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| __NOTOC__ | | __NOTOC__ |
| {{SI}}
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| {{CMG}} {{AE}} {{AKI}}
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| {{SK}} Fetal varicella syndrome, Congenital varicella-zoster syndrome, Varicella embryo-fetopathy, Varicella embryopathy, Varicella fetopathy, Fetal varicella-zoster syndrome | | {{Roseola}} |
| ==Overview==
| | {{CMG}}:{{AE}}{{DAMI}} |
| Congenital Varicella syndrome is a rare disease resulting from [[Varicella Zoster virus]](VZV) infection during the period of [[gestation]]. [[Viremia]] during the primary infection can result in [[transplacental]] transmission of the infection to the developing [[fetus]]. 25% of women are estimated to have [[varicella]] infection during the [[pregnancy]] but the risk of developing congenital varicella syndrome is around 2%, therefore majority of the patients have normal [[newborns]]. Patients with primary infection before 20 weeks of [[gestation]] are at a higher risk of developing the severe form of infection, affecting the [[eyes]], [[limbs]], [[skin]] and the [[central nervous system]]. Diagnosis requires a documented history of primary infection in the mother and serial [[ultrasound]] demonstrating features suggestive of congenital [[varicella]]. There is no definitive treatment, termination of [[pregnancy]] in fetuses with severe features is recommended. [[Vaccination]] to prevent maternal [[varicella]] infection and proper counseling to avoid contact with infected people are important for the management options to reduce the incidence of congenital varicella syndrome.
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| ==Historical Perspective==
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| *In 1947, Lynch reported the first case of [[congenital varicella syndrome]].<ref name="LaforetLynch1947">{{cite journal|last1=Laforet|first1=Eugene G.|last2=Lynch|first2=Charles L.|title=Multiple Congenital Defects Following Maternal Varicella|journal=New England Journal of Medicine|volume=236|issue=15|year=1947|pages=534–537|issn=0028-4793|doi=10.1056/NEJM194704102361504}}</ref>
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| *In 1987, Alkalay coined the term fetal varicella syndrome.
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| ==Pathophysiology== | | ==[[Roseola overview|Overview]]== |
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| ===Pathogenesis=== | | ==[[Roseola historical perspective|Historical Perspective]]== |
| '''Primary infection during the period of gestation:'''
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| *Once a [[pregnant]] [[women]] has a primary [[varicella infection]], [[transplacental]] transmission of the [[virus]] can take place as a result of the [[viremia]] affecting the [[fetus]] in utero. The resulting clinical manifestations are dependent on the [[gestational]] age of the [[fetus]] at the time of infection.<ref name="pmid4682642">{{cite journal| author=McKendry JB, Bailey JD| title=Congenital varicella associated with multiple defects. | journal=Can Med Assoc J | year= 1973 | volume= 108 | issue= 1 | pages= 66-8 | pmid=4682642 | doi= | pmc=1941110 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4682642 }} </ref>
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| *An estimated of 25% [[fetuses]] are infected with [[varicella]] when the mother has a primary infection during the period of [[gestation]], but only less than 2% of [[fetus]] develop congenital varicella syndrome.<ref name="ParyaniArvin1986">{{cite journal|last1=Paryani|first1=Sharon G.|last2=Arvin|first2=Ann M.|title=Intrauterine Infection with Varicella-Zoster Virus after Maternal Varicella|journal=New England Journal of Medicine|volume=314|issue=24|year=1986|pages=1542–1546|issn=0028-4793|doi=10.1056/NEJM198606123142403}}</ref><ref name="pmid942245">{{cite journal| author=Brice JE| title=Congenital varicella resulting from infection during second trimester of pregnancy. | journal=Arch Dis Child | year= 1976 | volume= 51 | issue= 6 | pages= 474-6 | pmid=942245 | doi= | pmc=1546018 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=942245 }} </ref>
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| *The risk of developing severe manifestations is high when the infection occurs before 20 weeks of [[gestation]], which co-relate to the period of [[gestation]] when the innervation of the eyes and limbs occur.<ref name="PastuszakLevy1994">{{cite journal|last1=Pastuszak|first1=Anne L.|last2=Levy|first2=Maurice|last3=Schick|first3=Betsy|last4=Zuber|first4=Carol|last5=Feldkamp|first5=Marcia|last6=Gladstone|first6=Johnathan|last7=Bar-Levy|first7=Fanny|last8=Jackson|first8=Elaine|last9=Donnenfeld|first9=Alan|last10=Meschino|first10=Wendy|last11=Koren|first11=Gideon|title=Outcome after Maternal Varicella Infection in the First 20 Weeks of Pregnancy|journal=New England Journal of Medicine|volume=330|issue=13|year=1994|pages=901–905|issn=0028-4793|doi=10.1056/NEJM199403313301305}}</ref>
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| *The risk of developing congenital varicella is (lower) 0.55% between weeks 0 and 12 and is higher (1.4%) between weeks 13 and 20.<ref name="pmid15979274">{{cite journal| author=Tan MP, Koren G| title=Chickenpox in pregnancy: revisited. | journal=Reprod Toxicol | year= 2006 | volume= 21 | issue= 4 | pages= 410-20 | pmid=15979274 | doi=10.1016/j.reprotox.2005.04.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15979274 }} </ref>
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| *[[VZV]] is a neurotrophic virus and the pathogenesis of the wide variety of manifestations in the fetus is unclear, but it is proposed to be related to reactivation of the virus in the [[fetus]], as it cannot mount a immune response aganist the infection.<ref name="pmid3027637">{{cite journal| author=Higa K, Dan K, Manabe H| title=Varicella-zoster virus infections during pregnancy: hypothesis concerning the mechanisms of congenital malformations. | journal=Obstet Gynecol | year= 1987 | volume= 69 | issue= 2 | pages= 214-22 | pmid=3027637 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3027637 }} </ref><ref name="pmid2560525">{{cite journal| author=Grose C| title=Congenital varicella-zoster virus infection and the failure to establish virus-specific cell-mediated immunity. | journal=Mol Biol Med | year= 1989 | volume= 6 | issue= 5 | pages= 453-62 | pmid=2560525 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2560525 }} </ref>
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| *[[VZV]] virus is present in the [[sensory ganglia]] of the [[posterior roots]] of the [[spinal cord]] during the latent phase, reactivation of the virus in results in the destruction of the nervous tissue resulting in the characteristic cicatrical skin lesions, limb hypoplasia, bladder denervation, and [[bulbar palsy]].<ref name="pmid15655777">{{cite journal| author=Nikkels AF, Delbecque K, Pierard GE, Wienkotter B, Schalasta G, Enders M| title=Distribution of varicella-zoster virus DNA and gene products in tissues of a first-trimester varicella-infected fetus. | journal=J Infect Dis | year= 2005 | volume= 191 | issue= 4 | pages= 540-5 | pmid=15655777 | doi=10.1086/426942 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15655777 }} </ref>
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| *The presence of diffuse [[calcifications]] in the [[liver]], [[spleen]], [[myocardium]] and [[brain]] support a mechanism of [[hematogenous]] spread.<ref name="pmid9285750">{{cite journal| author=Rigsby CK, Donnelly LF| title=Fetal varicella syndrome: association with multiple hepatic calcifications and intestinal atresia. | journal=Pediatr Radiol | year= 1997 | volume= 27 | issue= 9 | pages= 779 | pmid=9285750 | doi=10.1007/s002470050229 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9285750 }} </ref>
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| ==Epidemiology and Demographics== | | ==[[Roseola classification|Classification]]== |
| *Congenital varicella syndrome is a rare disease and only 135 cases are reported in literature.
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| ==Causes== | | ==[[Roseola pathophysiology|Pathophysiology]]== |
| Congenital Varicella Syndrome is caused by Varicella zoster virus (VZV), a human alpha herpes virus.
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| ==Differentiating Congenital Varicella Syndrome From Other Diseases== | | ==[[Roseola causes|Causes]]== |
| The most important congenital infections, which can be transmitted vertically from mother to fetus are the [[TORCH infections]]. These infections have overlapping features and hence, must be differentiated from Congenital Varicella Syndrome:<ref name="pmid25677998">{{cite journal |vauthors=Neu N, Duchon J, Zachariah P |title=TORCH infections |journal=Clin Perinatol |volume=42 |issue=1 |pages=77–103, viii |year=2015 |pmid=25677998 |doi=10.1016/j.clp.2014.11.001 |url=}}</ref><ref name="pmid25654000">{{cite journal |vauthors=Ajij M, Nangia S, Dubey BS |title=Congenital rubella syndrome with blueberry muffin lesions and extensive metaphysitis |journal=J Clin Diagn Res |volume=8 |issue=12 |pages=PD03–4 |year=2014 |pmid=25654000 |pmc=4316306 |doi=10.7860/JCDR/2014/10271.5293 |url=}}</ref>
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| <small>
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| {| class="wikitable"
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| !Congenital Infection
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| !Cardiac Findings
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| !Skin Findings
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| !Ocular Findings
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| !Hepatosplenomegaly
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| !Hydrocephalus
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| !Microcephaly
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| !Intracranial Calcifications
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| !Hearing deficits
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| |-
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| !Congenital Varicella Syndrome
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| | -
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| *Cicatrical Skin Lesions
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| *Skin Edema
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| *Micropthalmus
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| *Cataracts
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| |✔
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| |✔
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| |✔
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| |-
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| ![[Toxoplasmosis congenital|Toxoplasmosis]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Maculopapular rash]]
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| * [[Chorioretinitis]]
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| |✔
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| |✔
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| |✔
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| |Diffuse intracranial calcifications
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| |-
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| ![[Congenital Syphils]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Maculopapular rash]]
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| * [[Chorioretinitis]]
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| * [[Glaucoma]]
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| |✔
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| |-
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| ![[Rubella, congenital|Rubella]]
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| * [[Patent ductus arteriosus (PDA)]]
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| * [[Pulmonary artery stenosis]]
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| * [[Coarctation of the aorta]]
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| * [[Myocarditis]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Chorioretinitis]]
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| * [[Cataracts]]
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| * [[Glaucoma]]
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| * [[Microphthalmia]]
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| |✔
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| |✔
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| |✔
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| |✔
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| |-
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| ![[Cytomegalovirus (CMV)]]
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| |✔
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Chorioretinitis]]
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| |✔
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| |✔
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| |Periventricular calcifications
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| |✔
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| |-
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| ![[Herpes simplex virus (HSV)]]
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| * [[Myocarditis]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Vesicles]]
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| * [[Chorioretinitis]]
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| |✔
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| |✔
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| |✔
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| |✔
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| |-
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| ![[Parvovirus B19]]
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| * [[Myocarditis]]
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| * [[Petechiae]]
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| * [[Subcutaneous]] [[edema]]
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| * [[Chorioretinitis]]
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| * [[Cataracts]]
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| |✔
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| |}
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| </small>
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| ==Natural History, Prognosis and Complications== | | ==[[Roseola differential diagnosis|Differentiating Any Disease from other Diseases]]== |
| ===Natural History===
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| [[VZV]] infection during [[pregnancy]] result in a normal newborn birth in majority of the patients, however, in a few patients it can result in congenital varicella syndrome, [[neonatal varicella]] and [[clinical zoster]] during [[infancy]], the outcomes are dependent on the [[gestational]] age of [[fetus]]. Early gestational period infection via the [[transplacental]] route can result in congenital varicella syndrome resulting in a [[misscarriage]], [[abortion]] or a [[newborn]] with features affecting the [[limbs]], [[eyes]], [[central nervous system]], [[autonomic nervous system]] and present with features such as [[low birthweight]], cutaneous scarring, limb hypoplasia, [[microcephaly]], cortical atrophy, [[chorioretinitis]] and [[cataracts]].<ref name="pmid7802767">{{cite journal| author=Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M| title=Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. | journal=Lancet | year= 1994 | volume= 343 | issue= 8912 | pages= 1548-51 | pmid=7802767 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7802767 }} </ref><ref name="pmid402633">{{cite journal| author=Frey HM, Bialkin G, Gerson AA| title=Congenital varicella: case report of a serologically proved long-term survivor. | journal=Pediatrics | year= 1977 | volume= 59 | issue= 1 | pages= 110-2 | pmid=402633 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=402633 }} </ref> | |
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| ===Prognosis=== | | ==[[Roseola epidemiology and demographics|Epidemiology and Demographics]]== |
| In fetuses with severe infection it results in [[abortion]]. [[Infants]] born with signs of congenital varicella syndrome the prognosis is poor and die during the first few months of life.<ref name="pmid11190597">{{cite journal| author=Sauerbrei A, Wutzler P| title=The congenital varicella syndrome. | journal=J Perinatol | year= 2000 | volume= 20 | issue= 8 Pt 1 | pages= 548-54 | pmid=11190597 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11190597 }} </ref><ref name="pmid7802767">{{cite journal| author=Enders G, Miller E, Cradock-Watson J, Bolley I, Ridehalgh M| title=Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. | journal=Lancet | year= 1994 | volume= 343 | issue= 8912 | pages= 1548-51 | pmid=7802767 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7802767 }} </ref> Infants with milder symptoms can have a normal development and good [[prognosis]].<ref name="pmid6328456">{{cite journal| author=Kotchmar GS, Grose C, Brunell PA| title=Complete spectrum of the varicella congenital defects syndrome in 5-year-old child. | journal=Pediatr Infect Dis | year= 1984 | volume= 3 | issue= 2 | pages= 142-5 | pmid=6328456 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6328456 }} </ref><ref name="pmid11113846">{{cite journal| author=Schulze A, Dietzsch HJ| title=The natural history of varicella embryopathy: a 25-year follow-up. | journal=J Pediatr | year= 2000 | volume= 137 | issue= 6 | pages= 871-4 | pmid=11113846 | doi=10.1067/mpd.2000.109005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11113846 }} </ref>
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| ===Complications=== | | ==[[Roseola risk factors|Risk Factors]]== |
| Congenital varicella infection can result in the following complications:<ref name="pmid4121940">{{cite journal| author=Savage MO, Moosa A, Gordon RR| title=Maternal varicella infection as a cause of fetal malformations. | journal=Lancet | year= 1973 | volume= 1 | issue= 7799 | pages= 352-4 | pmid=4121940 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4121940 }} </ref>
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| *[[Fetal demise]]
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| *[[Intrauterine growth restriction]]
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| *[[Premature]] delivery
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| *[[Developmental Delay]]
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| ==Diagnosis== | | ==[[Roseola screening|Screening]]== |
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| ===History and Symptoms=== | | ==[[Roseola natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| '''Symptoms of primary infection in Mother :'''
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| *Primary infection in the mother presents with [[fever]], [[malaise]] and a [[maculopapular]] skin rash in the beginnning which becomes [[vesicular]] and crust over with healing.<ref name="pmid8533407">{{cite journal| author=Katz VL, Kuller JA, McMahon MJ, Warren MA, Wells SR| title=Varicella during pregnancy. Maternal and fetal effects. | journal=West J Med | year= 1995 | volume= 163 | issue= 5 | pages= 446-50 | pmid=8533407 | doi= | pmc=1303168 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8533407 }} </ref>
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| '''Symptoms in the Neonate'''
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| *[[Skin Rash]]<ref name="pmid17180380">{{cite journal| author=Sauerbrei A, Wutzler P| title=Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections. | journal=Med Microbiol Immunol | year= 2007 | volume= 196 | issue= 2 | pages= 95-102 | pmid=17180380 | doi=10.1007/s00430-006-0032-z | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17180380 }} </ref>
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| *Shortened hands and legs with malformed fingers
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| *Cloudiness of the [[cornea]]<ref name="pmid8540940">{{cite journal| author=Andreou A, Basiakos H, Hatzikoumi I, Lazarides A| title=Fetal varicella syndrome with manifestations limited to the eye. | journal=Am J Perinatol | year= 1995 | volume= 12 | issue= 5 | pages= 347-8 | pmid=8540940 | doi=10.1055/s-2007-994493 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8540940 }} </ref>
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| *Small head size
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| *[[Seizures]]<ref name="pmid519294">{{cite journal| author=Alexander I| title=Congenital varicella. | journal=Br Med J | year= 1979 | volume= 2 | issue= 6197 | pages= 1074 | pmid=519294 | doi= | pmc=1596860 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=519294 }} </ref>
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| *Yellowish discolouration of the [[eyes]] and [[skin]]
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| ===Physical Examination=== | | ==Diagnosis== |
| Clinical manifestations suggestive of Congenital varicella syndrome include:<ref name="pmid1733414">{{cite journal| author=Magliocco AM, Demetrick DJ, Sarnat HB, Hwang WS| title=Varicella embryopathy. | journal=Arch Pathol Lab Med | year= 1992 | volume= 116 | issue= 2 | pages= 181-6 | pmid=1733414 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1733414 }} </ref><ref name="pmid1336591">{{cite journal| author=Mendívil A, Mendívil MP, Cuartero V| title=Ocular manifestations of the congenital varicella-zoster syndrome. | journal=Ophthalmologica | year= 1992 | volume= 205 | issue= 4 | pages= 191-3 | pmid=1336591 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1336591 }} </ref>
| | [[Roseola history and symptoms|History and Symptoms]] | [[Roseola physical examination|Physical Examination]] | [[Roseola laboratory findings|Laboratory Findings]] | [[Roseola electrocardiogram|Electrocardiogram]] | [[Roseola chest x ray|Chest X Ray]] | [[Roseola CT|CT]] | [[Roseola MRI|MRI]] | [[Roseola echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Roseola other imaging findings|Other Imaging Findings]] | [[Roseola other diagnostic studies|Other Diagnostic Studies]] |
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| {| border="1"
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| !
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| !'''Clinical Manifestations in congenital varicella syndrome'''
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| |-
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| !'''Skin'''
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| *Cicatricial lesions( Zig-Zag scarring in dermatomal distribution)<ref name="pmid2322006">{{cite journal| author=Lloyd KM| title=Skin lesions as the sole manifestation of the fetal varicella syndrome. | journal=Arch Dermatol | year= 1990 | volume= 126 | issue= 4 | pages= 546-7 | pmid=2322006 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2322006 }} </ref>
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| *Hypopigmentation
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| !'''Eye'''
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| *[[Chorioretinitis]] <ref name="pmid411463">{{cite journal| author=Charles NC, Bennett TW, Margolis S| title=Ocular pathology of the congenital varicella syndrome. | journal=Arch Ophthalmol | year= 1977 | volume= 95 | issue= 11 | pages= 2034-7 | pmid=411463 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=411463 }} </ref>
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| *[[Cataracts ]]<ref name="pmid717518">{{cite journal| author=Cotlier E| title=Congenital varicella cataract. | journal=Am J Ophthalmol | year= 1978 | volume= 86 | issue= 5 | pages= 627-9 | pmid=717518 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=717518 }} </ref>
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| *[[Micropthalmia]]
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| *[[Anisocoria]]
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| |-
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| !'''Central Nervous System'''
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| *[[Cortical atrophy]]/[[porencephaly]]
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| *Developmental Delay
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| *[[Microcephaly]]<ref name="pmid1743417">{{cite journal| author=Scheffer IE, Baraitser M, Brett EM| title=Severe microcephaly associated with congenital varicella infection. | journal=Dev Med Child Neurol | year= 1991 | volume= 33 | issue= 10 | pages= 916-20 | pmid=1743417 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1743417 }} </ref>
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| *[[Autonomic instability]]
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| !'''Musculoskeletal system'''
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| *Limb hypoplasia
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| *Muscle hypoplasia
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| !'''Systemic Manifestations'''
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| *[[Intrauterine growth retardation]]
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| !'''Urinary Tract'''
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| *[[Hydroureter]]
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| *[[Hydronephrosis]]
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| |}
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| <small>Table adopted from varicella in fetus and newborn<ref name="SmithArvin2009">{{cite journal|last1=Smith|first1=Candice K.|last2=Arvin|first2=Ann M.|title=Varicella in the fetus and newborn|journal=Seminars in Fetal and Neonatal Medicine|volume=14|issue=4|year=2009|pages=209–217|issn=1744165X|doi=10.1016/j.siny.2008.11.008}}</ref></small>
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| ===Laboratory Findings===
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| The diagnosis of congenital varicella syndrome is based on a documented history of varicella infection during the pregnancy and the presence of fetal manifestations on [[ultrasound]].<ref name="pmid2175786">{{cite journal| author=Scharf A, Scherr O, Enders G, Helftenbein E| title=Virus detection in the fetal tissue of a premature delivery with a congenital varicella syndrome. A case report. | journal=J Perinat Med | year= 1990 | volume= 18 | issue= 4 | pages= 317-22 | pmid=2175786 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2175786 }} </ref><br>
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| {| border="1"
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| |- | |
| !
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| !'''Key findings for diagnosis of congenital varicella syndrome'''
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| |-
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| !'''History'''
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| *Positive history for [[varicella]] infection during the [[period of gestation]]
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| |- | |
| !'''Fetus / Neonatal Findings'''
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| *Presence of characteristic cicatrical skin lesions, eye lesions, neurological deficits, limb abnormalities
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| |-
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| !'''Proof of Intrauterine Varicella infection'''
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| *Positive [[PCR]] for [[VZV]] [[DNA]]
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| *Persistence of [[IgG]] [[antibodies]] at 7 months of age
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| |} | |
| <small>Table adopted from Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections<ref name="SauerbreiWutzler2006">{{cite journal|last1=Sauerbrei|first1=A.|last2=Wutzler|first2=P.|title=Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections|journal=Medical Microbiology and Immunology|volume=196|issue=2|year=2006|pages=95–102|issn=0300-8584|doi=10.1007/s00430-006-0032-z}}</ref></small><br>
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| '''Diagnosis of primary infection in the mother :''' In pregnant women diagnosis of a primary infection requires a combination of clinical manifestations and series of diagnostic tests. The tests are performed on the samples from the vesicular skin lesions and include the following:
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| *[[Culture]] for [[VZV]], but takes 10 to 12 days to obtain the results.
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| *Direct fluroscent [[antigen]] staining with [[monoclonal]] [[antibodies]] detects the [[VZV]] glycoproteins in the cells.
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| *[[PCR]] for [[VZV]] [[DNA]]
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| *[[Serological]] tests are not useful for the dectection of primary infection in the [[mother]] as it takes time for the [[IgG]] antibodies to be produced aganist [[VZV]].
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| '''Prenatal Diagnosis'''
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| *Sequential [[ultrasound]] of the [[fetus]] is helpful to establish the presence of [[varicella]] infection and assess the severity of intrauterine infection.<ref name="pmid10215075">{{cite journal| author=Hartung J, Enders G, Chaoui R, Arents A, Tennstedt C, Bollmann R| title=Prenatal diagnosis of congenital varicella syndrome and detection of varicella-zoster virus in the fetus: a case report. | journal=Prenat Diagn | year= 1999 | volume= 19 | issue= 2 | pages= 163-6 | pmid=10215075 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10215075 }} </ref><ref name="pmid16601342">{{cite journal| author=Meyberg-Solomayer GC, Fehm T, Muller-Hansen I, Enders G, Poets C, Wallwiener D et al.| title=Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella syndrome. | journal=Fetal Diagn Ther | year= 2006 | volume= 21 | issue= 3 | pages= 296-301 | pmid=16601342 | doi=10.1159/000091360 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16601342 }} </ref>
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| *[[Amniocentesis]] should be performed 4 weeks after the primary infection in the mother, positive [[amniotic fluid]] [[PCR]] for [[VZV]] can establish the presence of infection in the amniotic fluid but does not provide evidence regarding the presence of infection or the severity of infection in the [[fetus]]. There is no established evidence to recommend amniocentesis for the diagnosis and is not performed on regular basis.<ref name="pmid9369842">{{cite journal| author=Mouly F, Mirlesse V, Méritet JF, Rozenberg F, Poissonier MH, Lebon P et al.| title=Prenatal diagnosis of fetal varicella-zoster virus infection with polymerase chain reaction of amniotic fluid in 107 cases. | journal=Am J Obstet Gynecol | year= 1997 | volume= 177 | issue= 4 | pages= 894-8 | pmid=9369842 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9369842 }} </ref>
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| *Presence of [[VZV]] [[IgM]] [[antibodies]] in [[fetal blood]].
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| ===Imaging Studies===
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| ====Ultrasound====
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| *Sequential ultrasound in women with [[varicella]] infection during the [[period of gestation]] is the preffered diagnostic investigation to identify anomalies in the fetus. [[Ultrasound]] is usally done 4 weeks after the primary infection as earlier [[ultrasound]] might fail to detect anomalies. The findings suggestive of congenital varicella syndrome include limb deformities, microcephaly and hydrops.
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| *The following is a list of features that can be present in the fetus<ref name="pmid1337112">{{cite journal| author=Pretorius DH, Hayward I, Jones KL, Stamm E| title=Sonographic evaluation of pregnancies with maternal varicella infection. | journal=J Ultrasound Med | year= 1992 | volume= 11 | issue= 9 | pages= 459-63 | pmid=1337112 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1337112 }} </ref><ref name="pmid8994252">{{cite journal| author=Hofmeyr GJ, Moolla S, Lawrie T| title=Prenatal sonographic diagnosis of congenital varicella infection--a case report. | journal=Prenat Diagn | year= 1996 | volume= 16 | issue= 12 | pages= 1148-51 | pmid=8994252 | doi=10.1002/(SICI)1097-0223(199612)16:12<1148::AID-PD7>3.0.CO;2-J | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8994252 }} </ref>
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| **Cutaneous scars
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| **Musculoskeletal deformities such as [[limb hypoplasia]] and contractures
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| **[[Intrauterine growth restriction]]
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| **[[Ventriculomegaly]], [[microcephaly]] with [[polymicrogyria]], and [[porencephaly]]
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| **[[Micropthalmia]] and congenital [[cataracts]]
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| **Calcification in the [[brain]], [[spleen]] and [[liver]]<ref name="pmid9285750">{{cite journal| author=Rigsby CK, Donnelly LF| title=Fetal varicella syndrome: association with multiple hepatic calcifications and intestinal atresia. | journal=Pediatr Radiol | year= 1997 | volume= 27 | issue= 9 | pages= 779 | pmid=9285750 | doi=10.1007/s002470050229 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9285750 }} </ref>
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| **Features of [[Hydrops fetalis]] such as [[skin edema]], [[hepatosplenomegaly]]
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| **[[Colonic Atresia]]<ref name="pmid8523241">{{cite journal| author=Hitchcock R, Birthistle K, Carrington D, Calvert SA, Holmes K| title=Colonic atresia and spinal cord atrophy associated with a case of fetal varicella syndrome. | journal=J Pediatr Surg | year= 1995 | volume= 30 | issue= 9 | pages= 1344-7 | pmid=8523241 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8523241 }} </ref>
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| **[[Polyhydramnios]]
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| ====MRI====
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| Prenatal MRI is a useful investigation to assess the extent of CNS involvement and to confirm the findings of ultrasound.<ref name="pmid12975778">{{cite journal| author=Verstraelen H, Vanzieleghem B, Defoort P, Vanhaesebrouck P, Temmerman M| title=Prenatal ultrasound and magnetic resonance imaging in fetal varicella syndrome: correlation with pathology findings. | journal=Prenat Diagn | year= 2003 | volume= 23 | issue= 9 | pages= 705-9 | pmid=12975778 | doi=10.1002/pd.669 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12975778 }} </ref>
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| '''Postnatal Diagnosis'''
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| *[[Postnatal]] diagnosis of [[intrauterine]] [[varicella]] infection in the [[infant]] is by [[serological]] persistance of [[VZV]] [[IgG]] [[antibodies]] at 7 months of life.<ref name="pmid185578">{{cite journal| author=Gershon AA, Raker R, Steinberg S, Topf-Olstein B, Drusin LM| title=Antibody to Varicella-Zoster virus in parturient women and their offspring during the first year of life. | journal=Pediatrics | year= 1976 | volume= 58 | issue= 5 | pages= 692-6 | pmid=185578 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=185578 }} </ref>
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| ==Treatment== | | ==Treatment== |
| | [[Roseola medical therapy|Medical Therapy]] | [[Roseola surgery|Surgery]] | [[Roseola primary prevention|Primary Prevention]] | [[Roseola secondary prevention|Secondary Prevention]] | [[Roseola cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Roseola future or investigational therapies|Future or Investigational Therapies]] |
|
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| ===Medical Therapy=== | | ==Case Studies== |
| *In patients with established infection early in the [[period of gestation]], regular follow up and [[ultrasound]] examination is recommended.<ref name="SauerbreiWutzler2006">{{cite journal|last1=Sauerbrei|first1=A.|last2=Wutzler|first2=P.|title=Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections|journal=Medical Microbiology and Immunology|volume=196|issue=2|year=2006|pages=95–102|issn=0300-8584|doi=10.1007/s00430-006-0032-z}}</ref>
| | [[Roseola case study one|Case #1]] |
| *[[Termination]] of [[pregnancy]] is indicated in cases with the presence of definitive signs of congenital varicella infection.
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| *There is insufficient evidence regarding the prevention of transmission and treatment of congenital varicella syndrome with [[IgG]] [[immunoglobulins]] and [[acyclovir]].<ref name="pmid15979274">{{cite journal| author=Tan MP, Koren G| title=Chickenpox in pregnancy: revisited. | journal=Reprod Toxicol | year= 2006 | volume= 21 | issue= 4 | pages= 410-20 | pmid=15979274 | doi=10.1016/j.reprotox.2005.04.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15979274 }} </ref>
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| *Varicella infection doesnot progress [[postnatally]], so treatment with [[acyclovir]] is not indicated.<ref name="HarishJamwal2009">{{cite journal|last1=Harish|first1=Rekha|last2=Jamwal|first2=Ashu|last3=Dang|first3=Ketan|title=Congenital varicella syndrome/ vericella zoster virus VZV fetopathy|journal=The Indian Journal of Pediatrics|volume=77|issue=1|year=2009|pages=92–93|issn=0019-5456|doi=10.1007/s12098-009-0259-y}}</ref>
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| *[[Isolation]] is recommended in patients with active skin lesions.
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| ===Surgical Therapy===
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| There are no surgical therapies for treatment of congenital varicella syndrome.
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| ==Prevention==
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| ===Primary Prevention===
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| *Documentation of previous [[varicella]] [[infection]] and [[vaccination]] status in all [[pregnant]] [[women]] at the first [[antenatal]] visit.<ref name="urlPrevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP)">{{cite web |url=https://www.cdc.gov/Mmwr/Preview/Mmwrhtml/rr5604a1.htm |title=Prevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP) |format= |work= |accessdate=}}</ref>
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| *If the [[pregnant]] women has no previous infection or is not [[vaccinated]], [[VZV]] [[IgG]] [[antibody]] testing must be done to determine the maternal immune status. <ref name="pmid22385673">{{cite journal| author=Shrim A, Koren G, Yudin MH, Farine D, Maternal Fetal Medicine Committee| title=Management of varicella infection (chickenpox) in pregnancy. | journal=J Obstet Gynaecol Can | year= 2012 | volume= 34 | issue= 3 | pages= 287-92 | pmid=22385673 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22385673 }} </ref>
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| *In [[pregnant]] [[women]] with [[positive]] [[IgG]], [[pregnant]] women are reassured that the [[IgG]] [[antibodies]] would protect the baby.
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| *In [[pregnant]] [[women]] with [[negative]] [[IgG]], counseling regarding the risks of [[varicella]] infection and education regarding the measures to avoid contact with [[varicella]] are recommended as [[vaccination]] aganist [[VZV]] is contraindicated during the [[pregnancy]].
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| *Women who are [[seronegative]] should recieve two doses of the vaccine during the [[postpartum]] period 4 to 8 weeks apart with no effect on [[breast feeding]].
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| *Women can be [[vaccinated]] during the [[preconception]] period, but are adviced to avoid conceiving for a month after the last dose of the [[vaccine]].
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| ===Secondary Prevention===
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| *In [[pregnant]] women with exposure to [[varicella]], [[passive immunization]] with [[varicella zoster virus]] [[antibodies]] (VZV IgG) should be administered after 72-96 hours of exposure as [[postexposure prophylaxis]]. [[Passive immunization]] is not proven to reduce viremia therefore its role in preventing congenital varicella syndrome is not well established. Only indication at present it to prevent [[maternal]] complications of [[varicella]] in [[pregnancy]].<ref name="pmid21262937">{{cite journal| author=Cohen A, Moschopoulos P, Maschopoulos P, Stiehm RE, Koren G| title=Congenital varicella syndrome: the evidence for secondary prevention with varicella-zoster immune globulin. | journal=CMAJ | year= 2011 | volume= 183 | issue= 2 | pages= 204-8 | pmid=21262937 | doi=10.1503/cmaj.100615 | pmc=3033924 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21262937 }} </ref>
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| ==References==
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| {{reflist|2}}
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