OVERVIEW: What every practitioner needs to know
Are you sure your patient has varicella? What are the typical findings for this disease?
Varicella (VZV) commonly causes a febrile childhood illness with a characteristic exanthem. The vesicular exanthem usually begins around the hairline on the face and then moves over the trunk and extremities within the following 5-7 days. Most children develop between 100 and 300 vesicles. Fevers generally are below 39 degrees Celsius. Typically the lesions crust within a week and full recovery is the norm. Varicella is one of few infections to cause a vesicular exanthem that involves the face and trunk and extremities.
What other disease/condition shares some of these symptoms?
Primary herpes simplex virus type 1 infection can cause a vesicular rash, usually around the mouth and extending over the face, though localized vesicular rash due to herpes simplex can occur on other parts of the body. When herpes infection extends over the trunk, the disease is called Kaposi’s varicelliform eruption.
What caused this disease to develop at this time?
Varicella or chickenpox is caused by the DNA virus called varicella-zoster virus (VZV), which is spread by airborne contagion. VZV is one of the human herpesviruses. Any child with varicella is contagious during the period of 1-2 days before the exanthem appears and for about 4 days after the exanthem erupts. The virus is easily spread to nonimmune children in close proximity (3-6 feet) to the infected child; for example, within a classroom at school.
Complications include a secondary bacterial infection of the skin vesicles. The bacteria are usually Staphylococcus or Streptococcus. Less common complications include an extension of the virus infection into the central nervous system, to cause a meningoencephalitis, especially cerebellitis. Varicella pneumonia is a rare complication.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Generally the characteristic vesicular rash can be quickly diagnosed by inspection by a physician or other health care provider who has seen other cases of varicella. If in doubt, a scraping of a vesicular skin lesion can be sent for rapid viral immunofluorescence diagnosis at the microbiology laboratory. Some clinical laboratories also offer PCR (polymerase chain reaction) testing for varicella virus from vesicle samples.
Would imaging studies be helpful? If so, which ones?
For a typical case of varicella, imaging is not indicated. However, if a child with varicella has symptoms suggestive of involvement of the central nervous system, then an MRI of the brain is indicated to define the site and extent of infection. Varicella also can be complicated by respiratory tract involvement, particularly in older adolescents as well as immunocompromised patients. If respiratory involvement is suspected, a chest x-ray should be performed.
If you are able to confirm that the patient has varicella, what treatment should be initiated?
Universal varicella vaccination programs have been implemented in the United States and Canada since 1995 and as a result, varicella is now an uncommon illness in North America. Nevertheless, if a case of varicella is diagnosed in an otherwise healthy child, treatment can be initiated with oral acyclovir suspension or tablets. The recommended dosage is 80 mg per kg per day, divided into 4 daily doses. The maximum dose is 800 mg 4 times daily. The duration of treatment is 5-7 days. As an alternative to acyclovir, adolescents with chickenpox can be treated with the second generation antiviral, valacyclovir, administered at 1 gram orally three times daily for 5-7 days.
Children with a secondary bacterial infection of the skin vesicles should receive initial treatment with an oral antibiotic that will treat community-acquired methicillin resistant Staphylococcus aureus; for example, clindamycin at a dosage of 20 mg per kg per day. If possible, a swab should be obtained for culture and sensitivity analysis. After obtaining these results, the antibiotic regimen can be adjusted for the duration of treatment. If a response is not observed in 2-3 days, admission for intravenous antibiotic administration may be indicated. Generally, intravenous treatment includes vancomycin (40 mg/kg/day) until culture and sensitivity results are available.
Children who are immunocompromised from diseases such as leukemia are at higher risk of complications if they develop varicella, especially if they were never immunized before the diagnosis of cancer. Recently, a report was published that one varicella vaccination may not protect a child who subsequently develops cancer from life-threatening breakthrough varicella. These children with breakthrough varicella should be admitted to the hospital and immediately treated with intravenous acyclovir at a dosage of 30 mg/kg/day, divided every 8 hours. The duration of treatment is usually 5-7 days.
What are the adverse effects associated with each treatment option?
Acyclovir is well tolerated by most children. Since acyclovir is metabolized in the kidney, the child must have normal renal function to take the recommended dosage. If there is any concern, obtain a serum creatinine level within 24 hours after starting oral acyclovir therapy. Acyclovir therapy can also cause leukopenia, but usually only after high-dosage intravenous administration.
What are the possible outcomes of varicella?
The vast majority of otherwise healthy children who contract varicella will have a complete recovery with no sequelae. Even those who have some central nervous system symptoms usually have no permanent residual symptoms. The most common complication of varicella is secondary bacterial infection. Usually the bacterial infection can be treated with appropriate intravenous or oral antibiotics. However, sepsis and even death has occurred in this subgroup.
What causes this disease and how frequent is it?
Varicella is caused by varicella-zoster virus, a DNA virus. Prior to universal immunization in the United States, outbreaks were common in the late fall and early winter seasons during the school year. Generally, over 90% of children contracted chickenpox by the time they completed grade school. Infection was typically spread within a classroom by the airborne route. Following universal varicella immunization, varicella outbreaks have become a rare occurrence.
How do these pathogens/genes/exposures cause the disease?
The disease is spread by a child with varicella to other nonimmune children via an airborne route. After an asymptomatic period of replication in the respiratory tract the virus enters the blood stream and is distributed throughout the body. The incubation period averages 14 days with a range of 10-20 days. A newly infected child becomes contagious in the last 2 days of the incubation period.
Other clinical manifestations that might help with diagnosis and management
There is a new disease called breakthrough varicella. Breakthrough varicella occurs in children who have only received one varicella immunization. Studies in the United States have demonstrated that one varicella immunization is not completely protective. Therefore, a child with only one varicella immunization can contract varicella if exposed to a child in the community with active disease. Generally breakthrough varicella is a mild illness lasting only 3-4 days, with a papulovesicular rash consisting of fewer than 20 pox lesions. Treatment is rarely indicated.
Zoster or shingles is the dermatomal exanthem that occurs when varicella virus re-emerges from a state of latency in the ganglia along the spinal column. Zoster is a very uncommon illness in children. Zoster in otherwise healthy children rarely leads to post herpetic neuralgia or any other complication. Therefore, treatment is not necessary.
Zoster in immunocompromised children can disseminate. Therefore zoster in this subgroup should be treated with acyclovir. The dosages are the same as those for varicella infection.
How can varicella be prevented?
Varicella can be prevented by immunization with the live attentuated varicella vaccine. The first dose is recommended between 12-15 months of age. The second dose is recommended at 4-6 years or before entering school. The vaccine is usually administered by subcutaneous injection into an arm. Another emergent option for non-immunized but immunocompromised children who are exposed to varicella is administration of VariZIG, an intramuscular formulation of VZV-immune globulin. The recommended dosage is 1 vial per 10 kg, up to a maximum of 5 vials.
What is the evidence?
Takahashi, M. “Effectiveness of live varicella vaccine”. Expert Opin Biol Ther. vol. 4. 2004. pp. 199-216.
Grose, C. “Varicella vaccination of children in the United States: assessment after the first decade 1995-2005”. J Clin Virol. vol. 33. 2005. pp. 89-95.
Gershon, AA, Arvin, AM, Levin, MJ. “Varicella vaccine in the United States: a decade of prevention”. J Infect Dis. vol. 197. 2008. pp. S39-40.
Shapiro, ED, Vazquez, M, Esposito, D. “Effectiveness of 2 doses of varicella vaccine in children”. J Infect Dis. vol. 203. 2011. pp. 312-5.
Yamada, M, Kamberos, N, Grose, C. “Breakthrough varicella in a cancer patient with persistent varicella antibody after one varicella vaccination”. J Pediatr. vol. 163. 2013. pp. 1511-3.
Ongoing controversies regarding etiology, diagnosis, treatment
The children at highest risk of life-threatening varicella are childrenwith cancer who have received only one varicella vaccination. Thesechildren who are immunosuppressed by cancer chemotherapy are not usuallyprotected by one prior varicella vaccination. Therefore, these childrenshould receive prophylaxis with either immune globulin or acyclovirfollowing an exposure to wild-type varicella.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has varicella? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- If you are able to confirm that the patient has varicella, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of varicella?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- Other clinical manifestations that might help with diagnosis and management
- How can varicella be prevented?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment