Varicella Pneumonia - Comprehensive MD Exam Answer (10 Marks)

1. Introduction / Definition

2. Aetiology / Causative Agent

• Pathogen: Varicella-zoster virus (VZV) - a double-stranded DNA virus belonging to the Herpesviridae family (Human Herpesvirus 3)
• Primary VZV infection produces varicella (chickenpox); reactivation produces herpes zoster (shingles)
• The virus is highly contagious; transmitted by respiratory droplets and direct contact with skin lesions

3. Epidemiology & Risk Factors

• HIV/AIDS patients with chickenpox are at especially high risk for varicella pneumonia
• Pre-vaccine era: 15-30% of invasive group A streptococcal infections were associated with varicella

4. Pathogenesis

1. Primary viremia - virus disseminates from infected lymphocytes/monocytes
2. Secondary viremia - more extensive dissemination producing the characteristic rash

• Multicentric haemorrhage and necrosis centred on airways
• Focal areas of necrosis with intranuclear inclusion bodies (Cowdry type A inclusions) in pneumocytes
• Interstitial pneumonitis with mononuclear cell infiltration
• Fibrin-rich oedema fluid filling alveolar spaces
• Multinuclear giant cells (especially in immunocompromised hosts)

5. Clinical Features

• Cough (often dry, non-productive initially)
• Dyspnoea and tachypnoea
• High fever - can persist or worsen despite skin lesion resolution
• Pleuritic chest pain
• Haemoptysis (may be present)
• Cyanosis (indicates severe disease)

Key exam point: "The severity of symptoms usually exceeds the physical findings" - physical examination of the chest may be relatively normal despite severe radiological changes.

• Tachycardia, tachypnoea
• Bilateral crackles on auscultation
• Typical varicella rash in various stages ("dewdrops on rose petals" - vesicles to pustules to crusts simultaneously present)
• The intensity of the rash does not necessarily correlate with severity of pneumonia

6. Investigations

A. Chest X-Ray

• Diffuse peribronchial nodular densities throughout both lung fields
• Concentrating in the perihilar regions and at the lung bases
• Bilateral infiltrates; hilar adenopathy may be present
• Pleural effusions can occur

B. HRCT Chest (most sensitive)

• Numerous nodular opacities, 5-10 mm diameter, bilateral and randomly distributed
• Some nodules have a surrounding halo of ground-glass opacity
• Patchy ground-glass opacities
• Coalescence of nodules forming areas of consolidation
• Miliary distribution may occur
• Late/healed stage: well-defined, randomly scattered 2-3 mm densely calcified nodules (pathognomonic late finding)

C. Pulmonary Function Tests

• Normal spirometric values but decreased carbon monoxide diffusing capacity (DLCO) - may persist for months after resolution

D. Laboratory Tests

• VZV PCR (blood, BAL fluid, skin lesion scraping - Tzanck smear)
• Serology: VZV IgM (acute), IgG (immunity)
• ABG: hypoxaemia (PaO2 reduced)
• FBC, LFTs (hepatitis may coexist in immunocompromised)

E. Bronchoscopy/BAL

• For diagnosis in immunocompromised or ventilated patients
• Cytology may show multinuclear giant cells with intranuclear inclusions

7. Histopathology

• Intranuclear inclusion bodies (Cowdry type A) in infected pneumocytes and alveolar macrophages
• Focal areas of necrobiosis (necrosis with surrounding inflammation)
• Alveolar haemorrhage and fibrin deposition
• Interstitial mononuclear cell infiltration
• Hyaline membrane formation in severe cases (diffuse alveolar damage pattern)
• Multinuclear giant cells with intranuclear inclusions (in immunocompromised)

8. Complications & Prognosis

• Healthy adults without treatment: 10-30%
• With prompt acyclovir therapy in immunocompetent adults: <10%
• Pregnant women (pre-antiviral era): 35-40%; reduced to 11-14% with acyclovir
• Immunocompromised patients: up to 50%
• Murray & Nadel quotes: "Mortality rate ranges from 11% in healthy adults to approximately 50% in pregnant women and immunocompromised persons"

9. Management

A. Antiviral Therapy (cornerstone)

• Dose: 10 mg/kg every 8 hours IV (for 7-10 days or until clinical improvement)
• Initiated within 36 hours of hospitalisation - reduces fever, tachypnoea, and improves oxygenation
• All gravidas with varicella pneumonia should be aggressively treated with IV acyclovir and admitted to ICU

• Acyclovir 800 mg 5x daily for 5-7 days
• Valacyclovir 1000 mg every 8 hours (more convenient)
• Famciclovir 500 mg every 8 hours

B. Supportive Care

• Hospitalisation - mandatory for varicella pneumonia
• Supplemental oxygen / High-flow oxygen
• ICU admission if hypoxaemia, respiratory failure, or need for mechanical ventilation
• Chest physiotherapy
• Monitor ABG, O2 saturation

C. Specific Situations

• Pregnant women: IV acyclovir + ICU admission; varicella-zoster immune globulin (VZIG) for post-exposure prophylaxis within 96 hours of exposure
• Immunocompromised: IV acyclovir within 72 hours of rash onset; controlled trials show decreased visceral complications; switch to oral therapy when new lesions stop appearing

D. Prophylaxis

• VZIG (Varicella-zoster immune globulin): Susceptible high-risk individuals (pregnant, immunocompromised) within 96 hours of exposure; reduces but does not abolish risk of infection
• Varicella vaccine (live attenuated): Pre-exposure prophylaxis in seronegative individuals; contraindicated in pregnancy and immunocompromised patients

E. Corticosteroids

• Data conflicting; cohort studies and literature reviews have not shown clear benefit and may cause harm - generally not recommended

10. Special Considerations

Varicella Pneumonia in Pregnancy

• Most dangerous in the third trimester
• Prior to acyclovir: maternal mortality 35-40% (vs. 11-17% in non-pregnant adults)
• Fetus at risk of: premature delivery, intrauterine death, congenital varicella syndrome (if maternal varicella occurs in first 20 weeks - risk ~1-2%)
• Perinatal varicella (within 10 days of birth) is particularly dangerous for the neonate
• Management: IV acyclovir + ICU monitoring; VZIG for exposed susceptible gravidas

Varicella Pneumonia in Immunocompromised

• Higher risk of visceral dissemination - prolonged fever, recurrent crops of lesions are warning signs
• Pneumonia, hepatitis, encephalitis, haemorrhagic complications may all co-occur
• Purpura fulminans with DIC is a feared complication
• Higher VZV viral loads; potentially resistant strains may emerge in severely immunosuppressed

Summary Table for Quick Revision