Dr.

Tahani Abualteen

Infections of the Oral Mucosa I

Common oral mucosal infections: Viral infections Bacterial infections Fungal infections HIV infection and AIDS Viral infections: The following viruses may cause oral infections or oral manifestations: 1. Herpes viradae (family) or Human Herpes viruses: o Generally speaking, these viruses tend to produce an initial primary infection, get latent somewhere in the body and then they may be reactivated for a reason or another to cause recurrent or secondary infections o These viruses include: Herpes Simplex (HSV) type 1 causing herpetic stomatitis (primary/recurrent) Herpes Simplex (HSV) type 2 causing herpetic stomatitis (primary/recurrent) Varicella Zoster (VZV) causing chickenpox (primary) & shingles "herpes zoster" (recurrent) Epstein-Barr virus (EBV) causing infectious mononucleosis "glandular fever" and hairy leukoplakia Cytomegalovirus (HHV5) causing cytomegalovirus infection Human Herpes Virus 6 (HHV6) not common Human Herpes Virus 7 (HHV7) not common Human Herpes Virus 8 (HHV8) thought to be associated with Kaposis sarcoma 2. 3. 4. 5. 6. Coxsackie A virus causing Herpangina and hand, foot & mouth disease Paramyxovirus causing measles and mumps (may be associated with non-specific stomatitis) Human Papilloma Virus (HPV) causing warts/epithelial hyperplasias Human Immunodeficiency Virus (HIV) Influenza Virus causing influenza (may be associated with non-specific stomatitis)

Lesions may be termed according to their size (depending on the 5mm or the 1 cm rule) Papule vs. nodule: Elevated Solid lesions Papule: small (< 5mm or 1 cm in diameter) Nodule: large (> 5mm or 1 cm in diameter) Macule vs. plaque: Represent areas distinguishable from surrounding tissue by color change, usually flat but may be slightly elevated Macule: small (< 5mm or 1 cm in diameter) Plaque: is larger (> 5mm or 1 cm in diameter) Vesicle vs. bulla: Elevated fluid-filled lesions Vesicle: small (<5mm or 1 cm in diameter) Bulla: large (> 5mm or 1 cm in diameter) 1/8

Dr. Tahani Abualteen

Herpes simplex virus (HSV): The most frequent cause of viral infections of the mouth There are two types of herpes simplex virus with serological, biological and clinical differences but they share the same histopathological features: o Type 1: is frequently associated with infections of the skin and oral mucosa o Type 2: is frequently associated with infections of the genitalia Primary Infection of HSV Type 1 (Acute Herpetic Gingivostomatitis): o Common infection o Occurs predominantly in young children (about 6 years of age) o Transmitted by droplet spread or contact with the lesion o The majority of cases are subclinical (causing no symptoms or just mild Pharyngitis) o However in some patients it presents as primary herpetic Gingivostomatitis (acute stomatitis with vesicles and ulcers) o The usual course of HSV Type 1 infection: 5 days incubation period, then: 2 days of Prodromal symptoms (acute onset of malaise, fever and lymphadenopathy) the disease process may stop here (subclinical case) or it may continue to result in: Multiple small vesicles (which can occur on any part of the oral mucosa and lips "keratinized & nonkeratinized") with widespread gingival inflammation (which is erythematous and edematous) Vesicles soon ulcerate and may become secondarily infected Circumoral crusting lesions on the lips may occur when the exudates (from ruptured vesicles) start to dry Extraoral lesions may also be present, particularly in children (for example: vesicles may occur on skin of chin as a result of drooling of saliva and on nail bed of fingers "herpetic whitlow" as a result of sucking, and on eyes as a result of rubbing) Herpes virus may be transmitted to fingers causing a primary infection which is extremely painful known as Herpetic whitlow this may arise in the same patient or in another person contacting the patient Mild Circumoral crusting

This infection is a self-limiting infection that usually takes 10-14 days to resolve (even if the patient has been given antibiotics) 2/8

Dr. Tahani Abualteen

o Following the primary infection, immunity to HSV develops but it does not fully protect against recurrent infections (but symptoms may be absent/minimal) However if the immunity is deficient, infections tend to occur more frequently and to be more pronounced and persistent o Microscopic features of HSV infection: Shows an infection of epithelial cells Shows an intraepithelial vesicle (within the thickness of epithelium NOT subepithelial) that contains fluid and cellular debris The vesicle results from degeneration and rupture of the virally infected epithelial cells by intracellular edema and the coalescence of disrupted cells The rupture of infected cells release new viral particles to infect adjacent cells A characteristic finding in herpetic infections (particularly herpes simplex and Varicella zoster) is the ballooning degeneration which is acantholysis in the prickle cell layer due to viral infection and which result in the formation of Tzanck cells which are large swollen infected cells that have eosinophilic cytoplasm and large pale vesicular nuclei (nuclei with thin and dispersed chromatin) Enlarged, multinucleated epithelial cells may result from fusion of cytoplasm of infected cells Tzanck cells The virus also gain access to the sensory axons of the trigeminal nerve and remain latent there (its DNA transcription is blocked), and this usually happens after reaching a balance between the virus and the immune system (cell-mediated immunity) Any factor that may disturb the immunity may reactivate the virus and induce viral replication and then viral particles start to travel down the nerve axons or branches to nerve endings where they may be shed asymptomatically into the mouth or re-infect the epithelial cells o Treatment: Supportive/symptomatic: Analgesics to relieve pain (e.g. Paracetamol) Mouthwashes may be given to prevent secondary infections It is a viral condition so antibiotics wont help Antiviral agent (e.g. Acyclovir) may be given in extreme cases

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o Prognosis: Self-limited infection Resolves in 10-14 days Secondary infection of HSV Type 1 (Recurrent Herpetic Stomatitis/ herpes labialis): o About one in three of those who have had a primary infection (either clinical or subclinical) later develop recurrent HSV infection o This is due to reactivation of the virus which, following the primary infection, has remained latent in the sensory ganglion of trigeminal nerve ** Latency is a characteristic property of the herpes viruses ** Herpes simplex in most of the cases prefers to stay in the sensory ganglion of trigeminal nerve, and usually doesnt affect the geniculate ganglion of facial nerve o Recurrence (viral reactivation) may be brought by a number of predisposing factors: Factors that may alter or suppress immunity (e.g. Menstruation, old age, stress, febrile illness "common cold", immunosuppressive drugs, AIDS ) Factors that damage epithelial cells (e.g. mechanical trauma, UV light ) o Systemic symptoms are usually absent in recurrent infections because of the immunity acquired at the primary infection and thus recurrent infections may result in asymptomatic shedding of HSV into the oral cavity or in local Prodromal symptoms prior to vesicles eruption (e.g. tingling, itching, burning, or paresthesia) o After that patients develop clusters of vesicles and ulcers o Vesicles soon rupture and become crusted, and they usually heal within a week o Herpes labialis is the most frequent type of recurrent infection and appears as clusters of vesicles on the lips and adjacent skin a few hours after local Prodromal symptoms of itching or tingling ** Herpes labialis is usually unilateral; however it may be bilateral and more severe especially in immunecompromised patients ** If the patient recognizes the recurrent herpes labialis in the Prodromal stage (at the period of tingling and burning sensation prior to vesicles eruption), then he may benefit from topical application of alcohol, ice , or acyclovir as it is thought that these agents may lessen symptoms or they may shorten the infection period o Recurrent intraoral lesions occur occasionally, almost always on the hard palate or gingiva (keratinized areas) and usually unilateral Summary: - When a patient acquires HSV, in most of the cases infection goes subclinical; however some may develop the symptomatic primary herpetic Gingivostomatitis - After primary infection, virus remains latent in the sensory ganglion of trigeminal nerve 4/8 - Recurrent/secondary infection results from reactivation of the virus particularly following immunosuppression or epithelial cells damage

A patient with herpetic infection (either primary or secondary) can transmit the virus to another one and cause primary infection if the recipient has never been exposed to the virus before Dr. Tahani Abualteen This recipient can't develop secondary infection immediately because secondary infection needs the virus to be already latent there and then reactivated Varicella zoster virus (VZV): Primary Infection of VZV (Varicella or Chickenpox ")" : o The lesions of chicken pox may be found on the oral mucosa especially the soft palate and may precede the characteristic skin rash o Lesions present as macules, papules, vesicles, or ulcers on skin and oral mucosa o Prodromal symptoms may arise (acute onset of malaise, fever and lymphadenopathy) o Skin lesions are pruritic & usually start in the trunk o Oral lesions are usually asymptomatic o Microscopic features of VZV: Identical to HSV Shows an infection of epithelial cells Shows an intraepithelial vesicle The vesicle results from degeneration and rupture of the virally infected epithelial cells The rupture of infected cells release new viral particles to infect adjacent cells A characteristic finding is the ballooning degeneration which is acantholysis in the prickle cell layer due to viral infection and which result in the formation of Tzanck cells which are large swollen infected cells that have eosinophilic cytoplasm and large pale vesicular nuclei Enlarged, multinucleated epithelial cells may result from fusion of cytoplasm of infected cells The virus also gain access to the sensory axons of the trigeminal nerve and remain latent there (its DNA transcription is blocked) probably for the reminder of the life of the host Reactivation of the virus to cause zoster is uncommon but may occur spontaneously or when the host defenses are depressed

o Treatment: Supportive/symptomatic: Antihistamines, topical lotions (e.g. calomine lotion) It is a viral condition so antibiotics wont help Vaccine is available Antiviral agent (e.g. Acyclovir) may be given in immune-compromised patients 5/8 3 02 -

Dr. Tahani Abualteen

o Prognosis: In children, it is a mild condition but in adults it may cause some complications Secondary infection of VZV (Shingles or Zoster "(" : o Multiple recurrence is rare (repeated attacks of Zoster are unusual since they require much more powerful predisposing factors compared to those needed for HSV recurrent infections) o Same latent state as HSV, in sensory ganglia of trigeminal nerve o Recurrence (viral reactivation) may be brought by a number of predisposing factors: Decreased immune-competence: Elderly patients Immunosuppressive drugs

o Prodromal symptoms of pain and paresthesia may arise for up to 2 weeks o Characterized by unilateral vesicular eruptions extending over one or more branches of trigeminal nerve (lesions are restricted to one side and may end sharply at the midline) o Shingles is an extremely painful condition o Trigeminal Nerve involvement: Ophthalmic division is most frequently involved Involvement of the maxillary or mandibular divisions results in facial and dental pain Intra, extra oral lesions or both o Lesions usually run a course of about 14 days o Complications of shingles/zoster: Post herpetic neuralgia (due to fibrosis around the nerves) so that pain will continue even after lesions subside Ramsay Hunt syndrome due to involvement of geniculate ganglion of facial nerve and subsequent facial paralysis Coxsackievirus (Enteroviradae): RNA virus which has over 30 types Infections worth mentioning are caused by group A Coxsackievirus: o Herpangina o Hand-foot and mouth o Acute lymphonodular Pharyngitis Herpangina: o Caused by Coxsackie Viruses, Group A, RNA o Seen most commonly in children

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o Sudden onset of mild illness with fever, sore throat, dysphasia, anorexia, nausea, vomiting, diarrhea and lymphadenopathy o Vesicles and ulcers in posterior oral cavity (tonsils, soft palate, and uvula) o Self-limiting, symptoms persist for 2-3 days only o Differential diagnosis: primary herpes (however herpes is a Gingivostomatitis, whereas Herpangina is an oropharyngitis) o Treatment is supportive/symptomatic Hand-foot and mouth: o Caused by Coxsackie viruses, group A, especially type 16, RNA o Occurs predominantly in children o Spread by close association e.g. in households o Oral lesions almost always present, characterized by shallow painful ulcers, they may resemble Herpangina but can be larger o The disease may be distinguished by the presence of hand and foot lesions o Self-limiting, usually lasts for 7-10 days Epstein-Barr virus (EBV): Infectious Mononucleosis (glandular fever): o Affects young adults o Transmitted by saliva o Clinically: Pharyngitis, lymph nodes enlargement, Fever, prolonged malaise (maybe be for months or more) o Oral lesions are non specific with ulceration or inflammation of the oral mucosa o Petecheial hemorrhages may be seen at the junction of hard and soft palate ** Petechia = small red spot on the body caused by minor hemorrhage (broken capillary) o Serology: atypical peripheral lymphocytes because EBV get latent in B-lymphocytes o Recall EBV is also associated with : Nasopharyngeal carcinoma Hairy leukoplakia Burkitts lymphoma Oral Sequamous cell carcinoma? (questionable role) Paramyxovirus: Measles (Rubella): o Occurs predominantly in children o Prodromal symptoms may resemble common cold 7/8

Dr. Tahani Abualteen

o Koplik spots on the oral mucosa pin-point bluish white spots/macules against an erythematous background mostly seen on the buccal mucosa opposite to molar teeth They usually disappear as skin rash starts so they may be overlooked or passed unnoticed o Skin rash (start on face, then go to trunk) o Complications of Measles: Otitis media, pneumonia, encephalitis, brain damage Noma may be a complication in malnourished patients ** Noma = gangrenous disease leading to tissue destruction of the face especially mouth and cheeks o The disease is now rare thanks to vaccines Cytomegalovirus: Rarely causes disease in immune-competent patients, however Subclinical infection is common affecting 40-80% of population Often affects immune-compromised individuals (e.g. AIDS patients, Neonates, patients with transplant, patients on immunosuppressant ) It tends to infect endothelial and epithelial cells It also commonly affects salivary glands asymptomatically, or causing Xerostomia especially in AIDS Oral lesions are non specific with ulceration of the oral mucosa Serology: Atypical peripheral lymphocytes might be one of the microscopic features

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