To The Editor: We were interested to read the article,“Association of Toxic Shock Syndrome Toxin-Secreting and Exfoliative Toxin-Secreting Staphylococcus aureus with Kawasaki Syndrome Complicated by Coronary Artery Disease” in Pediatric Research 1997;42:268-272. These authors remain the only group ever to report that Kawasaki syndrome (KS) is associated with toxic shock syndrome toxin-1(TSST-1)-producing Staphylococcus aureus(1). The idea that staphylococci or streptococci might be related to KS is not a new one; two studies of outbreaks of KS in the United States more than 15 years ago examined this issue and concluded that no relationship existed(2, 3). Since Leung and colleagues's initial report(1), several other groups have tried to reproduce their findings, without success(4–6), including one international multicenter study(4). Leung and colleagues have for several years claimed that their isolated S. aureus is somewhat less hemolytic and more white than other S. aureus isolates, including at the 5th International Kawasaki Disease Symposium in Fukuoka, Japan, May 1995. It is telling that no other group of investigators has been able to reproduce this finding. It is highly unlikely that others are unable to perform appropriate cultures for S. aureus; the more likely explanation is that TSST-1-producing staphylococci are not in fact associated with KS.

In the current article, isolates of S. aureus from mucosal sites of each of three children who had KS with coronary artery abnormalities were studied by the investigators. No information was given regarding the total number of Kawasaki patients at these institutions, or the percent of such patients who had TSST-1-producing S. aureus at mucosal sites. No controls from these institutions were provided; one would expect that many normal children also harbor this common organism at mucosal sites. That at least two of the reported patients had recent hospitalizations and courses of antibiotic therapy clearly would be expected to increase their likelihood of S. aureus colonization. Obviously, there is a marked selection bias in these three Kawasaki children. One could surely recover a variety of other bacteria from mucosal sites of three KS children with aneurysms, and one could surely identify three patients colonized with S. aureus who have, for example, pneumococcal meningitis, leukemia, or any other disorder. Thus, the authors' statement that, “In the current study, we demonstrate for the first time that acute KS complicated by coronary artery abnormalities is associated with infection and/or colonization by superantigen-producing S. aureus” is not supported by the current study; no association or causation can be inferred between KS and S. aureus from this study. We believe that such a statement without supportive data and without proper controls should not stand unchallenged.

Many etiologic agents have been proposed to be related to KS, but none has been confirmed with additional study. We believe that this is also the case with the TSST-1 hypothesis, which has not been confirmed by other groups. Although one could speculate that the inability to identify a single agent consistently associated with KS implies multiple possible etiologic agents, it is equally likely that the etiologic agent has simply not yet been identified. Whether Vβ-T cell receptor skewing occurs in acute KS is quite controversial(7). However, if present, it does not constitute sufficient evidence that TSST-1 causes KS. Confirmation of such an association has been sought by numerous investigators in the United States and Japan without success(4–6).

To suggest trials of antibacterial therapy based upon these data are inappropriate. Clinicians who care for Kawasaki patients regularly know that many KS patients have been given a variety of antistaphylococcal therapies without any effect, particularly KS patients in whom the diagnosis is delayed because a clinician initially has attributed cervical lymph gland swelling to staphylococcal or streptococcal cervical adenitis(8).

Sincerely,

Anne H. Rowley, M.D.

Associate Professor of Pediatrics and of Microbiology and Immunology; Section Head, Pediatric Infectious Diseases; Loyola University Medical Center

Stanford T. Shulman, M.D.

Professor of Pediatrics and Associate Dean for Academic Affairs; Northwestern University Medical School; Head, Division of Infectious Diseases; The Children's Memorial Hospital