Despite the depth of knowledge that has been accumulated about the molecular microbiology of Streptococcus pyogenes, the pathogenesis of ARF remains unknown. A direct effect of a streptococcal extracellular toxin, in particular streptolysin O, may be responsible for the pathogenesis of ARF, according to some hypotheses. Observations that streptolysin O is cardiotoxic in animal models support this hypothesis, but linking this toxicity to the valvular damage observed in ARF has been difficult.
A more popular hypothesis is that an abnormal host immune response to some component of the group A Streptococcus is responsible. The M protein of GAS shares certain amino acid sequences with some human tissues, and this has been proposed as a source of cross-reactivity between the organism and human host that could lead to an immunopathologic immune response. Also, antigenic similarity between the group-specific polysaccharide of S pyogenes and glycoproteins found in human and bovine cardiac valves has been recognized, and patients with ARF have prolonged persistence of these antibodies compared with controls with uncomplicated pharyngitis. Other GAS antigens appear to cross-react with cardiac sarcolemma membranes. [16]
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Invasive soft tissue infection due to Streptococcus pyogenes. This child developed fever and soft-tissue swelling on the fifth day of a varicella-zoster infection. Leading edge aspirate of cellulitis grew S pyogenes. Although the patient responded to intravenous penicillin and clindamycin, operative débridement was necessary because of clinical suspicion of early necrotizing fasciitis.
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Streptococcus group A infections. Beta hemolysis is demonstrated on blood agar media.
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Streptococcus group A infections. M protein.
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Streptococcus group A infections. Erysipelas is a group A streptococcal infection of skin and subcutaneous tissue.
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Streptococcus group A infections. White strawberry tongue observed in streptococcal pharyngitis. Image courtesy of J. Bashera.
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Streptococcus group A infections. Streptococcal rash. Image courtesy of J. Bashera.
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Group A Streptococcus on Gram stain of blood isolated from a patient who developed toxic shock syndrome.
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Streptococcus group A infections. Necrotizing fasciitis of the left hand in a patient who had severe pain in the affected area.
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Streptococcus group A infections. Patient who had had necrotizing fasciitis of the left hand and severe pain in the affected area (from Image 8). This photo was taken at a later date, and the wound is healing. The patient required skin grafting.
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Streptococcus group A infections. Gangrenous streptococcal cellulitis in a patient with diabetes.
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Erythema secondary to group A streptococcal cellulitis.
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Invasive soft tissue infection due to Streptococcus pyogenes. This child developed fever and soft-tissue swelling on the fifth day of a varicella-zoster infection. Leading edge aspirate of cellulitis grew S pyogenes. Although the patient responded to intravenous penicillin and clindamycin, operative débridement was necessary because of clinical suspicion of early necrotizing fasciitis.
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Streptococcus group A infections. Necrotizing fasciitis rapidly progresses from erythema to bullae formation and necrosis of skin and subcutaneous tissue.
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Throat swab. Video courtesy of Therese Canares, MD; Marleny Franco, MD; and Jonathan Valente, MD (Rhode Island Hospital, Brown University).
