Varicella-Zoster Virus

Human alphaherpesvirus 3 (HHV-3), also known as varicella zoster virus, is an enveloped double-stranded deoxyribonucleic acid (DNA) virus belonging to the family Herpesviridae. It is globally pervasive and one of eight herpes viruses known to infect humans. It is an exclusively human pathogen without any known animal or insect vector or host.

History and Epidemiology

Historically, varicella zoster virus was thought to be innocuous. It was even considered a rite of passage for children, especially compared to other equally prevalent but more dangerous childhood diseases, such as smallpox and poliomyelitis. That changed with the advent of effective chemotherapy, the rising number of bone and organ transplants, and the increasing use of immunocompromising medications. This resulted in rising numbers of immunocompromised children, some of whom died from varicella zoster virus.

Prior to 1995, when the one-dose varicella vaccine varivax was introduced in the United States, there were approximately 4 million varicella cases, 12,000 varicella-related hospitalizations, and 125 varicella-related deaths annually. Due to continued varicella outbreaks, a second dose of varicella vaccine was recommended in 2006. A 90% drop in varicella incidence occurred after the implementation of the two-dose varicella vaccine schedule.

Herpes zoster occurs in over 1.2 million individuals annually in the United States with an estimated 30% of people experiencing it in their lifetime. The two main risk factors for varicella zoster virus reactivation causing herpes zoster are age and immunocompromised status. It is estimated that 20% of herpes zoster cases occur in the fifth decade of life, 40% in the sixth decade, and over 50% in individuals over 85, which corresponds with the age-related decline in T cell-mediated immunity.

Presentation, Diagnosis, and Diagnostic Workup

There are two distinct clinical forms of varicella zoster virus infection: varicella (chickenpox) and herpes zoster (shingles). Varicella is typically a childhood infection and presents as a mild disease in the immunocompetent. Symptoms can be severe and even fatal in the immunocompromised. Transmission is via direct contact with vesicle fluid from skin lesions and close contact with aerosolized droplets. The incubation period after exposure ranges from 10 to 21 days, with symptoms lasting between four and seven days. Symptoms might start with fever and malaise one to two days prior to rash onset, but a rash may present first, especially in younger children. The rash is generalized and appears first on the face, chest, and back, and it then spreads to the entire body. The lesions are classically present in all stages of development simultaneously. People with varicella are contagious two days before the rash onset until all the lesions have crusted over without the appearance of any new lesions for 24 hours.

After the primary infection with HZV-causing varicella, the virus remains latent in the dorsal root ganglia and can reactivate later in an individual’s life. Only about 20% of individuals have a prodromal phase that includes headache, photophobia, or malaise. The rash is typically painful, itchy, and tingly. It often begins as erythematous papules, progresses to vesicles, and then becomes pustular until the vesicles crust over. The rash classically forms along one or two adjacent dermatomes and does not cross the body’s midline. Those with herpes zoster can transmit the HZV virus to close contacts who have never had varicella.

The diagnosis of varicella and herpes zoster is usually made clinically; however, additional diagnostic information can be useful in individuals who are immunocompromised and either have an atypical rash or disseminated disease without cutaneous lesions.

Polymerase chain reaction can confirm varicella zoster virus. It has the highest sensitivity, specificity, and turnaround time, as compared to direct fluorescent antibody and viral culture.

The varicella zoster virus EIA (enzyme immunoassay) screen detects both the immunoglobulin M (IgM) and varicella zoster virus IgG (immunoglobulin G), which demonstrates either acute infection (IgM) or chronic infection (IgG). Serologic testing can show the presence of varicella zoster virus antibodies, which corresponds to a history of varicella or vaccination and equates to protection from infection or reinfection with the virus. These varicella-zoster virus antibody immunity screens can help determine if an individual is at risk for contracting varicella (and therefore requires varicella zoster virus immunization). They have also been used in vaccine trials to assess response to immunization.

Differential Diagnoses

It is important to differentiate varicella zoster virus from other infections with similar symptomatology. The two most common differential diagnoses, their differentiating signs and symptoms, and differentiating tests are:

• Smallpox, which has a more prominent fever and constitutional symptoms. The lesion distribution is centrifugal (face and extremities), and they are all at the same stage of development. The PCR test will show positive confirmation for smallpox.
• Herpes simplex virus (HSV), which usually affects the oral and genital mucous lesions. Laboratory tests will be positive for HSV1 or HSV 2.

Management (Nonpharmacologic and Pharmacologic)

Individuals with varicella typically only require supportive care to manage their symptoms. The decision to initiate antiviral therapy depends on the patient’s age, clinical presentation, and the presence of comorbidities. Since varicella is usually self-limited in healthy children under 13 years without comorbidities (other than neonates), no antiviral therapy is needed. For patients who have risk factors for complications (eg, neonates, pregnant people, and people who are immunocompromised), antiviral therapy is administered to reduce symptom severity and risk of complications. Supportive care, such as antihistamines, can help alleviate symptoms. Salicylates should be avoided, as aspirin has been associated with the onset of Reye syndrome in the setting of a viral infection in pediatric patients.

The management of herpes zoster includes antiviral therapy for patients without additional risk factors and with uncomplicated herpes zoster if they present for treatment within 72 hours of clinical onset. There is minimal efficacy for treatment with antivirals beyond 72 hours except for individuals with herpes zoster ophthalmicus, neurologic complication, pregnant patients, and people who are immunocompromised. Antivirals increase healing of cutaneous lesions and reduce the severity of acute neuritis. Adjunctive therapy, such as gabapentin, tricyclic antidepressants, and glucocorticoids for patients with uncomplicated herpes zoster has a minimal role except for those with severe neuritis.

Herpes zoster ophthalmicus is a condition where the varicella zoster virus reactivates within the trigeminal nerve and can cause blindness. Early consultation with an ophthalmologist and treatment with antiviral therapy and adjunctive topical steroid drops is critical in preventing vision loss.

References

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Author Bio

Mark Arredondo, MD, is an internal medicine physician with years of diverse medical experience with a focus on helping the most medically underserved. He was a National Health Service Corps Scholar and currently serves as the Medical Director of his local health department. Dr. Arredondo is a member of the Master Teacher Guild and has taught medical and nurse practitioner students for over 25 years.