6 Important Ways to Treat Chickenpox

Varicella-zoster virus (VZV)

• it is one of eight herpes viruses known to cause human infection and is distributed worldwide.
• Primary infection with varicella causes chickenpox in susceptible hosts.
• While most healthy children have a self-limited infection with primary varicella.
• The incidence of hospitalisation and even mortality in selected groups is significant.
• Varicella can cause significant complications, such as soft tissue infection, pneumonia, hepatitis, Reye syndrome, and encephalitis.
• Patients at increased risk of complications include adults, pregnant women, and immunosuppressed hosts.
• The treatment of chickenpox reviewed here.
• The treatment of chickenpox includes symptomatic measures and the consideration of antiviral therapy.

• The following general measures can be used in the patient with significant disease:
• Antihistamines are helpful in the symptomatic treatment of pruritis.
• Fingernails should closely cropped to avoid significant excoriation and secondary bacterial

Infection by Chickenpox

• Acetaminophen should be used to treat fever, particularly in children, since the administration of aspirin has been associated with the onset of Reye syndrome in the setting of viral infection [1].

Antiviral therapy for Chickenpox

• Acyclovir, a synthetic nucleoside analogue that inhibits replication of human
• herpesviruses is an effective therapy for primary varicella in healthy and immunosuppressed hosts; it is also well-tolerated.
• There is no clinical data on famciclovir or valacyclovir for this clinical indication.
• VZV is inherently less susceptible to acyclovir than herpes simplex virus (HSV); 50 per cent inhibition of  VZV replication requires about 10-fold higher levels of acyclovir than those typically needed for HSV.
• In one study, the 50 per cent inhibitory dose (ID50) for acyclovir was between 1.4 and 6.4 micromol/L for five laboratory strains of VZV [7]. Some clinical viral strains have been less sensitive to acyclovir, with susceptibilities ranging from 4 to 17.5 micromol/L.
• Whether acyclovir is utilised or not for chickenpox will depend on the host, the time of presentation, and other comorbidities.

Children

• Most children under 12 who become infected with VZV develop the uncomplicated disease, although even healthy children can occasionally develop cerebellitis, pneumonia, purpura, hepatitis, and soft tissue infections.
• Secondary bacterial infections can be severe, particularly if associated with group A streptococcus.
• Older and immunocompromised children are at risk for complicated diseases, such as pneumonia, encephalitis, and Reye syndrome. 
• A seminal multicenter, double-blind, placebo-controlled study evaluating the effectiveness of oral acyclovir therapy compared to placebo was conducted in 815 healthy children who contracted varicella. 
• Acyclovir therapy (20 mg/kg PO four times daily) started within the first 24 hours after the onset of the rash and continued for five days.

Results of the trial included the following:

• Acyclovir-treated children had significantly fewer lesions than the placebo group (mean number 294 versus 347).
• Acyclovir treatment significantly reduced the timing of new lesions’ development and accelerated the healing and crusting of lesions.
• No new lesions formed after day three in the acyclovir group, while 20 per cent of the control group continued to develop lesions on day six or later.

Acyclovir for Children

• The duration of fever was generally shorter in the acyclovir group (three to four days); 20 per cent of placebo-treated children had a fever for more than four days.
• In addition, the acyclovir-treated children developed equivalent antibody responses to those given a placebo. In a Cochrane review that included this trial and two others, acyclovir significantly reduced the number of days with fever by 1.1 days and the maximum number of lesions by 76 compared to the placebo
• There were no clinically significant differences between acyclovir and placebo concerning complications.
• Acyclovir is safe and effective for varicella if given during the first 24 hours of rash.
• However, we agree with the Committee on Infectious Diseases of the American Academy of Pediatrics that oral acyclovir should not be used routinely in otherwise healthy children with varicella due to its modest effects.
• We also agree with the academy that oral acyclovir should be administered in the following groups of individuals at increased risk of moderate to severe varicella.
• Older children (greater than 12 years of age).
• Secondary household cases (since varicella can be more severe in secondary than in primary cases)
• History of chronic cutaneous or cardiopulmonary disorders, since secondary bacterial infections may have severe consequences
• Those children taking intermittent oral or inhaled steroid therapy, which can put them at risk for more severe disease
• Those individuals are taking chronic salicylates. These individuals are at higher risk of developing Reye syndrome. (See “Acute toxic-metabolic encephalopathy in children”, the section on ‘Reye syndrome.)

Treatment of Adults With Chickenpox

• Most adults infected with VZV have uncomplicated varicella, although they are at increased risk of developing pneumonia compared to children.
• Varicella pneumonia in adults usually leads to hospitalisation and carries overall mortality of between 10 and 30 per cent.
• A double-blind, placebo-controlled trial in 148 healthy adults conducted at a naval hospital randomly assigned patients with confirmed varicella to receive either oral acyclovir (800 mg five times daily) or a placebo for seven days.

The following significant benefits are noted with acyclovir therapy:

• Early therapy (initiated within 24 hours of rash onset) reduced the total time to full crusting of lesions from 7.4 days to 5.6 days
• A 46 per cent reduction in the maximum number of lesions
• A shorter duration of fever and lesser severity of symptoms

Treatment of Chickenpox

• with oral acyclovir from 25 to 72 hours after the appearance of the rash did not affect the course of the illness.
• Whether acyclovir effectively reduces complications related to varicella is not assessed in this study.
• As since only four patients developed pneumonia, no encephalitis cases or other fatalities were reported.
• However, retrospective analyses suggested that acyclovir treatment improves the clinical outcome in adults with established varicella pneumonia.
• Acyclovir has also been used for other varicella-related complications, such as severe varicella-associated hepatitis and liver failure.
• Due to the increased risk of complications in adults, we recommend the initiation of acyclovir in adults with varicella infection if therapy can be initiated within 24 hours of symptom onset.
• Immunocompromised host — Immunosuppressed children have a mortality rate of 7 to 14 per cent from primary varicella infection and also can develop severe complications.
• In several studies, intravenous administration of acyclovir in immunosuppressed children with varicella significantly reduced the risk of visceral dissemination and severe complications.
• Thus, the immunosuppressed host is treated with intravenous acyclovir, even if more than 24 hours have passed since the onset of symptoms.
• Dosing and adverse effects of acyclovir — The Medical Letter recommends oral acyclovir 20 mg/kg PO (up to 800 mg per dose) four times daily for five days for uncomplicated varicella; the usual dose for adults is 800 mg four times daily.

Acyclovir for Chickenpox

• Acyclovir is given intravenously (10 mg/kg every 8 hours) for seven days in patients who are immunocompromised or in immunocompetent patients with serious complications, such as varicella pneumonia or encephalitis.
• As of November 2012, there is a shortage of IV acyclovir in the United States due to a manufacturing delay.
• Clinicians should check the US Food and Drug Administration’s website for information about the availability of IV acyclovir.
• If IV acyclovir is unavailable, an alternative regimen (either IV or oral) is used. Specific recommendations are presented separately.
• Acyclovir is generally very well tolerated; gastrointestinal side effects or headaches may occur.
• When given intravenously, acyclovir can cause reversible renal insufficiency.
• Risk factors for this complication include dehydration and rapid infusion. The prodrug of acyclovir, valacyclovir, and famciclovir does have activity against VZV in vitro.
• However, scant clinical data regarding their specific use in uncomplicated or complicated varicella infection; most data related to their effectiveness in herpes zoster infections.

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SUMMARY AND RECOMMENDATIONS

• We suggest NOT treating uncomplicated varicella in otherwise healthy children under 12 years of age due to the modest benefits of acyclovir (Grade 2B). (See ‘Children’ above.)
• Moreover, recommend acyclovir for the treatment of varicella in the following children who are at increased risk of complicated disease: those who are 12 years of age or older, those with chronic cutaneous or pulmonary disorders, or those individuals taking steroid or salicylate therapy (Grade 1B).
• Therefore, suggest acyclovir treatment for secondary contacts since these individuals are at increased risk for more severe disease (Grade 2B).
• We recommend oral acyclovir (20 mg/kg PO four times daily for five days) for adults with uncomplicated varicella (Grade 1A). The usual dose for adults is 800 mg four times daily. (See ‘Dosing and adverse effects of acyclovir’ above.)
• We recommend intravenous acyclovir (10 mg/kg every eight hours) for immunosuppressed children with complicated or uncomplicated varicella (Grade 1A). (See ‘Immunocompromised host’ above.)
• Additionally, recommend intravenous acyclovir (10 mg/kg every eight hours) for children or adults who develop the disseminated disease, such as pneumonia or encephalitis (Grade 1A). (See ‘Dosing and adverse effects of acyclovir’above.)
• As of November 2012, there is a shortage of IV acyclovir in the United States.
• If IV acyclovir is not available, an alternative regimen is used. Specific recommendations presented separately. (See “Acyclovir: An overview”, the section on ‘If there is an acyclovir shortage’.)
• Antihistamines help relieve symptoms of pruritis. We recommend that acetaminophen, rather than aspirin, be used to treat fever (Grade 1C). (See ‘Therapy’ above.) Use of UpToDate is subject to the Subscription and License Agreement.