Rheumatic fever in the 21st century.

In the first half of the twentieth century, the group A streptococcus (GAS) was established as the sole etiologic agent of acute rheumatic fever (ARF). In the century's latter half, the clinical importance of variation in the virulence of strains of GAS has become clearer. Although still obscure, the pathogenesis of ARF requires primary infection of the throat by highly virulent GAS strains. These contain very large hyaluronate capsules and M protein molecules. The latter contain epitopes that are cross-reactive with host tissues and also contain superantigenic toxic moieties. In settings where ARF has become rare, GAS pharyngitis continues to be common, although it is caused by GAS strains of relatively lower virulence. These strains, however, colonize the throat avidly and stubbornly. Molecularly distinct pyoderma strains may cause acute glomerulonephritis, but they are not rheumatogenic, even though they may secondarily colonize and infect the throat. Guidelines for the diagnosis, treatment, and prevention of GAS pharyngitis and ARF are reviewed with particular reference to the prevalence of the latter in the community.