Staphylococcal Purpura Fulminans: A Toxin-Mediated Disease?
Henry F. Chambers
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Medical Service, San Francisco General Hospital, Department of Medicine, University of California-San Francisco
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Dramatic disease presentations create
strong impressions. Kravitz et al. [1]
describe 5 cases of purpura fulminansa
syndrome of sepsis, disseminated
intravascular coagulation, and purpuric skin
lesions [2]in association with
Staphylococcus aureus isolated from blood in 3
patients and from respiratory cultures in
the other 2 patients. All 5 patients had
either frank septic shock or severe sepsis
[3], at least 4 required pressor support,
and 3 died as a direct consequence of their
infections.
These cases occurred within a 4-year
period in the MinneapolisSt. Paul,
Minnesota, metropolitan area. The clinical
isolates produced 1 of 3 staphylococcal
superantigen toxins: staphylococcal
enterotoxin B (SEB; 1 strain), staphylococcal
enterotoxin C (SEC; 3 strains), and toxic
shock syndrome toxin1 (TSST-1; 1
strain). The 1 methicillin-resistant strain,
in addition to producing SEC, also had
the genes for Panton-Valentine leukocidin,
a hallmark of community strains of
methicillin-resistant S. aureus [4, 5]. The rarity
of S. aureusassociated purpura
fulminansplus the fact that all 5 strains
produced a superantigen that can cause a
septic or toxic shock by an inappropriately
massive release of cytokines from
macrophages and T cellsled the authors to
speculate that purpura fulminans may
represent a new and emerging
manifestation of severe staphylococcal disease.
Purpura fulminans is not a specific
diagnosis, but a syndrome. It is probably
caused by an inherited or acquired
abnormality of the protein C anticoagulant
pathway [2]. Most commonly, it is a
complication of severe bacterial infection
(typically meningococcemia), although
numerous noninfectious and infectious
agents also have been associated with it
[614]. Purpura fulminans complicating
staphylococcal sepsis has been reported
previously, and several case reports are
cited by Kravitz et al. [1]. In a study from
Finland of 12 cases of sepsis-associated
purpura fulminans, S. aureus was
responsible for 1 of the 10 cases in which a
bacterial infection was documented, with
Neisseria meningitides (5 cases),
Streptococcus pneumoniae (2 cases), and
Capnocytophaga canimorsus (2 cases) responsible
for the other 9 cases [15]. Thus, S. aureus
as a cause of purpura fulminans is new,
and it may be as common a cause as other
nonmeningococcal organisms.
Whether staphylococcal purpura
fulminans is emergingor, to be more
precise, increasing in prevalence or
incidenceis more difficult to assess, because
neither entity is reportable, and
surveillance data are unavailable. The absence of
this complication among 235 cases of
staphylococcal bacteremia reported in 2
publications [16, 17] cited by the authors
indicates that it is not common. But does
the occurrence of 5 cases over a 4-year
period represent an increase? It may not.
On the basis of the estimated 100,000
bacteremia cases per year, the incidence of
S. aureus bacteremia is 360 cases per
1,000,000 persons per year in the United
States. The MinneapolisSt. Paul
metropolitan area, with its population of
3,000,000, would be expected to have
slightly more than 4000 cases of
staphylococcal bacteremia in the 4-year period
during which these 5 cases were observed,
or 1 case of purpura fulminans per 800
cases of S. aureus bacteremia. Given this
case rate, it is not surprising that this
complication was not reported in case studies
that were both too small by an order of
magnitude to have detected it.
Regardless of whether staphylococcal
purpura fulminans is a new or emerging
problem, these 5 cases raise the intriguing
possibility that superantigen production
is the cause. Superantigen toxins certainly
can cause illness of a severity observed in
these cases, and the fact that, in each case,
a toxin-producing strain was isolated
seems compelling. However, this apparent
Genea
Vandenesch
et al.b [5]
Von Eiff
et al. [18]
Nashev
et al. [19]
Mehrotra
et al. [20]
Peacock
et al. [21]
Larsen
et al. [22]
NOTE. Data are percentage of isolates containing gene, unless otherwise indicated.
a seb, sec, tst, and lukFS-PV are genes encoding staphylococcal enterotoxin B, staphylococcal
enterotoxin C, toxic shock syndrome toxin1, and Panton-Valentine leukocidin, respectively.
b Community methicillin-resistant S. aureus strains.
association between superantigens and
purpura fulminans must be viewed in the
context of the prevalence of genes
encoding these toxins among S. aureus isolates.
Virulence factors and toxin-encoding
genes are ubiquitous among S. aureus
clinical isolates (table 1) [5, 1822].
Approximately one-half to three-quarters of
human carriage isolates contain superantigen
genes, and finding these in the 5 isolates
recovered from patients with purpura
fulminans could be the result of chance
alone. With respect to specific toxins,
10% (and perhaps up to 25%) of S.
aureus strains contain seb, the gene (...truncated)