Varicella and herpes zoster

• Varicella-zoster virus (VZV) causes primary infection as varicella (chickenpox) and, years later, reactivation as herpes zoster (shingles) in about one in three people.
• Varicella is usually mild in children but can disseminate in the immunocompromised and damage the fetus and newborn; shingles is most often a painful dermatomal rash but can leave postherpetic neuralgia.
• Oral acyclovir or valacyclovir shortens both illnesses when started early; intravenous acyclovir is used for severe or disseminated disease.
• A live attenuated varicella vaccine prevents chickenpox and lowers later zoster risk; a recombinant zoster vaccine (Shingrix) prevents shingles in adults aged 50 years and older and in immunocompromised adults aged 19 years and older. ^[7]
• In pregnancy, screen women at booking, avoid varicella vaccine, and treat exposures with antivirals as the first choice; neonatal varicella is a medical emergency.

By the end of this page you should be able to:

1. Explain VZV pathogenesis from inhalation to latency and reactivation, and define the main clinical terms.
2. Describe the typical course, infectious period and complications of varicella in immunocompetent and immunocompromised hosts, and of herpes zoster.
3. Choose and dose oral and intravenous antiviral therapy for varicella, zoster, and exposed high-risk patients, with renal cautions.
4. Plan varicella post-exposure prophylaxis in pregnant women, neonates and immunosuppressed contacts.
5. Apply the current varicella and shingles vaccine schedules, contraindications and precautions.
6. Counsel a pregnant patient about fetal and neonatal risk.

• Varicella (chickenpox): a generalised, pruritic vesicular rash with fever and malaise, usually in childhood. Recovery usually gives lifelong immunity.^[1]
• Herpes zoster (shingles): a unilateral vesicular eruption in one or two adjacent dermatomes, with pain or altered sensation in the same area.^[2]
• Breakthrough varicella: wild-type varicella occurring more than 42 days after varicella vaccination; it is usually milder, with fewer than 50 lesions.^[1]
• Postherpetic neuralgia (PHN): pain that continues in the area of the original zoster rash after the lesions have healed.^[2]
• Congenital varicella syndrome (CVS): fetal abnormalities (skin scarring, limb hypoplasia, microcephaly, chorioretinitis, low birth weight) after maternal varicella in the first 20 weeks of pregnancy.^[1][3]
• Neonatal varicella: severe infection in a newborn whose mother develops varicella from 5 days before to 2 days after delivery.^[1][3]

Varicella occurs worldwide. In temperate climates it is mainly a childhood disease, with most children infected by age 10 years; in tropical areas children are infected later and more young adults remain susceptible.^[1] Before vaccination, varicella was endemic in the United States with an estimated 4 million cases each year.^[1] Since the national programme began in 1995, overall incidence has fallen by an average of 97% (1993-1995 to 2013-2014).^[1] Hospitalizations and deaths have declined by 93% and 94% respectively.^[1]

The virus is spread by direct contact with vesicular fluid or by inhalation of aerosols from the lesions, and from respiratory secretions. It is highly contagious: secondary attack rates among susceptible household contacts range from 61% to 100%.^[1] The infectious period runs from 1 to 2 days before the rash appears until all lesions have crusted.^[1] The incubation period is 14 to 16 days (range 10 to 21 days).^[1]

Herpes zoster occurs worldwide. About one in three people develop zoster during their lifetime, and about 50% of those who live to 85 years have had it.^[2][7] An estimated 1 million episodes occur annually in the United States.^[7] The incidence rises with age because cell-mediated immunity wanes; the lifetime risk is at least 32%.^[2] Zoster is about one fifth as infectious as varicella, and a person with localised zoster is contagious from rash onset until the lesions crust.^[2] Rates of zoster in children under 18 years and in older adults in the United States have decreased.^{[2] [6]}

The only reservoir is humans. VZV is transmitted person to person by direct contact with vesicular fluid or by inhalation of aerosols from the lesions of acute varicella or zoster.^[1][2]

Risk factors for zoster are advancing age, immunosuppression (solid organ or bone marrow transplant, cancer, HIV infection, or immunosuppressive drugs including corticosteroids), intrauterine exposure to VZV, and having had varicella before 18 months of age.^[2] Women develop shingles more often than men, and the illness is less common in Black people than in White people in US data.^[7]

VZV enters through the respiratory tract and conjunctiva and replicates in the nasopharynx and regional lymph nodes. A primary viraemia occurs 4 to 6 days after infection and spreads the virus to the liver, spleen and sensory ganglia. Further replication is followed by a secondary viraemia with infection of the skin.^[1] Virus can be cultured from mononuclear cells from 5 days before to 1 to 2 days after the rash appears.^[1]

Recovery gives lifelong immunity in most people. The virus remains latent in the sensory ganglia, kept in check by the host immune system. When cell-mediated immunity falls, the virus reactivates, travels down the sensory nerve, and produces a vesicular rash in the dermatome it supplies. The immunological control of latency is not fully understood.^[2]

Children who receive varicella vaccine have lower rates of herpes zoster than children who have natural infection, because vaccination avoids persistent wild-type latency and the risk of reactivating vaccine-strain virus is lower than that of wild-type virus.^[7]

In unvaccinated children the rash is often the first sign of illness; adults may have 1 to 2 days of fever and malaise beforehand.^[1] The rash is generalised, pruritic, and progresses within 24 hours from macules to papules to fragile vesicles on an erythematous base, before crusting. It starts on the scalp, face or trunk and spreads to the extremities, with the heaviest concentration on the trunk. Lesions (1 to 4 mm) appear in crops over several days, so lesions at all stages are present at once. Healthy children usually have 200 to 500 (averaging 250 to 500) lesions in 2 to 4 successive crops.^[1] Fever up to 102 degrees Fahrenheit and systemic symptoms usually settle within 2 to 4 days.^[1]

Immunocompromised children may develop severe, progressive varicella with high fever, extensive vesicular eruption (new lesions for more than 7 days, lesions on palms and soles, haemorrhagic lesions) and visceral dissemination.^[1][3] People with HIV infection are also at high risk, and varicella can be severe or fatal in otherwise healthy children on high-dose corticosteroids (2 milligrams per kilogram per day or more of prednisone equivalent).^[1]

Complications in the prevaccine era included about 10,500 hospitalisations a year in the United States. Hospitalization rates were about 1 to 2 per 1,000 cases in healthy children and 14 per 1,000 in adults; fatality rates were about 1 per 100,000 in children aged 1 to 14 years, 6 per 100,000 in those aged 15 to 19 years, and 21 per 100,000 in adults.^[1] Dissemination occurs in up to 36% of immunocompromised patients.^{[1] [7]}

The main complications are:

• secondary bacterial infection of skin lesions with Staphylococcus or Streptococcus, the most common reason for hospitalisation and outpatient visits;^[1]
• pneumonia, which is the most common complication in adults with primary viral pneumonia, and secondary bacterial pneumonia in infants under 1 year;^[1]
• central nervous system disease, ranging from aseptic meningitis to encephalitis (about 1 per 50,000 cases in unvaccinated children) and cerebellar ataxia (about 1 per 4,000, usually self-limiting with complete recovery in 2 to 4 weeks);^[1]
• Reye syndrome, now very rare with the advice not to use aspirin or salicylates for fever in children with varicella;^[1]
• rare complications such as thrombocytopenia, haemorrhagic varicella, purpura fulminans, glomerulonephritis, myocarditis and arthritis.^[1]

Adults have more severe disease and more complications than children, and most deaths occur in immunocompetent children and adults.^[1]

Pain, itching or tingling in the affected area begins 2 to 4 days before the rash. The rash is unilateral, in one or two adjacent dermatomes, most often on the trunk or face, and usually does not cross the midline. It progresses from macules and papules to clustered vesicles that crust. The rash lasts 7 to 10 days and heals in 2 to 4 weeks. Healthy people have few systemic symptoms; immunocompromised people may have disseminated zoster with generalized skin lesions and central nervous system, pulmonary or hepatic involvement.^[2]

Shingles complications include postherpetic neuralgia, hearing or vision loss, encephalitis and pneumonia.^[7] The cranial nerve most often involved is the ophthalmic division of the trigeminal nerve, which can threaten sight. Localised zoster can also lead to cranial and peripheral nerve palsies and bacterial superinfection.^[2]

Postherpetic neuralgia is pain that persists after the rash has resolved. It can last weeks or months and occasionally longer than a year. Treatment is complex with varying success.^[2]

Varicella is usually diagnosed clinically. In the immunocompromised or in severe disease, other vesicular illnesses (disseminated herpes simplex, hand-foot-and-mouth disease, smallpox and mpox, bullous impetigo, varicella in a vaccinated person) may mimic it. Herpes zoster is usually diagnosed clinically once the rash is present, but zoster sine herpete (pain without rash) and recurrent disease in the immunocompromised can be difficult to recognise. Laboratory confirmation by polymerase chain reaction (PCR) of VZV DNA from unroofed vesicle fluid or scabs is the most helpful test when the diagnosis is uncertain.^{[2] [1]}

• Clinical diagnosis first. Recognise the typical rash pattern and distribution.^[2]
• PCR for VZV DNA on vesicle fluid or crusts is the test of choice; it distinguishes varicella from zoster and is the most useful test for atypical cases and immunocompromised patients.^[1][2]
• Direct fluorescent antibody and Tzanck smear are not recommended because of limited sensitivity. Serology has limited usefulness for zoster.^[2]
• VZV IgG antibodies can determine susceptibility for post-exposure assessment: less than 100 milli-international units per millilitre (mIU/ml) means susceptible in pregnant or immunocompetent contacts; immunosuppressed patients and infants are treated as susceptible below 150 mIU/ml.^[8]
• Blood tests for immunocompromised patients (full blood count, renal and hepatic function) and blood cultures if the picture could be sepsis. Children with HIV and low CD4 counts are at risk.^[3]

There is no formal scoring system in the sources used here. Severity is judged clinically: number and distribution of lesions, systemic features, and risk group. High risk features that move a patient to closer monitoring are immunosuppression, age under 1 year or over 15 years, pregnancy, and chronic skin or lung disease.^[1][3][4]

In healthy children varicella is self-limiting and treatment is symptomatic. Do not give aspirin (risk of Reye syndrome) and avoid ibuprofen if possible (associated with life-threatening bacterial skin infections); use paracetamol (acetaminophen) for fever.^[4] Keep fingernails short, wash hands after scratching, and bathe to reduce secondary infection.^[4]

Oral acyclovir or valacyclovir can be considered for groups at increased risk of moderate to severe varicella, and should be given for maximum benefit within the first 24 hours after the rash starts.^[3][4] High-risk groups include otherwise healthy people older than 12 years, people with chronic skin or lung disease, people on long-term salicylate therapy, pregnant women, and immunocompromised patients.^[3][4]

Doses from the medicine labels and the UKHSA PEP guide:

• acyclovir 20 milligrams per kilogram (mg/kg) per dose orally 4 times daily (80 mg/kg per day, maximum by weight) for 5 days in children 2 years and older; children over 40 kg and adults receive 800 mg orally 4 times daily for 5 days.^[8][11]
• valacyclovir 20 mg/kg three times daily for 5 days, to a maximum of 1 gram three times daily, in immunocompetent people aged 2 to 18 years.^[10]

Intravenous acyclovir is recommended for severe disease (disseminated VZV such as pneumonia, encephalitis, thrombocytopenia or severe hepatitis) and for varicella in immunocompromised patients, including those treated with high-dose corticosteroids for more than 14 days.^[3] Dosing for intravenous acyclovir in children is 20 mg/kg every 8 hours (minimum duration depends on severity and host).^[8]

Antivirals for children under 2 years, and valacyclovir for children under 12 years for varicella, are not from the labels cited here and should be directed by local guidance.

Famciclovir is available for adults but efficacy and safety in children are unclear; foscarnet is reserved for acyclovir-resistant infections, usually in the immunocompromised, with infectious diseases advice.^[3]

Diagnose and treat early: antivirals are most effective when started within 72 hours of symptom onset, and they accelerate lesion healing, reduce new lesions and viral shedding, and reduce acute pain.^[7] Three oral drugs are used:

• acyclovir 800 mg every 4 hours, 5 times daily for 7 to 10 days;^[11]
• valacyclovir 1 gram 3 times daily for 7 days, most effective when started within 48 hours of the rash; efficacy when started after 72 hours is not established;^{[10] [8]}
• famciclovir 500 mg every 8 hours for 7 days, started as soon as zoster is diagnosed.^[12]

Therapy should be initiated at the earliest sign or symptom; for valacyclovir within the first 48 hours where possible.^[10]

In immunocompromised patients with zoster, oral therapy may be insufficient; intravenous acyclovir is used when disease is severe or disseminated, and specialist advice is needed.

PHN is difficult to treat and prevention by early antiviral therapy is the best approach. Analgesia follows local guidance; postherpetic neuralgia management uses anticonvulsants and topical agents as second-line care, which should be guided by local formularies. This page does not state specific regimens for these beyond the available sources.

Ophthalmic zoster requires same-day ophthalmology assessment because of the risk to sight. Cover lesions and avoid contact between people with active lesions and susceptible contacts (pregnant women, newborns, immunocompromised people) until lesions are dry and scabbed. Zoster is about one fifth as infectious as varicella.^[2]

Reduce doses in renal impairment and after haemodialysis according to the product labels and the BNF. For acyclovir 800 mg every 4 hours for herpes zoster, the acyclovir label reduces the frequency to every 8 hours for creatinine clearance 10 to 25 ml/min and every 12 hours below 10 ml/min; for valacyclovir 1 gram three times daily for zoster the dose is reduced to 1 gram every 12 hours for 30 to 49 ml/min, every 24 hours for 10 to 29 ml/min, and 500 mg every 24 hours below 10 ml/min.^[11][10]

• Skin and soft tissue: bacterial superinfection, cellulitis, and rarely necrotising fasciitis.^[1]
• Pneumonia: primary viral pneumonia (commonest serious complication in adults) or secondary bacterial pneumonia.^[1]
• Neurological: aseptic meningitis, encephalitis, cerebellar ataxia, transverse myelitis, Guillain-Barre syndrome.^[1]
• Haematological: thrombocytopenia, haemorrhagic varicella, purpura fulminans.^[1]
• Hepatic, renal or cardiac rare complications such as hepatitis, glomerulonephritis and myocarditis.^[1]
• Congenital varicella syndrome after infection in the first 20 weeks of pregnancy.^[1][3]
• Neonatal varicella after rash near delivery.^[1][3]

• Postherpetic neuralgia.^[2]
• Ophthalmic zoster and vision loss.^[7]
• Cranial and peripheral nerve palsies.^[2]
• Bacterial superinfection of lesions.^[2]
• Visceral dissemination in the immunocompromised.^[2]
• Death from zoster is rare (estimated 96 deaths per year in the US).^[7]

Healthy children with varicella recover fully in a few days; adults and immunocompromised patients have higher morbidity. After recovery, most people have lifelong immunity and zoster is the only route of recurrence. Breakthrough varicella after vaccination is mild in most cases but can resemble natural disease in about 25 to 30% of one-dose breakthrough cases.^[1]

For shingles, most immunocompetent patients heal within 2 to 4 weeks but one in three will develop zoster in a lifetime, and recurrence is possible. Postherpetic neuralgia is the main cause of long-term disability.^[2][7]

VZV is prevented by live attenuated vaccines: single-antigen varicella (VAR) and the combined measles-mumps-rubella-varicella (MMRV) vaccine.^[1][5]

Routine schedule:

• first dose at 12 to 15 months; ^[5]
• second dose at 4 to 6 years.^[1][5]

Catch-up and specific groups:

• adolescents and adults 13 years and older without evidence of immunity: two doses 4 to 8 weeks apart;^[5]
• minimum interval 3 months for children 12 months to 12 years (4 weeks is valid if the second dose was given at least 4 weeks after the first);^[1]
• health care personnel, HIV-infected patients with adequate CD4 counts, and household contacts of immunocompromised people are targeted groups.^[1][5]

Effectiveness: two doses are about 90% effective at preventing chickenpox; a meta-analysis found 82% effectiveness for one dose against any varicella and 98% against severe disease, and 92% for two doses against any varicella.^[1][5]

Contraindications include a severe allergic reaction to a component or previous dose, significant immunosuppression (as defined for live vaccines), pregnancy, and family history of congenital immunodeficiency in first-degree relatives unless competence is verified.^[1] Women of childbearing age should avoid pregnancy for 1 month after each dose.^[1] Acyclovir, famciclovir or valacyclovir taken within 24 hours before vaccination are a precaution; these antivirals should be avoided for 14 days after vaccination.^[1]

Evidence of immunity includes age-appropriate vaccination, laboratory confirmation, a clinician-verified history, birth in the United States before 1980 (except for health care staff, pregnant women and immunocompromised people), or a history of zoster.^[1][5] Commercial antibody tests detect disease-induced antibody poorly after vaccination, so routine post-vaccination testing is not recommended.^[1]

Post-exposure vaccination: ACIP recommends varicella vaccine within 3 to 5 days after exposure for susceptible people aged 12 months or older; efficacy in this setting is 70% to 100% at preventing or modifying disease.^[1][5] For people who cannot receive live vaccine, VZIG (VariZIG) is given as soon as possible and within 10 days of exposure.^[3]

The only vaccine currently licensed and available in the United States is recombinant zoster vaccine (RZV, Shingrix), a non-live adjuvanted subunit vaccine.^[2][6]

• Adults 50 years and older: two doses 2 to 6 months apart (minimum interval 4 weeks; if the second dose is given less than 4 weeks after the first it should be repeated).^[2][6]
• Adults 19 years and older who are or will be immunodeficient or immunosuppressed: two doses 2 to 6 months apart, which can be given 1 to 2 months apart in those who would benefit from a shorter course.^[6][7]
• Prior zoster is not a contraindication; vaccination should wait until the acute episode has resolved.^[6]
• Previously given Zostavax (live zoster vaccine, no longer available in the US) recipients should receive Shingrix; wait at least 8 weeks (and preferably 5 years) after Zostavax.^[6]
• No varicella screening is needed before vaccinating immunocompetent adults 50 years and older.^[6]
• Contraindication: severe allergic reaction. Precautions: moderate or severe acute illness and pregnancy (no ACIP recommendation; consider delaying until after delivery and lactation).^[2][6]

Efficacy against shingles after more than 3 years is 96.6% in adults aged 50 to 59 years, 97.4% in those 60 to 69 years, and 91.3% in those 70 years and older; efficacy against PHN is 91.2% in adults 50 years and older.^[2] RZV does not transmit VZV because it contains no live virus. ^[6]

Women booking for antenatal care should be asked about previous chickenpox or shingles, or varicella vaccination.^[9] Women without immunity should be counselled to avoid contact with people with varicella or zoster during pregnancy.

• Fetal risk. Varicella in the first or early second trimester carries a small risk (0.4% to 2.0%) of congenital varicella syndrome, with skin scarring, limb abnormalities, and central nervous system and eye defects.^[3]
• Maternal risk. Pregnant women, particularly in the second and third trimesters, are at risk of varicella pneumonia, which can be serious.^[3][9]
• Vaccination. Varicella vaccine and MMRV are contraindicated in pregnancy; non-immune women should be vaccinated before conception or postpartum. Women should avoid pregnancy for 1 month after each varicella dose.^[1]
• Treatment of infection. Pregnant women who develop varicella are treated with acyclovir (800 mg five times daily for 7 days from rash onset for those at 20 weeks or more gestation, or intravenous acyclovir if severe).^[8]
• Exposure and PEP. For susceptible pregnant women, antivirals are now the first choice: acyclovir 800 mg four times daily, or valacyclovir 1 gram three times daily, from day 7 to day 14 after exposure, for any stage of pregnancy, if VZV IgG is under 100 mIU/ml. Give appropriate treatment from the onset of the rash if infection has occurred.^[8][9]
• Susceptibility testing. Ask about history at booking; if there is no reliable history, test VZV IgG urgently.^[9]

If a pregnant woman develops varicella from 5 days before to 2 days after delivery, the newborn is at risk of neonatal varicella, which carried mortality up to 30% before VZIG and intensive care but is now about 7%.^[1][3] Newborns with peripartum exposure should receive intravenous varicella immunoglobulin or intravenous immunoglobulin, plus prophylactic intravenous acyclovir 20 mg/kg every 8 hours for at least 48 hours, continuing until day 21. If neonatal varicella develops despite prophylaxis, give intravenous acyclovir 20 mg/kg every 8 hours for at least 7 days.^[8]

Babies born more than 7 days after the onset of maternal varicella usually have a mild course because of transplacental antibody.^[1] Premature infants born before 28 weeks or weighing under 1,000 g at birth, and some high-risk neonates, need individual assessment and prophylaxis if exposed.^[3][8] Breastfeeding is safe.^[9]

Immunocompromised patients with varicella are at risk of visceral dissemination (pneumonia, hepatitis, encephalitis, disseminated intravascular coagulation) and atypical rash that may persist for weeks. Treat with intravenous acyclovir, consider foscarnet for resistant virus, and seek specialist advice.^[3] In patients with HIV and adequate CD4 counts, varicella vaccine (but not MMRV) may be given; zoster vaccine (Shingrix) is recommended from age 19 years for those who are or will be immunodeficient.^[1][6][7]

• Varicella vaccine may not be available; natural infection remains common. Counsel pregnant women to avoid contact with cases; identify susceptible women at booking.^[9]
• When laboratory testing is unavailable, rely on a clear history of varicella and on clinical appearance; suspect disseminated disease in the immunocompromised.^[3]
• Oral acyclovir should be given as early as possible in severe varicella or zoster; for varicella in high-risk groups within 24 hours of onset, and in zoster within 72 hours.^[3][4][7]
• Intravenous acyclovir and VZIG may be scarce; plan referral pathways and stock management for high-risk patients, and for pregnant women and neonates.^[3][8]
• Good outcome in neonatal varicella depends on early recognition and supportive care even without VZIG.^[1][3]

Pregnancy infection, immunosuppression and vaccine programmes; plain-text names only: measles, mumps, rubella and varicella (MMRV) vaccination, human immunodeficiency virus, pneumonia, stroke, encephalitis.