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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: Sujitha Yadlapati MD, Belinda Tan MD, PhD, Carl Allen DDS, MSD, Sook-Bin Woo MS, DMD, MMSc, Susan Burgin MD
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. Although this is 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 HIV. Either virus may be involved in genital infections.

HSV is highly contagious. It is spread by direct contact with the lesions. 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. Herpetic gingivostomatitis occurs most often in children between ages 10 months and 5 years, but it can occur at any age. 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 lifelong 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 they 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 of developing 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 blepharitis, HSV conjunctivitis, HSV encephalitis, HSV gladiatorum, HSV keratitis, HSV pneumonia, and neonatal HSV.


B00.2 – Herpesviral gingivostomatitis and pharyngotonsillitis

235055003 – Oral herpes simplex infection

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Differential Diagnosis & Pitfalls

May affect both perioral and intraoral surfaces:
  • Herpes zoster – Oral findings of zoster may be secondary to involvement of the maxillary or mandibular branch of the trigeminal nerve (V2 or V3, respectively). The upper cutaneous lip, palate, and upper gingiva are involved in V2. The remainder of the V2 dermatome, including the cheek and temple, may also be involved. In V3 zoster, the tongue, lower gingiva, buccal mucosa, floor of the mouth, and lower cutaneous lip may be affected. Cutaneous involvement of V3 includes the chin, lower cheek over the mandible, preauricular area, and temporal scalp.
  • Erythema multiforme – A history of HSV infection is often elicited 2-3 weeks before the appearance of these oral ulcers.
  • Fixed drug eruption
  • Reactive infectious mucocutaneous eruption (RIME)
  • Stevens-Johnson syndrome – Typical skin findings as well as severe oral ulcerations differentiate this from HSV infection.
  • Paraneoplastic pemphigus
  • Oral erosive lichen planus – Lips may be involved with white, scaly papules or plaques.
  • Pemphigus vulgaris – These oral ulcers and erosions usually do not heal completely but rather get better and worse.
  • Behçet syndrome
Lip and perioral involvement only:
Intraoral involvement only:
  • 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 HSV almost always involves the keratinized mucosa in healthy hosts.
  • Contact stomatitis – A history of recurrent ulcers or blisters caused by a contactant differentiates between the two.
  • Hand-foot-and-mouth disease – Rare in adults; involvement of the palms 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.
  • Acute necrotizing ulcerative gingivitis – These lesions may resemble recrudescent HSV because ulcers and necrosis are located on the keratinized gingiva. Culture differentiates between the two.
  • Fissured tongue – On the differential for herpetic geometric glossitis.

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Last Reviewed:11/26/2022
Last Updated:12/08/2022
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Patient Information for Orofacial herpes simplex virus - Oral Mucosal Lesion
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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 (Recurrent Infection) : Face, Lips, Mouth
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.
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