What are the diagnosis and management options for varicella zoster?

Varicella Zoster Diagnosis and Management

Diagnosis

Clinical diagnosis is sufficient for typical presentations of varicella (chickenpox) and herpes zoster (shingles), but laboratory confirmation is essential for immunocompromised patients with atypical presentations. 1

Clinical Presentation

• Varicella: Generalized, pruritic vesicular rash with 250-500 lesions in different stages (crops) of development and crusting, typically accompanied by low-grade fever 1
• Herpes zoster: Prodromal pain often precedes skin findings by 24-72 hours, followed by unilateral dermatomal vesicular eruption 2
• In immunocompetent hosts, lesions erupt for 4-6 days with total disease duration of approximately 2 weeks 2
• In immunocompromised patients, skin lesions may develop over 7-14 days and heal more slowly without effective antiviral therapy 2

Laboratory Testing

• Serology is NOT useful for diagnosing active chickenpox or shingles 1
• PCR from vesicular fluid or scab scraping is the gold standard, with sensitivity and specificity both approaching 100% 1
• Direct fluorescent antibody assay or VZV-specific culture can also confirm diagnosis 1
• Laboratory confirmation is mandatory for immunocompromised patients with atypical presentations 2
• Avoid testing samples that may contain passively acquired VZV IgG (e.g., from blood transfusion) 1

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Management

Antiviral Therapy for Herpes Zoster

Oral valacyclovir 1 gram three times daily for 7 days is the preferred first-line treatment for uncomplicated herpes zoster, initiated within 72 hours of rash onset. 3

First-Line Oral Options (Immunocompetent Patients)

• Valacyclovir 1000 mg orally three times daily for 7 days (preferred due to better bioavailability and less frequent dosing) 3
• Famciclovir 500 mg orally three times daily for 7 days 3
• Acyclovir 800 mg orally five times daily for 7-10 days 4
• Treatment should continue until all lesions have scabbed, which may require extending beyond 7 days 5, 3

Intravenous Therapy Indications

Intravenous acyclovir 5-10 mg/kg every 8 hours is indicated for:

• Disseminated or invasive herpes zoster 5
• Multi-dermatomal involvement 3
• Immunocompromised patients with severe disease 3, 2
• Ophthalmic involvement 6
• Inability to take oral medications 6
• CNS involvement 1

Special Populations

Immunocompromised patients:

• All immunocompromised patients require antiviral treatment regardless of timing of presentation 3
• High-dose IV acyclovir remains the treatment of choice for VZV infections in severely compromised hosts 5, 2
• Consider temporarily reducing immunosuppressive medications for disseminated or invasive disease 5, 3
• Immunosuppression may be restarted after commencing antiviral therapy and resolution of skin vesicles 3
• Do NOT commence immunomodulator therapy during active chickenpox or herpes zoster infection 1

Facial/ophthalmic zoster:

• Use same antiviral regimens as other locations but with heightened vigilance for complications 3
• Elevate affected area to promote drainage and keep skin well hydrated with emollients 3

Acyclovir-resistant cases:

• Foscarnet 40 mg/kg IV every 8 hours is recommended 3, 6

Varicella (Chickenpox) Treatment

Children (2 years and older):

• Acyclovir 20 mg/kg orally four times daily (maximum 800 mg per dose) for 5 days 4
• Valacyclovir 20 mg/kg orally three times daily for 5 days (not to exceed 1 gram three times daily) 7

Adults and children over 40 kg:

• Acyclovir 800 mg orally four times daily for 5 days 4

Immunocompromised patients:

• Intravenous acyclovir is indicated 4
• Treatment should be initiated at earliest sign or symptom, ideally within 24 hours of rash onset 4

Critical Management Pitfalls to Avoid

• Never use topical antiviral therapy alone - it is substantially less effective than systemic therapy 5, 3
• Do not delay treatment waiting for laboratory confirmation in typical presentations 3
• Do not stop treatment at 7 days if new lesions continue to form or healing is incomplete 3
• Avoid corticosteroids in immunocompromised patients due to increased risk of disseminated infection 3
• Corticosteroids (prednisone) may provide modest benefits in reducing acute pain in select cases of severe, widespread disease in immunocompetent patients, but should generally be avoided in elderly patients and those with immunosuppression 5, 3

Renal Dosing Adjustments

For creatinine clearance 10-25 mL/min:

• Acyclovir 800 mg every 8 hours 4

For creatinine clearance 0-10 mL/min:

• Acyclovir 800 mg every 12 hours 4

Hemodialysis patients:

• Administer additional dose after each dialysis session 4

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Prevention

Vaccination

The recombinant zoster vaccine (Shingrix) is recommended for all adults aged 50 years and older, regardless of prior herpes zoster episodes. 5, 3

• Vaccination should ideally occur before initiating immunosuppressive therapies 3
• The vaccine can be considered after recovery from herpes zoster to prevent future episodes 5

Pre-Exposure Prophylaxis for Varicella

Screening and vaccination strategy:

• Screen all patients by history for chickenpox, shingles, or receipt of two doses of varicella vaccine 1
• Test for VZV IgG if history is uncertain, negative, or patient grew up in tropical/subtropical climate 1
• Seronegative immunocompetent patients should receive two doses of varicella vaccine at least one month apart, completing the course at least 3 weeks before starting immunomodulators 1
• Subsequent immunization can only be administered 3-6 months after cessation of all immunosuppressive therapy 1

Post-Exposure Prophylaxis

For varicella-susceptible patients exposed to active VZV infection:

• Varicella zoster immunoglobulin (or IVIG) within 96 hours of exposure 5, 2
• If immunoglobulin unavailable or >96 hours have passed: 7-day course of oral acyclovir beginning 7-10 days after exposure 5

Long-Term Prophylaxis

• Recipients of allogeneic blood and bone marrow transplants routinely take acyclovir or valacyclovir during the first year following transplant for prevention of VZV and HSV reactivation 2

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Complications and Prognosis

Immunocompromised patients face significantly higher morbidity and mortality:

• Chickenpox can cause life-threatening pneumonia, hepatitis, encephalitis, or hemorrhagic disorders 1
• In one review, 5 of 20 varicella cases in IBD patients proved fatal 1
• Herpes zoster has increased risk of visceral dissemination, including CNS disease 1
• Without adequate treatment, chronic ulcerations with persistent viral replication may develop, complicated by secondary bacterial and fungal superinfections 2
• Viral shedding peaks in the first 24 hours after lesion onset when most lesions are vesicular 2