Petros I. Rafailidis
Matthew E. Falagas
DESCRIPTION 
Rheumatic fever is a clinical syndrome that occurs following group A streptococcal pharyngitis. A constellation of signs and symptoms is associated with this illness, and they range from arthritis and atypical fleeting rashes to pancarditis with cardiac valve dysfunction (1).
EPIDEMIOLOGY
Incidence
- Rheumatic fever is a worldwide disease.
- It accounts for 40% of the heart disease in developing countries.
- Rates in the US have dropped secondary to antibiotic use.
- The estimated incidence within the US is 0.5 per 100,000.
- Rheumatic fever is a disease of the childhood, usually affecting children aged 6–15 years.
- One-third of cases occur after a subacute or asymptomatic case of group A streptococcal pharyngitis.
- The attack rate following untreated cases of streptococcal pharyngitis ranges from 0.4–3.0%.
- Epidemics of disease reflect the specific strain of Streptococcus present in the community.
Prevalence
In the US, the prevalence is ~2/10,000 (1) and it is more common in Hispanics.
RISK FACTORS
- Overcrowding
- HISTORY of rheumatic fever
Genetics
A variety of HLA-associations, B cell alloantigens (D 8/17 positive) or immune gene polymorphisms (TNF-a promoter) have been implicated in patients with susceptibility; however, the issue remains to be elucidated) (1).
GENERAL PREVENTION
- For streptococcal pharyngitis, penicillin treatment for 10 days prevents rheumatic fever. Penicillin can be given up to 9 days following the start of sore throat.
- Patients with a history of rheumatic fever have a high chance of developing recurrent disease and need secondary prophylaxis.
- Many possible regimes are available, including benzathine penicillin G, to be given intramuscularly every month. Alternatives also include sulfadiazine orally, penicillin VK orally, or erythromycin orally.
- Patients with valvular disease require antibiotic prophylaxis for dental procedures.
PATHOPHYSIOLOGY
Molecular mimicry between Streptococcus group A infections and host tissues elicits a generalized autoimmune response (2)
ETIOLOGY
- Group A streptococcal pharyngitis initiates rheumatic fever. The incubation time is 1–5 weeks, with an average of 19 days.
- Specific strains (including 1, 3, 5, 6, and 18) have been associated with this disease.
- Pathogenesis is related to antibodies that cross-react between streptococcal antigens and heart valves.
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HISTORY
- Patients may report a variety of symptoms such as: Fever, skin manifestations and involuntary movements, fatigue, dyspnea, and ankle edema.
- The diagnosis of rheumatic fever is a clinical diagnosis, and there are many diseases with which it may be confused. This is especially true if the rheumatic fever is chronic or recurrent, in which case, manifestations may be less obvious.
- Clinical diagnosis is made with two major criteria, or one major criteria and two minor criteria plus laboratory confirmed evidence of antecedent streptococcal infection.
- The symptoms, if untreated, last an average of 3 months but may last up to 6 months in the case of carditis.
PHYSICAL EXAM
Major Criteria
Polyarthritis
- Rheumatic fever often begins with fevers and polyarthritis.
- It involves the knees, ankles, elbows, and wrists. Most children have multiple joints involved. They may have arthralgias or frank arthritis.
- Symptoms resolve within 1 month.
Carditis
Chorea
- Chorea is defined as irregular, purposeless (dancing-like) movement of the muscles.
- It may occur at all times of the day, and it includes the face and extremities.
- Chorea is often present, along with carditis and arthritis.
Subcutaneous Nodules
- Painless nodules appear over tendons, often near the joints.
- They may be as large as 2 cm.
- They occur often in conjunction with carditis.
Erythema Marginatum
- These irregular areas of erythema may be macular and are often present on the trunk and extremities.
- The rash is evanescent and may be hard to detect.
Minor Criteria
- Fever
- Arthralgias without frank arthritis
- Laboratory evidence that can constitute minor criteria includes a prolonged PR interval or elevated, acute-phase reactants such as an elevated erythrocyte sedimentation rate or C-reactive protein.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Initial lab tests
- Evidence of a recent streptococcal infection needs to be determined (however, this is not required for the case of Sydenham's chorea or indolent carditis).
- A positive throat culture or a serum ASO titer >200 Todd units/mL is necessary.
- Other serologic tests that should be elevated following a significant streptococcal infection include an antihyaluronidase antibody or anti-DNAse B.
- A rapid streptococcal antigen test may be positive.
- Should all serology be negative, the diagnosis needs to be questioned.
Follow Up & Special Considerations
In acute rheumatic carditis, levels of troponin-I and of troponin T are usually normal (3,4).
Imaging
Initial Approach
Echocardiography may be especially helpful to document clinical findings and detect potential pathology (5,6)
Follow Up & Special Considerations
Echocardiography may be needed in case of deterioration.
Pathological Findings
Patients with rheumatic fever have inflammatory lesions in connective tissue and Aschoff nodules in the myocardium. This is a pancarditis involving all parts of the heart.
DIFFERENTIAL DIAGNOSIS
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MEDICATION
First Line
- Treatment with salicylates is necessary.
- Steroids are used if inflammation cannot be reduced with salicylates alone.
- Steroids are used when carditis leads to congestive heart failure.
- Aspirin is often given in high doses for 8 weeks. Start with 90 to 100 mg/kg/d and decrease after 2 weeks to 60–70 mg/kg/day. When used in conjunction with steroids (prednisone 40–60 mg/d), aspirin should be continued for 4 weeks after steroids are finished (usually steroids are given over a 1-month period).
Second Line
- Secondary prophylaxis is a mainstay in the management of rheumatic fever. Compliance with this is a crucial factor regarding prognosis of rheumatic fever.
- In rheumatic fever with carditis and residual valvular pathology, prophylaxis should be provided for 10 years or until the patient is 40 years old (select the longest duration option), while some patient will need lifelong prophylaxis (depending on the probability of being exposed to group A streptococci [teachers, children, and closed community residents] and the multitude of previous attacks.
- In case there is carditis but without remaining cardiac pathology, prophylaxis for 10 years or up to when the patient is 21 years old (select the longest duration option).
- In case there is rheumatic fever without carditis, give prophylaxis for 5 years or up to when the patient is 21 years old (whichever is longer).
- Sole manifestation of Sydenham's chorea is sufficient to warrant prophylaxis.
ADDITIONAL TREATMENT
Issues for Referral
Failure of medical treatment needs prompt referral to a cardiothoracic surgeon.
Additional Therapies
Extracorporeal support (8) may be a valuable intermediate management option before surgery (if needed).
SURGERY/OTHER PROCEDURES
- Rheumatic fever remains a significant cause of need for cardiac surgery.
- Cusp extension of the aortic valve for aortic insufficiency (9).
- Mitral valve commissurotomy is among the most common procedures performed. For patients surviving over 20 years, reoperation is needed (8).
IN PATIENT CONSIDERATIONS
Admission Criteria
Discharge Criteria
- Symptom control
- No heart failure
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FOLLOW-UP RECOMMENDATIONS
In patients with carditis, follow up with the pediatrician and pediatric cardiologist.
Patient Monitoring
Echocardiography monitoring may be needed in cases of carditis.
PATIENT EDUCATION
Education regarding secondary prophylaxis
PROGNOSIS
- ~14.8 per 100,000 of hospitalized children annually for acute rheumatic fever with a median length of hospital stay of 3 days and an in-hospital mortality of 0.6% (10).
- Recurrences may occur.
COMPLICATIONS
- Valve dysfunction, leading to refractory heart failure.
- Patients may develop endocarditis.
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