ISRAA UNIVERSITY COLLEGE

Department of dentistry

Pathogenesis of Acute Rheumatic Fever (ARF)

Submitted By
‫حسن علي نبأ‬
4th stage/Group D

Supervised By
Dr.Modni Abdulmajeed

July 2020
Introduction
ARF is a multiorgan inflammatory disorder affecting the heart (carditis), joints
(arthritis and arthralgia), brain (Sydneham's chorea), skin (erythema marginatum),
and subcutaneous tissue (subcutaneous nodules) (Figure.1). Rheumatic heart disease
(RHD) is characterized by typical heart valve lesions, classified clinically as
regurgitation and stenosis, and histopathologically by the presence of
pathognomonic granulomatous Aschoff bodies. It is well established that ARF
follows infection with group A Streptococcus (GAS), otherwise known as
Streptococcus pyogenes, through an inflammatory process in susceptible
individuals, and that RHD occurs as a result of a severe initial or multiple episodes
of ARF. Researchers have attempted to unravel the inflammatory basis of the
pathogenesis of ARF, focusing on humoral and cellular immune responses with
molecular mimicry as the central mediator of cross-reactivity with GAS. Molecular
mimicry is where a foreign antigen shares
sequence or structural similarities with self-
antigens." Many questions remain, including
whether skin infection can trigger ARF,
whether groups C and G streptococci might
also lead to the disease, and whether there is a
genetic basis to susceptibility to ARF.
(Figure.1)Rheumatic fever‐pathogenesis
Epidemiology

• Age: 5-15 yrs, rare <3 yrs • Incidence:

• Girls>boys - related to frequency and severity of

Streptococcal pharyngeal infection
• Common in 3rd world countries - more during winter & early spring

- environmental factors- poor sanitation,

poverty, overcrowding : greater spread of
infection, following epidemics of Strep
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pharyngitis.
Pathophysiology

Rheumatic fever develops in children and adolescents following pharyngitis with

GABHS (ie, Streptococcus pyogenes). (Figure.2)

 The organisms attach to the epithelial cells of the upper

(Figure.2)Streptococcus
respiratory tract and produce a battery of enzymes, which pyogenes bacteria
(Pappenheim’s stain)
allows them to damage and invade human tissues.
 After an incubation period of 2-4 days, the invading organisms elicit an acute
inflammatory response, with 3-5 days of sore throat, fever, malaise, headache, and
elevated leukocyte count.
 In a small percentage of patients, infection leads to rheumatic fever several
weeks after a sore throat has resolved; only infections of the pharynx have been
shown to initiate or reactivate rheumatic fever.
 Direct contact with oral (PO) or respiratory secretions transmits the organism,
and crowding enhances transmission; patients remain infected for weeks after
symptomatic resolution of pharyngitis and may serve as a reservoir for infecting
others. Severe scarring of the valves develops during a period of months to years
after an episode of acute rheumatic fever, and recurrent episodes may cause
progressive damage to the valves.

The mitral valve is affected most commonly and severely (65-70% of patients); the
aortic valve is affected second most commonly (25%).

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Etiopathogenesis‐ Immunological evidence

• Symptoms occur after 2-3 weeks of infection

• Organism cannot be isolated from the lesions in target tissues

• Antibodies against M-proteins of Strep cross react with glycoproteins in the heart,
joints and other tissues

• Patients with RF have elevated titres of anti-streptolysin O and S,

antistreptokinase, antistreptohyaluronidase and anti-DNAase B Antibodies against
cell wall polysaccharide of group A streptococcus: cross reactive against cardiac
valves and their levels are elevated in patients with cardiac valvular involvement

Antibodies against Hyaluronate capsule: cross reactive against the human

hyaluronate present in the joints

• Membrane antigens: cross react with smooth and cardiac muscle, dermal
fiberoblasts and neurons of caudate nucleus.

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REFERENCES

 Acute rheumatic fever and rheumatic heart disease Dougherty, Carapetis, &
Wilson - Elsevier – 2019.
 Carapetis JR, Beaton A, Cunningham MW, et al. Acute rheumatic fever and
rheumatic heart disease. Nature Reviews Disease Primers. 2016;2:15084.
 Bisno AL Acute pharyngitis. N Engl
(Figure.3) J Med. 2001;344(3):205-211
pathogenesis of ARF
 Wannamaker LW. The chain that links the throat to the heart. Circulation.
1973;48:9--18.
 Cunningham MW. Molecular Mimicry, Autoimmunity and Infection: The
Cross-Reactive Antigens of Group A Streptococci and Their Sequelae. 2nd ed.
American Society for Microbiology Press; 2018.
 Sikder S, Williams NL, Sorenson AE, et al. Group G streptococcus induces an
autoimmune IL-17A/IFN-gamma

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