Version May 2024
INTRODUCTION — Varicella-zoster virus (VZV) is one of eight herpesviruses known to cause human infection and is distributed worldwide. Primary infection with VZV causes varicella (chickenpox) in susceptible hosts. Most healthy children have self-limited infection with primary varicella. However, varicella can cause severe complications such as soft tissue infection, pneumonia, hepatitis, Reye syndrome, and encephalitis. Patients at increased risk of complications include adolescents, adults, pregnant women, and immunocompromised hosts.
The treatment of primary varicella infection will be reviewed here. Issues related to the transmission, clinical manifestations, and complications of varicella, as well as the management of pregnant women and neonates, are discussed separately. (See "Clinical features of varicella-zoster virus infection: Chickenpox" and "Varicella-zoster virus infection in pregnancy" and "Varicella-zoster infection in the newborn".)
APPROACH TO TREATMENT — Patients with varicella typically develop a fever and a vesicular rash that is pruritic. Many patients require supportive care to manage these symptoms. (See 'Supportive care' below.)
The decision to initiate antiviral therapy depends upon the patient’s age, the presence or absence of comorbid conditions, and the patient’s clinical presentation. Although varicella is usually a self-limited disease, if complications develop, they can be life-threatening. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Complications of varicella'.)
Our approach to antiviral therapy is as follows (see 'Individuals without complications' below and 'Individuals with complications' below):
●For healthy children ≤12 years, varicella is typically self-limited and we do not routinely offer antiviral therapy. The management of neonatal varicella is discussed elsewhere. (See "Varicella-zoster infection in the newborn".)
●For individuals who present with, or are at high risk for complications (eg, unvaccinated adolescents, adults, pregnant women, immunocompromised hosts), we administer antiviral therapy to reduce the severity of symptoms and/or reduce the risk of complications.
We use oral therapy (eg, valacyclovir or acyclovir) for immunocompetent individuals without evidence of complications. The oral agents are well tolerated and there are few serious side effects associated with their use. For most others, we use intravenous acyclovir rather than oral therapy since the bioavailability of intravenous therapy is better than that of the oral agents and it has been widely used for the treatment of immunocompromised hosts.
All patients with varicella should be educated about potential complications, including secondary bacterial infections. (See 'Patient monitoring' below.)
SUPPORTIVE CARE — The following general measures can be used for the symptomatic management of rash and fever, and can also help reduce the risk of developing certain complications:
●Antihistamines are helpful for the symptomatic treatment of pruritus.
●Fingernails should be closely cropped to avoid significant excoriation and secondary bacterial infection.
●Acetaminophen should be used to treat fever, particularly in children. Nonaspirin nonsteroidal antiinflammatory agents can also be used. However, some providers discourage NSAIDS because of the uncertain association with streptococcal superinfection [1,2]. Salicylates should be avoided since aspirin has been associated with the onset of Reye syndrome in the setting of a viral infection [3]. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)
ANTIVIRAL THERAPY — Acyclovir and its analogues (valacyclovir, famciclovir) are effective for the treatment of primary varicella in both healthy and immunocompromised hosts [4-11]. Higher doses of acyclovir are used to treat VZV compared with herpes simplex virus (HSV). VZV is less susceptible to acyclovir, and 50 percent inhibition of VZV replication requires about 10-fold higher levels of acyclovir than those typically required for HSV [8,12]. Acyclovir and its analogues are dependent upon renal function for clearance and dose adjustment is needed in moderate to severe renal insufficiency.
Oral agents are generally very well tolerated, especially in adults; however, gastrointestinal side effects or headache may occur. Acyclovir is also available in an intravenous form which can cause local reactions (phlebitis) and reversible acute kidney injury. Risk factors for acute kidney injury include dehydration, failure to dose adjust for reduced kidney function, and overly rapid infusion (eg, <1 hour) [13]. In addition, for obese adults, weight-based dosing should be scaled to ideal body weight (IBW) rather than total body weight (TBW) to avoid an increased risk of toxicity (calculator 1).
Additional discussions on the use of acyclovir and its analogues are found in the Lexicomp drug information topics within UpToDate and within individual topic reviews. (See "Acyclovir: An overview" and "Valacyclovir: An overview" and "Famciclovir: An overview".)
INDIVIDUALS WITHOUT COMPLICATIONS
Immunocompetent children and adolescents
Indications — Our approach to antiviral therapy for children and adolescents is consistent with the recommendations of the American Academy of Pediatrics [14].
We suggest oral antiviral therapy for immunocompetent children and adolescents who are at increased risk of developing complications from varicella (eg, pneumonia, skin infection) [14-16], since antiviral therapy may theoretically reduce the risk of complications in these patients and is generally well tolerated. These individuals include:
●Unvaccinated adolescents (ie, children ≥13 years of age) since these patients are more likely to have severe disease compared with younger children [17].
●Secondary cases in household contacts since these cases are usually more severe than primary cases [18].
●Patients with a history of chronic cutaneous or pulmonary disorders since secondary bacterial infections may have severe consequences.
●Children taking intermittent oral or inhaled steroid therapy. The risk is greatest when corticosteroids are administered during the incubation period.
●Individuals taking chronic salicylates. These individuals are at risk of developing Reye syndrome. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)
Although many providers treat immunocompetent children and adolescents at increased risk of complications, others prefer to avoid antiviral agents given the modest decrease in symptoms in immunocompetent hosts [4,19].
We suggest not administering antiviral therapy for healthy children ≤12 years. Varicella is typically a self-limited disease in this population. Although acyclovir may modestly reduce the duration and severity of symptoms, these benefits must be weighed against the adverse effects (including rare but potentially serious adverse effects), cost, and potential transmission of infection during the office visit to obtain the prescription.
The modest effects of oral acyclovir are summarized below:
●A randomized trial of 815 healthy children with varicella evaluated the effects of oral acyclovir [4]. Individuals received placebo or acyclovir therapy (20 mg/kg PO four times daily), which was started within the first 24 hours after the onset of the rash and continued for five days. Acyclovir-treated children had fewer lesions than the placebo group (mean number 294 versus 347), and no new lesions formed after day three in the acyclovir group, while 20 percent of the control group continued to develop lesions on day six or later. In addition, the acyclovir-treated children developed equivalent antibody responses to those given placebo.
●In a meta-analysis of three studies (including the one described above), acyclovir significantly reduced the duration of fever by 1.1 days (95% CI -1.3 to -0.9) in healthy children with varicella [19]. However, there were no clinically important differences between acyclovir and placebo with respect to developing varicella-related complications or adverse drug events. Acyclovir did not reduce school absence in the only study that evaluated it [20].
Timing and regimen — If antiviral therapy is initiated (eg, immunocompetent patients at increased risk of developing complications from varicella), treatment should be started within 24 hours after the rash develops, if possible. Clinical trial data found greater benefits when antiviral therapy was initiated within 24 hours of symptoms onset [5,21]. In addition, in immunocompetent hosts, viral replication typically stops by 72 hours after the onset of rash.
For patients ≥2 years with normal renal function, we administer oral acyclovir or valacyclovir as follows [22,23]:
●Acyclovir – 20 mg/kg per dose (maximal dose 800 mg) four times daily for five days for children 2 to 12 years and for adolescents.
●Valacyclovir – 20 mg/kg per dose (maximal dose 1000 mg) three times daily for five days or longer if lesions have not resolved.
We check baseline renal function in children if there is concern for dehydration. Dose adjustments for individuals with reduced kidney function are found in the Lexicomp drug information topic within UpToDate.
There is no consensus regarding the optimal dose of oral therapy for children <2 years old. However, some providers would use oral acyclovir at the same doses as those recommended for children ≥2 years old. Acyclovir is preferred to valacyclovir for such patients because the safety and efficacy of valacyclovir have not been established in infants younger than two years of age. The treatment of neonatal varicella infection is discussed elsewhere. (See "Varicella-zoster infection in the newborn", section on 'Treatment'.)
Immunocompetent adults
Indications — We suggest oral antiviral therapy (valacyclovir, acyclovir, famciclovir) for immunocompetent adults with uncomplicated varicella infection. Although most adults who develop varicella have an uncomplicated course, they are at increased risk of developing pneumonia, which often leads to hospitalization and carries an overall mortality of between 10 and 30 percent [24]. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Pneumonia'.).
We administer antiviral therapy to adults even if they were previously vaccinated. There are no data that describe the natural history of varicella in immunized adults. Thus, we prefer to treat with antiviral therapy given the low risk of toxicity with oral agents and the severe potential complications of varicella in adults.
Antiviral therapy can reduce the duration and severity of symptoms in adults, and there is a theoretical benefit of antiviral therapy in reducing complications. As an example, in a randomized trial of 148 healthy adults with varicella, which compared oral acyclovir (800 mg five times per day) with placebo, acyclovir reduced the time to full crusting of lesions (5.6 versus 7.4 days), the maximum number of lesions (46 percent reduction), the duration of fever, and the severity of symptoms [5]. Although this trial did not describe a reduced risk of complications, it was not designed to assess this outcome.
Timing and regimen — We initiate treatment if the patient has evidence of ongoing disease (eg, active skin lesions). However, the benefit of antiviral therapy has been best described when treatment was initiated within 24 hours of symptom onset [5].
We typically administer oral valacyclovir (1 g three times per day) because it can be given in fewer doses compared with acyclovir and has equivalent activity. Famciclovir can also be used, but valacyclovir provides higher antiviral drug concentrations compared with famciclovir. If oral acyclovir is used, it should be administered as 800 mg five times per day; a randomized trial in adults supports this regimen [5]. Dose adjustments for reduced kidney function are described in the Lexicomp drug information topics within UpToDate.
We treat such patients with uncomplicated varicella for five to seven days. However, the course should be extended if there is delayed crusting of lesions.
Pregnant women — We suggest antiviral therapy for pregnant women who present with varicella since they are at high risk for complications. A detailed discussion of varicella in pregnancy is found elsewhere. (See "Varicella-zoster virus infection in pregnancy", section on 'Treatment of varicella infection'.)
Immunocompromised hosts
Indications — We recommend antiviral therapy for immunocompromised hosts who present with varicella. Immunocompromised hosts include those with an underlying malignancy or HIV infection, as well as those who are receiving high-dose corticosteroid therapy for more than 14 days (eg, ≥20 mg or ≥2 mg/kg body weight [for children who weigh <10 kg] of prednisone or equivalent) or other immunosuppressive therapies [25-27].
Immunocompromised hosts are at risk for developing disseminated varicella due to impaired cellular immunity. Immunocompromised hosts who develop varicella also experience more frequent severe morbidity and higher mortality rates compared with immunocompetent hosts. As an example, while only 0.1 percent of varicella infections develop in this population, this group accounted for as many as 25 percent of varicella-related deaths in the pre-vaccine era [28]. (See "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Immunosuppressed hosts'.)
Timing and regimen — We initiate treatment if active (ie, non-crusted) varicella lesions are present. Clinical trials that evaluated the use of intravenous (IV) acyclovir in small numbers of immunocompromised children with varicella found that the risk of visceral dissemination and severe complications were reduced in those who received antiviral therapy [7,29].
For most patients, we suggest initial therapy with intravenous acyclovir. However, the antiviral regimen varies with age, disease severity, and baseline laboratories, as follows:
●Adults – Acyclovir 10 mg/kg IV every 8 hours (using ideal body weight [IBW] if obese (calculator 1)).
For adults with mild disease (ie, <50 lesions) and normal baseline laboratories (ie, complete blood count, liver function tests, renal function), initiating therapy with valacyclovir is an option if the patient can be followed closely as an outpatient.
●Children ≥1 year of age and adolescents – Acyclovir 1500 mg/m2 per day in three divided doses or 30 mg/kg/day in three divided doses.
Initiating therapy with valacyclovir (20 mg/kg per dose [maximal dose 1000 mg] three times daily) may be reasonable in selected immunocompromised children considered to be at low risk of developing severe varicella if the patient can be followed closely as an outpatient.
Additional dosing recommendations for individuals with reduced kidney function, as well as children <1 year of age, are provided in the Lexicomp drug information topics within UpToDate and within individual topic reviews. (See "Acyclovir: An overview", section on 'Dose adjustments' and "Varicella-zoster infection in the newborn".)
The typical duration of treatment is 7 to 10 days. Intravenous therapy is continued until no new lesions are occurring. Patients can then be transitioned to oral therapy until all of the lesions have crusted.
INDIVIDUALS WITH COMPLICATIONS — We administer intravenous (IV) antiviral therapy for individuals who present with varicella-related complications, such as severe hepatitis, pneumonia, and encephalitis (see "Clinical features of varicella-zoster virus infection: Chickenpox", section on 'Complications of varicella'). Retrospective analyses and case reports suggest that acyclovir treatment improves the clinical outcome in adults and children who develop these complications [30-36].
The dose of acyclovir varies with age, as follows:
●Adults – 10 mg/kg IV every eight hours (using IBW if obese (calculator 1)).
●Children ≥1 year and adolescents – 1500 mg/m2 per day in three divided doses or 30 mg/kg/day in three divided doses.
The dose of IV acyclovir for patients with reduced kidney function, as well as children <1 year of age, are provided in the Lexicomp drug information topics within UpToDate and within individual topic reviews. (See "Acyclovir: An overview", section on 'Dose adjustments' and "Varicella-zoster infection in the newborn".)
Antiviral therapy should be continued for 7 to 10 days. Individuals who have a more rapid response to treatment (eg, significant improvement in symptoms and no new lesions) can be transitioned to oral therapy to complete the treatment course.
PATIENT MONITORING — Patients who are treated as an outpatient should be instructed to call their providers if they develop signs and symptoms of complicated varicella (eg, cough, severe headache, confusion, nausea, and vomiting) or a secondary bacterial infection (eg, cellulitis).
Individuals who require intravenous acyclovir should have their blood urea nitrogen level and creatinine followed while receiving intravenous treatment. (See "Acyclovir: An overview", section on 'Toxicity'.)
INFECTION CONTROL PRECAUTIONS — Hospitalized patients with primary varicella should be placed on standard, contact, and airborne precautions to prevent the spread of infection to others. A detailed discussion on infection control precautions for patients with primary varicella is found elsewhere. (See "Prevention and control of varicella-zoster virus in hospitals", section on 'Isolation precautions for patients with varicella'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Varicella-zoster virus".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Chickenpox (The Basics)")
●Beyond the Basics topics (see "Patient education: Chickenpox prevention and treatment (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Patients with varicella typically develop a fever and a vesicular rash that is pruritic. Many patients require supportive care to manage these symptoms. (See 'Supportive care' above.)
●For healthy children ≤12 years, varicella is typically self-limited and we suggest not administering antiviral therapy (Grade 2C). However, we suggest antiviral therapy for immunocompetent children and adolescents who are at increased risk of developing complications from varicella (eg, unvaccinated patients ≥13 years old, individuals with chronic cutaneous or pulmonary disorders, those taking chronic salicylates or inhaled steroids) (Grade 2B). (See 'Immunocompetent children and adolescents' above.)
●For immunocompetent adults with uncomplicated varicella infection, we suggest oral antiviral therapy in addition to supportive care rather than supportive care alone (Grade 2B). Antiviral therapy can reduce the severity of symptoms and may decrease the risk of complications. We initiate antiviral therapy, regardless of the individual’s vaccination status. We typically administer oral valacyclovir because it can be given in fewer doses compared with acyclovir and has equivalent activity. (See 'Immunocompetent adults' above.)
●For immunocompromised individuals who present with varicella, we recommend antiviral treatment in addition to supportive care rather than supportive care alone (Grade 1B). For most patients, we suggest initial therapy with intravenous acyclovir rather than oral agents (Grade 2C). Treatment should be administered for 7 to 10 days. (See 'Immunocompromised hosts' above.)
●For pregnant women who develop uncomplicated varicella, we suggest oral antiviral therapy rather than supportive care (Grade 2C). The management of pregnant women with varicella is discussed elsewhere. (See "Varicella-zoster virus infection in pregnancy", section on 'Treatment of varicella infection'.)
●For individuals who present with complications related to varicella, intravenous acyclovir should be initiated. Antiviral therapy should be continued for 7 to 10 days. (See 'Individuals with complications' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
