164: Herpes Simplex Flashcards
What are the two types of Herpes Simplex Virus (HSV) and their associated diseases?
- HSV-1: Mostly associated with orofacial disease.
- HSV-2: Mostly causes genital infection.
What are the common diagnostic methods for Herpes Simplex Virus (HSV) infections?
Diagnosis is made by:
1. PCR
2. Viral culture
3. Serology
What are the treatment options for Herpes Simplex Virus (HSV)?
Treatment for HSV includes:
1. Acyclovir
2. Famciclovir
3. Valacyclovir
What are the potential complications associated with Herpes Simplex Virus (HSV)?
HSV can cause diseases involving:
1. Eye
2. CNS
3. Neonatal infection
What is the significance of asymptomatic shedding in the transmission of Herpes Simplex Virus (HSV)?
Most transmissions of HSV occur during asymptomatic shedding, which means that individuals can spread the virus without showing any symptoms.
What is the relationship between Herpes Simplex Virus (HSV) and HIV?
HSV is an important risk factor for the acquisition and transmission of HIV.
What are the primary clinical manifestations of Herpes Simplex Virus (HSV) infections?
The main clinical manifestations of HSV infections are mucocutaneous.
How does the acquisition of HSV-2 correlate with sexual behavior?
Acquisition of HSV-2 correlates with sexual behavior, indicating that sexual activity is a significant risk factor for contracting this type of herpes virus.
What is the age group most affected by primary infection with HSV-1 responsible for recurring labial herpes?
Primary infection with HSV-1 is greatest during childhood, when 30% to 60% of children are exposed to the virus.
How does the frequency of recurrent episodes of herpes labialis vary among the population?
The frequency of recurrent episodes of herpes labialis is extremely variable, averaging approximately once per year in some studies.
What are the common symptoms associated with herpetic gingivostomatitis and pharyngitis?
Common symptoms include:
1. Fever
2. Malaise
3. Myalgias
4. Pain on swallowing
5. Irritability
6. Cervical adenopathy
What are the clinical findings in primary infections with HSV in persons without preexisting immunity?
Primary infections with HSV in persons without preexisting immunity are usually:
1. More severe
2. Frequently involve systemic signs and symptoms
3. Higher rate of complications
What is the most commonly affected area during reactivation of the virus from primary HSV infections?
The most commonly affected area during reactivation of the virus is the perioral facial area, mainly the lips, with the outer one-third of the lower lip being the most commonly affected area.
What factors influence the rates of infection with HSV-1 in children?
Rates of infection with HSV-1 increase with age and reduced socioeconomic status. Primary infection is greatest during childhood, affecting 30% to 60% of children exposed to the virus.
How can oral herpes resemble other conditions, and what are the implications for diagnosis?
Primary oral herpes may resemble aphthous stomatitis and include ulcerative lesions involving the hard and soft palate, tongue, and buccal mucosa. This resemblance can complicate the diagnosis, as it may be difficult to differentiate from other conditions like streptococcal pharyngitis.
What are the stages of classical herpes lesions progression?
- Prodromal, erythema, and papule (the developmental stage)
- Vesicle, ulcer, and hard crust (disease stage)
- Dry flaking and residual swelling (resolution stage)
What are common triggers for oral herpes recurrences?
- Emotional stress
- Illness
- Sun exposure
- Trauma
- Fatigue
- Menses
- Chapped lips
- Season of the year
How does HSV-2 orolabial infection compare to HSV-1 in terms of reactivation likelihood?
HSV-2 orolabial infections are 120 times less likely to reactivate than orolabial HSV-1 disease.
What is the major clinical presentation of HSV-2 infection?
Genital herpes is the major clinical presentation of HSV-2 infection.
What is the clinical course of acute first-episode genital herpes among patients with HSV-1 and HSV-2 infections?
The clinical course is similar among patients with HSV-1 and HSV-2 infections, associated with extensive genital lesions in different stages of evolution, including vesicles, pustules, and erythematous ulcers that may require 2 to 3 weeks to resolve.
What should patients with previously known HSV-1 genital infection do if they develop frequent genital herpes recurrences?
They should be tested for HSV-2 infection.
What is the clinical significance of viremia in primary genital herpes?
Viremia occurs in approximately 25% of persons during primary genital herpes, indicating a systemic spread of the virus which may influence the severity and duration of the infection.
What are the potential presentations of HSV cervicitis in women?
HSV cervicitis can present as:
1. Purulent or bloody vaginal discharge; examination reveals areas of diffuse or focal friability
2. Redness, extensive ulcerative lesions of the exocervix
3. Rarely, necrotic cervicitis
What are some less classical signs and symptoms of genital HSV infection that can divert one from the correct diagnosis?
- Small erythematous lesions
- Fissures
- Pruritus
- Urinary symptoms
What are the classical clinical manifestations of recurrent HSV-2 infection?
- Multiple small, grouped, vesicular lesions in the genital area
- Lesions can occur anywhere in the perigenital region, including the groin, buttocks, and thighs
- Lesions may recur at the same site or change location
- Recurrence may be heralded by a prodrome of tenderness, itching, burning, or tingling
- Outbreaks are less severe than primary infection
What are the common systemic signs and symptoms associated with HSV infections?
- Fever
- Headache
- Malaise
- Myalgias
How frequently do infections caused by HSV-2 reactivate compared to HSV-1 genital infections?
Infections caused by HSV-2 reactivate approximately 16 times more frequently than HSV-1 genital infections, averaging 3 to 4 times per year, but may appear virtually weekly.
What are the common symptoms of herpetic proctitis?
Herpetic proctitis presents with:
1. Anorectal pain
2. Anorectal discharge
3. Tenesmus
4. Constipation
5. Ulcerative lesions of distal rectal mucosa
What is herpetic whitlow and how is it typically acquired?
Herpetic whitlow is an infection of the fingers by HSV, acquired by direct inoculation or direct spread from mucosal sites during primary infection. It often occurs in children who suck their fingers during a primary gingivostomatitis outbreak and is a documented occupational hazard for medical personnel.
What distinguishes eczema herpeticum from other skin lesions in HSV infections?
Eczema herpeticum results from widespread infection following inoculation of HSV into skin damaged by eczema. It is usually a manifestation of primary HSV-1 infection in children with atopic dermatitis.
What skin conditions may be complicated by cutaneous dissemination of HSV?
The following skin diseases may be complicated by cutaneous dissemination of HSV:
1. Mycosis fungoides
2. Sézary syndrome
3. Darier disease
4. Various bullous diseases (especially with immunosuppressive therapy)
5. Second-degree and third-degree burns
In what populations can cutaneous herpes lead to small outbreaks or epidemics?
Cutaneous herpes can be transmitted between athletes involved in contact sports, such as wrestling (herpes gladiatorum) and rugby (herpes rugbiorum or scrum pox). These infections may lead to outbreaks or small epidemics among team members.
What is the range of severity for eczema herpeticum and its associated mortality rate before antiviral therapy?
The severity of eczema herpeticum ranges from mild to fatal, with mortality rates of up to 10% being reported before antiviral therapy was available.
What are the common pathogens associated with mortality in eczema herpeticum?
Common pathogens include:
1. Staphylococcus aureus
2. Beta-hemolytic Streptococcus
3. Pseudomonas aeruginosa
What are the typical symptoms and progression of vesicles in a severe primary attack of eczema herpeticum?
In a typical severe primary attack, vesicles develop in large numbers over areas of active or recently healed atopic dermatitis, particularly the face, several days after exposure. The vesicles become pustular and markedly umbilicated, quickly progressing to monomorphic erosions. Patients commonly have high fever and adenopathy.
What is the risk of neonatal infection associated with primary maternal genital herpes?
Primary maternal genital herpes is associated with a risk of neonatal infection of 25% to 50% for vaginally-delivered babies, accounting for 50% to 80% of cases of neonatal HSV infection.
What are the risk factors for the development of neonatal herpes?
Other risk factors for development of neonatal herpes include:
1. Vaginal delivery
2. Presence of cervical HSV infection
3. Use of invasive monitors
4. Isolation of HSV from the genital tract
5. Prolonged rupture of membranes
What are the three forms in which neonatal herpes infections can manifest?
Neonatal herpes infections manifest in 1 of 3 forms:
- Skin, eye, and mouth involvement
- Encephalitis
- Disseminated disease
What is the significance of recurrent HSV infection in relation to erythema multiforme?
Recurrent HSV infection is the most common precipitating event in cases of recurrent erythema multiforme, which is usually an acute, self-limited, recurrent disease lasting approximately 3 weeks.
A patient with recurrent erythema multiforme is suspected to have an underlying trigger. What is the most common precipitating event for this condition?
Recurrent HSV infection is the most common precipitating event in cases of recurrent erythema multiforme.
A child with atopic dermatitis develops widespread vesicular lesions and high fever. What is the likely diagnosis and the immediate treatment?
The child likely has eczema herpeticum, a medical emergency. Early treatment with acyclovir can be lifesaving.
A patient with genital herpes is concerned about the risk of neonatal transmission. What factors increase the risk of neonatal HSV infection?
Risk factors include primary maternal genital herpes, vaginal delivery, presence of cervical HSV infection, use of invasive monitors, and prolonged rupture of membranes.
What are the common pathogens associated with mortality in eczema herpeticum and how does this condition typically present in patients?
Common pathogens include:
1. Staphylococcus aureus
2. Beta-hemolytic Streptococcus
3. Pseudomonas aeruginosa
In a typical severe primary attack, vesicles develop in large numbers over areas of active or recently healed atopic dermatitis, particularly on the face, several days after exposure.
What is the significance of viremia in eczema herpeticum and how does it affect patient outcomes?
Viremia with infection of internal organs can be fatal in cases of eczema herpeticum. This highlights the severity of the condition and the importance of early intervention.
What are the risk factors for developing neonatal herpes and how do they differ between primary and recurrent maternal infections?
Risk factors for developing neonatal herpes include:
1. Vaginal delivery
2. Presence of cervical HSV infection
3. Use of invasive monitors
4. Isolation of HSV from the genital tract
5. Prolonged rupture of membranes
Primary maternal genital herpes is associated with a risk of neonatal infection of 25% to 50%, while recurrent maternal infection has a risk of transmission of less than 3%.
How does the presentation of neonatal herpes differ based on the form of infection, and what are the implications for treatment?
Neonatal herpes infections manifest in one of three forms:
1. Skin, eye, and mouth involvement
2. Encephalitis
3. Disseminated disease
The encephalitic and disseminated forms account for more than 50% of cases of neonatal herpes.
What is the typical duration and nature of HSV-associated erythema multiforme?
HSV-associated erythema multiforme is usually an acute, self-limited, recurrent disease that lasts approximately 3 weeks.
What is the overall mortality rate of neonatal herpes without therapy?
The overall mortality rate of neonatal herpes without therapy is 65%.
What percentage of untreated neonates with CNS infection will develop normally?
Fewer than 10% of untreated neonates with CNS infection will develop normally.
What are the common ocular infections associated with HSV?
Common ocular infections associated with HSV include:
1. Keratoconjunctivitis
2. Corneal opacification
3. Visual loss
What is the most common cause of HSV eye disease?
The majority of HSV eye disease is caused by reactivation of the virus in the trigeminal ganglia.
What are the manifestations of HSV meningitis?
HSV meningitis is manifested by:
1. Headache
2. Fever
3. Stiff neck
4. Mild photophobia
5. Lymphocytic pleocytosis in the CSF
What is the most common diagnostic technique for HSV encephalitis?
The most common diagnostic technique for HSV encephalitis is PCR of the cerebrospinal fluid for HSV DNA.
What is the typical recovery time for most cases of HSV meningitis and what strain usually causes it?
Most cases of HSV meningitis resolve spontaneously in 2 to 7 days. Most cases result from HSV-2 infection.
What are the potential complications of HSV infection involving the sacral nerves?
Complications of HSV infection involving the sacral nerves may include:
1. Autonomic nervous system dysfunction
2. Pelvic pain and numbness
3. Tingling
4. Urinary retention
5. Constipation
6. Cerebrospinal fluid pleocytosis
A neonate presents with encephalitis and disseminated disease but no cutaneous vesicles. What is the likely cause and how should it be managed?
The neonate likely has neonatal herpes caused by HSV. Without therapy, mortality is 65%. Early treatment with intravenous acyclovir is critical.
A patient presents with Bell’s palsy. What viral reactivation is associated with this condition, and what is the underlying mechanism?
Reactivation of HSV or varicella-zoster virus is associated with Bell’s palsy, caused by compression of the facial nerve in the temporal bone.
A patient with suspected HSV encephalitis presents with acute focal neurologic symptoms and fever. What diagnostic test should be performed?
PCR of the cerebrospinal fluid for HSV DNA is the most common diagnostic technique for HSV encephalitis.
A patient with HSV-1 infection develops keratoconjunctivitis. What is the most likely cause, and what are the potential complications?
The keratoconjunctivitis is caused by reactivation of HSV-1 in the trigeminal ganglia. Complications include corneal opacification and visual loss.
What is the usual initial manifestation of herpetic eye disease?
A superficial infection of the eyelids and conjunctiva (blepharoconjuncivitis) or corneal surface (dendritic or geographic epithelial ulcer with pain and blurred vision).
What are the common ocular manifestations of HSV infections, and which type of HSV is more prevalent in neonates?
Common ocular manifestations of HSV infections include keratoconjunctivitis and associated corneal opacification and visual loss. In neonates, HSV-2 is more prevalent than HSV-1.
What are the more serious forms of herpetic eye disease?
Deeper involvement of the cornea (stromal keratitis) or anterior uvea (iritis) which can lead to permanent visual loss.
What is the most common diagnostic technique for HSV encephalitis, and what are its typical clinical presentations?
The most common diagnostic technique for HSV encephalitis is PCR of the cerebrospinal fluid for HSV DNA. Typical clinical presentations include acute focal neurologic symptoms, fever, and involvement of the temporal lobe.
It is the most commonly identified acute, sporadic viral encephalitis in the US, accounting for 10-20% of all cases.
HSV encephalitis.
What are the characteristics of HSV infections in immunocompromised patients compared to immunocompetent patients?
In immunocompromised patients, HSV infections are usually more severe, more extensive, more difficult to treat, and have more frequent recurrences.
What is the relationship between cellular immune competence and the risk of severe HSV disease?
The risk of severe HSV disease and the recurrence rate correlate with the level of cellular immune competence of the host.
What role do CD8+ and CD4+ T-lymphocyte subsets play in the immune response to HSV?
CD8+ and CD4+ T-lymphocyte subsets, along with natural killer cells and inflammatory cytokines like interferon-gamma, are important in mediating protection against HSV.
How do patients with defects in humoral immunity respond to HSV infections?
Patients with defects in humoral immunity have no increase in HSV disease severity, but the humoral immune response is important in reducing virus titers at the site of inoculation and in regional neural tissues during primary infection.
What is the significance of the transfer of HSV-specific antibodies from mother to child?
The transfer of HSV-specific antibodies from mother to child is a key factor in protecting against neonatal herpes.
How long do lesions from recurrent HSV-2 infection heal without treatment?
6-10 days.
Where do genital HSV infections in males usually occur?
Glans penis and penile shaft.
What mutations are associated with herpes simplex encephalitis and their importance?
Mutations in proteins important for interferon responses, including STAT1, TYK2, and UNC-93B, are associated with herpes simplex encephalitis.
What is the preferred method for diagnosing HSV infections and why?
PCR is the preferred method for diagnosing HSV infections because it is more sensitive than viral isolation.
What is the main function of serologic testing in HSV diagnosis?
The main function of serologic testing is to differentiate a primary episode of HSV from a recurrent infection.
What are the key steps involved in performing the Tzanck test?
The Tzanck test involves scraping the base of a freshly-ruptured vesicle, staining the slides with Giemsa or Wright stain, and examining for multinucleated giant cells.
What are some diseases that can mimic genital herpes?
Diseases that can mimic genital herpes include chancroid, syphilis, and lymphogranuloma venereum.
What are the differential diagnoses for orolabial herpes?
The differential diagnosis of orolabial herpes includes aphthous ulcers, syphilis, and herpangina.
Where do lesions of genital HSV infection usually occur in females?
- Vulva
- Perineum
- Buttocks
- Vagina
- Cervix
What is the best stage to collect a sample for viral culture in suspected HSV infection? What other conditions / situations is viral isolation more successful?
The vesicular stage is the best time to collect a sample for viral culture.
Viral isolation is also most successful when specimens are taken from immunocompromised patients or from a primary infection.
What findings on a positive Tzanck smear are diagnostic of herpetic infection?
The Tzanck smear shows multinucleated giant cells, which are diagnostic of herpetic infection.
T or F: Herpes cervicitis is more common in recurrent disease.
False. It is LESS common in recurrent disease and occurs in 12% of patients.
What is the significance of the Tzanck test in the diagnosis of herpesvirus infections?
The Tzanck test is significant for rapid diagnosis of herpesvirus infections, as it identifies multinucleated giant cells indicative of herpetic infection.
For patients with active lesions, HSV can be isolated in cell culture. Most specimens will prove positive within how many hours after inoculation?
48 to 96 hours.
What is the clinical course and prognosis of HSV infections?
Most patients with HSV infections are asymptomatic, but primary infections can be severe. Most recurrences are also asymptomatic.
What are the recommendations for managing pregnant women with recurrent genital herpes?
Recommendations include clinical evaluation at delivery, considering cesarean section if there are signs of active infection, and antiviral therapy for primary HSV infection during pregnancy.
What counseling should be provided to patients with genital herpes regarding sexual practices?
Patients should refrain from sexual intercourse during outbreaks and for 1 to 2 days after, use condoms between outbreaks, and understand that transmission occurs in asymptomatic phases.
What is the role of Acyclovir in the treatment of HSV infections?
Acyclovir has a highly favorable therapeutic index due to its preferential activation in infected cells and inhibition of viral DNA polymerase.
What management strategy should be implemented for a pregnant woman with a history of genital herpes at 36 weeks of gestation?
Suppressive antiviral therapy is recommended to decrease viral shedding and the incidence of active lesions near term. It also decreases the need for cesarean delivery.
What management strategy can be recommended for a patient with genital herpes who is asymptomatic but concerned about transmission?
Suppressive antiviral therapy can reduce the rate of viral shedding and the risk of transmission to a partner.
How long should patients with genital herpes refrain from intercourse after an outbreak?
Patients should refrain from sexual intercourse during outbreaks and for 1 to 2 days after.
T or F: HSV-2 can cause orolabial infections that can be distinguished from those caused by HSV-1.
False. They are indistinguishable.
A strain that requires more than what concentration of acyclovir to be inhibited is considered relatively drug resistant?
3 μg/mL
What are the advantages of using valacyclovir over acyclovir?
Valacyclovir is an oral prodrug of acyclovir that achieves 3- to 5-fold higher bioavailability.
What is the recommended treatment for disseminated or severe herpes infections?
The treatment of choice for disseminated or severe herpes infections is intravenous acyclovir at a dosage of 10 to 15 mg/kg every 8 hours.
What is the pediatric dosage of acyclovir for primary HSV gingivostomatitis?
The pediatric dose of acyclovir for primary HSV gingivostomatitis is 15 mg/kg of acyclovir suspension orally 5 times a day for 7 days.
How does long-term suppressive therapy with acyclovir affect individuals with frequent genital recurrences?
Long-term suppressive therapy with acyclovir or its analogs is the most effective management strategy for individuals with frequent or complicated genital recurrences.
What should be done when acyclovir resistance is suspected?
When acyclovir resistance is suspected, the virus should be cultured and tested for sensitivity to acyclovir.
What is the role of foscarnet in the treatment of HSV?
Foscarnet does not require activation by HSV thymidine kinase and is usually effective in the treatment of acyclovir-resistant HSV.
What alternative drug can be used for a patient with acyclovir-resistant HSV and what are its potential side effects?
Foscarnet can be used for acyclovir-resistant HSV and can cause nephrotoxicity, electrolyte disturbances, anemia, and seizures.
What is the dose of IV acyclovir for neonatal herpes?
20 mg/kg/dose gven every 8 hours.
What is the role of cidofovir in treating HSV infections?
Cidofovir is used in cases of acyclovir-resistant HSV and its topical form has been effective in treating progressive herpetic lesions.
What are the preventive measures for HSV infection?
Preventive measures for HSV infection include total abstinence and using condoms.
Acyclovir, famciclovir and valacyclovir all decrease both symptomatic and subclinical shedding of HSV-2.
No vaccine is licensed as prophylaxis or therapy to prevent recurrent infections.
How do antivirals such as famciclovir, acyclovir and valacyclovir reduce the time of healing, viral shedding and symptoms in a patient with recurrent genital HSV?
Healing: 7 to 5 days.
Viral shedding: 4 to 2 days.
Symptoms: 4 to 3 days.
For 1st episodes of genital HSV-2 infections, what can be given?
Acyclovir, famciclovir, and valacyclovir PO all speed healing and resolution of symptoms.
T or F: HSV-2 asymptomatic patients shed the virus more frequently and shed a greater amount of the virus compared to symptomatic patients.
False. Asymptomatic patients shed LESS frequently and shed a SIMILAR amount of the virus compared to tehir symptomatic counterparts.
T or F: Orofacial lesions can be caused by HSV-1 but cannot be caused by HSV-2.
False.
What is the frequency of reactivation for HSV-2 compared to HSV-1?
Infections caused by HSV-2 reactivate 16 times more frequently than HSV-1 genital infections.
T or F: Herpetic whitlow is only caused by HSV-1.
False. It may be caused by both HSV-1 and -2.
What is the role of cidofovir in treating acyclovir-resistant HSV infections?
Cidofovir is used in cases of acyclovir-resistant HSV and does not require activation by HSV thymidine kinase.
It is the most prevalent STD worldwide and the most common cause of genital disease.
Genital herpes.
This antiviral drug for herpes is associated with considerable nephrotoxicity which requires coadministration of saline hydration and probenecid.
Cidofovir.
T or F: Surgical drainage is often needed for herpetic whitlow and speeds up healing.
False. It worsens the condition.
What are the effects of antiviral therapy on HSV-2 shedding?
Antiviral therapies such as acyclovir, famciclovir, and valacyclovir decrease both symptomatic and subclinical shedding of HSV-2, reducing the shedding days from approximately 8% in the placebo group to 0.3% to 0.6% in the treatment group, as assessed by culture.
Dosing regimen for acyclovir PO for primary orolabial herpes simplex infection?
200 mg 5x/day for 7-10 days.
T or F: Antibodies to HSV-2 are common in people who are active in sexual behavior, indicating a higher likelihood of exposure to the virus.
True.
T or F: Most of the adult population is seropositive for HSV-2, which they usually acquire from childhood.
False. HSV-1.
T or F:
Orofacial lesions can be caused by HSV-1, while HSV-2 cannot cause orofacial lesions.
False. Both strains can cause orofacial lesions.
What is the reactivation frequency of HSV-2 compared to HSV-1?
Infections caused by HSV-2 reactivate 16 times more frequently than HSV-1 genital infections, highlighting the higher reactivation rate of HSV-2.
T or F: The clinical course of the acute first episode genital herpes differs in presentation between patients with HSV-1 and those with HSV-2, which may affect diagnosis and management.
False. They are common in presentation.
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Herpetic whitlow is only caused by HSV-1, while HSV-2 does not cause whitlow, which is important for clinical recognition and treatment.
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Cutaneous dissemination of HSV can be seen as a complication in: Mycosis Fungoides, Sezary syndrome, Darier disease, Other unspecified conditions.
Most cases of HSV meningitis is caused by?
HSV-2.
What is the preferred method for diagnosis of HSV?
PCR.
What polymorphisms are associated with increased rates of genital lesions in seropositive persons?
TLR2 polymorphisms.
T or F: Both culture and PCR can enable typing of HSV isolate as HSV-1 or -2.
True.
What 3 stains can be used in Tzanck smears?
Giemsa, Wright, Papanicolaou.
What is the recommendation for pregnant women with genital herpes regarding the risk of transmission during childbirth?
Pregnant women who are known to have genital herpes should be counseled that the risk of transmitting herpes to the baby during childbirth is extremely low.
What antimicrobial peptides are known to inhibit HSV replication?
Cathelicidin and beta-defensins. The expression of these peptides in the skin may be a fector in controlling susceptibility to eczema herpeticum in patients with atopic dermatitis.
T or F: Cesarean section may not reliably prevent neonatal HSV when membranes are ruptured for long periods (>24 hours).
True.
