Herpes simplex orofacial infection

Herpesviral vesicular dermatitis
Herpes lesion on upper lip and face

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

Overview

• 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.

Epidemiology

• Based on a study, lifetime prevalences of herpes simplex orofacial infection are 42.1% and 32.4%, in women and men, respectively. Moreover HSV1 prevalence was estimated 50.3%.

Clinical Presentations

• A majority of primary HSV-1 infections occur during childhood and if the virus comes into contact with the mucosa or abraded skin, it can cause acute herpetic gingivostomatitis (inflammation of the cheek's mucosa and gums) within 5–10 days. Some other symptoms may also develop, including fever and sore throat, and painful ulcers may appear.
• Prodromal symptoms often precede a recurrence, which typically begins with reddening of the skin around the infected site, with eventual ulceration to form fluid-filled blisters that affect the lip (labial) tissue and the area between the lip and skin (vermillion border).
• Primary HSV infection in adolescents frequently manifests as severe pharyngitis with lesions developing on the cheek and gums. Some individuals develop difficulty in swallowing (dysphagia) and swollen lymph nodes (lymphadenopathy). Primary HSV infections in adults often presents as pharyngitis similar to that observed in glandular fever (infectious mononucleosis), but gingivostomatitis is less likely. The symptoms of primary HSV infection generally resolve within two weeks.

Disease Progression And Recurrence

• 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.
• The recurrent infection is thus often called herpes simplex labialis. Rare occasions of reinfections occur inside the mouth (intraoral HSV stomatitis), affecting the gums, alveolar ridge, hard palate, and the back of the tongue. This may be accompanied by herpes labialis.
• It seems that some factors are responsible for recurrent herpes simplex infection due to decreasing the cell mediated immunity (either antigen dependent or no antigen dependent). the following list contains some of these factors:
  • Other viral infections with fever
  • Fatigue
  • Menstural period
  • Stress
  • Local trauma
  • Ultraviolet light
  • Local injury due to high temprature or frostbite

• Oral herpes is spread by direct contact with an active sore in an infected person, for instance, by kissing. However, the virus can be transmitted through the skin in the absence of a lesion.
• Oral herpes and cold sores can sometimes be confused with canker sores.

Differential diagnosis

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

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Dentures users Poor controlled diabetes Medication's adverse effect, most commonly due to antibiotics and inhaled corticosteroids (treatment of lung conditions such as asthma or COPD) can result in oral candidiasis. (It may be reduced by regularly rinsing the mouth with water after taking the medication) Patients with poor nutrition, especifically vitamin A, iron and folate deficiencies. Patient with Immunodeficiency (such as AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	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	Fever Sore throat Painful ulcers	Stress Recent URTI Female gender	Physical examination Viral culture Tzanck smear	Orofacial infection Anogenital infection Ocular infection Herpes encephalitis Neonatal herpes Herpetic whitlow Herpes gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Female gender Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	It is elf-limiting and pain usually decreases in 7 to 10 days, with a complete healing in 1 to 3 weeks	By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia	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	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive subtype with multiple lesions and higher conversion to warts or carcinoma	Leukoplakia - By Aitor III - Own work, Public Domain, https://commons.wikimedia.org/w/index.php?curid=9873087
Melanoma	A lesion with ABCD: Asymmetry Border irregularity Color variation Diameter changes (or diameter more than 6 mm) Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	Presence of ABCD characteristics Bleeding or ulceration may be related to malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved	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	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for patients primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster	Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is mild in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical examination Types: Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic patients	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	Painful mouth sores Acne like skin lesions Headache, fever, poor balance and disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Overactive immune system	Physical examination	Mouth Genitals Gastrointestinal tract Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels	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	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibody (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro liter Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types: Drug-induced Malignant Autoimmune
Syphilis	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Homosexual men Residence in highly prevalent areas HIV infection Presence of other Sexually transmitted diseases Previous history of Sexually transmitted diseases Intravenous drug use	Dark field microscopy Non treponemal tests like VDRL and RPR test) Treponemal tests, such as FTA-ABS tests, TPPA assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis	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	Fever Sores in the mouth Rash with blisters Aches	Pregnancy Immunodeficiency	History and physical examination Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh equal to 1000 grams Immunocompromised	History and physical examination PCR to detect VZV in skin lesions (such as vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated	Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles	Fever Rash Cough Rhinorrhea (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals 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	History and physical examination PCR for measles-specific IgM antibody PCR for measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles	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

• Leukemia:
  • Herpes simplex orofacial infection has been reported in 40% of patients with acute leukemia.

Treatment

• Based on a double-blind, placebo controlled, randomized trial done on patients with recurrent herpes simplex orofacial infection showed efficacy of 5% acyclovir cream containing propylene glycol in reducing the period of vesiculation (P = 0.016), healing time (P = 0.022) and itching duration.