treatment and prevention of acute rheumatic fever

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Official reprint from UpToDate

www.uptodate.com

2012 UpToDate

AuthorsAllan Gibofsky, MD, JD, FACP,

FCLM

John B Zabriskie, MD

Section EditorsRobert Sundel, MD

Daniel J Sexton, MD

Deputy EditorElizabeth TePas, MD, MS

Treatment and prevention of acute rheumatic fever

Disclosures

All topics are updated as new evidence becomes available and ourpeer review process is complete.

Literature review current through: Aug 2012. | This topic last updated: Jul 17, 2012.

INTRODUCTION Acute rheumatic fever (ARF) is a nonsuppurative complication of pharyngeal infection with

group A streptococcus. Signs and symptoms of ARF develop two to three weeks following pharyngitis and

include arthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum [1]. (See "Clinicalmanifestations and diagnosis of acute rheumatic fever" .)

In developing areas of the world, acute rheumatic fever and rheumatic heart disease are estimated to affect

nearly 20 million people and are the leading causes of cardiovascular death during the first five decades of life

[2]. In the United States and other developed countries, the incidence of ARF is much lower, likely due to

improved hygienic standards and routine use of antibiotics for acute pharyngitis [3]. (See "Epidemiology and

pathogenesis of acute rheumatic fever".)

There is no therapy that slows progression of valvular damage in the setting of ARF. There are three major goals

of treatment:

Symptomatic relief of acute disease manifestationsEradication of the group A beta-hemolytic streptococcus (GAS)

Prophylaxis against future GAS infection to prevent recurrent cardiac disease

Issues related to treatment and secondary prevention of rheumatic fever will be reviewed here. Issues related to

primary prevention (eg, treatment of streptococcal tonsillopharyngitis) and the epidemiology, pathogenesis,

clinical manifestations and diagnosis of acute rheumatic fever are discussed in detail separately. (See

"Treatment and prevention of streptococcal tonsillopharyngitis" and "Epidemiology and pathogenesis of acute

rheumatic fever" and "Clinical manifestations and diagnosis of acute rheumatic fever".)

TREATMENT Treatment of acute rheumatic fever consists of antibiotic therapy, heart failure management,

and anti-inflammatory therapy.

Antibiotic therapy Patients with acute rheumatic fever should be initiated on antibiotic therapy to eradicate

GAS carriage. Treatment should proceed as delineated for management of streptococcal pharyngitis, whether or

not pharyngitis is present at the time of diagnosis (table 1) [4]. In addition, household contacts should have

throat cultures performed; those with positive results should also receive a full course of antibiotic therapy, even

if asymptomatic. (See "Treatment and prevention of streptococcal tonsillopharyngitis".)

Carditis Patients with severe carditis (significant cardiomegaly, congestive heart failure, and/or third-degree

heart block) should be treated with conventional therapy for heart failure. (See "Clinical manifestations and

diagnosis of acute rheumatic fever" and "Overview of the therapy of heart failure due to systolic dysfunction" .)

Valve surgery may be necessary when heart failure due to regurgitant lesions cannot be managed with medicaltherapy alone [5-7]. Surgical outcomes are generally better if valve surgery can be performed when carditis is

quiescent [6]. Valve repair, if feasible, is preferred over valve replacement since repair avoids the need for long-

term anticoagulation associated with mechanical valves and the long-term risk of deterioration of a bioprosthesis

[5,7].


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Aspirin (80 to 100 mg/kg per day in children and 4 to 8 g/day in adults) is the major anti-inflammatory agent for

relief of symptoms due to acute rheumatic fever [8]. The efficacy of other anti-inflammatory drugs in the setting

of active rheumatic carditis is uncertain [9-13]. A meta-analysis of eight randomized trials including 996 patients

with acute rheumatic fever found no significant difference in the risk of cardiac disease at one year between the

corticosteroid-treated and aspirin-treated groups [13]. No reduction in the risk of heart valve lesions was

observed with corticosteroids or intravenous immunoglobulin [13].

Arthritis and rash Anti-inflammatory agents are the mainstay of symptomatic management due to acute

rheumatic fever [8]. Aspirin (80 to 100 mg/kg per day in children and 4 to 8 g/day in adults) is helpful forreducing discomfort related to arthritis and fever. Anti-inflammatory therapy should be continued until all

symptoms have resolved. Normalization of inflammatory markers (erythrocyte sedimentation rate and C-reactive

protein concentration) may be used as indicator of resolution. The rash associated with ARF is temporary and

does not require specific treatment, although antihistamines may help to alleviate pruritus. (See "Aspirin:

Mechanism of action, major toxicities, and use in rheumatic diseases".)

PREVENTION Prevention of initial and recurrent attacks of rheumatic fever depends on control of group A

streptococcal tonsillopharyngitis [14,15].

Primary prevention Prevention of initial attack of rheumatic fever (primary prevention) is accomplished by

prompt diagnosis and antibiotic treatment of group A streptococcal tonsillopharyngitis. These issues are

discussed in detail separately. (See "Evaluation of acute pharyngitis in adults" and "Approach to diagnosis of

acute infectious pharyngitis in children and adolescents" and "Treatment and prevention of streptococcal

tonsillopharyngitis" .)

Appropriate antibiotic treatment of streptococcal pharyngitis prevents acute rheumatic fever in most cases [16].

However, at least one third of acute rheumatic fever episodes occur in the setting of inapparent streptococcal

infection [17]. In addition, rheumatic fever is not preventable in symptomatic patients who do not seek medical

care.

Streptococcal skin infections (such as impetigo or pyoderma) have not been proven to lead to acute rheumatic

fever. (See "Impetigo".)

Secondary prevention Patients who have had an attack of rheumatic fever and develop subsequent GAS

pharyngitis are at high risk for a recurrent attack of rheumatic fever, with progression in severity of rheumatic

heart disease from the initial episode. The most effective method to limit progression of rheumatic heart disease

severity is prevention of recurrent GAS pharyngitis, especially since GAS infection need not be symptomatic to

trigger a recurrent attack of rheumatic fever.

For these reasons, prevention of recurrent rheumatic fever (secondary prevention) requires continuous

antimicrobial prophylaxis, rather than recognition and treatment of acute GAS pharyngitis episodes. Continuous

prophylaxis is warranted for patients with well-documented history of rheumatic fever (including cases with

Syndenham chorea as the sole manifestation) and those with definite evidence of rheumatic heart disease. (See

"Clinical manifestations and diagnosis of acute rheumatic fever".)

Prior to initiation of prophylaxis, a full therapeutic course of antibiotic therapy should be given to patients with

acute rheumatic fever to eradicate residual GAS, even if a throat culture is negative (table 1). (See 'Primary

prevention' above.)

Prophylactic antibiotics should be initiated immediately at the end of the therapeutic antibiotic course. During

the course of prophylaxis, patients and their household contacts who develop acute episodes of group A

streptococcal pharyngitis should be evaluated and treated promptly as outlined separately. (See "Treatment and

prevention of streptococcal tonsillopharyngitis".)

Duration Secondary prevention for prevention of recurrent rheumatic fever consists of years of

prophylact ic antibiotic administration. The total duration depends risk of recurrent rheumatic fever and severity of

disease.

The risk of recurrent rheumatic fever depends on several factors [4,10]:


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The preferred oral agent is penicillin V (table 3). Sulfadiazine or sulfisoxazole is appropriate for patients allergic

to penicillin; this antibiotic class is effective for preventing GAS infection although it cannot be used to achieve

eradication. An oral macrolide such as azithromycin is acceptable for patients allergic to both penicillin and

sulfa drugs.

Prior to initiation of prophylaxis, a full therapeutic course of antibiotic therapy should be given to patients with

acute rheumatic fever to eradicate residual GAS, even if a throat culture is negative (table 1). Prophylactic

antibiotics should be initiated immediately at the end of the therapeutic antibiotic course.

During the course of prophylaxis, patients and their household contacts who develop acute episodes of group A

streptococcal pharyngitis should be evaluated and treated promptly. (See "Treatment and prevention of

streptococcal tonsillopharyngitis".)

Poststreptococcal reactive arthritis Poststreptococcal reactive arthritis (PSRA) is a reactive arthritis

that occurs after a symptom-free interval following GAS pharyngitis. It differs from the arthritis associated with

ARF, as outlined separately. (See "Clinical manifestations and diagnosis of acute rheumatic fever", section on

'Differential diagnosis'.)

PSRA can be difficult to distinguish from arthritis associated with ARF on clinical grounds, and a small

proportion of patients with PSRA have been observed to develop valvular heart disease [28,29].

For this reason, some favor administering secondary prophylaxis in the setting of suspected PSRA for up to one

year after the onset of symptoms, although the efficacy of this approach is not well established [ 4]. Evidence of

valvular disease after one year should prompt continued prophylaxis as outlined in the preceding sections, and it

may be presumed that the presenting symptoms were manifestations of acute rheumatic fever. In the absence

of valvular disease after one year, antibiotic prophylaxis may be discontinued.

SUMMARY AND RECOMMENDATIONS

We recommend that patients with acute rheumatic fever be initiated on antibiotic therapy as delineated

for eradication of streptococcal pharyngitis, whether or not pharyngitis is present at the time of diagnosis

(table 1) (Grade 1C). (See 'Treatment' above.)

Patients with severe carditis should be treated with conventional therapy for heart failure. Valve surgery

may be necessary when heart failure due to regurgitant lesions cannot be managed with medical therapy

alone.Aspirin is the mainstay of symptomatic management due to acute rheumatic fever. (See

'Carditis' above and 'Arthritis and rash' above.)

Prevention of initial attack of rheumatic fever (primary prevention) is accomplished by prompt diagnosis

and antibiotic treatment of group A streptococcal tonsillopharyngitis. (See "Treatment and prevention of

streptococcal tonsillopharyngitis".)

Prevention of recurrent rheumatic fever (secondary prevention) requires prevention of recurrent GAS

pharyngitis. We recommend continuous antimicrobial prophylaxis, rather than recognition and treatment

of acute GAS pharyngitis episodes (Grade 1B). (See 'Secondary prevention' above.)

In general, prophylaxis for in the setting of carditis should continue until the patient is a young adult (18

years of age), which is usually 10 years from an acute attack with no recurrence (table 2). At the end of a

planned course for secondary prophylaxis, the risk for GAS exposure and severity of valvular disease

should be reviewed. (See 'Duration' above.)

We suggest long-acting benzathine penicillin G for secondary prevention of recurrent rheumatic fever

(table 3) (Grade 2B). Switching from intramuscular to oral prophylaxis once patients have reached young

adulthood and have remained free of rheumatic attacks is appropriate. (See 'Antibiotic selection' above.)

We suggest administering secondary prophylaxis in the setting of suspected poststreptococcal reactive

arthritis for up to one year after the onset of symptoms (Grade 2C). Evidence of valvular disease after

one year should prompt continued prophylaxis; otherwise, antibiotic prophylaxis may be discontinued.


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GRAPHICS

Treatment of pharyngitis due to group A streptococcus

Adults and adolescents (>27kg)

Children (27 kg)

Oral penicillin V* (phenoxymethyl penicillin)

500 mg two to three times dailyfor 10 days

250 mg two to three times daily for 10 days

Intramuscular penicillin, single dose

Penicillin G benzathine andpenicillin G procaine (Bicillin C-R)2.4 million units or penicillin Gbenzathine (Bicillin L-A) 1.2million units

Penicillin G benzathine and penicillin G procaine(Bicillin C-R 900/300) 1.2 million units. Consistsof benzathine penicillin G 900,000 units mixed withprocaine penicillin G 300,000 units.

Amoxicillin

875 mg orally twice daily or 500mg three times daily for 10 days

50 mg/kg per day orally (maximum 1000 mg perday). May be administered once daily or in two orthree equally divided doses; duration is 10 days

Cephalexin

500 mg orally twice daily for 10days 25-50 mg/kg per day orally in two equally divided

doses (maximum 1000 mg per day) for 10 days

For patients with potential severe hypersensitivity to beta-lactam antibiotics (eg,penicillin, cephalosporins):

Azithromycin

500 mg orally on day one followedby 250 mg daily on days twothrough five

12 mg/kg orally once daily for five days

Clindamycin

28 to 70 kg: 20 mg/kg/day orallyin three equally divided doses for10 days

>70 kg: 450 to 600 mg orally

three times daily for 10 days

20 mg/kg per day orally in three equally divideddoses for 10 days

* Oral penicillin V is the drug of choice for GAS pharyngitis.

Penicillin G benzathine and penicillin G procaine (Bicillin C-R 900/300) requires further study

before routine use in adults or large ado lescents is acceptable. Bicillin L-A (benzathine

penicillin G 600,000 units IM) is an acceptable alternative regimen for patients


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Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on

Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and

Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research.

Circulation 2009; 119(11):1541-51. Copyright 2009 Lippincott Williams & Wilkins.

Additional data from: American Academy of Pediatrics. Group A Streptococcal infections. In: Red

Book: 2006 Report of the Committee on Infectious Diseases, 27th ed, Pickering, LK (Ed), American

Academy of Pediatrics, Elk Grove Village, IL 2006. p.610.


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Secondary prophylaxis for rheumatic fever - Duration of therapy

Category Duration after last attack

Rheumatic fever w ith carditis and residualheart disease

(persistent valvular disease*)

10 years or until 40 years of age(whichever is longer);

sometimes lifelong prophylaxis (see text)

Rheumatic fever with carditis but no residualheart disease

(no valvular disease*)

10 years or until 21 years of age

(whichever is longer)

Rheumatic fever without carditis5 years or until 21 years of age

(whichever is longer)

* Clinical or echocardiographic evidence.Modified with permission from: Gerber MA, BaltimoreRS, Eaton CB, et al. Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute

Streptococcal Pharyngitis: A Scientific Statement From the American Heart Association Rheumatic

Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in

the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the

Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2009;

119(11):1541-51. Copyright 2009 Lippincott Williams & Wilkins.


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Secondary prophylaxis for rheumatic fever - Selection of therapy

Continuous regimen

Adults >27 kg Children 27 kg

Penicillin G benzathineintramuscular (Bicillin LA)

1.2 million units every4 weeks*

600,000 units every 4weeks*

Penicillin V oral 250 mg orally twicedaily

250 mg orally twice daily

Sulfadiazine 1000 mg orally oncedaily

500 mg orally once daily

Allergy to penicillin and sulfadiazine:

Azithromycin 250 mg orally once daily 5 mg/kg orally once daily (upto 250 mg)

* In high-risk situations, administration every three weeks is justified and recommended.

For small children and infants: 25,000 units per kg intramuscularly every 4 weeks or 3 weeks

(high-risk).

Macrolide susceptibility testing should be pursued prior to use of this drug class .

Erythromycin is an acceptable alternative to azithromycin, although the latter has fewer

adverse effects and permits once daily dosing. Erythromycin dosing for adults: 250 mg orally

twice daily. Dosing for children: 20 mg/kg/day divided tw ice daily (maximum 500 mg per day).

Modified with permission from: Gerber MA, Baltimore RS, Eaton CB, et al. Prevention of Rheumatic

Fever and Diagnosis and Treatment of Acute Streptococcal Pharyngitis: A Scientific Statement

From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease

Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on

Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care

and Outcomes Research. Circulation 2009; 119(11):1541-51. Copyright 2009 Lippincott

Williams & Wilkins.

treatment and prevention of acute rheumatic fever

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