Varicella-zoster virus (VZV) causes two distinct clinical diseases, the first one is varicella or commonly known as chickenpox and the other is herpes zoster or shingles. Chickenpox is a ubiquitous and highly contagious disease (infection). But it is usually a benign illness of childhood characterized by an exanthematous vesicular rash.

Varicella-zoster virus:

Varicella-zoster virus is a member of the family Herpesviridae, which shares with other members certain structural characteristics like lipid envelope surrounding a nucleocapsid with icosahedral symmetry, a total diameter of approximately 180–200 nm, and centrally located double-stranded DNA that is approximately125,000 bp in length.

What is the Pathogenesis of chickenpox?

The mode of transmission is through respiratory route. The replication of the virus takes place presumably in the nasopharynx, which leads to seeding of the reticuloendothelial system with virus and ultimately to the development of viremia. Viremia in chickenpox is reflected by the diffuse and scattered skin lesions. The viremia can be demonstrated by the recovery of VZV (Varicella-zoster virus) from the blood or by the detection of viral DNA in blood or chickenpox lesions (exanthematous vesicular rash) by PCR (polymerase chain reaction). Vesicles usually involve the dermis with degenerative changes characterized by ballooning of the dermis. Multinucleated giant cells and eosinophilic intranuclear inclusions are present in the vesicular fluid. Sometimes infection of varicella-zoster virus may involve blood vessels of the skin which results in necrosis and epidermal bleeding. As the disease (chickenpox) progresses the vesicular fluid becomes cloudy due to presence of polymorphonuclear leukocytes and also degenerated cells and fibrin. Finally the vesicles either rupture and release their fluid (which includes infectious virus) or are gradually reabsorbed (generally which occurs during recovery phase).

What is the Epidemiology of Chickenpox?

The incubation period of chickenpox is 10 to 21 days but generally it Secondary attack rates in susceptible young family members (siblings) within a household are 70–90%. Patients are usually infectious approximately 48 h before onset of the vesicular rash, during the period of vesicle formation (which generally lasts 4–5 days), and until all vesicles are crusted (14–17 days). The infectiousness of the patients before onset of the vesicular rash makes it practically impossible to prevent (except through vaccination) the disease.

Humans are the only known reservoir for Varicella-zoster virus. Chickenpox is highly contagious, with an attack rate of mote than 90% among susceptible (seronegative for VZV) individuals. Chickenpox all the races equally as well as both the sexes (male and females are equally affected by chickenpox). Children of 5–9 years old are most commonly affected and they account for at least half of all cases. Most of the remaining cases involve children 1–4 and 10–14 years old. Older than 14 years of age, chickenpox is not frequent. Varicella-zoster virus is endemic in almost all parts of the world and becomes epidemic among susceptible individuals during seasonal peaks (late winter and early spring). The above epidemiology of chickenpox is changing dramatically due to VZV vaccination during the second year of life.

What are the clinical symptoms of chickenpox?

The common symptoms of chickenpox are a skin rash, low-grade fever, and malaise (generalized body ache). Their severity of chickenpox varies from person to person and some individuals have very few lesions, while others have as many as 2000 lesions. Younger children generally have fewer vesicles than older individuals. If patient’s immune system is normal chickenpox is usually a benign illness which is associated with lassitude and mild fever [temperature of 37.8°–39.4°C (100°–103°F)] of 3–5 days duration. The skin lesions (maculopapules, vesicles, and scabs in various stages of evolution) of chickenpox are the hallmark of the infection. The skin lesions are generally pruritic and cause itching. The skin lesions generally appear on the trunk and face and rapidly spread to involve other areas of the body and evolve from maculopapules to vesicles over hours to days. The skin lesions are small with a diameter of 5–10 mm. Successive crops of skin lesions appear over a 2–4 day period. The lesions (maculopapules and vesicles) can also be found on the mucosa of the pharynx as well as in the vagina. Secondary and tertiary cases within families are generally associated with a relatively large number of vesicles and more severe chickenpox.

Immunocompromised patients (children as well as adults), especially those with leukemia usually have lesions (often with a hemorrhagic base) of large numbers and take longer to heal than those patients with normal immune system. In immunocompromised patients the risk of visceral complications are higher, which occur in 30–50% of cases (in immunocompromised patients) and 15% of the complications may be fatal, especially in the absence of antiviral therapy.

What are the complications of chickenpox?

The most common complication of chickenpox is secondary bacterial superinfection of the skin. The common organisms involved in bacterial superinfection are Streptococcus pyogenes or Staphylococcus aureus, including methicillin resistant strains. The superinfection generally results from scratching the skin lesions. Gram's staining of skin lesions can help in identifying the organisms. The next important complication is involvement; especially in children is the CNS (central nervous system). The symptoms of CNS involvement include acute cerebellar ataxia and meningeal inflammation, which generally appears approximately 3 weeks after onset of the rash. But the CNS involvement in children is a benign complication of chickenpox infection and generally does not require hospitalization. Other CNS complications of chickenpox include aseptic meningitis, encephalitis, transverse myelitis, Guillain-Barré syndrome, Reye's syndrome etc. Encephalitis can occur in 0.1–0.2% of children with chickenpox.

The most serious complication of chickenpox is Varicella pneumonia, which generally occurs in adults and it can occur in as many as 20% of adult cases of chickenpox and is particularly severe in pregnant women. Varicella pneumonia due to VZV usually starts on 3–5 days into the illness and is associated with tachypnea (high respiratory rate), cough, dyspnea (breathlessness), and fever. Cyanosis, pleuritic chest pain, and hemoptysis are also common symptoms of vericella pneumonia. X-ray shows nodular infiltrates and interstitial pneumonitis (inflammation of alveoli). The reolution of X-ray findings usually correlates with improvement of the skin rash.

Other complications (other than CNS and respiratory) of chickenpox include myocarditis, corneal lesions, nephritis, acute glomerulonephritis, arthritis, bleeding diatheses, and hepatitis.

Chickenpox during pregnancy:

Chickenpox in mother, within 5 days before delivery or within 48 hours after delivery is associated with a high mortality rate (as high as 30%). Chickenpox in newborn is unusually severe due to immature immune system and absence of protective antibodies which are not received transplacentally. Congenital varicella is extremely uncommon and the clinical manifestations are limb hypoplasia, cicatricial skin lesions, and microcephaly at birth. Varicella pneumonia (respiratory complication of chickenpox) is generally severe in pregnant women.

How chickenpox is diagnosed?

The diagnosis of chickenpox is not difficult and clinically characteristic rash and a history of recent exposure can easily lead to a prompt and correct diagnosis. Unequivocal confirmation of the diagnosis of chickenpox is possible only by isolation of VZV, demonstration of seroconversion (from negative serologic test for chickenpox to positive) or a fourfold or greater rise in antibody titer between convalescent and acute phase serum specimens, or the detection of VZV DNA by PCR (polymerase chain reaction). Polymerase chain reaction can detect the VZV DNA in vesicular fluid, but this is available only in a limited number of diagnostic laboratories. The most frequently used serologic tests for assessing host response to VZV are the fluorescent antibody to membrane antigen (FAMA) test, enzyme-linked immunosorbent assay (ELISA) and the immunofluorescent detection of antibodies to VZV membrane antigens. Out of these the FAMA test and the ELISA most sensitive.

Differential diagnosis of chickenpox:

Some viral infections can mimic chickenpox and those include coxsackievirus infection, echovirus infection, atypical measles, disseminated HSV (herpes simplex virus) infection in patients with atopic dermatitis etc. But the rashes due these viruses generally have a hemorrhagic component rather than being vesicular or vesiculopustular. Rickettsialpox can also sometimes be confused with chickenpox. But rickettsialpox occurs due to bite of mite and there is typical "herald spot" at the site of the mite bite and also there is headache which may be pronounced. In case of confusion, serologic test should confirm diagnosis.

How chickenpox is treated?

In chickenpox patients with normal immune system, the medical management is essentially symptomatic and directed towards prevention of complications of chickenpox. Secondary bacterial infection of the skin can be avoided by meticulous skin care and skin care should include close cropping of fingernails. Good hygiene like daily bathing and soaks are essential part of management of chickenpox. Itching can be a problem in chickenpox and it can be decreased with topical dressings or the administration of antipruritic (anti-itching) drugs. Tepid water baths and wet compresses should be done which are better than drying lotions for the relief of itching.

Drug (anti viral) therapy of chickenpox: Acyclovir therapy at the dose of 800 mg by mouth five times daily for 5–7 days should be given for adolescents and adults with chickenpox of less than or equal to 24 hours duration. Acyclovir may also be given to children of less than 12 years of age and may be beneficial if treatment started early in the disease (less than 24 hours) at a dose of 20 mg/kg every 6 hourly. The second generation antiherpetic drugs valacyclovir and famciclovir are recommended these days as they are equally efficacious (as that of acyclovir) or superior to acyclovir in treatment of chickenpox. But there are no controlled clinical trials of these second generation drugs (valacyclovir and famciclovir) although there are certain pharmacokinetic advantages of these drugs.

In severely immunocompromised patients (transplant recipients, patients with certain cancers) with chickenpox treatment with intravenous acyclovir (at the dose of 10-12.5 mg per kg every 8 hourly for one week) should be started as early in the disease as possible, which can reduce complications of chickenpox, but has no effect on skin lesions. Immunosuppressive treatment should be reduced while administering intravenous acyclovir. For low-risk immunocompromised patients, oral therapy with valacyclovir or famciclovir appears sufficient.

Treatment of complications of chickenpox: Complications like varicella pneumonia may require removal of bronchial secretions and ventilatory support, along with other forms of symptomatic management described above.

How to prevent chickenpox?

At present three methods of prevention of VZV (mainly chickenpox) are available. These methods are vaccination (with live attenuated varicella vaccine), administer varicella-zoster immune globulin (VZIG) to individuals who are at risk of development of complication if chickenpox is contacted and prophylaxis with antiviral therapy and to individuals at high risk who are ineligible for vaccine.

The first method of prevention of chickenpox:

A live attenuated varicella vaccine (Oka) is available, which is safe as well as highly efficacious and is recommended for all children of 1 year of age to 12 years of age, who have not had chickenpox and for adults who are seronegative for VZV. In children single dose of vaccine is given and in adults two doses are given. After vaccination the infection (known as breakthrough infection) which occurs is mild and helps in spreading vaccine virus to susceptible contacts. In many developed countries universal vaccination is done for chickenpox and it has reduced the incidence of chickenpox dramatically. This vaccine can also reduce herpes zoster (incidence by more than 50%, severity of illness by more than 60% and postherpetic neuralgia by 66%). That is the reason Advisory Committee on Immunization Practices in the United States has recommended that persons in the age group of more than 60 years should be offered this vaccine in order to reduce the frequency of shingles as well as the severity of postherpetic neuralgia.

The second method of prevention of chickenpox:

The second method of prevention of chickenpox is administration of VZIG (varicella-zoster immune globulin) to individuals who are susceptible to chickenpox and are at high risk for developing complications and have had a confirmed exposure. VZIG should be given within 96 hours of the exposure to chickenpox, but ideally it should be given within 72 hours of exposure. But the availability of VZIG is limited (and in the future also it will be limited).

The following are recommendations for VZIG administration:

1. Individual should receive VZIG as soon as possible, preferably within 96 hours of exposure and not beyond that.

2. The exposure criteria are residing in the same house as that of patient of chickenpox, playmate (face-to-face indoor play) of a chickenpox patient, in newborn infants (if mother develop chickenpox 5 days before delivery or 48 hours after delivery). VZIG should not be given in mother if mother has herpes zoster. In hospital same bed room with chickenpox patient with 2-4 beds or adjacent beds in large ward or face-to-face contact with infectious person, visit by a person deemed contagious etc.

3. Susceptible pregnant women should also receive VZIG, so are immunocompromised children who are susceptible as they are without a history of varicella or varicella immunization.

4. Premature infants (28 weeks of gestation) if mother lacks a reliable history of chickenpox or if there are no serologic evidence of protection against chickenpox.

The third method of prevention of chickenpox:

The third method of prevention of chickenpox is antiviral prophylaxis therapy (acyclovir, valacyclovir and famciclovir) which should be given to individuals at high risk (who are not eligible for vaccination or who are beyond the 96 hours window after direct contact with chickenpox). Previously acyclovir was used for this purpose, but these days valacyclovir or famciclovir are preferred. Therapy should be started (7 days after exposure) when the host is midway into the incubation period. This can significantly decrease disease severity even if not able to prevent the disease completely.