Alternative Hypothesis to Explain Disease Progression in Rheumatic Heart Disease

There is nothing more deceptive than an obvious fact. — Sir Arthur Conan Doyle, The Boscombe Valley Mystery Acute rheumatic fever (ARF) is the result of an immunologic reaction after group A streptococcal (GAS) pharyngitis. The precise pathogenic mechanisms causing valve involvement in ARF are not known. The dominant theory suggests that in susceptible individuals, specific strains of GAS trigger the formation of autoantibodies to host tissues (including the heart) through molecular mimicry, causing valve damage. Cumulative injury from recurrences of ARF (attributable to recurrent GAS infections) is believed to result in the permanent valve lesions characteristic of rheumatic heart disease (RHD). On the basis of this premise, long-term penicillin prophylaxis to prevent GAS infections remains the cornerstone of control efforts. This approach is supported by strong biological plausibility, but at present no good-quality evidence exists from either randomized trials or observational studies to indicate that secondary prophylaxis reduces disease progression. Whereas secondary prophylaxis remains an important public health measure for reducing RHD burden, additional mechanisms behind disease initiation and progression may be at play, and understanding these may yield novel therapeutic approaches.