Major criteria
Joint manifestations are the unique clinical signs that have different implications for different population-risk categories : Only polyarthritis (a temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards) is considered as a major criterion in low-risk populations, whereas monoarthritis, polyarthritis and polyarthralgia (joint pain without swelling) are all included as major criteria in high-risk populations. Carditis: Carditis can involve the pericardium (pericarditis which resolves without sequelae), some regions of the myocardium (which might not provoke systolic dysfunction), and more consistently the endocardium in the form of valvulitis. Carditis is diagnosed clinically (palpitations, shortness of breath, heart failure, or a new heart murmur) or by echocardiography/Doppler studies revealing mitral or aortic valvulitis. Both of clinical and subclinical carditis are now considered a major criterion. Subcutaneous nodules: Painless, firm collections of collagen fibers over bones or tendons. They commonly appear on the back of the wrist, the outside elbow, and the front of the knees. Erythema marginatum: A long-lasting reddish rash that begins on the trunk or arms as macules, which spread outward and clear in the middle to form rings, which continue to spread and coalesce with other rings, ultimately taking on a snake-like appearance. This rash typically spares the face and is made worse with heat. Sydenhams chorea (St. Vitus dance): A characteristic series of involuntary rapid movements of the face and arms. This can occur very late in the disease for at least three months from onset of infection.
The pathogenesis of RHD is complex and not fully understood, but it is known to involve molecular mimicry and genetic predisposition that lead to autoimmune reactions.Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as "foreign" due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD. Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration.While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6.