Varicella• A case-controlled study of the varicella vaccine in children showed that the vaccine had 85% (CI, 78% to 90%) efficacy for preventing chickenpox and 97% efficacy against
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Quality Ratings: The preponderance of data supporting guidance statements are derived from:
level 1 studies, which meet all of the evidence criteria for that study type;
level 2 studies, which meet at least one of the evidence criteria for that study type; or
level 3 studies, which meet none of the evidence criteria for that study type or are derived from expert opinion, commentary, or consensus.
Study types and criteria are defined at http://smartmedicine.acponline.org/criteria.html
Disclaimer: The information included herein should never be used as a substitute for clinical judgement and does not represent an official position of the American College of Physicians. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete.
Therefore, PIER users should compare the module updated date on the offical web site with any printout to ensure that the information is the most
current available.
CME Statement: The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide
continuing education for physicians. The American College of Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1
CreditTM. Physicians should claim only credit commensurate with the extent of their participation in the activity. Purpose: This activity has been
developed for internists to facilitate the highest quality professional work in clinical applications, teaching, consultation, or research. Upon completion
of the CME activity, participants should be able to demonstrate an increase in the skills and knowledge required to maintain competence, strengthen
their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Joseph Truglio, MD, current author of this
module, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Deborah Korenstein, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or
health-care related organizations. Richard B. Lynn, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies,
biomedical device manufacturers, or health-care related organizations.
Offer varicella vaccine to all susceptible individuals.
1.1 Vaccinate all children under age 13 years and all individuals aged 13 years or older who do not have evidence of immunity.
Recommendations
• Immunize all children under age 13 years with two doses of varicella-containing vaccine:
Administer the first dose at age 12 months to 15 months
Administer the second dose at age 4 years to 6 years or earlier if the interval between the first and second
dose is more than 3 months
For the first dose of varicella vaccine at age 12 months to 47 months, use the individual varicella vaccine unless the parent or caregiver express a preference for the combined live attenuated MMRV vaccine
• Administer a second dose catch-up varicella vaccine to children, adolescents, and adults who
previously received only one dose:
Note that the minimum recommended interval between the first and second dose is 3 months for children aged 12 years or younger, and 4 weeks for persons aged 13 years or older
For the second dose at age 15 months to 12 years or for the first dose at age 48 months or older, use combined live attenuated MMRV vaccine
• Assess all healthy adults for varicella immunity (see information on soliciting a reported history),
and give those without evidence of immunity two doses of single-antigen varicella vaccine 4 weeks
to 8 weeks apart.
• Target the following specific susceptible groups for vaccination:
Persons who have close contact with other individuals who are at high risk for serious varicella
complications, including health care workers and family contacts of immunocompromised persons
Persons in environments in which VZV transmission is likely, including teachers of young children, daycare employees, and residents and staff in institutional settings
Persons in other environments in which varicella transmission can occur, including college students, inmates, and military personnel
Nonpregnant women of childbearing age
International travelers
• Note that the use of varicella vaccine is not approved in pregnant women; upon completion of
pregnancy, give women without evidence of varicella immunity the first dose of vaccine before
discharge from the hospital, and a second dose 4 to 8 weeks later.
• Be aware that varicella vaccine is contraindicated in individuals with altered cellular immunity
caused by disease or drug therapy; however, consider vaccination for HIV-infected children aged 1
year to 8 years with CD4+ T-lymphocyte percentages of 15% or higher, and HIV-infected
individuals aged over 8 years with CD4+ T-lymphocyte counts ≥200 cells/µL, giving eligible
individuals two doses of single-antigen vaccine 3 months apart.
Evidence
• A case-controlled study of the varicella vaccine in children showed that the vaccine had 85% (CI,
78% to 90%) efficacy for preventing chickenpox and 97% efficacy against severe and moderately
severe disease (1).
• A 2008 structured review of varicella vaccination in the U.S. found that vaccination had 80% to
85% efficacy for the prevention of clinical disease and over 95% efficacy for the prevention of
severe disease. The review also found that the U.S. vaccination program resulted in substantial
reductions in hospitalizations for varicella (by over 75%) and varicella deaths (by over 74%) (2).
• A review of active surveillance data collected from 350,000 subjects from 1995 to 2004 found that
the annual rate of breakthrough cases significantly increased with time from vaccination, from 1.6
Recognize that typical cases of varicella can be diagnosed reliably on the basis of history and physical exam.
3.1 Suspect varicella in an adolescent or adult with constitutional symptoms, a diffuse vesicular rash in various stages of development, and no previous
history of chickenpox.
Recommendations
• Suspect varicella in an adolescent or adult who presents with the following:
No previous history of varicella
A history of exposure to varicella or herpes zoster approximately 2 weeks before the onset of illness (but exposure is not often recognized)
Fever and constitutional symptoms
A distinctive diffuse rash with vesicles, papules, and scales in various stages of development
• Ask adults with varicella about respiratory symptoms, because pneumonitis is relatively common.
• Look for superinfection of skin lesions, cerebellar ataxia, and evidence of pneumonitis on lung
exam.
• Obtain lab confirmation only if the diagnosis is uncertain.
• See figure Crops of Vesicles and Pustules on the Back of a 27-Year-Old Female Nurse.
• See figure Close-up of Vesicles and Pustules on the Arm of an 18-Year-Old Man with Chickenpox.
• See figure Vescicle of Early Chickenpox.
Evidence
• Consensus.
• Among adults with varicella, 15% to 20% have radiographic evidence of pneumonitis; 5% to 10%
have respiratory symptoms (22; 23; 24).
Rationale
• The appearance of varicella is distinctive, and a clinical diagnosis is usually accurate and reliable.
Comments
• Immunocompromised patients with acyclovir-resistant virus can have hyperkeratotic, verrucous
lesions.
• Constitutional symptoms may precede the rash by 24 to 48 hours.
• As the use of varicella vaccine becomes more widespread, physicians may have less experience
with clinical diagnosis of varicella, which may place increased reliance on laboratory diagnostic
methods.
• The rash of varicella is characterized by rapid evolution of lesions over 8 to 12 hours and by
successive crops of new lesions. Lesions first appear on the head, then move to the trunk, and
finally to the extremities.
• Cerebellar ataxia is the most common neurological abnormality associated with varicella, occurring
in approximately 1 of every 4000 cases; less common CNS complications of varicella include
encephalitis, transverse myelitis, and aseptic meningitis (25).
3.2 Obtain lab confirmation of varicella only when the clinical diagnosis is uncertain using direct immunofluorescent staining of material from skin
Consider consultation with an appropriate specialist when the clinical diagnosis is uncertain and/or the patient is seriously ill. Consider consultation with an appropriate specialist for patients with suspected visceral involvement; otherwise, management of uncomplicated varicella is straightforward.
4.1 Seek consultation with an infectious diseases specialist, dermatologist, and/or other specialist to help clarify the differential diagnosis.
Recommendations
• Ask an infectious diseases specialist to review the differential diagnosis and advise appropriate
diagnostic testing.
• Ask a dermatologist to review the differential diagnosis and to consider obtaining a skin biopsy for
cultures and histopathology.
• Consider asking a clinical microbiologist to assist with collecting samples for specialized virologic
testing.
• Note that a pediatrician who is experienced with diagnosing and managing varicella may be a
valuable resource.
Evidence
• Consensus.
Rationale
• Establishing a diagnosis of varicella in a seriously ill adolescent or adult is an essential prerequisite
for the initiation of appropriate antiviral therapy.
4.2 Obtain expert consultation to assist with the management of patients with varicella pneumonitis, encephalitis, or severe cutaneous bacterial
infection.
Recommendations
• Consult an infectious disease specialist for help in using intravenous acyclovir, if necessary.
• Consult a pulmonary medicine or critical care specialist to assist with the ventilatory management
in patients with varicella pneumonitis and significant hypoxemia.
• Consult a neurologist for assistance with the management of varicella with CNS involvement.
Evidence
• Consensus.
Rationale
• Complications of varicella in adults, while uncommon, can result in substantial morbidity and
mortality.
4.3 Obtain expert consultation to assist with the management of pregnant
women with varicella.
Recommendations
• Consult an obstetrician or fetal-maternal medicine specialist to assist with the management of
Use antiviral drugs to reduce the duration of illness and other medications to alleviate symptoms in adolescents and adults with uncomplicated varicella.
6.1 Prescribe oral acyclovir to shorten the duration of constitutional
symptoms and the formation of new lesions.
Recommendations
• Begin treatment within the first 24 hours of the onset of rash, when possible.
• Administer acyclovir, 800 mg, po qid for 5 days, to immunocompetent adults and adolescents with
uncomplicated varicella.
• See table Drug Treatment for Varicella.
Evidence
• A 1992 randomized, controlled trial compared acyclovir with placebo in adults with varicella.
Patients receiving acyclovir had a shorter duration of new lesion formation (2.7 compared with 3.3
days), a 46% reduction in the maximum number of lesions, faster healing (5.6 compared with 7.4
days), and shorter duration of fever (0.5 days) (43).
• A 2005 Cochrane review of acyclovir to treat varicella in healthy children and adolescents included
three randomized, controlled trials which were of moderate quality. Acyclovir resulted in fewer days
with fever (−1.1 days [CI, −1.3 to −0.9]) and a reduction in the maximum number of lesions (−76
lesions [CI, −145 to −8]) but no other significant differences (44).
• A study of children, adolescents, and adults with varicella who were treated at various times after
onset of rash showed that the maximum benefit of acyclovir occurred in those treated within 24
hours of onset compared with those treated after 48 hours, but some benefit was apparent in
persons treated between 24 hours and 48 hours (45).
• Although antiviral therapy is considered optional for healthy children with varicella, the higher
potential for morbidity clearly favors treatment in adults (46).
Rationale
• Any decrease in the duration of acute illness is beneficial given that immunocompetent adolescents
and adults with varicella can be seriously ill (with high fever, hundreds of cutaneous lesions, and
incapacitating constitutional symptoms) and that they are likely to miss >7 days of school or work.
Comments
• Valacyclovir and famciclovir are effective against VZV, but have not been studied for chickenpox.
• It is not clear whether acyclovir therapy reduces the risk for complications such as pneumonitis or
encephalitis.
• For immunocompromised patients, use acyclovir, 10 to 15 mg/kg, iv every 8 hours for 7 to 10 days
(47).
6.2 Treat patients who have varicella complicated by visceral dissemination with iv acyclovir.
Recommendations
• Administer acyclovir, 10 to 12.5 mg/kg iv every 8 hours (for patients with normal renal function),
in adolescents or adults hospitalized with varicella pneumonitis or CNS involvement.
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Viral culture Sensitivity 30-70%; specificity 100%. Recovery of VZV is highly dependent on the stage of the lesions,
the quality of the specimen collected, and the time elapsed between specimen collection and tissue
culture inoculation. Fluid from fresh vesicles should be aspirated into a tuberculin syringe containing viral transport media and then delivered immediately to the virology laboratory. If delay is
unavoidable, refrigerate the specimen on wet ice; do not freeze. Growth of VZV in tissue culture may
take 3-14 days (33; 34)
Antigen detection DFA detection is more sensitive than viral culture (28). Using a modified Tzanck technique, cells are
scraped from the base of the lesion with a scalpel or needle, smeared on a glass slide, and stained
using fluorescein-conjugated monoclonal antibodies to detect viral glycoproteins. DFA can distinguish
between HSV and VZV
Serology Most laboratories use ELISA or latex agglutination. Serum antibodies appear several days after the
onset of varicella and peak at 2-3 weeks; a four-fold rise in serum IgG between acute and convalescent
sera is diagnostic (35). Demonstration of VZV-specific IgM indicates acute infection, but often lacks
sensitivity and specificity
PCR Useful for detecting VZV DNA in cerebrospinal fluid, serum, or blood, but is not widely available; PCR
has been found to be more sensitive than culture isolation (30)
DFA = direct fluorescent antibody; DNA = deoxyribonucleic acid; ELISA = enzyme-linked immunosorbent assay; HSV = herpes simplex virus; IgG = immunoglobulin G; IgM = immunoglobulin M; PCR =
Varicella Successive crops of new lesions evolving into small vesicles with a small area of surrounding erythema
Mild cases can occur in vaccinated individuals. Often preceded or accompanied by constitutional
symptoms in adults
Impetigo Pustular and crusted lesions, usually on the extremities and face; usually afebrile
Caused by group A streptococci; uncommon in adults
Insect bites Biting and stinging insects (e.g., fire ants) can cause multiple vesicular or pustular lesions with fever
Competent adults should relate a history of insect exposure
Disseminated HSV Generalized cutaneous vesicles that may be difficult to distinguish from varicella
Only occurs in immunocompromised individuals
Rickettsialpox (R. akari) A painless papule with eschar forms at the mite bite site; a generalized papulovesicular rash appears 3-
7 days later
Uncommon disease; patient may report exposure to mice
Enterovirus infection (e.g., hand, foot, and mouth disease) Febrile illness with vesicular eruption that involves the mouth, hands, and feet; unlike varicella, the
vesicular rash rarely becomes widespread
Caused by coxsackievirus A16 and other enteroviruses; occurs most often in children aged <10 years
Allergic reactions (e.g., drug reaction) Highly variable syndromes of fever and rash (e.g., Stevens-Johnson syndrome, toxic epidermal
necrolysis)
Skin changes are often large bullae rather than small discreet vesicles
Sweet's syndrome Pustular neutrophilic dermatitis accompanied by fever, arthritis, and leukocytosis
Associated with underlying malignancy in 25% of cases
Smallpox Deep-seated, firm, well-circumscribed vesicles or pustules all in the same stage of development in any
one part of the body. Lesions occur after a prodrome of 1-4 days with high fever and have a centrifugal
distribution (more on face and distal extremities)
syndrome; IM = intramuscular; IV = intravenous; PO = oral; q8hr = every 8 hours; qd = once daily; qid = four times daily; SC = subcutaneous; tid = three times daily; TTP = thrombotic thrombocytopenic
purpura.
PIER provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.
Crops of Vesicles and Pustules on the Back of a 27-Year-Old Female Nurse
The rash of varicella is characterized by rapid evolution of lesions over 8 to 12 hours and by successive crops of new lesions. Lesions may first appear on the head, then move to the trunk, and finally to the extremities. On any part of the body lesions can be identified in different stages of development (macules, papules, vesicles, pustules).
Early varicella lesions present as a thin-walled, clear vesicle (dew drop) which develops on top of the area of redness. This "dew drop on a rose petal" lesion is characteristic for early chickenpox.