Varicella zoster

Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3) is a DNA virus that is a part of the herpesviridae family. A primary infection by VZV leads to varicella zoster (chickenpox) while a latent infection leads to herpes zoster (shingles).

In this CCC we will cover both of these.

Chickenpox is a common acute disease that is associated with a vesicular rash (blistered rash), fever and general malaise. It is self-limiting and affects 75% of children by the age of 5 years old.

Pathophysiology

VZV is transmitted through direct contact or through respiratory droplets. Once acquired, the virus spreads to regional lymph nodes, causing a primary viraemic phase.

• Primary viraemic phase - on days 4-6 the infection spreads to the liver, spleen and other cells within the reticuloendothelial system.
• Secondary viraemic phase - occurs at around day 9. Mononuclear cells such as lymphocytes, monocytes, dendritic cells transport the virus to the skin and mucous membranes → vesicular rash.

The virus causes inflammation of small blood vessels and epithelial cell degeneration, allowing for the vesicles to be filled with fluid that contain high levels of the virus. Direct contact with these vesicles allows for transmission.

There is an incubation period of 1-3 weeks and the individual begins to be infectious 1-2 days before the onset of the rash. Until all vesicles have dried out which is usually 5 days after onset of the rash. It is therefore mandatory for children to remain home throughout this time, until the vesicles have crusted over and they are no longer infectious.

😷 Presentation

Prodromal symptoms - these appear 1-2 days prior to the rash.

• High fever
• General malaise
• Myalgia
• Anorexia
• Headache
• Nausea

⭐️ Vesicular rash

These are small erythematous macules present on the scalp and face first, then trunk and proximal limbs.

Over the next 12-14 hours they transform from macules → papules → clear pruritic vesicles with pustules. The itch is very intense at this stage.

The vesicles may also occur on palms, soles, mucous membranes (accompanied by painful and shallow oral/genital ulcers).

🔍 Investigations

It is a clinical diagnosis based on examination findings.

🧰 Management

Interestingly, chickenpox is a notifiable disease in Scotland and Northern Ireland, but within England and Wales it is not.

🚨 Complications

• In the foetus:
• Foetal varicella syndrome - if VZV is contracted in the first 28 weeks of pregnancy. It is characterised by neurological abnormalities (such as microcephaly, eye defects and hypoplasia of limbs.
• In neonates and immunocompromised individuals:
• Haemorrhagic zoster - if the mother is infected during 4 weeks prior to delivery then up to 50% of babies will be infected and around 25% will develop chickenpox despite having passively acquire maternal antibodies. Haemorrhagic varicella is when there is haemorrhage associated with the disease.

• In children:
• Secondary bacterial infection - such as impetigo, furuncles, cellulitis, erysipelas, necrotising fasciitis.
• Scarring
• Neurological complications - Reye’s syndrome, acute cerebellar ataxia, encephalitis, meningitis, polyradiculitis, myelitis.
• In adults and pregnant women:
• Varicella pneumonia - this is the most common complication in adults. Smokers are at increased risk.
• Hepatitis
• Encephalitis

HERPES ZOSTER (SHINGLES)

Herpes zoster (HZ), also known as shingles is caused by reactivation of VZV that was acquired during primary varicella infection. It is characterised by dermatomal pain and popular rash that is acute, unilateral, painful and blistering. The pain typically precedes the rash by several days and can persist for several months after the rash resolves within 4-5 weeks (post-herpetic neuralgia).

Pathophysiology

Latent infection occurs as the virus lies dormant in the dorsal root ganglia as well as the cranial nerve ganglia. It is able to remain latent and evade the immune system as it reduces gene expression and down regulates MHC Class 1 antigen expression on infected cell surfaces.

What triggers reactivation of the virus is a decline in the virus-specific cell-mediated immunity that may occur due to HIV, malignancy, chemotherapy, chronic corticosteroid use. This causes the virus to travel anterograde from the ganglia to the tissue of the affected nerve segment and its correlating cutaneous dermatome. This causes ganglionitis - leading to inflammation and destruction of neurons and supporting cells.

In immunocompetent individuals, the infection usually affects a single dermatome, but in the immunocompromised the involvement of several dermatomes is not uncommon → disseminated disease. The most commonly affected dermatomes are T1-L2.

⚠️ Risk factors

• Increasing age - >50 years old
• Immunocompromised - such as HIV, malignancy, chemotherapy, chronic steroid use.

😷 Presentation

There is a prodromal period followed by a rash once again:

• Prodrome
• Burning pain - over the affected dermatome for 2-3 days. It may be severe and interfere with sleep.
• Fever, headache, lethargy
• Rash
• Initially it is erythematous and macular and is over the affected dermatome.
• It quickly turns into a vesicular rash.
• It is well demarcated by the dermatome and does not cross the midline (although it may cross into adjacent dermatomes slightly).
• Corneal ulceration is a common finding if the trigeminal nerve is affected.

🔍 Investigations

Clinical diagnosis without any testing required, a history and physical examination is required.

🧰 Management

🚨 Complications

• Post-herpetic neuralgia - occurs in 5-30% of patients. This is a long lasting pain in the dermatome region affected by herpes zoster.
• Bacterial superinfection - secondary infections of the lesions may lead to cellulitis, osteomyelitis or necrotising fasciitis and sepsis.
• Herpes zoster ophthalmicus - this is when it affects the ophthalmic division of the trigeminal nerve (V1) leading to a variety of ocular complications such as corneal abrasions. If there is a lesion along the tip, root, or side of the nose, there is a strong likelihood of ocular involvement (this is known as Hutchinson’s sign).
• Ramsay Hunt syndrome (herpes zoster oticus) - this is a neurological manifestation of the disease characterised by facial weakness/paralysis unilaterally. It needs to be treated with aciclovir promptly.