M. Bruce Edmonson, Erica L. Riedesel, Gary P. Williams and... ; originally published online March 1, 2010;

Generalized Petechial Rashes in Children During a Parvovirus B19 Outbreak
M. Bruce Edmonson, Erica L. Riedesel, Gary P. Williams and Gregory P. DeMuri
Pediatrics 2010;125;e787; originally published online March 1, 2010;
DOI: 10.1542/peds.2009-1488
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Generalized Petechial Rashes in Children During a
Parvovirus B19 Outbreak
AUTHORS: M. Bruce Edmonson, MD, MPH,
Erica L. Riedesel, MD, Gary P. Williams, MD, and
Gregory P. DeMuri, MD
Division of General Pediatrics and Adolescent Medicine,
Department of Pediatrics, University of Wisconsin School of
Medicine and Public Health, Madison, Wisconsin
parvovirus, epidemiology
IgM—immunoglobulin M
IgG—immunoglobulin G
PCR—polymerase chain reaction
GAS— group A ␤-hemolytic Streptococcus
WHAT’S KNOWN ON THIS SUBJECT: Reports about petechial or
purpuric rashes that are associated with acute parvovirus
infection usually describe only sporadic cases with distinctively
focal (eg, “gloves and socks”) rash distributions.
WHAT THIS STUDY ADDS: During a community outbreak of fifth
disease, parvovirus proved to be a common cause of generalized
petechial rash in children. Associated fever, leukopenia, and
serologic test results link this rash to the viremic phase of
Accepted for publication Oct 28, 2009
Address correspondence to M. Bruce Edmonson, MD, MPH, 2870
University Ave, Madison, WI 53705. E-mail:
[email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2010 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
PEDIATRICS Volume 125, Number 4, April 2010
OBJECTIVES: Human parvovirus B19 infection is associated not only
with erythema infectiosum (fifth disease) but also, rarely, with purpuric or petechial rashes. Most reports of these atypical rashes describe sporadic cases with skin lesions that have distinctively focal
distributions. During a community outbreak of fifth disease, we investigated a cluster of illnesses in children with generalized petechial
rashes to determine whether parvovirus was the causative agent and,
if so, to describe more fully the clinical spectrum of petechial rashes
that are associated with this virus.
METHODS: Systematic evaluation was conducted by general pediatricians of children with petechial rashes for evidence of acute parvovirus infection.
RESULTS: During the outbreak, acute parvovirus infection was confirmed in 13 (76%) of 17 children who were evaluated for petechial
rash. Confirmed case patients typically had mild constitutional symptoms, and most (11 [85%] of 13) had fever. Petechiae were typically
dense and widely distributed; sometimes accentuated in the distal
extremities, axillae, or groin; and usually absent from the head/neck.
Most case patients had leukopenia, and several had thrombocytopenia. Parvovirus immunoglobulin M was detected in 8 (73%) of 11 acutephase serum specimens, and immunoglobulin G was detectable only in
convalescent specimens. Parvovirus DNA was detected in all 7 tested
serum specimens, including 2 acute-phase specimens that were immunoglobulin M–negative. All case patients had brief, uncomplicated illnesses, but 6 were briefly hospitalized and 1 underwent a bone marrow
examination. Two case patients developed erythema infectiosum during convalescence.
CONCLUSIONS: During an outbreak of fifth disease, parvovirus proved
to be a common cause of petechial rash in children, and this rash was
typically more generalized than described in case reports. Associated
clinical features, hematologic abnormalities, and serologic test results
are consistent with a viremia-associated illness that is distinct from
and occasionally followed by erythema infectiosum. Pediatrics 2010;
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In addition to erythema infectiosum
(fifth disease), acute infection with human parvovirus B19 can be associated
with purpuric or petechial rashes.
These parvovirus-associated hemorrhagic rashes seem to be uncommon,
and published reports have described
only solitary or sporadic cases (reviewed by McNeely et al1 and additionally reported by others2–7). Most case
reports emphasized the distinctively
focal (“gloves and socks,”8 “bathing
trunk,”5,7 or “acropetechial”9) distribution of these atypical rashes, and
only a few reports have described
generalized petechial rashes associated with parvovirus infection.1–3,10
We could find no description of an outbreak of parvovirus-associated petechial rash in the English-language medical literature.
During a recent community outbreak
of fifth disease, we obtained serologic
confirmation of acute parvovirus infection in a 13-year-old boy with an index
case of fever, generalized petechial
rash, and neutropenia. After confirming parvovirus infection in a second
child with a similar illness, we instituted prospective case finding in our
network of pediatric practices and began to evaluate systematically petechial rash illnesses for evidence of
parvovirus infection. Our objectives
were, first, to determine whether additional cases of parvovirus-associated
petechial rash illness might be occurring during the fifth disease outbreak
and, then, to describe more fully the
spectrum of clinical and laboratory
features of this infrequently reported
In early March 2007, we sent a short
e-mail description of the index case to
all 32 office-based general pediatricians who are associated with the UW
Health, a network of medical providers
that are affiliated with the University of
Wisconsin in south central Wisconsin.
To encourage case finding, network
pediatricians were (1) alerted to the
possible relationship between petechial rashes and parvovirus B19 infection, (2) asked to watch for any suspected case (defined as a petechial
rash of unknown cause in a child), and
(3) informed about procedures for serologic and virologic testing for parvovirus infection. Throughout the remainder of winter and spring, network
pediatricians received e-mail updates
about the outbreak investigation and
were encouraged to obtain parvovirus
tests in suspected cases.
A confirmed case of parvovirusassociated petechial rash was defined
as an otherwise unexplained petechial
rash in a child for whom there was either laboratory evidence of acute parvovirus B19 infection or, when no serum specimen was available for
testing, a temporal linkage to an illness consistent with erythema infectiosum (transient “slapped cheek” appearance followed by a reticular rash
on the extremities). Laboratory evidence of acute parvovirus infection
was defined as any of the following: (1)
detectable parvovirus-specific immunoglobulin m (IgM) antibody in an
acute or convalescent serum specimen;
(2) specific immunoglobulin G (IgG) antibody seroconversion in paired specimens; or (3) positive polymerase chain
reaction (PCR).
Serologic tests for IgM- and IgGspecific parvovirus B19 antibodies
were performed in the 2 reference laboratories that routinely provide serologic testing services to UW Health. The
Wisconsin State Laboratory of Hygiene
(Madison, WI) used an indirect fluorescent antibody assay (Biotrin, Dublin,
Ireland), and the ARUP Laboratories
(Salt Lake City, UT) used an enzymelinked immunosorbent assay (Biotrin).
Serum testing for parvovirus B19 DNA
was performed by PCR by using 2 primers directed at the VP1 gene.
To place confirmed cases in epidemiologic context, we used administrative
data from the 2 reference laboratories
to calculate both the number of parvovirus B19 IgM antibody tests ordered
by UW Health providers and the number of tests that were positive during
each quarter of the outbreak year
(2007) and the 3 preceding years
(2004 –2006).
Clinical data and laboratory test results from all confirmed cases were
obtained by retrospective medical
chart review and by interviews with
providers and patient families. Written consent for study participation
was obtained from the families of all
case patients, in accordance with a
study protocol that was approved by
the Health Sciences Human Subjects Committee of the University of
Network pediatricians reported 17
suspected cases of initially unexplained petechial rash in Madisonarea children between February and
November 2007. A total of 13 cases
were eventually confirmed with laboratory or clinical evidence of acute
parvovirus B19 infection. Most confirmed cases had onset of rash between February and April (10 cases)
with a peak in March (6 cases). Confirmed cases coincided with an abrupt
increase in the number of serologically confirmed parvovirus infections
among UW Health patients of all ages
during the first 3 quarters of 2007 (Fig
1). There was no difference in the timing of confirmed cases and the 4 suspected cases that were not confirmed
(data not shown).
Table 1 provides descriptive information about confirmed case patients.
The median age of patients was 7 years
(range: 3–16 years). Patients lived in a
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TABLE 1 Selected Clinical Characteristics of
Confirmed Cases
Serum specimens submitted
IgM-positive serum specimens
IgM-positive specimens
indicates a confirmed case of
parvovirus-associated petechial rash
Specimens submitted
Study Period
Timing of confirmed cases of parvovirus-associated petechial rash in children compared with secular
trends in laboratory serologic testing for acute parvovirus infection, UW Health, 2004 –2007. Serologic
data reflect specimen submission for patients of all ages, regardless of clinical indication, by providers of all specialties. Information about the timing of parvovirus-associated petechial rashes is
confined to cases in children that were reported by system pediatricians during the study year only.
variety of urban, suburban, and rural
locations in and around Dane County,
Wisconsin. Only 2 patients, sisters 3
and 6 years old, had a known common
household or school exposure. All but 1
patient received usual medical care at
UW Health. Most (9 [69%] of 13) patients were initially evaluated in a primary physician’s office, and the remainder were evaluated in local
emergency departments or urgent care
In most cases, the presenting complaint was fever and petechial rash. Fever was reported in 11 (85%) of 13
cases, and body temperature was objectively measured in 8 of these 11
cases with maximum recorded values
ranging from 38.6 to 40.0°C. Fever was
brief, ranging from 1 to 3 days, and its
onset typically just preceded or coincided with discovery of the petechial
rash. Associated symptoms were common and included sore throat, headache, and fatigue. Two case-patients
PEDIATRICS Volume 125, Number 4, April 2010
complained that their rash was
On physical examination, most confirmed case patients appeared well,
but 4 patients were reported to be
mildly or moderately ill. Petechiae
were described as small (1–2 mm),
flat, red or purple spots that were often present in large numbers (described, eg, as “100s” or “too many to
count”) and did not blanch. Petechiae
were generalized in all cases and locally accentuated in 7 (54%) of 13
cases (Table 1).
Additional physical findings included
other skin abnormalities in 5 case patients: 3 had solitary, flat, ecchymotic
lesions on the chin or shin; 1 had tiny,
blanching, pink papules on the back;
and 1 had transient pink, blanching
papules on the distal extremities,
palms, and soles that preceded the
generalized petechial rash. No case
had palpable purpura. Six case pa-
Age, y
Male gender
Presenting complaint
Fever and rash
Associated symptoms
Sore throat
Arthralgia (elbow, shoulder)
Local accentuation
Groin, perineum, and/or buttocks
Distal extremities
Other physical findings
Cutaneous ecchymosis (chin, shin)
Intra-oral erythema, petechiae,
ulcers, or papules
White blood cell count, 1000 cells/␮L
⬍5.0 (range: 0.9–4.8)
Not tested
Platelet count, 1000 cells/␮L
⬍150 (range: 34–144)
Not tested
(N ⫽ 13)
tients had at least 1 intra-oral finding:
3 had mucosal erythema, 2 had palatal
petechiae, 1 had ulcers, and 1 had
tongue papules.
Complete blood counts were available for 12 patients with confirmed
cases (Table 1). Leukopenia (⬍5000
white blood cells/␮L) was found in
10 (83%) of 12 patients. Two patients
had isolated neutropenia (⬍1500
neutrophils/␮L), 5 had isolated lymphopenia (⬍1500 lymphocytes/␮L),
and 5 had both. Four patients had
thrombocytopenia (⬍150 000 platelets/␮L) but only 1 patient had a platelet count (34 000/␮L) ⬍100 000/␮L.
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TABLE 2 Parvovirus Serum Antibody and PCR Test Results in Confirmed Cases
Type of Specimen Tested
Cases, n
IgM, n Positive/n
IgG, n Positive/n
PCR, n Positive/n
Unpaired acute serum
Paired sera
Unpaired convalescent serum
Serologic data were unavailable for 1 confirmed case (see Results).
Borderline or low hemoglobin concentrations (range: 10.9 –11.4 g/dL) were
noted in 3 patients. A reticulocyte
count was measured in only 1 patient
and was low (0.2%). Throat cultures
were negative for group A
␤-hemolytic Streptococcus (GAS) in
4 patients, and a rapid antigen test
was positive for GAS in 1 (subsequently parovirus-seroconfirmed)
Acute parvovirus infection was laboratory confirmed in 12 of 13 cases (Table
2). Acute serum specimens were available in 11 laboratory-confirmed cases,
and 3 of these cases were parvovirus
IgM-negative acutely. In 2 of these IgMnegative cases, acute serum specimens were also tested for parvovirus
DNA and were positive by PCR in both
cases. Overall, parvovirus DNA was detectable in all 7 serologically confirmed cases tested by PCR. In the single confirmed case that was not
laboratory confirmed, no serum specimen was available; however, this case
was considered to be clinically confirmed because of development of
classic erythema infectiosum after
resolution of the petechial rash.
Six of the 13 children with confirmed
cases were hospitalized. Initial diagnostic considerations for these patients included bacteremia, GAS infection, ehrlichiosis, pancytopenia,
leukemia, and viral illness. Hospitalized stays were short (range: 2–3
days). All hospitalized case patients
had blood cultures obtained. One case
patient underwent bone marrow biopsy to evaluate neutropenia and
thrombocytopenia. Two case patients
developed erythema infectiosum after
their petechial rash resolved; in each
case, this second rash developed 2 to 3
weeks after the appearance of the first
(petechial) rash.
In this investigation, parvovirus proved
to be a common cause of petechial rash
during a community outbreak of fifth disease. Relying only on passive surveillance, we were able to identify and confirm 13 cases among children and
adolescents in a single health care system. This is surprising because previous
English-language reports of parvovirusassociated petechial rashes described
only solitary cases or small numbers of
seemingly sporadic cases,1–7 although
the authors of 1 report did refer (in Japanese) to an apparent cluster of 8 pediatric cases examined at a single Japanese hospital during a period of 6
Parvovirus-associated petechial rashes
may be more common than generally
appreciated. Illnesses that are characterized by fever and petechial rash are,
themselves, not rare in children11 and
can be caused by a wide variety of viral, bacterial, and rickettsial agents.12
Such illnesses are not routinely evaluated for acute parvovirus infection
and, typically, are attributed to unspecified (and presumed viral)
agents.11,13–15 In the past, petechial or
purpuric rashes may have been overlooked during “classic” investigations
of large outbreaks of erythema infectiosum reported in the 1920s to
1940s,16–18 and it is notable that 2 outbreak reports from the 1950s did describe, in passing, exceptional cases
of hemorrhagic rash amid hundreds of typical cases of erythema
Even with the advent of serologic and
direct virologic methods for detecting
parvovirus infection, it is still possible
that cases of parvovirus-associated
hemorrhagic rashes are being overlooked because previous case reports
emphasized the distinctively focal nature of these rashes. Petechiae rashes
in some of our cases had focal accentuation (in the distal extremities,
groin, or axillae), but petechiae were
widely distributed in all cases and, in
this respect, more closely resembled
the generalized rashes described in a
few case reports.1–3,10
On the basis of the clinical characteristics of our cases, it seems that
parvovirus-associated petechial rash
is closely linked to the viremic phase of
parvovirus infection. Our case patients
typically had fever, systemic symptoms, leukopenia (and occasional
thrombocytopenia), and detectable parvovirus DNA in their blood, and acutephase serum tests indicated that a
specific antibody response had either
not yet developed (IgM-negative) or
was just developing (IgM-positive/IgGnegative). Except for the petechial rash
itself, these clinical characteristics
closely mimic the viremic phase described in human experimental parvovirus infection, at the point (postinoculation days 9 –10) when platelet and
leukocyte counts reach a nadir and IgMspecific antibody begins to appear.21
We speculate that the pathogenesis
of parvovirus-associated petechial
rash is similar to that of the papularpurpuric gloves and socks syndrome, in which parvovirus antigens
can be detected directly in dermal
vessel walls, as well as in the cells of
sweat glands and ducts and epider-
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mal cells.22 Erythrocyte P antigen, the
receptor on the erythrocyte progenitor cell associated with the pathogenesis of the hematologic manifestations of parvovirus infection, is
also present in other cell lines, including fetal cardiac myocytes and
endothelial cells, and may be responsible for its skin manifestations.23
The presence of a petechial rash during the acute phase of infection,
when patients have viremia, could be
explained by the binding of virus to P
antigen on capillary endothelial
cells, thereby causing capillary disruption and extravasation of erythrocytes into dermal tissues. Endothelial cells also express the ␣5␤1
integrin, which is a cell surface receptor necessary for infection by
parvovirus B19.24
The acute petechial rash and associated illness in our cases had little in
common clinically with erythema infectiosum. Erythema infectiosum is believed to be a postviremic manifestation of parvovirus infection that
develops 2 to 3 weeks after infection
and is attributable to immune complex
deposition.6,22,25 Typically, by the time
erythema infectiosum develops in the
course of acute parvovirus infection,
any fever or constitutional symptoms
have resolved, the peripheral white
blood cell and platelet counts have
normalized,18,26 and specific IgG antibodies have become detectable.21 Although erythema infectiosum did de-
velop in 2 of our case patients, this
occurred long after disappearance
of their petechial rashes. This
sequence—petechial rash followed by
erythema infectiosum— has been previously described3,6 and further distinguishes petechial rash in our patients
from erythema infectiosum.
The principal limitation of our study is
that cases were detected by passive
surveillance and, as a result, cannot be
used to estimate the incidence of
parvovirus-associated petechial rash.
Although laboratory administrative
data provide evidence that a community outbreak of parvovirus infection
did occur during the study period,
they provide no basis for accurately
estimating the number of children
infected. Moreover, although the majority of petechial rashes reported
during the study period proved to be
parvovirus-associated, it is possible
that additional cases of petechial rash
were unreported, either because they
were unevaluated for parvovirus or because they were attributed to some
other cause. It is also theoretically possible that the occurrence of petechial
rashes in our cases reflects some variation in the strain of parvovirus that
was circulating locally during the outbreak. Another limitation of our study
is that diagnostic testing was not uniform in suspect cases, and results of
initial acute serum tests may have influenced whether additional (PCR or
antibody) tests were ordered. Thus,
the apparent sensitivity of parvovirus
IgM (73%) and PCR (100%) tests in confirmed cases may be distorted by verification bias.27
Results of our investigation during an
outbreak of fifth disease showed that
petechial rashes may be a more common manifestation of parvovirus infection in children than suggested by previous reports of isolated cases. These
rashes are typically more generalized
than the focal petechial or purpuric
rashes described in most reports. Associated clinical features, hematologic
abnormalities, and results of serologic
tests are consistent with a viremic illness that is distinct from and is occasionally even followed by erythema
We thank the following physicians for
evaluating and reporting cases: Gail
Allen, James Conway, Timothy Drews,
Greg Landry, Jeffrey Meade, Amy
Plumb, Jeffrey Sleeth, Melissa Stiles,
Eric Warbasse, Robin Wright, and KokPeng Yu. We also thank Leanne
Wheeler, UW Medical Foundation Laboratories, and David Warshauer, PhD,
Wisconsin State Laboratory of Hygiene,
for helping collect administrative data
on parvovirus testing at UW Health
and Akihiro Ikeda, PhD, for translating and reviewing Japanese medical
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Generalized Petechial Rashes in Children During a Parvovirus B19 Outbreak
M. Bruce Edmonson, Erica L. Riedesel, Gary P. Williams and Gregory P. DeMuri
Pediatrics 2010;125;e787; originally published online March 1, 2010;
DOI: 10.1542/peds.2009-1488
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
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