PBL 29

Question 1

Pathophysiology of shingles:

1. Mechanism
2. Clinical features
3. Complications
4. Prevention
5. Transmission
6. Risk factors
7. Treatment

Answer 1

1. Mechanism
   - Caused by the reactivation of the varicella-zoster virus (VZV)
   - Primary infection with VZV causes varicella. Once it resolves, the virus remains latent in the dorsal root ganglion & can re-activated

3 phases of illness:

1. Pre-eruptive phase AKA Pre-herpetic neuralgia
   - Nerve pain prior to eruption of herpetiform vesicles
   - Pain
   - Paraesthesia in 1 or more dermatomes
   - Headache
   - Malaise
   - Myalgia
   - Fatigue
2. Acute eruptive phase
   - Herpetiform vesicles on an erythematous base along 1 or more dermatomes (does not cross midline as it is localised to a dermatome)
   - Regional lymphadenopathy
   - Clear vesicles that become cloudy, then rupture, crust over and involute
   - Thoracic and lumbar dermatomes mostly effected
3. Chronic phase AKA Post-herpetic neuralgia
   - After 2-3 days of acute eruptive phase.
   - Persistent or recurring pain in the area of the prior acute eruption
   - Higher rates in elderly
   - Can last 30 days or more
4. Clinical features
   - Rash, most commonly on trunk along thoracic dermatome. Usually painful, itchy or tingly
   - Headache
   - Photophobia
   - Malaise
   - Erythematous base rash develops into clusters of vesicles. The vesicles form over 3-5 days then progressively dry and crust over
5. Complications
   - Post-herpetic neuralgia is the most common complication
   - It is pain that persists in the area that the rash once was for 90 days after rash onset
   - Risk of having PHN increases with age, with older adults more likely to have longer lasting, more severe pain.

• Other complications:
  Ophthalmic involvement - vision loss
  Bacterial superinfection of the lesions - due S. aureus
  Cranial and peripheral nerve palsies
  Visceral involvement - meningoencephalitis

4. Prevention
   - Vaccine = SHINGRIX
   - Recommended for adults 50 y/o and older
   - Shingrix provides strong protection against herpes zoster and PHN
   - Two doses are more than 90% effective, protection stays above 85% for at least the first 4 years post-vaccination
   - MMR vaccine will reduce likelihood of getting the VZV infection earlier in life
5. Transmission
   - Direct contact with vesicular fluid until they dry and crust over
   - You can spread VZV infection and cause varicella in people who have never had varicella or received the vaccine
6. Risk factors
   - Immunocompromised
   - Transplant patients
   - Auto-immune conditions - immune system issues
   - Female gender - tend to have more auto-immune conditions
   - European descent
   - Chronic disease states - lead to immunocompromised state
   - New-borns whose mothers have varicella from five days before to two days after delivery
   - Premature babies exposed to varicella or herpes zoster
7. Treatment
   - Antiviral medications: acyclovir, famciclovir, valacyclovir given within 72hrs of onset
   - Treatment for PHN: analgesics, gabapentin, pregabalin

Question 2

Pathophysiology of varicella / chicken pox

1. Microbiology
2. Mechanism
3. Complications
4. Symptoms
5. Treatment

Answer 2

1. Microbiology
   - Herpes virus
   - Ds DNA virus protected by a capsid protein coat which is enveloped in the lipid membrane. It fuses with cell membranes, releasing its capsid inside. Capsid binds nucleus, injecting its vDNA which is transcribed into RNA, this goes to the ribosome where it is translated into capsid proteins. Capsid and vDNA fuse together and go to the golgi complex in order to gain a lipid membrane and the newly formed virus leves the cell, leaving a dead cell behind!
2. Mechanism
   - An infected person sneezes or coughs, or it can be transmitted through oral or skin lesions from the infected
   - Virus comes into contact with respiratory mucosa or skin of a new person, it begins replicating in the epithelial cells.
   - It is picked up by immune cells and transported to a near lymph node, the virus now causes primary infection called varicella.

2 stages of varicella infection:

1. Primary viremia:
   - Virus infects a part of the immune system in the liver and spleen called the reticuloendothelial system (composed of phagocytic cells)
2. Secondary viremia:
   - 2 weeks after entering the body, the virus starts infecting immune cells themselves, specifically T cells
   - Infected T cells start expressing proteins that bind receptors on skin cells
   - On reaching the skin, they release viruses that infect keratinocytes and the infection spreads from skin-skin contact
   - Infected keratinocytes can fuse together to form Tzank cells which are multi-nucleated.
   - Uninfected cells secrete INFa and INFb which inhibits viral protein synthesis and protects those cells from infection, so you see tiny lesions on the skin separated by normal areas of skin

• In addition to infecting keratinocytes, the virus infects sensory neurons in the skin, and in those neurons it travels retrogradely to the dorsal root ganglion. The adaptive immune response will eliminate most viruses, but some in the ganglion remain for years. So the virus enters a latent stage which can be reactivated if the immune system weakens in the future, travel anterogradely to the skin and cause infection in the innervated dermatome = shingles

3. Complications
   - Secondary bacterial infection of the skin lesions
   - If the liver is infected = hepatitis can occur
   - If the lung is infected = pneumonia can occur
   - If the brain or its membrane is infected = encephalomeningitis
4. Symptoms
   - Begin 2 weeks after entering body
   - Fever
   - Headaches
   - Weakness
   - Skin lesions on scalp, face and trunk. First they are flat, red, itchy spots called macules. Over time they become elevated and develop into papules, and then into small fluid-filled vesicles which crust over and form scabs within 1-2 days
5. Treatment
   - Topical anti-puritic medications for itching
   - Analgesics and anti-inflammatory medications for fever
   - ASPIRIN SHOULD NOT BE USED as it can trigger Reye Syndrome - the liver is affected by both VZV and aspirin, leading to ammonia build up
   - Antiviral medication: acyclovir, famiclovir, valacyclovir
   - Varicella vaccine for prevention beforehand