Chapter 57: Acute Rheumatic Fever

BACKGROUND

Acute rheumatic fever (ARF) is an inflammatory condition manifested by the nonsuppurative sequelae of a preceding group A β-hemolytic streptococcal (GAS) pharyngitis. ARF involves the heart, central nervous system, joints, and skin and is the most common cause of acquired heart disease in many regions of the world. Historically, the relationship between streptococci and rheumatic fever was not evident; however, investigation over the past several decades has shown that only GAS infections are associated with ARF. Diagnosis of the disease relies on the identification of major and minor criteria that include clinical observations and laboratory data, an approach that has been modified occasionally since its introduction in 1944 by Jones.¹ The greatest impact of the illness lies in its potential to cause progressive valvular heart disease, which is more likely with recurrent episodes of ARF. Antibiotic prophylaxis is therefore important to minimize the likelihood of recurrent GAS pharyngitis.

EPIDEMIOLOGY

It is well accepted that the frequency of ARF has declined in part because of the use of antibiotics to treat pharyngitis. Investigations have shown that appropriate antimicrobial therapy has led to fewer episodes of ARF in the United States,^2-4 although the prevalence remains high in many parts of the world, especially in crowded populations of lower socioeconomic status.^5,6 Nevertheless, sporadic outbreaks have been identified in the United States among populations not thought to be at risk for such events.^7-11 Given the frequency of ARF as well as the clinical presentation among different populations, the Jones Criteria was modified recently to define the two populations more precisely.¹²

PATHOPHYSIOLOGY

Only GAS pharyngitis is rheumatogenic,¹³ and certain types of group A streptococci predispose to the development of ARF, based on the virulence of the organism. Group A streptococci with high concentrations of M protein, a component of the cell wall, are believed to be the most virulent strains and therefore the most likely to cause ARF. These types of streptococci often form mucoid-appearing colonies in culture. The number of M serotype GAS infections decreased in association with a similar decline in the incidence of ARF.¹⁴

The actual pathogenetic mechanism by which GAS pharyngitis leads to ARF is still somewhat speculative. The organism adheres to the pharyngeal mucosa, with subsequent destruction of epithelial cells. The immune reaction to this interaction results in both a humoral and a cell-mediated response to streptococcal antigens of the cell membrane. These antigens mimic those of cardiac tissue, whereas M proteins have similar antigenicity to myosin and sarcolemma,^15,16 as well as cartilage and synovium.¹⁷ The cross-reactivity may result in damage to these target tissues. In addition, the GAS carbohydrate components mimic antigens of cardiac valves, a possible explanation for valvular involvement in ARF.¹⁸ Cell-mediated involvement in the pathogenesis is supported by the presence of CD⁴⁺ helper ...