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Orofacial herpes simplex virus - Oral Mucosal Lesion
See also in: Overview
Other Resources UpToDate PubMed

Orofacial herpes simplex virus - Oral Mucosal Lesion

See also in: Overview
Contributors: Susan Burgin MD, Belinda Tan MD, PhD, Carl Allen DDS, MSD, Sook-Bin Woo MS, DMD, MMSc
Other Resources UpToDate PubMed


Orofacial herpes simplex virus (HSV) infections are common and should be considered within the differential diagnosis of a patient presenting with facial vesicles or crusts or alternatively intraoral vesicles, erosions, or ulcers. Though usually an infection of herpes simplex virus type 1 (HSV-1), orofacial infection can be caused by herpes simplex virus type 2 (HSV-2). Oral infection with HSV-2 is more frequent in patients with human immunodeficiency virus (HIV). Either virus may be involved in genital infections.

HSV is highly contagious. It is spread by direct contact with the lesions. Childhood infection is common via child-to-child contact or kissing by a parent. Primary herpetic gingivostomatitis is an acute infection of the oral mucous membranes by HSV that results from initial exposure to the virus. Most primary exposures (approximately 90%) are subclinical and asymptomatic. Symptomatic primary infection manifests in the first and second decade of life. Patients experience a flu-like illness with fever, loss of appetite, malaise, and lymphadenopathy. Painful mouth sores and a sore throat develop, and difficulty eating and swallowing places the patients at risk for dehydration. The systemic and oral signs and symptoms develop within days of each other.

The virus establishes life-long latency and both asymptomatic reactivation as well as recrudescence are common. In recrudescence, patients report a prodrome of burning, itching, and a tingling sensation before the actual lesions appear. HSV recrudescence on the lips is also known as cold sores, fever blisters, or herpes labialis; inside the mouth, lesions only occur on the keratinized tissues of the tongue dorsum, hard palatal mucosa, and gingiva in healthy hosts, but may occur on any surface in the immunocompromised host. Intraoral involvement in recrudescent disease in immunocompetent hosts is rare.

HSV can also disseminate, occurring on skin areas distant from the lips. Two general groups of patients are at risk to develop disseminated HSV: patients with underlying skin disease and immunocompromised patients. Pregnant individuals with primary HSV infection are at increased risk for severe illness, ie, dissemination and hepatitis, particularly in the third trimester.

Localized HSV in areas other than the face and mouth, such as herpetic whitlow, are discussed separately. Other related topics include HSV gladiatorum, neonatal HSV, HSV conjunctivitis, HSV blepharitis, HSV keratitis, HSV encephalitis, and HSV pneumonia.


B00.1 – Herpesviral vesicular dermatitis

235055003 – Oral herpes simplex infection

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Differential Diagnosis & Pitfalls

  • Aphthous stomatitis – This is a common recurrent ulcerative condition, most often misdiagnosed as recrudescent herpes infection. Aphthous ulcers almost always involve only the nonkeratinized mucosa while recrudescent herpes simplex almost always involves the keratinized mucosa in healthy hosts.
  • Herpes zoster – Presents unilaterally in general without crossing the midline; culture differentiates between the two.
  • Contact dermatitis (irritant, allergic)
  • Contact stomatitis – A history of recurrent ulcers or blisters caused by contactant differentiates between the two.
  • Herpangina – This tends to occur in spring or fall and in epidemics. Oral ulcers tend to localize to the back of the mouth and oropharynx.
  • Erythema multiforme – A history of herpes simplex infection is often elicited 2-3 weeks prior to the appearance of these oral ulcers.
  • Impetigo
  • Hand-foot-and-mouth disease – Involvement of the palm and dorsa of feet is characteristic.
  • Stomatitis associated with chemotherapy (see chemotherapy-induced mucositis) – These lesions occur within 7-10 days of the beginning of chemotherapy; however, HSV may recrudesce within these lesions.
  • Stevens-Johnson syndrome – Typical skin findings as well as severe oral ulcerations differentiate this from herpes simplex infection.
  • Pemphigus vulgaris – These oral ulcers and erosions usually do not heal completely but rather get better and worse.
  • Acute necrotizing ulcerative gingivitis – These may resemble recrudescent herpes simplex because ulcers and necrosis are located on the keratinized gingiva. Culture differentiates between the two.
  • Differential diagnosis of herpetic geometric glossitis: fissured tongue.
With primary HSV infection, fever and systemic complaints are more extensive than in immunobullous diseases such as pemphigus.

In pediatric patients also consider:

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Last Updated:08/12/2021
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Orofacial herpes simplex virus - Oral Mucosal Lesion
See also in: Overview
A medical illustration showing key findings of Orofacial herpes simplex virus : Crust, Grouped configuration, Oral erosions, Recurring episodes or relapses, Pharyngitis, Umbilicated vesicles
Clinical image of Orofacial herpes simplex virus - imageId=428508. Click to open in gallery.  caption: 'Grouped vesicles with a background of erythema and edema on the right upper lip.'
Grouped vesicles with a background of erythema and edema on the right upper lip.
Copyright © 2023 VisualDx®. All rights reserved.