Kathryn Edwards, MD, remembers a time when chickenpox was so common that clinicians could diagnose it at a glance, and children were hospitalized for complications of the disease.

Today, less than 150,000 cases of varicella occur annually, a 97% decrease since the vaccine against the virus became available in 1995. Younger clinicians may only know of varicella from textbooks and struggle to recognize its hallmark symptoms: fever, lethargy, and lesions.

As overall rates of child vaccination have declined and cases rise, infectious disease experts are revisiting the illness caused by the varicella-zoster virus. Edwards and her colleagues recently published a review on treatment and management of varicella in Pediatrics.

“People need to realize that chickenpox can be a very complicated illness. The day the vaccine was licensed, several decades ago, I was in the intensive care unit with a child who needed to get her arm amputated because she had necrotizing fasciitis,” said Edwards, an emerita professor of pediatrics at Vanderbilt University in Nashville, Tennessee.

Most healthy children recover without serious complications, aided by supportive care. But varicella can lead to bacterial superinfection, including cellulitis, pneumonia, lymphadenitis, and invasive group A streptococcal disease. Severe cases can result in toxic shock syndrome, cerebellar ataxia, and necrotizing fasciitis.

Dozens of states, including Minnesota, Texas, and New Jersey have recently reported an unusual uptick in varicella cases. Meanwhile, kindergarten vaccination rates for the full two-dose series have trended downward since the COVID pandemic — dropping from 94.8% in the 2019-2020 school year to 92.2% in 2025-2026, according to recent data from the CDC.

“As vaccine hesitancy increases, clinicians are increasingly asked to have in depth conversations with families about the benefits of routine childhood vaccines,” said Caitlin Li, MD, an attending physician in the Division of Infectious Diseases at Ann & Robert H. Lurie Children’s Hospital of Chicago, who led the review.

Edwards said vaccination status can provide an important diagnostic clue.

“Whenever we’re seeing children that have fever or rashes, one of the first things we need to ask is, ‘what is the vaccination status?’” she said.

Recognizing Disease

Varicella typically develops 14-16 days after exposure. About half of the children experience several days of fever, malaise, and headache before a rash appears. The characteristic eruption consists of hundreds of itchy lesions that develop in successive crops over as long as a week.

The lesions progress from red macules to thin-walled, clear vesicles surrounded by erythema before becoming cloudy and crusting within about 24-48 hours, the review outlined.

“Classically, in varicella the lesions are in multiple stages of development,” Li said. “The vesicles also tend to be discrete, not clustered.”

In breakthrough cases, children experience a milder form of the disease, with fewer than 50 lesions, less itching, and a shorter duration of illness. Studies suggest breakthrough varicella can occur in 0.39% for children who received one-dose of the vaccine, and in 0.10% among those who have received two doses.

When laboratory confirmation is needed, testing of fluid from unroofed vesicles or scabs using the polymerase chain reaction (PCR) is standard of care. Serologic testing is not recommended when PCR is available because varicella-specific immunoglobulin M has limited sensitivity and specificity.

A key sign of potential severity is when a child appears to worsen after initially improving, Li said.

“Clinicians should be concerned about pain out of proportion to the child’s exam or a fever that comes back after initial resolution because these can signal a bacterial superinfection,” she said. “Changes in mental status can signal a neurologic complication.”

Central nervous system complications occur in 0.5-1.5 per 1000 pediatric cases and include encephalitis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, and cranial nerve palsies, according to the review. Varicella can last for weeks and spread to multiple organs. 

Immunocompromised children are especially vulnerable because they generally cannot receive the live-attenuated varicella vaccine, said Coleen Cunningham, MD, a pediatric infectious disease specialist at the University of California, Irvine, and Rady Children’s Health in San Diego. Viral pneumonitis occurs in up to half of immunocompromised cases, with a mortality rate as high as 20%. 

“Those children are going to be at risk when people are not vaccinated and they’re exposed,” she said. “I think that’s a big deal.”

Cunningham said limited clinical experience can make early or atypical cases harder to diagnose.

“It wouldn’t surprise me if the younger doctors were a little slow in recognizing it because if you haven’t seen multiple cases, it’s hard to recognize it early or to recognize it when it’s a little bit atypical,” she said.

Treatment Depends on Risk

For otherwise healthy children, the authors recommend calamine lotion for itching, acetaminophen for fever, and keeping fingernails short to reduce scratching and secondary bacterial infection.

Clinicians should avoid salicylate-containing medications because of the risk for Reye syndrome. Ibuprofen also generally should be avoided because of a possible association with invasive streptococcal infection, although the review notes that the association is not definitively established.

Antiviral therapy may be considered for patients older than 12 years and those with chronic skin or lung disease, long-term use of salicylates, or exposure to corticosteroids. Immunocompromised patients and those with severe or disseminated disease should receive intravenous acyclovir. Treatment in these cases should start within 72 hours of diagnosis.

Vaccination remains the primary prevention strategy, with a strong safety record, according to the review. For the varicella vaccine alone, injection-site tenderness and redness occur in about 20% of recipients and fever in about 15%. A mild rash at the injection site occurs in up to 3% of children within 3 weeks of vaccination.

The combination measles-mumps-rubella (MMR) and varicella vaccine, however, carries a higher risk for fever and febrile seizures than administering MMR and varicella versions separately in children aged 12-24 months. 

Recognizing the symptoms, knowing best treatments, and vaccine strategies are crucial for trainees and young physicians, Edwards said. While many children had relatively minor cases of chickenpox before vaccination, others developed serious complications. 

“In the old days, getting chickenpox was a rite of passage and many times, people wouldn’t be very sick, although they’d have to stay home,” Edwards said. “But a number of them would get infections, and they would have to be treated.”

Natural infection also carries a longer-term risk of developing herpes zoster, also known as shingles, Edwards said.

The practical consequences of infection can also extend to families. Children with chickenpox must remain home while contagious, potentially keeping them out of school for several days and requiring a parent or caregiver to miss work.

“These infections, they can be very disruptive in your life,” Edwards said. “And if you can prevent those disruptions, it makes your life much easier.”

For clinicians, the disease’s relative rarity should not lead clinicians or families to underestimate it.

“We already see cases of varicella breaking through because not everyone can or does get the varicella vaccine,” Li said. “If more people opt out, cases of varicella are likely to increase.”

Cunningham, Edwards, and Li reported having no relevant conflicts of interest.

Lara Salahi is a health journalist based in Boston.