Contents

Search

Herpes simplex (HSV) or Herpes hominis

Epidemiology: 1) viral shedding occurs during active infection 2) viral shedding may also occur in asymptomatic individuals - most common source of HSV transmission to sexual partners [1] 3) asymptomatic shedding is more prevalent in HIV-infected patients 4) infection is spread via respiratory droplets & direct contact - secretions, including saliva are infective 5) Herpes gladiatorum is acquired & passed through contact sports 6) Herpetic whitlow (an infection of the fingers) common among dentists, dental hygienists & pulmonary nurses prior to adherence to universal precautions 7) eczema herpiticum, a widespread viral infection in patients with pre-existing cutaneous disorders, i.e. atopic dermatitis 8) neonatal infection a) may be life-threatening b) linked to mothers with primary infection during pregnancy 9) humans are only known reservoir 10) seroprevalence of HSV1 is 54% & HSV2 is 16% [14] - lower among teens 30% & 1.2% - higher among adults 40-49 years of age 64% & 26% Pathology: 1) ballooning degeneration of epidermal cells 2) intra-epidermal vesicle 3) histology indistinguishable from Herpes zoster 4) putative receptor is heparan sulfate proteoglycan [2] 5) following primary infection, the virus enters nerve endings & ascends to the dorsal root ganglia where it remains in a latent stage until reactivated 6) TNFSF14 (CD258) acts as a receptor Genetics: - TNFRSF14 mediates HSV entry into activated human T-cells Clinical manifestations: 1) primary infections a) tend to occur in children & young adults 3-7 after exposure b) asymptomatic primary infections also occur c) constitutional symptoms of include: - low-grade fever, headache, myalgias, malaise d) primary infection typically involves orofacial or genital skin - also see genital Herpes e) regional lymphadenopathy may occur f) vesicular lesions (grouped) 1] erythematous base, surrounding erythema 2] transition to pustules with ulceration or crusting within 48 hours is common 3] lesions generally last 2-6 weeks & heal without scarring 4] may rapidly evolve into superficial mucocutaneous ulcers or fissures in immunocompromised hosts 5] persistent, painful, non-healing ulcers suggests chronic mucocutaneous Herpes simplex in an immunocompromised host 6] in later stages of HIV infection, ulcers may coalesce to form large denuded areas in the anogenital region g) lesions may be painful, or burning 2) recurrent or reactivation infection a) generally result from changes in the immune system b) fatigue, stress, menses, local skin trauma, exposure to sunlight may contribute c) prodrome of fatigue, paresthesias to the affected area, lasting 12-24 hours d) may involve orofacial or genital skin e) grouped vesicular lesions with surrounding erythema 1] begin to evolve within 24 hours 2] vesicles coalesce & rupture within 4 days leaving crusted lesions 3] crusted lesions shed in 7-10 days leaving pink surface f) recurent HSV has been linked to recurrent erythema multiforme * images [16,17,20] Laboratory: 1) Herpes simplex virus DNA (most sensitive & specific) [1] - obtain swab from ulcer base 2) Herpes simplex virus identified by culture: 10-14 days - characteristic ballooning of cultured cells 3) Herpes simplex virus Ag in tissue - direct fluorescence antigen testing - unroof vesicle - scrape lesion with wooden spatula 4) Herpes simplex serology a) Latex antibody, types 1 & 2 b) > 4-fold rise in acute & convalescent antibody titers c) of limited value: most adults are seropositive [1] 5) acyclovir-resistance (if indicated) 6) Tzanck smear (older test, neither sensitive nor specific) [1] 7) see ARUP consult [9] Complications: 1) ocular Herpes (keratitis) 2) acute retinal necrosis may occur in patients with AIDS 3) Herpes encephalitis or meningitis in immunocompromised patients [5] - see Herpes simplex encephalitis 4) secondary infection may occur - complication of atopic dermatitis (eczema herpeticum) Differential diagnosis: 1) impetigo 2) Behcet's syndrome 3) Coxsackie virus 4) syphilis 5) Stevens-Johnson syndrome 6) herpangina 7) aphthous stomatitis 8) varicella (Herpes zoster, shingles) 9) see Herpes simplex type 2 for differential diagnosis of genital lesions Management: 1) reconfirmation of HSV diagnosis not needed prior to treatment unless clinical picture suggests another diagnosis [1] 2) acyclovir, famciclovir or valacyclovir a) most effective if started at presentation [1] b) diminish symptoms of HSV-1 & HSV-2 c) reduce subsequent outbreaks & viral shedding d) even high-dose antivirals do not eliminate HSV-2 viral shedding [8] 3) acyclovir a) begin therapy as soon as possible b) empiric therapy with IV acyclovir while workup in progress for clinically severe Herpes infection [1] c) 200 mg PO 5 times/day or 400 mg PO TID for 7-10 days d) the dose is doubled for immunocompromised hosts e) suppressive dose: 400 mg PO BID f) topical acylovir available; 1] marginal effectiveness [1] 2] not recommended; not cost-effective [1] g) neonatal herpes simplex treated for 6 months with acyclovir (300 mg/m2 body surface area TID) improves neurologic outcomes [7] h) topical acyclovir not effective for genital herpes [1] 4) valacyclovir 500-1000 mg PO BID for 7-10 days - chronic daily valacyclovir 500-1000 mg PO QD may reduce risk of sexual transmission of HSV-2 [4] 5) famciclovir 500 mg every 8 hours for 7-10 days - suppressive dose: 250 mg PO BID 6) acyclovir-resistant HSV infections a) foscarnet 40-60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours, or b) cidofovir (dosing not clear) c) plus trifluorothymidine (ophthalmic) applied topically d) duration of therapy: at least 10 days 7) prognosis: a) most patients recover from primary & recurrent infections without complications b) patient with HIV or other immunological disorders are at higher risk of complications 8) prevention a) vaccine development has been unsuccessful [8] b) condoms useful for HSV2 prevention c) antiviral prophylaxis 1] indications: a] immunosuppressed patients b] > 6 episodes/year 2] self-initiated vs long-term suppression 3] chronic daily valacyclovir 500-1000 mg PO QD may reduce risk of sexual transmission of HSV-2 [4] 4] topical acyclovir not effective for genital herpes d) HIV1 patients should optimize antiretroviral therapy

Related

Herpes simplex keratitis; dendritic keratitis herpes simplex virus DNA Herpes virus infection ocular Herpes simplex

Useful

acyclovir (ACV, Zovirax, Sitavig) foscarnet (Foscavir) valacyclovir (Valtrex)

Specific

Herpes simplex encephalitis Herpes simplex type 1 (HSV-1, HHV-1); human herpesvirus 1 Herpes simplex type 2 (HSV-2); human herpesvirus 2

General

herpesviridae

Properties

KINGDOM: virus GENOME-TYPE: deoxyribonucleic acid (DNA) DOUBLE-STRANDED GENOME-SIZE: 120-200 kB ENVELOPE: PRESENT CAPSID-SYMMETRY: ICOSAHEDRAL

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 769
  3. Journal Watch 21(22):176, 2001 (mouse studies) Sawtell NM et al Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo. J Infect Dis 184:964, 2001 PMID: 11574910
  4. Journal Watch 24(4):31, 2004 Corey L et al Once-daily valacyclovir to reduce the risk of transmission of genital herpes. N Engl J Med 350:11, 2004 PMID: 14702423
  5. Ferri's Clinical Advisor, Instant Diagnosis and Treatment, Ferri FF (ed), Mosby, Philadelphia, 2003
  6. Cherpes TL et al, Cunnilingus and vaginal intercourse are risk factors for herpes simplex type 1 acquisition in women. Sex Transm Dis 32:84, 2005 PMID: 15668613
  7. Kimberlin DW et al. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med 2011 Oct 6; 365:1284. - Gershon AA. Neonatal herpes simplex infection and the three musketeers. N Engl J Med 2011 Oct 6; 365:1338.
  8. Johnston C et al Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials The Lancet, Early Online Publication, 5 January 2012 PMID: 22225814 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61750-9/fulltext - Van de Perre P and Nagot N Herpes simplex virus: a new era? The Lancet, Early Online Publication, 5 January 2012 PMID: 22226046 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61614-0/fulltext
  9. ARUP Consult: Herpes Simplex Virus - HSV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/herpes-simplex-virus
  10. Van Wagoner NJ, Hook EW 3rd. Herpes diagnostic tests and their use. Curr Infect Dis Rep. 2012 Apr;14(2):175-84 PMID: 22311664
  11. Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence- based review. Arch Intern Med. 2008 Jun 9;168(11):1137-44. PMID: 18541820
  12. Ichihashi M, Nagai H, Matsunaga K. Sunlight is an important causative factor of recurrent herpes simplex. Cutis. 2004 Nov;74(5 Suppl):14-8. PMID: 15603217
  13. Caviness AC, Oelze LL, Saz UE, Greer JM, Demmler-Harrison GJ. Direct immunofluorescence assay compared to cell culture for the diagnosis of mucocutaneous herpes simplex virus infections in children. J Clin Virol. 2010 Sep;49(1):58-60. PMID: 20620099
  14. Bradley H et al. Seroprevalence of herpes simplex virus types 1 and 2 - United States, 1999-2010. J Infect Dis 2014 Feb 1; 209:325 PMID: 24136792 http://jid.oxfordjournals.org/content/209/3/325 - Kimberlin DW. The scarlet H. J Infect Dis 2014 Feb 1; 209:315 PMID: 24136793 http://jid.oxfordjournals.org/content/209/3/315
  15. Frisch S, Guo AM. Diagnostic methods and management strategies of herpes simplex and herpes zoster infections. Clin Geriatr Med. 2013 May;29(2):501-26 PMID: 23571042
  16. Herpes simplex (image) American Academy of Dermatology https://www.aad.org/public/diseases/contagious-skin-diseases/herpes-simplex
  17. Salvaggio MR, Bronze MS (images) Medscape: Herpes Simplex http://emedicine.medscape.com/article/218580-overview
  18. Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence- based review. Arch Intern Med. 2008 Jun 9;168(11):1137-44. Review. PMID: 18541820
  19. Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol. 2007 Nov;57(5):737-63; Review. PMID: 17939933
  20. Brady MP (images) Cutaneous and Mucosal Manifestations of Viral Diseases. Medscape. March 2017 http://reference.medscape.com/features/slideshow/viral-skin