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| __NOTOC__ | | __NOTOC__ |
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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 the fetus 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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| ![[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 and 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 fetal demise or 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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| !'''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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| !'''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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| |}
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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 the VZV
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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 PCR for VZV can establish the presence of infection 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 with varicella fetopathy:<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 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.
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| *Only indication at present is 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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