Diagnosis and Management of Varicella Infection in Pregnancy

By Patrick Duff, M.D.

Perinatology 2010; 1:6-12

Clinical Case

A 27-year-old woman, gravida 3 para 2002, was exposed to chicken pox two days ago as a result o contact with her youngest child. Upon questioning by her obstetrician, she indicates that she canno whether she ever had chicken pox as a young child. She also has no memory of ever being vaccina chicken pox. What are the most appropriate next steps in the evaluation and management of this patient?

Dr. Duff is Professor of Clinical Obstetrics and Gynecology, Division of Maternal-Fetal Medicine at the Univers College of Medicine. duffp@obgyn.ufl.edu

Overview Varicella-zoster virus is a DNA virus. It is highly contagious; varicella will develop in approximately susceptible household contacts. The virus is spread from person to person via respiratory droplets contact. The incubation period of the infection is 10-14 days [1].

The incidence of varicella in pregnancy is 1-5 cases per 10,000 pregnancies. The frequency of infe increased among pregnant women. However, adults, including pregnant women, are much more lik children to develop serious complications of varicella. Less than 10% of all cases of varicella occur older than ten years, yet a disproportionate number of deaths occur in older individuals [1].

The most common serious sequela of varicella in adults is pneumonia, and approximately 20% of adults develop this complication. The most ominous hazard of varicella is encephalitis, which occur adults[1].

Women who develop varicella during pregnancy may experience spontaneous abortion, fetal demis congenital anomalies. Fortunately, all these complications are unusual. In an excellent large-scale Enders et al [2] evaluated 1373 women who experienced varicella during the first 36 weeks of preg cases of congenital varicella syndrome were identified; all resulted from maternal infection in the fir of pregnancy. The highest risk of congenital infection (2%) resulted from maternal infection in week pregnancy (7 affected infants in 351 pregnancies, 95% CI of risk 0.8-4.1%). Only two cases of cong varicella were identified in 472 pregnancies in which maternal infection occurred before 13 weeks ( 0.4%, 95% CI 0.05-1.5%). Interestingly, in 366 women who had herpes zoster infection (shingles) pregnancy, there were no instances of congenital varicella (95% CI 0-1.0%).

In a smaller study, Pastuszak et al [3] compared 106 women who contracted varicella in the first 20 pregnancy with 106 age-matched, non-exposed controls. The proportion of spontaneous abortions mean birth weights were similar in the two groups. There were more preterm births in the women w

(14.3 vs 5.6%, p = 0.05). The risk of varicella embryopathy was 1.2% (95% CI 0-2.4%).

Diagnosis of Varicella in the Mother Varicella usually causes a typical skin eruption. The lesions begin as raised red papules that progress quickly to clear vesicles. The vesicles then become cloudy pustules and, subsequently, dry to form crusted lesions. The lesions usually begin on the face and trunk and spread centripetally to the extremities. The lesions are intensely pruritic and occur in crops. The image to the right depicts a number of varicella lesions on the face of a young woman. Adult patients usually will have moderately severe systemic manifestations such as malaise, fatigue, and fever. Tachypnea and dyspnea may signal the onset of varicella pneumonia which, in turn, can be complicated by a superimposed bacterial infection. The presence of headache and photophobia suggests the possibility of encephalitis [1]. The diagnosis of acute varicella infection can usually be established on the basis of clinical findings alone. However, in problematic cases, varicella-zoster serology can be performed to confirm the diagnosis. Acutely infected patients typically have positive IgM antibody and negative IgG antibody [4 ].

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Diagnosis of Congenital Infection

As noted previously, the frequency of congenital malformations due to varicella infection, even in th pregnancy, is = 2% [2,3] The single best test for diagnosis of fetal injury is ultrasound examination. ultrasound findings suggestive of congenital varicella infection are intrauterine growth restriction, m ventriculomegaly, the presence of echogenic foci in the fetal liver, and circular scarring and deform limbs. Chorionic villus sampling, amniocentesis, and cordocentesis do not play an important role in of congenital varicella infection [1] Management of the Patient with Exposure to Varicella or an Acute Varicella Infection

At the time of the first prenatal appointment, the patient should be carefully questioned about prior v infection. Approximately 90-95% of patients of reproductive age will be immune to varicella, and the be at risk for second infections. If the patient has a well-documented history of natural infection, no

testing is indicated. If she is uncertain about prior infection, a varicella-zoster IgG antibody assay sh obtained [4]. If this test is positive, the patient can be reassured that she is immune and, therefore, for a second infection. If IgG antibody is not detected, the patient should be counseled that she is s and she should be told to avoid exposure to other individuals who may have acute varicella. She al counseled to avoid contact with patients who have herpes-zoster infection because she may acquir pox as a result of direct contact with skin lesions in these individuals.

If a susceptible pregnant woman is exposed to someone with chicken pox, prophylactic treatment is [5]. The most well-studied method of prophylaxis is administration of varicella zoster immune globu This agent is administered intramuscularly in a dose of one vial per 10 kg of actual weight, up to a m five vials. Ideally, VZIG should be administered within 96 hours of exposure. Because VZIG may pr incubation of the virus for at least one week, a patient who receives this agent should be observed possible infection for at least 28 days after receipt of VZIG.

Unfortunately, VZIG no longer is readily available in the United States from a domestic manufacture product is available only by special order from a Canadian pharmaceutical firm, through the U.S. di Enterprises and, thus, it may not be readily accessible to most practitioners.

If VZIG is not immediately available, clinicians should provide prophylaxis with acyclovir (80 5 times daily for 7 days) or valacyclovir (1000 mg orally 3 times daily for seven days)[5,6] Bo should be comparable in effectiveness, but the former is less expensive.

If a patient develops acute varicella, with or without prophylaxis, she should be treated immediately acyclovir or valacyclovir, in the doses presented previously [5]. In a landmark investigation by Dunk acyclovir reduced the duration and severity of chicken pox in normal children when therapy was init 24 hours of the onset of the rash. In a subsequent randomized, placebo-controlled trial of oral acyc Wallace and coworkers [8] demonstrated that treatment (800 mg five times daily for 7 days) reduce crusting of lesions from 7.4 to 5.6 days (P = 0.001), reduced the maximum number of lesions by 46 and also significantly decreased the duration of fever and severity of symptoms.

If a patient develops evidence of pneumonia, encephalitis, severe disseminated infection, or if she immunosuppressed, she should be hospitalized and treated with intravenous acyclovir. The approp intravenous administration of acyclovir is 10 mg per kg every 8 hours for 10 days. In obese patients weight should be used to calculate the dose of acyclovir.

Regrettably, there are no data indicating that treatment of the mother infected with varicella will pre congenital varicella infection. Therefore, if evidence of fetal injury is documented, the only managem are expectant observation vs. pregnancy termination. Neonatal Varicella Infection

As outlined above, when maternal infection occurs early in pregnancy, the risk to the fetus is very lo when infection occurs in the period five days prior to, and two days after delivery, the newborn infan considerable risk for developing neonatal varicella. Prior to the availability of antiviral drugs such as

20-30% of infants delivered in this situation developed varicella, and up to 30% of affected infants d manifestations of neonatal varicella include disseminated mucocutaneous infection, visceral infectio pneumonia [1].

In order to prevent neonatal varicella, the newborn should be isolated from the mother until all her crusted and dried. The infant should also be treated immediately with either VZIG or antiviral chem Prevention of Varicella Infection

Fortunately, a highly effective vaccine for prevention of varicella now is available [5,9]. The varicella (Varivax) is a live virus, single-valent vaccine. The vaccine also can be administered in quadraval combination with the measles, mumps, and rubella vaccine (MMRV). The efficacy of the varicella v 80% in adults and higher in children. Children in the age range 1-12 years require one subcutaneou vaccine. Individuals greater than 12 years of age should receive two doses of the vaccine, separate weeks. Since wide-spread vaccination was begun in the mid to late 1990s, mortality due to varicella declined [10].

Women of reproductive age who are susceptible to varicella should be offered the varicella vaccine of their annual examination or preconception counseling appointment. Similarly, susceptible pregna should be offered the vaccine immediately after delivery. Secure contraception is indicated for a mi month after the second dose of the vaccine is administered [11]. Adverse reactions to the vaccine uncommon. The principal ones include mild fever, inflammation and pain at the injection site, and a Contraindications to the varicella vaccine are listed in Table 1.

Table 1. Principal Contraindications to the Live Virus Varicella Vaccine

Pregnancy Immunodeficiency disorder* High dose systemic steroid therapy Allergy to neomycin Untreated active tuberculosis Severe systemic illness

*Immunodeficiency is a relative contraindication to vaccination. The vaccine has been tested and found to be safe and relatively effective in immunosuppressed patients [12] . In immunocompromised patients, the risks and benefits of vaccination must be weighed, and each decision must be individualized.

Conclusion

In the clinical case presented at the beginning of this article, the patient was uncertain about immun varicella. Therefore, once exposure was documented, she should have a varicella-zoster IgG assay

assay is positive, she can be reassured that she is immune. If the IgG is negative, she should be of prophylaxis with either VZIG or acyclovir. If she develops infection despite prophylaxis, she should with therapeutic doses of acyclovir for seven days. Should she develop one of the serious sequelae she should be hospitalized and treated with intravenous acyclovir. Following treatment, serial ultras examinations should be performed to assess for findings suggestive of congenital varicella. Figure 1 summarizes the management algorithm for varicella infection in pregnancy.

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