Rheumatic fever pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Lance Christiansen, D.O.; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Anthony Gallo, B.S. [3]

Rheumatic fever is the result of an autoimmunological sequela to a virulent Streptococcus pyogenes infection in a patient who was immunologically sensitized from prior infections. During a streptococcal infection, activated antigen-presenting cells, such as macrophages, present the bacterial antigen to helper T cells. Helper T cells subsequently activate B cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies also act against the myocardium and joints, producing the symptoms of rheumatic fever.

• Rheumatic fever is the result of an autoimmunological sequelae to a virulent Streptococcus pyogenes infection in a patient who was immunologically sensitized from prior infections, affecting periarteriolar connective tissue.
• During a streptococcal infection, activated antigen-presenting cells, such as macrophages, present the bacterial antigen to helper T cells.
  • Helper T cells subsequently activate B cells and induce the production of antibodies against the cell wall of Streptococcus.
• However the antibodies may also act against the myocardium and joints, producing the symptoms of rheumatic fever.
  • Contrary to the immunological protection developed during most infections, infections by Streptococcus pyogenes cause both a protective immunological and pathological autoimmunological stimulation.
  • Repeated infections by Streptococcus pyogenes will cause both a heightened protective and pathological immune response

• Lesions may occur in endocardium, myocardium, or pericardium.
  • The inflammation may cause serofibrinous pericardial exudates described as “bread-and-butter” pericarditis, which usually resolves without sequelae.
• Involvement of the endocardium typically results in fibrinoid necrosis and verrucae formation along the lines of closure of the heart valves.
  • These warty projections and irregular thickenings are known as MacCallum plaques.^[1]

• Lesions may occur in the mitral valve.
• Valve thickening may result in stenosis or regurgitation.

On gross pathology, the following are characteristic findings of rheumatic fever:^[2]

• “Fish-mouth appearance”
  • Slit-like morphology; elliptical cross-sectional flow area (mitral valve) with abnormally small semi-minor axis
• Significant valvular thickening
• Thickening and shortening of the chorda tympani

On microscopic histopathological analysis, the following are characteristic findings of rheumatic fever:^[2][3]

• Caterpillar cells
  • Abundant eosinophilic cytoplasm
  • Moderately-poorly defined cell border
  • Well-defined central ovoid nucleus with a prominent wavy ribbon-like chromatin
• Aschoff bodies found within the heart
  • Jumbled, eosinophilic collagen
  • Surrounded by T cells

The following are gross and microscopic images associated with rheumatic fever:^[4]

• 
  Aortic stenosis (Tricuspid aorta): gross, an example of aortic stenosis due to rheumatic fever.
• 
  Mitral scarring: gross, an example of mitral scarring due to rheumatic fever (healing phase of an infectious lesion).
• 
  Rheumatic mitral valvulitis: gross, an example of fibrosis, chorda thickening and shortening with thrombus around the large left atrium.
• 
  Rheumatic mitral valvulitis: gross, an example of acute rheumatic fever lesion along line of closure of mitral valve.
• 
  Mitral valve: gross, acute rheumatic fever.
• 
  Aschoff bodies: microscopic histopathological analysis, Aschoff bodies in rheumatic heart disease.