e186 | www.pidj.

com The Pediatric Infectious Disease Journal Volume 32, Number 5, May 2013
ORIGINAL STUDIES
Background: Children with petechial rash are more likely to undergo inva-
sive diagnostics, to be treated with antibiotics for potential bacterial infec-
tion and to be hospitalized. However, viruses have also been associated with
petechial rash. Nonetheless, a systematic analysis of viral infections with
modern available techniques as quantitative real-time polymerase chain
reaction in the context of petechial rash is lacking. The purpose of this pedi-
atric study was to prospectively uncover viral pathogens that may promote
the emergence of petechiae and to analyze the correlation with the clinical
characteristics and course.
Methods: We conducted a prospective study in children (0 to 18 years) pre-
senting with petechiae and signs or symptoms of infection at the emergency
department between November 2009 and March 2012. In nasopharyngeal
aspirates the following viruses were analyzed by quantitative real-time poly-
merase chain reaction: cytomegalovirus, EpsteinBarr virus, parvovirus
B19, inuenza A and B, parainuenza viruses, human respiratory syncytial
virus A and B, human metapneumovirus, rhinovirus, enterovirus, adenovi-
rus, human coronavirus OC43, 229E, NL63 and human bocavirus.
Results: A viral pathogen was identied in 67% of the analyzed 58 cases
with petechial rash. Virus positive patients showed a signicantly higher
incidence of lower respiratory tract infections. Forty-one percent were viral
coinfections, which were signicantly younger than virus negative patients,
had a higher leukocyte count and were hospitalized for a longer time.
Conclusions: A petechial rash is frequently associated viral single- and
coinfections and can rapidly be identied via quantitative real-time poly-
merase chain reaction.
Key Words: petechiae, fever, viral infections, management, polymerase
chain reaction
(Pediatr Infect Dis J 2013;32: e186e191)
P
etechiae in children often pose a diagnostic dilemma lead-
ing to an enhanced rate of hospitalizations, invasive proce-
dures such as blood sampling for blood cultures, assessment of
the inammation parameters and lumbar punctures, as well as
antibiotic treatment for possible sepsis or meningitis with bac-
teria such as Neisseria meningitidis.
16
In the past, the probabil-
ity of a severe bacteremia in children with petechiae and fever
was estimated at 10% to 20% with the presence of skin hemor-
rhages (diameter >2 mm) as a risk factor.
2,3,5,6
In up to 72% of the
patients with fever and a petechial rash, no causing pathogen was
identied, whereas viruses were only identied in 11% to 15%
of the cases.
2
Human respiratory syncytial virus (RSV), EpsteinBarr
virus (EBV), cytomegalovirus (CMV), adenovirus, enterovirus
(EV) and parvovirus B19 are reported to be associated with a pete-
chial rash. The proportion of viral infections in children with pete-
chiae and fever is understated.
2,711
Additionally, currently avail-
able studies on children with a petechial rash (with the most recent
being performed in 2001) noted an association between evolve-
ment of petechiae in children and upper respiratory tract infec-
tions (URTIs) commonly caused by so called respiratory viruses
as inuenza types (Inf) A, B and H1N1, parainuenza type 1, 2
and 3, RSV, rhinovirus (RV), EV and adenovirus.
3,1214
Moreover,
previously unknown viruses as human metapneumovirus, human
coronavirus and human bocavirus (HBoV) associated with URTI
and specic viral diagnostics have been discovered recently.
1420

It is now possible to specically detect viruses within hours with
nucleic acid amplication tests as quantitative real-time polymer-
ase chain reaction (q-PCR).
3,15
Modern viral diagnostics might
help further itemize the 45% of URTI in children with a petechial
rash as systematic analysis of the presence of viral pathogens in
children with petechiae is lacking.
2
The main aim of the study was
to analyze prospectively the rate of viral (single and co-) infec-
tions in children with a petechial rash applying q-PCR techniques
of nasopharyngeal aspirates (NPAs), to identify viruses associated
with the emergence of petechiae and to correlate them with disease
severity.
MATERIALS AND METHODS
Study Population
The prospective clinical study was performed from Novem-
ber 2009 to March 2012 at the University Childrens Hospital
Mannheim, Heidelberg University and the Childrens Hospital St.
Annastiftkrankenhaus in Ludwigshafen. Identication and recruit-
ment of patients was made by the responsible physician in the
emergency department or the unit within the hospital after admis-
sion. We included children between 0 and 18 years presented with
a nonblanching rash not greater than 2 mm in diameter of unknown
origin with signs and symptoms of an ongoing infection. Patients
with thrombocytopenia, preexisting coagulation disorder, clinical
vasculitis (purpuric lesion with a diameter of >2 mm), meningo-
coccal disease or with primary or secondary immune dysfunction
were excluded. Clinical data were prospectively collected using a
standard data collection form. Additional diagnostics apart from
nasopharyngeal aspirates (NPA) as chest radiogram, blood sam-
pling for laboratory parameters or blood cultures, analysis of the
urine or lumbar puncture were not a study requirement. Results of
additional diagnostics were documented and analyzed within the
study when available.
Copyright 2013 by Lippincott Williams & Wilkins
ISSN: 0891-3668/13/3205-0e186
DOI: 10.1097/INF.0b013e318280618d
Clinical Characteristics of Children With Viral Single- and
Co-infections and a Petechial Rash
Henriette Schneider, MD,* Ortwin Adams, MD, Christel Weiss, ScD, Ulrich Merz, MD,
Horst Schroten, MD,* and Tobias Tenenbaum, MD*
Accepted for publication November 28, 2012.
From the *Paediatric Infectious Diseases, University Childrens Hospital
Mannheim, Heidelberg University, Mannheim, Germany; Institute of Virol-
ogy, University Childrens Hospital, Heinrich-Heine-University, Dsseldorf,
Germany; Department of Statistics, Medical Faculty Mannheim, Heidel-
berg University, Mannheim, Germany; and Childrens Hospital St. Annas-
tiftkrankenhaus, Ludwigshafen, Germany.
H.S. and O.A. contributed equally to this article and share rst authorship.
The concept of the study was honored in 2011 by the German Society of Paediat-
ric Infectious Diseases (DGPI) with an Investigator Award (5000 Euro). The
authors have no other funding or conicts of interest to disclose.
Address for correspondence: Henriette Schneider, MD, Paediatric Infectious
Diseases, University Childrens Hospital Mannheim, Heidelberg University,
Theodor-Kutzer-Ufer 13, 68167 Mannheim, Germany. E-mail: henriette.
schneider@medma.uni-heidelberg.de.
The Pediatric Infectious Disease Journal
32
5
Copyright 2013 by Lippincott Williams & Wilkins
0891-3668
INF
203077
Viral Infections and Petechial Rash
Schneider et al
2013
May
00
00
10.1097/INF.0b013e318280618d
2013
Pediatr Infect Dis J
Lippincott Williams & Wilkins
Hagerstown, MD
Divya J
XXX
The Pediatric Infectious Disease Journal Volume 32, Number 5, May 2013 Viral Infections and Petechial Rash
2013 Lippincott Williams & Wilkins www.pidj.com | e187
Ethical Statement
Approval was provided by the local ethics committees (Med-
ical Faculty of Mannheim, Heidelberg University [2009-323N-
MA] and Mainz [837.021.10 (7030)]). Written informed consent
was obtained from parents and children (when possible according
to their age) before any study procedures being performed.
Analysis of Nasopharyngeal Aspirates
On the day of admission or detection of petechial rash, NPAs
were collected and evaluated in the Institute of Virology in Dssel-
dorf with q-PCR for CMV, EBV, parvovirus B19, Inf A and B, Inf
A H1N1 (H1N1), parainuenza 1, 2 and 3, RSV A and B, human
metapneumovirus, RV, EV (coxsackie A and B viruses and echo-
viruses except for polioviruses 13), adenovirus, human corona-
virus and HBoV. The quantication of the viruses was performed
by a previously described 1-step real-time PCR method of which
sensitivity and specicity have been demonstrated elsewhere.
14,2123

In brief, the Quantitect Multiplex q-PCR kit (No. 204643, Qiagen,
Hilden, Germany) containing HotStarTaq DNA Polymerase was
used for the assay. Amplication was performed in an ABI7500
thermocycler using conditions as recommended by the manufac-
turer of the multiplex RT-PCR kit. As standards, DNA plasmids that
encompass the amplied region were created and serially diluted
after purication. Standard graphs of the CT values obtained from
serial dilutions of the standards were constructed and the numbers
of specic genomes were calculated by the software. NPA as a
method for the detection of a viral infection was chosen as non-
invasive procedure, of which reference values for the viral load in
copies per milliliter (mL) of respiratory viruses exist.
21
In cases in
which lumbar puncture was performed, the cerebrospinal uid was
send for bacterial culture and analyzed with a standard commer-
cial multiplex PCR (Reverse Hybridization Assay kit CNS, Labo
Bio-Medical Products B.V., the Netherlands) for herpes simplex
virus type 1, herpes simplex virus type 2, EV, CMV, varicella zoster
virus, EBV, human John Cunningham virus, human herpes virus
type 6 and Toxoplasma gondii.
Statistics
Qualitative variables are presented as absolute and rela-
tive frequencies; quantitative parameters are given as mean and
standard deviation or median and range. Clinical characteristics
and laboratory variables have been compared using t tests of the
pooled method (identical variances) and Satterthwaite method (dif-
fering variances). For skewed distributed quantitative data, Mann
Whitney U test has been performed. To compare frequencies of 2
samples, test or Fishers exact test has been used, for ordinal
scaled data CochranArmitage trend test was preferred. A 2-sided
P value <0.05 was considered statistically signicant. All statistical
calculations have been done with the SAS system, release 9.2 (SAS
Institute Inc., Cary, NC).
RESULTS
Patient Characteristics
During the study period, 69 children with petechiae of
unknown origin presented at the emergency department. Three
patients were excluded because 2 developed a purpuric vasculitis,
the third had idiopathic thrombocytopenic purpura and 8 naso-
pharyngeal aspirates were lost during posting. Fifty-eight patients
could further be analyzed in the study. The male to female ratio was
41 to 17, the mean age 3.8 3.7 (range: 0.1714.58) years. There
was only a minor interseasonal variation with an enhanced num-
ber of patients presenting with a petechial rash in winter (20/58;
34%) and almost equal numbers of cases in spring (14/58; 24%),
summer (11/58; 19%) and autumn (13/58; 22%). The major-
ity of the patients (42/58; 72%) has been hospitalized and 17 of
58 patients (29%) received an antibiotic treatment (Table 1). The
reasons for hospitalizations were fever and/or dehydration (7/42;
17%), sore throat (2/42; 5%), headache (5/42; 12%), nuchal rigid-
ity (7/42; 17%) and (complicated) febrile seizure (3/42; 7%). These
signs in combination with petechial rash were interpreted by the
clinicians as warning signs for meningitis. Thirty children (52%)
presented respiratory tract infection such as URTI (20/58 patients;
34%), bronchitis/ bronchiolitis or pneumonia (Table 1). All chil-
dren were dismissed in a good state of health.
Clinical Characteristics in Virus Positive and Virus
Negative Patients
Regarding the clinical symptoms at hospital presentation,
a higher number of the virus positive children (21/39; 54%) were
coughing compared with the virus negative patients (7/19; 37%)
(Table 1). Interestingly, all cases of bronchitis/ bronchiolitis (8/58;
21%) were linked to a viral pathogen within the NPA (P = 0.0437).
Lymphadenitis was only found in virus positive patients (4/58;
7%) with EBV as the causative agent. Concerning the number of
petechiae, the majority of virus positive patients displayed 10 to
100 petechiae (26/39; 67%). Moreover, there was a statistically sig-
nicant difference in the group 10 to 100 (P = 0.0037) and >100
petechiae (P = 0.0247) between virus positive and virus negative
patients (Table 1). The distribution of petechiae did not differ sig-
nicantly in virus positive and negative patients.
Blood samples were taken in the majority of the analyzed
children (45/58; 78%) to examine full blood cell count and the
C reactive protein value (14 virus negative and 31 virus positive
patients) and revealed no signicant difference between virus posi-
tive and virus negative patients (Table 2). Blood cultures were only
analyzed in hospitalized children without any antibiotic treatment
before admission. In 3 of 38 blood culture samples (8%), bacteria
were detected (Flavimonas oryihabitans, Streptococcus agalac-
tiae and coagulase negative staphylococci each in 1 patient). Only
the patient with proven S. agalactiae infection received antibiotic
treatment.
Identication of Viral Causes in Children With a
Petechial Rash
In 39 of the 58 patients analyzed during the study period,
at least 1 virus was detected within the NPA. The majority were
single viral infections (23/39; 59%) whereas coinfections with
2 pathogens were as frequent as coinfections with >2 pathogens
(each 8/39; 20.5%). Children with viral coinfections were signi-
cantly younger (2.3 2.16 years) than the children with a single
viral infection (4.18 3.26 years) (P = 0.0440) (data not shown).
Coinfections led to a signicant higher hospitalization rate (15/16;
93.75%) compared with virus negative patients (12/19; 63%;
P = 0.0472) (data not shown). Interestingly, children with viral
coinfections presented with a signicant higher leukocyte count
(12641 3274/L) compared with virus negative (8455 3155/L;
P = 0.0063) and single viral infections (9393 4780/L;
P = 0.0642) (data not shown).
The most frequent pathogens in association with a petechial
rash were CMV and EBV (each 11/58; 18% of all patients) fol-
lowed by EV and RV (each 8/58; 14% of all patients) and H1N1
and HBoV (each 5/58; 9% of all patients). EBV and CMV were
frequently found as coinfections (only 1 single infection with EBV
and CMV within the study collective). Ten of 11 CMV positive
patients (91%) and 9 of 11 EBV positive patients (82%) were
hospitalized. CMV positive patients were with 2.07 2.53 years
younger than virus negative (4.19 3.84 years; P = 0.01108) and
Schneider et al The Pediatric Infectious Disease Journal Volume 32, Number 5, May 2013
e188 | www.pidj.com 2013 Lippincott Williams & Wilkins
CMV negative (4.57 4.88 years; P = 0.0208) patients. As to the
laboratory ndings, the CMV positive patients showed elevated
platelet counts (297970 99617/L) compared with the CMV neg-
ative patients (251142 70249/L; P = 0.0818) and a signicant
leukocytosis (13630 3337/L) compared with the CMV nega-
tive (8455 3155/L; P = 0.0109) and all virus negative patients
(9251 3979/L; P = 0.0043). Moreover, the EBV positive patients
showed a signicantly higher rate of lymphadenitis (3/11; 27%)
compared with EBV negative patients (1/47; 2%; P = 0.0191) and
virus negative patients (0/19; 0%; P = 0.0406). EV was detected
in 5 cases as single and in 3 cases as coinfection. The EV positive
patients were likely to present in summer (5/8; 63%) compared with
EV negative patients (6/50; 12%; P = 0.0164) and 3 of 5 patients
(60%) received a lumbar puncture for neurological symptoms as
febrile seizures, meningism or even meningitis. The majority of RV
positive patients (7/8; 87.5%) was hospitalized. Nine (23%) of the
39 virus positive patients were well appearing, treated as outpa-
tients without antibiotics and scheduled for a clinical control on the
consecutive days despite a high number of petechiae (6/67% had
around 100 petechiae).
PCR-positive samples could qualitatively clearly be distin-
guished from negative samples with mean viral loads ranging from
438 10
3
for coronavirus to 805 10
9
for adenovirus (Fig. 1), but it
should be emphasized that there exist no clear cutoffs for clinical
signicant values for respiratory virus infections. Especially adeno-
virus, RSV and HBoV were found with a high viral load.
TABLE 2. Laboratory Findings in Children With or Without a Viral Infection and Petechial Rash
All Patients Positive Patients Negative Patients P
Total number 58 39 19
Hemoglobin (g/dL) 12 1 12 1 12 2 0.7886
Thrombocytes (/L) 257,556 82,567 260,197 87,981 25,1143 70,250 0.9614
Leukocytes (/L) 10,080 4200 10,767 4446 8455 3155 0.5775
Segmented neutrophils* 38 24 39 24 36 29 0.4302
Banded neutrophils* 10 19 9 20 14 16 0.7628
Lymphocytes* 35 23 36 21 33 30 0.7720
Monocytes* 8 6 9 7 6 3 0.2971
C reactive protein (mg/L) 23 34 20 25 31 49 0.9393
INR 1.07 0.11 1.07 0.12 1.06 0.08 0.5735
Ptt (s) 29 8 30 9 25 7 0.0638
*% of total leukocytes.
TABLE 1. Clinical Characteristics of All Patients, Virus Positive and Negative Patients With Petechiae
All Patients Positive Patients Negative Patients P
Total number 58 39 19
Age (yr) 3.8 3.7 3.4 3.0 4.6 4.9 0.7972
Gender
Male 41 (71%) 26 (67%) 15 (79%) 0.3349
Female 17 (29%) 13 (33%) 4 (21%)
Number of petechiae
<10 13 (22.8%) 7 (18%) 6 (33%) 0.3079
10100 30 (52.6%) 26 (67%) 4 (22%) 0.0037
>100 14 (24.6%) 6 (15%) 8 (45%) 0.0247
Symptoms
Coughing 28 (48%) 21 (54%) 7 (37%) 0.2239
Vomiting 16 (28%) 11 (28%) 5 (26%) 0.8799
Diarrhea 14 (24%) 11 (28%) 3 (16%) 0.3495
Meningism 7 (12%) 4 (10%) 3 (16%) 0.6726
Swelling of joints 2 (3%) 1 (3%) 1 (5%) 1
Maximal temperature (C) at admission 38.3 1 38.8 1 38.5 1.3 0.8737
Diagnosis
URTI 20 (34%) 13 (33%) 7 (37%) 0.7919
Bronchitis 8 (14%) 8 (21%) 0 (0%) 0.0437
Pneumonia 2 (3%) 0 (0%) 2 (11%) 0.1034
Gastroenteritis 11 (19%) 8 (21%)* 3 (16%) 1
Lymphadenitis 4 (7%) 4 (10%) 0 (0%) 0.2921
Febrile seizure 3 (5%) 3 (8%) 0 (0%) 1
Meningitis 2 (3%) 1 (3%) 1 (5%) 1
Presumed sepsis 5 (9%) 2 (5%) 3 (17%) 0.3125
Others 14 (24%) 8 (21%) 6 (32%) 0.5141
Invasive diagnostics
Lumbar puncture 10 (17%) 5 (13%) 5 (26%)

0.2704
Therapeutic strategies
Antibiotics 17 (29%) 11 (28%) 6 (32%) 0.7911
Hospitalization rate 42 (72%) 30 (77%) 12 (63%) 0.271
*Of the patients with diarrhea, 4 were positive for an enteric virus (2 norovirus and 2 rotavirus).

In 1 of the patients with presumed sepsis, blood cultures were positive for S. agalactiae.

Of the patients who underwent a lumbar puncture, 1 of the virus positive and 2 of the virus negative patients underwent lumbar puncture for their young age <6 months.
The Pediatric Infectious Disease Journal Volume 32, Number 5, May 2013 Viral Infections and Petechial Rash
2013 Lippincott Williams & Wilkins www.pidj.com | e189
Central Nervous System Symptoms in Children
With Petechial Rash
As to central nervous system symptoms, 7 of the 58
(12%) presented with nuchal rigidity and 3 of the 58 (5%) with
a febrile seizure. Ten children (17%) received a lumbar puncture
at admission. In 5 out of these, a virus was detected in the NPA (1
coinfection of H1N1, CMV, EBV and EV, 1 coronavirus, 2 single
infections with EV and 1 coinfection of parainuenza and CMV).
All 7 children with meningism were hospitalized. Four of them (2
virus positive and 2 virus negative within the NPA) were treated with
antibiotics. Additionally, 4 children underwent lumbar puncture due
to the presence of a petechial rash in combination either with their
young age <4 months (3 patients) or with a complicated febrile
seizure (1 patient). Meningitis (with an elevated total cell count in
the cerebrospinal uid) was diagnosed in 2 cases (patient 1: EBV
positive, patient 2: no pathogen identied). In all the children with
febrile seizure, viral pathogens were detectable within the NPA (1
single infection with EV, 2 viral coinfections with H1N1, CMV,
EBV and EV in 1 patient and RV, adenovirus and EBV in another
patient).
DISCUSSION
Petechial rash in children is often interpreted as a warning
sign for sepsis or meningitis and leads to an elevated rate of inva-
sive diagnostics as lumbar punctures and intensied therapies as
antibiotic treatments and hospitalization.
26
Data on the association
of viral pathogens with a petechial rash in children are sparse.
3,4,12

In 2 studies conducted in newborns, the existence of a petechial
rash (up to 3 spots) has been evaluated as harmless.
24,25
In the underlying study, we analyzed systematically the fre-
quency of viral infections within the NPA of children with a pete-
chial rash over 2 consecutive years. Children with purpuric lesions
with a diameter >2 mm were excluded from the study as they seem
more likely to suffer from meningococcal disease.
6
Main aim was
to estimate the amount of viral pathogens within the nasopharynx
measured with q-PCR analysis in the context of a petechial rash
with a noninvasive procedure for which information about the viral
load in disease exit. In 67% of the included patients, 1 or several
viral pathogens have been detected. The viral loads in the NPA
for the different viruses in this study (Fig. 1) were comparable to
described viral loads for infections with respiratory viruses either
in single or in coinfections and in a higher range than viral loads
in healthy children.
21,26
Still, there is no consensus in the literature
on clinical signicant values for respiratory infections. As a result
of low case numbers for each pathogen viral load results have to be
interpreted with caution. For RV, a previous prospective study with
healthy children has shown that shedding of picornavirus RNA was
episodic with positive q-PCRs for 1 to 3 weeks followed by weeks
of negative tests; chronic carriage did not occur.
27
The mean viral
load of the RV samples in our study was with 136 10
5
copies/
mL equal or higher than viral loads found with other viruses (ie,
inuenza or parainuenza) indicating that the detection of RV may
be associated with an acute infection. Otherwise it cannot com-
pletely be excluded that in some cases we detected RV RNA from
a previous episode of infection. Concerning herpesviruses (CMV
and EBV), a critical point with the detection is the long lasting oral
shedding after primary infection. In adults, CMV and EBV can be
detected in 10%20% of asymptomatic individuals and is assumed
to be more frequent during childhood.
28
Consequently, a combi-
nation of q-PCR of NPA with a serological analysis may help to
differentiate between acute viral infection and reactivation. As our
study was meant to apply as few additional invasive diagnostics in
the children as possible, serological correlation with the ndings,
which was part of the study design, was not always possible. This
might limit the interpretation of the study. Blood culture sampling
FIGURE 1. Mean viral load detected in children with viral infections and petechial rash. The highest viral load values were
detected in children with adenovirus (AV), RSV and HBoV infections. PVB19 indicates parvovirus B19; hMPV, human metap-
neumovirus; HCoV, human coronavirus; Para, parainfuenza.
Schneider et al The Pediatric Infectious Disease Journal Volume 32, Number 5, May 2013
e190 | www.pidj.com 2013 Lippincott Williams & Wilkins
was performed in the hospitalized patients without prior antibiotic
treatment (38/58; 66%) and revealed only 1 clinically relevant case
of bacterial blood stream infection (S. agalactiae) in the study pop-
ulation.
Between virus negative and virus positive patients with
a petechial rash, there were no signicant differences in clinical
appearance, cardinal symptoms, diagnostic parameters, treat-
ment and hospitalization rate despite the higher rate of bronchitis/
bronchiolitis in virus positive patients and the number of pete-
chiae (Table 1). Patients with viral coinfections were signicantly
younger than virus negative patients, had a higher leukocyte count
and were longer hospitalized.
Interestingly, within the small subgroup of patients with
central nervous system symptoms (10 patients), virus positive
patients displayed the petechial rash in a more generalized fashion
(head: 3/5; 60%; upper extremities: 2/5; 40%; trunk: 4/5; 80% and
the lower extremities: 3/5; 60%), whereas in virus negative patients
the rash was centered on the trunk (2/5; 40%) and lower extremities
(3/5; 60%).
In previous studies, authors suggested to combine the clini-
cal criteria general appearance and skin lesion (either petechiae or
purpuric lesions) with the WBC to detect children with bacterial
sepsis whereas viral pathogens were not investigated due to compli-
cated virus diagnostics.
4,15
Applying these criteria (either general
appearance, WBC and skin lesions or irritability, lethargy and
low capillary rell) to our study population, all children with viral
coinfections fulll the criteria for bacterial septicemia/bacteremia
and would receive an antibiotic treatment at least until bacterial
cultures were proven negative.
4,12
Thus, our study provides evidence
that also viral infections can lead to a reduced clinical appearance
and an elevated WBC. Due to efcient vaccination programs within
Europe and the United States, herd immunity and herd protection
against Streptococcus pneumoniae, N. meningitidis and Haemophi-
lus inuenzae improved.
2932
Consequently, the use of the clinical
and diagnostic criteria (see above) set the era before the availabil-
ity of elaborate viral diagnostics as q-PCR and before the imple-
mentation of directed vaccination programs might lead nowadays
in Europe and the United States to an overestimation of bacterial
infections in such children with a petechial rash.
3,4,12
Additional
studies have to further clarify whether rather the infection with a
specic pathogen or coinfections with different viruses determine
the appearance of a petechial rash in children.
In our study, 17 (11 virus positive and 6 virus negative)
children in total were treated with antibiotics due to suspicion of
potential bacterial infection and/or young age. In the 11 virus posi-
tive patients (8 viral single and 3 coinfections), viral infection fully
accounted for the symptoms they presented and antibiotic treatment
might have been dispensable. There is strong discordance about
the suitable treatment for children with a petechial rash that are in
a good general state of health and young aged children are more
likely to be treated with antibiotics or to be admitted to hospital for
a petechial rash even when their clinical condition is not reduced
1,13
Petechial rash in children needs thorough examination to
distinguish between life threatening diagnosis as fulminant sepsis
and self-limiting viral infection. Novel viral diagnostics as multi-
plex q-PCR enables the rapid detection of viral causes and might
avoid unnecessary antibiotic treatment, invasive diagnostics and
hospitalizations.
ACKNOWLEDGMENTS
We are grateful for the support offered by the staff of the
2 childrens hospitals, the University Childrens Hospital Man-
nheim, Germany Heidelberg University and the Childrens Hospi-
tal St. Annastiftkrankenhaus in Ludwigshafen, Germany, and the
members of the working group of Prof. O. Adams in the Institute of
Virology, University Childrens hospital, Heinrich-Heine-Univer-
sity, Dsseldorf, Germany.
REFERENCES
1. Nelson DG, Leake J, Bradley J, et al. Evaluation of febrile children with
petechial rashes: is there consensus among pediatricians? Pediatr Infect Dis
J. 1998;17:11351140.
2. Baker RC, Seguin JH, Leslie N, et al. Fever and petechiae in children. Pedi-
atrics. 1989;84:10511055.
3. Nielsen HE, Andersen EA, Andersen J, et al. Diagnostic assessment of
haemorrhagic rash and fever. Arch Dis Child. 2001;85:160165.
4. Mandl KD, Stack AM, Fleisher GR. Incidence of bacteremia in infants and
children with fever and petechiae. J Pediatr. 1997;131:398404.
5. Van Nguyen Q, Nguyen EA, Weiner LB. Incidence of invasive bacterial dis-
ease in children with fever and petechiae. Pediatrics. 1984;74:7780.
6. Wells LC, Smith JC, Weston VC, et al. The child with a non-blanching
rash: how likely is meningococcal disease? Arch Dis Child. 2001;85:
218222.
7. Cofn SE, Gest KL, Shimamura A. Respiratory syncytial virus as a
cause of fever and petechiae in infants. Clin Pediatr (Phila). 1993;32:
355356.
8. Sahler OJ, Wilfert CM. Fever and petechiae with adenovirus type 7 infec-
tion. Pediatrics. 1974;53:233235.
9. DeVries J. The ABCs of CMV. Adv Neonatal Care. 2007;7:248255;
quiz 256.
10. Elling R, Hufnagel M, Henneke P. Infektionsassoziierte Hauteinblutungen.
Monatsschr Kinderheilkd. 2012;160:111.
11. McNeely M, Friedman J, Pope E. Generalized petechial eruption induced
by parvovirus B19 infection. J Am Acad Dermatol. 2005;52(5 suppl 1):
S109S113.
12. Brogan PA, Rafes A. The management of fever and petechiae: making
sense of rash decisions. Arch Dis Child. 2000;83:506507.
13. Legg JP, Warner JA, Johnston SL, et al. Frequency of detection of picornavi-
ruses and seven other respiratory pathogens in infants. Pediatr Infect Dis J.
2005;24:611616.
14. Bonzel L, Tenenbaum T, Schroten H, et al. Frequent detection of viral coin-
fection in children hospitalized with acute respiratory tract infection using a
real-time polymerase chain reaction. Pediatr Infect Dis J. 2008;27:589594.
15. Mahony JB. Detection of respiratory viruses by molecular methods. Clin
Microbiol Rev. 2008;21:716747.
16. van den Hoogen BG, de Jong JC, Groen J, et al. A newly discovered human
pneumovirus isolated from young children with respiratory tract disease.
Nat Med. 2001;7:719724.
17. Peiris JS, Lai ST, Poon LL, et al.; SARS study group. Coronavirus as a
possible cause of severe acute respiratory syndrome. Lancet. 2003;361:
13191325.
18. Viazov S, Ratjen F, Scheidhauer R, et al. High prevalence of human metap-
neumovirus infection in young children and genetic heterogeneity of the
viral isolates. J Clin Microbiol. 2003;41:30433045.
19. Allander T, Jartti T, Gupta S, et al. Human bocavirus and acute wheezing in
children. Clin Infect Dis. 2007;44:904910.
20. Allander T, Tammi MT, Eriksson M, et al. Cloning of a human parvovirus by
molecular screening of respiratory tract samples. Proc Natl Acad Sci USA.
2005;102:1289112896.
21. Franz A, Adams O, Willems R, et al. Correlation of viral load of respiratory
pathogens and co-infections with disease severity in children hospitalized
for lower respiratory tract infection. J Clin Virol. 2010;48:239245.
22. Klein RM, Jiang H, Niederacher D, et al. Frequency and quantity of the
parvovirus B19 genome in endomyocardial biopsies from patients with
suspected myocarditis or idiopathic left ventricular dysfunction. Z Kardiol.
2004;93:300309.
23. Schnberger S, Meisel R, Adams O, et al. Prospective, comprehensive, and
effective viral monitoring in children undergoing allogeneic hematopoi-
etic stem cell transplantation. Biol Blood Marrow Transplant. 2010;16:
14281435.
24. Soheilifar J, Ahmadi M, Ahmadi M, et al. Prevalence and location of pete-
chial spots in well infants. Arch Dis Child. 2010;95:518520.
25. Downes AJ, Crossland DS, Mellon AF. Prevalence and distribution of pete-
chiae in well babies. Arch Dis Child. 2002;86:291292.
The Pediatric Infectious Disease Journal Volume 32, Number 5, May 2013 Viral Infections and Petechial Rash
2013 Lippincott Williams & Wilkins www.pidj.com | e191
26. Jansen RR, Wieringa J, Koekkoek SM, et al. Frequent detection of
respiratory viruses without symptoms: toward dening clinically relevant
cutoff values. J Clin Microbiol. 2011;49:26312636.
27. Winther B, Hayden FG, Hendley JO. Picornavirus infections in children
diagnosed by RT-PCR during longitudinal surveillance with weekly sam-
pling: Association with symptomatic illness and effect of season. J Med
Virol. 2006;78:644650.
28. Frana TRT, Albuquerque Tavares Carvalho A, Gomes VB, et al. Salivary
shedding of EpsteinBarr virus and cytomegalovirus in people infected or
not by human immunodeciency virus 1. Clin Oral Invest. 2011;16:659664.
29. Ardanuy C, Tubau F, Pallares R, et al. Epidemiology of invasive pneumo-
coccal disease among adult patients in barcelona before and after pediatric
7-valent pneumococcal conjugate vaccine introduction, 1997-2007. Clin
Infect Dis. 2009;48:5764.
30. Pollard AJ, Perrett KP, Beverley PC. Maintaining protection against invasive
bacteria with protein-polysaccharide conjugate vaccines. Nat Rev Immunol.
2009;9:213220.
31. Ladhani SN, Ramsay M, Slack MP. The impact of Haemophilus inuen-
zae serotype B resurgence on the epidemiology of childhood invasive Hae-
mophilus inuenzae disease in England and Wales. Pediatr Infect Dis J.
2011;30:893895.
32. Trotter CL, Gay NJ, Edmunds WJ. Dynamic models of meningococcal car-
riage, disease, and the impact of serogroup C conjugate vaccination. Am J
Epidemiol. 2005;162:89100.