The management of acute rheumatic fever involves treatment of the infection, management of the inflammatory process and complications, and secondary prevention.
Eradication of streptococcal infection
The clinical onset of acute rheumatic fever is typically 1–4 weeks after group A streptococcal infection (longer for Sydenham’s chorea).1 Given this time frame, it is often not possible to isolate streptococci from cultures, but antibiotic eradication therapy is recommended nonetheless (Table 2).1,14-16 Acute rheumatic fever is well documented to occur following group A streptococcal pharyngitis (throat infection).17 In Australian indigenous communities, there is much circumstantial evidence that high rates of acute rheumatic fever can also occur after skin infection with group A streptococci.18,19 A recent case report from New Zealand implicates antecedent skin streptococcal infection or non-group A streptococci in acute rheumatic fever.20
In most instances, penicillin can be used to clear group A streptococcal infection. It should be given as a single intramuscular dose of benzathine penicillin G (also known as benzylpenicillin). The injection forms the first of the 21- or 28-day dosing schedule required for continuing secondary prophylaxis.
It is estimated that only 10–20% of patients reporting penicillin allergy are truly allergic when assessed by skin testing.21 However, in rare instances of true allergy, azithromycin is now recommended by Therapeutic Guidelines: Antibiotic,14 Therapeutic Guidelines: Rheumatology15 and US guidelines22 for clearance of the antecedent streptococcal infection due to drawbacks with other macrolides. For example, roxithromycin appears poorly effective in achieving group A streptococci microbiological cure,23 and erythromycin is poorly tolerated.
Group A streptococci are consistently penicillin-susceptible, probably due to a lack of capacity to express beta-lactamase or to develop low-affinity penicillin-binding proteins under antibiotic pressure.24 However, macrolide resistance was present in 3.4% of invasive group A streptococcus isolates in Darwin in 2005–2009,25 and in at least 30% of isolates in international studies.26,27 This is a further reason to ensure that penicillin is the treatment used whenever possible. It is important to note that penicillin or other antibiotic therapy does not influence the course or outcome of the acute rheumatic fever episode itself.
Symptomatic management of joint symptoms
Once a diagnosis of acute rheumatic fever is made, aspirin is commenced for symptomatic management. Non-steroidal anti-inflammatory drugs (NSAIDs) also appear effective. However, a major Jones criterion is migratory arthritis. If this is masked, the opportunity to make a definite diagnosis can be missed. Since joint symptoms of acute rheumatic fever often respond promptly to salicylates or NSAIDs, these should be withheld pending diagnostic certainty, with other analgesics used in the interim (Table 2).
Aspirin
Previously the recommended dose of aspirin was 80–100 mg/kg/day in divided doses. However, due to toxicity (gastrointestinal, tinnitus), the revised starting dose is 50–60 mg/kg/day although up-titration may be needed (Table 2).1,15 This is then tapered as symptoms improve and continued for 1–2 weeks after they resolve. Rebound of symptoms can occur with a rapid taper or early cessation, hence acute rheumatic fever symptoms within approximately three months of an initial episode are counted as the same episode rather than a recurrence.28
NSAIDs
The effectiveness of naproxen has been reported in a retrospective chart review of 19 patients,4 and in an open-label comparative study of naproxen and aspirin in 33 children.3 In the open-label trial, efficacy was similar to aspirin, but gastrointestinal adverse effects were fewer with naproxen. Hence although published data are scanty, NSAIDs are endorsed as an alternative to aspirin.1
Symptomatic management of chorea
Sydenham’s chorea is usually self-limiting and treatment is only considered in severe cases. Carbamazepine and sodium valproate appear to have similar efficacy,5,6 with carbamazepine being recommended as first line due to a better safety profile.1 This replaces older recommendations to use haloperidol.5 A recent case report from South America describes successful use of leviteracitam for Sydenham’s chorea.29 This may warrant further investigation.
Management of cardiac failure
Acute rheumatic fever with severe carditis may require pharmacological management of cardiac failure, in addition to bed rest and fluid restriction. Drugs typically include furosemide (frusemide), spironolactone, enalapril and digoxin.
Disease-modifying treatments
There are currently no drugs for acute rheumatic fever that effectively target the immune perturbation, or reduce the progression to, or severity of, rheumatic heart disease. Trials of corticosteroids or related compounds (adrenocorticotrophic hormone) have been unconvincing, including a comparative study of methylprednisolone and oral prednisolone in 18 patients.30 Meta-analyses have also failed to show benefit.31 Despite this, the national guideline observes that ‘corticosteroids are sometimes used for severe carditis, although there is no evidence that they alter the longer-term outcome’.1 Internationally, steroids are used as a treatment of last resort. A randomised trial of intravenous immunoglobulin, with outcomes being time to resolution of inflammation and severity of cardiac disease, also identified no benefit in the intervention arm.32