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Chickenpox (Varicella) - Clinical Overview
Definition
Varicella (chickenpox) is an acute, highly infectious disease caused by Varicella-Zoster Virus (VZV), also called Human (alpha) herpesvirus 3. It is characterized by a generalized vesicular rash accompanied by fever and malaise. Chickenpox represents the primary infection with VZV; the same virus establishes latency in dorsal root ganglia and can reactivate decades later as herpes zoster (shingles).
- Goldman-Cecil Medicine, p. 3608
- Harrison's Principles of Internal Medicine 22E, p. 1548
Pathogen
VZV is a member of the Herpesviridae family with the following features:
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Structure: Lipid envelope + icosahedral nucleocapsid; ~180-200 nm diameter; double-stranded DNA (~125,000 bp)
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Glycoproteins on the viral envelope are targets for neutralizing antibodies
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Encodes a thymidine kinase that phosphorylates acyclovir → inhibits viral DNA polymerase (basis of antiviral therapy)
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Harrison's Principles of Internal Medicine 22E, p. 1548
Epidemiology
| Parameter | Detail |
|---|
| Global disease burden | ~4.2 million severe complications/year; ~4,200 deaths/year |
| Pre-vaccine case fatality rate | ~3 per 100,000 cases (high-income countries) |
| Transmission | Respiratory droplets + direct contact with skin lesions |
| Attack rate | ≥90% in susceptible (seronegative) contacts |
| Reservoir | Humans only |
| Incubation period | 14-16 days (range: 10-21 days) |
| Period of communicability | 1-2 days before rash to 6 days after onset |
| Peak age | Children (most cases <10 years); adults are more severely affected |
- Park's Textbook of Preventive and Social Medicine, p. 163
Clinical Features
Prodrome
- Children: Usually absent or mild (low-grade fever, malaise 1-2 days before rash)
- Adults: More pronounced prodrome - fever, headache, malaise, myalgia, arthralgia precede the rash by 2-4 days
Rash - The Hallmark
The rash appears in successive crops (new crops every 3-4 days), giving lesions at different stages simultaneously:
- Macule → Papule → Vesicle ("dew drop on a rose petal") → Pustule → Crust/Scab
- Distribution: Centripetal - starts on trunk/face/scalp, then spreads to extremities (face, trunk > limbs)
- Mucous membrane involvement: Oral mucosa, conjunctiva, genitalia
- Pruritus is intense
- Lesions at different stages simultaneously is pathognomonic
- Harrison's Principles of Internal Medicine 22E, p. 1548
Pathogenesis
- Respiratory droplets inhaled → replicate in nasopharynx → seed lymphatics/reticuloendothelial system → viremia (primary)
- Virus seeds skin → vesicle formation: ballooning degeneration, multinucleated giant cells, eosinophilic intranuclear inclusions
- Vesicular fluid becomes cloudy with PMNs → ruptures or reabsorbs
- After primary infection: VZV travels via sensory nerves to dorsal root ganglia → establishes lifelong latency
- Reactivation → Herpes zoster (shingles)
- Harrison's Principles of Internal Medicine 22E, p. 1548
Complications
In Healthy Children
- Usually mild and self-limiting
Serious Complications (especially adults, immunocompromised, neonates, pregnant women)
| Complication | Notes |
|---|
| Varicella pneumonia | Most common life-threatening complication in adults; rare in healthy children; interstitial pneumonitis |
| Encephalitis | Perivascular cuffing in brain; less common than in measles |
| Acute cerebellar ataxia | More common in children |
| Reye's syndrome | Acute encephalopathy + fatty liver degeneration (associated with aspirin use - NEVER give aspirin) |
| Secondary bacterial infections | Group A beta-hemolytic Streptococcus, Staphylococcus aureus → cellulitis, erysipelas, epiglottitis, osteomyelitis |
| Hemorrhagic varicella | Rare, life-threatening |
| DIC | In immunocompromised; rapidly fatal |
| Congenital varicella syndrome | Maternal infection → cutaneous scars, limb atrophy, microcephaly, cataracts, chorioretinitis, deafness |
| Neonatal varicella | Mother develops rash within 5 days before/48 hours after delivery → severe disseminated neonatal disease |
| Acute retinal necrosis | Major VZV manifestation, especially in AIDS patients |
- Park's Textbook of Preventive and Social Medicine, p. 163
Laboratory Diagnosis
| Test | Notes |
|---|
| PCR (vesicular fluid, crusts, saliva, CSF) | Gold standard - most sensitive and specific |
| Cell culture | VZV isolation; slower |
| Direct immunofluorescence (DIF) | Rapid but lower sensitivity than PCR |
| IgM antibody | Less sensitive; not method of choice for acute varicella |
| IgG serology | Used to assess immunity in unvaccinated individuals (e.g., healthcare workers) |
Clinical diagnosis is usually sufficient; labs reserved for atypical or complicated cases, or post-eradication era differentiation from smallpox.
- Park's Textbook of Preventive and Social Medicine, p. 163
Treatment
Supportive (All Cases)
- Antipyretics: Paracetamol (acetaminophen) - NEVER aspirin (risk of Reye's syndrome)
- Antihistamines and calamine lotion for pruritus
- Keep nails trimmed; avoid scratching (prevents secondary infection and scarring)
- Maintain hydration
Antiviral Therapy
| Drug | Dose | Duration | Indication |
|---|
| Acyclovir (oral) | 800 mg 5x/day (adults); 20 mg/kg/dose 4x/day (children >2 yrs, max 800 mg) | 5-7 days | Healthy adolescents >13 yrs, adults, secondary household cases |
| Valacyclovir | 1 g PO 3x/day | 5-7 days | Preferred over acyclovir (better bioavailability, less frequent dosing) |
| Famciclovir | 500 mg PO 3x/day | 7 days | Alternative; at least as effective as acyclovir |
| IV Acyclovir | 10 mg/kg every 8 hours | 7 days | Severely immunocompromised, varicella pneumonia, encephalitis |
Start antivirals within 24 hours of rash onset for maximum benefit.
- Harrison's Principles of Internal Medicine 22E, p. 1548
Prevention
1. Live Attenuated Varicella Vaccine (Oka strain - VAR)
- Children 12-15 months: First dose
- 4-6 years: Second dose (booster)
- Seronegative persons >13 years: Two doses at least 1 month apart
- Contraindicated if CD4 count <200 cells/mm³ (immunocompromised)
- Results in significant decline in chickenpox incidence in vaccinated communities
2. Varicella-Zoster Immunoglobulin (VZIG) - Post-Exposure Prophylaxis
Given within 96 hours of exposure to high-risk individuals:
- Immunocompromised susceptible children (no prior varicella or vaccination)
- Susceptible pregnant women
- Newborn whose mother had chickenpox within 5 days before or 48 hours after delivery
- Hospitalized premature infants (≥28 weeks) whose mother is seronegative
- Premature infants <28 weeks (regardless of maternal history)
3. Control Measures
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Isolation of cases for ~6 days after onset of rash
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Notification to public health authorities
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Disinfection of articles soiled with discharge
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Harrison's Principles of Internal Medicine 22E, p. 1548
-
Park's Textbook of Preventive and Social Medicine, p. 163
Special Situations
| Situation | Management |
|---|
| Pregnancy | Oral acyclovir for mild disease; IV acyclovir for severe/pneumonia; VZIG for susceptible women exposed; delivery-associated varicella requires neonatal VZIG |
| Immunocompromised | IV acyclovir initially; reduce immunosuppression if possible |
| Neonatal varicella | VZIG + IV acyclovir |
| Varicella pneumonia | IV acyclovir + ventilatory support if needed |
Key Differentials
| Condition | Distinguishing features |
|---|
| Smallpox | All lesions in same stage; centrifugal distribution; deeper lesions; ERADICATED |
| Herpes simplex (disseminated) | Localized clusters; history of HSV |
| Hand-foot-mouth disease | Lesions on palms/soles/oral mucosa |
| Impetigo | Honey-crusted; no systemic features |
| Insect bites | Grouped, no multiple stages simultaneously |
Summary Table
| Feature | Detail |
|---|
| Causative agent | VZV (Human herpesvirus 3) |
| Transmission | Respiratory droplets, direct contact |
| Incubation | 10-21 days (mean 14-16 days) |
| Infectivity | 1-2 days before rash to 6 days after |
| Rash | Centripetal, polymorphic, crops of vesicles |
| Key diagnostic sign | Lesions at multiple stages simultaneously |
| Complication to fear | Varicella pneumonia (adults), Reye's (aspirin), bacterial superinfection |
| Treatment | Acyclovir/Valacyclovir; NO aspirin |
| Prevention | Live attenuated vaccine (Oka); VZIG post-exposure |
Sources: Harrison's Principles of Internal Medicine 22E (2025) | Goldman-Cecil Medicine | Park's Textbook of Preventive and Social Medicine | Andrews' Diseases of the Skin