165: Varicella and Herpes Zoster Flashcards
What is the primary cause of varicella and herpes zoster?
Both varicella (chickenpox) and herpes zoster (shingles) are caused by the varicella-zoster virus (VZV), a member of the herpesvirus family.
What are the main characteristics of varicella?
Varicella is characterized by:
- Exogenous primary infection of a susceptible individual.
- Highly contagious, most often occurring in childhood.
- A rash that begins on the trunk and spreads to the extremities, with lesions that can be papules, vesicles, and crusts.
How does herpes zoster develop?
Herpes zoster develops from the reactivation of endogenous virus that persists in latent form within ganglionic neurons following an earlier attack of varicella. It is localized, vesicular, and dermatomal, often characterized by unilateral radicular pain.
What is the epidemiological pattern of varicella in temperate climates without vaccination?
In temperate climates without varicella vaccination, varicella is:
- Endemic: regularly recurring seasonal prevalence in winter and spring.
- Associated with periodic epidemics that reflect the accumulation of susceptible persons.
What impact has the two-dose varicella vaccine had on incidence and hospitalizations?
The two-dose varicella vaccine has led to:
- A decline in incidence and outpatient visits by over 85%.
- A reduction in hospitalizations by ≥93%.
- The greatest decline in cases among children aged 1 to 4 years, contributing to herd immunity and a decrease in mortality.
What is the infectious period for varicella?
Varicella is infectious for:
- 1 to 2 days before the exanthem appears.
- 4 or 5 days thereafter, until the last crop of vesicles has crusted.
What are the routes of transmission for varicella?
The major routes of transmission for varicella include:
- Respiratory and airborne droplets or aerosols.
- Direct contact with the lesions.
What is the significance of lifelong immunity after varicella infection?
Lifelong immunity occurs as subsequent exposure to VZV boosts humoral and cell-mediated immune responses, which can lead to subclinical reinfection without significant symptoms.
What are the primary differences between varicella and herpes zoster?
Varicella is caused by exogenous primary infection of a susceptible individual and is highly contagious, most often occurring in childhood. In contrast, herpes zoster results from the reactivation of endogenous virus that persists in latent form within ganglionic neurons after an earlier varicella infection. Herpes zoster is characterized by localized, vesicular, dermatomal lesions and unilateral radicular pain.
How does the epidemiology of varicella differ in temperate climates compared to tropical regions?
In temperate climates, varicella is endemic with regularly recurring seasonal prevalence in winter and spring, leading to periodic epidemics due to the accumulation of susceptible persons. In contrast, tropical regions show a higher mean age of varicella and increased susceptibility among adults.
What are the implications of lifelong immunity following varicella infection or vaccination?
Lifelong immunity following varicella infection or vaccination means that subsequent exposure to VZV boosts humoral and cell-mediated immune responses, which can lead to subclinical reinfection.
What are the infectious periods for varicella in immunocompromised individuals?
Varicella is infectious for 1 to 2 days before the exanthem appears and for 4 or 5 days thereafter until the last crop of vesicles has crusted. In immunocompromised individuals, the infectious period may be longer due to successive crops of lesions.
What are the common clinical features of varicella in young children?
Young children typically exhibit uncommon prodromal symptoms. The rash usually begins on the face and scalp, spreading rapidly to the trunk, with relative sparing of the extremities.
What is the typical progression of varicella lesions?
The progression of varicella lesions occurs rapidly, over 12 hours, transitioning from rose-colored macules to papules, then to vesicles, pustules, and crusts.
What are the complications associated with varicella?
The most common complication of varicella is secondary bacterial infection, often caused by Staphylococci or Streptococci. In adults, varicella pneumonia is a major severe complication.
What distinguishes breakthrough varicella disease in vaccinated individuals?
Breakthrough varicella disease occurs in 10% to 15% of vaccinees immunized with a single dose of varicella vaccine after exposure to active VZV. It is usually atypical, predominantly maculopapular, with fewer lesions and fewer vesicles.
What is the relationship between fever and the severity of the rash in varicella?
Fever persists as long as new lesions continue to appear, and its height is generally proportional to the severity of the rash.
What is the distinctive feature of varicella lesions?
The distinctive feature is the simultaneous presence of lesions in all stages of development in any one area of the skin.
What is breakthrough varicella?
This condition is called breakthrough varicella. It is usually milder, with fewer lesions and fewer vesicles, and is less contagious than natural varicella.
What is the likely pathogen in secondary bacterial infections associated with varicella?
The likely pathogen is Staphylococcus producing exfoliative toxins, leading to bullous lesions.
What is the typical progression of the rash in varicella?
The rash progresses from rose-colored macules to papules, vesicles, pustules, and crusts over 12 hours.
What does a fever of 40.5°C and a prolonged rash in varicella indicate?
This could indicate a secondary bacterial infection or another complication.
What causes hypopigmented macules after varicella?
The hypopigmented macules are likely due to the healing process of the rash. Scarring is rare unless the lesions are traumatized.
What happens to vesicles in the mouth and pharynx during varicella?
The vesicles rupture rapidly, leaving only shallow ulcers. The vesicular stage is typically missed because of this rapid rupture.
Why is household exposure to varicella more severe than school exposure?
Household exposure involves more intense and prolonged contact, leading to a higher virus inoculum.
Where does the rash of varicella typically begin?
The rash typically begins on the face and scalp and spreads rapidly to the trunk, with relative sparing of the extremities.
What is the relationship between fever and new lesions in varicella?
Fever persists as long as new lesions continue to appear. The height of the fever is generally proportional to the severity of the rash.
Where do vesicles appear earlier in varicella?
Examples include areas of diaper rash or sunburn, where vesicles often appear earlier and in larger numbers.
What does the description ‘dewdrops on a rose petal’ refer to in varicella?
This description refers to the early vesicles, which are superficial, thin-walled, and surrounded by an irregular area of erythema.
What are the common clinical features of varicella in young children compared to older children and adults?
In young children, varicella often presents with uncommon prodromal symptoms. In contrast, older children and adults typically experience a prodrome of mild fever, chills, malaise, headache, anorexia, backache, sore throat, and dry cough.
How does the rash of varicella typically progress?
The rash of varicella usually begins on the face and scalp, spreading rapidly to the trunk with relative sparing of the extremities. It progresses from rose-colored macules to papules to vesicles, pustules, and crusts.
What distinguishes breakthrough varicella from natural varicella?
Breakthrough varicella is typically atypical, predominantly maculopapular, and presents with fewer lesions and fewer vesicles compared to unmodified varicella.
What are the most common complications associated with varicella in adults?
The most common complications of varicella include secondary bacterial infections and varicella pneumonia, which is the major severe complication in adults.
What factors influence the severity of varicella in household exposure?
Cases of varicella resulting from household exposure tend to be more severe due to more intense and prolonged exposure at home.
What are the potential maternal and fetal complications associated with varicella during pregnancy?
- Maternal complications: Disseminated infection and varicella pneumonia can lead to maternal death.
- Fetal complications: The fetus may die due to premature labor or maternal death caused by severe varicella pneumonia.
What are the common complications of varicella in immunocompromised individuals?
- High morbidity and mortality due to continued virus replication and dissemination.
- Common prodrome: Severe abdominal and back pain.
- Complications: Pneumonia, hepatitis, encephalitis, and hemorrhagic conditions.
What are the neurological complications associated with varicella?
- Acute cerebellar ataxia: More common than other neurologic complications (1 in 4000), with an excellent prognosis.
- Encephalitis: Much less common (1 in 33,000), frequently causes death or permanent neurologic sequelae.
What is the epidemiology of herpes zoster in relation to varicella?
Herpes zoster occurs sporadically, without seasonal prevalence, and is independent of the prevalence of varicella.
What complications should be considered in an immunocompromised patient with varicella?
The patient may have disseminated varicella with complications such as pneumonia, hepatitis, encephalitis, or hemorrhagic manifestations.
What is the seasonal prevalence of herpes zoster?
Herpes zoster occurs sporadically and does not have seasonal prevalence, independent of the prevalence of varicella.
What characterizes herpes zoster?
It is characterized by unilateral dermatomal pain and rash resulting from reactivation and multiplication of latent VZV that persisted within neurons following varicella.
What complications should be considered in an immunocompromised patient with prolonged high fever and rash?
The patient may have disseminated varicella with complications such as pneumonia, hepatitis, encephalitis, or hemorrhagic manifestations.
What is the risk to the fetus if a pregnant woman contracts varicella during the first trimester?
The fetus is at risk of congenital varicella syndrome, with an overall risk of 1% if maternal varicella occurs during the first 20 weeks of gestation.
What is the highest risk period for congenital varicella syndrome?
The highest risk is 2% between 13-20 weeks of gestation.
What is the likely diagnosis for a patient with severe abdominal pain and vesicular rash?
The likely diagnosis is varicella pneumonia.
What is the mortality rate of varicella pneumonia if untreated?
The mortality rate in adults is 10%-30%, but it is less than 10% if immunocompromised patients are excluded and prompt antiviral therapy is administered.
What is the prognosis for encephalitis due to varicella?
Encephalitis due to varicella frequently causes death or permanent neurologic sequelae.
How can VZV involvement in the CNS be confirmed?
VZV involvement in the CNS can be confirmed by detecting VZV antigens, antibodies, or DNA in the cerebrospinal fluid (CSF).
What are the maternal complications associated with varicella during pregnancy?
Maternal complications include disseminated infection and varicella pneumonia, which can lead to maternal death.
What are the fetal complications associated with varicella during pregnancy?
Fetal complications include premature labor or death due to severe maternal varicella pneumonia.
How does varicella affect immunocompromised individuals compared to healthy individuals?
Immunocompromised individuals experience high morbidity and mortality, continued virus replication, more extensive rash, and increased risk of severe complications. Healthy individuals typically have milder symptoms.
What are the common CNS complications associated with varicella?
CNS complications include Reye Syndrome, acute cerebellar ataxia, and encephalitis.
What is Reye Syndrome?
Reye Syndrome is rare and associated with fatty degeneration of the liver, particularly in children treated with salicylates.
What is the incidence of acute cerebellar ataxia in varicella cases?
Acute cerebellar ataxia is more common than other neurologic complications, with an excellent prognosis (1 in 4000).
What is the incidence of encephalitis in varicella cases?
Encephalitis is much less common (1 in 33,000) and often leads to death or permanent neurologic sequelae.
What are the major risk factors for herpes zoster?
Major risk factors include age, decreased VZV-specific cell-mediated immunity, female sex, physical trauma, IL-10 gene polymorphisms, family history, and white race.
How does herpes zoster present clinically?
Prodrome includes pain and paresthesia in the involved dermatome, followed by a unilateral rash that begins as dermatomal erythematous macules and papules.
What is the significance of the rash distribution in herpes zoster?
The rash is generally unilateral and limited to the area of skin innervated by a single sensory ganglion.
What are the differences in herpes zoster presentation between older adults and children?
Older adults experience a more severe rash that lasts longer, while children have a less severe rash of shorter duration.
What are the potential complications associated with ophthalmic zoster?
Ophthalmic zoster may involve the eye in 20% to 70% of cases and can lead to serious complications.
What does it indicate if a herpes zoster patient has vesicles that continue to appear for more than seven days?
This indicates disseminated herpes zoster, which may transmit via aerosols.
What is Hutchinson’s sign?
Hutchinson’s sign indicates that ophthalmic zoster involves the tip and side of the nose, which can lead to corneal ulceration.
What are the key symptoms of Ramsay Hunt Syndrome?
Ramsay Hunt Syndrome is characterized by facial palsy, herpes zoster of the external ear, tinnitus, vertigo, and deafness.
What is postherpetic neuralgia (PHN)?
PHN is defined as pain persisting after rash healing, with a prevalence ranging from 5% to 30%.
What is allodynia in relation to herpes zoster?
Allodynia is pain elicited by normally non-painful stimuli, present in 90% of patients with postherpetic neuralgia.
What are the potential visceral complications associated with herpes zoster?
Visceral complications can include esophagitis, pleuritis, and peritonitis.
What are the potential complications of herpes zoster in immunocompromised patients?
Complications may include necrosis of skin, scarring, cutaneous dissemination, and widespread visceral dissemination.
How does VZV establish latency after primary infection?
VZV becomes latent in neurons.
What complications may arise from herpes zoster in immunocompromised patients?
Complications may include:
1. Necrosis of skin
2. Scarring
3. Cutaneous dissemination
4. Widespread visceral dissemination, particularly to the lungs, liver, and brain.
How does VZV establish latency after primary infection?
VZV becomes latent in sensory neurons after primary infection, which is characteristic of α-herpesviruses.
What role do T cells play in the pathogenesis of varicella?
T cells play a crucial role by:
1. Carrying the virus to the reticuloendothelial system, which is the major site of virus replication.
2. Disseminating the virus via blood and lymphatics during the primary viremia.
What factors contribute to the development of skin lesions in varicella?
Skin lesions develop due to:
1. Cyclic viremia that occurs during the infection.
2. Immunopathology, which contributes to rash development.
3. VZV-specific T cell-mediated immune responses that terminate viremia after about 3 to 5 days.
What is the significance of VZV genome structure in relation to other herpesviruses?
The VZV genome contains at least 71 genes, most of which have functional and DNA-sequence homology to genes of other herpesviruses, indicating evolutionary relationships and potential similarities in replication mechanisms.
What is the likely cause of multiple recurrences of vesicular lesions in a patient with HIV?
The likely cause is herpes zoster due to reactivation of VZV. Complications may include cutaneous and visceral dissemination, chronic verrucous or hyperkeratotic lesions, and acyclovir-resistant VZV.
What is the likely cause of contralateral hemiplegia weeks after ophthalmic zoster?
The likely cause is segmental granulomatous angiitis, leading to a contralateral stroke. This condition is associated with reactivation of latent VZV in cranial and dorsal root ganglia.
What visceral complications might occur in a patient with herpes zoster experiencing severe pain in the thoracic dermatome?
Visceral complications include gastric mucosal lesions, hemicystitis, esophagitis, pleuritis, and peritonitis, corresponding to the affected dermatome.
What does a rash with lesions in all stages of development in varicella indicate?
This indicates cyclic viremia, where skin lesions appear in successive crops due to the virus’s replication and spread.
What are the clinical manifestations of secondary viremia in varicella, and how is it terminated?
Secondary viremia leads to systemic symptoms and skin lesions. It is terminated after about 3 to 5 days by VZV-specific T cell–mediated immune responses.
What is the likely explanation for visceral lesions without skin involvement in herpes zoster?
The likely explanation is latent VZV in enteric neurons, leading to episodes of visceral herpes zoster in the absence of skin lesions.
How does VZV enter the body and lead to systemic infection?
VZV enters through the mucosa of the upper respiratory tract and oropharynx, infecting tonsillar T cells. These T cells disseminate the virus via blood and lymphatics, leading to primary viremia and subsequent systemic symptoms and skin lesions.
What is the role of T cell-mediated immune responses in the progression of varicella?
T cell-mediated immune responses are crucial for:
1. Recovery from varicella
2. Termination of viremia after about 3 to 5 days, which helps control the infection and contributes to the development of skin lesions.
What is the significance of VZV’s ability to establish latency in sensory neurons?
The ability of VZV to establish latency in sensory neurons is significant because it allows the virus to persist for life, leading to potential reactivation as herpes zoster later in life, especially under conditions of stress or immunocompromise.
What are the characteristics of VZV compared to other herpesviruses?
VZV is a member of the herpesvirus family and shares the following characteristics:
- Morphologically indistinguishable from other herpesviruses.
- Establishes latent infections that persist for life.
- Classified as an α-herpesvirus due to its latency in sensory neurons after primary infection.
What is the role of VZV in the pathogenesis of herpes zoster?
During varicella, VZV passes from skin lesions into sensory nerves, establishing latent infections in neurons. The density of latent VZV is greatest in ganglia innervating areas of skin with the most varicella lesions.
How does VZV reactivate and what are the consequences?
Latent VZV can reactivate sporadically, producing infectious virus, often associated with immunosuppression. When VZV-specific T cell-mediated immunity falls below a critical level, the reactivated virus can no longer be contained, leading to neuronal necrosis and intense inflammation, often resulting in severe neuropathic pain.
What are the clinical implications of VZV spreading antidromically down the sensory nerve?
VZV spreads antidromically down the sensory nerve, leading to the release of the virus from sensory nerve endings in the skin, which results in the characteristic cluster of zoster vesicles. This spread can also lead to complications such as local leptomeningitis, CSF pleocytosis, and segmental myelitis.
What factors contribute to the development of post-herpetic neuralgia (PHN)?
Injury to the peripheral nerve and neurons in the ganglion triggers afferent pain signals. Inflammation in the skin also triggers nociceptive pain signals. Damage to neurons in the spinal cord and ganglion, as well as to the peripheral nerve, is important in the pathogenesis of PHN, leading to persistent neuropathic pain.
What changes occur in the dorsal horn of the spinal cord in patients with persistent pain from PHN?
In patients with persistent pain from PHN, there is dorsal horn atrophy and loss of cell, axon, and myelin with fibrosis in sensory ganglia. This damage may lead to spontaneous activity and hypersensitivity of primary afferent nerves to peripheral stimuli and sympathetic stimulation.
What is the diagnosis for a 60-year-old patient with unilateral radicular pain and a vesicular rash localized to a single dermatome?
The diagnosis is herpes zoster. The underlying pathogenesis involves reactivation of latent varicella-zoster virus (VZV) in sensory ganglia, leading to neuronal necrosis, inflammation, and antidromic spread of the virus down sensory nerves.
What is the pathogenesis of segmental myelitis in a patient with herpes zoster?
Segmental myelitis occurs due to the spread of ganglionic infection proximally along the posterior nerve root to the meninges and spinal cord, causing local leptomeningitis and CSF pleocytosis.
What is the underlying mechanism of persistent neuropathic pain in a patient with herpes zoster?
The underlying mechanism involves injury to peripheral nerves and neurons in the ganglion, triggering afferent pain signals. Structural changes include dorsal horn atrophy, cell loss, and fibrosis in sensory ganglia.
What is the pathogenesis of transverse myelitis in a patient with herpes zoster?
Transverse myelitis occurs due to the extension of VZV infection within the CNS, leading to inflammation and neuronal damage in the spinal cord.
What is the role of T cell–mediated immunity in severe neuropathic pain from herpes zoster?
T cell–mediated immunity is critical for containing VZV reactivation. A decline in VZV-specific T cell immunity allows the virus to multiply and spread, leading to neuronal necrosis and neuropathic pain.
What is the role of VZV in establishing latent infections in neurons during varicella?
During varicella, VZV passes from skin lesions into sensory nerves, establishing latent infections in neurons that persist for life. The density of latent VZV is greatest in ganglia innervating areas of skin with the highest density of varicella lesions.
How does the reactivation of VZV relate to immunosuppression?
Latent VZV in ganglia can reactivate sporadically, producing infectious virus, and this reactivation is often associated with immunosuppression. If VZV-specific T cell-mediated immunity falls below a critical level, the reactivated virus can no longer be contained, leading to neuronal necrosis and intense inflammation.
What are the clinical implications of VZV spreading antidromically down the sensory nerve?
When VZV spreads antidromically down the sensory nerve, it is released from the sensory nerve endings in the skin, leading to the characteristic cluster of zoster vesicles. This spread can also result in local leptomeningitis, CSF pleocytosis, and segmental myelitis.
What factors contribute to the development of post-herpetic neuralgia (PHN)?
The development of post-herpetic neuralgia (PHN) is influenced by injury to the peripheral nerve and neurons in the ganglion, which trigger afferent pain signals. Inflammation in the skin also triggers nociceptive pain signals, and damage to neurons in the spinal cord and ganglion is important in the pathogenesis of PHN.
How does excessive nociceptor activity contribute to the symptoms of PHN?
Excessive nociceptor activity and ectopic impulse generation may sensitize CNS neurons, augmenting and prolonging central responses to both innocuous and noxious stimuli, leading to symptoms such as allodynia in patients with post-herpetic neuralgia.
What are the key clinical features that distinguish varicella from other generalized rashes?
- Rapid evolution of lesions from macules to papules, to vesicles, to pustules and crusts.
- Simultaneous presence of lesions at all stages of development.
- History of exposure within the preceding 2 to 3 weeks.
What laboratory findings are indicative of varicella and herpes zoster infections?
- Multinucleated giant cells and acidophilic intranuclear inclusion bodies in epithelial cells.
- Acanthosis and ballooning degeneration of epithelial cells.
- PCR is the best diagnostic test for VZV, offering high sensitivity and specificity.
How can disseminated herpes zoster be mistaken for varicella?
Disseminated herpes zoster may be mistaken for varicella when there is widespread dissemination of VZV from a small, painless area of herpes zoster from the affected sensory ganglion, especially in severely immunocompromised patients.
What is the significance of PCR in the diagnosis of VZV?
PCR is the best diagnostic test for detection of VZV due to its:
1. Very high sensitivity and specificity.
2. Ready availability.
3. Quick turnaround time (1 day or less).
4. Ability to distinguish VZV from HSV and wildtype VZV from Oka vaccine strains.
What are the clinical implications of distinguishing herpes zoster from herpes simplex?
- In the absence of profound immune deficiency, a history of multiple recurrences in the same dermatome distinguishes zosteriform herpes simplex from herpes zoster.
- The character and dermatomal location of the rash, along with dermatomal pain and localized sensory abnormalities, usually make the diagnosis of herpes zoster obvious.
A 65-year-old patient presents with a cluster of vesicles near the mouth and dermatomal pain. How would you differentiate between herpes zoster and recurrent HSV infection?
Herpes simplex is often impossible to distinguish from herpes zoster on clinical grounds. However, a history of multiple recurrences in the same dermatome without profound immune deficiency suggests zosteriform herpes simplex rather than herpes zoster.
A patient with suspected varicella has lesions at all stages of development. What laboratory test would you use to confirm the diagnosis?
PCR is the best diagnostic test for detecting VZV due to its high sensitivity, specificity, and quick turnaround time. Vesicle fluid is the best specimen.
A severely immunocompromised patient presents with widespread vesicular lesions and marked toxicity. What is the likely diagnosis?
Disseminated herpes zoster, which is rare and limited to severely immunocompromised patients, often involves marked toxicity and visceral involvement.
A patient with suspected varicella has a history of exposure 2 weeks ago. What clinical features would help confirm the diagnosis?
Varicella is usually diagnosed by the appearance and evolution of the rash, characterized by rapid evolution of lesions from macules to papules, vesicles, pustules, and crusts, with simultaneous presence of lesions at all stages of development.
A patient with suspected herpes zoster has vesicular lesions. What bedside test can be used to confirm the diagnosis?
Tzanck smears prepared from material scraped from the base of vesicular lesions and stained with H&E, Giemsa, or similar stains can demonstrate multinucleated giant cells and eosinophilic intranuclear inclusion bodies.
What laboratory findings are indicative of varicella and herpes zoster infections?
- Multinucleated giant cells and acidophilic intranuclear inclusion bodies in epithelial cells.
- Acanthosis and ballooning degeneration of cells.
- Intraepithelial vesicles formation within 12 to 24 hours post-infection.
How can disseminated herpes zoster be mistaken for varicella?
Disseminated herpes zoster may be mistaken for varicella when there is widespread dissemination of VZV from a small, painless area of herpes zoster, especially in severely immunocompromised patients, where the absence of an obvious dermatomal eruption can lead to confusion.
What is the best diagnostic test for detecting VZV and why?
-
PCR is the best diagnostic test for VZV due to its:
- Very high sensitivity and specificity.
- Quick turnaround time (1 day or less).
- Ability to distinguish VZV from HSV and wildtype VZV from Oka vaccine strains.
What are the clinical implications of the presence of multinucleated giant cells in vesicular lesions?
The presence of multinucleated giant cells in vesicular lesions indicates a VZV infection and helps distinguish it from other vesicular eruptions, as these cells form by the fusion of infected epithelial cells with adjacent infected and uninfected cells.
What factors can complicate the diagnosis of herpes zoster?
- The prodromal pain of herpes zoster can be confused with other localized pain causes.
- The character and dermatomal location of the rash, along with dermatomal pain and localized sensory abnormalities, are crucial for diagnosis but can be misinterpreted.
What is the significance of selecting new vesicles containing clear fluid for aspiration in VZV diagnosis?
Selecting new vesicles containing clear fluid for aspiration is crucial because the probability of isolating VZV diminishes rapidly as lesions become pustular, making early aspiration more effective for diagnosis.
How does the clinical presentation of herpes zoster differ from herpes simplex?
Herpes zoster typically presents with a dermatomal rash and associated localized pain, while herpes simplex may present with clusters of vesicles that are often impossible to distinguish from herpes zoster on clinical grounds, especially in the absence of profound immune deficiency.
What role do serologic tests play in the diagnosis of varicella and herpes zoster?
Serologic tests allow for the retrospective diagnosis of varicella and herpes zoster, particularly when acute and convalescent sera are available for comparison, although they are rarely done.
What are the limitations of virus isolation techniques in diagnosing VZV?
Virus isolation techniques are less sensitive and may take a week or more. They yield infectious VZV for further analysis but are only positive in 30% to 60% of cultures from proven cases, making them less reliable than PCR.
What are the clinical features of herpes zoster that aid in its diagnosis?
- Dermatomal rash with vesicles.
- Localized pain in the affected dermatome.
- History of prior varicella infection or vaccination may also support the diagnosis.
What is the importance of Tzanck smears in the diagnosis of VZV?
Tzanck smears are important as they can demonstrate multinucleated giant cells and intranuclear inclusion bodies, which are indicative of VZV infection and help differentiate it from other vesicular diseases.
What are the differential diagnoses to consider when evaluating a varicelliform eruption?
Differential diagnoses for varicelliform eruption include:
- Disseminated herpes simplex
- Contact dermatitis
- Burns
- Other viral exanthems (e.g., Coxsackievirus, echovirus)
What is the clinical significance of dermatomal pain in herpes zoster?
Dermatomal pain is a key feature of herpes zoster that helps differentiate it from other conditions. It typically precedes the rash and is localized to the area innervated by the affected sensory ganglion, aiding in diagnosis.
What are the characteristics of lesions in varicella that can aid in diagnosis?
Lesions in varicella typically show:
- Rapid evolution from macules to papules to vesicles.
- Simultaneous presence of lesions at different stages of development.
- Lesions often appear in crops, leading to a characteristic appearance.
What is the role of immunofluorescent staining in the diagnosis of VZV?
Immunofluorescent staining of cellular material from fresh vesicles or prevesicular lesions can detect VZV significantly more often and faster than virus culture, making it a valuable diagnostic tool.
How does the presence of eosinophilic intranuclear inclusion bodies assist in diagnosing VZV?
The presence of eosinophilic intranuclear inclusion bodies in epithelial cells is a hallmark of VZV infection, helping to distinguish it from other viral infections and confirming the diagnosis when observed in lesions.
What are the implications of a history of multiple recurrences in the same dermatome for herpes zoster diagnosis?
A history of multiple recurrences in the same dermatome is indicative of herpes zoster and helps differentiate it from zosteriform herpes simplex, which typically does not recur in the same dermatome in immunocompetent individuals.
What factors influence the sensitivity of virus isolation techniques for VZV?
Factors influencing the sensitivity of virus isolation techniques include:
- Timing of specimen collection (new vesicles are more likely to yield positive results).
- The type of specimen collected (vesicle fluid is preferred).
- The viability of the virus, as VZV is extremely labile.
What is the significance of the character and dermatomal location of the rash in herpes zoster?
The character and dermatomal location of the rash in herpes zoster are significant as they provide critical diagnostic clues, indicating the involvement of a specific sensory ganglion and helping to differentiate it from other conditions.
What are the advantages of enzyme immunoassays in diagnosing VZV?
Enzyme immunoassays offer a rapid and sensitive method for antigen detection, providing a faster turnaround time than traditional virus culture, although they lack the sensitivity and specificity of PCR.
What is the clinical relevance of marked toxicity and visceral involvement in disseminated herpes zoster?
Marked toxicity and visceral involvement in disseminated herpes zoster indicate a severe form of the disease, often seen in immunocompromised patients, and can complicate the clinical picture, making diagnosis and management more challenging.
How does the timing of lesion aspiration affect the diagnosis of VZV?
The timing of lesion aspiration is critical; aspirating new vesicles containing clear fluid is more likely to yield VZV, while aspiration of pustular lesions significantly reduces the likelihood of isolating the virus, impacting diagnostic accuracy.
What are the common clinical presentations of varicella in immunocompetent children?
In immunocompetent children, varicella typically presents with:
- Fever and malaise.
- Itchy rash that progresses from macules to vesicles to crusts.
- Lesions appear in crops, often with a characteristic distribution on the trunk and face.
What is the importance of differentiating between varicella and herpes zoster in clinical practice?
Differentiating between varicella and herpes zoster is crucial for appropriate management, as varicella is primarily a childhood illness with vaccination options, while herpes zoster can lead to complications like postherpetic neuralgia, especially in older adults and immunocompromised patients.
What are the nucleoside analogs effective in treating VZV infections?
The nucleoside analogs effective in treating VZV infections include:
- Acyclovir
- Famciclovir
- Valacyclovir
- Brivudin
Additionally, the pyrophosphate analog Foscarnet is also used.
What is the role of topical antiviral therapy in the treatment of varicella?
Topical antiviral therapy has no role in the treatment of varicella and is not recommended due to its limited efficacy against herpes zoster.
What are the preferred antiviral agents for oral therapy of VZV infections?
The preferred antiviral agents for oral therapy of VZV infections are famciclovir or valacyclovir due to their superior pharmacokinetics and reduced sensitivity of VZV compared to HSV.
What is the recommended treatment for immunocompetent children with varicella?
For immunocompetent children with varicella, routine antiviral treatment is not recommended. However, if treatment is initiated within 24 hours of rash onset, oral acyclovir (20 mg/kg 4 times per day for 5 days) can modestly reduce the maximum number of lesions, the time to cessation of new lesion formation, and the duration of rash, fever, and constitutional symptoms.
What should be avoided when treating varicella in children due to the risk of Reye Syndrome?
When treating varicella in children, salicylates must be avoided due to their association with Reye Syndrome.
A patient with varicella is treated with oral acyclovir. What is the optimal timing for initiating this treatment?
Oral acyclovir should be initiated within 24 hours of rash onset to modestly reduce the maximum number of lesions, time to cessation of new lesion formation, and duration of rash, fever, and symptoms.
A patient with herpes zoster is started on valacyclovir. Why is this drug preferred over acyclovir?
Valacyclovir is preferred due to its greater oral bioavailability, higher and more reliable blood levels of antiviral activity, and less frequent dosing schedule.
What are the key antiviral agents used in the treatment of VZV infections and their mechanisms of action?
The key antiviral agents include:
Antiviral Agent | Mechanism of Action |
|——————|——————–|
| Acyclovir | Guanosine analog, selectively phosphorylated by VZV thymidine kinase, inhibits viral DNA synthesis by inhibiting viral DNA polymerase. |
| Valacyclovir | Prodrug of acyclovir, better absorbed, converted enzymatically to acyclovir after absorption. |
| Famciclovir | Prodrug of penciclovir, similar mechanism to acyclovir, converted enzymatically to penciclovir after absorption. |
| Brivudin | Thymidine analog activated by viral thymidine kinase, very high activity against VZV. |
| Foscarnet | Inhibits replication of all known herpesviruses, does not require phosphorylation by thymidine kinase, active against nucleoside-resistant VZV mutants. |
| Cidofovir | Directly inhibits viral DNA polymerase, considered a third-line drug due to toxicity. |
| Amenamevir | Helicase-primase inhibitor active against acyclovir-resistant VZV and HSV.
What is the recommended treatment protocol for immunocompetent children with varicella?
The recommended treatment protocol includes:
-
Acyclovir Treatment:
- Administer oral acyclovir (20 mg/kg) 4 times per day for 5 days.
- Initiate treatment within 24 hours of rash onset for effectiveness.
-
Symptomatic Relief:
- Use cool compresses, calamine lotion, or antihistamines to relieve itching.
- Tepid baths with baking soda or colloidal oatmeal can also help.
-
Avoidance of Certain Medications:
- Avoid glucocorticoids and occlusive ointments.
- Avoid salicylates due to the risk of Reye Syndrome.
-
Management of Secondary Infections:
- Treat minor bacterial infections with warm soaks.
- Use systemic antimicrobial.
What is the recommended timing for initiating antiviral therapy for varicella?
Antiviral therapy should be initiated within 24 hours of rash onset for effectiveness.
What are the strategies for symptomatic relief in varicella?
Use cool compresses, calamine lotion, or antihistamines to relieve itching. Tepid baths with baking soda or colloidal oatmeal can also help.
What medications should be avoided in varicella treatment?
Avoid glucocorticoids, occlusive ointments, and salicylates due to the risk of Reye Syndrome.
How should secondary infections in varicella be managed?
Treat minor bacterial infections with warm soaks and use systemic antimicrobial therapy for bacterial cellulitis effective against Staphylococcus aureus and GAS.
What are the clinical implications of acyclovir-resistant VZV in immunosuppressed patients?
Acyclovir resistance is often due to mutations in the viral thymidine kinase gene, leading to cross-resistance to other antivirals. Resistant strains usually respond to foscarnet and are sensitive to amenamevir.
What are the limitations of topical antiviral therapy in varicella treatment?
Topical antiviral agents have no role in the treatment of varicella and are not recommended. They show limited efficacy against herpes zoster.
When is foscarnet considered in VZV infection treatment?
Foscarnet is used as a second-line treatment for acyclovir-resistant VZV infections and inhibits viral DNA polymerases without requiring phosphorylation.
What are the recommended strategies for managing itching in children with varicella?
Apply cool compresses or calamine lotion, use Caladryl Clear locally, administer tepid baths with baking soda or colloidal oatmeal, and consider oral antihistamines.
What is the role of systemic therapy in varicella management?
Systemic therapy is the standard treatment for varicella, especially in cases with complications or in immunocompromised patients.
What are the risks associated with salicylates in children with varicella?
Salicylates are associated with Reye Syndrome, a serious condition that can cause liver and brain damage. They should be avoided in children with varicella.
What is the significance of ELISA testing in varicella vaccination?
ELISA testing has limitations in sensitivity and may fail to detect antibodies in immune individuals, which is crucial for patient management.
What are the recommended antiviral treatments for varicella in immunocompetent adolescents and adults?
Acyclovir 800 mg 5 times a day for 7 days, valacyclovir 1000 mg every 8 hours, or famciclovir 500 mg every 8 hours.
What factors influence the decision to use antiviral therapy for varicella in pregnant women?
Antiviral therapy is recommended in the third trimester due to the risk of varicella pneumonia and infection spread to the newborn.
What is the standard treatment for varicella in immunocompromised patients?
IV Acyclovir is the standard of care, especially if treatment is initiated within 72 hours of rash onset.
What are the major goals of antiviral therapy for herpes zoster?
Limit the extent, duration, and severity of pain and rash in the primary dermatome.
What topical treatments are recommended during the acute phase of herpes zoster?
Application of cool compresses, calamine lotion, or baking soda may lessen local symptoms. Occlusive ointments should not be used.
What treatment options are recommended for a pregnant woman in her third trimester with varicella?
Oral antiviral therapy is recommended, and IV acyclovir is considered for extensive disease.
What is the recommended treatment for a patient with varicella pneumonia?
Early treatment with IV acyclovir (10 mg/kg every 8 hours) is recommended.
What is the recommended dosage for valacyclovir in herpes zoster treatment?
The recommended dosage for valacyclovir is 1000 mg orally every 8 hours.
What factors influence the decision to use antiviral treatment for varicella in patients?
Factors include cost, timing of treatment initiation, and the need for resolution of infection.
What are the considerations for treating pregnant women with varicella?
Oral acyclovir is not typically prescribed in uncomplicated cases, and IV acyclovir is considered for extensive disease.
What is the standard of care for varicella in patients with substantial immunodeficiency?
IV Acyclovir should be initiated within 72 hours of rash onset.
What are the major goals of antiviral therapy for herpes zoster?
Limit the extent of the rash, reduce the duration of symptoms, and alleviate pain severity.
What are the recommended topical treatments during the acute phase of herpes zoster?
Recommended treatments include cool compresses, calamine lotion, and baking soda.
What is the recommended treatment for bacterial super-infection of herpes zoster lesions?
Bacterial super-infection should be treated with warm soaks and systemic antibiotic therapy if cellulitis is suspected.
What are the implications of early treatment with acyclovir for varicella in adolescents and adults?
Early treatment reduces the maximum number of lesions and decreases the time to cessation of new lesion formation.
What is the significance of initiating treatment with IV acyclovir within 36 hours of hospitalization for varicella pneumonia?
It reduces fever and tachypnea and improves oxygenation.
What are the recommendations for antiviral therapy in patients with chronic pulmonary disorders and varicella?
Valacyclovir or famciclovir is recommended for those over 12 years of age.
What are the recommended antivirals for treating herpes zoster in immunocompetent adolescents and adults?
Famciclovir and valacyclovir are preferred due to their efficacy and dosing schedule.
When should antiviral treatment be initiated for herpes zoster, even if more than 72 hours have elapsed?
Initiate treatment if patients have herpes zoster involving cranial nerves, continue to have new vesicle formation, or are of advanced age.
What is the role of glucocorticoids in the treatment of herpes zoster?
Glucocorticoids are used to reduce acute pain but do not change the incidence of chronic pain.
What analgesic strategies are recommended for managing acute pain in herpes zoster?
Prescribing analgesics to limit pain severity to less than 3 on a 0-to-10 scale and considering regional anesthetic nerve blocks.
What treatments have demonstrated efficacy for pain relief in postherpetic neuralgia (PHN)?
Gabapentin, pregabalin, tricyclic antidepressants, opioid analgesics, tramadol, 5% lidocaine patch, and high-concentration capsaicin patch.
Under what circumstances is antiviral treatment justified for a patient with herpes zoster started 4 days after rash onset?
Treatment is justified if the patient has herpes zoster involving cranial nerves, continues to have new vesicle formation, or is of advanced age.
What is the recommended management for a patient with herpes zoster involving the ophthalmic branch of the trigeminal nerve?
The patient should be examined by an ophthalmologist and treated with oral antivirals.
What is the goal of analgesic therapy for a patient with herpes zoster experiencing severe acute pain?
The goal is to limit the severity of pain to less than 3 on a 0-to-10 scale.
What factors influence the severity and duration of postherpetic neuralgia (PHN)?
The severity and duration of PHN are influenced by age, with older patients experiencing more severe symptoms.
What is the expected outcome of a single epidural injection of corticosteroids and local anesthetics for herpes zoster?
The injection may reduce acute pain but does not prevent the development of postherpetic neuralgia.
What factors influence the severity and duration of postherpetic neuralgia (PHN)?
The severity and duration of PHN are a function of age, with older patients experiencing more severe and prolonged symptoms.
What is the expected outcome of a single epidural injection of corticosteroids and local anesthetics for a patient with herpes zoster?
The injection may reduce acute pain but does not prevent the subsequent development of postherpetic neuralgia (PHN).
What pharmacological options are available for acute pain relief in herpes zoster?
Options include oxycodone, which has shown significantly greater pain relief than placebo, and gabapentin, which has also demonstrated efficacy in acute pain relief.
What is the major goal of antiviral therapy for herpes zoster?
The major goals are to limit the extent, duration, and severity of pain and rash in the primary dermatome and to prevent disease elsewhere.
What are the advantages of famciclovir for treating herpes zoster?
Famciclovir is preferred due to its thrice-daily dosing schedule, greater oral bioavailability, and higher and more reliable blood levels of antiviral activity.
What is the rationale for using glucocorticoids during the acute phase of herpes zoster?
The rationale is that inflammation within the sensory ganglion and contiguous neural structures may contribute to postherpetic neuralgia (PHN). Glucocorticoids can reduce acute pain but do not change the incidence of chronic pain.
What is the expected outcome of IV acyclovir treatment for herpes zoster?
IV acyclovir halts disease progression, accelerates the rate of virus clearance from vesicles, and reduces the incidence of subsequent visceral and progressive cutaneous dissemination.
What are the recommended antivirals for treating herpes zoster in adults within 72 hours of rash onset?
The recommended antivirals are famciclovir and valacyclovir due to their:
- Thrice-daily dosing schedule
- Greater oral bioavailability
- Higher and more reliable blood levels of antiviral activity achieved
What is the significance of initiating antiviral treatment within 72 hours of rash onset for herpes zoster?
Initiating antiviral treatment within 72 hours of rash onset can:
- Reduce the time to rash healing
- Decrease the duration and severity of acute pain in older adults
- Potentially reduce the duration of chronic pain, although this is not FDA approved for prevention of PHN
In what scenarios should treatment be considered even after 72 hours have elapsed since rash onset in herpes zoster patients?
Treatment should be considered for:
1. Patients with herpes zoster involving cranial nerves (e.g., ophthalmic zoster)
2. Patients who continue to have new vesicle formation
3. Patients of advanced age who may have delayed immune responses
What are the therapeutic challenges associated with ophthalmic zoster?
The therapeutic challenges include:
- Risk of ocular complications
- Need for examination by an ophthalmologist when there is eye involvement or when the nasociliary nerve is involved
- Oral acyclovir is effective in preventing ocular complications of ophthalmic zoster
What is the role of glucocorticoids in the treatment of herpes zoster and PHN?
Glucocorticoids are used during the acute phase to:
- Address inflammation within the sensory ganglion that contributes to PHN
- Reduce acute pain, although they do not change the incidence of chronic pain
- In older patients, routine use is not recommended due to adverse effects outweighing benefits
What analgesic strategies are recommended for managing acute pain in herpes zoster?
Analgesic strategies include:
- Using standardized pain scales to assess severity
- Prescribing analgesics to limit pain severity to less than 3 on a 0-10 scale
- Considering regional or local anesthetic nerve blocks if pain control remains inadequate
What findings support the use of gabapentin in the acute phase of herpes zoster?
RCTs have shown that:
- A single dose of 900 mg of gabapentin during the acute phase provides greater pain relief than placebo
- Gabapentin is effective in managing moderate-to-severe pain in herpes zoster patients
What is the expected course of postherpetic neuralgia (PHN) in most patients?
PHN typically resolves spontaneously in most patients, although this often requires several months. The severity and duration of PHN are influenced by the patient’s age.
What are the efficacy results of various drugs for pain relief in PHN according to RCTs?
RCTs have demonstrated efficacy for pain relief in PHN for the following drugs:
- Gabapentin
- Pregabalin
- Tricyclic anti-depressants
- Opioid analgesics
- Tramadol
- 5% lidocaine patch
- High-concentration capsaicin patch
What is the impact of acute pain severity on the risk of developing postherpetic neuralgia (PHN)?
Greater severity of acute pain is a risk factor for developing PHN. Acute pain may contribute to central sensitization and the genesis of chronic pain, making aggressive pain control essential.
What are the recommended doses of varicella vaccine for healthy children aged 12 months and older?
The CDC Advisory Committee on Immunization Practices (ACIP) recommends 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 the significance of breakthrough varicella in vaccinated individuals?
Breakthrough varicella occurs in vaccinated individuals at a rate of 1% to 3% per year, with cumulative rates of approximately 15%. This indicates that while the vaccine is effective, it does not provide complete immunity, and breakthrough cases can be clinically similar to varicella in unvaccinated children.
What preventive measures are recommended when exposure to varicella is recognized?
Preventive measures include:
1. Varicella vaccine
2. High-titer varicella-zoster immune globulin (VARIZIG)
3. Postexposure chemoprophylaxis with acyclovir
These measures are effective in preventing illness or modifying varicella severity if administered within 3 days after exposure.
How does the incidence of herpes zoster (HZ) compare between vaccinated and unvaccinated children?
Among children under 18 years of age in a managed care plan, the incidence of HZ was 79% lower among recipients of varicella vaccine compared to unvaccinated children. Half of the cases of HZ in vaccinated children were caused by Oka vaccine VZV, while all cases in unvaccinated children were caused by wildtype VZV.
What factors should guide the choice of pharmacotherapy for postherpetic neuralgia (PHN)?
The choice of pharmacotherapy for PHN should be guided by:
- Adverse event profiles
- Potential for drug interactions
- Patient comorbidities
- Treatment preferences
This ensures that the selected treatment is appropriate for the individual patient’s needs.
What pharmacological options are evidence-based for pain relief in postherpetic neuralgia (PHN)?
Evidence-based options for PHN pain relief include gabapentin, pregabalin, tricyclic antidepressants, opioid analgesics, tramadol, 5% lidocaine patch, and high-concentration capsaicin patch.
What is the likely cause of herpes zoster in a child vaccinated with the varicella vaccine?
HZ in vaccinated children can be caused by reactivation of the vaccine virus (Oka VZV) or wildtype VZV that established latent infection during unrecognized varicella acquired prior to or after vaccination.
What is the clinical significance of breakthrough varicella cases in vaccinated individuals?
Breakthrough varicella cases occur at a rate of 1% to 3% per year in vaccinated individuals, with a cumulative rate of approximately 15%. These cases can be clinically similar to varicella in unvaccinated children and are often as contagious as cases in unvaccinated persons.
What is the recommended action for susceptible healthcare providers regarding varicella vaccination?
All susceptible healthcare providers should be identified and vaccinated to protect against exposure or transmission of varicella, especially those who may infect immunocompromised persons or susceptible pregnant women.
What are the implications of the decline in vaccine effectiveness over time?
Several studies have indicated that vaccine effectiveness declines over 10 years, leading to an increased annual rate of breakthrough varicella cases as time since vaccination increases.
What is the recommended approach for postexposure treatment in susceptible children?
Chemoprophylaxis with acyclovir has been studied in susceptible children following household exposure to varicella, showing that those who had either no varicella or experienced fewer and less severe cases of varicella.
What is the recommended vaccination strategy for children who previously received only one dose of varicella vaccine?
A second-dose catch-up varicella vaccination is recommended for children, adolescents, and adults who previously received only one dose of the vaccine.
What is the clinical significance of the reactivation of wildtype VZV in vaccinated individuals?
HZ occurs in vaccinees at a lower rate than in those who had wild-type VZV infection, with many cases caused by reactivation of wildtype VZV that established latent infection during unrecognized varicella acquired prior to or after vaccination.
What are the recommendations for testing hospital personnel regarding varicella immunity?
Hospital and long-term care facility personnel without a clear history of varicella or herpes zoster should be tested for antibody to VZV prior to employment, and susceptible personnel should be vaccinated against varicella.
What is the recommended timing for administering varicella vaccine after exposure?
Active immunization with varicella vaccine is effective in preventing illness or modifying varicella severity if administered within 3 days after exposure.
What is the importance of identifying susceptible adults in relation to varicella vaccination?
Identifying susceptible adults is crucial as they may be at increased risk for exposure or transmission, and vaccination can help prevent outbreaks, especially among vulnerable populations.
What are the preferred antiviral agents for postexposure prophylaxis (PEP) in immunocompromised patients?
Oral famciclovir or valacyclovir are preferable to oral acyclovir for postexposure prophylaxis (PEP) in immunocompromised patients.
What are the potential adverse effects of the varicella vaccine?
The varicella vaccine is remarkably safe and well tolerated, with minor rashes and injection site reactions being common; serious adverse events have been rare.
What is the recommended vaccination strategy for international travelers regarding varicella?
International travelers should be vaccinated against varicella if they are susceptible, as they may be at increased risk for exposure during travel.
What is the significance of the immune response to varicella vaccine compared to wildtype VZV infection?
The immunity to varicella induced by the varicella vaccine is not as solid as that induced by wildtype VZV infection, and the duration of vaccine-induced immunity is not yet known.
What is the recommended action for nonpregnant women of childbearing age regarding varicella vaccination?
Nonpregnant women of childbearing age should be vaccinated against varicella to prevent potential complications during pregnancy and protect against transmission.
What is the role of postexposure chemoprophylaxis with acyclovir?
Postexposure chemoprophylaxis with acyclovir is recommended for individuals who have been exposed to varicella to reduce the severity of the disease if administered promptly.
What are the implications of the findings regarding the incidence of herpes zoster in vaccinated children?
The findings indicate that while HZ occurs in vaccinated children, it is at a lower rate than in unvaccinated children, suggesting the vaccine provides some level of protection against HZ.
What is the recommended vaccination strategy for adolescents and adults without evidence of immunity to varicella?
Adolescents and adults without evidence of immunity to varicella should receive two doses of the varicella vaccine to ensure adequate protection.
What is the clinical significance of the timing of varicella vaccination in relation to exposure?
Timing is critical; immunity to varicella may not be achieved if vaccination occurs too late after exposure, especially with early postexposure treatment.
What are the recommendations for managing exposure to varicella in immunocompromised patients?
Exposure of susceptible immunocompromised patients to VZV warrants a reduction in the dosage of glucocorticoids and other immunosuppressive drugs, along with administration of VARIZIG.
What is the importance of vaccination in preventing varicella transmission in community settings?
Vaccination is crucial in preventing varicella transmission in community settings, particularly among vulnerable populations such as immunocompromised individuals and pregnant women.
What is the recommended approach for managing breakthrough varicella cases in vaccinated individuals?
Management of breakthrough varicella cases should focus on symptomatic relief and monitoring for complications, as these cases can be clinically similar to varicella in unvaccinated individuals.
What are the implications of the findings regarding the annual rate of breakthrough varicella?
The findings suggest that the annual rate of breakthrough varicella increases with time since vaccination, indicating the need for ongoing monitoring and potential booster strategies.
What is the significance of the recommendation for second-dose catch-up varicella vaccination?
The recommendation for second-dose catch-up varicella vaccination is significant as it aims to enhance immunity and reduce the risk of breakthrough cases in those who previously received only one dose.
What is the role of high-titer varicella-zoster immune globulin (VARIZIG) in postexposure prophylaxis?
High-titer varicella-zoster immune globulin (VARIZIG) is used in postexposure prophylaxis for individuals at high risk of severe disease, providing transient protection against varicella.
What are the recommendations for vaccination in children living in households with children?
Children living in households with children should be vaccinated against varicella to prevent transmission and protect vulnerable family members.
What is the clinical significance of the recommendation for varicella vaccination in nonpregnant women of childbearing age?
Vaccination in nonpregnant women of childbearing age is clinically significant as it helps prevent varicella during pregnancy, which can lead to serious complications for both mother and child.
What is the importance of monitoring for varicella immunity in healthcare settings?
Monitoring for varicella immunity in healthcare settings is important to prevent outbreaks and protect both healthcare workers and patients, particularly those who are immunocompromised.
Why should households with children be vaccinated against varicella?
To prevent transmission and protect vulnerable family members.
What is the clinical significance of the recommendation for varicella vaccination in nonpregnant women of childbearing age?
It helps prevent varicella during pregnancy, which can lead to serious complications for both mother and child.
What is the importance of monitoring for varicella immunity in healthcare settings?
To prevent outbreaks and protect both healthcare workers and patients, particularly those who are immunocompromised.
What is the primary goal of preventing herpes zoster (HZ)?
To prevent the reactivation of latent VZV that results in clinical disease.
What are the recommendations for the administration of the live attenuated Oka VZV zoster vaccine (ZVL)?
Routine administration of ZVL to adults 60 years of age and older for the prevention of herpes zoster and its complications, particularly postherpetic neuralgia (PHN).
What is the efficacy of the live attenuated Oka VZV zoster vaccine (ZVL) in reducing the burden of illness due to herpes zoster?
ZVL reduced the burden of illness due to HZ by 61.1%, reduced the incidence of clinically significant PHN by 66.5%, and reduced the incidence of herpes zoster by 51.3%.
What is the recommended age for receiving the adjuvanted glycoprotein E subunit zoster vaccine (RZV)?
RZV is recommended for immunocompetent adults aged 50 years and older.
How does the immune response induced by RZV compare to that induced by ZVL?
The VZV/gE-specific CD4+ T-cell and humoral responses induced by RZV were much more robust and long-lasting than those induced by ZVL.
What precautions should be taken for ZVL recipients with susceptible pregnant or immunocompromised contacts?
They need not take any special precautions following vaccination, except in the rare situation that a vesicular rash develops, in which case standard contact precautions are adequate.
How effective is the live attenuated zoster vaccine (ZVL) in reducing the burden of illness due to herpes zoster?
ZVL reduces the burden of illness due to herpes zoster by 61.1%, the incidence of clinically significant PHN by 66.5%, and the incidence of herpes zoster by 51.3%.
What precautions should be taken for healthcare personnel who are not vaccinated against VZV following exposure?
Appropriate leave from work should be instituted for any susceptible personnel who are not vaccinated following VZV exposure.
What is the clinical rationale for administering the live attenuated Oka VZV zoster vaccine (ZVL) to older adults?
To boost VZV-specific cellular immunity in older adults to prevent or attenuate herpes zoster, addressing the substantial morbidity of HZ in this population.
What is the recommended time frame for initiating antiviral therapy after the onset of herpes zoster rash for maximum benefit?
Antiviral therapy should be initiated within 72 hours of rash onset for maximum benefit.
What is the FDA licensure age for the live attenuated zoster vaccine (ZVL)?
The FDA licensure for ZVL is at age 50 years or older.
What is the ACIP recommendation regarding the administration of ZVL?
The ACIP recommends ZVL for individuals aged 60 years and older.
What are the recommendations for immunocompetent older adults in contact with immunocompromised patients regarding ZVL?
Immunocompetent older adults in contact with immunocompromised patients should receive ZVL to reduce the risk of developing HZ and transmitting wild-type VZV to their susceptible contacts.
What is the significance of the AS01B adjuvant system in the new adjuvanted glycoprotein E subunit zoster vaccine (RZV)?
The AS01B adjuvant system enhances the immune response to the recombinant VZV glycoprotein E (gE), leading to stronger and longer-lasting T-cell and humoral responses.
What is the recommended schedule for administering the RZV vaccine?
RZV is administered intramuscularly on a 2-dose schedule with a 2- to 6-month interval between doses.
What is the primary advantage of RZV over ZVL for the prevention of herpes zoster?
RZV is preferred over ZVL for initial immunization due to its stronger and longer-lasting immune response.
What is the risk associated with the RZV vaccine in immunocompromised individuals?
RZV is safe and immunogenic in persons with various immunosuppressive conditions, including HIV infection and hematopoietic cell transplant recipients, and it is incapable of replication, posing no risk of vaccine virus replication causing disease.
What is the impact of ZVL on the quality of life for individuals with herpes zoster?
ZVL decreased the adverse impact of HZ on the capacity to perform activities of daily living and health-related quality of life.
What should be done if an immunocompromised contact develops significant illness caused by the vaccine virus?
They can be treated with antiviral agents.
What is the effect of ZVL on the duration and severity of pain in vaccinees who develop herpes zoster?
ZVL reduced the duration and severity of pain in vaccinees who developed herpes zoster.
What is the significance of the Shingles Prevention Study regarding ZVL?
The study demonstrated that ZVL reduced the burden of illness due to HZ by 61.1% and reduced the incidence of herpes zoster by 51.3%.
What is the recommended action for older adults who have a current episode of herpes zoster regarding vaccination?
ZVL is not indicated to treat acute herpes zoster or PHN.
What is the relationship between age and the effectiveness of ZVL?
ZVL effectiveness in persons vaccinated when they were ≥70 years of age was similar to vaccine effectiveness in younger vaccinees.
What are the contact precautions recommended for immunocompromised patients with localized herpes zoster?
Contact precautions are recommended to prevent transmission.
What is the clinical significance of the findings from the Phase III trials of RZV?
The trials assessed safety and efficacy, concluding that the vaccine significantly reduced the risk of HZ in adults aged 50 years and older.
What is the importance of the interval between the onset of herpes zoster and vaccination with ZVL?
An interval of 2 to 3 years after the onset of a well-documented case of herpes zoster is reasonable before vaccination with ZVL.
What is the role of the glycoprotein E (gE) in the RZV vaccine?
gE is essential for virus replication and cell-to-cell spread, making it a target for VZV-specific CD4+ T-cell responses.
What is the significance of the findings regarding the immune response induced by RZV compared to ZVL?
The immune responses induced by RZV were much more robust and long-lasting than those induced by ZVL.
What is the recommended vaccination strategy for older adults who have already received ZVL?
The ACIP has recommended RZV for prevention of HZ in immunocompetent adults ≥50 years of age.
What is the impact of long-term suppressive acyclovir treatment in immunocompromised patients at risk for herpes zoster?
It is only practical in patients at proven risk of developing herpes zoster within a defined time period.
What are the implications of the ZVL safety profile in immunocompromised patients?
ZVL is contraindicated in immunocompromised persons but has been administered to a number of these patients with very rare adverse events.
What is the significance of the findings regarding the incidence of HZ after vaccination with ZVL?
ZVL efficacy for HZ burden of illness and incidence of HZ declined over time but persisted through 5 to 7 years postvaccination.
What is the recommended action for older adults who are VZV seronegative?
They should be vaccinated against varicella according to current recommendations.
What is the role of the Shingles Prevention Study in understanding the effectiveness of ZVL?
It provided evidence that ZVL significantly reduced the burden of illness due to HZ and the incidence of clinically significant PHN.
What is the clinical definition of clinically significant postherpetic neuralgia (PHN)?
It is defined as pain and discomfort due to herpes zoster scored as ≥3 on a 0-10 scale that persists for more than 90 days after rash onset.
What is the efficacy decline of RZV for incidence of HZ from year 1 to year 4 postvaccination?
The overall RZV efficacy for incidence of HZ declines from 97.6% in year 1 to 87.9% in year 4 postvaccination.
What is the recommendation for additional immunization for persons vaccinated with RZV at 50 years of age?
They may require additional immunization to ensure an adequate level of protection later in life.
How does RZV compare to ZVL in terms of immunogenicity for persons previously immunized with ZVL?
RZV appears to be substantially more immunogenic in persons previously immunized with ZVL.
What is the significance of the AS01B adjuvant system in RZV?
The powerful AS01B adjuvant system might induce or aggravate autoimmune diseases.
Can RZV be coadministered with other vaccines?
Yes, RZV can be safely coadministered with other vaccines.
What are the benefits of RZV over ZVL for a 55-year-old patient previously vaccinated with ZVL?
RZV is substantially more immunogenic and induces more robust and long-lasting immune responses.
How does the recombinant zoster vaccine (RZV) work?
RZV contains recombinant VZV glycoprotein E (gE) and the AS01B adjuvant system, which induces strong humoral and CD4+ T-cell responses.
What is the recommended dosing schedule for RZV?
RZV is administered intramuscularly on a 2-dose schedule with a 2- to 6-month interval.
How does RZV differ from ZVL?
RZV contains only the gE subunit of VZV and is incapable of replication, whereas ZVL is a live attenuated vaccine.
What are the potential side effects of the AS01B adjuvant system?
It might induce or aggravate autoimmune diseases.
How effective is RZV in preventing herpes zoster?
Pooled data indicate that RZV efficacy for herpes zoster incidence declines from 97.6% in year 1 to 87.9% in year 4 post-vaccination.
What is the role of the glycoprotein E (gE) component in RZV?
gE is essential for virus replication and cell-to-cell spread, and it is a major target for VZV-specific CD4+ T-cell responses.
What is the role of the AS01B adjuvant system in RZV?
It contains monophosphoryl lipid A and QS21, which stimulate strong humoral and CD4+ T-cell responses to gE.
What is the recommended age for vaccination with RZV?
The ACIP recommends RZV for immunocompetent adults aged 50 years and older.
Can RZV be given to patients previously vaccinated with ZVL?
Yes, RZV can be given to patients previously vaccinated with ZVL.
What is the expected duration of protection for RZV?
RZV efficacy for herpes zoster incidence declines from 97.6% in year 1 to 87.9% in year 4 post-vaccination.
What is the significance of RZV being coadministered with other vaccines for individuals previously vaccinated with ZVL?
RZV can be safely coadministered with other vaccines, enhancing immunization strategies for individuals who have previously received ZVL and those with a history of herpes zoster (HZ).
How does RZV’s immunogenicity compare to ZVL in previously immunized individuals?
RZV appears to be substantially more immunogenic in persons previously immunized with ZVL than a booster dose of ZVL.
What trend is observed in the efficacy of RZV for the incidence of HZ over time?
Pooled data from ZOE-50 and ZOE-70 indicate that the overall RZV efficacy for incidence of HZ declines from 97.6% in year 1 to 87.9% in year 4 postvaccination.
What recommendation does the ACIP make regarding additional immunization for individuals vaccinated with RZV at age 50?
If the rate of decline in efficacy continues, persons vaccinated with RZV at 50 years of age may require additional immunization to ensure an adequate level of protection later in life, as recommended by the ACIP.
What potential risk is associated with the AS01B adjuvant system in RZV?
The powerful AS01B adjuvant system might induce or aggravate autoimmune diseases.
What is the best diagnostic test to detect VZV?
The best diagnostic test to detect VZV is PCR (Polymerase Chain Reaction) testing.
Is routine antiviral treatment recommended for immunocompetent children with varicella?
False. Routine antiviral treatment for varicella is not recommended for immunocompetent children unless they are at high risk for complications.
What is the recommended treatment regimen for normal adult patients with varicella?
The complete treatment regimen includes:
1. Valacyclovir: 1,000 mg three times daily for 7 days
2. Famciclovir: 500 mg three times daily for 7 days
3. Acyclovir: 800 mg five times daily for 7 days
What are three reasons why valacyclovir and famciclovir are preferred in the treatment of herpes zoster (HZ)?
- Oral bioavailability: Valacyclovir and famciclovir have better oral bioavailability compared to acyclovir.
- Dosing frequency: They require less frequent dosing, improving patient compliance.
- Efficacy: They have been shown to be more effective in reducing pain and duration of HZ.
What is the time frame for initiating antiviral treatment for HZ to be effective?
The utility of antiviral agents for HZ is unproven if treatment is initiated more than 72 hours after rash onset.
In what instances can antiviral treatment be given even if more than 72 hours have elapsed after rash onset?
- Severe disease: If the patient has severe or complicated herpes zoster.
- Immunocompromised patients: If the patient is immunocompromised.
- Persistent pain: If the patient has persistent pain or other complications.
What is defined as adequate pain relief on a 0 to 10 point scale?
Adequate pain relief is defined as the reduction of pain to below 3 on a 0 to 10 point scale or by 3 on a visual analog scale.
What does the CDC Advisory Committee on Immunization Practices (ACIP) recommend for varicella vaccination in healthy children?
The ACIP recommends 2 doses of varicella vaccine for healthy children aged 12 months and for all adolescents and adults without evidence of immunity.
How effective is active immunization with varicella vaccine if administered within a certain time frame after exposure?
Active immunization with varicella vaccine is effective in preventing illness or modifying varicella severity in immunocompetent children if administered within 3 days after exposure.
What precautions are recommended for immunocompetent patients with localized herpes zoster?
Contact precautions are recommended for immunocompetent patients with localized herpes zoster to prevent transmission.
Does antiviral therapy prevent postherpetic neuralgia (PHN)?
False. Antiviral therapy does not prevent postherpetic neuralgia (PHN).
What age does the ACIP recommend RZV for prevention of HZ in immunocompetent adults?
The ACIP has recommended RZV for prevention of HZ in immunocompetent adults aged 50 years and older.
