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Herpes Labialis

Herpes simplex labialis (orolabial herpes or cold sores) is a viral infection which occurs on the lips or around the mouth. It affects people worldwide. The primary causative agent is HSV-1.  


Prodromal symptoms of primary herpes labialis:

The duration of latency (when HSV-1 is dormant) is variable. Reactivation results in the development of  lesions in the face, orolabial and ocular mucosae, attended by pain and paresthesia, ulceration or crust formation, usually in the vermillion border. Untreated cases last approximately 1 week. Primary HSV-1 infection may be self-limiting or asymptomatic. Otherwise, young children may present with febrile herpetic stomatitis, with small blisters and 2 to 10 mm ulcers in the mouth, tongue, and lips [15]. Adults may complain of sore throat and cervical lymphadenopathy, resembling infectious mononucleosis.

Relapses are accompanied by skin rash on the lips, papules, vesicles, and crusts around the mouth. Healing may occur before blisters are formed in 25% of recurrent cases. Prodromal symptoms of reactivation are associated with itching, burning sensation and/or paresthesia prior to the appearance of erythema and papules [16]. Vesicles, pustulation, ulceration, scabbing or crust formation signify a late stage in the course of the disease. Peak viral titres occur in the first 24 h (when most lesions are in the vesicular stage). The infectious cycle gradually subsides with scab or crust formation after which the virus will recede into the latency phase [16] [17].

  • Toddlers with primary herpes experience fever, malaise, loss of appetite, and severe intraoral pain. Increased salivation and foul breath may also be present.[dentalresource.org]
  • Other symptoms include malaise, fever, and anorexia. There also can be involvement of neural structures and the manifestation of neurologic symptoms.[medical-dictionary.thefreedictionary.com]
  • Systemic symptoms are often present, including fever (38.4 to 40 C [101 to 104 F]), malaise and myalgia. The pharyngitis and flu-like symptoms are difficult to distinguish from mononucleosis in older patients.[web.archive.org]
  • A 29-year-old Turkish woman with allergic contact cheilitis from a lipstick was misdiagnosed as herpes labialis and subsequently worsened with the application of Zovirax cream.[ncbi.nlm.nih.gov]
  • In other languages: French Italian Portuguese Romanian German Dutch Swedish Russian Polish Czech Greek Turkish Chinese Japanese Korean Arabic Advertisements Word of the day: mean freak Advertisements Infórmanos de los anuncios inapropiados.[wordreference.com]
  • Some individuals develop difficulty in swallowing (dysphagia) and swollen lymph nodes (lymphadenopathy).[11] Primary HSV infections in adults often results in pharyngitis similar to that observed in glandular fever (infectious mononucleosis), but gingivostomatitis[en.wikipedia.org]
  • A 29-year-old Turkish woman with allergic contact cheilitis from a lipstick was misdiagnosed as herpes labialis and subsequently worsened with the application of Zovirax cream.[ncbi.nlm.nih.gov]
  • […] to avoid wrong diagnosis not use antifungal or antibiotics you must use antiviral.jpg 720 960; 33 KB Mouth with 3 herpeses.jpg 2 743 1 636; 880 KB Mouth with 5 herpeses.jpg 2 364 1 881; 481 KB Photographic Comparison of a Canker Sore, Herpes, Angular Cheilitis[commons.wikimedia.org]
  • "Angular cheilitis, part 1: local etiologies". Cutis; Cutaneous Medicine for the Practitioner. 87 (6): 289–95. PMID 21838086. Scully C (2013). Oral and maxillofacial medicine : the basis of diagnosis and treatment (3rd ed.).[en.wikipedia.org]
Aphthous Stomatitis
  • The prevalence was related to the place of living, income, and college, but not to gender, marital status, medical history, smoking, or aphthous stomatitis.[ncbi.nlm.nih.gov]
  • […] recurrent aphthous stomatitis (MaRAS).[en.wikipedia.org]
  • But, in doubtful cases, various recurrent and acute conditions causing oral ulcerations such as acute necrotizing ulcerative gingivitis, herpangina, aphthous stomatitis, varicella zoster infection, erythema multiform, allergic stomatitis should be considered[omicsonline.org]
Lip Blisters
  • RECURRENT HERPES LABIALIS: Tingling or itching (prodromal signs) occurs at the infection site before the lip blisters actually appear. Then, clusters of blisters (vesicles) erupt.[dentalresource.org]
Vesicular Rash
  • Physical findings include a painful vesicular rash ranging from multiple lesions with primary infection to a few lesions with recurrent infection in the immune competent host.[cancertherapyadvisor.com]
Vesicular Rash
  • Physical findings include a painful vesicular rash ranging from multiple lesions with primary infection to a few lesions with recurrent infection in the immune competent host.[cancertherapyadvisor.com]
Mental Distress
  • It gives rise to painful vesicles on the lips that form unsightly crusts, causing an unpleasant look and mental distress. We aimed to examine the effects of available measures for preventing recurrence of cold sores in people with normal immunity.[doi.org]


Diagnosis of herpes labialis commences with physical examination of the characteristic lesions, history-taking and assessment of symptoms. Laboratory confirmation may be required in atypical or special cases e.g., immunocompromised or pregnant patients. 

Virus culture from the skin vesicles helps in typing of HSV. Virus isolation and identification from lesions, tears or saliva are done using polymerase chain reaction (PCR) [18]. Tzanck test entails microscopic examination of Giemsa-stained smears from freshly ruptured vesicle to detect the presence of multinucleate giant cells as in HSV or varicella-zoster virus infections. Seroconversion with specific antibody is confirmatory in primary HSV infections. Direct fluorescent antibody testing on air-dried smears is another laboratory test with approximately 75% positivity rate. 


Although most HSV patients have experienced full or partial recovery without treatment, antimicrobial therapy serves to alleviate symptoms and to interrupt the transmission cycle (prevention) by eliminating the causative agent. In isolated cases, the clinical manifestations subside spontaneously. Some antiviral drugs e.g., acyclovir, valacyclovir, or famciclovir can be prescribed if needed [19], especially in primary HSV infections. Symptomatic treatment is recommended for all mucocutaneous herpes infections, with systemic analgesics for pain. Oral and topical acyclovir have been shown to be effective by shortening the duration of relapse by one day. Acyclovir-resistant strains are resistant to penciclovir.

Penciclovir 1% cream when applied every 2 hours  for 4 days, starting when the first lesion appears, can decrease recurrence, with minimal toxicity effects. Famciclovir 1500 mg single oral dose or valacyclovir 2 gm every 12 hours for 1 day is recommended for recurrent herpes labialis. Docosanol 10% cream requires repeated applications 5 times a day until symptoms subside [20]. Application of a sunscreen or zinc oxide minimizes recurrence [20] [21].


In primary infection, all of the oral mucosa can be involved. Recurrence is confined to the mucosa of the hard palate or the lips in older children and adults [13]. Relapses decrease in frequency after age 35 [14]. After the primary infection the virus migrates to the trigeminal ganglion where it remains dormant for life until it is reactivated by some stimuli.

In general, HSV infections are self-limiting and resolve without dire consequences; however, recurrence is common. About 30%of patients experience recurrences. Lifelong recurrences are associated with persistent virus infection in the trigeminal ganglion.


Herpes labialis is caused by herpes simplex virus type 1 (HSV-1). Primary infection in adolescents may manifest before age 20, 80% of them are positive for anti-HSV antibodies. The virus produces painful lesions on the lip and mucous membranes, annoying reactions in immunocompetent patients, which subsides spontaneously in 10 days. Immunocompromised and previously uninfected individuals are highly susceptible to infection [1]. Genital lesions can develop through orogenital contact [2].


Herpes labialis affects more than 30% of people around the world [3] and accounts for a wide spectrum of ailments from annoyance to death. Records show an annual incidence rate of 1.6 per 1000 patients and an annual prevalence rate of 2.5 per 1000 patients [4]. Relapses occur in about 30% of all infected patients [5]. Data from different countries show HSV-1 serology between 56 to 85% in early adulthood [6] [7]. The epidemiology of HSV-1 has changed in recent years, thus, from the traditionally non-sexual transmission, it has become a preeminent cause of primary genital HSV infections [8].

Sex distribution
Age distribution


Infection is initiated when HSV, a double-stranded DNA virus, enters the human body through abraded skin on the lips or intact oral mucosa [3]. HSV infects and replicates in epithelial cells which break up (cytolytic infection) releasing clear fluid with virus particles, then forming vesicles and merging with other cells becoming multinucleated giant cells.

HSV migrates to sensory nerve ganglia (trigeminal ganglion) where it remains as a latent lifelong virus infection and serving as a source of relapses [3]. Virus reactivation is triggered by stimuli such as trauma, immunodeficiency, fever, sunlight, menstruation, and sexual intercourse [3] [9] [10]. The role of emotional stress in HSV recurrence is not clear [11]. Reactivated virus returns to the oral epithelium to initiate a new infectious cycle. HSV infects and multiplies in both neurons and epithelial cells. Reactivated virus from the trigeminal ganglion affects the face, the oropharyngeal and ocular mucosae [12].


  • Awareness and avoidance of known stimuli that predispose to recurrent episodes.
  • Personal hygiene to prevent acquiring or passing the infection unknowingly [22].
  • Avoiding contact with persons with active infections and vice versa [22] [23].
  • Abstinence from oral and sexual contact.


Herpes simplex labialis is a common infection of the lips. It is manifested by ulcerations on the vermilion border of the lip and oral mucosa, which are highly contagious, cause pain, discomfort, or disfigurement and likely to recur since the virus which remains dormant in the trigeminal ganglion can become activated and initiate new infection.

Patient Information

  • Herpes labialis (cold sores) is a common infectious condition of the lip and oral mucosa caused by herpes simplex virus type-1 (HSV-1), reported worldwide.
  • Most patients experience full or partial recovery from primary HSV-1 infection spontaneously after 2 to 3 weeks. 
  • Treatment with topical applications  (e.g., zinc oxide, zinc sulfate, anesthetic, antiviral cream) helps lessen pain and the duration of symptoms if applied early.
  • Antiviral drugs can be prescribed if needed to mitigate the effects of HSV infection, to prevent complications and recurrences.
  • About one-third of all patients will experience relapses due to reactivation of the virus from the trigeminal ganglion. HSV migrates to the  sensory nerve ganglia after a primary infection, thereupon, remaining dormant until it is reactivated by some stimuli, then, to initiate new infections in the orofacial mucosa. 
  • Avoid contact with infected persons and vice versa (that is, transmitting the infection to others), through casual touch, kissing, or sexual intercourse.



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  2. Scoular A, Norrie J, Gillespie G, Mir N, Carman WF. Longitudinal study of genital infection by herpes simplex virus type 1 in Western Scotland over 15
    years. BMJ. 2002 Jun 8;324(7350):1366-7.
  3. Whitley RJ, Kimberlin DW, Roizman B. Herpes simplex viruses. Clin Infect Dis. 1998;26:541–55.
  4. Van der Linden MW, Westert GP, De Bakker DH, Schellevis FG. Second national study into diseases and actions in general practice. Utrecht, Bilthoven: Netherlands Institute for Health Services Research (NIVEL), National Institute of Public Health and the Environment (RIVM); 2004.
  5. Embil JA, Stephens RG, Manuel FR. Prevalence of recurrent herpes labialis and aphthous ulcers among young adults on six continents. Can Med Assoc J. 1975 Oct 4;113(7):627-30.
  6. Hellenbrand W, Thierfelder W, Müller-Pebody B, Hamouda O, Breuer T. Seroprevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in former East and West Germany, 1997-1998. Eur J Clin Microbiol Infect Dis. 2005 Feb. 24(2):131-5.
  7. Singh AE, Romanowski B, Wong T, Gourishankar S, Myziuk L, Fenton J, et al. Herpes simplex virus seroprevalence and risk factors in 2 Canadian sexually transmitted disease clinics. Sex Transm Dis. 2005 Feb. 32(2):95-100.
  8. Stanberry LR, Jorgensen DM, Nahmias AJ. Herpes simplex viruses 1 and 2. In: Evans AS, Kaslow R, eds. Viral infections of humans: epidemiology and control. 4th ed. Plenum Publishers; New York: 1997: 419–54.
  9. Annunziato PW, Gershon A. Herpes simplex virus infections. Pediatr Rev. 1996;17:415–24.
  10. Clark JL, Tatum NO, Noble SL. Management of genital herpes. Am Fam Physician. 1995;51:175–82.
  11. Green J, Kocsis A. Psychological factors in recurrent genital herpes. Genitourin Med. 1997;73:253–8.
  12. Wheeler CE Jr. The herpes simplex problem. J Am Acad Dermatol. 1988 Jan;18(1Pt 2):163-8.
  13. Esmann J. The many challenges of facial herpes simplex virus infection. J Antimicrob Chemother. 2001 Feb;47 Suppl T1:17-27.
  14. Straus SE, Rooney JF, Sever JL, Seidlin M, Nusinoff-Lehrman S, Cremer K. NIH Conference. Herpes simplex virus infection: biology, treatment, and prevention.
    Ann Intern Med. 1985 Sep;103(3):404-19.
  15. Opstelten W. Minor ailments in children. In: Eekhof JAH, Knuistingh Neven A, Verheij TJM, eds. Stomatitis herpetica. Maarssen, The Netherlands: Elsevier; 2005: 273–5.
  16. 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; quiz 764-6.
  17. Daniels CA, LeGoff SG. Shedding of infectious virus/antibody complexes from vesicular lesions of patients with recurrent herpes labialis. Lancet. 1975 Sep
  18. Kaufman HE, Azcuy AM, Varnell ED, Sloop GD, Thompson HW, Hill JM. HSV-1 DNA in tears and saliva of normal adults. Invest Ophthalmol Vis Sci. 2005 Jan. 46(1):241-7.
  19. Gonsalves WC, Chi AC, Neville BW. Common oral lesions: Part I. Superficial mucosal lesions. Am Fam Physician. 2007 Feb 15;75(4):501-7.
  20. Worrall G. Herpes labialis. BMJ Clin Evid. 2009 Sep 23;2009. pii: 1704.
  21. Woo SB, Challacombe SJ. Management of recurrent oral herpes simplex infections. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Mar;103
  22. Herpes labialis. National Library of Medicine. Available at: www.nlm.nih.gov/medlineplus/ency/article/000606.htm. Accessed January 18, 2007.
  23. da Silva LM, Guimaraes AL, Victoria JM, et al. Herpes simplex virus type 1 shedding in the oral cavity of seropositive patients. Oral Dis. 2005;11:13-16.

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Last updated: 2019-07-11 21:55