Herpes simplex virus: Difference between revisions
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− | * |
+ | *Comprises herpes simplex virus 1 (HSV-1) and HSV-2, which are members of the [[Herpesviridae]] family |
− | * |
+ | *Cause typical painful vesicular lesions on labia or external genitals |
− | * |
+ | *Occasionally cause a viral encephalitis |
− | == |
+ | ==Background== |
− | === |
+ | ===Microbiology=== |
− | * Enveloped, double-stranded DNA virus |
||
− | * HSV-1 and HSV-2 are morphologically and genetically distinct viruses |
||
− | * Can be infected with both |
||
− | * '''Resistance''' to acyclovir is usually conferred by a deficiency in thymidine kinase (which phosphorylates acyclovir) |
||
− | ** Will also be resistant to valacyclovir and famciclovir |
||
+ | *Enveloped, double-stranded DNA virus |
||
− | === Epidemiology === |
||
+ | *HSV-1 and HSV-2 are morphologically and genetically distinct viruses |
||
− | * Worldwide distribution, and only found in humans |
||
+ | *Can be infected with both |
||
− | ** Most common cause of genital lesions |
||
− | ** Most common cause of acute viral encephalitis in the US, with age peaks at 5 to 30 years and over 50 years |
||
− | * Spread through person-to-person contact with skin or mucosa; not spread via fomits |
||
− | * HSV-1 has seroprevalence of 50-90% among Canadian adults[[CiteRef::howard2003re]] |
||
− | ** Often acquired in childhood in Asia and Africa |
||
− | ** More common in lower SES populations |
||
− | * HSV-2 has seroprevalence of 15-20% in Canada[[CiteRef::howard2003re]] |
||
− | ** More common in women than men, in HIV-infected people, and in MSM |
||
− | ** May be subclinical if already infected with HSV-1 |
||
+ | ===Mechanisms of Resistance=== |
||
− | === Pathophysiology === |
||
− | * Fusion of envelope and cell membrane is mediated by viral glycoproteins B, C, and D and host cell proteins cellular heparin sulfate, TNF receptors, and immunoglobulins |
||
− | * Internal capsid is released, which makes its way to the nucleus |
||
− | * Viral DNA polymerase enzyme and viral DNA helicase are targets of antivirals |
||
− | * Viral DNA may remain latent in about 10% of nearby neurons, characterized by latency-associated transcripts (LATs) |
||
− | ** Despite being latent, virus can still be shed in mucosa anywhere from 1/10 to 3/4 of days |
||
− | * HSV-1 prefers trigeminal ganglia as well as cervical ganglia, or sacral nerve root ganglia if genital |
||
+ | *'''Resistance''' to acyclovir is usually conferred by a deficiency in thymidine kinase (which phosphorylates acyclovir) |
||
− | == Clinical Presentation == |
||
+ | **Will also be resistant to valacyclovir and famciclovir |
||
− | === |
+ | ===Epidemiology=== |
− | * Incubation period usually within 5 days for primary infection |
||
− | * Mucocutaneous lesiosn may become secondarily infected |
||
+ | *Worldwide distribution, and only found in humans |
||
− | ==== Orofacial infection ==== |
||
− | * |
+ | **Most common cause of genital lesions |
+ | **Most common cause of acute viral encephalitis in the US, with age peaks at 5 to 30 years and over 50 years |
||
− | ** Includes lesions on hard and soft palate, gingiva, tongue, lips, and face |
||
+ | *Spread through person-to-person contact with skin or mucosa; not spread via fomits |
||
− | ** Pharyngeal lesions may be exudative or ulcerative |
||
+ | *HSV-1 has seroprevalence of 50-90% among Canadian adults[[CiteRef::howard2003re]] |
||
− | * May also have malaise, myalgias, anorexia or odynophagia, and cervical lymphadenopathy |
||
+ | **Often acquired in childhood in Asia and Africa |
||
− | * Self-resolving after 3 to 14 days |
||
+ | **More common in lower SES populations |
||
− | * Can cause a [[Bell palsy]] |
||
+ | *HSV-2 has seroprevalence of 15-20% in Canada[[CiteRef::howard2003re]] |
||
+ | **More common in women than men, in HIV-infected people, and in MSM |
||
+ | **May be subclinical if already infected with HSV-1 |
||
− | === |
+ | ===Pathophysiology=== |
− | * Genital lesions typically last 10 to 12 days, especially with first episode |
||
− | ** Often widely spaced bilateral lesions |
||
− | ** First episode often also involves fever, headache, malaise, and myalgias |
||
− | ** May have pain, itching, dysuria, genital discharge, and inguinal lymphadenopathy |
||
− | * May develop extragenital sites of infection, including buttock, groin, and thigh with HSV-2 and perioral area with HSV-1 |
||
− | ** Rarely fingers and eyes |
||
− | ** Develop around 14 days into the disease, likely from autoinoculation |
||
− | * HSV-2 genital infections are less severe if the person has had HSV-1 |
||
− | * 12-month recurrence rate is up to 90% for HSV-2 and 55% for HSV-1 |
||
+ | *Fusion of envelope and cell membrane is mediated by viral glycoproteins B, C, and D and host cell proteins cellular heparin sulfate, TNF receptors, and immunoglobulins |
||
− | ===== Neurological complications ===== |
||
+ | *Internal capsid is released, which makes its way to the nucleus |
||
− | * These can include aseptic meningitis, transverse myelitis, and sacral radiculopathy |
||
+ | *Viral DNA polymerase enzyme and viral DNA helicase are targets of antivirals |
||
− | * Typically occur in conjunction with first episode of genital HSV-2 infection |
||
+ | *Viral DNA may remain latent in about 10% of nearby neurons, characterized by latency-associated transcripts (LATs) |
||
− | * '''Aseptic meningitis''' |
||
+ | **Despite being latent, virus can still be shed in mucosa anywhere from 1/10 to 3/4 of days |
||
− | ** Mengitis is more common with HSV-2 than HSV-1 |
||
+ | *HSV-1 prefers trigeminal ganglia as well as cervical ganglia, or sacral nerve root ganglia if genital |
||
− | ** Often concurrent with primary genital infection, typically 3 to 12 days after start of symptoms |
||
− | ** HSV-2 may also cause Mollaret's meningitis (benign recurrent lymphocytic meningitis) |
||
− | * '''Autonomic dysfunction''' |
||
− | ** May have hyperesthesia or anaesthesia of perineum, lumbar or sacrum, as well as urinary retention and constipation |
||
− | ** Resolves over 4 to 8 weeks |
||
− | * '''Transverse myelitis''' |
||
− | ** Decreased strength and deep tendon reflexes in lower extremities in conjunction with autonomic dysfunction (as above) |
||
+ | ==Clinical Manifestations== |
||
− | ===== Pelvic inflammatory disease ===== |
||
− | * Rare cause of PID, possibly representing dual infection with a typical bacterial copathogen |
||
+ | ===Primary Infection=== |
||
− | ===== Disseminated disease ===== |
||
− | * Rarely can disseminate |
||
− | * Can be cutaneous, with concurrent meningitis, hepatitis, and pneumonitis |
||
− | * Can also involve monocular arthritis, thrombocytopenia, adrenal necrosis, and myoglobinuria |
||
− | * Patient factors include primary genital HSV in pregnancy, reactivation of genital HSV in a patient with cellular immunocompromise |
||
+ | *Incubation period usually [[Usual incubation period::within 5 days]] for primary infection |
||
− | === Reactivation === |
||
+ | *Mucocutaneous lesiosn may become secondarily infected |
||
− | * Typically localized to a single mucocutaneous area |
||
− | * Symptoms are usually more minor than first-episode or primary infection, and include itching and pain |
||
− | ** Lesions may be atypical, with fissures and unusual ulcers |
||
− | ** May be subclinical, with intermittent viral shedding |
||
− | ** May be preceded by a prodrome of tingling up to 2 days |
||
− | * Average duration of an episode of reactivation orolabial herpes is 5 days |
||
− | * HSV-1 reactivates more frequently around mouth, and HSV-2 in genitals |
||
− | * Frequency |
||
− | ** HSV-2 reactivates on average 4 to 5 times annually, with a gradual decrease over time |
||
− | === |
+ | ====Orofacial Infection==== |
− | * HSV infection of the finger, with acute onset swelling, pain, and tenderness with vesicles |
||
− | * Also fever and regional lymphadenopathy |
||
− | * Can be either acquired from parson-to-person exposure or through autoinoculation |
||
− | * Higher rates in healtcare settins |
||
+ | *Most common sites of primary infection are gingivostomatitis and pharyngitis |
||
− | === Herpes gladiatorum === |
||
+ | **Includes lesions on hard and soft palate, gingiva, tongue, lips, and face |
||
− | * Herpes simplex infection essentially anywhere on the body (chest, ears, face, and hands) associated with wrestling |
||
+ | **Pharyngeal lesions may be exudative or ulcerative |
||
+ | *May also have malaise, myalgias, anorexia or odynophagia, and cervical lymphadenopathy |
||
+ | *Self-resolving after 3 to 14 days |
||
+ | *Can cause a [[Bell palsy]] |
||
− | === |
+ | ====Genital Infection==== |
− | * '''Keratitis''', which presents with pain, blurred vision, chemosis, conjunctivitis, and corneal lesions |
||
− | * May also cause blepharitis and conjunctivitis |
||
− | * May cause '''chorioretinitis''' in infants and immunocompromised |
||
− | * '''Acute necrotizing retinitis''' |
||
− | ** Presents with painless vision loss in immunocompetent people as well as immunocompromised |
||
− | ** 25% of cases are bilateral |
||
+ | *Genital lesions typically last 10 to 12 days, especially with first episode |
||
− | === Encephalitis === |
||
+ | **Often widely spaced bilateral lesions |
||
− | * Most commonly caused by HSV-1 (95% of cases) |
||
+ | **First episode often also involves fever, headache, malaise, and myalgias |
||
− | * In children, it is often during primary infection |
||
+ | **May have pain, itching, dysuria, genital discharge, and inguinal lymphadenopathy |
||
− | * Less clear in adults, where it may be primary, infection with a new strain, or reactivation of latent infection |
||
+ | *May develop extragenital sites of infection, including buttock, groin, and thigh with HSV-2 and perioral area with HSV-1 |
||
− | * Characterized by acute onset fever and neurologic symptoms |
||
+ | **Rarely fingers and eyes |
||
− | ** Often affects temporal lobe, with behaviour changes |
||
+ | **Develop around 14 days into the disease, likely from autoinoculation |
||
− | * CSF findings |
||
+ | *HSV-2 genital infections are less severe if the person has had HSV-1 |
||
− | ** CSF PCR may be negative initially, so may need to repeat LP |
||
+ | *12-month recurrence rate is up to 90% for HSV-2 and 55% for HSV-1 |
||
− | ** ''May'' not have a cerebrospinal pleiocytosis (normal CSF in 3%) |
||
+ | =====Neurological Complications===== |
||
− | === Visceral/pulmonary herpes === |
||
− | * Can disseminate hematogenously to organs |
||
− | * Includes esophagus, lung, and liver most commonly |
||
− | * '''Esophagitis''' is more common in patients with advanced HIV |
||
− | ** Symptoms include odynophagia, dysphagia, chest pain, and weight loss |
||
− | * '''Pneumonitis''' may occur in patients with immunodupression |
||
− | ** Focal necrotizing pneumonitis or bilateral interstitial pneumonitis, depending on pattern of spread |
||
− | ** 80% mortality |
||
− | ** However, must be distinguished from asymptomatic shedding during an intercurrent illness |
||
− | * '''Hepatitis''' is rare but can be quite severe |
||
− | ** May also have fever, leukopenia, and DIC |
||
+ | *These can include aseptic meningitis, transverse myelitis, and sacral radiculopathy |
||
− | === HIV coinfection === |
||
+ | *Typically occur in conjunction with first episode of genital HSV-2 infection |
||
− | * HSV, and specifically HSV-2, may be persistent in HIV coinfection |
||
+ | *'''Aseptic meningitis''' |
||
− | * HSV-2 also predisposes to HIV infection |
||
+ | **Mengitis is more common with HSV-2 than HSV-1 |
||
− | * There is more frequent asymptomatic shedding of HSV, inversely proportional to CD4 count |
||
+ | **Often concurrent with primary genital infection, typically 3 to 12 days after start of symptoms |
||
− | * Frequency of lesions is lower on ART |
||
+ | **HSV-2 may also cause Mollaret's meningitis (benign recurrent lymphocytic meningitis) |
||
+ | *'''Autonomic dysfunction''' |
||
+ | **May have hyperesthesia or anaesthesia of perineum, lumbar or sacrum, as well as urinary retention and constipation |
||
+ | **Resolves over 4 to 8 weeks |
||
+ | *'''Transverse myelitis''' |
||
+ | **Decreased strength and deep tendon reflexes in lower extremities in conjunction with autonomic dysfunction (as above) |
||
+ | =====Pelvic Inflammatory Disease===== |
||
− | === Other immunocompromised patients === |
||
− | * Higher risk for severe HSV infections in organ transplantation, chemotherapy, malnutrition, or severe burns or eczema |
||
− | * In these patients, it can disseminate to adrenals, liver, bone marrow, and GI tract |
||
− | * Can also develop oropharyngeal and esophageal lesions |
||
− | ** May be difficult to distinguish from chemotherapy mucositis |
||
− | * Similar to other patients, asymptomatic shedding is also common, especially for 2 to 3 weeks after grafting |
||
+ | *Rare cause of PID, possibly representing dual infection with a typical bacterial copathogen |
||
− | === Pregnancy === |
||
− | * See [[HSV in pregnancy]] |
||
+ | =====Disseminated Disease===== |
||
− | === Neonatal herpes === |
||
− | * Can be acquired perinatally even without active lesions |
||
− | ** Mostly HSV-2 |
||
− | ** Rarely can be congenital, with microcephaly, hydrocephalus, and chorioretinitis |
||
− | * High risk for disseminated disease, including CNS in 70% of cases |
||
− | * Requires prolonged treatment, with initial IV acyclovir for 21 days followed by 6 months of oral |
||
+ | *Rarely can disseminate |
||
− | == Diagnosis == |
||
+ | *Can be cutaneous, with concurrent meningitis, hepatitis, and pneumonitis |
||
− | * Serology |
||
+ | *Can also involve monocular arthritis, thrombocytopenia, adrenal necrosis, and myoglobinuria |
||
− | ** Species-specific HSV-1 and HSV-2 antibody assays, most commonly to glycoproteins gG1 and gG2 |
||
+ | *Patient factors include primary genital HSV in pregnancy, reactivation of genital HSV in a patient with cellular immunocompromise |
||
− | ** Antibodies will be positive life-long, though you can use acute and convalescent titres for diagnosis of primary infection (not helpful for reactivation) |
||
− | * Molecular tests |
||
− | ** PCR is current standard, given its high sensitivity |
||
− | * Viral culture |
||
− | * Histology, with Wright, Giemsa, or Papanicolaou stains that show giant cells or intranuclear inclusions that are typical of HSV |
||
− | == |
+ | ===Reactivation=== |
+ | *Typically localized to a single mucocutaneous area |
||
− | === Genital and rectal herpes === |
||
+ | *Symptoms are usually more minor than first-episode or primary infection, and include itching and pain |
||
− | * Mild-to-moderate infection |
||
+ | **Lesions may be atypical, with fissures and unusual ulcers |
||
− | ** First episode |
||
+ | **May be subclinical, with intermittent viral shedding |
||
− | *** [[Is treated by::acyclovir]] 400 mg po tid, [[Is treated by::acyclovir]] 200 mg po 5x/day, [[Is treated by::famciclovir]] 250 mg po tid, or [[Is treated by::valacyclovir]] 1 g po bid |
||
− | ** |
+ | **May be preceded by a prodrome of tingling up to 2 days |
+ | *Average duration of an episode of reactivation orolabial herpes is 5 days |
||
− | ** Recurrence |
||
+ | *HSV-1 reactivates more frequently around mouth, and HSV-2 in genitals |
||
− | *** [[Is treated by::acyclovir]] 400 mg po tid, [[Is treated by::acyclovir]] 800 mg po bid, [[Is treated by::acyclovir]] 800 mg po tid, [[Is treated by::valacyclovir]] 500 mg po bid, [[Is treated by::famciclovir]] 125 mg po tid |
||
+ | *Frequency |
||
− | *** Duration 5 days, except valacyclovir that is 3 days |
||
+ | **HSV-2 reactivates on average 4 to 5 times annually, with a gradual decrease over time |
||
− | ** Suppressive therapy |
||
− | *** [[Is treated by::Acyclovir]] 400 mg po bid, [[Is treated by::famciclovir]] 250 mg po bid, [[Is treated by::valacyclovir]] 500 mg po daily, or [[Is treated by::valacyclovir]] 1 g po daily |
||
− | * HIV patients |
||
− | ** Recurrence |
||
− | *** [[Is treated by::acyclovir]] 400 mg po tid, [[Is treated by::valacyclovir]] 1 g po bid, [[Is treated by::famciclovir]] 500 mg po tid |
||
− | *** Duration 5 to 10 days |
||
− | ** Suppressive therapy |
||
− | ** [[Is treated by::Acyclovir]] 400 to 800 mg po bid to tid, [[Is treated by::famciclovir]] 500 mg po bid, or [[Is treated by::valacyclovir]] 500 mg po bid |
||
− | * Severe infections, including CNS or ocular involvement, or disseminated disease |
||
− | ** [[Is treated by::Acyclovir]] 5 to 10 mg/kg IV q8h for 5 to 7 days and until clinical resolution |
||
− | ** For encephalitis, extend to 21 days |
||
− | ** For neonates, extend IV to 21 days then step down to oral for 6 months |
||
− | * Pregnant: use [[Is treated by::acyclovir]] |
||
− | === |
+ | ===Herpetic Whitlow=== |
− | * [[Is treated by::Acyclovir]] 400 mg po tid, [[Is treated by::acyclovir]] 200 mg po 5x/d, [[Is treated by::famciclovir]] 250 mg po tid, [[Is treated by::valacyclovir]] 1 g po bid |
||
− | * Duration 7 to 10 days |
||
+ | *HSV infection of the finger, with acute onset swelling, pain, and tenderness with vesicles |
||
− | === Esophagitis === |
||
+ | *Also fever and regional lymphadenopathy |
||
− | * [[Is treated by::Acyclovir]] 400 to 800 mg po 5x/day, [[Is treated by::famciclovir]] 500 mg po bid to tid, [[Is treated by::valacyclovir]] 1 g po bid, or [[Is treated by::acyclovir]] 5 mg/kg IV q8h |
||
+ | *Can be either acquired from parson-to-person exposure or through autoinoculation |
||
− | * Duration 7 to 10 days |
||
+ | *Higher rates in healtcare settins |
||
− | === |
+ | ===Herpes Gladiatorum=== |
− | * [[Is treated by::Acyclovir]] 400 mg po bid, [[Is treated by::famciclovir]] 250 mg po bid, [[Is treated by::valacyclovir]] 250 mg po bid or 500 mg po daily or 1 g po daily |
||
+ | *Herpes simplex infection essentially anywhere on the body (chest, ears, face, and hands) associated with wrestling |
||
− | === Encephalitis and meningitis === |
||
− | * [[Is treated by::Acyclovir]] 10 mg/kg IV q8h for 21 days |
||
− | * Duration 21 days for encephalitis or 7 to 10 days for meningitis |
||
− | * In neonates, this is followed by oral suppressive therapy |
||
− | === |
+ | ===Ocular Herpes=== |
− | * Consult Ophthalmology |
||
+ | *'''Keratitis''', which presents with pain, blurred vision, chemosis, conjunctivitis, and corneal lesions |
||
− | === Immunosuppressed patients === |
||
+ | *May also cause blepharitis and conjunctivitis |
||
− | * HSV seropositive transplant patients: [[Is treated by::Acyclovir]] 5 mg/kg IV q8h for 7 days, followed by 200 to 400 mg po 3-5x/day for 1 to 3 months |
||
+ | *May cause '''chorioretinitis''' in infants and immunocompromised |
||
− | * HIV patients: [[Is treated by::acyclovir]] 400 to 800 mg po bid to tid, [[Is treated by::valacyclovir]] 500 mg po daily, or [[Is treated by::famciclovir]] 500 mg po bid |
||
+ | *'''Acute necrotizing retinitis''' |
||
− | * Burn patients: [[Is treated by::acyclovir]] 5 mg/kg IV q8h for 7 days, followed by 200 mg po 5x/day for 7 to 14 days |
||
+ | **Presents with painless vision loss in immunocompetent people as well as immunocompromised |
||
+ | **25% of cases are bilateral |
||
− | === |
+ | ===Encephalitis=== |
+ | |||
− | * If unresponsive to acyclovir, consider [[Is treated by::foscarnet]] 40 to 80 mg/kg IV q8h until clinical resolution |
||
+ | *Most commonly caused by HSV-1 (95% of cases) |
||
− | * Can try [[Is treated by::cidofovir]] 5 mg/kg once weekly if severe infection |
||
+ | *In children, it is often during primary infection |
||
+ | *Less clear in adults, where it may be primary, infection with a new strain, or reactivation of latent infection |
||
+ | *Characterized by acute onset fever and neurologic symptoms |
||
+ | **Often affects temporal lobe, with behaviour changes |
||
+ | *CSF findings |
||
+ | **CSF PCR may be negative initially, so may need to repeat LP |
||
+ | **''May'' not have a cerebrospinal pleiocytosis (normal CSF in 3%) |
||
+ | |||
+ | ===Visceral and Pulmonary Herpes=== |
||
+ | |||
+ | *Can disseminate hematogenously to organs |
||
+ | *Includes esophagus, lung, and liver most commonly |
||
+ | *'''Esophagitis''' is more common in patients with advanced HIV |
||
+ | **Symptoms include odynophagia, dysphagia, chest pain, and weight loss |
||
+ | *'''Pneumonitis''' may occur in patients with immunosuppression |
||
+ | **Focal necrotizing pneumonitis or bilateral interstitial pneumonitis, depending on pattern of spread |
||
+ | **80% mortality |
||
+ | **However, must be distinguished from asymptomatic shedding during an intercurrent illness |
||
+ | *'''Hepatitis''' is rare but can be quite severe |
||
+ | **May also have fever, leukopenia, and DIC |
||
+ | |||
+ | ===HIV Coinfection=== |
||
+ | |||
+ | *HSV, and specifically HSV-2, may be persistent in HIV coinfection |
||
+ | *HSV-2 also predisposes to HIV infection |
||
+ | *There is more frequent asymptomatic shedding of HSV, inversely proportional to CD4 count |
||
+ | *Frequency of lesions is lower on ART |
||
+ | |||
+ | ===Other Immunocompromised Patients=== |
||
+ | |||
+ | *Higher risk for severe HSV infections in organ transplantation, chemotherapy, malnutrition, or severe burns or eczema |
||
+ | *In these patients, it can disseminate to adrenals, liver, bone marrow, and GI tract |
||
+ | *Can also develop oropharyngeal and esophageal lesions |
||
+ | **May be difficult to distinguish from chemotherapy mucositis |
||
+ | *Similar to other patients, asymptomatic shedding is also common, especially for 2 to 3 weeks after grafting |
||
+ | |||
+ | ===Pregnancy=== |
||
+ | |||
+ | *See [[HSV in pregnancy]] |
||
+ | |||
+ | ===Neonatal Herpes=== |
||
+ | |||
+ | *Can be acquired perinatally even without active lesions |
||
+ | **Mostly HSV-2 |
||
+ | **Rarely can be congenital, with microcephaly, hydrocephalus, and chorioretinitis |
||
+ | *High risk for disseminated disease, including CNS in 70% of cases |
||
+ | *Requires prolonged treatment, with initial IV acyclovir for 21 days followed by 6 months of oral |
||
+ | |||
+ | ==Diagnosis== |
||
+ | |||
+ | *Serology |
||
+ | **Species-specific HSV-1 and HSV-2 antibody assays, most commonly to glycoproteins gG1 and gG2 |
||
+ | **Antibodies will be positive life-long, though you can use acute and convalescent titres for diagnosis of primary infection (not helpful for reactivation) |
||
+ | *Molecular tests |
||
+ | **PCR is current standard, given its high sensitivity |
||
+ | *Viral culture |
||
+ | *Histology, with Wright, Giemsa, or Papanicolaou stains that show giant cells or intranuclear inclusions that are typical of HSV |
||
+ | **Large granular plasma cells in CSF are the hallmark of Mollaret meningitis |
||
+ | |||
+ | ==Management== |
||
+ | |||
+ | ===Genital and Rectal Herpes=== |
||
+ | |||
+ | *Mild-to-moderate infection |
||
+ | **First episode |
||
+ | ***[[Is treated by::Acyclovir]] 400 mg po tid, [[Is treated by::acyclovir]] 200 mg po 5x/day, [[Is treated by::famciclovir]] 250 mg po tid, or [[Is treated by::valacyclovir]] 1 g po bid |
||
+ | ***Duration 5 to 10 days |
||
+ | **Recurrence |
||
+ | ***[[Is treated by::Acyclovir]] 400 mg po tid, [[Is treated by::acyclovir]] 800 mg po bid, [[Is treated by::acyclovir]] 800 mg po tid, [[Is treated by::valacyclovir]] 500 mg po bid, [[Is treated by::famciclovir]] 125 mg po tid |
||
+ | ***Duration 5 days, except valacyclovir that is 3 days |
||
+ | **Suppressive therapy |
||
+ | ***[[Is treated by::Acyclovir]] 400 mg po bid, [[Is treated by::famciclovir]] 250 mg po bid, [[Is treated by::valacyclovir]] 500 mg po daily, or [[Is treated by::valacyclovir]] 1 g po daily |
||
+ | *HIV patients |
||
+ | **Recurrence |
||
+ | ***[[Is treated by::acyclovir]] 400 mg po tid, [[Is treated by::valacyclovir]] 1 g po bid, [[Is treated by::famciclovir]] 500 mg po tid |
||
+ | ***Duration 5 to 10 days |
||
+ | **Suppressive therapy |
||
+ | **[[Is treated by::Acyclovir]] 400 to 800 mg po bid to tid, [[Is treated by::famciclovir]] 500 mg po bid, or [[Is treated by::valacyclovir]] 500 mg po bid |
||
+ | *Severe infections, including CNS or ocular involvement, or disseminated disease |
||
+ | **[[Is treated by::Acyclovir]] 5 to 10 mg/kg IV q8h for 5 to 7 days and until clinical resolution |
||
+ | **For encephalitis, extend to 21 days |
||
+ | **For neonates, extend IV to 21 days then step down to oral for 6 months |
||
+ | *Pregnant: use [[Is treated by::acyclovir]] |
||
+ | |||
+ | ===Stomatitis=== |
||
+ | |||
+ | *[[Is treated by::Acyclovir]] 400 mg po tid, [[Is treated by::acyclovir]] 200 mg po 5x/d, [[Is treated by::famciclovir]] 250 mg po tid, [[Is treated by::valacyclovir]] 1 g po bid |
||
+ | *Duration 7 to 10 days |
||
+ | |||
+ | ===Esophagitis=== |
||
+ | |||
+ | *[[Is treated by::Acyclovir]] 400 to 800 mg po 5x/day, [[Is treated by::famciclovir]] 500 mg po bid to tid, [[Is treated by::valacyclovir]] 1 g po bid, or [[Is treated by::acyclovir]] 5 mg/kg IV q8h |
||
+ | *Duration 7 to 10 days |
||
+ | |||
+ | ===Herpes Labialis Prophylaxis=== |
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+ | |||
+ | *[[Is treated by::Acyclovir]] 400 mg po bid, [[Is treated by::famciclovir]] 250 mg po bid, [[Is treated by::valacyclovir]] 250 mg po bid or 500 mg po daily or 1 g po daily |
||
+ | |||
+ | ===Encephalitis and Meningitis=== |
||
+ | |||
+ | *[[Is treated by::Acyclovir]] 10 mg/kg IV q8h for 21 days |
||
+ | *Duration 21 days for encephalitis or 7 to 10 days for meningitis |
||
+ | *In neonates, this is followed by oral suppressive therapy |
||
+ | |||
+ | ===Ocular Infections=== |
||
+ | |||
+ | *Consult Ophthalmology |
||
+ | |||
+ | ===Immunosuppressed Patients=== |
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+ | |||
+ | *HSV seropositive transplant patients: [[Is treated by::Acyclovir]] 5 mg/kg IV q8h for 7 days, followed by 200 to 400 mg po 3-5x/day for 1 to 3 months |
||
+ | *HIV patients: [[Is treated by::acyclovir]] 400 to 800 mg po bid to tid, [[Is treated by::valacyclovir]] 500 mg po daily, or [[Is treated by::famciclovir]] 500 mg po bid |
||
+ | *Burn patients: [[Is treated by::acyclovir]] 5 mg/kg IV q8h for 7 days, followed by 200 mg po 5x/day for 7 to 14 days |
||
+ | |||
+ | ===Acyclovir Resistance=== |
||
+ | |||
+ | *If unresponsive to acyclovir, consider [[Is treated by::foscarnet]] 40 to 80 mg/kg IV q8h until clinical resolution |
||
+ | *Can try [[Is treated by::cidofovir]] 5 mg/kg once weekly if severe infection |
||
[[Category:Herpesviridae]] |
[[Category:Herpesviridae]] |
Latest revision as of 12:29, 2 May 2023
- Comprises herpes simplex virus 1 (HSV-1) and HSV-2, which are members of the Herpesviridae family
- Cause typical painful vesicular lesions on labia or external genitals
- Occasionally cause a viral encephalitis
Background
Microbiology
- Enveloped, double-stranded DNA virus
- HSV-1 and HSV-2 are morphologically and genetically distinct viruses
- Can be infected with both
Mechanisms of Resistance
- Resistance to acyclovir is usually conferred by a deficiency in thymidine kinase (which phosphorylates acyclovir)
- Will also be resistant to valacyclovir and famciclovir
Epidemiology
- Worldwide distribution, and only found in humans
- Most common cause of genital lesions
- Most common cause of acute viral encephalitis in the US, with age peaks at 5 to 30 years and over 50 years
- Spread through person-to-person contact with skin or mucosa; not spread via fomits
- HSV-1 has seroprevalence of 50-90% among Canadian adults1
- Often acquired in childhood in Asia and Africa
- More common in lower SES populations
- HSV-2 has seroprevalence of 15-20% in Canada1
- More common in women than men, in HIV-infected people, and in MSM
- May be subclinical if already infected with HSV-1
Pathophysiology
- Fusion of envelope and cell membrane is mediated by viral glycoproteins B, C, and D and host cell proteins cellular heparin sulfate, TNF receptors, and immunoglobulins
- Internal capsid is released, which makes its way to the nucleus
- Viral DNA polymerase enzyme and viral DNA helicase are targets of antivirals
- Viral DNA may remain latent in about 10% of nearby neurons, characterized by latency-associated transcripts (LATs)
- Despite being latent, virus can still be shed in mucosa anywhere from 1/10 to 3/4 of days
- HSV-1 prefers trigeminal ganglia as well as cervical ganglia, or sacral nerve root ganglia if genital
Clinical Manifestations
Primary Infection
- Incubation period usually within 5 days for primary infection
- Mucocutaneous lesiosn may become secondarily infected
Orofacial Infection
- Most common sites of primary infection are gingivostomatitis and pharyngitis
- Includes lesions on hard and soft palate, gingiva, tongue, lips, and face
- Pharyngeal lesions may be exudative or ulcerative
- May also have malaise, myalgias, anorexia or odynophagia, and cervical lymphadenopathy
- Self-resolving after 3 to 14 days
- Can cause a Bell palsy
Genital Infection
- Genital lesions typically last 10 to 12 days, especially with first episode
- Often widely spaced bilateral lesions
- First episode often also involves fever, headache, malaise, and myalgias
- May have pain, itching, dysuria, genital discharge, and inguinal lymphadenopathy
- May develop extragenital sites of infection, including buttock, groin, and thigh with HSV-2 and perioral area with HSV-1
- Rarely fingers and eyes
- Develop around 14 days into the disease, likely from autoinoculation
- HSV-2 genital infections are less severe if the person has had HSV-1
- 12-month recurrence rate is up to 90% for HSV-2 and 55% for HSV-1
Neurological Complications
- These can include aseptic meningitis, transverse myelitis, and sacral radiculopathy
- Typically occur in conjunction with first episode of genital HSV-2 infection
- Aseptic meningitis
- Mengitis is more common with HSV-2 than HSV-1
- Often concurrent with primary genital infection, typically 3 to 12 days after start of symptoms
- HSV-2 may also cause Mollaret's meningitis (benign recurrent lymphocytic meningitis)
- Autonomic dysfunction
- May have hyperesthesia or anaesthesia of perineum, lumbar or sacrum, as well as urinary retention and constipation
- Resolves over 4 to 8 weeks
- Transverse myelitis
- Decreased strength and deep tendon reflexes in lower extremities in conjunction with autonomic dysfunction (as above)
Pelvic Inflammatory Disease
- Rare cause of PID, possibly representing dual infection with a typical bacterial copathogen
Disseminated Disease
- Rarely can disseminate
- Can be cutaneous, with concurrent meningitis, hepatitis, and pneumonitis
- Can also involve monocular arthritis, thrombocytopenia, adrenal necrosis, and myoglobinuria
- Patient factors include primary genital HSV in pregnancy, reactivation of genital HSV in a patient with cellular immunocompromise
Reactivation
- Typically localized to a single mucocutaneous area
- Symptoms are usually more minor than first-episode or primary infection, and include itching and pain
- Lesions may be atypical, with fissures and unusual ulcers
- May be subclinical, with intermittent viral shedding
- May be preceded by a prodrome of tingling up to 2 days
- Average duration of an episode of reactivation orolabial herpes is 5 days
- HSV-1 reactivates more frequently around mouth, and HSV-2 in genitals
- Frequency
- HSV-2 reactivates on average 4 to 5 times annually, with a gradual decrease over time
Herpetic Whitlow
- HSV infection of the finger, with acute onset swelling, pain, and tenderness with vesicles
- Also fever and regional lymphadenopathy
- Can be either acquired from parson-to-person exposure or through autoinoculation
- Higher rates in healtcare settins
Herpes Gladiatorum
- Herpes simplex infection essentially anywhere on the body (chest, ears, face, and hands) associated with wrestling
Ocular Herpes
- Keratitis, which presents with pain, blurred vision, chemosis, conjunctivitis, and corneal lesions
- May also cause blepharitis and conjunctivitis
- May cause chorioretinitis in infants and immunocompromised
- Acute necrotizing retinitis
- Presents with painless vision loss in immunocompetent people as well as immunocompromised
- 25% of cases are bilateral
Encephalitis
- Most commonly caused by HSV-1 (95% of cases)
- In children, it is often during primary infection
- Less clear in adults, where it may be primary, infection with a new strain, or reactivation of latent infection
- Characterized by acute onset fever and neurologic symptoms
- Often affects temporal lobe, with behaviour changes
- CSF findings
- CSF PCR may be negative initially, so may need to repeat LP
- May not have a cerebrospinal pleiocytosis (normal CSF in 3%)
Visceral and Pulmonary Herpes
- Can disseminate hematogenously to organs
- Includes esophagus, lung, and liver most commonly
- Esophagitis is more common in patients with advanced HIV
- Symptoms include odynophagia, dysphagia, chest pain, and weight loss
- Pneumonitis may occur in patients with immunosuppression
- Focal necrotizing pneumonitis or bilateral interstitial pneumonitis, depending on pattern of spread
- 80% mortality
- However, must be distinguished from asymptomatic shedding during an intercurrent illness
- Hepatitis is rare but can be quite severe
- May also have fever, leukopenia, and DIC
HIV Coinfection
- HSV, and specifically HSV-2, may be persistent in HIV coinfection
- HSV-2 also predisposes to HIV infection
- There is more frequent asymptomatic shedding of HSV, inversely proportional to CD4 count
- Frequency of lesions is lower on ART
Other Immunocompromised Patients
- Higher risk for severe HSV infections in organ transplantation, chemotherapy, malnutrition, or severe burns or eczema
- In these patients, it can disseminate to adrenals, liver, bone marrow, and GI tract
- Can also develop oropharyngeal and esophageal lesions
- May be difficult to distinguish from chemotherapy mucositis
- Similar to other patients, asymptomatic shedding is also common, especially for 2 to 3 weeks after grafting
Pregnancy
- See HSV in pregnancy
Neonatal Herpes
- Can be acquired perinatally even without active lesions
- Mostly HSV-2
- Rarely can be congenital, with microcephaly, hydrocephalus, and chorioretinitis
- High risk for disseminated disease, including CNS in 70% of cases
- Requires prolonged treatment, with initial IV acyclovir for 21 days followed by 6 months of oral
Diagnosis
- Serology
- Species-specific HSV-1 and HSV-2 antibody assays, most commonly to glycoproteins gG1 and gG2
- Antibodies will be positive life-long, though you can use acute and convalescent titres for diagnosis of primary infection (not helpful for reactivation)
- Molecular tests
- PCR is current standard, given its high sensitivity
- Viral culture
- Histology, with Wright, Giemsa, or Papanicolaou stains that show giant cells or intranuclear inclusions that are typical of HSV
- Large granular plasma cells in CSF are the hallmark of Mollaret meningitis
Management
Genital and Rectal Herpes
- Mild-to-moderate infection
- First episode
- Acyclovir 400 mg po tid, acyclovir 200 mg po 5x/day, famciclovir 250 mg po tid, or valacyclovir 1 g po bid
- Duration 5 to 10 days
- Recurrence
- Acyclovir 400 mg po tid, acyclovir 800 mg po bid, acyclovir 800 mg po tid, valacyclovir 500 mg po bid, famciclovir 125 mg po tid
- Duration 5 days, except valacyclovir that is 3 days
- Suppressive therapy
- Acyclovir 400 mg po bid, famciclovir 250 mg po bid, valacyclovir 500 mg po daily, or valacyclovir 1 g po daily
- First episode
- HIV patients
- Recurrence
- acyclovir 400 mg po tid, valacyclovir 1 g po bid, famciclovir 500 mg po tid
- Duration 5 to 10 days
- Suppressive therapy
- Acyclovir 400 to 800 mg po bid to tid, famciclovir 500 mg po bid, or valacyclovir 500 mg po bid
- Recurrence
- Severe infections, including CNS or ocular involvement, or disseminated disease
- Acyclovir 5 to 10 mg/kg IV q8h for 5 to 7 days and until clinical resolution
- For encephalitis, extend to 21 days
- For neonates, extend IV to 21 days then step down to oral for 6 months
- Pregnant: use acyclovir
Stomatitis
- Acyclovir 400 mg po tid, acyclovir 200 mg po 5x/d, famciclovir 250 mg po tid, valacyclovir 1 g po bid
- Duration 7 to 10 days
Esophagitis
- Acyclovir 400 to 800 mg po 5x/day, famciclovir 500 mg po bid to tid, valacyclovir 1 g po bid, or acyclovir 5 mg/kg IV q8h
- Duration 7 to 10 days
Herpes Labialis Prophylaxis
- Acyclovir 400 mg po bid, famciclovir 250 mg po bid, valacyclovir 250 mg po bid or 500 mg po daily or 1 g po daily
Encephalitis and Meningitis
- Acyclovir 10 mg/kg IV q8h for 21 days
- Duration 21 days for encephalitis or 7 to 10 days for meningitis
- In neonates, this is followed by oral suppressive therapy
Ocular Infections
- Consult Ophthalmology
Immunosuppressed Patients
- HSV seropositive transplant patients: Acyclovir 5 mg/kg IV q8h for 7 days, followed by 200 to 400 mg po 3-5x/day for 1 to 3 months
- HIV patients: acyclovir 400 to 800 mg po bid to tid, valacyclovir 500 mg po daily, or famciclovir 500 mg po bid
- Burn patients: acyclovir 5 mg/kg IV q8h for 7 days, followed by 200 mg po 5x/day for 7 to 14 days
Acyclovir Resistance
References
- a b M. Howard, J. W. Sellors, D. Jang, N. J. Robinson, M. Fearon, J. Kaczorowski, M. Chernesky. Regional Distribution of Antibodies to Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 in Men and Women in Ontario, Canada. Journal of Clinical Microbiology. 2003;41(1):84-89. doi:10.1128/jcm.41.1.84-89.2003.