Herpes Zoster- Therapeutics Flashcards
Human Herpesviruses
8 herpesviruses routinely infect only humans:
– Herpes simplex virus types 1 and 2 (HHV-1, HHV-2)
– Varicella zoster virus (HHV-3)
– Epstein Barr virus (HHV-4)
– Cytomegalovirus (HHV-5)
– Human herpesvirus 6 (HHV-6, Roseola infantum)
– Human herpesvirus 7 (HHV-7, Roseola infantum)
– Human herpesvirus 8 (HHV-8, Kaposi’s sarcoma)
* Genetically and structurally similar (ds DNA viruses)
* Property of latency within specific host cells
– may reactivate
* Exhibit different clinical syndromes
EPV: mono, kissing virus
some of these viruses can actually lead to cancers
Roseola infantum: baby measles
ery common, fairly mild infant
infection, where babies can get very or young children, very high fever, followed by outbreak of a rash the next day, and it goes away very quickly.
Kaposi’s: It’s more common in more advanced stages of of infection, and again can lead to cancers. back in the day before, we had good treatment for HIV. Sometimes people would present with purplish lesions,
Etiology
- Varicella-zoster virus causes two clinical
presentations:
– Acute infection: “Chickenpox” or Varicella
– Reactivation: “Shingles” or Herpes zoster
The first time you are exposed to varicella it presents as chicken pox
it was in 2002. It became part of the regular Childhood Vaccine
Series,
Risk factors increase when you’re either a mutual compromised, or the severity certainly tends to be greater
Kids tend to be quite unwell for a few days, maybe have fever and and cranky. And then over time those those blisters heal up
So quite often, you know everybody in the household, if they didn’t have it, would would get it,
we know serology wise. More than 90% or 95% of
people in a certain age group have had a chicken pox.
slide 7 diagram
Once you heal up from that primary infection, the virus hangs out and and tides in a latent stage in some of the nerve root ganglia in the spinal cord area.
Not totally inactive but it’s really not causing any symptoms, even if there is a little bit of replication going on.
And then, once the virus reactivates and travels back down that nerve
ending. That’s when you get reactivation and and symptoms of zoster.
this threshold line is the critical level of
immunity. So again, our t-cells and our immune cells keep zoster in check
When immunity starts to decline we can get symptomatic reactivation
this shows there may be some minor reactivations or a little bit of viral replication happening in the neurons. But once we get that
drop in immunity, it can be sufficient to to the point of causing actually over disease.
Clinical Presentation – Herpes Zoster
- rash often proceeded by localized pain or itching (48-
72 hours) - begins as erythematous papules which evolve into
vesicles – coalesce into large confluent blisters with
hemorrhagic component - lesions continue to form over 3 to 5 days and healing
occurs over ~ 2 weeks - permanent skin changes such as scarring and
discoloration may occur - most commonly affected dermatomes: T1 – L2
- hallmark characteristic: unilateral; does NOT cross
the body’s midline - ~20% have systemic symptoms (fever, headache,
malaise, fatigue)
it can happen in other parts of the body, including in the the autic or in the ophthalmic region. Trigemical area
It tends to be unilateral, so that means that the rash
tends to be on one side of the body only, and it doesn’t cross over the Median.
Rarely it’s. It’s not super common, but it is possible to have those localized symptoms, and in some people not actually progress to a rash, harder to diagnose the pains and tingling
Diagnosis
- Can be diagnosed clinically
- Confirmatory laboratory tests:
- may be necessary to differentiate from HSV (depending
on location of rash) or in patients with typical pain but no
rash
Laboratory Tests
- Polymerase chain reaction (PCR)
– If available, rapid and sensitive in properly collected
specimens. - Immunohistochemistry
– Cells scraped from base of lesion and stained with
fluorescein conjugated monoclonal Abs to detect viral
glycoprotein. More sensitive than culture. - Viral culture from vesicular fluid
– Less sensitive than immunofluorescence (virus lability)
would be actually take a swab
of the lesion, and that would be sent off to the lab, and Pcr is the most common way of detecting the virus most most quick and most sensitive.
There are other ways you can do cell scrapings and do immuno chemistry or you can also do a viral culture if you have some of the
virus, especially from that vesiclar fluid, but it is less sensitive, and certainly there’s there’s risk of virus lability and not getting a good sample
Differential Assessment
- Herpes simplex virus
- Contact dermatitis
- Impetigo
- Cellulitis
- Candidiasis
- Dermatitis herpetiformis (skin manifestation
of Celiac disease) - Drug eruptions
Burden of disease
- ~130 000 new cases of herpes zoster (HZ) per year in
Canada
– incidence appears to be increasing - Lifetime risk of HZ is ~30%; recurrence rate ~6%
- Most common complication: post-herpetic neuralgia
Risk Factors for Herpes Zoster
- Major risk factors:
– Age > 50 years
– HIV (up to 15 times higher)
– Other immunosuppression (e.g., corticosteroids,
chemotherapy etc)
, some studies have shown, females have a higher risk, and some studies have shown that white ethnicity has a higher risk as compared to.
for example, black ethnicity. So those are not always consistent correlations.
HZ incidence and trends in
Australia, Japan, and the US
Impact of aging on burden of HZ
Seeing increase in herpes zoster worldwide and certainly in developed countries
Early theory:
we’re having less children with the introduction of the varicella vaccines
getting chicken pox, and that means those grandparents or other people in society are not exposed to the virus, and then it’s not causing that reactivation, or that stimulation of their immune cells
But this trend started before 2002
People are living longer, aging population and and older adults
we have all these fancy drugs to treat conditions. We’re we’re in general seeing more people immuno compromised. more people that are living longer with HIV, for example, and many other conditions. So it’s probably multi factorial,
there’s the various modeling looking at the impact of aging, but without intervention, As you might imagine, our population is aging. We’re going to see more impact of Foster if if there’s not interventions.
Neuropathic pain
- Acute herpetic neuralgia
₋ pain preceding or accompanying rash that persists up to
30 days from onset - Subacute herpetic neuralgia
₋ pain that persists beyond rash healing but resolves within
3 - 4 months - Post-herpetic neuralgia
₋ pain persisting > 3 - 4 months from initial onset of rash
It does vary from study to study but this is general defn
Subactue: pain associated w rahs and skin breakage, combination of pain
PHN is primarily persisting nerve pain
Post-herpetic neuralgia (PHN)
– ~15% of people with HZ with develop PHN
* incidence of PHN increases with age
– 3 types of pain described:
* constant pain without a stimulus (e.g., burning or throbbing)
* Intermittent pain without stimulus (e.g., stabbing, shooting)
* Evoked pain (allodynia and/or hyperalgesia)
– can persist for several months to years –
significantly impacts quality of life
– Major risk factors:
* Older age, severe acute pain, greater rash severity,
immunosuppressive conditions
Evoked pain: you know you might not notice the pain. But if you put on your clothing and it touched that area, your skin, or those nerve endings are super sensitive.
Goal of Therapy - HZ
∙ stop viral replication
∙ accelerating healing of lesions
∙ prevent post-herpetic neuralgia (decrease
duration)
∙ manage acute zoster associated pain
Counselling Tips -
nonpharmacologic
- Keep rash clean and dry to reduce risk of bacterial
superinfection - Prevent transmission of the virus to another person:
– keep the fluid-filled blisters and rash covered
– wash hands often
– do not touch or scratch the rash - Avoid use of topical antibiotics and dressing with adhesives as
these may cause irritation and delay rash healing - Use sterile wet (hydrocolloid) dressings to relieve discomfort
in some patients (e.g., Tegaderm (3M), Bandaid) - Wear loose-fitting clothing for comfort
unlike chicken box, which is very much an airborne, very, very highly contagious infection, it is possible to transmit the virus for someone who has an inacitve zoster infection
- It has to be someone who doesn’t have immunity to chicken pox or varicella
- you don’t want to risk it with someone that you know immunocompromised for sure, especially if you don’t know their status but if they already had chicken pox, touching that virus isn’t going to be activate chicken pox in in me
- But dont take the chance if you dont know hx
Can you transmit zoster (shingles) to someone else?
- NO, if someone had zoster reactivationYou would be passing the virus which would would end up causing chicken pox.
- You would not at risk of getting it faster
Mechanism of action of antiherpes agents
antivirals they are phosphorylated initially by viral specific thymidine kinase and then the host cell kinases further phosphorylate them
Then competitively inhibit viral DNA polymerase
There is an activation phase and viral yhmidine kinase plays a role
