Rheumatic Fever 

Updated: Mar 23, 2021
Author: Mark R Wallace, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD 

Overview

Background

Acute rheumatic fever (ARF) is an autoimmune inflammatory process that develops as a sequela of streptococcal infection. ARF has extremely variable manifestations, and remains a clinical syndrome for which no specific diagnostic test exists. Persons who have experienced an episode of ARF are predisposed to recurrence following subsequent group A streptococcal infections. The most significant complication of ARF is rheumatic heart disease, which usually occurs after repeated bouts of acute illness.

Clinical manifestations and time course. Clinical manifestations and time course.

Pathophysiology

ARF is characterized by nonsuppurative inflammatory lesions of the joints, heart, subcutaneous tissue, and central nervous system. An extensive literature search has shown that, at least in developed countries, rheumatic fever follows pharyngeal infection with rheumatogenic group A streptococci.[1, 2, 3, 4] The risk of developing rheumatic fever after an episode of streptococcal pharyngitis has been estimated at 0.3-3%.[1]  Investigations of rheumatic fever occurring in the aboriginal populations of Australia suggest that streptococcal skin infections might also be associated with the development of rheumatic fever.[5, 6]  and that group C and G streptococci may also serve as initiating pathogens.[7]  Although several classic group A streptococcal emm types are considered to be rheumatogenic and most likely to be associated with acute rheumatic fever, in Oceania and  Hawaii, group A streptococcal strains not traditionally associated with rheumatic fever have been found to cause the disease.[8]  This diversity of potential inciting group A streptococcal strains also appears to be a common phenomenon in lower and middle income countries.[9]

Molecular mimicry accounts for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient's immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues.[10] T helper 1 and cytokine Th17 appear to be key mediators of rheumatic heart disease.[11, 12] The resultant inflammation may persist well beyond the acute infection and produces the protean manifestations of rheumatic fever.

Epidemiology

Frequency

United States

The incidence of ARF has declined markedly in the past 50 years in both the United States and Western Europe. Most Western physicians see only the late sequelae of rheumatic heart disease; the diagnosis of an acute case is usually reason enough for a grand rounds presentation. This remarkable decline of rheumatic fever likely reflects improved socioeconomic conditions, as well the decline in prevalence of the classically described rheumatogenic strains of group A streptococci.

Following 2 decades of almost total absence, a resurgence of ARF occurred in the 1980s among middle-class White children in Salt Lake City, Utah.[13] Clusters were also reported in US Army and Navy training camps during the same period.[14] These limited outbreaks were associated with mucoid rheumatogenic strains that were rarely seen in the preceding 20 years. Today, ARF remains a rarity in most of the United States, although Hawaii and American Samoa continue to see a significant number of cases, many of which are caused by streptococcal strains not usually associated with rheumatic fever in persons of Polynesian descent.[8, 15]

International

In developing countries, the magnitude of ARF is enormous. Recent estimates suggest that 33.4 million people worldwide have rheumatic heart disease and that 300,000-500,000 new cases of rheumatic fever (approximately 60% of whom will develop rheumatic heart disease) occur annually, with 230,000 deaths resulting from its complications. Almost all of this toll occurs in the developing world.[16, 17, 18]

The incidence rate of rheumatic fever is as high as 50 cases per 100,000 children in many areas. Areas of hyperendemicity (eg, indigenous populations of Australia and New Zealand) see an incidence of 300-500 cases per 100,000 children, whereas the rates are approximately 50-fold lower in their nonindigenous compatriots.[6] Rheumatic fever in the 21st century appears to be largely a disease of crowding and poverty.

Even within developing countries with overall high rates of ARF, the segments of populations of poorer socioeconomic status and with higher rates of malnutrition suffer disproportionately.[19]

Mortality/Morbidity

Cardiac involvement is the most serious complication of rheumatic fever and causes significant morbidity and mortality. As stated above, about 60% of the approximately 470,000 patients diagnosed with ARF annually eventually develop carditis, joining the approximately 33 million worldwide with rheumatic heart disease. Those with rheumatic heart disease are at a high risk for additional cardiac damage with subsequent bouts of ARF and require secondary prophylaxis. Morbidity due to congestive heart failure (CHF), strokes, and endocarditis is common among individuals with rheumatic heart disease, and about 1-1.5% of persons with rheumatic carditis die of the disease annually.[6, 16, 18]

Race

ARF is predominantly a disease of developing countries and is concentrated in areas of deprivation and crowding. It is rampant in the Middle East, in sub-Saharan Africa, in the Indian subcontinent, in certain areas of South America, in Oceania, and especially among the indigenous populations of Australia and New Zealand. Although a genetic predisposition to ARF clearly exists,[1, 20, 21] the disease does not seem to have a major racial predisposition, as it was once common in the United States and Europe and seems to decline in any locale where living conditions improve.

Sex

Rheumatic fever does not have a clear-cut sexual predilection, although certain clinical manifestations, such as mitral stenosis and Sydenham chorea, are more common in females who have gone through puberty.

Age

ARF is most common among children aged 5-15 years. It is relatively rare in infants and uncommon in preschool-aged children. ARF occurs in young adults, but the incidence of first episodes of ARF falls steadily after adolescence and is rare after age 35 years.[6] The lower rate of ARF in adults may represent a decreased risk of streptococcal infections in this cohort. Recurrent episodes, with their predisposition to cause or exacerbate valvular damage, occur until middle age.

 

Presentation

History

Rheumatic fever manifests as various signs and symptoms that may occur alone or in various combinations.

Sore throat

Although estimates vary, only 35%-60% of patients with rheumatic fever recall having any upper respiratory symptoms in the preceding several weeks. Many symptomatic individuals do not seek medical attention, go undiagnosed, or do not take the prescribed antibiotic for acute rheumatic fever (ARF) prevention.[6, 14] If a course of penicillin or another appropriate antibiotic is taken at this time, the risk for ARF is reduced by approximately 80%.[22]

Arthritis

Overall, arthritis occurs in approximately 75% of first attacks of ARF. The likelihood increases with the age of the patient, and arthritis is a major manifestation of ARF in 92% of adults.[14] The arthritis is typically polyarticular, but monoarthritis may occur with ARF in select high-risk populations.

The arthritis of ARF is usually symmetrical and involves large joints, such as the knees, ankles, elbows, and wrists. Tenosynovitis is common in adults and may be severe enough to suggest a diagnosis of disseminated gonococcal disease.[14] Aseptic monoarticular arthritis is seen in a substantial minority of cases from higher-risk areas, especially South Asia and Oceania, and can occur when NSAIDs are used early in the course.[23, 24]

The evolution of polyarthritis in individual joints tends to overlap; therefore, multiple joints may be inflamed simultaneously, causing more of an additive than a migratory pattern.[14]

In most instances, the entire bout of arthritis subsides within 4-6 weeks without any permanent damage. If not, a different diagnosis should be entertained.

Carditis

Of first attacks of ARF, carditis occurs in 30%-60% of cases. It is more common in younger children but does occur in adults.[14]

Severe inflammation can cause congestive heart failure (CHF).

Patients with carditis may present with shortness of breath, dyspnea upon exertion, cough, paroxysmal nocturnal dyspnea, chest pain, and/or orthopnea. Carditis may also be asymptomatic and may be diagnosed solely via auscultation or echocardiography.[6, 24, 20]

Sydenham chorea

This occurs in up to 25% of ARF cases in children but is very rare in adults. It is more common in girls. Sydenham chorea in ARF is likely due to molecular mimicry, with autoantibodies reacting with brain ganglioside.[25]

Sydenham chorea may occur with other symptoms or as an isolated finding. It typically presents 1-6 months after the precipitating streptococcal infection and usually has both neurologic and psychological features.[25]

In the isolated form, laboratory evidence of a preceding streptococcal infection may be lacking.

Like the arthritis, Sydenham chorea usually resolves without permanent damage but occasionally lasts 2-3 years and be a major problem for the patient and her family.[6]

Erythema marginatum

In first attacks of ARF in children, erythema marginatum occurs in approximately 10%. Like chorea, it is very rare in adults.

Patients or parents may report a nonpruritic, painless, serpiginous, erythematous eruption on the trunk. It is usually noted only in fair–skinned patients.[2]

The lesions may persist intermittently for weeks to months.

Subcutaneous nodules

Subcutaneous nodules are rarely noticed by the patient.

Other symptoms

Other symptoms may include fever, abdominal pain, arthralgia, malaise, and epistaxis.

Physical

Arthritis

Joint involvement in ARF may range from arthralgia to frank arthritis characterized by swelling, redness, warmth, and joint tenderness. Monoarticular arthritis may occur if anti-inflammatory agents are used early in the course[23] and is increasingly seen in areas of medium-high endemicity.[24]

The joints frequently involved include the knees, ankles, elbows, and wrists. The small joints of the hands and the spine are rarely involved. Hand involvement tends to occur in poststreptococcal arthritis, a controversial related syndrome with a lower but apparently nonzero risk of carditis.[6, 24]

Inflammation begins to subside within a few days to a week and disappears within 2-6 weeks.

The arthritis is classically described as migratory, but, in many cases, new joints are affected before the previously involved joints improve, leaving the appearance of an additive arthritis.[14] Monoarthritis can also occur.

In most cases, the process does not leave any residual damage. On very rare occasions, periarticular fibrosis occurs after rheumatic arthritis, the so-called Jaccoud joint.

Carditis

Carditis is the only manifestation of ARF with significant potential to cause long-term disability and/or death. It is usually a pancarditis involving the pericardium, myocardium, and endocardium.

The signs of carditis include the development of new murmurs, cardiac enlargement, CHF, pericardial friction rub, and/or pericardial effusion.

Characteristic murmurs of acute carditis include the high-pitched, blowing, holosystolic, apical murmur of mitral regurgitation; the low-pitched, apical, mid-diastolic, flow murmur (Carey-Coombs murmur); and a high-pitched, decrescendo, diastolic murmur of aortic regurgitation heard at the aortic area. Murmurs of mitral and aortic stenosis are observed in chronic valvular heart disease. Isolated aortic disease is distinctly unusual.

The features of CHF include tachycardia, a third heart sound, rales, and edema.

Pericarditis presents as a pericardial rub or effusion.

The use of echocardiography to detect carditis often reveals "subclinical" rheumatic cardiac disease (both acute and chronic) not appreciated by the standard examination.[24, 26, 27, 28, 29, 20] Subclinical carditis has been a controversial topic in rheumatic fever diagnosis,[30, 31, 32] but the 2015 revision of Jones Criteria now includes echocardiographically diagnosed subclinical endocarditis as a major criterion and recommends echocardiography in all proven and suspected cases.

Subcutaneous nodules

Subcutaneous nodules are uncommon and are usually associated with severe carditis. They tend to occur several weeks after illness onset, are usually painless, and usually go unnoticed by the patient.

They are found primarily over the bony surfaces or prominences and in tendon sheaths. The common sites include the elbows, knees, wrists, ankles, over the Achilles tendon, the back of the scalp, and the spinous process of the vertebrae.[2]

They usually persist for 1-2 weeks. The main differential diagnosis is the nodules of rheumatoid arthritis.[14]

Erythema marginatum

The individual lesions of erythema marginatum are evanescent, moving over the skin in serpiginous patterns. Likened to smoke rings, they have a tendency to advance at the margins while clearing in the center.

The lesions may be macular and can develop and disappear in minutes, appearing to change shape while being examined.

They are found on the trunk and proximal aspects of the extremities and often go unnoticed by patients and parents, as they are usually covered by clothing.[2]

Sydenham chorea

This is a neurological disorder characterized by emotional lability, personality change, muscular weakness, and uncoordinated, involuntary, purposeless movements.

The classic weakness is characterized by the inability to sustain a tetanic contraction. Patients are unable to maintain a clenched fist when attempting to grip the examiner's hand. Other findings include dysarthric speech, gait problems, and poor fine-motor skills.[25]

The motor symptoms usually disappear during sleep and may be partially suppressed by sedation.

They can involve the face, hands, and feet.

Untreated rheumatic fever/chronic rheumatic fever

The average duration of an untreated ARF attack is 3 months. Chronic rheumatic fever, generally defined as disease persisting for longer than 6 months, occurs in less than 5% of cases.

Causes

Group A beta-hemolytic streptococcal infection may lead to rheumatic fever. The overall attack rate after streptococcal pharyngitis 0.3-3%, but certain genetically predisposed individuals, comprising perhaps 3%-6% of the population, account for those who develop rheumatic fever.[6] Ongoing research using genome-wide association studies may uncover more specifics of the gnetic suscepibilty patterns.[21]

Studies in developed countries have established that rheumatic fever followed only pharyngeal infections and that not all of the 230 serotypes of group A streptococci could cause rheumatic fever. The classic rheumatogenic strains include emm types 1, 3, 5, 6, 14, 18, 19,24,27 and 29.[2, 9] More recent data, largely from studies of the indigenous peoples of Australia, suggest that streptococcal skin infections (pyoderma) can predispose to ARF and that many other group A  emm types may be involved.[5, 9]  Some data also indicate that group C and G streptococci may precipiate acute rheumatic fever.[5, 7, 12]

Two basic theories have been postulated to explain the development of ARF and its sequelae following group A streptococcal infection: (1) a toxic effect produced by an extracellular toxin of group A streptococci on target organs such as the myocardium, valves, synovium, and brain and (2) an abnormal immune response to streptococcal components. Increasing and compelling evidence now strongly favors the autoimmune explanation. It seems clear that an exaggerated immune response in a susceptible individual leads to rheumatic fever. This probably occurs through molecular mimicry, in which the immune response fails to differentiate between epitopes of the streptococcal pathogen and certain host tissues.[6, 10, 29, 20]

 

DDx

 

Workup

Laboratory Studies

No single specific laboratory test can confirm the diagnosis of acute rheumatic fever (ARF). Evidence of preceding group A streptococcal infection is an integral part of the Jones criteria for ARF diagnosis unless the patient has chorea (which may occur months after the inciting infection) or indolent rheumatic heart disease (see Diagnosis).[6, 24]

Throat culture

Throat culture remains the criterion standard for confirmation of group A streptococcal infection. Rapid antigen detection tests are not as sensitive.

If a rapid antigen detection test result is negative, obtain a throat culture in patients with suspected rheumatic fever.

On the other hand, because of the high specificity of these tests, a positive rapid antigen test confirms a streptococcal infection.

Antibody titer tests

Antibody titer tests used include ASO test, antistreptococcal DNAse B (ADB) test, and the antistreptococcal hyaluronidase (AH) test.

ASO is a test used to detect streptococcal antibodies directed against streptococcal lysin O. An elevated titer is proof of a previous streptococcal infection. It is usually more elevated after a pharyngeal than skin infection, while the ADB is typically elevated regardless of the site of the infection.[33]

Acute and convalescent sera, if available, are helpful for proving recent streptococcal infection.

The antibody tests must be interpreted with caution in areas with high rates of streptococcal infection and ARF, as relatively high titers are commonly encountered in the population. These tests are of greater utility in areas with lower prevalence (eg, in most Western countries).[34]

Acute-phase reactants, erythrocyte sedimentation rate, and C-reactive protein

Acute-phase reactants, the erythrocyte sedimentation rate (ESR), and C-reactive protein levels (CRP) are usually elevated at the onset of ARF and serve as a minor manifestation in the Jones criteria. These tests are nonspecific, but they may be useful in monitoring disease activity.

Blood cultures

Blood cultures are obtained to help rule out infective endocarditis, bacteremia, and disseminated gonococcal infection.

Imaging Studies

Chest radiography

Chest radiography can reveal cardiomegaly and CHF in patients with carditis.

Echocardiography

Echocardiography may demonstrate valvular regurgitant lesions in patients with ARF who do not have overt clinical manifestations of carditis. This is now considered an integral part of the evaluation of proven or suspected ARF everywhere.[24, 29, 20] Echocardiography was  used as a diagnostic criterion in New Zealand and Australia before being advocated universally,[23, 26, 27, 28, 31, 32]  and reveals 16%-47% more cases of carditis[35, 36] than clinical criteria alone. Patients with echocardiographically diagnosed subclinical carditis cases should receive the same long-term penicillin prophylaxis as those with the more classic clinical carditis,[24, 30] since they are also at risk for poor outcomes due to recurrent rheumatic heart disease.[20]

Valvular stenotic lesions, especially of the mitral valve, can be observed in rheumatic heart disease. Pathological mitral and/or aortic regurgitation are also frequently encountered,[20]  though isolated echocardiographic disease of the aortic valve is uncommon with rheumatic heart disease.

Other Tests

The most common finding on electrocardiography is a prolongation of the PR interval, which is a nonspecific finding, but counts as a minor manifestation in the Jones diagnostic criteria. It does not count as proof of carditis. On rare occasions, second- or third-degree heart block is present. In patients with chronic rheumatic heart disease, electrocardiography may show left atrial enlargement secondary to mitral stenosis.

Various other studies may be needed to rule out other illnesses in the differential diagnoses. Common tests would include rheumatoid factor, antinuclear antibody (ANA), Lyme serology, blood cultures, and evaluation for gonorrhea.

Procedures

Arthrocentesis can be performed to rule out septic arthritis but is often unnecessary.

Histologic Findings

Rheumatic fever is characterized pathologically by exudative and proliferative inflammatory lesions of the connective tissue in the heart, joints, blood vessels, and subcutaneous tissue.

In the early stage, fragmentation of collagen fibers, cellular infiltration that is predominantly lymphocytic, and fibrinoid deposition followed by the appearance of a myocardial Aschoff nodule (a perivascular focus of inflammation that has an area of central necrosis surrounded by a rosette of large mononuclear and giant multinuclear cells) occur. The nuclei of these cells resemble owl eyes and are called Anichkov cells.

Subcutaneous nodules histologically resemble Aschoff nodules. The brain may show scattered areas of arteritis and petechial hemorrhages, which have an uncertain relationship to Sydenham chorea.

Diagnosis

Because acute rheumatic fever (ARF) can have diverse manifestations and since no specific diagnostic test for the disease exists, arriving at the correct diagnosis is particularly important. This is essential not only in terms of prescribing appropriate therapy for the acute attack but also because of the need for continuous antistreptococcal prophylaxis to prevent subsequent attacks and additional damage.

The Jones criteria were first established in 1944 and have been modified or updated several times, most recently in 2015. The 2015 revision, for the first time, uses slightly different, more specific, diagnostic criteria in areas of low endemicity than the more sensitive criteria for moderate- to high-risk areas. Low-risk areas, by this definition, have an ARF incidence of less than 2 per 100,000 school-aged children or an all-age rheumatic heart prevalence of less than 1 per 1000 persons. Medium- to high-risk countries exceed these thresholds. Additional major changes include the recommended use of echocardiography and the inclusion of subclinical carditis as a major criterion, as well as the inclusion of monoarthritis in higher-risk areas.[24, 35, 36, 37]

Jones Criteria, 2015 revision, low-risk populations (United States, Europe, other high-income areas)

Major criteria are as follows:

  • Carditis (clinical or echocardiographic diagnosis)
  • Polyarthritis (not monoarthritis)
  • Chorea (rare in adults)
  • Erythema marginatum (uncommon; rare in adults)
  • Subcutaneous nodules (uncommon; rare in adults)

Minor criteria are as follows:

  • Polyarthralgia (cannot count arthritis as a major criterion and arthralgia as a minor criterion)
  • Fever exceeding 38.5°C
  • Elevated ESR (>60 mm/hr) or CRP level (>3 mg/L)
  • Prolonged PR interval

Jones criteria, 2015 revision, high-risk populations (Oceania, Africa, South Asia, other lower-income areas)

Major criteria are as follows:

  • Carditis (clinical or echocardiographic diagnosis)
  • Polyarthritis or monoarthritis: Polyarthralgias can also be considered but only after careful consideration of the differential diagnoses.
  • Chorea (rare in adults)
  • Erythema marginatum (uncommon; rare in adults)
  • Subcutaneous nodules (uncommon; rare in adults)

Minor criteria are as follows:

  • Polyarthralgia (cannot count arthritis as a major criterion and arthralgia as a minor criterion)
  • Fever exceeding 38°C (note lower cutoff)
  • Elevated ESR (>30 mm/hr; note lower ESR standard) or CRP level (>3 mg/L)
  • Prolonged PR interval

Universal criteria

In both higher- and lower-risk settings, evidence of group A streptococcal disease is required for diagnosis, except when rheumatic fever is first discovered after a long latent period (eg, Sydenham chorea, indolent carditis), as follows:

  • Evidence of preceding group A streptococcal infection - Positive throat culture or rapid antigen test result
  • Elevated or rising streptococcal antibody titer

Scoring

If supported by evidence of preceding group A streptococcal infection, the presence of two major manifestations or one major and two minor manifestations indicates a high probability of ARF. Failure to fulfill the Jones criteria makes the diagnosis unlikely but not impossible. Clinical judgment is required.

Recurrent ARF can be diagnosed based on 2 major, 1 major plus 2 minor, or 3 minor criteria.

 

Treatment

Medical Care

Management and prevention of acute rheumatic fever (ARF) can be divided into the following 4 approaches.

Treatment of the group A streptococcal infection that led to the disease

Although never proven to improve the one-year outcome, this is a standard practice.[1, 6, 29]  It may at least serve to reduce the spread of cauasative strain.

General treatment of the acute episode

Anti-inflammatory agents are used to control the arthritis, fever, and other acute symptoms. Salicylates are the preferred agents, although other nonsteroidal agents are probably equally efficacious.and maybe preferred in children.[38]  Steroids are also effective but should probably be reserved for patients in whom salicylates fail, since there is a risk of rebound when they are withdrawn.[29] None of these anti-inflammatory agents has been shown to reduce the risk of subsequent rheumatic heart disease.

Bed rest is a traditional part of ARF therapy and is especially important in those with carditis. Patients are typically advised to rest through the acute illness and to then gradually increase activity; some clinicians monitor the patient’s ESR and restart activity only as it normalizes.[1, 6]

Intravenous immunoglobulin has not been shown to reduce the risk of rheumatic heart disease or to substantially improve the clinical course.[39]

Chorea is usually managed conservatively in a quiet nonstimulatory environment; valproic acid is the preferred agent if sedation is needed. Intravenous immunoglobulin, steroids, and plasmapheresis have all been used successfully in refractory chorea, although conclusive evidence of their efficacy is limited.[6, 25, 29]

Some promising work suggests a possible role for hydroxychloroquine in the treatment of ARF, although no clinical data are yet available to recommend its use.[40]

Cardiac management

Bedrest is essential in patients with cardiac involvement. Carditis resulting in heart failure is treated with conventional measures; some use corticosteroids for severe carditis, although data to support this are scant.[6] Diuretics and vasodilators are the mainstays of therapy.[29] Monitor for development of arrhythmias in patients with active myocarditis. Atrial fibrillation requires aggressive management to reduce the risk of stroke.[20]

Prophylaxis

For details about penicillin prophylaxis, see Medication.

Surgical Care

Surgical care is not typically indicated in ARF. Surgical intervention is often required  to treat long-term valvular cardiac sequelae of ARF including aortic and mitral regurgitation as well as mitral stenosis.[20]

Consultations

Consultation with a cardiologist may be required to manage heart block,arrhythmias and CHF.

Consultation with a neurologist or psychiatrist may be required to confirm the diagnosis of chorea and to assist in its management.

Consultations with an infectious disease specialist and rheumatologist may be helpful in diagnosis.

Diet

No specific dietary recommendation exists. CHF may require salt restriction.

Activity

Bed rest is a time-honored part of ARF therapy and is especially important in those with carditis. Patients are typically advised to rest through the acute illness and to then gradually increase activity; some clinicians monitor the ESR and restart activity only as it normalizes.[1, 6]

Prevention

Group A streptococcal vaccines hold out the promise of preventing rheumatic fever, and some are in development. Such vaccines will need to take into account the increase in rheumatogenic strains[9]  and the possibilty that groups C and G streptococci may be involved in the causation of rheumatic fever.[7]

 

Medication

Antibiotics

Class Summary

Antibiotic treatment in patients who present with acute rheumatic fever (ARF) is necessary irrespective of the throat culture result. Such therapy probably does not alter the risk of developing rheumatic heart disease but at least minimizes the possible transmission of the responsible streptococcal strain.[1]

Primary prophylaxis (treatment of streptococcal pharyngitis) dramatically reduces the risk of ARF and should be provided whenever a group A streptococcal pharyngitis is confirmed. In areas where streptococcal pyoderma has been implicated as a cause of rheumatic fever, such therapy should be also be employed.Treatment of pharyngitis (or pyoderma) without proof of group A streptococcal etiology may be reasonable in areas of high endemicity.[29]

Although definitive evidence to support the practice is lacking,[29] secondary prevention is recommended to prevent additional streptococcal infections and is believed by most experts to be a critical step in management of ARF. Patients with a history of rheumatic fever are at a high risk of recurrent ARF, which may further the cardiac damage. The exact duration of chronic antimicrobial prophylaxis remains controversial, but the WHO guidelines are commonly used.[1] There had been concern that sustained benzathine penicillin as secondary prophylaxis would lead to the development of resistant strains of Streptococcus viridans, but a  2008 study found no support for this hypothesis.[41]

Rheumatic fever with carditis and clinically significant residual heart disease requires antibiotic treatment for a minimum of 10 years after the latest episode; prophylaxis is required until the patient is aged at least 40-45 years and is sometimes continued for life.

Rheumatic fever with carditis and no residual heart disease aside from mild mitral regurgitation requires antibiotic treatment for 10 years or until age 25 years (whichever is longer).

Rheumatic fever without carditis requires antibiotic treatment for 5 years or until the patient is aged 18-21 years (whichever is longer).

Children given penicillin G benzathine at a dose of 1.2 million U IM q4wk experienced a recurrence rate of 0.4 cases per 100 patient-years of observation. ARF recurrence rates have been found to be even lower if penicillin is administered q3wk instead of q4wk. This regimen may be appropriate in patients with severe rheumatic heart disease. Weigh the benefits of a 3-week regimen against patient compliance and cost; compliance is often poor to start with, at least partially due to the pain of the injections.[19] Long-term administration of oral penicillin may be used in lieu of the intramuscular route. Erythromycin or sulfadiazine may be used in patients who are allergic to penicillin.[1, 6]

Penicillin G benzathine (Bicillin L-A)

Long-acting depot form of penicillin G. DOC for prophylaxis of streptococcal pharyngitis. Avoids compliance problems of oral regimens.

Penicillin VK (Beepen-VK, Betapen-VK, Pen-Vee K, Robicillin VK, V-Cillin K)

Phenoxymethyl derivative of penicillin G is acid-stable, enhancing oral bioavailability. Patient compliance is essential for effectiveness.

Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin, E-Mycin)

Macrolides inhibit protein synthesis, in contrast to penicillin cell wall effects. DOC for primary treatment of streptococcal pharyngitis in penicillin allergy. May use for secondary prophylaxis in patients allergic to penicillin.

Sulfadiazine (Microsulfon)

Exerts bacteriostatic action through competitive antagonism with para-aminobenzoic acid (PABA). Microorganisms that require exogenous folic acid and do not synthesize folic acid are not susceptible to the action of sulfonamides. Used in secondary prophylaxis of ARF.

Anti-inflammatory agents

Class Summary

Salicylates and corticosteroids are the mainstay of the anti-inflammatory treatment of ARF. Other nonsteroidal agents (ibuprofen,naprosyn) are likely about as good as aspirin and maybe preferable in children[38] .Avoid anti-inflammatory drugs until diagnosis is confirmed, as they may mask symptoms essential to the diagnosis. Analgesics without anti-inflammatory properties (ie, codeine) are used for mild disease. Corticosteroids and salicylates cannot prevent or modify the development of subsequent rheumatic heart disease but are used for symptomatic relief. Some experts believe steroids are of value in patients with severe or fulminant carditis, but data are sparse.[6, 29]

Clinical or laboratory manifestations of rheumatic inflammation may recur upon cessation of anti-inflammatory therapy. Rebound occurs frequently with corticosteroids; hence, they require gradual tapering rather than abrupt cessation. Nonsteroidal agents are usually continued for a month following corticosteroid discontinuance.

Aspirin (Anacin, Ascriptin, Bayer Aspirin, Bayer Buffered Aspirin)

Used in patients with moderate-to-severe arthritis and carditis without heart failure. Treatment is administered for at least 8 wk.

Prednisone (Deltasone, Liquid-Pred, Meticorten, Orasone, Sterapred)

Used in severe carditis and CHF. High-dose prednisone is administered for 2-3 wk, then tapered over 3 wk. IV corticosteroids are reserved for fulminant cases.

NSAIDs

Naproxen (Naprosyn, Aleve, Anaprox)

An alternative to aspirin

Ibuprofen (Motrin, Advil, PediaCare Children's Pain Reliever/Fever Reducer IB)

An alternative to aspirin

 

Follow-up

Further Outpatient Care

Patients should be closely observed until all acute symptoms have resolved and they have returned to their normal state of health. Secondary prophylaxis lasts for years and is the critical step in maintaining the health of the recovered patient.

Compliance with long-term secondary antibiotic prophylaxis is often poor, so close follow-up is mandatory.

Further Inpatient Care

Most patients with acute rheumatic fever (ARF) can be treated at home.

Inpatient care may be appropriate when the patient has severe constitutional symptoms, chorea, carditis with CHF, or major toxicity with the anti-inflammatory drugs.

Inpatient & Outpatient Medications

Patients with ARF need prolonged antibiotic prophylaxis to prevent recurrent attacks.

The anti-inflammatory drugs are not usually required for more than 4-8 weeks.

Deterrence/Prevention

Primary prophylaxis (treatment of streptococcal pharyngitis) dramatically reduces the risk of ARF and should be provided whenever possible. Secondary prophylaxis is essential in all patients with rheumatic fever.

Ultimately, a vaccine will be the prevention of choice for ARF. Research on such a product is ongoing.[42, 43]

Complications

Immediate complications

Pancarditis that causes CHF, heart blocks, or pericardial effusion requires emergent inpatient care and cardiology evaluation.

Chorea can present months after the inciting infection and can be quite debilitating.[25]

Long-term sequelae

The only long-term sequela is rheumatic heart disease, which can present years later as valvular stenosis, most commonly involving the mitral valve. These patients are prone to infective endocarditis and stroke.

Valvular stenosis can lead to heart failure and may require surgery.

Prognosis

The prognosis of ARF has been improved by preventing recurrent attacks with secondary antimicrobial prophylaxis. The ultimate prognosis of an individual attack is related directly to the severity of cardiac involvement during the acute phase.

About 60% of patients with carditis improve over a decade; in some, murmurs disappear. However, the overall prognosis is worse in those with severe carditis at first presentation,[6] and most develop significant rheumatic heart disease.

Only 6% of patients without carditis (or questionable carditis) during their attack of ARF have an audible heart murmur in 10 years.

Patient Education

Patients, especially children, should receive medical attention when they develop a sore throat. Compliance with oral primary prophylaxis ("strep throat" treatment) and secondary prophylaxis regimens is essential to prevent ARF and its sequelae.

 

Questions & Answers

Overview

What is acute rheumatic fever (ARF)?

What is the role of group A streptococci (GAS) in the pathogenesis of acute rheumatic fever (ARF)?

What is the pathophysiology of acute rheumatic fever (ARF)?

What is the incidence of acute rheumatic fever (ARF) in the US?

What is the global incidence of acute rheumatic fever (ARF)?

What are the cardiac complications and mortality rate of acute rheumatic fever (ARF)?

How does the prevalence of acute rheumatic fever (ARF) vary by race?

How does the prevalence of acute rheumatic fever (ARF) vary by sex?

How does the prevalence of acute rheumatic fever (ARF) vary by age?

Presentation

How does acute rheumatic fever (ARF) manifest?

How prevalent are respiratory symptoms in acute rheumatic fever (ARF)?

What are the features of arthritis in patients with acute rheumatic fever (ARF)?

What are the symptoms of carditis in acute rheumatic fever (ARF)?

What is the prevalence of Sydenham chorea in acute rheumatic fever (ARF)?

What are the symptoms of erythema marginatum in acute rheumatic fever (ARF)?

What are the symptoms of subcutaneous nodules in acute rheumatic fever (ARF)?

What are the signs and symptoms that suggest acute rheumatic fever (ARF)?

What are physical findings of subcutaneous nodules in acute rheumatic fever (ARF)?

What are the physical findings of arthritis in acute rheumatic fever (ARF)?

What are the physical findings of carditis in acute rheumatic fever (ARF)?

What are the physical findings of acute carditis in acute rheumatic fever (ARF)?

What are the symptoms of congestive heart failure (CHF) in acute rheumatic fever (ARF)?

What are the symptoms of pericarditis in acute rheumatic fever (ARF)?

What are echocardiographic findings suggestive of carditis in acute rheumatic fever (ARF)?

What are physical exam findings of erythema marginatum in acute rheumatic fever (ARF)?

What are physical findings of Sydenham chorea in acute rheumatic fever (ARF)?

What is the duration of untreated acute rheumatic fever (ARF) and chronic rheumatic fever?

Which infections may lead to acute rheumatic fever (ARF)?

How does group A streptococcal infection cause acute rheumatic fever (ARF)?

DDX

What are the differential diagnoses for Rheumatic Fever?

Workup

What is the role of lab testing in the diagnosis of acute rheumatic fever (ARF)?

What is the indication for a throat culture in the diagnosis of acute rheumatic fever (ARF)?

Which antibody titer tests are performed in the workup of acute rheumatic fever (ARF)?

What does a finding of acute and convalescent sera suggest in acute rheumatic fever (ARF)?

What are the limitations of antibody testing in acute rheumatic fever (ARF)?

Which lab tests are useful in monitoring disease activity in acute rheumatic fever (ARF)?

What is the role of blood cultures in the workup of acute rheumatic fever (ARF)?

What is the role of chest radiography in the diagnosis of acute rheumatic fever (ARF)?

What is the role of echocardiography in the workup of acute rheumatic fever (ARF)?

How effective is echocardiography in detecting carditis in acute rheumatic fever (ARF)?

What are possible echocardiography findings in rheumatic heart disease?

What is the most common finding on an electrocardiography for acute rheumatic fever (ARF)?

Which lab tests may be useful in narrowing the differential diagnoses in acute rheumatic fever (ARF)?

What is the role of arthrocentesis in the evaluation of acute rheumatic fever (ARF)?

What is the pathologic characterization of acute rheumatic fever (ARF)?

What are the expected histologic findings of acute rheumatic fever (ARF)?

What are the challenges to diagnosing acute rheumatic fever (ARF) correctly?

What are the Jones criteria for diagnosis of acute rheumatic fever (ARF)?

Treatment

What are the approaches to the treatment of acute rheumatic fever (ARF)?

How does treatment of group A streptococcal infection affect outcomes for acute rheumatic fever (ARF)?

What are the treatment options for acute rheumatic fever (ARF)?

What are the treatment options for acute rheumatic fever (ARF) with cardiac involvement?

What is the role of penicillin prophylaxis in the management of acute rheumatic fever (ARF)?

What is the indication for surgery in acute rheumatic fever (ARF)?

Which specialists should be consulted in the treatment of acute rheumatic fever (ARF)?

What are the dietary recommendations for acute rheumatic fever (ARF)?

What are the activity restrictions in the treatment of acute rheumatic fever (ARF)?

Follow-up

What monitoring is needed following initial treatment of acute rheumatic fever (ARF)?

When is inpatient care indicated for acute rheumatic fever (ARF)?

What medications are used in the treatment of acute rheumatic fever (ARF)?

What is the primary and secondary prophylaxis for acute rheumatic fever (ARF)?

What are the immediate complications of acute rheumatic fever (ARF)?

What are the long-term sequelae of acute rheumatic fever (ARF)?

What factors have led to improved prognosis of acute rheumatic fever (ARF)?

What is the prognosis of acute rheumatic fever (ARF)?

What education about acute rheumatic fever (ARF) should patients receive?

Medications

Which medications in the drug class Anti-inflammatory agents are used in the treatment of Rheumatic Fever?

Which medications in the drug class Antibiotics are used in the treatment of Rheumatic Fever?

Which medications in the drug class NSAIDs are used in the treatment of Rheumatic Fever?