DESCRIPTION

• Acute rheumatic fever (ARF) is an immune-mediated inflammatory disease occurring as a sequela to a superficial infection by group A β-hemolytic Streptococcus (GABHS), 2 to 5 weeks after the original infection.
• ARF results in a wide range of manifestations, ranging from mild joint involvement to transient central nervous system affects (Sydenham chorea) to carditis, which may evolve into rheumatic heart disease (RHD).
• RHD constitutes the most commonly acquired heart disease in children and young adults, carrying a high socioeconomic impact. Although rarely fatal in the acute phase, RHD may result in significant disability and shortened lifespan.

EPIDEMIOLOGY

• Occurs usually following acute pharyngitis with GABHS
• GABHS strains causing skin infections have also been associated with ARF in the developing world.
• Initial episode of ARF is seen primarily in patients 5 to 14 years of age; complications from chronic RHD present in young adults.
• Incidence and prevalence rates show increasing trends in locations with a low sociodemographic index (SDI), whereas locations with a middle-high and high SDI show a decreasing trend.
• ARF has an incidence of 2 per 100,000 per year in the United States. Global incidence of ARF is 8 to 51 per 100,000 people per year with >1,000 per 100,000 people in some endemic regions.
  • It is estimated that untreated GABHS infection results in ARF in 0.1–0.3% of cases, with attack rates as high as 3% in endemic areas.
  • 30–50% of patients with RHD do not have a recognized episode of ARF.
  • RHD is associated with an estimate of 300,000 deaths annually.
  • A profound decrease in incidence in the developed world has been seen due to increased use of antibiotics, improved living conditions, nutrition, and changing virulence patterns of GABHS strains.
• An estimate of 38 to 40 million people are affected by RHD worldwide.
  • Higher prevalence, disability, and mortality is seen in Oceania, sub-Saharan Africa, and South Asia.
  • RHD accounts for 25–40% of all cardiac disease worldwide. Prevalence peaks in those between 25 and 45 years of age. RHD accounts for the greatest cardiovascular-related loss of disability-adjusted life years.

ETIOLOGY

Autoimmune-mediated inflammatory reaction after GABHS infection

RISK FACTORS

Strongly associated with household overcrowding and socioeconomic deprivation

GENERAL PREVENTION

• Primary prevention
  • Interventions to address social factors including poverty, crowding, and housing challenges
  • Hand washing
  • Appropriate and early recognition and treatment of GABHS pharyngitis. Treatment within 9 days of onset of symptoms may reduce the risk of ARF by 70–80%.
• Treatment of ARF
  • Antibiotics: full course of penicillin or equivalent to eradicate active infection; does not alter course of carditis
  • Arthritis: high-dose aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen.
  • Carditis:
    • Supportive treatment; tailored depending on type of effects and severity; in congestive heart failure, the use of guideline-directed medical therapy is indicated.
    • Surgical valvuloplasty or valve replacement is rarely necessary in ARF. Used in severe cases with chordae tendineae or valve leaflet rupture.
  • Sydenham chorea: typically self-limited; education and support to patient and family
• Surveillance screening for RHD
  • 10 times more RHD can be detected by echocardiography than by auscultation.
  • Simplified echocardiographic criteria and screening with handheld devices, including by nonexperts, need to be validated with prospective longitudinal studies before adoption.
• Secondary prevention of recurrence
  • Penicillin G benzathine IM injection every 4 weeks is superior to oral daily penicillin. The pain of injection is reduced when reconstituted with lidocaine 1%. Oral penicillin or erythromycin are second line.
  • Duration: based on clinical presentation and degree of cardiac involvement (American Heart Association):
    • ARF without cardiac involvement: 5 years or until age 21 years, whichever is longer
    • ARF with mild or resolved carditis: 10 years or until age 21 years, whichever is longer
    • ARF with RHD: 10 years or until age 40 years, whichever is longer; consider lifelong if high risk.

PATHOPHYSIOLOGY

• GABHS triggers a complex inflammatory response in the host.
• Classic example of molecular mimicry. The host produces antibodies to certain GABHS antigens, which are similar in structure to host proteins such as laminin, vimentin (valve proteins), or myosin, resulting in cross-reactive autoimmune tissue damage, affecting the heart, joints, brain, blood vessels, and subcutaneous tissue.
• Aschoff nodules, a type of granulomatous lesions, form in the valves below the endocardium leading to valvar damage and subsequent valvar stenosis or regurgitation. Further breakdown of the valve leads to increased immune-mediated damage. This cycle may persist for months to years after initiation of disease.