What is rheumatic fever?

Rheumatic Fever: Definition, Pathophysiology, and Management

Rheumatic fever is an autoimmune inflammatory disease that occurs as a delayed sequela to group A β-hemolytic streptococcal (GAS) pharyngitis, potentially leading to rheumatic heart disease which remains the most common cardiovascular disease in young people under 25 years globally. 1

Pathophysiology

• Rheumatic fever begins with a GAS throat infection that triggers an abnormal autoimmune response in genetically susceptible individuals after a symptom-free interval of 14-21 days 2
• The immune response is directed against the M-protein serotypes of the GAS organism, which share structural similarities with human cardiac tissues, creating an autoimmune reaction 2
• After recovery from the initial episode of rheumatic fever, 60-65% of patients develop valvular heart disease (rheumatic heart disease) 1, 2
• Recurrent GAS infections can lead to progressive valve damage, which causes atrial fibrillation and heart failure as the disease advances 1

Clinical Manifestations

• Major manifestations include migratory polyarthritis, carditis, chorea, subcutaneous nodules, and erythema marginatum occurring in varying combinations 3
• Carditis primarily affects the mitral valve, with the anterior leaflet showing abnormal coaptation and regurgitation typically directed posterolaterally 2
• Aortic valve involvement is less common and rarely occurs in isolation 2
• As the disease progresses, valvular fibrosis and calcification lead to permanent structural changes characterized by progressive valvular stenosis and/or regurgitation 2

Diagnosis

• Diagnosis is entirely clinical, without any laboratory gold standard, based on the revised Jones criteria 2, 4
• Carditis can be clinical or subclinical, with echocardiography now playing an important role in diagnosis 5
• The diagnosis should be considered in patients with evidence of recent GAS infection followed by the characteristic clinical manifestations 1

Prevention

Primary Prevention

• Primary prevention is accomplished by proper identification and adequate antibiotic treatment of GAS pharyngitis 1
• Penicillin (either oral penicillin V or injectable benzathine penicillin) is the treatment of choice for GAS pharyngitis 1
• For penicillin-allergic individuals, acceptable alternatives include narrow-spectrum oral cephalosporins, oral clindamycin, or various macrolides/azalides 1

Secondary Prevention

• Individuals who have had an attack of rheumatic fever are at very high risk of recurrences after subsequent GAS pharyngitis and need continuous antimicrobial prophylaxis to prevent such recurrences. 1
• Benzathine penicillin G is the most effective agent for secondary prophylaxis: 1.2 million units IM every 4 weeks or 600,000 units every 2 weeks 6, 7
• Oral penicillin V is less effective than intramuscular benzathine penicillin G but may be used in some cases 8
• For penicillin-allergic patients, sulfadiazine, erythromycin, or other macrolides are acceptable alternatives 1

Duration of Secondary Prophylaxis

• For patients with rheumatic fever with carditis and residual heart disease: 10 years or until 40 years of age (whichever is longer), sometimes lifelong prophylaxis 1, 6
• For patients with rheumatic fever with carditis but no residual heart disease: 10 years or until 21 years of age (whichever is longer) 1, 6
• For patients with rheumatic fever without carditis: 5 years or until 21 years of age (whichever is longer) 1, 6

Treatment of Acute Episodes

• Anti-inflammatory agents provide dramatic clinical improvement but do not prevent the subsequent development of rheumatic heart disease 3
• The role of corticosteroids in treatment of carditis remains uncertain, as controlled studies have failed to demonstrate improved long-term prognosis 3
• Chorea may require more aggressive treatment, particularly with sedatives 3

Complications and Long-term Outcomes

• Long-term complications include atrial fibrillation, heart failure, stroke, infective endocarditis, and pregnancy-related complications 2
• Rheumatic heart disease remains the largest global cause of cardiovascular disease in young people under 25 years 8
• The disease disproportionately affects populations living in poverty and in overcrowded conditions 4

Important Considerations

• At least one-third of rheumatic fever cases result from asymptomatic GAS infections, making prevention challenging 6
• Even when GAS pharyngitis is treated optimally, rheumatic fever can still occur in susceptible individuals 6
• Continuous rather than episodic prophylaxis is essential as rheumatic fever can recur even with appropriate treatment 6
• Streptococcal infections in family members of patients with current or previous rheumatic fever should be treated promptly 1

Rheumatic fever remains a significant public health challenge, particularly in developing countries and resource-poor settings, requiring continued vigilance in prevention, early diagnosis, and long-term management to reduce morbidity and mortality 1, 4.