25 - 165 - VARICELLA AND HERPES ZOSTER Flashcards
What virus causes varicella and herpes zoster?
varicella-zoster virus (VZV)
What virus causes herpes zoster
varicella-zoster virus (VZV).
Clinical manifestations of varicella
The rash of varicella usually begins on the face and scalp and spreads rapidly to the trunk, with relative sparing of the extremities. Lesions are scattered, rather than clustered, reflecting viremic spread to the skin, and they progress sequentially from rose-colored macules to papules, vesicles, pustules, and crusts. Lesions in all stages are usually present at the same time.
Compare the severity of varicella in children and adults
In immunocompetent children, systemic symptoms are usually mild and serious complications are rare.
In adults and immunocompromised persons of any age, varicella is more likely to be severe and can be associated with life-threatening complications.
Herpes zoster is most common in what population
Older adults and immunocompromized individuals
Most common debilitating complication of herpes zoster
Chronic neuropathic pain (Postherpetic neuralgia)
Varicella is common in what age population
Children
Infectious period of varicella
1-2 days before appearance of exanthem until 4 - 5 days therafter, until all vesicles have crusted
Mean incubation period of varicella infection
14 - 17 days
major route by which varicella is acquired and transmitted
respiratory tract by airborne droplets or aerosols, but infection also may be spread by direct contact
T/F: Varicella crusts are not infectious
True
occurs in individuals who develop varicella early in infancy in the presence of maternal antibody or following postexposure prophylaxis with varicella-zoster immune globulin or varicella vaccine
Modified varicella
occurs when vaccinated individuals are reinfected following exposure to wildtype VZV
Breakthrough varicella
T/F: Herpes zoster can be acquired through exposure to Varicella and herpes zoster
False
There is no convincing evidence that herpes zoster can be acquired by contact with persons with varicella or herpes zoster. 1 Rather, the incidence of herpes zoster is determined by factors that influence the host–virus relationship and the presence of immune responses necessary to prevent reactivation of latent VZV
major risk factor for herpes zoster
- Age
- Decreased VZV-specific cell-mediated immunity (Immunocompromising conditions associated with increased risk of herpes zoster include bone marrow and solid organ transplants, hematologic and solid tumor malignancies, and immune-mediated diseases (eg, systemic lupus erythematous, rheumatoid arthritis)
- Other factors reported to correlate with the risk of herpes zoster include female sex, 32 physical trauma in the affected dermatome, 46 IL-10 gene polymorphisms,47 family history of herpes zoster, 48-50and white race
characteristic feature of varicella lesions
A characteristic feature of varicella lesions is their rapid progression, over as little as 12 hours, from rosecolored macules to papules, and then to vesicles, pustules, and crusts
Describe the typical vesicle of varicella
The typical vesicle is 2 to 3 mm in diameter and elliptical, with its long axis parallel to the folds of the skin. The early vesicle is superficial and thin-walled, and surrounded by an irregular area of erythema, which gives the lesions the appearance of a “dewdrop on a rose petal.
distinctive feature of varicella
simultaneous presence, in any one area of the skin, of lesions in all stages of development
Prodrome in varicella is more common what age group
Older children and adults
In young children, prodromal symptoms are uncommon. In older children and adults, the rash is often preceded by 2 to 3 days of mild fever, chills, malaise, headache, anorexia, backache and, in some patients, sore throat and dry cough.
Most common complication of varicella in normal children
Secondary bacterial infection of skin lesions, usually by Staphylococci or Streptococci, which may produce impetigo, cellulitis, erysipelas, and, rarely, necrotizing fasciitis
Can varicella produce bullous lesions?
Yes.
Bullous lesions may develop when vesicles are superinfected by Staphylococci that produce exfoliative toxins.
characterize varicella in adults based on symptoms, rash and complications
In adults, fever and constitutional symptoms are more prominent and prolonged, the rash of varicella is more profuse, and complications are more frequent.
major severe complication of varicella in adults
Varicella Pneumonia
Varicella pneumonia is characterized by cough, dyspnea, tachypnea, high fever, pleuritic chest pain, cyanosis, and hemoptysis beginning 1 to 6 days after rash onset.
The severity of the symptoms usually exceeds the physical findings, but imaging typically reveals diffuse, peribronchial nodular densities throughout both lung fields with a tendency to concentrate in the perihilar regions and at the bases. The mortality in adults with frank varicella pneumonia is estimated to be between 10% and 30%, but it is less than 10% if immunocompromised patients are excluded and patients receive prompt antiviral therapy
The highest risk (2%) of occurrence of congenital varicella syndrome when maternal varicella occurs between what AOG?
13 - 20 weeks AOG.
varicella-associated Reye syndrome (acute encephalopathy with fatty degeneration of the liver) may occur in patients treated with what drug?
Salicylates
In herpes zoster, Pain and paresthesia in the involved dermatome often precede the eruption by how many days
1 to 3 days but occasional a week or longer
A few patients experience acute segmental neuralgia without ever developing a cutaneous eruption—a condition known as
zoster sine herpete
Most frequently affected nerve in herpes zoster
trigeminal nerve, particularly the ophthalmic division (10%-15%), and the trunk from T3 to L2 (>50%),
Differentiate herpes zoster and varicella based on virus spread
intraneural (axonal) spread of virus to the skin in herpes zoster, as opposed to viremic spread in varicella.
Describe the evolution of lesions of herpes zoster
Herpes zoster lesions begin as erythematous macules and papules in a dermatomal distribution.
Vesicles form within 12 to 24 hours and evolve into pustules by the third day (Fig. 165-3E).
These dry and crust in 7 to 10 days. The crusts generally persist for 2 to 3 weeks.
In normal individuals, new lesions continue to appear for 1 to 4 days (occasionally for as long as 7 days).
The rash is most severe and lasts longest in older people, and is least severe and of shortest duration in children.
What nerve is associated with hutchinson sign
Nasociliary branch of the ophthalmic division of the trigeminal nerve
Involvement of the nasociliary branch, which innervates the eye, as well as the tip and side of the nose, provides VZV with direct access to intraocular structures. Thus, when ophthalmic zoster involves the tip and the side of the nose (Hutchinson sign), careful attention must be given to the condition of the eye.
Involvement of the nasociliary branch is frequently accompanied by unilateral conjunctivitis and impaired corneal sensation, which can lead to corneal ulceration and sight-threatening bacterial infection. The eye is involved in 20% to 70% of patients with ophthalmic zoster.
Syndrome that results from involvement of facial and auditory nerves
Ramsay Hunt syndrome (facial palsy in combination with herpes zoster of the external ear, ear canal, or tympanic membrane, with or without tinnitus, vertigo, and deafness)
Cardinal symptom of herpes zoster
Pain
Complications of Herpes Zoster
most significant risk factor for PHN
Age
Most serious complications of herpes zoster are more common in immunocompromised persons. These include _____
necrosis of skin and scarring, and cutaneous dissemination
Patients with cutaneous dissemination may also have widespread, often fatal, visceral dissemination, particularly to the lungs, liver, and brain.
best diagnostic test for detection of VZV
Polymerase chain reaction (PCR) because of its very high sensitivity and specificity, ready availability, and relatively quick (1 day or less) turnaround time.
best specimen for PCR analysis of VZV
Vesicle fluid
but lesion scrapings, crusts, tissue biopsy, or cerebrospinal fluid are equally useful
Papular lesions of varicella evolve into intraepithelial vesicles within how many hours
12 - 24 hours
guanosine analogs that are selectively phosphorylated by VZV thymidine kinase; they are poor substrates for cellular thymidine kinase and thus are not activated in, and are not toxic for, uninfected cells
acyclovir and penciclovir
Prodrug of penciclovir
Famciclovir
thymidine analog, also activated by viral thymidine kinase, with very high activity against VZV
Brivudin
- second-line drug that is an analog of inorganic pyrophosphate, inhibits the replication of all known herpesviruses in vitro
- it does not require phosphorylation by thymidine kinase to be activated and is therefore active against nucleoside-resistant VZV mutants
Foscarnet
potent helicase-primase inhibitor that is active against acyclovir-resistant VZV and HSV
Amenamevir
True or false: Topical antiviral therapy is an option for treatment of varicella
False
Topical antiviral therapy has no role in the treatment of varicella. It has limited efficacy against herpes zoster and is not recommended
Preferred oral therapy for VZV infections
FAMCICLOVIR OR VALACYCLOVIR
Because of their superior pharmacokinetics and the reduced sensitivity of VZV compared to HSV to acyclovir and penciclovir, famciclovir, or valacyclovir are preferred over acyclovir for oral therapy of VZV infections.
Topical therapy for varicella
- Cool compresses,
- calamine lotion or Caladryl Clear (zinc acetate 0.1% + pramoxine 1%) locally,
- tepid baths with baking soda or colloidal oatmeal (3 cups per tub of water), and
- oral antihistamines may relieve itching.
- Creams and lotions containing glucocorticoids and occlusive ointments should not be used.
- Antipyretics may be needed, but salicylates must be avoided because of their association with Reye syndrome.
In what instances can you give antiviral medication for varicella?
- Some experts favor its use where cost is not a concern;
- when it can be begun in time to benefit the patient (within 24 hours of rash onset); and
- where there is a perceived need to speed resolution of the infection.
Recommendations for initiation of oral antiviral therapy for varicella
- preferably valacyclovir or famciclovir, for persons >12 years of age
- persons with chronic cutaneous or pulmonary disorders or other debilitating diseases,
- persons receiving long-term salicylate therapy, and
- persons receiving short, intermittent, or aerosolized courses of corticosteroids because these individuals are at increased risk for moderate-to-severe varicella
Why is famciclovir or valacyclovir preferred over acyclovir for treatment of herpes zoster?
because of their thrice-daily dosing schedule, their greater oral bioavailability, and the higher and more reliable blood levels of antiviral activity achieved.
This is important because of the reduced sensitivity to acyclovir of VZV compared with HSV, and the potential existence of barriers to the entry of antiviral agents into tissues that are sites of VZV replication.
In VZV infections, the utility of antiviral agents is unproven if treatment is initiated more than how many hours?
72 hours after rash onset
Antiviral Treatment of Varicella in the Normal and Immunocompromised Host
VARICELLA Treatment regimen for Adolescent (≥40 kg) or adult, especially with mild immunocompromise (eg, use of inhaled glucocorticoids)
- Valacyclovir 1 g orally every 8 h for 7 d or
- Famciclovir 500 mg orally every 8 h for 7 d or
- Acyclovir 800 mg orally 5 times a day for 7 days
Varicella treatment regimen for neonates
- Acyclovir 10mg/kg or 500 mg/m2 q8 x 10 days
Varicella treatment regimen for patients who develop pneumonia
Acyclovir 10 mg/kg IV q8 x 7-10d
Varicella Treatment regimen for Acyclovir resistant patients (advanced AIDS)
Foscarnet 40 mg/kg IV q8 until healed
Instances where administration of antiviral meds is prudent to initiate even after 72 hours of rash onset
it is prudent to initiate antiviral therapy even if more than 72 hours have elapsed after rash onset in patients with:
- herpes zoster involving cranial nerves (eg, ophthalmic zoster),
- in patients who continue to have new vesicle formation, or
- in patients who are of advanced age and may thus have a delay in development of effective immune responses
Herpes zoster regimen for patients < 50 y/o
- symptomatic treatment alone or
- famciclovir 500 mg orally q8 x 7d or
- valacyclovir 1g orally q8 x 7 days or
- acyclovir 800 mg orally 5x/day for 7 days
Herpes zoster treatment regimen for e ≥50 y, and patients of any age with cranial nerve involvement (eg, ophthalmic zoster)
- famciclovir 500 mg orally q8 x 7d or
- valacyclovir 1g orally q8 x 7 days or
- acyclovir 800 mg orally 5x/day for 7 days
Treatment regimen for patients with severe varicella or severe immunocompromise (varecella or zoster)
Acyclovir 10 mg/kg IV q8 x 7 - 10 days
Varicella and herpes zoster treatment regimen for Mild immunocompromise, including HIV-1 infection
- Valacyclovir 1 g orally every 8 h for 7-10 d or
- Famciclovir 500 mg orally every 8 h for 7-10 d or
- Acyclovir 800 mg orally 5 times a day for 7-10 days
What vaccine is effecacious in protecting susceptible children agaist varicella
Live attenuated Oka VZV varicella vaccines
2 doses given 4 to 8 weeks apart
In 2005, the FDA approved a combined measles, mumps, rubella, and varicella (MMRV) vaccine for routine immunization of children what age?
12 months to 12 years of age
Because of the frequency of breakthrough varicella, the CDC Advisory Committee on Immunization Practices (ACIP) now recommends hoe many doses of varicella vaccine
two 0.5-mL doses of varicella vaccine for healthy children aged ≥12 months, and for all adolescents and adults without evidence of immunity.
What is considered significant exposure to varicella and herpes zoster?
risk period of 1-2 days before rash until crusting is well under way
When exposure is recognized (risk period of 1-2 days before rash until crusting is well under way), preventive measures include _________
- varicella vaccine,
- high-titer varicella-zoster immune globulin (VARIZIG), and
- postexposure chemoprophylaxis with acyclovir
Active immunization with varicella vaccine is effective in preventing illness or modifying varicella severity in immunocompetent children if administered within how many days of exposure?
Within 3 days after exposure
VARIZIG, a purified human immune globulin prepared from plasma containing high levels of immunoglobulin G antibody to VZV, may be considered for patients who have been exposed to varicella and are at increased risk for severe disease and complications. It is dosed on a weight basis and should be given as soon as possible, preferably within how many hours of exposure?
Within 96 hours of exposure, although current recommendations permit an interval of up to 10 days
T/F: Protection afforded by VARIZIG is TRANSIENT, varicella vaccine induces LONG-LASTING VZV immunity and protection against subsequent exposures.
TRUE
Therefore, the ACIP recommends varicella vaccine for postexposure prophylaxis in unvaccinated susceptible immunocompetent persons
Clinically significant PHN is defined as pain and discomfort (eg, allodynia, severe pruritus) due to herpes zoster scored as ______ on a 0-10 scale that persists for more than _____ days after rash onset.
≥3
90
In 2006, the ACIP recommended routine administration of _____________ to adults 60 years of age and older for the prevention of herpes zoster and its complications, particularly PHN.
live attenuated Oka/Merck strain VZV zoster vaccine (ZVL; Zostavax® )
Varicella is infectious ______ days before to ______ days after.
a. 2-3 days before to 3-4 days after
b. 1-2 days before to 3-4 days after
c. 2-3 days before to 4-5 days after
d. 1-2 days before to 4-5 days after
C
A distinctive feature of varicella is ____________.
a. Dewdrop on a rose petal
b. Crusting with shallow pink depressions
c. Simultaneous presence, in any one area of the skin, of lesions in all stages of development
d. Localization and distribution of rash – unilateral, generally limited to the area of skin innervated by a single sensory ganglion
C
The following are risk factors for herpes zoster infection except _____ .
a. Increasing age
b. Physical trauma
c. Family history
d. Male gender
D
A distinctive feature of herpes zoster:
a. Dewdrop on a rose petal
b. Crusting with shallow pink depressions
c. Simultaneous presence, in any one area of the skin, of lesions in all stages of development
d. Localization and distribution of rash – unilateral, generally limited to the area of skin innervated by a single sensory ganglion
D
Hutchinson sign involves the ______.
a. Upper eyelid
b. Lower eyelid
c. Tip and side of the nose
d. Temporal side of face
C
_____________ is required for recovery from varicella.
a. T-cell mediated immunity
b. B-cell mediated immunity
c. IL-10 mediated
d. NK-cell mediated
A
Antiviral treatment of Herpes Zoster for immunocompetent host include the ff. Except _______ .
a. Symptomatic treatment
b. Famciclovir 500 mg q8 x 7 days
c. Valacyclovir 1g q8 x 7 days
d. Foscarnet 40mg/kg IV q8 until healed
D
what is the % likelihood of recurrent herpes zoster
1 - 6 %
- Recurrent herpes zoster is more common in patients who are immunocompromised, and they are more likely to have multidermatomal or bilateral disease
- Immunocompetent patients thought to be suffering multiple episodes of herpes zoster, especially when they occur in the same dermatome, are more likely to have recurrent zosteriform
