Acute rheumatic fever (ARF) is a multisystem disease that occurs in people previously affected with streptococcal (group A) sore throat, as a result of an autoimmune reaction. Although ARF may involve many parts of the body, almost all the manifestations resolve completely; except the cardiac valvular damage, which is called as rheumatic heart disease (RHD).

Group A Streptococcus (S. pyogenes) principally causes infections of skin and soft tissues and is discussed in Chapter 52.

Pathogenesis

 Primary ARF is mainly a disease of children age 5–14 years, and it is rare in persons aged more than 30 years. However, recurrent episodes of ARF is more common in adolescents and young adults. There is no clear gender association for ARF, but RHD more commonly affects females.

ARF results following upper respiratory tract infection with group A streptococci (usually by M-serotypes 1, 3, 5, 6, 14, 18, 19, 24, 27, and 29). Genetic predisposition may play a role; people with HLA-DR7 and HLA-DR4 appear to be more susceptible as compared to others. Pathogenesis is unclear. It may be due to:

- Autoimmune theory: Pathogenesis is based on theory of molecular mimicry—the antibodies targeted against streptococcal antigens (M protein) cross react with human tissue antigens (e.g. heart and joint). These cross reactive antibodies bind to valvular endothelium, leading to damage of the heart valves

- Cytotoxic theory: Streptococcal toxins (e.g. streptococcal pyrogenic toxin) and enzymes (streptolysin O) are directly toxic to human heart.

clinical Manifestations

 The clinical manifestations usually appear after period of ~3 weeks following precipitating group A streptococcal infection. The prior streptococcal infection may be either subclinical (more common) or presents as sore throat.

Acute rheumatic fever affects heart, joints, skin and brain. The common manifestations in the order of frequency include:

- Migrating polyarthritis: It is the most common manifestation, characterized by migratory polyarthritis (hot, swollen, red, and/or tender joints), which moves from one joint to another over a period of hours. It is asymmetric and affects the large joints—most commonly the knees, ankles, hips, and elbows

- Pancarditis, affecting endocardium, pericardium, or myocardium

* Valvular damage is the hallmark; leading to mitral regurgitation (most common) and aortic regurgitation

* Myocardial inflammation may affect electrical conduction pathways, leading to P-R interval prolongation.

- Subcutaneous nodules: Occur as painless, small, mobile lumps beneath the skin overlying bony prominences, particularly of the hands, feet, and elbows

- Chorea (Sydenham’s): It is an abnormal involuntary movement disorder, mainly affecting head and limbs

- Erythema marginatum: They are pink macular rashes that appear and disappear before the examiner’s eyes.

diagnosis of arf (Jones criteria)

 The diagnosis of ARF is made based on diagnostic criteria known as revised Jones criteria (2015). It is based on the presence of a combination of typical clinical features together with ECG and laboratory (ESR, CRP) findings (Table 1).

Table1. Diagnostic criteria for rheumatic fever—modified Jones criteria (2015).

Supportive evidence (of previous group A streptococcal infection within the last 45 days) was a part of the previous version of Jones criteria (1992); which was diagnosed by detection of one of the following:

- Elevated ASO titre—which will be much higher in patients with ARF than that seen in patients with GAS infections without ARF

- A positive throat culture

- Rapid antigen test for GAS

- Recent scarlet fever.

Prevention

Primary Prevention

 It includes timely and complete treatment of group A streptococcal sore throat with antibiotics (penicillin) within 9 days of sore throat onset, which will prevent almost all cases of ARF.

Secondary Prevention

The mainstay of controlling ARF and RHD is secondary prevention. Patients with ARF are at much higher risk of developing recurrent ARF. Therefore, long-term penicillin prophylaxis is indicated to prevent recurrences. The drug of choice for secondary prophylaxis is intramuscular benzathine penicillin G given every 4 weeks. In case of penicillin allergy, erythromycin (250 mg, twice a day) can be given as an alternative. The duration depends upon underlying carditis.

- ARF without carditis: For 5 years after the last attack or 21 years of age (whichever is longer)

- ARF with carditis but no residual valvular disease: For 10 years after the last attack, or 21 years of age (whichever is longer)

- ARF with persistent valvular disease: For 10 years after the last attack, or 40 years of age (whichever is longer) or sometimes lifelong prophylaxis.

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