Rheumatic fever pathogenesis: Approach in research needs change

Area of Science:

• Immunology
• Cardiology
• Pathology

Background:

• Rheumatic fever (RF) follows group-A streptococcal infection, but its pathogenesis is unclear.
• RF is incorrectly believed to cause pancarditis and myocarditis.
• Current research targeting myosin for myocarditis has been unsuccessful for decades.

Purpose of the Study:

• To re-evaluate the primary site of cardiac damage in rheumatic fever.
• To determine if RF is a connective tissue disorder or an endothelial disease.
• To redirect research efforts toward the valvular endothelium for understanding RF pathogenesis.

Main Methods:

• Histopathological evaluation of cardiac tissue.
• Immunopathological analysis.
• Review of existing research on RF and myocarditis.

Main Results:

• Rheumatic fever causes permanent damage to heart valves, particularly the mitral valve.
• The left ventricle's myocardium and intermyocardial connective tissues are not involved in RF.
• Evidence points to valvular and vascular endothelium as the primary site of RF damage.

Conclusions:

• Rheumatic fever is a disease of the valvular and vascular endothelium.
• RF is not a connective tissue disorder.
• Future research into RF pathogenesis should focus on the valvular endothelium.