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

Orofacial herpes simplex virus in Adult

See also in: Oral Mucosal Lesion
Contributors: Sujitha Yadlapati MD, Belinda Tan MD, PhD, 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 aged between 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
Copyright © 2023 VisualDx®. All rights reserved.
Patient Information for Orofacial herpes simplex virus in Adult
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Contributors: Medical staff writer


Herpes simplex infection of the mouth and face, also known as orofacial herpes simplex, herpes labialis, cold sores, or fever blisters, is a common infection caused by the herpes simplex virus (HSV). Infections with HSV are very contagious and are spread by direct contact with the skin lesions. There are 2 types of HSV: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). Infections around the mouth, lips, nose, or face are most commonly caused by HSV-1 but can be caused by HSV-2. Both HSV-2 and HSV-1 are common causes of infection of the genitals or buttocks.

HSV causes what is known as a primary infection in most people who are exposed to the virus. Appearing 2-12 days after a person's first exposure to HSV, the sores of the primary infection last about 1-3 weeks. In the case of orofacial HSV, the sores are usually scattered inside the mouth and are small and painful. These sores will heal completely, but the virus remains in the body, hibernating (latent) in nerve cells.

Certain triggers can cause the hibernating virus to wake up, become active, and travel back to the skin. This is known as recurrent HSV. Recurrent HSV infections may develop frequently (every few weeks), or they may rarely develop. Recurrent infections are milder than primary infections and generally occur in the same general location each outbreak. Recurrent HSV usually appears as a group of blisters (tiny, raised fluid-filled bumps), usually on the lips or around the mouth and nose. These tiny blisters may be preceded by papules (smooth, solid bumps). The papules appear pink or red in lighter skin, and in darker skin, the redness may be more subtle.

Most people get cold sores as children, through contact with a friend or family member who is already infected with HSV. It can be spread (transmitted) by kissing, sharing eating utensils or drinking glasses, or by using personal care items such as the same towel.

Who’s At Risk

HSV infections occur in people of all races / ethnicities, ages, and sexes. Up to 80% of Americans are infected with HSV-1 by the time they are 30.

Signs & Symptoms

The most common location for primary orofacial HSV infection is inside the mouth. For recurrent HSV, locations include the:
  • Lips.
  • Nose.
  • Chin.
  • Cheeks.
There may also be sores inside the mouth, especially if your immune system has been affected, such as by cancer or HIV, or if you have undergone organ transplantation.

In primary HSV, there are painful sores anywhere inside the mouth. The lymph nodes in the neck may or may not be swollen. In severe cases of HSV infection, cold sores may involve the entire lining of the mouth and both lips. These severe infections may be accompanied by fever, sore throat, foul breath, and difficulty eating.

In recurrent HSV infection, there may be one or more tiny blisters that break open and form a scab. Some people experience a warning that blisters are about to appear (called a prodrome), such as tingling or burning of the area. Then, papules appear, followed by blisters.

Additionally, some people never develop the symptoms of a primary HSV infection and may mistake a recurrent infection for a primary infection. A recurrent infection typically lasts 7-10 days. As it fades, it may leave a pink, purplish, or brownish color in lighter skin colors. In darker skin colors, HSV may fade to leave a darker brown color. People who are prone to recurrent outbreaks tend to get them 3-4 times per year.

Triggers of recurrent HSV infections include:
  • Fever or illness.
  • Sun exposure.
  • Hormonal changes, such as those due to menstruation or pregnancy.
  • Stress.
  • Trauma, such as that caused by dental work or cuts from shaving.
  • Surgery.

Self-Care Guidelines

Acetaminophen (Tylenol) and ibuprofen (Advil, Motrin) may help reduce fever, muscle aches, and pain caused by cold sores. Try to drink as many fluids as possible to prevent dehydration. Applying ice packs may relieve some of the swelling and discomfort.

Because HSV is very contagious, it is important to take the following steps to prevent spread (transmission) of the virus during the prodromal phase (burning, tingling, or itching) and active phase (presence of blisters or sores) of HSV infections:
  • Avoid sharing cups and eating utensils.
  • Avoid kissing and performing oral sex.
  • Avoid sharing lip balm and lipstick.
  • Avoid sharing razors, towels, and other personal care items.
  • Wash your hands with soap and water if you touch an active lesion.
Unfortunately, the virus can still be transmitted, even when someone does not have active lesions.

When to Seek Medical Care

If you develop tender, painful sores in the mouth or on the lips or nose, see a health professional.

Contact your health professional immediately if an HSV outbreak has not gone away in 2 weeks, if you are avoiding eating or drinking because of the pain, or if you develop blisters or sores near your eye.

If you have an underlying medical condition such as cancer or HIV, or if you have undergone organ transplantation, you are at higher risk for more serious complications. Seek medical advice as soon as possible, especially if you are at risk for more serious complications.


Most HSV infections are easy for health professionals to diagnose. On occasion, however, a swab from the infected skin may be sent to a laboratory for viral culture, which takes a few days to grow. Blood tests may also be performed.

Untreated HSV infections will go away on their own, but medications can reduce the symptoms and shorten the duration of outbreaks. There is no cure for HSV infection.

Primary HSV can be treated with oral antiviral medication, such as acyclovir (Zovirax), valacyclovir (Valtrex), or famciclovir (Famvir).

More severe primary HSV infections may require additional medications, for example, a topical anesthetic such as viscous lidocaine, if the areas inside the mouth are very painful. In addition, very severe infections may require intravenous (IV) fluids and even IV antiviral medications or painkillers if the pain prevents you from drinking fluids.

For recurrent HSV, these same oral antiviral medications may help to shorten the outbreak and make it less severe, if taken at the first signs of the outbreak, such as when the prodrome or blisters first appear. People who experience prodromes before recurrent infections may benefit from episodic treatment.

Other people have recurrent infections that are frequent enough or severe enough to justify suppressive therapy, in which medications are taken every day to decrease the frequency and severity of attacks.
Copyright © 2023 VisualDx®. All rights reserved.
Orofacial herpes simplex virus in Adult
See also in: Oral Mucosal Lesion
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.
Copyright © 2023 VisualDx®. All rights reserved.