Acute Rheumatic Fever (ARF)Dz

ICD-9 Codes: With arthritis, 390.0; with carditis, 391.9.
ICD-9 Codes: ARF with heart involvement I00;  ARF without heart involvement I01;  Rheumatic chorea I02

Definition: ARF is a febrile illness occurring as a delayed sequela of infection with group A streptococci and is characterized by inflammatory lesions of connective tissue.

Etiology: ARF occurs 2 to 3 weeks after untreated severe group A 13-hemolytic streptococcal pharyngitis (in as many as 3% of untreated cases). It may be more common with some streptococcal M serotypes. Cutaneous infections (impetigo) never cause ARF.

Pathology: The exact mechanisms are unclear. Humoral response leads to immunecomplex deposition. Cell-mediated immune damage to the heart is potentially owing to molecular mimicry secondary between streptococcal cell wall antigens (M proteins or group A carbohydrate) and myocardial tissue. Streptococcal extracellular toxins, which can act as superantigens, may also be pathogenic. Host factors, including some HLA and non-HLA antigens, may increase susceptibility to rheumatogenic strains.

Demographics: The peak age of incidence is 5 to 15 years. Although ARF remains endemic and is the major cause of valvular heart disease in the developing world, its frequency has declined significantly in the antibiotic era.   Current estimated incidence is 19 per 100,000 children. Risk factors include poverty, crowded living conditions, and youth. Nonetheless, outbreaks of ARF have recently appeared in some regions and populations in the United States.

Cardinal Findings: Only two-thirds of patients recall an antecedent pharyngitis. The onset is heralded by a migratory or additive polyarthritis (knees, ankles, wrists) that may last 2 to 4 weeks. Abdominal pains occur early and may be severe. Jones Criteria serve as a guideline for diagnosis. Carditis occurs early in <15% and is less common in adults. Post-streptococcal reactive arthritis may be a form fruste of ARF, without carditis and with different extraarticular manifestations (i.e., tenosynovitis).

Uncommon Findings: Erythema marginatum (an evanescent, erythematous eruption of the torso with a serpiginous border and central clearing) and nodules are rare in adults. Most cases of Sydenham chorea occur in women. Arthritis of the small joints of the hands or feet alone occurs in <1% of cases. Jaccoud arthropathy, a nonerosive, reducible, deforming arthritis of the hands, occurs rarely when there are repeated episodes. Epistaxis and pneumonia are other uncommon findings.

Diagnostic Testing: Elevated levels of anti-streptolysin O, anti-DNase B, anti- NADase, antistreptokinase, and antihyaluronidase all provide presumptive evidence of recent streptococcal infection. Although none of these tests is specific for ARF, at least one titer is elevated in 90% of streptococcal infections. Elevated levels of acutephase reactants [erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)] and anemia of chronic inflammation are often present. Throat culture for streptococcal infection is usually negative at the time of ARF; if positive, it may only indicate noninfectious carriage. An electrocardiogram, chest radiograph, or echocardiogram may also be necessary to diagnose first-degree atrioventricular block or carditis.

Diagnostic Criteria: Jones Criteria define classic features of ARF. Major manifestations include polyarthritis, carditis, chorea, subcutaneous skin nodules, and erythema marginatum. Minor manifestations include previous ARF or rheumatic heart disease, arthralgias, fever, elevated acute-phase reactants, and a prolonged PR interval on the electrocardiogram. The presence of two major or one major and two minor criteria indicates a high probability of ARF, if supported by evidence of recent streptococcal infection.

Keys to Diagnosis: A young patient with fever and painful migratory polyarthritis after pharyngitis may be suggestive of ARF.

Therapy: Treatment with antibiotics (penicillin or alternative) is necessary to eradicate group A streptococci. Although the arthritis is sensitive to high-dose salicylates (4–8 g/day in divided doses or a serum salicylate level of 20–30 mg/dL), other NSAIDs may be used with success. A prompt and prominent response to salicylates/NSAIDs supports the diagnosis. Refractory arthritis and severe carditis may require corticosteroids. Prevention and prompt management of recurrent pharyngitis is essential. Long-term prophylactic penicillin (or erythromycin if penicillin allergic) is often recommended. Post-streptococcal reactive arthritis is less responsive to nonsteroidal antiinflammatory drugs (NSAIDs) than ARF.

Prognosis: Acute mortality secondary to carditis is very uncommon. The most serious chronic sequela is rheumatic heart disease, which most commonly involves the mitral valve. Rheumatic heart disease develops within 10 to 20 years of the initial attack. Joint disease in ARF is generally self-limiting, lasting less than 6 weeks on average, and chronic arthropathy is rare. Poststreptococcal reactive arthritis has a generally benign prognosis.

BIBLIOGRAPHY

Amigo MC, Martinex-Lavin M, Reyes P. Acute rheumatic fever. Rheum Dis Clin North Am 1993;19;333–350. PMID:8502775

Rullan E, Sigal LH. Rheumatic fever. Curr Rheumatol Rep 2001;3:445–452.PMID:11564377

Tani LY, Veasy LG, Minich LL, et al. Rheumatic fever in children younger than 5 years: is the presentation different? Pediatrics 2003;112:1065–1068. PMID:14595047 

Burke RJ, Chang C.  Diagnostic criteria of acute rheumatic fever. Autoimmun Rev. 2014;13:503-7. PMID:  24424191