What are the pathophysiology, symptoms, diagnosis, management, and counseling for a patient with chickenpox (varicella-zoster virus infection), including differential diagnoses and treatment options such as antiviral medications like acyclovir (generic name)?

Chickenpox (Varicella): Comprehensive Clinical Overview

Pathophysiology

Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that enters through the nasopharyngeal mucosa or conjunctiva, causing a generalized infection with dermal tropism. 1

• The virus replicates initially at the portal of entry, followed by viremia that disseminates the virus to skin and internal organs 1
• VZV establishes latency in dorsal root ganglia neurons, where it can reactivate years later as herpes zoster (shingles) 1
• Histopathological findings include ballooning degeneration of epithelial cells, multinucleated giant cells, and eosinophilic intranuclear inclusions 2
• The virus has worldwide distribution but is more prevalent in temperate climates 1

Clinical Symptoms

Chickenpox presents with gradual onset of constitutional symptoms, upper respiratory tract signs, and a characteristic polymorphous rash that evolves through stages. 2

Typical Presentation

• Prodrome: Fever, malaise, anorexia, and headache typically precede the rash by 1-2 days 2
• Rash characteristics: Begins on the face and trunk, then spreads peripherally with lesions in varied stages (macules → papules → vesicles → pustules → crusts) appearing simultaneously 3
• Systemic symptoms: Fever, fatigue, loss of appetite, and pruritus 4
• The rash typically continues to erupt for 4-6 days in immunocompetent patients 5

High-Risk Populations

• Adults over 20 years: At increased risk of severe disease and complications 6
• Immunocompromised patients: May develop lesions for 7-14 days with slower healing and risk of disseminated disease 5, 3
• Pregnant women: Risk of severe maternal disease and vertical transmission (25% probability), with 3% risk of congenital varicella syndrome if infection occurs in early pregnancy 2
• Neonates: Perinatal varicella carries significant mortality risk, especially if maternal infection occurs within 5 days before to 2 days after delivery 7

Diagnosis

The diagnosis of chickenpox is primarily clinical, based on history and the characteristic appearance of the rash, but laboratory confirmation is required for atypical presentations or immunocompromised patients. 2, 6

Clinical Diagnosis

• Characteristic polymorphous rash with lesions in multiple stages of development 2
• History of exposure to varicella (incubation period 10-21 days) 1
• Presence of fever and constitutional symptoms 2

Laboratory Confirmation (when indicated)

• Direct fluorescent antibody (DFA) or PCR for VZV from vesicular fluid or lesion scrapings 1
• Viral culture from vesicular fluid (less sensitive, takes longer) 1
• Serology: Detection of VZV-specific IgM and IgG antibodies (IgM indicates acute infection) 1
• Laboratory confirmation is essential for immunocompromised patients with atypical presentations 6

Differential Diagnoses

The differential diagnosis includes other vesicular rashes, particularly in severe or atypical presentations. 6

• Disseminated herpes simplex virus (HSV): Can appear similar, especially in immunocompromised patients 6
• Smallpox (variola): Historical concern; smallpox has centrifugal distribution (more lesions on extremities) versus chickenpox's centripetal pattern 6
• Generalized vaccinia: In vaccinated individuals, can mimic chickenpox 6
• Impetigo or other bacterial skin infections: Secondary bacterial infection can complicate chickenpox 2
• Drug eruptions: Particularly in patients on multiple medications 2
• Hand, foot, and mouth disease (enteroviral): Lesions on hands, feet, and mouth 6
• Severe eczema vaccinatum: In patients with atopic dermatitis 6

Management

Immunocompetent Patients

For healthy children and adults with uncomplicated chickenpox, treatment is primarily supportive, though oral acyclovir may be considered to reduce symptom duration and severity. 4, 7

Supportive Care

• Hygiene measures: Regular bathing with stringent soaks to prevent secondary bacterial infection 2
• Isolation: Patient should be isolated until all lesions have crusted (typically 5-7 days after rash onset) 5
• Symptomatic relief: Oral antihistamines for pruritus, acetaminophen for fever (avoid aspirin due to Reye's syndrome risk) 6
• Skin care: Keep lesions clean and dry; avoid scratching to prevent secondary bacterial infection 2

Antiviral Therapy (Optional for Healthy Patients)

• Oral acyclovir 20 mg/kg (maximum 800 mg) four times daily for 5 days if initiated within 24 hours of rash onset 8
• Treatment decreases number of lesions, shortens duration of new lesion formation, and reduces systemic symptoms (fever, fatigue, anorexia) 4
• Most beneficial if started within 24 hours of rash onset 8

High-Risk and Immunocompromised Patients

Intravenous acyclovir is mandatory for immunocompromised patients, neonates, pregnant women with severe disease, and those with disseminated or visceral involvement to prevent life-threatening complications. 7, 3

Indications for IV Acyclovir

• Immunocompromised patients (HIV/AIDS, cancer, organ transplant recipients, those on immunosuppressive therapy) 7, 2
• Neonates during first 2 weeks of life 7
• Preterm infants in neonatal nursery 7
• Severe varicella in any patient (pneumonia, encephalitis, hepatitis) 7, 2
• Disseminated disease (multi-dermatomal involvement, visceral organs) 3
• Pregnant women with severe disease 7, 2
• Children younger than 2 years with severe disease 7

IV Acyclovir Dosing

• 10 mg/kg every 8 hours for immunocompromised patients and disseminated disease 3
• Continue for minimum 7-10 days and until all lesions have completely scabbed 3
• Monitor renal function closely and ensure adequate hydration to prevent acyclovir-induced crystalline nephropathy 3
• Adjust dose for renal impairment per manufacturer guidelines 8

Adjunctive Measures

• Temporary reduction or discontinuation of immunosuppressive medications if clinically feasible in cases of disseminated disease 3
• Aggressive supportive care including hemodynamic support for severe cases 6
• Monitor for and treat secondary bacterial or fungal infections 6

Special Considerations

Pregnant Women

• Varicella-zoster immune globulin (VZIG) within 96 hours of exposure for varicella-susceptible pregnant women 5
• If VZIG unavailable or >96 hours post-exposure, consider 7-day course of oral acyclovir beginning 7-10 days after exposure 5
• IV acyclovir for severe maternal disease 7

Neonates

• Early IV acyclovir for neonates with perinatal varicella, especially if maternal infection occurred 5 days before to 2 days after delivery 7
• VZIG for exposed neonates born to mothers without immunity 5

Counseling and Prevention

Patient Education

Patients must understand that chickenpox is highly contagious from 1-2 days before rash onset until all lesions have crusted, requiring strict isolation to prevent transmission. 5, 1

• Contagiousness: 90% of susceptible persons exposed will develop infection 4
• Isolation period: Avoid contact with susceptible individuals (pregnant women, immunocompromised, neonates) until all lesions have crusted 5
• Transmission: Spread via respiratory droplets and direct contact with vesicular fluid 1
• Complications to watch for: High fever, difficulty breathing, severe headache, altered mental status, spreading rash beyond initial distribution 2
• Secondary bacterial infection: Watch for increasing redness, warmth, purulent drainage from lesions 2

Vaccination

Live attenuated varicella vaccine (Varivax) is recommended for routine childhood immunization and is the most effective prevention strategy. 1, 9

• Recommended for all healthy children without history of varicella 1
• Contraindicated in immunocompromised patients and pregnant women 1
• Vaccine-induced immunity lasts at least 6-10 years in majority of vaccinees 2
• Vaccine virus is sensitive to acyclovir and not transmissible to non-vaccinated children 2

Post-Exposure Prophylaxis

VZIG within 96 hours of exposure is critical for high-risk susceptible individuals to prevent or attenuate disease. 5

Indications for VZIG

• Immunocompromised patients without VZV immunity 5
• Pregnant women without immunity 5
• Neonates born to mothers with varicella 5 days before to 2 days after delivery 5
• Preterm infants exposed in neonatal nursery 7

Alternative if VZIG Unavailable

• Oral acyclovir for 7 days beginning 7-10 days after exposure if VZIG unavailable or >96 hours post-exposure 5

Critical Pitfalls to Avoid

• Never delay IV acyclovir in immunocompromised patients or those with severe disease while waiting for laboratory confirmation 3
• Never use oral antivirals as initial therapy for disseminated or potentially disseminated disease in immunocompromised patients 3
• Never use topical antivirals for chickenpox treatment, as they are substantially less effective than systemic therapy 5
• Never administer aspirin to children with chickenpox due to risk of Reye's syndrome 6
• Never discontinue antiviral treatment at exactly 7 days if lesions are still forming or have not completely scabbed 5
• Do not underestimate severity in adults and immunocompromised patients, who have significantly higher morbidity and mortality 6, 2