Infectious Diseases

Varicella-Zoster Virus (VZV)

OVERVIEW: What every practitioner needs to know

Are you sure your patient has infection caused by varicella-zoster virus? What should you expect to find?

  • Varicella-zoster virus (VZV) causes chickenpox as a primary infection and shingles with recurrent infection. The symptoms of the former are a febrile, vesicular-pustular, pruritic rash. Those of the latter are pain and unilateral localized vesicles.

  • Chickenpox causes a vesicular rash with lesions in all stages of development, including macules, papules, vesicles, pustules, and scabs. Shingles causes a dermatomal rash that evolves from maculopapules to vesicles, pustules, and scabs.

How did the patient develop disease caused by varicella-zoster virus infection? What was the primary source from which the infection spread?

  • Primary infection is acquired by a susceptible individual exposed to someone excreting VZV either immediately prior to the development of the rash of chickenpox or during active infection. Shingles is the consequence of reactivation of latent virus from the sensory ganglia.

  • Historically, chickenpox occurred in children and was one of the most common childhood infections with an incidence approaching the US birthrate. With the licensure of a vaccine, disease incidence and attendant complications have plummeted. Nevertheless, some adults did not get vaccinated and remain susceptible to primary infection. Shingles increases in incidence in individuals with advancing age. Approximately 1 million cases occur annually in the United States.

Which individuals are of greater risk of developing varicella-zoster virus infection?

  • Immunocompromised hosts are most at risk for both chickenpox and shingles and the complications of both diseases. For these individuals, dissemination to involve visceral organs is a concern. In addition, pregnant women during the second and third trimesters are at increased risk for the complications of chickenpox. For pregnant women, the major concern is the development of pneumonia.

  • The predisposing factor is immunosuppression that is the consequence of an underlying disease or drugs, including, among others, hematopoietic cell transplantation, solid organ transplantation, AIDS, receipt of steroids or anti-tumor necrosis factor monoclonal antibodies, etc.

Beware: there are other diseases that can mimic varicella-zoster virus infection:

  • Vesiculopapular diseases that mimic chickenpox include disseminated herpes simplex virus infection, and enterovirus disease.

  • Dermatomal vesicular disease can be caused by herpes simplex virus and can be recurrent.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

  • The white blood cell (WBC) count will usually be normal in the immunocompetent host. However, laboratory values in the immunocompromised host will reflect the nature of the immune compromise.

  • Liver enzymes may be elevated in chickenpox, because the spread of the virus is by blood. Such tests reflect the state of immunocompromise in other populations.

Results that confirm the diagnosis

  • Vesicular lesions can be cultured, but the virus does not survive well in transport media, even when the sample is placed on ice. As a consequence, retrieval of virus in cell culture is limited and should only be performed by experienced personnel. Polymerase chain reaction (PCR) detection of viral DNA is the most sensitive and specific diagnostic for both chickenpox and shingles. The laboratory performing such tests must be reliable.

  • Saliva is an excellent source of viral DNA detected by PCR.

What imaging studies will be helpful in making or excluding the diagnosis of varicella-zoster virus infection?

  • Imaging studies are not required in the routine management of either chickenpox or shingles. However, with both infections, complications can occur that require imaging. For example, chickenpox can cause a syndrome of cerebellar ataxia or, rarely, encephalitis. With shingles, granulomatous arteritis can occur after the infection has resolved. In both circumstances, a magnetic resonance imaging (MRI) scan or a magnetic resonance angiogram (MRA) would be of value in delineating the pathology.

  • The costs of MRI scans and MRAs vary dramatically from one institution to another.

  • For adults, and especially pregnant women, with chickenpox, a chest radiograph is important to assess whether pneumonia is present.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

An infectious diseases consultation should be sought for an immunocompromised patient who has VZV infection.

If you decide the patient has this disease, what therapies should you initiate immediately?

Chickenpox in the normal host is usually a benign infection and is treated at the discretion of both the family and physician. Chickenpox in the immunocompromised host should always be treated. Shingles should be treated regardless of the age of the patient.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection what anti-infective should I order?

Empiric therapy for the immune-competent adult without complications should be either valaciclovir or famciclovir. The oral suspension of aciclovir is used in children who are thought to require therapy. Table I summarizes treatment options. Of note, the second generation antiviral drugs, valaciclovir and famciclovir, are superior to aciclovir and have improved pharmacokinetics and pharmacodynamics. However, neither is available in a useful pediatric formulation.

Table I.

Treatment of varicella-zoster virus infection
Organism Antibiotic Dose Alternative
ChickenpoxNormal host – child Aciclovir oral suspension 20mg/kg every 8 hours for 5–7 days
ChickenpoxNormal host – adult Valaciclovir 1g 3 times a day for 7 days FamciclovirAciclovir
ChickenpoxHospitalized patient Aciclovir intravenously Child: 500mg/M every 8 hours for 5–7 daysAdult: 10mg/kg every 8 hours for 7 days
Shingles ValaciclovirFamciclovir 1g 3 times a day for 5–7 days500mg 3 times a day for 5–7 days Aciclovir

2. Other key therapeutic modalities

  • No other therapies are required for either chickenpox or shingles.

  • Although controversial, the administration of concomitant corticosteroids to patients with shingles will improve the quality of life.

  • The administration of pregabalin may be of benefit in the management of post-herpetic neuralgia.

What complications could arise as a consequence of varicella-zoster virus infection?

The major concern for shingles is post-herpetic neuralgia as noted below.

What should you tell the family about the patient's prognosis?

  • The most common complication of chickenpox is secondary skin infection, usually with a Gram-positive organism. Rarer complications include infection of the central nervous system (CNS). In the immunocompromised host, lesion formation is longer than with the immunocompetent host.

  • The most important problem with shingles is both acute pain and post herpetic neuralgia. For individuals older than 50 years of age, 20% will have persistent dermatomal pain 6 months after the resolution of cutaneous infection.

  • In addition, herpes gangrenosum, disseminated disease, CNS involvement, motor paralysis, zoster ophthalmicus, Ramsay-Hunt syndrome, and granulomatous arteritis are all rare complications.

  • The immunocompromised host is more likely to develop disseminated disease.

What-if scenario:

  • If a patient presents with recurrent dermatomal disease, it is more likely to be caused by herpes simplex virus than VZV.

How do you contract varicella-zoster virus infection and how frequent is this disease?

The epidemiology of VZV infections is changing. We now have a vaccine for both chickenpox and shingles (two different vaccines) that has decreased the incidence of both diseases. With the two administration schedule for the chickenpox vaccine, the overall incidence of disease has decreased dramatically. Whether there will be waning immunity in young adults who received the chickenpox vaccine remains to be determined.

Similarly, the shingles vaccine is licensed for individuals older than 50 years of age and has decreased the incidence of disease by 50%. Shingles can recur, but it is extremely uncommon in the normal host. However, patients with HIV/AIDS can have multiple episodes of shingles for reasons that are not entirely clear.

Chickenpox historically occurred in late winter and early spring; however, with routine vaccination, the epidemiology has changed.

There is no seasonal variation in shingles.

Spread of chickenpox is airborne.

What pathogens are responsible for this disease?

Both chickenpox and shingles are caused by VZV. The virus associated with shingles is the same strain that infected the individual as a child.

How do these pathogens cause varicella-zoster virus infection?

VZV infections are spread by an airborne route. With primary infection, the virus infects the mucosa of the oropharynx, where an initial round of virus replication takes place, leading to viremia and the appearance of disseminated vesicles that involve the trunk to a greater extent than the extremities. The incubation period is generally 14 days.

Shingles is the reactivation of latent virus from a sensory ganglion. The triggers for reactivation are not well defined.

Importantly, chickenpox can result in another case of chickenpox but does not result in shingles. Conversely, shingles can cause chickenpox in a susceptible individual, but cannot cause shingles.

What other clinical manifestations may help me to diagnose and manage this disease?

Both chickenpox and shingles are clinical diagnoses.

What other additional laboratory findings may be ordered?

Supportive laboratory tests are not required.

How can varicella-zoster virus infection be prevented?

There are now licensed vaccines for both chickenpox and shingles. These vaccines differ according the amount of attenuated virus in each (i.e., chickenpox vaccine has significantly less virus). These vaccines have demonstrated efficacy and safety.

WHAT'S THE EVIDENCE for specific management and treatment recommendations?

There are no treatment guidelines that have been established by organized societies.

Gershon, AA, Breuer, J, Cohen, J, Cohrs, RJ. "Varicella zoster virus infection". Nat Rev Dis Primers.. vol. 1. 2015 Jul 2. pp. 15016.

Oxman, MN, Levin, MJ, Johnson, GR. "A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults". N Engl J Med. vol. 352. 2005. pp. 2271-84.

(This clinical trial is the basis of licensure of the adult shingles vaccine. The endpoints clearly define what a physician can expect in the deployment of the vaccine.)

Whitley, RJ.. "A 70-year-old woman with shingles: review of herpes zoster". JAMA. vol. 302. 2009. pp. 73-80.

(This case summarizes all aspects of the management of shingles.)

DRG CODES and expected length of stay

With the exception of the immunocompromised host with complications, these diseases are managed on an ambulatory care basis.

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