Varicella zoster virus and VZV pneumonia

This virus was asked about in Question 29.1 from the first paper of 2009. In that specific instance, the college had asked the candidates to recognise the rash of chicken pox from a photograph.

In Oh's Manual, Varicella doesn't even appear in the index. Though it appears around the book as a differential for various things (eg. viral encephalitis), it receives no attention beyond that.

For the CICM felloship candidates, this brief summary of what a CICM trainee is expected to know about VZV has been cobbled together from the following sources:

• Varicella Zoster Virus (Clinical Microbiology Reviews, 1996) - if you were to use only one resource, this should be it.
• Intensive care management of varicella pneumonia (1997)
• Varicella-zoster virus: atypical presentations and unusual complications (2002)

Virology

• VZV is a double-stranded DNA alphaherpesvirus
• It is highly human-specific
• It causes varicella (chicken pox) and herpes zoster (shingles).

Clinical features:

• An incubation period is usually expected (10-21 days)
• A rash develops, typically starting on the trunk and spreading to the limbs and face.
  • It ƒ begins as red papules and develops rapidly into teardrop vesicles (1-2mm
    diameter)
  • Vesicles become cloudy , break, and form crusty scabs
  • Crops of lesions occur so that there are several stages of lesion present
  • Vesicles often involve mucous membranes.
• One is usually infectious from about 24 hrs prior to the development of the rash, until the formation of the scabs. Transmission occurs by contact, or by exhaled droplets.
• As the lesions heal, some may become infected and progress to cellulitis or abscesses - the typical pathogens here are S.aureus and S.pyogenes
• After this primary infection, VZV establishes itself in the dorsal root ganglia.

Clinical Manifestations of VZV

Immunocompetent host Rash Oral/mucosal lesions Conjunctivitis, iritis, denditic ulcer Herpetic whitlow (nail cuticle lesion) Hepatitis Meningitis Encephalitis Pneumonia Purpura fulminans Hypersplenism

Risks factors for VZV pneumonia Immunocompromise Pregnancy Chronic lung disease Adults (25 × greater risk compared to children) Smoking Number of spots - over 100 (yes, somebody counted them) These risk factors are also elaborated upon in this article. In addition to the above, one can mention "contact with an infected person" - in one case series, such contact was mentioned by 16 of the varicella pneumonia patients, and only by 10 of the non-pneumonia patients.

Complications associated with severe disseminated VZV infection: Varicella ARDS Fulminant necrotic hepatitis Thrombocytopenia and DIC Adrenal gland necrosis Myocarditis

Diagnosis of VZV infection

Clinically: characteristic rash; this is usually unambigous.

Histologically: the Tzanck test: a scraping or smear of the base of an ulcer, which looks for giant multinucleated monocytes, swarming with the virus. This is a way of confirming that the rash is indeed VZV.

VZV PCR: this is the investigation of choice for CSF

Management of VZV

• Acyclovir, famciclovir, and valacyclovir are the modern agents.
  • Acyclovir is the IV drug of choice
  • Valaciclovir is the valine ester of aciclovir and improves oral bioavailability from ∼15% to ∼75%. It is the oral agent of choice.
  • VZV is ∼10-times less sensitive to aciclovir compared with the Herpes Simplex virus.
• The key is to use these agents early, as it reduces mortality.
• Occasionally, resistance to these may be present.
• Vaccination against VZV is available and is remarkably effective
• VZV immunoglobulin is available as post-exposure prophylaxis for particularly susceptible individuals (eg. the AIDS patients)

Varicella Pneumonia

This is of greatest relevance to the intensivist, because it is one fo the two major reasons the varicella patient might end up in the ICU. The other reason is VZV encephalitis, resulting in a decreased level of consciousness, requiring intubation.

From this article, I mined various factoids the ICU trainee should be aware of:

• VZV pneumonia is 25 times more common in adults.
• 5-50% of adults with cutaneous VZV develop CXR changes.
• Usually presents 1–6 days after the onset of the rash.
• Management consists of IV acyclovir for 7–10 days
• The disease tends to result in a diffusion defect which persists indefinitely (some studies have found the defect is still present more than 8 years later following the episode of pneumonia).