Rheumatic Fever

A 10-year-old boy presents with fever, migratory joint pain, and a new heart murmur 3 weeks after having a sore throat. His ECG shows a prolonged PR interval.

Pathophysiology

Rheumatic fever is an inflammatory disease that occurs as a delayed immune response to infection with Group A beta-haemolytic Streptococcus (GABHS), also known as Streptococcus pyogenes. The immune system, having produced antibodies against the M-protein in the call wall of GABHS cross-reacts with the body's own tissues due to molecular mimicry. This immune reaction affects various tissues, including the heart, joints, skin, and central nervous system.

The heart is the most seriously affected organ in rheumatic fever, with inflammation affecting all layers (pancarditis). Acute rheumatic fever can cause valvulitis, leading to valve thickening, scarring, and dysfunction, most commonly affecting the mitral valve.

Histologically, Aschoff bodies are characteristic findings in rheumatic heart disease.

Aetiology

The sole cause of rheumatic fever is infection with GABHS. This typically involves the pharynx (pharyngitis) but can also be a skin infection.

Epidemiology & Risk Factors

While rheumatic fever remains a significant health concern in developing countries, its incidence has dramatically declined in developed countries due to improved hygiene and access to healthcare.

• Peak incidence: 5-15 years of age
• Recurrence: Tends to recur unless prevented
• Susceptibility: Affects approximately 2% of those infected with GABHS

Risk factors:

• Age: Most commonly affects children aged 5-15 years.
• Socioeconomic factors: Overcrowding and poor living conditions increase the risk of GABHS transmission.
• Genetic predisposition: Certain HLA types are linked to an increased risk of developing rheumatic fever.

Clinical Features

The clinical presentation of rheumatic fever is highly variable and can range from mild to severe. The diagnosis is based on the Revised Jones Criteria, which require evidence of a preceding GABHS infection and the presence of either 2 major criteria or 1 major and 2 minor criteria.

Evidence of preceding GABHS infection:

• Positive throat culture or rapid streptococcal antigen test.
• Elevated or rising streptococcal antibody titre (antistreptolysin O or DNase B).
• Recent scarlet fever.

Major criteria:

• Carditis: Inflammation of the heart, manifested as pericarditis, myocarditis, or endocarditis. It can present with pleuritic chest pain, shortness of breath, heart murmurs, and arrhythmias.
  • A Carey-Coombes murmur, a mid-diastolic murmur of left ventricle filling across an acutely inflamed mitral valve, may be present.
  • Other common valvular pathology includes mitral regurgitation (acute), mitral stenosis (chronic) and aortic regurgitation.
• Arthritis: Migratory oligo- or poly-arthritis affecting large joints, typically the knees, ankles, elbows and wrists. The pain and swelling typically last a few days in each joint and then move to another joint.
• Chorea: Sydenham's chorea is characterised by involuntary, jerky movements, emotional lability and muscle weakness. It can occur weeks or months after the initial infection.
• Erythema marginatum: A distinctive, non-pruritic rash with pink, ring-shaped lesions that appear on the trunk and limbs but spare the face. The rash is transient and can fade and reappear within hours.
• Subcutaneous nodules: Painless, firm rheumatoid nodules that develop over bony prominences and tendons. These nodules are less common and usually occur in patients with carditis.

Minor criteria:

• Fever: A temperature of 38.5°C or higher
• Arthralgia: Joint pain without swelling.
• Elevated ESR or CRP.
• Prolonged PR interval on ECG: A sign of heart block, indicating inflammation of the heart's conduction system.
• Previous rheumatic fever or rheumatic heart disease: Increases the likelihood of recurrence.

Investigations

Investigations are essential to confirm the diagnosis of rheumatic fever and assess the extent of cardiac involvement.

• Throat swab: To culture for GABHS.
• ASO titre: Measures antibodies against streptolysin O, an enzyme produced by GABHS. A rising titre indicates a recent infection.
• DNase B titre: Measures antibodies against DNase B, another enzyme produced by GABHS.
• ESR and CRP.
• ECG: Can detect a prolonged PR interval and other arrhythmias.
• Echocardiogram: Assesses heart function, valve morphology and the presence of pericardial effusion.

Management

The management of rheumatic fever focuses on eradicating GABHS infection, controlling inflammation, and preventing long-term complications, particularly rheumatic heart disease.

Medical management:

• Antibiotics: Penicillin remains the mainstay of treatment for eradicating GABHS.
  • Benzyl penicillin G: A single intramuscular injection is typically effective.
  • Oral penicillin: prescribed for 10 days.
• Anti-inflammatory medications:
  • Aspirin or NSAIDs: Used to relieve joint pain and inflammation.
  • Corticosteroids: Prednisolone may be added for severe carditis or heart failure.
• Management of Sydenham's Chorea:
  • Haloperidol or Diazepam

Lifestyle management:

• Rest: Adequate rest is essential during the acute phase of illness.
• Activity restriction: Strenuous activities should be avoided until inflammation subsides and cardiac function is assessed.

Surgical management:

Valve replacement or repair may be necessary for individuals who develop severe valvular heart disease as a complication of rheumatic fever.

Prophylaxis:

Secondary prophylaxis with antibiotics is crucial to prevent recurrent GABHS infections and subsequent episodes of rheumatic fever. The duration of prophylaxis depends on the severity of cardiac involvement:

• Without carditis: 5 years or until age 18 years, whichever is longer.
• With mild carditis or mitral regurgitation: 10 years or until age 21 years, whichever is longer.
• With chronic carditis, severe valvular heart disease or after valve surgery: Lifelong prophylaxis.

Complications & Prognosis

The most serious complication of rheumatic fever is rheumatic heart disease, which can lead to:

• Valvular stenosis: Mitral stenosis is the most common valvular lesion.
• Valvular regurgitation: Leakage of blood back through the valve, reducing the heart's pumping efficiency.
• Heart failure.
• Arrhythmias: Including atrial fibrillation.

The prognosis for rheumatic fever varies depending on the severity of cardiac involvement.

• Without carditis: Most individuals recover fully.
• With carditis: The risk of developing chronic rheumatic heart disease is significant, particularly with recurrent episodes.
• Early diagnosis and treatment: Significantly reduce the risk of long-term complications.