Acute rheumatic fever (ARF) is a systemic, immune-mediated disease that is triggered by pharyngeal infection with group A streptococci (GAS). Fever, migratory polyarthritis, and carditis are the most common clinical manifestations. ARF is most frequent among 5–15 year olds with a declining incidence in adults. It is extremely rare in children under age 3, prompting speculation that more than one GAS infection is needed before ARF can develop. ARF is not considered a sequela of cutaneous GAS infection.

The pathogenesis of ARF is not clearly understood but appears to involve an immune response to group A streptococcal antigens that then cross-reacts with human tissue through molecular mimicry. Strains of GAS differ in their ability to trigger ARF, and changes in the prevalence of rheumatogenic strains can affect the incidence of ARF. Recent evidence supports the conclusion that ARF has declined in the United States over the past decades largely because of a decline in rheumatogenic types of GAS causing pharyngitis.

The reported attack rate of ARF among patients with untreated GAS pharyngitis is 0.4–3% in epidemic circumstances, with a much lower rate endemically. Genetic factors appear to influence the person’s susceptibility to ARF. Observational studies in the 19th century recognized familial tendencies to develop ARF, and in the early 1940s, studies showed familial clustering of the disease, with greatest risk occurring in children if both parents had rheumatic heart disease. Genetic susceptibility to develop ARF has been characterized as autosomal recessive or autosomal dominant with variable penetrance and has been linked with HLA types. Significant increases in the frequency of DRB1*0701, DR6, and DQB1*0201 confer susceptibility to rheumatic fever in several international studies. Monozygotic twins, however, are not usually concordant for ARF, indicating that there are also important environmental factors involved in the pathogenesis of the disease.

Clinical Findings

Diagnostic Criteria

In 1944, Dr. T. Duckett Jones developed diagnostic criteria for ARF—the “Jones criteria”—based on his observations of hundreds of patients. The Jones criteria have been revised several times, most recently in 1992 (Table 52–1), and continue to form the basis for the clinical diagnosis of ARF. Exceptions to these criteria include patients who present with chorea or indolent carditis; these patients often do not fulfill the requirement for evidence of antecedent GAS infection because their antistreptococcal antibody levels usually have returned to normal at the time of presentation.

Major Clinical Criteria

Arthritis occurs in approximately 75% of patients with ARF. The arthritis is migratory, which is in contrast to poststreptococcal reactive arthritis, and polyarticular. The arthritis usually affects the larger joints, especially knees, ankles, wrists and elbows, and less commonly involves the smaller joints of the hands and feet. The axial skeleton is rarely affected. Inflamed joints are often red, hot, swollen, and exquisitely tender—to the point that even minimal contact with the affected joint can cause exquisite pain. Left untreated, inflammation of an individual joint resolves spontaneously over days, but the polyarthritis persists for 1–4 weeks. The arthritis of ARF responds dramatically to salicylates. This response is so characteristic that the lack of response to salicylate therapy within 48 hours should prompt the clinician to doubt the diagnosis of ARF and to consider other possibilities.

Carditis occurs in approximately 50–60% of ARF cases and accounts for significant morbidity and even mortality. When ARF affects the heart, it usually involves the endocardium, myocardium, and pericardium to varying degrees. Endocarditis leading to mitral or aortic valvulitis (or both) is most characteristic and occurs most frequently; the tricuspid and pulmonary valves are rarely affected. The revised Jones criteria for ARF require auscultation of a new valvular murmur in order to meet the criterion of “carditis”; echocardiography findings of valvular regurgitation without a murmur do not fulfill either major or minor criteria. When chronic rheumatic heart disease results, valvular regurgitation can be replaced by valvular stenosis. Myocarditis manifests as tachycardia that is disproportionate to the degree of fever and is persistent even in sleep. Pericarditis is the least common finding in rheumatic carditis. It usually manifests as a pericardial effusion or friction rub. The presence of myocarditis or pericarditis in the absence of valvular involvement is unlikely to be due to ARF, and other diagnoses should be explored in this circumstance.

Sydenham chorea (St. Vitus dance), which occurs in 10–15% of patients, is usually a later manifestation of ARF. The characteristic features of chorea are purposeless involuntary movements, incoordination, facial grimacing, and emotional lability. Chorea is a self-limited illness, and full recovery takes several months. Rarely, symptoms can occur over years and are exacerbated by stress, pregnancy, oral contraceptives, and intercurrent illnesses. Chorea is thought to be due to antibodies that cross-react with basal ganglia neurons.

Erythema marginatum occurs in less than 2% of patients. It is an erythematous, flat, serpiginous macular rash with pale central clearing. The rash usually occurs on the trunk and extremities and characteristically spares the face. The rash waxes and wanes and may be transient.

Subcutaneous nodules develop in less than 1% of cases of ARF, most often in those with severe carditis. The nodules are firm, nontender, and usually less than 2 cm in diameter. They are typically located over bony prominences or tendon sheaths. Nodules usually resolve spontaneously without permanent sequelae.

Minor Clinical Criteria