Acute rheumatic fever (ARF)
ARF occurs within 10 days to six weeks after an episode of GAS pharyngitis, although the causative infection may be subclinical. It occurs as a nonsuppurative complication of GAS pharyngitis in susceptible hosts. While the underlying mechanisms of ARF are not well understood, the key event is inappropriate activation of the immune system, leading to autoimmune attack.
Invading pathogens trigger innate immune responses, leading to inflammation. During the inflammatory response, immune cells are attracted to the site of infection and are exposed to antigenic compounds. Antigenic compounds in GAS infections include the M-protein, hyaluronic acid coat and exotoxins.
The presentation of an antigen to the cells of the immune system (Tlymphocytes) is mediated by the human leucocyte antigen (HLA) system and leads to the production of antibodies and memory cells. HLA genes are subject to variation: the incidence of ARF is associated with certain types of HLA complexes. GAS antigens, in particular M-protein, associated with HLA, mimic protein complexes of host tissues and trigger cross-reactivity. The antibodies produced against GAS begin to attack host tissues. (7)
GAS M-protein antigens mimic myosin found in cardiac muscle and other types of extracellular proteins. This causes an immune attack against cardiac, subcutaneous and central nervous tissues and the joints. Infiltration of T-lymphocytes and macrophages leads to pain and inflammation, with subsequent fibrosis and scarring. It is important to note there are no bacteria present in these inflammation sites.
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Diagnosis is based on the modified Jones criteria. The presence of two major symptoms, or one major and two minor, are required to diagnose ARF. (13)