Herpes simplex orofacial infection

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Herpesviral vesicular dermatitis
Herpes lesion on upper lip and face

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Orofacial Infection
Anogenital Infection
Ocular Infection
Herpes Encephalitis
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Epidemiology and Demographics

Asymptomatic Shedding

Recurrences and Triggers

Natural History, Complications and Prognosis


History and Symptoms

Physical Examination

Laboratory Findings

Direct detection of Genital Lesions


Antiviral Therapy

Antivirals for First Episode of Genital Herpes
Antivirals for Recurrent Genital Herpes

Primary Prevention


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Anahita Deylamsalehi, M.D.[2] ; Cafer Zorkun, M.D., Ph.D. [3]


Infection by HSV-1 is the most common cause of herpes that affects the face and mouth (orofacial herpes), although within the recent years an increase in oral HSV-2 infections has been reported. Studies demonstrated different rate of herpes simplex orofacial infection prevalence in different populations, nevertheless lifetime prevalences of herpes simplex orofacial infection has been estimated 42.1% and 32.4%, in women and men, respectively. There are some evidences that report higher rate of herpes simplex orofacial infection in low socioeconomic status. A majority of primary HSV-1 infections occur during childhood. Early HSV infection could be asymptomatic without any obvious skin lesions. Transmission commonly occurs when infection source comes in contact with the mucosa or abraded skin. However there are other rout of transmission such as infants born to infected mothers who are also at risk of catching the HSV-1 during the delivery. The estimated duration of primary HSV infection has been estimated between 2-20 days after contact with the source of infection. Skin involvement usually appear as grouped ulcers or vesicles on an erythematous base. Subsequently skin vesicles may ulcerate and then become crusted. Primary HSV infection in adolescents frequently manifests as severe pharyngitis with lesions developing on the cheek and gums. Some individuals develop difficulty in swallowing. Once a primary oral HSV-1 infection has resolved, the HSV enters the nerves surrounding the primary lesion, migrates to the cell body of the neuron, and becomes latent in the trigeminal ganglion. In some patients, the virus reactivates to cause recurrent infection, which is more common with HSV-1 than HSV-2 oral infection. Even though trigeminal ganglion is the most common location for HSV-1 infection, inferior and superior cervical ganglia could also become infected with this serotype of herpes simplex. Prodromal symptoms often precede a recurrence, which typically begins with reddening of the skin around the infected site. Pain, itching and paresthesia are some of the other prodromal symptoms in herpes simplex infection. Duration of the prodromal symptoms can range between few hours to several days before lesions develop. Some factors such as concurrent viral infection, trauma, menstural period, fatigue, stress and sun exposure could trigger recurrent herpes simplex lesions. It has been estimated that patients with HSV-1 orofacial infection could experience recurrent infections 1-6 times in a year. Each episode of orofacial infection is less sever and shorter, compared to previous episodes of orofacial infections. There are numerous differential diagnosis such as oral candidiasis, aphthous ulcers, squamous cell carcinoma, leukoplakia, behcet's disease, crohn's disease and burning mouth syndrome. Some conditions such as leukemia, bell's palsy, chronic atopic dermatitis and Human immunodeficiency virus infection have been known as associated conditions in orofacial herpes. Orofacial herpes simplex infection is usually diagnosed clinically, nevertheless PCR test, immunodot glycoprotein G-specific (IgG) test, skin biopsy, virus culture and direct fluorescent anti body (DFA) studies are some of the available laboratory investigations to better diagnose orofacial infection due to herpes simplex. Unfortunately there is no approved treatment to completely eradicate the herpes simplex virus from body. Nevertheless antiviral treatments have been successful in lowering the severity and duration of skin lesions. The available antiviral drugs that can be used for herpes simplex infection include acyclovir, valaciclovir, famciclovir and penciclovir. Acyclovir is effective in decreasing the viral shedding period in infected patients (median of 2.5 days when patients received acyclovir, compared to 17 days). It also has been reported to be efficient in augmenting pain resolution and healing of the skin lesions.


Clinical Presentations

HSV-1 infection of external ear and adjacent periauricular area in an immunodeficient patient which resembles knife cuts.[10]

Disease Progression And Recurrence

Differential diagnosis

Herpes simplex orofacial infection must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.[29]

Disease Presentation Risk Factors Diagnosis Affected Organ Systems Important features Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis
  • Clinical diagnosis
  • Confirmatory tests rarely needed
Localized candidiasis

Invasive candidasis

Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions
Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers
  • It is elf-limiting and pain usually decreases in 7 to 10 days, with complete healing in 1 to 3 weeks
By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma
Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots
Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome
Torus palatinus
Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease
Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease
oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus Hand-foot-and-mouth disease
Chicken pox
Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
  • Unvaccinated individuals[33][34]
  • Crowded and/or unsanitary conditions
  • Traveling to less developed and developing countries
  • Immunocompromized
  • Winter and spring seasons
  • Born after 1956 and never fully vaccinated
  • Health care workers
Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483

Associated Conditions




Unfortunately, there is no approved treatment to completely eradicate the herpes simplex virus from the body. Nevertheless, antiviral treatments have been successful in lowering the severity and duration of skin lesions. Soft, smooth, and cold foods are helpful in lowering the symptoms severity during meals.

Antiviral drugs

Famciclovir - Single dose Famciclovir - Single day Placebo
Median Healing Time (days) 4.4 4 6.2

There is no significant difference in famciclovir single dose or famciclovir single day treatement, based on the mentioned study.


Topical Anesthetics

Topical Corticosteroids

Future or Investigational Therapies

  • There have been some investigations of a vaccine to prevent orofacial herpes simplex infection. Attacking messenger RNA (mRNA) of essential HSV-1 genes (such as UL20 gene) is how one of the investigated vaccines works. The aforementioned vaccine has been studied on rabbits and showed lower risk of ocular infection due to HSV-1 in them. [59]
  • Another idea which requires more study to be approved suggests a medication (such as antagomir) to force all copies of HSV-1 virus to become active at a same time (from the latent status). Since there would be no latent virus in body, antiviral treatments could be successful in destroying the whole virus population.
  • Another possible treatment try to target microRNA in order to prevent viruses from become latent.
  • A study done on mice reported the possible effectiveness of phosphonoacetic acid in preventing skin lesion development. Based on this study phosphonoacetic acid prevented viruses from become latent when this ointment has been applied three times a day topically.
  • Oral or topical use of a new antiviral agent named 2'-Nor-2'-deoxyguanosine (2'NDG) on mice demonstrated reduced severity in orofacial lesions. Minimum effective dose has been estimated as 0.2 mg/kg per day in one study. [60]



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