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Beyond Microcephaly: Other manifestations of neonatal and infantile congenital Zika Virus

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While microcephaly may be considered the most common manifestation in neonates and infants infected with Zika Virus (ZIKV), recent studies have documented rarer CNS and non-CNS findings of ZIKV in infected children. The aim of our study was to describe these other findings.
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of fever, emesis and worsening of a chronic right knee effu-
sion. White blood cell count was normal, but the erythro-
cyte sedimentation rate (ESR) was elevated to 76 mm/hr and
her C-reactive protein (CRP) was elevated at 38.6 g/dL
(normal <0.3 g/dL). Contrasted magnetic resonance
imaging of the right knee revealed a large effusion. She
underwent 7 arthrotomies over a 34-day period, which all
demonstrated purulent synovial uid. The rst 3 surgeries
(over 5 days) produced growth of Group G Streptococcus
(GGS) on synovial uid cultures despite receipt of anti-
microbial therapy (vancomcyin and ampicillin). Though
subsequent cultures were sterile, she continued to be febrile
with elevated inammatory markers (ESR=22 and
CRP=1.3 after 82 days of treatment, despite a history of
normal inammatory markers prior to admission). After 8
weeks of ampicillin therapy, she was discharged home on a
prolonged course of amoxicillin therapy.
Literature Search A search of PubMed and Web of
Knowledge (WOK) on June 30th, 2016 utilizing the terms
Septic arthritisor Pyogenic arthritisor arthritisand
Group G Streptococcuswithout any lters produced 129
publications. Review of all articles produced two publica-
tions describing 3 cases in children. A review of references
from these articles and references from the 4 systematic
reviews of Group G Streptococcus found produced no add-
itional reports. Citation tracker on WOK was utilized for
the two articles, but did not produce any additional cases.
Conclusion Our patient is only the fourth reported case of
GGS septic arthritis in a child. Contrary to previous cases, our
patient exhibited a prolonged and complicated clinical course.
This may be attributable to her pre-existing charcot arthropa-
thy, a phenomenon which has been described in adults.
45 ERYTHEMA SWEETOBULLOSUM; NOT VERY
SWEET-LOOKING
Abukamleh H, Chahine H, Patel J, Heidari A. Kern Medical, Victorville, CA.
10.1136/jim-2016-000365.45
Purpose of Study To describe a case of a rare skin manis-
tation in acute coccioidomycosis infection
Methods Used Patient is 45 year old male who presented
to ER with worsening blistering rash over his bilateral fore-
arms that started 5 days prior. Rash was described as
diffuse macular, painful, pruritic, localized mostly to the
forearms and associated with fever. It had increased in size
as well as forming blisters, no drainage reported. He
worked for a tree spraying company. Physical exam is
signicant for multiple tense bullae with central crusting
covering bilateral forearms, worse on posterior forearms;
anterior forearms had multiple erythematous macules
Summary of Results Labs were signicant for WBC 12.3
with 800 eosinophils, ESR>100, and CRP 4.35. Lesions
were thought to possibly be due to occupational exposure
vs. autoimmune disorder. Patient was started on
Vancomycin and Zosyn, chest X-ray was normal, skin
biopsy showed subepidermal vesicular dermatitis with lym-
phocytes and histiocytes,negative stains. Coccioidomycosis
fungal serology showed reactive IgM with titers <1/2.
Patient was started on uconazole and lesion regressed sig-
nicantly within 2 days
Conclusions Erythema Sweetobullosum is a rare manista-
tion of acute Coccidioidomycosis infection that is not
Erythema nodosum or Multiforme. It is a third entity that
was discussed in the past and called toxic erythema. It is a
parainammatory skin eruption presenting with erythema-
tous plaques and pseudoblistering on face, chest, neck, and
extremities in a striking photo distribution, Diagnoses is
made clinically, histology is changed based on when the
patient is seen. Earlier on its lymphocytic, later neutrophilic
then histiocytic and sometimes granulomatous.
46 BEYOND MICROCEPHALY: OTHER MANIFESTATIONS
OF NEONATAL AND INFANTILE CONGENITAL ZIKA
VIRUS
Lawicki J,
1,2
Pham A,
2
Le M,
2
Miao K,
2
Lee S,
2
Kim S,
2
Afghani B
2,3
.
1
Tufts
University, Medford, MA;
2
UC Irvine, Irvine, CA;
3
CHOC Childrens Hospital,
Orange, CA.
10.1136/jim-2016-000365.46
Purpose of Study While microcephaly may be considered
the most common manifestation in neonates and infants
Abstract 44 Table 1 Summary of Published Cases of Group
G Streptococcal Septic Arthritis in Children
Author Year Age Gender Joint Outcome
Brahmadathan 1989 1.5 Years Male Knee Recovered 1
Brahmadathan 1989 30 days Female Not stated Recovered 1
Tuazon 1980 7 years Male Ankle Recovered 2
1=Treatment not stated
2=Received 2 weeks of parenteral penicillin
Abstract 45 Figure 1
J Investig Med 2017;65:97293 117
Abstracts
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infected with Zika Virus (ZIKV), recent studies have docu-
mented rarer CNS and non-CNS ndings of ZIKV in
infected children. The aim of our study was to describe
these other ndings.
Methods Used We used search engines such as PubMed
and Google Scholar in our preliminary literature review.
Studies included in our review must have satised the fol-
lowing criteria: A) reported both CNS and non-CNS nd-
ings; B) studied subjects aged in utero up to infants less
than 1-year-old; C) included more than one case report,
and were related to the recent epidemic; and D) documen-
ted that a diagnosis of ZIKV was conrmed in either the
mother or infant via a laboratory test.
Summary of Results Of the 20 articles initially found, 5
satised our inclusion criteria. Our ndings are summar-
ized in table below.
Conclusions While microcephaly is a very common nding
in patients with congenital ZIKV infection, our review of the
literature demonstrates other major ndings include ventricu-
lomegaly, enlarged cisternae magnae, brain calcications,
hearing loss, arthrogryposis, and craniofacial anomalies. By
noting the existence of manifestations other than microceph-
aly, our study aims to assist physicians to better interpret man-
ifestations of ZIKV infection and be able to pinpoint the
diagnosis in a neonate with a potential congenital infection.
47 PULMONARY COCCIDIOIDOMYCOSIS AND
TUBERCULOSIS COINFECTION
Heidari A, Parekh A, Munoz A, Petersen G. Kern Medical UCLA,
Bakerseld, CA.
10.1136/jim-2016-000365.47
Purpose of Study Coccidioidomycosis is endemic in the
Southwest US, South and Central America. San Joaquin
Valley accounts for two third of the reported cases in
Abstract 46 Table 1
Reference
# Patients
Studied
Method of
Diagnosis
Timing of infection in
Mother
Microcephaly
Frequency Other CNS findings Non-CNS findings
Martines,
2016
5 neonates
(includes 2
miscarriages)
ZIKV-positive PCR
from brain matter
or placental tissues
Symptoms developed
during first trimester
3/3 (100%) neonates;
inconclusive in aborted
fetuses
(report on other 2
neonates not available)
2/5 (40%)combination of
lissencephaly, parenchymal
microcalcification,
degenerating glial cells
1/5 (20%)genital
malformation;
2/5 (40%)
combination of death,
arthrogryposis,
pulmonary
hypoplasia,
craniofacial
malformations
Vasco
Aragao,
2016
23 neonates Paired serology of
mother and
newborn
17 mothers reported
having rashes in the first
trimester, 5 in the
second, and 0 in the
third; 1 recalled having
rash, but forgot when
20/23 (87%) neonates
microcepahlic based on
head circumference
(HC); other 13% had
normal HC but
microcephaly on brain
imaging
30/30 underwent brain
imaging, and all (100%)
showed calcification
between cortical and
subcortical white matter, 19/
22 (86%) who had CT scan
had ventriculomegaly; 7 of 8
(88%) who underwent MRI
had enlarged cisternae
magnae
18/23 (78%)
craniofacial
disproportion
7/23 (30%)
exuberant external
occipital protuberance
12/23 (52%)
redundant scalp skin
Brasil,
2016
42/70 fetuses
had in-utero
ultrasounds (U/
S)
ZIKV-positive serum
and urine PCR in
70 mothers with
clinical findings c/w
Zika infection
6 to 35 weeks of
gestation among the 42
women in whom fetal
ultrasonography was
performed
14/42 had abnormal in
utero U/S
2/14 stillbirth
6/14 were born and 2/6
were normal at birth
1/6 had microcephaly
2/6 still in utero had
micocephaly
21%) fetuses had
microcephaly and
cerebral calcifications
(utero)
3/6 still in uterocerebral
calcifications with or without
microcephaly
2/6 still in uteroabnormal
or severely blocked middle
cerebral artery
1/6 still in utero
ventriculomegaly
1/6 still in uteromega
cisterna magna
1/6 born with cerebral
calcifications
5/12intrauterine
growth restriction
2/14stillbirth
1/12club foot
1/6 bornpoor
sucking reflexes at
birth
Leal,
2016
69 infants ZIKV-positive serum
in CSF
54 (86%) of 63 mothers
reported rashing during
the first trimester
Information needed to
determine degree of
microcephaly was
available for 65 (93%)
infants, among whom
44 (68%) had severe
microcephaly
Not mentioned 4/69 (6%)
sensorineural hearing
loss also had
microcephaly
Calvet,
2016
2 neonates Amniotic fluid at
28 weeks
pregnancy
Signs of fetal
malformation began via
U/S at 21 and 25 weeks
of gestation for Mother A
and B, respectively
2/2 (100%) neonates 2/2 (100%)hypoplasia of
cerebellar vermis (utero);
ventriculomegaly
1/2 (50%)absent
cerebellar vermis
1/2 (50%)enlarged
posterior fossa
1/2 (50%)
arthrogryposis in arms
and legs, cataract,
microphthalmia
118 J Investig Med 2017;65:97293
Abstracts
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California and majority of these patients were from Kern
County. Mycobacterium tuberculosis infection is virtually
found all over the world. In the US, California remains in
the top 5 states with highest incidence of tuberculosis.
Tuberculosis (TB) and Coccidioidomycosis share many
similarities in clinical presentation, radiologic character-
istics, demographics, and risk factors. Therefore,
co-infection of TB and coccidioidomycosis can be over-
looked which can lead to under diagnosis and underreport-
ing of these cases. This is an update of our previously
reported data. The objective of this study is to describe the
clinical, epidemiologic, laboratory, and radiologic features
of pulmonary TB and Coccidioidomycosis coinfection. We
have reported our data in 2010 and this is an update
Methods Used This is a retrospective review of medical
records of patients in Kern Medical. All patients with diag-
nosis of pulmonary TB or Coccidioidomycosis were identi-
ed and matched for coinfection. Patients demographics,
radiologic, serologic, microbiologic and laboratory results
were reviewed.
Summary of Results Fourteen patients with pulmonary TB
and Coccidioidomycosis coinfection were identied. All
patients were immigrants from Mexico and Philippines.
Majority of the patients were male (85%) and Hispanics
(85%). Coccidioidomycosis and pulmonary TB were diag-
nosed at the same time on (64%) of the cases. On 14% of
the cases, Coccidioidomycosis was diagnosed rst before
TB, and in 21% of the cases TB was diagnosed before
Coccidioidomycosis. We had one reported mortality due to
massive hemoptysis. Risk factors and co morbidities asso-
ciated with the confection were diabetes, HIV positive,
alcohol, tobacco, eld worker, and homelessness. Majority
of the patients had apical or bi-apical lesions (50%), the
rest presented as miliary, mediastinal, left or right lower
lung inltrates and cavitation.
Conclusions Pulmonary tuberculosis and
Coccidioidomycosis coinfection can occur. Patients from
geographic areas with endemicity of both infections with
predisposing conditions such as diabetes, history of immi-
gration, positive HIV, alcohol and tobacco abuse should be
screened for both TB and Coccidioidomycosis.
Neonatal Pulmonary I
Concurrent Session
12:45 PM
Thursday, January 26, 2017
48 EXPOSURE TO THIRDHAND SMOKE RESULTS IN
OXIDATIVE DAMAGE, INCREASED APOPTOSIS, AND
ALTERED DIFFERENTIATION IN FETAL LUNG
FIBROBLASTS
Sakurai R,
1
Shen H,
1
Hang B,
3
Schick S,
2
Lee C,
1
Rehan V
1
.
1
Harbor-UCLA
Medical Center, Torrance, CA;
2
University of California, San Francisco,
San Francisco, CA;
3
Lawrence Berkeley National Laboratory, Berkeley, CA.
10.1136/jim-2016-000365.48
Purpose of Study Thirdhand smoke (THS), the residual
tobacco smoke remaining in the environment after tobacco
has been smoked, represents an underestimated public
health hazard. THS contains a large number of
constituents, but the effect of composite THS exposure on
the developing lung has not been reported. Given the toxic
nature of the many of its constituents, we hypothesized
that THS results in oxidative damage, increased apoptosis,
and myogenic differentiation when exposed to lung bro-
blasts, which are key determinants of lung development.
Methods Used Using standard methods, embryonic day
(e) 19 lung broblasts were isolated from Sprague Dawley
rat pups. At 8090% conuence, these cells were exposed
for either 24 or 72 h to composite THS (0.1x, 0.25x, 0.5x,
1x), which was generated according to previously described
methods (Hang et al, Mutagenesis; 28:38191; 2013).
Oxidative damage [qRT-PCR for hypoxanthine phosphori-
bosyltransferase 1 (HPRT) and polymerase β(POLB)
genes]; cell proliferation (thymidine incorporation), cell
apoptosis (BcL-2, Bax, and p-Caspase 3 by Western ana-
lysis), mesenchymal markers of differentiation (bronectin,
calponin, peroxisome proliferator-activated receptor
(PPAR-γ), lymphoid enhancer binding factor-1 (LEF-1),
and activation of nicotinic acetylcholine receptor (nAchR)
α3 by Western analysis) were determined.
Summary of Results Compared to the control group, the
THS group showed 1) dose-dependent oxidative damage (
RT-PCR products of HPRT and POLB); 2) decrease in cell
proliferation (thymidine incorporation) and increase in
cell apoptosis (BcL-2/Bax ratio andp-Caspase ); 3) dose
dependent alterations in mesenchymal differentiation
markers (PPAR-γ,bronectin, and calponin), indicative of
myogenic differentiation; and 4) nAchR stimulation (in
nAchRα3 protein levels).
Conclusions THS causes oxidative damage, cell apoptosis,
and differentiation to a myogenic phenotype in fetal rat
lung broblasts. These data indicate a potentially disruptive
effects of THS on alveolar epithelial-mesenchymal para-
crine signaling, setting the stage for chronic lung damage in
THS exposed infants. [Grant Support: HL27137;
HD71731;TRDRP: 23RT-0018].
49 MATERNAL TOBACCO SMOKE EXPOSURE ALTERS
MRNA LEVELS OF WNT SIGNALING GENES IN
NEWBORN RAT LUNG
Cox A, Wang H, Joss-Moore L. University of Utah, Salt Lake City, UT.
10.1136/jim-2016-000365.49
Purpose of Study Fetal exposure to maternal tobacco
smoke (MTS) causes growth restriction and alters lung
development in humans and animal models, with sex-
divergent outcomes. Lung development depends upon Wnt
signaling and expression of Wnt target genes. We previ-
ously demonstrated that surgically induced fetal growth
restriction impaired Wnt signaling and output of Wnt
target genes in the rat lung, also in a sex-divergent manner.
However, the effect of MTS on Wnt signaling and expres-
sion of Wnt target genes in the rat lung is unknown. We
hypothesized that MTS causes sex-divergent changes in
mRNA levels of Wnt transducers Lef1, and Tcf4, and Wnt
target genes, MMP-9, MMP-12, AXIN2, and TGFb1 in the
newborn rat lung.
Methods Used Pregnant rats were exposed to room air
(Control) or tobacco smoke (MTS) from gestational day 11
J Investig Med 2017;65:97293 119
Abstracts
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28, 2017
) Camel, California, January 26Meeting
Formerly Western Regional2017 (
Western Medical Research Conference
doi: 10.1136/jim-2016-000365.1
2017 65: 98-193 J Investig Med
http://jim.bmj.com/content/65/1/98
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