Basics
Description
- A postinfectious inflammatory disease caused by rheumatogenic strains of group A ²-hemolytic Streptococcus (GABHS)
- Acute rheumatic fever (ARF) results in a wide range of disease, from mild joint involvement to chronic carditis.
- The most significant socioeconomic impact is caused by its most severe form, rheumatic heart disease (RHD). Although rarely fatal in the acute phase, RHD may result in significant disability and shortened lifespan. Therefore, the elimination of RHD is a main goal of the World Health Federation.
Epidemiology
- Occurs following pharyngitis with rheumatogenic GABHS strains
- GABHS strains causing skin infections have been associated with ARF in tropical and underdeveloped areas of the world.
- Initial episode seen primarily in patients 5 " 15 years of age
- No racial or ethnic predilections
Incidence
- Historically, untreated GABHS infection results in ARF in 0.1 " 0.3% of cases, with attack rates as high as 3% in endemic areas.
- Decrease in incidence due to increased use of antibiotics, improved environmental factors such as overcrowding, and changing virulence patterns of GABHS strains
Prevalence
- 12 million people are affected by ARF worldwide, with 400,000 cases of RHD.
- RHD accounts for 25 " 40% of all cardiac disease worldwide.
Risk Factors
Genetics
No specific genetic risk factor identified, although numerous studies have demonstrated an association of ARF with specific human leukocyte antigen (HLA) alleles.
Pathophysiology
- GABHS triggers a complex inflammatory host response, affecting the heart, joints, brain, blood vessels, and subcutaneous tissue.
- Classic example of molecular mimicry, in which the host produces antibodies to certain GABHS M proteins, which are similar in structure to host proteins such as myosin, resulting in autoimmune tissue damage
- Aschoff nodules are proliferative lesions noted in the myocardium that may persist for months to years after initiation of disease.
Etiology
Immune-mediated inflammatory reaction to specific rheumatogenic strains of GABHS
Diagnosis
History
Diagnosis is based on the modified Jones criteria (updated 1992):
- Evidence of recent GABHS infection PLUS 2 major OR 1 major and 2 minor criteria
- Major criteria (% affected)
- Polyarthritis (70%): migratory arthritis of major joints; more common in adults
- Carditis (50%): 85% of those with carditis have mitral regurgitation, and 54% have aortic valve involvement. Symptoms range from asymptomatic murmur to fulminant heart failure; carditis is more common and more severe in children.
- Sydenham chorea (15%): abnormal behavior and/or involuntary, purposeless movements
- Erythema marginatum (10%): evanescent, pink rash with serpiginous borders
- Subcutaneous nodules (2 " 10%): painless nodules over extensor surfaces of large joints, the occiput, and/or vertebral processes
- Minor criteria
- Fever
- Arthralgia (mild pain without objective findings): can only be considered without finding of arthritis
- Elevated acute-phase reactants: ESR, C-reactive protein
- Prolongation of the PR interval on ECG
- Exceptions to the Jones criteria include the following:
- Sydenham chorea alone
- Subclinical carditis (echocardiogram evidence of RHD) in the absence of other criteria should be treated as ARF.
- Jones criteria not useful with recurrence; World Health Organization (WHO) recommends treating recurrence in a patient with RHD history and presence of any new major or minor criterion.
Physical Exam
- Cardiac
- Murmur of valvulitis: holosystolic mitral regurgitant murmur, Carey-Coombs apical mid-diastolic murmur, or a basal diastolic murmur of aortic insufficiency (major criterion)
- Pericardial friction rub: pericardial effusion
- Musculoskeletal
- Pain, limited motion, erythema, warmth of 2 or more large joints: arthritis (major criterion)
- Neurologic
- Choreiform movements (must be differentiated from tics, athetosis, and hyperkinesis)
- Sydenham chorea (major criterion)
- Dermatologic
- Evanescent, pink rash with pale centers and serpiginous borders on the trunk and proximal extremities: erythema marginatum (major criterion)
- Firm, painless nodules over the extensor surface of large joints, occiput, and/or spinous processes: subcutaneous nodules (major criterion)
Diagnostic Tests & Interpretation
Lab
- Specific tests: No specific diagnostic test is available.
- Nonspecific tests
- Throat culture: neither sensitive nor specific; false negative in up to 2/3 of affected patients or false positive in patients who are colonized
- Elevated or rising streptococcal antibody titers, antistreptolysin O, anti-DNase B, and antihyaluronidase may be helpful.
- ESR and C-reactive protein elevation
Imaging
- ECG: prolonged PR interval (minor criterion), junctional rhythm, transient arrhythmias, ST-T wave changes
- Chest radiograph: Cardiomegaly may indicate carditis or pericardial effusion. Pulmonary edema may reflect left heart failure due to valvulitis.
- Echocardiogram: Assess valve involvement, ventricular dilatation, function, and pericardial effusion.
Differential Diagnosis
- Carditis
- Viral
- Bacterial
- Rickettsial
- Parasitic
- Mycoplasma myocarditis
- Kawasaki disease
- Arthritis
- Poststreptococcal reactive arthritis (PSRA)
- Serum sickness
- Septic arthritis (e.g., gonococcal)
- Lyme disease
- Collagen vascular disease
- Juvenile rheumatoid arthritis (small joints, not migratory, and not relieved promptly with aspirin)
- Systemic lupus erythematosus
- Bacterial endocarditis
- Chorea
- Congenital choreoathetosis
- Brain tumors
- Huntington chorea
- Wilson disease
- Pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
- Hematologic disorders with joint involvement
- Sickle cell anemia
- Leukemia
- Congenital heart defects: previously undiagnosed valvular heart disease
- Mitral valve prolapse with regurgitation
Treatment
Medication
First Line
- Anti-inflammatory
- Aspirin 60 " 100 mg/kg/24 h PO divided q6 " 8h; may be reduced when fever and acute-phase reactants have normalized for 6 " 8 weeks
- Antibiotics in ARF
- Penicillin V potassium
- Children: 250 mg 2 " 3 times/day for 10 days
- Adolescents, adults: 500 mg 2 " 3 times/day for 10 days
- Secondary prophylaxis
- Penicillin G benzathine IM (600,000 U for weight <27 kg or 1,200,000 U for weight >27 kg) every 3 " 4 weeks
Second Line
- Anti-inflammatory
- Prednisone 2 mg/kg/24 h for 2 weeks, then taper
- Antibiotics in ARF
- Erythromycin, amoxicillin, 1st-generation cephalosporin
- Secondary prophylaxis
- Penicillin V potassium 250 mg b.i.d.
- Erythromycin, sulfadiazine
Additional Treatment
General Measures
- Primary prevention: appropriate and early treatment of GABHS pharyngitis
- Interventions to address poverty, crowding, and housing challenges
- Treatment of ARF
- Antibiotics: full course of penicillin or equivalent to eradicate active infection; does not alter course of carditis
- Anti-inflammatory: High-dose aspirin is standard; steroids may help for severe carditis but remain controversial.
- Cardiac support: aggressive support of cardiac function and use of systemic afterload reduction for severe disease
- Surgical valvuloplasty or valve replacement may be necessary in severe cases.
- Bed rest: controversial; recommended at times for severe cases
- Secondary prevention of recurrence
- Ideally administered as penicillin G benzathine as a monthly IM injection, but oral daily penicillin or erythromycin is acceptable in areas of low prevalence.
- Duration is based on clinical presentation and degree of cardiac involvement:
- ARF without cardiac involvement: 5 years or until age 18 years, whichever is longer
- ARF with mild or resolved carditis: 10 years or until age 25 years, whichever is longer
- ARF with severe carditis or cardiac surgery: lifelong
- Treatment of chorea
- Usually supportive
- Phenobarbital and haloperidol are most commonly used; chlorpromazine, diazepam, or valproic acid also used
Issues for Referral
Patients with new murmurs or clinical evidence of heart failure should be referred to a cardiologist.
Inpatient Considerations
Initial Stabilization
- Full treatment of streptococcal pharyngitis infection and cardiac support if heart failure present
- Treatment phases include primary prevention, management of ARF, and secondary prevention of recurrence.
Ongoing Care
Follow-up Recommendations
- Patients without carditis
- Close follow-up is needed for 2 " 3 weeks to assess patient 's condition for development of acute carditis.
- Long-term pediatric follow-up is needed to diagnose patients with indolent carditis.
- Long-term follow-up is needed to evaluate patients who develop chorea.
- Prophylaxis should be stressed even in patients without carditis.
- Patients with carditis
- Cardiology follow-up is needed to assess development or evolution of RHD.
- Symptoms of worsening heart failure suggest progression of valvular or myocardial disease, recurrent ARF, or endocarditis.
- Secondary prophylaxis and bacterial endocarditis prophylaxis should be stressed.
Prognosis
- ARF recurrence rate as high as 36% without prophylaxis
- Chorea may last weeks to months and has a similarly high recurrence rate.
- Carditis may resolve spontaneously (70 " 80%) or progress. Severity of the initial carditis is a major determinant of progression.
Complications
Long-term complications related to evolution of RHD
- Mitral stenosis
- Mitral regurgitation
- Aortic stenosis
- Aortic regurgitation
- Chronic heart failure
Additional Reading
- Carapetis JR, McDonald M, Wilson NJ. Acute rheumatic fever. Lancet. 2005;366(9480):155 " 168. [View Abstract]
- Cilliers AM, Manyemba J, Saloojee H. Anti-inflammatory treatment for carditis in acute rheumatic fever. The Cochrane Library. 2006;4:1 " 37.
- Kerdemelidis M, Lennon DR, Arroll B, et al. The primary prevention of rheumatic fever. J Paediatr Child Health. 2010;46(9):534 " 548. [View Abstract]
- Lawrence JG, Carapetis JR, Griffiths K, et al. Acute rheumatic fever and rheumatic heart disease: incidence and progression in the Northern Territory of Australia, 1997 to 2010. Circulation. 2013;128(5):492 " 501. [View Abstract]
- Van Driel M, De Sutter AI, Keber N, et al. Different antibiotic treatments for group A streptococcal pharyngitis. The Cochrane Library. 2013;4:1 " 49.
Codes
ICD09
- 390 Rheumatic fever without mention of heart involvement
- 398.90 Rheumatic heart disease, unspecified
- 714.0 Rheumatoid arthritis
- 391.9 Acute rheumatic heart disease, unspecified
ICD10
- I00 Rheumatic fever without heart involvement
- I09.9 Rheumatic heart disease, unspecified
- M06.9 Rheumatoid arthritis, unspecified
- I09.89 Other specified rheumatic heart diseases
SNOMED
- 58718002 Rheumatic fever (disorder)
- 194708008 Rheumatic fever with heart involvement
- 14175009 Rheumatic joint disease (disorder)
- 703119002 Carditis due to rheumatic fever (disorder)
- 240041006 Rheumatic fever nodule (disorder)
- 24363009 rheumatic fever without heart involvement (disorder)
FAQ
- Q: Does a negative throat culture rule out ARF?
- A: No. Throat cultures may be negative in 2/3 of patients.
- Q: Is there a vaccine available that is effective in preventing ARF?
- A: Not at present. Given that >90 antigenic strains of group A Streptococcus have been identified; vaccines development is focused on strains with the greatest virulence.
- Q: What genetic factors predispose to ARF?
- A: Patients with certain HLA-DR antigens are predisposed to ARF. The specific antigen/allele varies with the ethnic group.
- Q: Can ECG evidence of carditis alone be used to diagnose rheumatic fever?
- A: An ECG finding of carditis in the absence of a murmur does not fulfill the Jones criteria. However, many experts would agree to treat subclinical carditis as ARF, especially in areas of high prevalence.