Probable role ofStreptococcus pyogenes in Kawasaki disease

Abstract

Over the past 25 years, the clinical course of Kawasaki disease has been defined, the prevalence and nature of the cardiovascular effects widely understood, and pathological changes in the most severe cases well described. However, the aetiology and pathogenesis of this puzzling disease have remained unclear, thus specific therapy is not yet available. Because of some close clinical similarities between this disease and streptococcal scarlet fever, particular attention has been paid to the possible role of Streptococcus pyogenes as an aetiological agent in this illness. Until now, however, group A beta-haemolytic streptococci have never been consistently isolated from any patients; in addition, the titre of anti-streptolysin 0 is not raised, and lack of response to antibiotics is a feature of this disease. Our long series of investigations over more than 10 years, which will be covered in the present review, were performed in an attempt at elucidating causative agent(s) of Kawasaki disease. This has led to our firm belief in the probable role of S. pyogenes in the pathogenesis of this disease, despite the lack of fulfillment of Koch's postulates, on the basis of the following findings. Patients with Kawasaki disease recovering from the acute, febrile phase of the illness exhibited an exaggerated cell-mediated reactivity, as measured by the macrophage migration inhibition test, to group A beta-haemolytic streptococci, their pyrogenic exotoxin and streptolysin 0 as well as to several mammalian muscle cell extracts which are allegedly related antigenically to the cell wall and/or cytoplasmic membrane of S. pyogenes. Protoplast-like "spherical bodies" varying in diameter from 0.5 to 1.5 microns, and devoid of cell walls, were detected in the buffy coats of peripheral blood from patients with this disease, and stained distinctly by immuno-electron microscopy using, as a primary antibody, a rabbit antiserum to S. pyogenes- derived protoplasts, and followed by absorption with protoplasts from Staphylococcus aureus and Escherichia coli. Newborn mice infected with S. pyogenes having no capacity to confer cell-mediated immunity even in adult murine hosts, and reinfected 4-6 weeks later with another strain of the same species of bacteria which is able to elicit cellular immunity, showed a lack of humoral response to streptococcal antigens, leaving intact cell-mediated immunity. Such a biased immunological characteristic is an exact counterpart of that of Kawasaki disease patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Kawasaki disease shock syndrome: Unique and severe subtype of Kawasaki disease

“…55,56 The opposite, however, has occurred in pediatric patients, in that patients are often initially diagnosed with TSS and then diagnosed with KDSS when coronary abnormalities are found. There are numerous reports of Streptococcus and Staphylococcus in KD patients: [57][58][59][60][61][62][63][64][65][66] Benseler et al reported concomitant infections in 33% of 129 patients with KD, and 16 patients presented with Streptococcus-positive tonsillitis. 63 Streptococcus and Staphylococcus infections have also been reported in KDSS patients.…”

Epidemiology, Etiology, and Management of Kawasaki Disease: State of the Art

“…However, Terai et al [92] and Nishiori et al [72] measured serum TSST-1 in acute Kawasaki disease cases and found 2 of 26 and 1 of 18 positive compared to 1 of 22 and 0 of 12 control patients, thus not supporting the evidence for TSST-1 as the cause of Kawasaki disease. The exact toxin responsible for streptococcal toxic shock has not been defined, but the streptococcal pyrogenic exotoxins function as superantigens and have been postulated to be the etiologic agents in Kawasaki disease although a causal relationship has not been demonstrated [5,96]. An important link between the toxic shock syndromes and Kawasaki disease is the common response to IVIG.…”

Vasculitis and Anaphylactoid Shock Induced in Mice by Cell Wall Extract of the Fungus Candida metapsilosis

“…Currently, the etiology of KS is largely unknown. However, many recent studies reported that KS might be triggered by a response to infectious agents, e.g., fungi, bacteria, and viruses (Akiyama and Yashiro 1993;Esper et al, 2005;Wang et al, 2005). Moreover, invasive Candida infection in neonates can cause mycetoma of the right atrium and candidal endocarditis (Levy et al, 2006).…”