adolescents following group A beta-hemolytic streptococcal pharyngitis, and only streptococcal infections of the pharynx initiate or reactivate rheumatic fever.

Genetic studies show strong correlation between progression to rheumatic heart disease and human leukocyte antigen (HLA)-DR class II alleles and the inflammatory protein-encoding genes MBL2 and TNFA.[5] Furthermore, both clones of heart tissue–infiltrating T cells and antibodies have been found to be cross-reactive with beta-hemolytic streptococcus. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10-(+) cells are consistently predominant in valvular tissue, whereas IL-4 regulatory cytokine expression is consistently low.

Decreased levels of regulatory T cells have also been associated with rheumatic heart disease and with increased severity. In utero precursors predisposing to rheumatic heart disease have also been proposed[6, 7] ; Eriksson et al suggest increased spiraling of the umbilical cord may increase risk of developing rheumatic heart disease secondary to presumed change in hemodynamic conditions during formation of the mitral valve.[8]

The proposed pathophysiology for development of rheumatic heart disease is as follows: Cross-reactive antibodies bind to cardiac tissue facilitating infiltration of streptococcal-primed CD4+ T cells, which then trigger an autoimmune reaction releasing inflammatory cytokines (including TNF-alpha and IFN-gamma). Because few IL-4–producing cells are present in valvular tissue, inflammation persists, leading to valvular lesions.

Epidemiology

United States data

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[9] , 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. The incidence of acute rheumatic fever in other developed countries, such as Italy, is comparable.[10]

International data

In contrast to trends in the United States, the incidence of rheumatic fever and rheumatic heart disease has not substantially decreased in developing countries. Retrospective studies reveal developing countries to have the highest figures for cardiac involvement and recurrence rates of rheumatic fever. Worldwide, there are over 15 million cases of RHD, with 282,000 new cases and 233,000 deaths from this disease each year.[11]

A study of school children in Cambodia and Mozambique with rheumatic fever showed that rheumatic heart disease prevalence when echocardiography is used for screening is 10 fold greater compared with the prevalence when clinical examination alone is performed.[12]

Race-, sex-, and age-related demographics

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.

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

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

Prognosis

Manifestations of acute rheumatic fever resolve over a period of 12 weeks in 80% of patients and may extend as long as 15 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 ago. At that time, the mortality rate was 8-30% from carditis and valvulitis but decreased to a 1-year mortality rate of 4% by the 1930s.

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

In patients who develop murmurs from valve insufficiency from acute rheumatic fever, numerous factors, including the severity of the initial carditis, the presence or absence of recurrences, and the amount of time since the episode of rheumatic fever, affect the likelihood that valve abnormalities and the murmur will disappear. The type of treatment and the promptness with which treatment is initiated does not affect the likelihood of disappearance of the murmur.

In general, the incidence of residual rheumatic heart disease at 10 years is 34% in patients without recurrences but 60% in patients with recurrent rheumatic fever. Disappearance of the murmur, when it occurs, happens within 5 years in 50% of patients. Thus, significant numbers of patients experience resolution of valve abnormalities even 5-10 years after their episode of rheumatic fever. The importance of preventing recurrences of rheumatic fever is evident.

Morbidity/mortality

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.

Complications

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

 

Presentation

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.[13]

The Jones criteria require the presence of 2 major or 1 major and 2 minor criteria along with evidence for recent streptococcal infection for the diagnosis of rheumatic fever. The major diagnostic criteria include carditis, polyarthritis, chorea, subcutaneous nodules, and erythema marginatum. The minor diagnostic criteria include fever, arthralgia, prolonged PR interval on ECG, elevated acute phase reactants (increased erythrocyte sedimentation rate [ESR]), presence of C-reactive protein, and leukocytosis.

Evidence of previous group A streptococcal pharyngitis is required to diagnose rheumatic fever. One of the following must be present:

  • Positive throat culture or rapid streptococcal antigen test result

  • Elevated or rising streptococcal antibody titer

  • 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 Examination

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

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. For a graph illustrating the time course for the carditis relative to the other clinical manifestations of rheumatic fever, see the Medscape Reference article Pediatric Rheumatic Fever.

Upon 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.

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)[14] ; however, given the sensitivity of modern Doppler devices, this remains controversial.

Other cardiac manifestations include congestive heart failure and pericarditis.

Patients in whom the diagnosis of acute rheumatic fever is made should be frequently examined because of the progressive nature of the disease.

New or changing murmurs

The murmurs of acute rheumatic fever are typically due to valve insufficiency.

The following murmurs are most commonly observed during acute rheumatic fever:

  • 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.

  • Apical diastolic murmur (also known as a Carey-Coombs murmur) is heard with active carditis and accompanies severe mitral insufficiency. The mechanism for this murmur is postulated to be due to mitral valvulitis, relative mitral stenosis, as the large volume of regurgitant flow traverses the mitral valve during ventricular filling, or combination thereof. 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.

  • Basal diastolic murmur is an early diastolic murmur of aortic regurgitation and is high-pitched, blowing, decrescendo, and heard best along the right upper and mid-left sternal border after deep expiration while the patient is leaning forward.

Congestive heart failure

Heart failure may develop secondary to severe valve insufficiency or myocarditis.

The physical findings associated with heart failure include tachypnea, orthopnea, jugular venous distention, rales, hepatomegaly, a gallop rhythm, edema, and swelling of the peripheral extremities.

Pericarditis

A pericardial friction rub indicates that pericarditis is present.

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

A paradoxical pulse (and accentuated fall 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, the pericardial effusion should be evacuated by pericardiocentesis.

Noncardiac manifestations

Common noncardiac (and diagnostic) manifestations of acute rheumatic fever include polyarthritis, chorea, erythema marginatum, and subcutaneous nodules.

Other clinical, noncardiac manifestations include abdominal pain, arthralgia, epistaxis,[15] fever, and rheumatic pneumonia.

Polyarthritis is the most common symptom and is frequently 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 rapidly responds 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.

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.

In the absence of a family history of Huntington chorea, the diagnosis of acute rheumatic fever is almost certain. A long latency period (1-6 mo) between streptococcal pharyngitis and the onset of chorea is observed; a history of an antecedent sore throat is frequently not obtained. Patients with chorea often do not demonstrate other Jones criteria. Chorea is slightly more common in females than males. It is also 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. However, cases have been reported in which symptoms wax and wane for several years.

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 (somatic obsessions and checking, cleaning, and repeating compulsions), 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.

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. For an example of the typical rash of erythema marginatum, see the Medscape Reference article Pediatric Rheumatic Fever.

Subcutaneous nodules are currently 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. These nodules are strongly associated with severe rheumatic carditis, and, in the absence of carditis, the diagnosis of subcutaneous nodules should be questioned.

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.

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 initially present 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.

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. Upon 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 is typically 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. Upon 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 and balloon valvuloplasty techniques for addressing the valve abnormality.

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

Atrial arrhythmias are typically 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.

 

DDx

Diagnostic Considerations

Important considerations

The incidence of rheumatic heart disease, the facilities available for identifying and treating the illness, and the caring physicians training and experience with this disorder all vary widely with geographic location. Furthermore, scientific understanding of rheumatic heart remains incomplete. For these reasons, recommending a fixed set of guidelines that apply for all situations is difficult.

Special concerns

The American Heart Association no longer recommends subacute bacterial endocardial prophylaxis in patients with aortic or mitral valve abnormalities secondary to rheumatic heart disease.[16]

Differential Diagnoses

 

Workup

Laboratory Studies

Throat culture

Throat culture findings for group A beta hemolytic Streptococcus are usually negative by the time symptoms of rheumatic fever or rheumatic heart disease appear. Attempts should be made to isolate the organism before the initiation of antibiotic therapy to help confirm a diagnosis of streptococcal pharyngitis and to allow typing of the organism if it is isolated successfully.

Rapid antigen detection test

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

Antistreptococcal antibodies

The clinical features of rheumatic fever begin at the time antistreptococcal antibody levels are at their peak. Thus, antistreptococcal antibody testing is useful for confirming previous group A streptococcal infection. The elevated level of antistreptococcal antibodies is useful, particularly in patients that present with chorea as the only diagnostic criterion. Sensitivity for recent infections can be improved by testing for several antibodies. Antibody titers should be checked at 2-week intervals in order to detect a rising titer.

The most common extracellular antistreptococcal antibodies tested include antistreptolysin O (ASO), antideoxyribonuclease (DNAse) B, antihyaluronidase, antistreptokinase, antistreptococcal esterase, and anti-DNA. Antibody tests for cellular components of group A streptococcal antigens include antistreptococcal polysaccharide, antiteichoic acid antibody, and anti–M protein antibody.

In general, the ratio of antibodies to extracellular streptococcal antigens rises during the first month after infection and then plateaus for 3-6 months before returning to normal levels after 6-12 months. When the ASO titer peaks (2-3 wk after the onset of rheumatic fever), the sensitivity of this test is 80-85%. The anti-DNAse B has a slightly higher sensitivity (90%) for detecting rheumatic fever or acute glomerulonephritis. Antihyaluronidase results are frequently abnormal in rheumatic fever patients with a normal level of ASO titer and may rise earlier and persist longer than elevated ASO titers during rheumatic fever.

Acute phase reactants

The C-reactive protein and erythrocyte sedimentation rate are elevated in rheumatic fever due to the inflammatory nature of the disease. Both tests have a high sensitivity but low specificity for rheumatic fever. They may be used to monitor the resolution of inflammation, detect relapse when weaning aspirin, or identify the recurrence of disease.

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 positive in 90% of patients with rheumatic fever. It may be useful for identifying patients who are at risk for developing rheumatic fever.

Electrocardiography

On ECG, sinus tachycardia most frequently accompanies acute rheumatic heart disease. Alternatively, some children develop sinus bradycardia from increased vagal tone. No correlation between bradycardia and the severity of the carditis is noted.

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

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

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

Patients with rheumatic heart disease also may develop atrial flutter, multifocal atrial tachycardia, or atrial fibrillation from chronic mitral valve disease and atrial dilation. Left atrial enlargement may be seen in patients with mitral stenosis. Left ventricular hypertrophy may be observed in patients with significant mitral insufficiency or aortic insufficiency.

Imaging Studies

Chest roentgenography

Cardiomegaly, pulmonary congestion, and other findings consistent with heart failure may be seen on chest radiography. When the patient has fever and respiratory distress, chest radiography helps differentiate heart failure from rheumatic pneumonia.

Doppler echocardiography

In acute rheumatic heart disease, Doppler echocardiography identifies and quantitates valve insufficiency and ventricular dysfunction. Studies in Cambodia and Mozambique demonstrated a 10-fold increase in the prevalence of rheumatic heart disease when echocardiography is used for clinical screening compared with strictly clinical findings.[12] A recent study suggests that simplified echocardiographic screening criteria is highly accurate in the recognition and risk stratification of rheumatic heart disease.[17]

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

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

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

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

The image below depicts the typical systolic mitral insufficiency jet observed with rheumatic heart disease.

Parasternal long-axis view demonstrating the typic Parasternal long-axis view demonstrating the typical systolic mitral insufficiency jet observed with rheumatic heart disease (blue jet extending from the left ventricle [LV] into the left atrium [LA]). The jet is typically directed to the lateral and posterior wall. Ao = aorta; RV = right ventricle.

The image below depicts the typical diastolic aortic insufficiency jet observed with rheumatic heart disease.

Parasternal long-axis view demonstrating the typic Parasternal long-axis view demonstrating the typical diastolic aortic insufficiency jet observed with rheumatic heart disease (red jet extending from the aorta [Ao] into the left ventricle [LV]). LA = left atrium; RV = right ventricle.

The World Heart Federation has published guidelines for identifying individuals with rheumatic heard disease without a clear history of acute rheumatic fever. Based on 2-dimensional (2D) imaging and pulsed and color Doppler interrogation, patients are divided into 3 categories: definite rheumatic heart disease, borderline rheumatic heart disease, and normal. For pediatric patients (defined as age < 20 y), definite echo features include pathologic mitral regurgitation (MR) and at least 2 morphological features of rheumatic heart disease of the mitral valve, mitral stenosis mean gradient of more than 4 mm Hg, pathological aortic regurgitation and at least 2 morphological features of rheumatic heart disease of the aortic valve, or borderline disease of both the aortic valve and mitral valve.[18]

Handheld echocardiography has been investigated as a screening tool and found to be 90% sensitive and 92% specific for identifying patients with rheumatic heart disease in Ugandan children.[19]

Cardiac catheterization

In acute rheumatic heart disease, this procedure is not indicated. With chronic disease, heart catheterization has been performed to evaluate mitral and aortic valve disease and preparatory to balloon valvuloplasty of the stenotic mitral valves.

Postcatheterization precautions include hemorrhage, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm. Complications may include mitral insufficiency after balloon dilation of the mitral valve, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.

Histologic Findings

Pathologic examination of the insufficient valves may reveal verrucous lesions at the line of closure.

Aschoff bodies (perivascular foci of eosinophilic collagen surrounded by lymphocytes, plasma cells, and macrophages) are found in the pericardium, perivascular regions of the myocardium, and endocardium. The Aschoff bodies assume a granulomatous appearance with a central fibrinoid focus and eventually are replaced by nodules of scar tissue.

Anitschkow cells are plump macrophages within Aschoff bodies.

In the pericardium, fibrinous and serofibrinous exudates may produce an appearance of "bread and butter" pericarditis.

 

Treatment

Medical Care

Medical therapy in rheumatic heart disease includes attempts to prevent rheumatic fever (and thus rheumatic heart disease). In patients who develop rheumatic heart disease, therapy is directed toward eliminating the group A streptococcal pharyngitis (if still present), suppressing inflammation from the autoimmune response, and providing supportive treatment for congestive heart failure. Following the resolution of the acute episode, subsequent therapy is directed towards preventing recurrent rheumatic heart disease in children and monitoring for the complications and sequelae of chronic rheumatic heart disease in adults.

Prevention of rheumatic fever in patients with group A beta hemolytic streptococci (GABHS) pharyngitis

For patients with GABHS pharyngitis, a meta-analysis supports a protective effect against rheumatic fever when penicillin is used following the diagnosis.[13]

Oral (PO) penicillin V remains the drug of choice for treatment of GABHS pharyngitis, but ampicillin and amoxicillin are equally effective.

When PO penicillin is not feasible or dependable, a single dose of intramuscular benzathine penicillin G or benzathine/procaine penicillin combination is therapeutic. Because the noncompliance rates for 10 days of oral penicillin are high, some clinicians recommend a single dose of intramuscular benzathine penicillin G.

For patients who are allergic to penicillin, administer erythromycin or a first-generation cephalosporin. Other options include clarithromycin for 10 days, azithromycin for 5 days, or a narrow-spectrum (first-generation) cephalosporin for 10 days. As many as 15% of patients who are allergic to penicillin are also allergic to cephalosporins.

Do not use tetracyclines or sulfonamides to treat GABHS pharyngitis.

For recurrent group A streptococci (GAS) pharyngitis, a second 10-day course of the same antibiotic may be repeated. Alternate drugs include narrow-spectrum cephalosporins, amoxicillin-clavulanate, dicloxacillin, erythromycin, or other macrolides.

Control measures for patients with GABHS pharyngitis are as follows:

  • Hospitalized patients: Place hospitalized patients with GABHS pharyngitis of pneumonia on droplet precautions, as well as standard precautions, until 24 hours after initiation of appropriate antibiotics.

  • Exposed persons: People in contact with patients having documented cases of streptococcal infection first should undergo appropriate laboratory testing if they have clinical evidence of GABHS infection and should undergo antibiotic therapy if infected.

  • School and childcare centers: Children with GABHS infection should not attend school or childcare centers for the first 24 hours after initiating antimicrobial therapy.

GABHS carriage is difficult to eradicate with conventional penicillin therapy. Thus, PO clindamycin (20 mg/kg/d PO in 3 divided doses for 10 days) is recommended.

In general, antimicrobial therapy is not indicated for pharyngeal carriers of GABHS. Exceptions include the following:

  • Outbreaks of rheumatic fever or poststreptococcal glomerulonephritis

  • Family history of rheumatic fever

  • During outbreaks of GAS pharyngitis in a closed community

  • When tonsillectomy is considered for chronic GABHS carriage

  • When multiple episodes of documented GABHS pharyngitis occur within a family despite appropriate therapy

  • Following GAS toxic shock syndrome or necrotizing fasciitis in a household contact

Treatment for patients with rheumatic fever and rheumatic heart disease

Therapy is directed towards eliminating the GABHS pharyngitis (if still present), suppressing inflammation from the autoimmune response, and providing supportive treatment of congestive heart failure.

Treat residual GABHS pharyngitis as outlined above, if still present.

Treatment of the acute inflammatory manifestations of acute rheumatic fever consists of salicylates and steroids. Aspirin in anti-inflammatory doses effectively reduces all manifestations of the disease except chorea, and the response is typically dramatic.

If rapid improvement is not observed after 24-36 hours of therapy, question the diagnosis of rheumatic fever.

Attempt to obtain aspirin blood levels from 20-25 mg/dL, but stable levels may be difficult to achieve during the inflammatory phase because of variable GI absorption of the drug. Maintain aspirin at anti-inflammatory doses until the signs and symptoms of acute rheumatic fever are resolved or residing (6-8 wk) and the acute phase reactants (APRs) have returned to normal.

Anti-inflammatory doses of aspirin may be associated with abnormal liver function tests and GI toxicity, and adjusting the aspirin dosage may be necessary.

When discontinuing therapy, withdraw aspirin gradually over weeks while monitoring the APRs for evidence of rebound. Chorea is most frequently self-limited but may be alleviated or partially controlled with phenobarbital or diazepam.

If moderate to severe carditis is present as indicated by cardiomegaly, third-degree heart block or congestive heart failure, substitute PO prednisone for salicylate therapy. Continue prednisone for 2-6 weeks depending on the severity of the carditis, and taper prednisone during the final week(s) of therapy. Weaning prednisone therapy after a shorter period (2-4 weeks) while initiating and maintaining salicylates for several weeks can minimize adverse effects of the steroids while preventing rebound of the carditis.

Include digoxin and diuretics, afterload reduction, supplemental oxygen, bed rest, and sodium and fluid restriction as additional treatment for patients with acute rheumatic fever and heart failure. The diuretics most commonly used in conjunction with digoxin for children with heart failure include furosemide and spironolactone. Initiate digoxin only after checking electrolytes and correcting hypokalemia.

The total digitalizing dose is 20-30 mcg/kg PO, with 50% of the dose administered initially, followed by 25% of the dose 12 hours and 24 hours after the initial dose. Maintenance doses typically are 8-10 mcg/kg/d PO in 2 divided doses. For older children and adults, the total loading dose is 1.25-1.5 mg PO, and the maintenance dose is 0.25-0.5 mg PO every day. Therapeutic digoxin levels are present at trough levels of 1.5-2 ng/mL.

Afterload reduction (ie, using ACE inhibitor captopril) may be effective in improving cardiac output, particularly in the presence of mitral and aortic insufficiency. Start these agents judiciously. Use a small, initial test dose (some patients have an abnormally large response to these agents), and administer only after correcting hypovolemia.

When heart failure persists or progresses during an episode of acute rheumatic fever in spite of aggressive medical therapy, surgery is indicated and may be life-saving for severe mitral and/or aortic insufficiency.

Treatment for patients following rheumatic heart disease (RHD)

Preventive and prophylactic therapy is indicated after rheumatic fever and acute rheumatic heart disease to prevent further damage to valves.

Primary prophylaxis (initial course of antibiotics administered to eradicate the streptococcal infection) also serves as the first course of secondary prophylaxis (prevention of recurrent rheumatic fever and rheumatic heart disease).

An injection of 0.6-1.2 million units of benzathine penicillin G intramuscularly every 4 weeks is the recommended regimen for secondary prophylaxis for most US patients. Administer the same dosage every 3 weeks in areas where rheumatic fever is endemic, in patients with residual carditis, and in high-risk patients.

Although PO penicillin prophylaxis is also effective, data from the World Health Organization indicate that the recurrence risk of GABHS pharyngitis is lower when penicillin is administered parentally.

The duration of antibiotic prophylaxis is controversial. Continue antibiotic prophylaxis indefinitely for patients at high risk (eg, health care workers, teachers, daycare workers) for recurrent GABHS infection. Ideally, one could argue for continuing prophylaxis indefinitely, because recurrent GABHS infection and rheumatic fever can occur at any age; however, the American Heart Association currently recommends that patients with rheumatic fever without carditis receive prophylactic antibiotics for 5 years or until aged 21 years, whichever is longer.[16] Patients with rheumatic fever and carditis but no valve disease should receive prophylactic antibiotics for 10 years or well into adulthood, whichever is longer. Finally, patients with rheumatic fever with carditis and valve disease should receive antibiotics for at least 10 years or until age 40 years.

Patients with rheumatic heart disease and valve damage require a single dose of antibiotics 1 hour before surgical and dental procedures to help prevent bacterial endocarditis. Patients who had rheumatic fever without valve damage do not need endocarditis prophylaxis. Do not use penicillin, ampicillin, or amoxicillin for endocarditis prophylaxis in patients already receiving penicillin for secondary rheumatic fever prophylaxis (relative resistance of PO streptococci to penicillin and aminopenicillins).

Alternate drugs recommended by the American Heart Association for these patients include PO clindamycin (20 mg/kg in children, 600 mg in adults) and PO azithromycin or clarithromycin (15 mg/kg in children, 500 mg in adults). The guidelines for endocarditis prophylaxis in patients with valve damage from rheumatic heart disease have changed. Antibiotic prophylaxis is no longer recommended.[16]

A study that investigated the difference in clinical manifestations and outcomes between first episode and recurrent rheumatic fever concluded that subclinical carditis occurred only in patients experiencing the first episode, and that all deaths occurred in patients with recurrent rheumatic fever, emphasizing the need for secondary prophylaxis.[20]

Consultations

In addition to cardiology consultation, complications may require cardiothoracic surgery consultation (heart failure and progressive valve insufficiency) and neurology consultation (chorea, PANDAS).

Diet and activity

The diet should be nutritious and without restrictions except in the patient with congestive heart failure. In these patients, fluid and sodium intake should be restricted. Potassium supplementation may be necessary if steroids or diuretics are used.

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

Patient education

Emphasize the importance of prophylaxis against recurrent streptococcal pharyngitis and rheumatic fever with each patient.

For patient education resources, see Heart Health Center, as well as Mitral Valve Prolapse.

Surgical Care

When heart failure persists or worsens after aggressive medical therapy for acute rheumatic heart disease, surgery to decrease valve insufficiency may be life-saving.

Forty percent of patients with acute rheumatic heart disease subsequently develop mitral stenosis as adults.

In patients with critical stenosis, mitral valvulotomy, percutaneous balloon valvuloplasty, or mitral valve replacement may be indicated.

Percutaneous balloon mitral valvuloplasty using the Inoue balloon, initially described in 1984,[21] appears to produce good results and has been extensively used in countries with a high incidence of rheumatic fever. The more recently described percutaneously implantable mitral clip may be useful in selected cases of mitral insufficiency; further studies are needed to confirm the utility in rheumatic mitral insufficiency.[22, 23, 24, 25]  

In the past, due to high rates of recurrent symptoms after annuloplasty or other repair procedures, valve replacement appeared to be the preferred surgical option. However, modifications of standard repair techniques, adherence to the importance of good leaflet coaptation and strict quality control with stringent use of intraoperative transoesophageal echocardiography have all contributed to the improved long-term results.[26]

Long-Term Monitoring

Patients usually show significant improvement after initiation of anti-inflammatory therapy. However, they should not be allowed to resume full activities until all clinical symptoms have abated and laboratory values have returned to normal levels.

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

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

Deterrence/Prevention

Primary prevention of rheumatic fever consists of prompt diagnosis and treatment of group A beta-hemolytic streptococcal pharyngitis.

 

Medication

Medication Summary

Medical therapy is directed at eliminating the group A streptococcal pharyngitis (if still present), suppressing inflammation from the autoimmune response, and providing supportive treatment for congestive heart failure. The treatment and prevention of group A streptococcal pharyngitis outlined here is based on the current recommendations of the Committee on Infectious Disease (American Academy of Pediatrics). See the Medscape Reference article Pediatric Pharyngitis.

Penicillin V is the drug of choice for treatment of group A streptococcal pharyngitis. Ampicillin or amoxicillin may be used instead of penicillin V but have no microbiologic advantage. Tetracyclines 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 repeated. Alternate drugs include narrow-spectrum cephalosporins, amoxicillin-clavulanate, dicloxacillin, erythromycin, or other macrolides for 10 d. As many as 15% of patients allergic to penicillin are also allergic to cephalosporins.

Antibiotics

Class Summary

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

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.

Penicillin G benzathine/penicillin G procaine (Bicillin L-A, Wycillin)

Used when PO 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. 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.

Erythromycin ethylsuccinate (Ilosone, E.E.S, EryPed)

Used to treat patients allergic to penicillin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest.

Anti-inflammatory agents

Class Summary

The manifestations of acute rheumatic fever (including carditis) typically respond rapidly to therapy with anti-inflammatory agents. Aspirin, in anti-inflammatory doses, is the drug of choice. Prednisone is added when evidence of worsening carditis and heart failure is noted.

Aspirin (Anacin, Ascriptin, Bayer Aspirin)

Also called acetylsalicylic acid. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Start immediately after the diagnosis of rheumatic fever has been made. Initiation of therapy may mask manifestations of the disease.

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 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.

Angiotensin-converting enzyme (ACE) inhibitors

Class Summary

These agents are competitive inhibitors of ACE. They reduce angiotensin II levels and thus decrease aldosterone secretion.

Enalapril (Vasotec)

Indicated for chronic aortic and/or mitral regurgitation. Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased plasma renin levels and a reduction in aldosterone secretion. Helps control blood pressure and proteinuria. Decreases pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively low pulmonary vascular resistance. Has favorable clinical effect when administered over a long period. Helps prevent potassium loss in distal tubules. Body conserves potassium; thus, less oral potassium supplementation needed. Goal is to decrease afterload to left ventricle (by reducing systemic blood pressure and by peripheral vasodilatation).

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Rapidly absorbed, but bioavailability is significantly reduced with food intake. It achieves a peak concentration in 1 h and has a short half-life. The drug is cleared by the kidneys.

Impaired renal function requires reduction of dosage. Absorbed well PO. Give at least 1 h before meals. If added to water, use within 15 min.

Can be started at low dose and titrated upward as needed and as patient tolerates.