Rheumatic fever

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

monoarthritis in unconfirmed rheumatic fever

1st line – analgesia

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1st line –

analgesia

If a diagnosis of rheumatic fever has not been established, aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) should be withheld and simple analgesics, such as acetaminophen, are recommended.

Aspirin and NSAIDs are withheld to facilitate diagnosis; they reduce arthritic pain but do not affect the long-term outcome of the disease. For example, if there is doubt about the diagnosis in a patient with monoarthritis, the appearance of migratory polyarthritis will confirm rheumatic fever.

A preferable strategy in patients with suspected rheumatic fever is bed rest and regular acetaminophen while performing investigations to confirm the diagnosis as quickly as possible. Once the diagnosis is confirmed, start the patient on regular NSAIDs.

Opioid analgesics are generally not recommended, especially in children. They should be avoided wherever possible. If they are necessary, they should be used with extreme caution. Codeine is contraindicated in children aged younger than 12 years, and it is not recommended in adolescents aged 12-18 years who are obese or have conditions such as obstructive sleep apnea or severe lung disease as it may increase the risk of breathing problems.[97] It is generally recommended only for the treatment of acute moderate pain, which cannot be successfully managed with other analgesics, in children aged 12 years and older. It should be used at the lowest effective dose for the shortest period and treatment limited to 3 days.[98][99]

Primary options

acetaminophen: children: 10-15 mg/kg every 4-6 hours when required, maximum 75 mg/kg/day; adults: 325-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

Secondary options

codeine sulfate: children: contraindicated in children <12 years of age and use caution in children 12-18 years of age; adults: 15-60 mg orally every 4-6 hours when required, maximum 360 mg/day

ACUTE

possible rheumatic fever

1st line – secondary prophylaxis

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1st line –

secondary prophylaxis

In patients with possible rheumatic fever (i.e., patients, generally in high-incidence settings, in whom the clinician is highly suspicious of the diagnosis of acute rheumatic fever but who do not quite meet the Jones criteria, perhaps because full testing facilities are not available),[2] it is reasonable to offer a shorter period of secondary prophylaxis followed by re-evaluation (including an echocardiogram). This should be done in consultation with the child and family, and with careful consideration of the patient's individual circumstances and family history.

The most effective antibiotic is penicillin and the most effective method of delivery is intramuscular injection of long-acting penicillin G benzathine every 3-4 weeks.[113][114] Intramuscular penicillin G benzathine reduces streptococcal pharyngitis by 71% to 91% and reduces recurrent rheumatic fever by 87% to 96%.[114]

Oral penicillin is an option reserved for patients who refuse intramuscular penicillin G benzathine; however, it is less effective and associated with a higher risk of recurrence.[63][114]

Patients with proven penicillin allergy can be managed with oral erythromycin.[1] Penicillin is safe in pregnancy.[1] Anticoagulation is not a contraindication to intramuscular injections of penicillin G benzathine. Penicillin allergy should be thoroughly investigated. Refer to a specialist if required, as penicillin remains first choice for secondary prophylaxis and desensitization may be appropriate in some circumstances.

In patients with recurrent or atypical joint symptoms despite being adherent to the secondary prophylaxis regimen, particularly for those without echocardiographic evidence of valvulitis, other rheumatologic diagnoses should be considered, such as juvenile idiopathic arthritis.

Primary options

penicillin G benzathine: children ≤27 kg body weight: 600,000 units intramuscularly every 3-4 weeks; children >27 kg body weight and adults: 1.2 million units intramuscularly every 3-4 weeks

Secondary options

penicillin V potassium: children and adults: 250 mg orally twice daily

erythromycin base: children and adults: 250 mg orally twice daily

confirmed rheumatic fever

1st line – antibiotic therapy

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1st line –

antibiotic therapy

A single injection of penicillin G benzathine is the recommended primary option. Oral penicillin is an option if intramuscular penicillin is refused; however, adherence needs to be closely monitored.

Oral erythromycin is an option for patients allergic to penicillin; adherence should be closely monitored.

Penicillin allergy should be thoroughly investigated; refer to a specialist if required as penicillin remains first choice for secondary prophylaxis.

Primary options

penicillin G benzathine: children ≤27 kg: 600,000 units intramuscularly as a single dose; children >27 kg and adults: 1.2 million units intramuscularly as a single dose

Secondary options

penicillin V potassium: children ≤27 kg: 250 mg orally two to three times daily for 10 days; children >27 kg and adults: 500 mg orally two to three times daily for 10 days

erythromycin base: children: 30-50 mg/kg/day orally given in 3-4 divided doses for 10 days, maximum 1000-2000 mg/day; adults: 250-500 mg orally four times daily for 10 days

with arthritis

Plus – salicylate therapy or NSAID

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Plus –

salicylate therapy or NSAID

Treatment recommended for ALL patients in selected patient group

Aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) usually have a dramatic effect on the arthritis of rheumatic fever. Increasingly, clinicians are recommending NSAID treatment. Naproxen has been used successfully, and some experts recommend naproxen as first-line treatment because of its twice-daily dosing, superior side-effect profile, and reduced risk of Reye syndrome.[105] Ibuprofen has been successfully used in children, although there are no specific data regarding its effectiveness in children with rheumatic fever.

Most patients will only require treatment for 1-2 weeks, although some patients need it for up to 6-8 weeks.

Very high and prolonged doses of aspirin should be avoided due to the risk of salicylate toxicity. Toxic effects of aspirin include tinnitus, headache, and tachypnea, and may start to occur above levels of 20 mg/100 dL. They will usually resolve within a few days of stopping aspirin. Salicylate levels should be monitored if facilities are available.

As the dose is reduced, joint symptoms may recur (so-called “rebound phenomenon”). This does not represent a recurrence of rheumatic fever, and can be simply treated with another brief course of high-dose aspirin.

Stopping aspirin therapy should be considered in the setting of a concurrent viral illness because of the risk of Reye syndrome. If aspirin is given during the influenza season, then influenza vaccine may be given as a precautionary measure.

Primary options

aspirin: children: 50-60 mg/kg/day orally given in divided doses every 4 hours, may increase to 80-100 mg/kg/day if required; adults: 4000 mg/day orally given in divided doses every 4-6 hours

naproxen: children >2 years of age: 10-20 mg/kg/day orally given in divided doses every 12 hours, maximum 1000 mg/day; adults: 250-500 mg orally twice daily, maximum 1250 mg/day

ibuprofen: children >6 months of age: 5-10 mg/kg orally every 8 hours, maximum 40 mg/kg/day; adults 400-800 mg orally every 8 hours, maximum 2400 mg/day

with heart failure

Plus – diuretic ± ACE inhibitors

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Plus –

diuretic ± ACE inhibitors

Treatment recommended for ALL patients in selected patient group

Diuretics are usually used first and are effective in mild to moderate heart failure. Furosemide and spironolactone are the most commonly used diuretics.

For severe heart failure, particularly when aortic regurgitation is present, then angiotensin-converting enzyme (ACE) inhibitors can be given in addition to furosemide. Enalapril, captopril, and lisinopril are the most commonly used ACE inhibitors. Spironolactone is not usually used in combination with ACE inhibitors as the combination can result in hyperkalemia.

Primary options

furosemide: children (intravenous): 1-2 mg/kg intravenously every 6-12 hours initially, increase by 1 mg/kg every 2 hours according to response, maximum 6 mg/kg/dose; children (oral): 1-2 mg/kg orally every 6-8 hours initially, increase by 1-2 mg/kg every 6-8 hours according to response, maximum 6 mg/kg/dose; adults (intravenous): 20-40 mg intravenously initially, increase by 20 mg/dose every 2 hours according to response; adults (oral): 20-80 mg orally every 6-8 hours, increase by 20-40 mg/dose every 6-8 hours according to response, maximum 600 mg/day

spironolactone: children: 1-3 mg/kg/day orally given in divided doses every 6-12 hours; adults: 25-200 mg/day orally given in 1-2 divided doses

Secondary options

enalapril: children: consult specialist for guidance on dose; adults: 2.5 mg orally twice daily initially, increase gradually according to response, maximum 40 mg/day

lisinopril: children: consult specialist for guidance on dose; adults: 2.5 to 5 mg orally once daily initially, increase gradually according to response, maximum 40 mg/day

captopril: children: consult specialist for guidance on dose; adults: 6.25 mg orally three times daily initially, increase gradually according to response, maximum 450 mg/day

-- AND --

Consider – glucocorticoids

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Consider –

glucocorticoids

Treatment recommended for SOME patients in selected patient group

Corticosteroids are not indicated for patients with mild and moderate carditis, but may be indicated for a subset of patients with severe carditis, cardiac failure, and/or pericardial effusion.

The side effects of glucocorticoids include gastrointestinal bleeding and fluid retention, both of which can worsen heart failure. Glucocorticoids also have immunosuppressive effects.

Concurrent administration of omeprazole should be considered to reduce the risk of gastrointestinal bleeding.

Glucocorticoids will usually also control joint pain and fever, and so anti-inflammatory drugs may not be required while the patient is being treated with glucocorticoids. Nonsteroidal anti-inflammatory drugs (NSAIDs) may need to be restarted after the patient completes the course of glucocorticoids, particularly if this course is short.

If more than 1 week of treatment is required, taper by 20% to 25% each week.

Despite the absence of high-quality evidence to support the use of glucocorticoid therapy for patients with carditis and severe heart failure, some clinicians treating rheumatic fever believe that the use of glucocorticoids can speed recovery. Two meta-analyses have failed to show any benefit of glucocorticoids over placebo, although contributing studies were old and generally of low quality.[96][106] [ ]

Primary options

prednisone: children and adults: 1-2 mg/kg/day orally for 7 days, maximum 80 mg/day

with atrial fibrillation

Plus – amiodarone or digoxin

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Plus –

amiodarone or digoxin

Treatment recommended for ALL patients in selected patient group

Rarely, a patient with atrial fibrillation may require antiarrhythmic treatment with amiodarone or digoxin. The advice of a cardiologist is recommended before starting therapy.

Thyroid function should be monitored with amiodarone therapy.

Digoxin is very rarely used in children. It has a narrow therapeutic window and its use is associated with increased mortality in patients with rheumatic heart disease.[116] Serum levels should be monitored during treatment.

Primary options

digoxin: children and adults: consult specialist for guidance on dose

amiodarone: children and adults: consult specialist for guidance on dose

with valve leaflet or chordae tendineae rupture

Plus – assessment for emergency valve surgery

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Plus –

assessment for emergency valve surgery

Treatment recommended for ALL patients in selected patient group

This may be necessary in patients with acute decompensated heart and/or multiorgan failure. Valve repair surgery is normally preferred for elective surgery of a rheumatic valve, but may not be possible in acute rupture due to the friability of inflamed tissue.

with severe or disabling chorea

Consider – anticonvulsants

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Consider –

anticonvulsants

Treatment recommended for SOME patients in selected patient group

Treatment is not usually required unless the chorea is severe and puts the person at risk of injury, or is extremely disabling or distressing for the patient.

Valproic acid or carbamazepine may be used. Valproic acid may be more effective than carbamazepine, but carbamazepine is preferred as first-line treatment because of the potential for liver toxicity with valproic acid.[63][108] Valproic acid and its derivatives may cause major congenital malformations, including neurodevelopmental disorders and neural tube defects, after in utero exposure. These agents must not be used in female patients of childbearing potential unless other options are unsuitable, there is a pregnancy prevention program in place, and certain conditions are met. Precautionary measures may also be required in male patients owing to a potential risk that use in the 3 months leading up to conception may increase the likelihood of neurodevelopmental disorders in their children. Regulations and precautionary measures for female and male patients may vary between countries and you should consult your local guidance for more information.

Treatment may ameliorate symptoms of chorea completely or simply reduce them. Usually it takes 1-2 weeks for medication to have an effect and it is recommended that treatment continue for 2-4 weeks after chorea has subsided.

Liver transaminases should be monitored with carbamazepine.

Primary options

carbamazepine: children and adults: consult specialist for guidance on dose

Secondary options

valproic acid: children and adults: consult specialist for guidance on dose

ONGOING

all patients following acute treatment

1st line – secondary prophylaxis

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1st line –

secondary prophylaxis

Secondary prophylaxis can reduce the clinical severity and mortality of rheumatic heart disease (RHD) and lead to regression of RHD by about 50% to 70% if patients are adherent over a decade.[111][112]

The duration of secondary prophylaxis is determined by a number of factors, including age, time since last episode of acute rheumatic fever, and severity of cardiac disease. Recommended duration of prophylaxis also varies across clinical guidelines.[1][63][95][117]

Following growing evidence that patients with RHD who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following penicillin G benzathine injections, the American Heart Association (AHA) now strongly advises that patients with RHD at elevated risk receive oral antibiotic prophylaxis, preferably oral penicillin, if readily available.[115] The AHA notes that patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insufficiency, those with decreased left ventricular systolic dysfunction, and those with no symptoms; for these patients, the AHA believes the risk of adverse reaction to penicillin G benzathine, specifically cardiovascular compromise, may outweigh its theoretical benefit.[115]

Patients with proven penicillin allergy can be managed with oral erythromycin.[1] Penicillin is safe in pregnancy.[1]

Penicillin allergy should be thoroughly investigated. Refer to a specialist if required, as penicillin remains first choice for secondary prophylaxis and desensitization may be possible. Anticoagulation is not a contraindication to intramuscular injections of penicillin G benzathine.

Primary options

penicillin G benzathine: children ≤27 kg body weight: 600,000 units intramuscularly every 3-4 weeks; children >27 kg body weight and adults: 1.2 million units intramuscularly every 3-4 weeks

Secondary options

penicillin V potassium: children and adults: 250 mg orally twice daily

erythromycin base: children and adults: 250 mg orally twice daily

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Rheumatic fever

Treatment algorithm

monoarthritis in unconfirmed rheumatic fever

analgesia

Primary options

Secondary options

possible rheumatic fever

secondary prophylaxis

Primary options

Secondary options

confirmed rheumatic fever

antibiotic therapy

Primary options

Secondary options

salicylate therapy or NSAID

Primary options

diuretic ± ACE inhibitors

Primary options

Secondary options

glucocorticoids

Primary options

amiodarone or digoxin

Primary options

assessment for emergency valve surgery

anticonvulsants

Primary options

Secondary options

all patients following acute treatment

secondary prophylaxis

Primary options

Secondary options