Two cases of chickenpox complicating pregnancy and an update on management

Transcription

1 Hong Kong Journal of Emergency Medicine Two cases of chickenpox complicating pregnancy and an update on management CL Tang, SH Tsui, HK Tong Susceptible pregnant women with chickenpox exposure are uncommon but are medical emergency conditions. Chickenpox infection in the first trimester is associated with the congenital varicella syndrome and in the third trimester is associated with fatal complications and the neonatal varicella syndrome. In this article, two cases and the management of chickenpox during pregnancy are discussed. (Hong Kong j.emerg.med. 2009;16: 46-50) Keywords: Acyclovir, immunoglobulins, infectious pregnancy complications, vertical disease transmission Introduction Susceptible pregnant women with chickenpox exposure are uncommon emergency conditions. Early recognition of the condition and prompt treatment are essential to minimise complications and fatal outcome. Case 1 A 28-year-old primigravida came to our department at her 33 weeks and 4 days gestation in October She sat next to a child for three hours during her meal four days ago, the latter developed chickenpox rash after one day. She was not certain of her chickenpox history. She was asymptomatic and on examination she had no skin rash. An urgent blood for varicellazoster IgG test was arranged and the result was negative. She was given varicella-zoster immunoglobulin (VZIG) injection and the course was unremarkable. She was reminded to come back if symptoms and complications of chickenpox, such as vesicular rash, shortness of breath, fever and cough developed. She had an uneventful delivery and postnatal course. Case 2 Correspondence to: Tang Chung Leung, FHKCEM, FHKAM(Emergency Medicine), PDipID(HKU) Queen Mary Hospital, Accident & Emergency Department, 102 Pokfulam Road, Pokfulam, Hong Kong cltepoch@hotmail.com Tsui Sik Hon, MRCP(UK), FHKCEM, FHKAM(Emergency Medicine) Tong Hon Kuan, FHKCEM, FHKAM(Emergency Medicine) A 30-year-old primigravida came to our department in February 2007 because of developing chickenpox rash at her 35 weeks gestation. Her domestic helper had chickenpox two weeks ago. She had feverish feeling and malaise at the day of attendance. She noted rash on the thigh and thus came to our

2 Tang et al./chickenpox complicating pregnancy 47 department for consultation. On examination, she was afebrile, and vesicular rash was noted at her abdomen and right thigh. She was transferred to Princess Margaret Hospital isolation ward for further management. Vesicular fluid for varicella-zoster virus (VZV) direct immunofluorescence test was done and was positive. She was given acyclovir for the treatment of the rash. No new rash developed during her stay in hospital. She was discharged and referred back to the antenatal clinic. Discussion Varicella-zoster virus is a DNA virus which belongs to the herpes family. It is highly contagious and transmitted through air, direct contact with vesicular fluid or via fomites. The incubation period is between 10 to 21 days, but it can be prolonged to 28 days for those who receive VZV immunoglobulin injection. The course of infection includes fever, crops of pruritic maculopapular rash which then become vesicular and then crusted. It takes 4-5 days for the vesicular rash to crust. The disease is infectious two days before the onset of rash until the vesicles crust over. Complications are usually mild in children but can be serious in adults especially pregnant women and smokers. Varicella complicating pregnancy Chickenpox rarely occurs in pregnancy as over 90% of women of childbearing age possess virus-specific immunoglobulin (IgG) antibodies. A past history of chickenpox signifies acquisition of immunity; however, patient may not be certain about her history. 1 Though the disease is rare, it should be considered as medical emergency. Pregnant women infected with varicella have higher risk of getting varicella pneumonia, and the risk is higher in the third trimester. 2 Other risk factors include cigarette smoking, advanced maternal age, immunosuppression, history of chronic obstructive pulmonary disease, history of household contact and more than 100 skin lesions. Varicella pneumonia has a mortality of 45% among pregnant women, compared with 10-20% in the general population. 3 It is postulated that there are two viremic phases during the incubation period. The first is from days 4 to 6 and the second from days 10 to 14. At that time there may be transplacental transmission of virus. Prophylaxis with varicella-zoster immunoglobulin is effective only if given before the primary viremia and acyclovir should be considered for the prevention of the secondary viremia. 4 Following the secondary viremia, a maculopapular rash develops. Congenital varicella syndrome Maternal infection can infect the foetus either transplacentally or ascending from the birth canal. Primary infection during the first and second trimesters of pregnancy is associated with spontaneous abortion and congenital malformation of the foetus. Congenital varicella syndrome (CVS) was first described by Laforet and Lynch in It is characterised by skin lesions with dermatomal distribution, segmental maldevelopment of the musculoskeletal system, and segmental dysfunction of the somatic and autonomic nervous systems. It is hypothesised that the syndrome is the result of herpes-zoster reactivation of the foetus in utero rather than primary varicella infection. 5 The incidence is about 1-2% in the first 20 weeks, 6 and none can be found in the third trimester pregnancy. 7 Nearly 30% of infants born with CVS died during the first few months of life. 3 The diagnosis of CVS can be confirmed by both serology and ultrasonography during the antenatal period. Polymerase chain reaction (PCR) of amniotic fluid and foetal blood can detect the presence of viral DNA whereas ultrasound can detect structural abnormality, such as limb deformity and microcephaly, and intrauterine growth retardation of the foetus. Neonatal varicella Neonates can be infected by transplacental spread, ascending infection during birth, or contact with infectious subject after birth. Neonatal varicella can cause fatal newborn illnesses including necrotizing hepatitis, necrotizing pneumonia and necrosis of brain, adrenal glands and spleen. 8 The severity of neonatal infection is related to the time of onset of maternal

3 48 Hong Kong j. emerg. med. Vol. 16(1) Jan 2009 infection, as transplacental spread of antibodies reduces the severity of infection. If maternal rash develops near the delivery date, the infant will be exposed to maternal viremia without protecting antibodies, thus a fatal outcome is likely to happen. Neonatal chickenpox in the first 12 days of life is caused by intrauterine transmission. 3 Miller et al noted that antibodies were present in all babies if the mothers had rash more than 7 days before delivery. Fewer infants got antibodies if the mothers had rash 7-3 days before and no antibody if the babies were delivered within 3 days after the onset of rash. It is concluded that the severity of neonatal varicella would be increased if the mother has rash from 7 days before, and up to 7 days after delivery. 9 Complications will be less, and fatality will be decreased if the neonate can get sufficient antibody from the mother. Maternal zoster Herpes zoster is the reactivation of VZV in nerve tissue. During reactivation, it is not associated with viremia. Moreover, the infant has already acquired IgG antibodies from the mother. 9 Hence it will not cause any congenital varicella syndrome. Enders et al found no evidence of neonate VZV infection whose mother had perinatal zoster. 10 As a result, VZIG is not indicated for the newborn whose mother developed herpes zoster infection. Treatment The management includes two aspects, first, post-exposure prophylaxis with VZIG before the first viremic phase to kill the virus before its replication; and second, the administration of acyclovir during the viremic phase to inhibit virus replication, thus avoiding the complications and fatality. Susceptible pregnant women who have significant chickenpox exposure should be considered for VZIG therapy. Significant exposure means face-to-face contact with a chickenpox patient for at least five minutes, household contact, and stay in the same ward. Serological test should be considered as the majority of pregnant women are immune. VZIG should be given within 96 hours after exposure if the pregnant women have no antibody. VZIG should also be considered for neonates whose mother had chickenpox rash from 7 days before to 7 days after delivery. 11 The primary concern of giving VZIG is to prevent maternal complication in pregnancy such as pneumonia. It has no evidence in preventing foetal viremia or the congenital varicella syndrome. As the supply of VZIG is limited and expensive, it should be given for pregnant women who have indications. Anaphylactoid reaction can happen in those who receive VZIG injection. It is noted that VZIG can prolong the incubation period to 28 days. A longer period of isolation and observation is required. Despite VZIG injection, maternal complication and death have been reported. VZIG is of no use once the chickenpox rash and complication have developed. 12 Acyclovir inhibits viral DNA polymerase, thus stopping replication of the herpes virus. When given within 24 hours of the onset of rash, it has been shown to reduce mortality and morbidity associated with varicella. 13 However, there is no evidence that it can prevent CVS or neonatal varicella. Neonatal chickenpox can be treated with acyclovir to avoid complications. Acyclovir is a FDA pregnancy category C agent. It should be given cautiously before 20 weeks of gestation, though no teratogenic effect has been reported. Preventive measures It is important to advise non-immune pregnant women to avoid contact with chickenpox and zoster patient. In case of pregnant women with significant exposure and who are near term, ward isolation should be considered. For non-immune women, varicella vaccine can be considered. It provides greater than 70% protection against infection and 95% against severe disease. 14 The effect lasts for 7 to 10 years. It is a live attenuated vaccine and therefore women should avoid pregnancy for three months post-vaccination. Conclusion Though uncommon, we should regard susceptible pregnant women with chickenpox exposure a

4 Tang et al./chickenpox complicating pregnancy 49 medical emergency. Prompt recognition and treatment of the condition is essential to prevent fatal outcomes. The main aim of the use of VZIG is to prevent maternal complications such as varicella pneumonia and to reduce mortality. It has no use if chickenpox rash and complications have already developed. VZIG should also be considered for the infant whose mother has chickenpox rash from 7 days before to 7 days after delivery. Acyclovir can be considered for pregnant women who develop chickenpox rash and complications. A suggested management flowchart for susceptible pregnancy with chickenpox exposure is shown in Figure 1. IgG = immunoglobulin G VZV = varicella-zoster virus VZIG = varicella-zoster immunoglobulin Figure 1. Suggested management flowchart for susceptible pregnant women with chickenpox exposure.

5 50 Hong Kong j. emerg. med. Vol. 16(1) Jan 2009 References 1. Byrne BMP, Crowley PA, Carrington D. Chickenpox in pregnancy. Royal College of Obstetricians and Gynaecologists Green-top Guideline No.13. [September 2007]. [cited 2008 Dec 3]. Available from: rcog.org.uk/index.asp?pageid= Smego RA Jr, Asperille MO. Use of acyclovir for varicella pneumonia during pregnancy. Obstet Gynecol 1991;78(6): Sauerbrei A, Wutzler P. Herpes simplex and varicellazoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus infections. Med Microbiol Immunol 2007;196(2): Grose C. Varicella infection during pregnancy. Herpes 1999;6: Higa K, Dan K, Manabe H. Varicella-zoster virus infections during pregnancy: hypothesis concerning the mechanisms of congenital malformations. Obstet Gynecol 1987;69(2): Pastuszak AL, Levy M, Schick B, Zuber C, Feldkamp M, Gladstone J, et al. Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N Engl J Med 1994;330(13): Tan MP, Koren G. Chickenpox in pregnancy: revisited. Reprod toxicol 2006;21(4): Sauerbrei A, Wutzler P. Neonatal varicella. J Perinatol 2001;21(8): Miller E, Cradock-Watson JE, Ridehalgh MK. Outcome in newborn babies given anti-varicella zoster immunoglobulin after perinatal maternal infection with varicella-zoster virus. Lancet 1989;2(8659): Enders G, Miller E, Cradock-Watsons J, Bolley I, Ridehalgh M. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet 1994;343(8912): Task force on Infection Control. Fact sheet on chickenpox. Hong Kong: Hospital Authority; Mar Nathwani D, Maclean A, Conway S, Carrington D. Varicella infections in pregnancy and the newborn. A review prepared for the UK Advisory Group on Chickenpox on behalf of the British Society for the Study of Infection. J Infect 1998;36(Suppl 1): Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization (ACIP). MMWR 1996; 45(RR-11): Maupin RT. Obstetric infectious disease emergencies. Clin Obstet Gynecol 2002;45(2): Erratum Chan YC, Tse ML, Lau FL. Hong Kong Poison Information Centre: Annual Report Hong Kong J Emerg Med 2008;15(4): An error occurred in the article by Chan et al, titled Hong Kong Poison Information Centre: Annual Report 2006 published in the October 2008 issue of the Hong Kong Journal of Emergency Medicine. On page 250, Case 12, Line 8, the authors wrote: Ethylene glycol solution... This should have been: Polyethylene glycol solution...