Rheumatic fever (RF) is an autoimmune disorder that remains incompletely characterized with regard to its basic elements—cause, pathophysiology, diagnosis, and treatment—despite evidence of its existence dating to at least the 1600s. The classic understanding that the disease is a post–suppurative streptococcal pharyngitis cascade, leading variably to arthritis, chorea, dermal manifestations, and, most important, carditis, has largely withstood challenge. Immunologic studies have confirmed the presence of epitopes on the bacterial surface that mimic cardiac myosin as well as antigens found in valve, skin, joint, and brain tissue that account for the …