What is the natural history and evaluation of Rheumatic (Acute Rheumatic) Fever?

From the Guidelines

Rheumatic fever is an inflammatory disease that develops as a delayed complication of untreated group A streptococcal pharyngitis, typically occurring 2-3 weeks after the initial infection, and its evaluation involves applying the Jones criteria, which includes major and minor manifestations, as well as laboratory tests and echocardiography to assess for valvular damage 1. The natural history of rheumatic fever begins with a streptococcal throat infection that triggers an abnormal immune response in genetically susceptible individuals, causing inflammation in various tissues including the heart, joints, skin, and central nervous system. The disease primarily affects children aged 5-15 years and is more common in developing countries with overcrowded living conditions. Some key points to consider in the evaluation of rheumatic fever include:

• The Jones criteria, which includes major manifestations (carditis, polyarthritis, chorea, erythema marginatum, and subcutaneous nodules) and minor manifestations (fever, arthralgia, elevated acute phase reactants, and prolonged PR interval on ECG) 1
• Diagnosis requires evidence of a preceding streptococcal infection plus either two major criteria or one major and two minor criteria
• Laboratory tests should include throat culture, anti-streptolysin O titers, C-reactive protein, and erythrocyte sedimentation rate
• Echocardiography is essential to assess for valvular damage, particularly mitral and aortic regurgitation Without proper treatment, rheumatic fever can lead to permanent heart valve damage (rheumatic heart disease), which may necessitate valve replacement later in life. The risk of recurrence is highest in the first 5 years after the initial episode, making preventive measures crucial during this period, and the recommended duration of secondary prophylaxis depends on the number of previous attacks, the time elapsed since the last attack, the risk of exposure to GAS infections, the age of the patient, and the presence or absence of cardiac involvement, with penicillin being the agent of choice for secondary prophylaxis 1. Some specific guidelines for secondary prophylaxis include:
• 10 years or until 40 years of age (whichever is longer) for patients with rheumatic fever with carditis and residual heart disease
• 10 years or until 21 years of age (whichever is longer) for patients with rheumatic fever with carditis but no residual heart disease
• 5 years or until 21 years of age (whichever is longer) for patients with rheumatic fever without carditis 1

From the FDA Drug Label

Prevention of Initial Attacks of Rheumatic Fever Penicillin is considered by the American Heart Association to be the drug of choice in the prevention of initial attacks of rheumatic fever (treatment of Streptococcus pyogenes infections of the upper respiratory tract e.g., tonsillitis, or pharyngitis). Erythromycin tablets are indicated for the treatment of penicillin-allergic patients. The therapeutic dose should be administered for ten days.

The natural history and evaluation of Rheumatic (Acute Rheumatic) Fever is not directly addressed in the provided drug labels. However, the prevention of initial attacks of rheumatic fever is mentioned, which involves the treatment of Streptococcus pyogenes infections with penicillin as the drug of choice, or erythromycin for penicillin-allergic patients, for a duration of ten days 2.

• Key points:
  • Penicillin is the preferred treatment for preventing initial attacks of rheumatic fever.
  • Erythromycin is an alternative for patients allergic to penicillin.
  • Treatment should be administered for ten days. However, the question of the natural history and evaluation of Rheumatic Fever remains unanswered as this information is not provided in the drug labels.

From the Research

Natural History of Rheumatic Fever

• Rheumatic fever (RF) is a non-suppurative, inflammatory sequela of group A Streptococcus pharyngitis that can occur at two to four weeks after infection 3
• The incidence of acute rheumatic fever (ARF) is 8 to 51 per 100,000 people worldwide, and it most commonly affects children 5 to 15 years of age after a group A streptococcal infection 4
• Overcrowding and poor socioeconomic conditions are directly proportional to the incidence of ARF 4
• Rheumatic carditis is a manifestation of ARF that may lead to rheumatic heart disease (RHD) 4

Evaluation of Rheumatic Fever

• ARF is diagnosed using the 2015 modified Jones criteria, and there is no gold standard laboratory test 4
• Clinicians need to be aware of the clinical signs and symptoms of ARF to include in their differential diagnosis when seeing such patients 4
• Diagnostic criteria for the disease were revised, and improving the capabilities of echocardiography can improve the prognosis of the disease through the early use of treatment and prevention 5
• The level of ORL / RHD correlates with the economic development of countries 5

Prevention and Treatment of Rheumatic Fever

• Timely treatment of group A streptococcal infection can prevent ARF, and penicillin prophylaxis can prevent recurrence of ARF 4
• Prevention of recurrent ARF is the most effective way to prevent RHD 4
• Secondary prophylaxis with benzathine penicillin G has been shown to decrease the incidence of RHD and is key to RHD control 4
• Antibiotic prophylaxis likely reduces the risk of recurrence of rheumatic fever compared to no antibiotics, and intramuscular benzathine benzylpenicillin is probably superior to oral antibiotics 3
• A 2-weekly regimen of benzathine penicillin G for rheumatic fever prophylaxis is more effective than a 4-weekly regimen in preventing recurrences of rheumatic fever 6
• Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections 7