INTRODUCTION — Acute rheumatic fever (ARF) is a nonsuppurative complication of pharyngeal infection with group A Streptococcus (GAS). Signs and symptoms of ARF develop two to three weeks following pharyngitis and include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum [1].
Treatment and secondary prevention of rheumatic fever are reviewed here. Primary prevention (eg, treatment of streptococcal tonsillopharyngitis) and the epidemiology, pathogenesis, clinical manifestations, and diagnosis of ARF are discussed in detail separately. (See "Treatment and prevention of streptococcal pharyngitis in adults and children" and "Acute rheumatic fever: Epidemiology and pathogenesis" and "Acute rheumatic fever: Clinical manifestations and diagnosis".)
TREATMENT — Treatment of ARF consists of antibiotic therapy, antiinflammatory therapy, heart failure management, and commencement of ongoing care (secondary prevention and provision of education) [2-4]. Hospitalization is advisable for optimal management of ARF, especially for an initial episode, so that all tests can be completed, response to therapy can be observed, and long-term preventative measures can be started with appropriate education for the patient and their caregivers.
Goals of treatment — The six major goals of treatment are:
●Eradication of group A beta-hemolytic Streptococcus (GAS)
●Symptomatic relief of acute disease manifestations (eg, arthritis, fever)
●Manage rheumatic heart disease (RHD; eg, carditis, heart failure) if present
●Manage chorea if present
●Prophylaxis against future GAS infection to prevent progression of cardiac disease (see 'Secondary prevention (antibiotic prophylaxis)' below)
●Provision of education for the patient and patient's caregivers
There is no therapy that slows progression of valvular damage in the setting of ARF.
Eradication of GAS carriage — Patients with newly diagnosed ARF are started on antibiotic therapy to eradicate group A Streptococcus (GAS) carriage [2]. When a patient is diagnosed with ARF, they are presumed to have an associated GAS infection (typically pharyngitis, though pyoderma may also trigger ARF, particularly in tropical regions), even if GAS is not identified in culture. Thus, affected patients should receive prompt antibiotic therapy to eradicate GAS carriage, prevent ARF recurrences, and reduce the risk of developing RHD [2].
GAS pharyngitis — Treatment should proceed as delineated for management of GAS pharyngitis whether or not pharyngitis is present at the time of diagnosis (table 1 and table 2). Treatment is given even if throat cultures are negative to ensure eradication of streptococci that may persist in the upper respiratory tract. (See "Treatment and prevention of streptococcal pharyngitis in adults and children", section on 'Antibiotic treatment'.)
In practice, the most convenient and sensible approach is to administer long-acting intramuscular (IM) penicillin G benzathine, which serves two purposes:
●To eradicate GAS carriage
●As the first dose of secondary prophylaxis that is given every 21 to 28 days (see 'Secondary prevention (antibiotic prophylaxis)' below)
Oral alternatives, which should be used in the case of shortages of penicillin G benzathine [5] or in the case of penicillin allergy, are listed in the tables (table 1 and table 2). These treatment options vary somewhat from those preferred for secondary prevention (table 3). Penicillin allergy should be verified by history and confirmed with testing by an allergy specialist if necessary before choosing an alternative to penicillin G benzathine. (See "An approach to the patient with drug allergy" and "Penicillin skin testing".)
The efficacy of penicillin in this setting is supported by landmark controlled studies performed in the 1950s and 1960s that demonstrated dramatic reductions in rates of ARF and risk of ARF recurrence and/or complications in patients who were given prompt penicillin therapy [6-8]. It is also supported by decades of clinical experience [2,3].
GAS pyoderma — Patients from tropical regions such as Northern Australia, in whom ARF may be triggered by group A Streptococcus (GAS) pyoderma, require antibiotic therapy, as for GAS pharyngitis, for any skin infections present. (See 'GAS pharyngitis' above and "Impetigo", section on 'Treatment' and "Acute rheumatic fever: Epidemiology and pathogenesis", section on 'Role of Streptococcus pyogenes'.)
Household contacts — Throat cultures (or evaluation for pyoderma if that was the GAS infection that identified the patient) should be performed on household contacts. Those with positive results should also receive a full course of antibiotic therapy, even if asymptomatic.
Arthritis management — Antiinflammatory agents are the mainstay of symptomatic management of ARF-associated arthritis.
●First-line agents – For most patients with symptomatic ARF-associated arthritis, we suggest a nonsteroidal antiinflammatory drug (NSAID; eg, naproxen, ibuprofen) as the first-line antiinflammatory agent because NSAIDs have a lower risk of adverse effects compared with other agents (eg, aspirin, glucocorticoids). We typically use naproxen in this setting since it has the advantage of less frequent dosing. Dosing for naproxen is as follows:
•For children >2 years old – 10 to 20 mg/kg/day in two divided doses given orally every 12 hours (maximum daily dose 1000 mg)
•For adults – 250 to 500 mg twice daily (maximum daily dose 1250 mg)
The efficacy of naproxen in this setting is supported by limited clinical trial data and observational studies [9,10].
Ibuprofen has been used successfully in younger children with ARF, as was shown in one small observational study [11].
●Duration of treatment – NSAIDs are given as a standing dose until symptoms resolve and inflammatory markers have improved, provided the medication is well tolerated. Improvement is typically noted in one to two weeks, although longer courses (6 to 12 weeks) may be needed for persistent or rebound symptoms and elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) [12]. (See 'Monitoring' below.)
●Alternative agents – Alternatives to naproxen and ibuprofen include:
•Aspirin – Aspirin was historically the first-line antiinflammatory agent for ARF based upon extensive clinical experience [13-15]. However, limited clinical trial data and observational studies suggest that naproxen has similar efficacy with fewer adverse effects and less frequent dosing [9,10]. When aspirin is used in this setting, it is given at a starting dose of 50 to 60 mg/kg per day, up to 80 to 100 mg/kg/day in children and 4 to 8 g/day in adults, given in four to five divided doses. (See "Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases".)
•Glucocorticoids – Low-dose glucocorticoids are a second-line option for patients who do not tolerate or are allergic to NSAIDs and/or aspirin.
●Risk of gastrointestinal toxicity – Patients taking NSAIDs for an extended duration (ie, several weeks) are at risk of developing gastrointestinal toxicity (eg, bleeding, ulcer).
For pediatric patients taking naproxen or ibuprofen, prophylaxis is generally not necessary so long as the patient is otherwise well without any history of previous gastrointestinal upset with NSAIDs, gastroesophageal reflux disease, or bleeding diathesis.
However, we do typically add a proton pump inhibitor (PPI; eg, omeprazole) if the patient develops gastrointestinal upset on an NSAID or an oral glucocorticoid. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity", section on 'Proton pump inhibitors'.)
●Recurrences – Resolution occurs in 90 percent within 12 weeks [12]. Recurrence of arthritis with reduction in the dose of antiinflammatory treatment most likely reflects the "rebound phenomenon" of ARF. This does not represent a recurrent episode of ARF, but rather that a longer course of treatment is required.
Carditis management — The mainstays of management of rheumatic carditis are early diagnosis and assessment of severity using echocardiography, management of heart failure and other complications when present, and commencement of secondary antibiotic prophylaxis. Management of rheumatic carditis and valve disease in RHD are discussed in greater detail separately. (See 'Secondary prevention (antibiotic prophylaxis)' below and "Management and prevention of rheumatic heart disease", section on 'Management of carditis in acute rheumatic fever' and "Management and prevention of rheumatic heart disease", section on 'Management of rheumatic heart disease'.)
Sydenham chorea management — Sydenham chorea (SC) is generally self-limited, and most cases do not require treatment beyond the usual chronic antibiotic therapy to prevent recurrence of ARF and minimize the risk of RHD (see 'Secondary prevention (antibiotic prophylaxis)' below). Patients with significant impairment related to their chorea may be treated with chorea-suppressing medication and/or antiinflammatory treatment (ie, glucocorticoids). Referral to a child neurologist or movement disorder specialist can help guide management.
The management of SC is discussed in greater detail separately. (See "Sydenham chorea", section on 'Treatment'.)
Other — The rash associated with ARF is temporary and does not require specific treatment, although antihistamines may help to alleviate pruritus.
MONITORING — Measurement of C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) may be useful for monitoring the acute disease process. The CRP is probably more useful since it typically normalizes over a matter of days once an episode of acute inflammation has resolved, while the ESR may stay elevated for up to two months after a transient inflammatory stimulus. However, the susceptibility of this measurement to artefact and other causes of inflammation may limit its use for this purpose. This monitoring can be performed by an experienced primary care clinician or ARF specialist.
We check CRP twice weekly initially and then every one to two weeks until levels have normalized off therapy. Normalization of inflammatory markers is an indication of resolution, whereas an increase as treatment is tapered suggests a rebound of inflammation. A normal result obtained a few weeks after discontinuing antiinflammatory therapy suggests that the course of the illness is complete (unless chorea appears).
RISK FACTORS FOR RECURRENT DISEASE — Several factors are associated with an increased risk of recurrent ARF, including [2,16]:
●Poor adherence to secondary prophylaxis.
●A greater number of previous attacks.
●A shorter time interval since the last attack.
●A higher likelihood of ongoing exposure to streptococcal infections, which includes children, those in close contact with children (parents/caregivers, health care workers), and those living in crowded situations (college students, military personnel) [17].
●Younger age.
●Presence of cardiac involvement. Patients who have had rheumatic carditis (with or without valvular disease) are at relatively high risk for recurrent carditis and are likely to sustain increasingly severe cardiac involvement with each recurrence [18,19].
PRIMARY PREVENTION — Prevention of initial development of rheumatic fever (primary prevention) is accomplished by prompt diagnosis and antibiotic treatment of group A Streptococcus (GAS) tonsillopharyngitis and, in some settings, GAS pyoderma [20-22]. These issues are discussed in detail separately. (See "Evaluation of acute pharyngitis in adults" and "Treatment and prevention of streptococcal pharyngitis in adults and children" and "Group A streptococcal tonsillopharyngitis in children and adolescents: Clinical features and diagnosis", section on 'Diagnosis'.)
Appropriate antibiotic treatment of streptococcal pharyngitis prevents ARF in most cases [6]. However, at least one-third of ARF episodes occur in the setting of subclinical streptococcal infection [23]. In addition, ARF is not preventable in symptomatic patients who do not seek medical care.
SECONDARY PREVENTION (ANTIBIOTIC PROPHYLAXIS)
Rationale and efficacy — Patients who have had an attack of ARF and develop subsequent group A Streptococcus (GAS) pharyngitis are at high risk for a recurrent attack of ARF. Rheumatic heart disease (RHD) becomes more severe with each recurrent episode. Thus, the most effective method to limit progression of RHD severity is prevention of recurrent GAS pharyngitis. We recommend long-term antimicrobial prophylaxis, rather than recognition and treatment of acute GAS pharyngitis episodes, because GAS infection does not need to be symptomatic to trigger a recurrent attack of ARF [24]. Long-term prophylaxis is warranted for patients with a well-documented history of ARF (including cases with Sydenham chorea [SC] as the sole manifestation), as well as those with definite evidence of RHD. Antibiotic prophylaxis is usually provided in the primary care setting rather than by tertiary care organizations and consulting cardiologists. (See "Acute rheumatic fever: Clinical manifestations and diagnosis".)
During the course of prophylaxis, patients and their household contacts who develop acute episodes of GAS pharyngitis should be evaluated and treated promptly.
Although randomized trial data in patients with a known history of ARF are largely lacking, the efficacy of routine secondary prophylaxis in preventing disease progression is supported by observational data demonstrating substantially reduced rates of ARF recurrence and disease progression in the penicillin era compared with the pre-penicillin era [17,25-27]. Additional support comes from a study demonstrating considerably lower rates of GAS infection and recurrent ARF among patients treated with monthly penicillin G benzathine injections compared with intermittent oral penicillin V [28]. Secondary prophylaxis was also shown to decrease the risk of disease progression in a randomized trial of children aged 5 to 17 years in resource-limited settings diagnosed with latent RHD by population-wide screening and confirmatory echocardiograms [29]. (See "Management and prevention of rheumatic heart disease", section on 'Secondary prevention'.)
Antibiotic selection — For most patients, we suggest long-acting penicillin G benzathine administered intramuscularly (IM) every 28 days rather than other regimens (table 3). However, there is regional variation in use of penicillin G benzathine depending upon availability and cost. In regions where ARF is endemic, penicillin G benzathine continues to be the preferred agent since it is highly effective, low cost, and readily available. By contrast, in nonendemic regions (eg, the United States and Europe), penicillin G benzathine is more costly, and recurrent shortages are a substantial and recurring problem [5]. Thus, oral agents (eg, penicillin V) are more commonly used in nonendemic compared with endemic regions.
Oral agents are also appropriate for patients with the following features:
●Penicillin allergy (where a macrolide such as azithromycin is used)
●Severe valvular disease from RHD due to increased risk for sudden death following IM injections
●Bleeding problems following injections that cannot be addressed
●Ongoing concerns regarding IM injections despite attempts to address them
Parenteral prophylaxis — The preferred parenteral antibiotic for prophylaxis is long-acting penicillin G benzathine administered IM (table 3) [2,30,31]. Most patients are started on an every-28-day dosing regimen (600,000 units if ≤27 kg; 1.2 million units if >27 kg). A shorter dosing interval (eg, administration every 21 days) may be appropriate for populations in which the incidence of ARF is particularly high. This approach is also warranted for persons in low-incidence regions who have had recurrent ARF despite adherence to a regimen administered every 28 days [32]. Barriers to injections should be identified and addressed in patients with poor adherence before switching to oral therapy.
Switching from IM to oral prophylaxis (eg, penicillin V 250 mg twice daily) once patients have reached young adulthood and have remained free of rheumatic attacks is appropriate if antibiotic prophylaxis is continued. However, individual circumstances should be carefully considered, including frequency of exposure to population groups (eg, school-aged children and adolescents) that have a higher incidence of GAS pharyngitis.
Oral prophylaxis — Options for oral prophylaxis include penicillin V, macrolides, and sulfadiazine (table 3). The preferred oral agent in patients without penicillin allergy is penicillin V (250 mg twice daily).
Success with oral prophylaxis depends on patient adherence, so clear communication regarding the importance of prophylaxis and how antibiotics should be taken is critical. Even with optimal adherence, the risk of recurrence is higher in persons receiving oral prophylaxis than those receiving IM penicillin G benzathine [25]. This was illustrated in a controlled trial of 405 children and adolescents with rheumatic fever assigned to receive four weeks of IM penicillin G benzathine, oral penicillin G potassium, or oral sulfadiazine. In the first two years of the study, streptococcal infections recurred in 7, 20, and 24 percent of patients, respectively, and ARF recurred in 0, 4.8, and 2.7 percent of the patients, respectively. Penicillin V is now used rather than penicillin G because of its greater bioavailability (approximately 60 versus 30 percent, respectively) [33].
Penicillin allergy — Penicillin allergy should be verified by history and confirmed with testing by an allergy specialist if indicated before choosing an alternative to penicillin G benzathine. Penicillin allergy is the most commonly reported drug allergy. However, most patients evaluated for this allergy have negative testing for IgE-mediated sensitivity, usually because they were inaccurately labeled as penicillin-allergic or the allergy resolved over time. A macrolide (eg, azithromycin 6 mg/kg/day, maximum dose 250 mg) is usually the most appropriate agent for patients allergic to penicillin (table 3). (See "An approach to the patient with drug allergy" and "Penicillin skin testing".)
The long-term benefits of IM penicillin G benzathine prophylaxis outweigh the risk of developing an allergic reaction since life-threatening allergic reactions are rare in patients who receive IM injections of penicillin [34].
Severe valvular disease — In patients with a history of ARF who have developed severe, symptomatic valvular disease (ie, mitral stenosis, aortic stenosis, aortic insufficiency), New York Heart Association class III or IV heart failure, or ventricular dysfunction (ie, ejection fraction <50 percent), we recommend prophylaxis with an oral antibiotic rather than IM penicillin G benzathine (table 3). This recommendation is based upon accumulating evidence of severe outcomes in a small number of patients and availability of a safe and effective alternative, as noted in an American Heart Association advisory following review of the data [35]. In patients who continue to receive IM penicillin G benzathine, measures can be taken to decrease the risk of cardiovascular compromise from a vasovagal reaction including reducing injection pain and related anxiety, ensuring the patient is well hydrated and fed, and administering the injection with the patient in the supine position.
Deaths occurring within hours of injection of penicillin G benzathine typically have been attributed to anaphylaxis [34]. However, on further review, many patients did not have signs and symptoms consistent with anaphylaxis and did not respond to appropriate therapy [36]. Limited observational data suggest that these patients died from cardiovascular compromise related to severe valvular disease [6,37-39]. The proposed mechanism is a physiologic response to the pain and/or fear related to the injection that triggers a vasovagal episode with hypotension, bradycardia, and syncope during or within minutes of administration. This is rapidly followed by decreased coronary perfusion, ventricular arrhythmia, and sudden death. These deaths primarily have occurred in younger patients with severe, symptomatic RHD. Those with symptomatic, severe mitral stenosis, particularly those with cachexia and decreased left ventricular systolic function (ejection fraction <50 percent), followed by those with severe aortic stenosis and severe aortic insufficiency, appear to be at highest risk.
Breakthrough GAS pharyngitis on antibiotic prophylaxis — Patients and their household contacts who develop symptoms suggestive of group A Streptococcus (GAS) pharyngitis while on antibiotic prophylaxis should be evaluated, including checking adherence to the prophylactic regimen, and treated promptly. Patients with breakthrough GAS pharyngitis on penicillin should be treated with an alternative agent such as clindamycin for the acute episode and then restart penicillin prophylaxis (table 3). Those on a 28-day dosing regimen of penicillin G benzathine should be switched to a 21-day regimen. Those on an oral antibiotic regimen may benefit from switching to IM penicillin G benzathine, particularly if adherence to the oral regimen is poor. (See "Treatment and prevention of streptococcal pharyngitis in adults and children".)
GAS pharyngitis in adults with a remote history of ARF — In adults with a remote history of ARF who develop acute group A Streptococcus (GAS) pharyngitis and are no longer on prophylaxis, any of the GAS pharyngitis treatment options are reasonable (table 2). Treatment is discussed in greater detail separately. (See "Treatment and prevention of streptococcal pharyngitis in adults and children".)
Duration — Based upon limited evidence, secondary prevention for recurrent ARF consists of years of prophylactic antibiotic administration. The total duration depends upon risk of recurrent ARF and severity of disease. The duration of prophylaxis following ARF is outlined by severity category in the table (table 4) [2,40]. In the setting of carditis, prophylaxis should continue until the patient is a young adult (21 years of age), which is usually approximately 10 years from the initial acute attack with no recurrence [2,41,42]. Antibiotic prophylaxis should continue even after valve surgery, including prosthetic valve replacement, because a recurrence of ARF can still affect perivalvular tissue, chordae, or another valve, with serious consequences.
Other patients may not require such lengthy duration of treatment. In a Chilean study of 59 patients with a history of ARF without carditis, prophylaxis was discontinued after five years or at age 18 years (whichever was longer) [42]. During 3349 patient-months of follow-up, only two ARF recurrences were observed (0.7 per 100 patient-years). These data suggest that ARF prophylaxis may be discontinued safely in young adults judged to be at low risk for recurrence who are maintained under careful prospective surveillance.
The risk for GAS exposure and severity of valvular disease should be reviewed upon reaching the end of a planned course for secondary prophylaxis. A decision regarding cessation or continuation of antibiotic prophylaxis should be made based upon individual clinical risks and benefits.
Administration of parenteral prophylaxis — Clinicians should recognize that minimizing the stress and pain of penicillin G benzathine injections is a key factor in patient willingness to continue with this therapy. Injecting penicillin G benzathine requires proper training and experience to lessen the pain [43].
Case reporting and prevention programs — Many countries require notification of all cases of ARF and RHD to the health authorities. Registration with a regional ARF/RHD prevention program with ongoing updating of all subsequent related clinical events is also recommended.
Ongoing care — Planning for ongoing care of the patient should begin during the admission and once the diagnosis is made. Coordination is required among health care teams providing specialist care (eg, cardiologists), community care (eg, pediatricians, general practitioners, and community nurses), and pharmacologic care. Frequency of appointments with specialty care teams will vary depending upon severity of RHD.
Education — During an admission, it is crucial that patents and their caregivers receive adequate and culturally appropriate information and education about ARF and RHD [44,45]. The most crucial advice for patients is the importance of continuing secondary prophylaxis even though they will be mostly asymptomatic. There are a variety of resources available to track adherence to secondary prophylaxis, including mobile apps (eg, RHD Australia and Take Heart). In addition, it is essential to educate patients about the importance of treating sore throats early and recommending a nonpenicillin antibiotic (eg, clindamycin) for this if the patient is taking penicillin prophylaxis.
Oral health is important in these patients because they are at high risk of developing infective endocarditis. Thus, patients should receive education about dental care. Patients with carditis should be encouraged to inform their doctor or dentist prior to any interventional procedure so that appropriate antibiotic prophylaxis can be given. A laminated card with the relevant details of the treatment can be helpful for patients and caregivers. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
Given the risks of ARF/RHD in pregnancy and labor, every female of childbearing age receiving secondary prophylaxis should also be given detailed family planning/contraception advice as an integral part of the education program. (See "Acquired heart disease and pregnancy".)
POSTSTREPTOCOCCAL REACTIVE ARTHRITIS — Poststreptococcal reactive arthritis (PSRA) is a reactive arthritis that occurs after a symptom-free interval following group A Streptococcus (GAS) pharyngitis. Whether it is a separate entity from arthritis associated with ARF is controversial since PSRA can be difficult to distinguish from arthritis associated with ARF on clinical grounds. In addition, a small proportion of patients with PSRA have been observed to develop valvular heart disease [46,47]. (See "Acute rheumatic fever: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)
For this reason, some favor administering secondary prophylaxis to children from a low-risk group with suspected PSRA for one to two years after the onset of symptoms, although the efficacy of this approach is not well established [2]. Follow-up echocardiogram is performed 12 to 24 months after instituting secondary prophylaxis. Evidence of valvular disease after one year should is evidence that the joint symptoms were manifestations of ARF and should lead to continued prophylaxis as outlined in the preceding sections. Antibiotic prophylaxis can be discontinued if a follow-up echocardiogram is normal.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acute rheumatic fever and rheumatic heart disease".)
SUMMARY AND RECOMMENDATIONS
●Goals of treatment – Treatment of acute rheumatic fever (ARF) consists of eradication of group A Streptococcus (GAS) infection with antibiotic therapy, symptomatic relief of arthritis with antiinflammatory therapy, management of heart failure and chorea if present, education, and commencement of secondary prevention. There is no therapy documented to slow progression of valvular damage in the setting of ARF. Measurement of inflammatory markers such as C-reactive protein (CRP) may be used to monitor resolution of the acute process. (See 'Treatment' above and 'Monitoring' above.)
•Eradication of GAS carriage – For all patients with ARF, we recommend starting antibiotic therapy as delineated for eradication of streptococcal pharyngitis, whether or not pharyngitis is present at the time of diagnosis (table 1 and table 2) (Grade 1B). In practice, this is often best achieved by administration of a dose of intramuscular (IM) penicillin G benzathine, which also serves as the first dose of secondary prophylaxis. In addition, patients from tropical regions such as Northern Australia, in whom ARF may be triggered by GAS pyoderma, require the same antibiotic therapy as for GAS pharyngitis for any skin infections present. (See 'Eradication of GAS carriage' above and "Impetigo".)
•Arthritis management – For patients with symptomatic ARF-associated arthritis, we suggest treatment with a nonsteroidal antiinflammatory drug (NSAID; eg, naproxen, ibuprofen) rather than other therapies (Grade 2C). NSAIDs are given as a standing dose until symptoms resolve and inflammatory markers improve, provided the medication is well tolerated. Improvement is typically noted in one to two weeks. (See 'Arthritis management' above.)
•Carditis management – Management of carditis in patients with ARF is discussed separately. (See "Management and prevention of rheumatic heart disease", section on 'Management of carditis in acute rheumatic fever'.)
•Chorea management – Sydenham chorea (SC) is generally self-limited, and most cases do not require treatment beyond the usual chronic antibiotic therapy to prevent recurrence of ARF and minimize the risk of RHD. Management of SC is reviewed separately. (See "Sydenham chorea", section on 'Treatment'.)
●Primary prevention – Primary prevention is accomplished by prompt diagnosis and antibiotic treatment of GAS infection, as discussed separately. (See "Treatment and prevention of streptococcal pharyngitis in adults and children".)
●Secondary prevention – We recommend chronic antimicrobial prophylaxis rather than no prophylaxis (ie, treating intermittently only if the patient develops a recurrent symptomatic acute GAS infection) (Grade 1B). The rationale for chronic therapy is to prevent subsequent episodes of GAS infection, since both symptomatic and asymptomatic GAS infections can trigger recurrence of ARF, which in turn leads to development/progression of RHD. (See 'Secondary prevention (antibiotic prophylaxis)' above.)
The choice of regimen is as follows (table 3):
•Preferred regimen – For most patients, we suggest long-acting penicillin G benzathine administered IM every 28 days rather than other regimens (Grade 2C). A 21-day regimen is appropriate if the patient has a breakthrough episode of ARF despite good adherence to the 28-day regimen. Penicillin G benzathine is widely available and inexpensive in endemic areas but may be costly or unavailable in nonendemic area. Thus, oral agents (eg, penicillin V) are more commonly used in nonendemic compared with endemic regions. (See 'Antibiotic selection' above.)
•Alternatives in select circumstances
-In patients with severe, symptomatic valvular heart disease, heart failure, or ventricular dysfunction, we recommend prophylaxis with an oral antibiotic (usually penicillin V) rather than IM penicillin G benzathine (Grade 1C). Oral agents are preferred because life-threatening cardiovascular events have been reported following IM injections in such patients.
-Macrolides (eg, azithromycin) are an acceptable alternative for those with an allergy to penicillin.
•Duration of prophylaxis – The duration of antibiotic prophylaxis depends upon risk of recurrent ARF and severity of disease as summarized in the table (table 4). (See 'Duration' above and 'Risk factors for recurrent disease' above.)
