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MariaSiponen

Viral Infections of the Oral Mucosa

Essentials

  • Viral infections may cause many different looking changes on the oral mucosa.
  • Ulcerating vesicles are caused by Herpes simplex (HSV), varicella zoster (VZV) and coxsackie viruses.
  • Petechiae appear in the pharyngeal area in mononucleosis caused by the Epstein-Barr virus (EBV). In immunosuppressed states, EBV may also cause white coated patches on the side of the tongue, i.e. oral hairy leukoplakia.
  • Various subtypes of human papillomavirus (HPV) cause either cauliflower-like (papilloma, condyloma, common wart) or smooth (Heck's disease) hyperplasias.
  • Some papillomaviruses are also associated with squamous cell carcinoma of the base of the tongue and in the pharyngeal area.

Herpes simplex virus (HSV)

  • Infections of the oral mucosa are usually caused by Herpes simplex virus (HSV) type 1. About 10-15% are caused by HSV-2.

Primary infection

  • In almost 99% of the cases the primary infection is asymptomatic or mildly symptomatic.
  • Primary infection is usually contracted in childhood, sometimes only after the age of 20 years.
  • In 1% of patients, primary oral HSV infection presents with a fulminant febrile stomatitis, in which painful blisters appear in both the gingival region and elsewhere in the oral mucosa (gingivostomatitis; picture 1). The infection may be carried by saliva to the skin around the mouth.

Recurrent HSV infection

  • Recurrence begins as a reddish itching area where clear, small and rapidly rupturing blisters develop. These result in superficial ulcers. Recurring herpes in the mouth cavity is usually located in the gingival rim and in the palate. The ulcers heal spontaneously in about one week.
  • Among the factors activating HSV-1 are common cold, exposure to excessive sunlight, stress or even menstruation. Impaired immunity (e.g. HIV infection, blood transfusion, cancer patients on cytostatic treatment) predisposes to frequent recurrence of HSV and to increased duration of the symptomatic phase.

Diagnosis

  • The diagnosis of oral HSV infection is made on the basis of the clinical appearance, or by demonstrating the virus in the scrape from the base of a blister by antigen detection, virus culture or gene cloning method. A cytological or biopsy specimen typically shows "raspberry-like" multinuclear epithelial cells where the virus can be demonstrated also immunohistochemically.
  • Examination of serum antibodies is useful only for demonstrating primary HSV infection.

Treatment Aciclovir and Valaciclovir in the Prevention and Treatment of Herpes Simplex Virus in Patients Being Treated for Cancer

Herpes varicella-zoster virus (VZV)

  • In varicella, in addition to the generalized rash with small pustules all over the body, small, yellowish blisters that rupture easily are sometimes found on the oral mucosa, most often in the palate.
  • Of all herpes zoster infections Shingles (Herpes Zoster), 20% appear in the head and neck region. In the area of the nerves innervating the maxilla and the mandible, herpes zoster often starts with pain localized in the teeth (simulating the pain of inflammatory dental pulpitis). After 3-4 days this is followed by the appearance of blisters both inside and outside the oral cavity. As in zoster elsewhere, the blisters do not cross the middle line of the body (except in the palate).

Diagnosis

  • The clinical picture is typical enough to enable a correct diagnosis.
  • If needed, VZV can be demonstrated from the base of a blister by antigen detection, virus culture or gene cloning method.

Treatment

Enterovirus infections

Herpangina

  • Caused by Coxsackie A virus
  • This disorder appears as epidemics (summer and early autumn), usually among children.
  • Symptoms include fever, malaise, abdominal pains, headache and muscular pain. The generalized symptoms appear before the oral symptoms.
  • Oral symptoms include blisters on the palatal arch, soft and hard palate, uvula and tonsils http://www.dynamed.com/condition/herpangina#HEENT. At the onset, the blisters are small and surrounded by a clear halo. They gradually increase in size and heal spontaneously in 4-6 days. The throat is diffusely reddened.
  • The diagnosis is clinical, or the enteroviruses may be detected by virus culture.
  • Differential diagnosis
    • In herpangina, no bullae appear in the gingival area, unlike in HSV infections.
    • HSV lesions also last markedly longer and are painful in contrast to those of herpangina.
    • With herpetiform aphthae, there are no blisters nor general symptoms.
    • In streptococcal tonsillitis, there are no blisters nor diffuse pharyngitis, and the general symptoms are more severe.

Hand-foot-and-mouth disease

Papillomaviruses (HPV)

  • Currently, over 100 different types of human papillomavirus (HPV) are recognized, of which some cause infections only on the skin and other types exclusively at mucosal sites. The oral mucosa is special in that it is capable of harbouring HPV infections of both the genital types (e.g. HPV 6, 11, 16, 18, 31, 33, 42) and the skin types (e.g. HPV 2, 4, 7, 57).
  • Exophytic, cauliflower-like warts (papillomas, condylomas) are encountered on the oral mucosa of some 0.4% of the population. In children, common hand warts can be transmitted to the oral mucosa, following sucking of the fingers.
  • The aetiological agent of another characteristic HPV lesion, focal epithelial hyperplasia (FEH) is HPV 13 or HPV 32. These lesions are multiple, smooth and resemble a small fibroma.
  • In addition to these well-defined clinical lesions, HPVs can also appear on healthy oral mucosa as latent infections (in around 12% of subjects).
  • HPV infection has been established as a risk factor for oral cancer mainly in the pharyngeal and tongue root region.
  • Diagnosis is based on the clinical appearance and on characteristic morphological HPV-induced squamous cell changes in a histological biopsy specimen.
  • Treatment
    • Some of these lesions resolve spontaneously. When appropriate, surgical excision may be carried out, or the lesions can be eradicated by using laser or cryotherapy. Whenever dysplastic changes are detected in the biopsy, careful follow-up of the patient is warranted.

Epstein-Barr virus (EBV)

Infectious mononucleosis (kissing disease)

  • In typical cases, the symptoms include fever, enlarged cervical and axillary lymph nodes (due to lymphadenitis), and an exudative tonsillitis that does not respond to penicillin. Sometimes, painful ulcers appear in the gingival area or petechiae on the palate. The infection is often associated with enlargement of the spleen and prolonged periods with fever. In 15% of cases, eyelid swelling is seen in the initial phase of the disease.
  • Diagnosis
    • If the rapid tests determining heterophilic antibodies remain negative, EBV-specific antibodies in the serum are analysed. EBV infection increases the number of mononuclear cells in the blood. If needed, EBV can be demonstrated in a tissue specimen by using immunohistochemistry or nucleic acid hybridization.
  • Oral changes due to mononucleosis do not require any active treatment.

Hairy leukoplakia

  • This is characteristically a lesion with a whitish covering on the tongue that in most cases affects both sides of the tongue symmetrically, starting from its posterior third. The aetiological factor has been confirmed to be EBV.
  • This lesion clearly associates with immunosuppressive states (of any cause), and is quite common in HIV infected subjects 3. Along with the implementation of the HAART treatment HIV Infection the occurrence of hairy leukoplakia has decreased.
  • The clinical hairy leukoplakia lesion is asymptomatic and according to current understanding it is completely harmless because, for example, no dysplastic changes are detected in biopsy. In HIV patients, however, the appearance of hairy leukoplakia is considered a sign of a poor outcome.
  • The differential diagnosis should take into account hyperkeratotic lesions due to mechanical irritation, fungal infections and lichen planus lesions.
  • The clinical picture and histological presentation are typical.
  • The lesion does not require any treatment http://www.dynamed.com/condition/oral-lesions#TOPIC_UQH_YVW_54B. In some cases, aciclovir has been administered according to the scheme used in the treatment of HSV infections.

References

  • Arduino PG, Porter SR. Oral and perioral herpes simplex virus type 1 (HSV-1) infection: review of its management. Oral Dis 2006;12(3):254-70. [PubMed]
  • de Paula Eduardo C, Aranha AC, Simões A et al. Laser treatment of recurrent herpes labialis: a literature review. Lasers Med Sci 2013;():. [PubMed]
  • Patton LL, Ramirez-Amador V, Anaya-Saavedra G et al. Urban legends series: oral manifestations of HIV infection. Oral Dis 2013;19(6):533-50. [PubMed]
  • Al-Maweri SA, Kalakonda B, AlAizari NA ym. Efficacy of low-level laser therapy in management of recurrent herpes labialis: a systematic review. Lasers Med Sci 2018;33(7):1423-1430. [PubMed]
  • de Almeida VL, Lima IFP, Ziegelmann PK ym. Impact of highly active antiretroviral therapy on the prevalence of oral lesions in HIV-positive patients: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2017;46(11):1497-1504. [PubMed]
  • Syrjänen S. Oral manifestations of human papillomavirus infections. Eur J Oral Sci 2018;126 Suppl 1():49-66. [PubMed]
  • Carmona Lorduy M, Harris Ricardo J, Hernández Arenas Y ym. Use of trichloroacetic acid for management of oral lesions caused by human papillomavirus. Gen Dent 2018;66(2):47-49. [PubMed]

Evidence Summaries ⬆