eMedicine - Viral Infections of the Mouth : Article by Sara C Gordon

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Viral Infections of the Mouth

Article Last Updated: Jan 4, 2007

Members of the human herpesvirus (HHV) and human papillomavirus (HPV) families are the most common causes of primary viral infections of the oral cavity. Nonetheless, many other viral infections can affect the oral cavity in humans, as either localized or systemic infections. This article discusses viral conditions of the oral cavity, including HHV infection, HPV infection, coxsackievirus infection, mumps, measles (rubeola), and rubella. See Cutaneous Manifestations of HIV Disease and Cutaneous Manifestations of Hepatitis C for information on these viral infections.

Background

HHV infections are common in the oral cavity. They may be primary or recurrent infections. Eight types of HHV have been linked with oral disease. These types have different disease patterns in their hosts.

Pathophysiology

Herpesvirus family members are icosahedral DNA viruses. A herpesvirus measures approximately 100 nm without an envelope or 150 nm with an envelope. HHVs replicate in the host cell nucleus. Infected saliva or droplets spread the viruses in the oral cavity. The viruses also may be transmitted via oral-genital contact. Viral shedding has been detected before, during, and after the appearance of clinical lesions in patients with recurrent HHV-1 and HHV-2 infections, so lack of visible lesions does not correlate with lack of potential infectivity. In a localized primary infection, the virus penetrates the mucosal epithelium and invades the cells of the basal layer, where the viral DNA inserts into the host DNA.

In HHV-1 and HHV-2 oral infections, viral replication within the oral epithelium may cause lysis of epithelial cells, with vesicle formation. Shallow ulcers with scabs that then heal without scarring follow the formation of vesicles. Herpesviruses establish latent permanent infections in their hosts, although clinical signs of disease may not be detected.

Frequency

Mortality/morbidity

In children and adults who are immunocompetent, primary herpetic infections may be annoying and uncomfortable, but they rarely cause significant morbidity or mortality.

In individuals who are immunosuppressed, primary herpetic infections can be severe, and occasionally they can cause esophagitis, encephalitis, keratoconjunctivitis, and other diseases. The other forms of HHV can result in death. Herpes infections occasionally trigger erythema multiforme.

Age

Primary herpes infections typically occur during childhood or youth, although occasional cases are observed in older individuals. Recurrent HHV-1 infections typically occur throughout life and are particularly triggered by stress, illness, immune compromise, or other factors. Herpes zoster usually affects patients older than 40 years.

Clinical history

When HHV-1 recurs, it has different and distinct oral and perioral presentations from primary herpetic gingivostomatitis.

Primary herpes infection (primary herpetic gingivostomatitis) usually occurs in children or adolescents who have not been previously exposed to the virus. Many primary infections are asymptomatic. Symptomatic primary infection, with multiple, small, clustered vesicles in numerous locations, can occur anywhere in the oral cavity, on the perioral skin, on the pharynx, or on the genitalia. Headache, fever, painful lymphadenopathy, and malaise are common. Antibody production follows, and the virus may become latent in sensory ganglia, often the trigeminal ganglion. Primary herpetic gingivostomatitis usually resolves within approximately 14 days.

Recurrent herpes lesions are commonly referred to as cold sores. Recurrent herpes occurs in approximately one third of patients who have experienced primary herpetic gingivostomatitis. When the disease manifests extraorally, prodromal burning or itching often precedes vesicle formation. Recurrent herpes is a more limited disease than primary herpes. Unlike primary herpes, it occurs on keratinized mucosa (usually the lips, attached gingiva, and/or the hard palate). Vesicles are present in one discrete area, typically the same site every time in any given patient. Such sites include the vermilion border of the lips, the perioral skin, the hard palate, or, occasionally, the gingiva or the dorsal aspect of the tongue. Because vesicles can easily rupture intraorally, only an ulcer may be observed in some cases. Lymphadenopathy and systemic manifestations are much milder than in the primary disease. One case report describes HHV-1 infection manifesting as a mass in the piriform sinus.

Triggers for recurrence may include sunlight exposure, physical or emotional stress, or systemic illness for extraoral lesions and trauma (eg, a dental procedure) for intraoral lesions.

In immunosuppressed individuals, recurrent herpes lesions may occur on any oral mucosal surface, including nonkeratinized sites. They also may manifest solely as lesions on the dorsal aspect of the tongue. Such a presentation has been variously reported as red or white nodules, painful nonvesicular ulcerations, fissured, and, rarely, as a tongue mass. Herpes lesions in immunocompromised individuals are often severe. Such atypical presentations in an individual who is immunocompetent may lead the clinician to further investigate the patient's immune status.

HHV-2 is less common in the oral cavity than HHV-1; however, its oral manifestations are clinically indistinguishable from HHV-1 infection. Recent assessment of HSV-2 shedding by polymerase chain reaction has detected oral HSV-2 shedding in the absence of an oral lesion, but concurrent with genital HSV-2 reactivation. This was more common in HIV-positive males.

Primary varicella, or chickenpox, usually occurs in children aged 3-6 years who are not immunized at the time of their first exposure to the virus. Itchy vesicles begin on the skin of the trunk and spread to the skin of the head. Intraoral and pharyngeal vesicles may occur. Antibody production follows, and the virus usually becomes latent in the dorsal root ganglia. Healthy children usually recover uneventfully, with a mortality rate of less than 2 deaths per 100,000 cases. However, older patients may experience more severe symptoms, and, in patients who are immunocompromised, the mortality rate may approach 18%.

Recurrent varicella, also known as herpes zoster or shingles, usually occurs in adults, and its incidence increases with age. It can occur in any patient who has had chickenpox and only rarely occurs in patients who have received chickenpox immunization. Recurrent varicella may occur when cellular immunity decreases. It results in a vesicular rash that usually affects a single dermatome. Inside the oral cavity, this may be observed as vesicles or ulcerations that stop sharply at the midline. A prodrome of pain, burning, or itching that mimics a toothache may occur.

After resolution of the rash, postherpetic neuralgia may linger for a month or longer, especially in patients who are immunosuppressed or in those older than 50 years.

Unusual complications can include devitalization of teeth, root resorption, osteonecrosis, and root resorption.

Ramsay-Hunt syndrome arises when the virus emerges from latency in the geniculate ganglion. It involves cranial nerve VII (facial nerve), which has both motor and sensory functions. Manifestations may include paralysis that involves the levator palati muscle and the face; hoarseness; loss of secretory function (eg, dry mouth, loss of taste); vertigo; tinnitus; pain; and vesicles involving the pharynx, the eardrum, the external ear, or the tympanic membrane. Persistent facial nerve weakness or deafness may follow.

HHV-4 is most commonly known as the agent that causes infectious mononucleosis, although it has been linked to African Burkitt lymphoma, other lymphoproliferative diseases, and some nasopharyngeal carcinomas.

Primary infection, infectious mononucleosis (colloquially referred to as mono or kissing disease), occurs on first exposure to the virus, usually during young adulthood. It is often a subclinical infection. The virus (usually acquired from infected saliva) replicates in the cells of the mucosa and salivary glands and spreads to B lymphocytes and the bloodstream. If the patient is immunocompetent, cytotoxic T cells become activated and a characteristic lymphadenopathy (notably involving the posterior cervical nodes) accompanies tonsillitis and hepatosplenomegaly. Tonsillitis may be severe and may encroach on the airway. Thrombocytopenia may complicate the infection, and petechiae may be noted at the junction of the hard and soft palates. The patient may report headache, fever, malaise, myalgia, and fatigue. Severe abdominal pain may indicate splenic rupture.

Latent infection of B lymphocytes follows acute disease. EBV has been detected in saliva as long as 18 months after recovery from clinically evident disease.

Hairy leukoplakia, caused by EBV, primarily occurs in adults who are immunosuppressed. Hairy leukoplakia manifests as asymptomatic white lesions on the lateral border of the tongue, often bilaterally. The lesions may be observed on the adjacent dorsal or ventral surface of the tongue. Occasionally, lesions are present in other sites, such as the buccal mucosa near the commissures. The lesions have a corrugated, linear appearance and may appear granular or nodular or may have hairlike projections. Hairy leukoplakia may be the first manifestation of immunosuppression and may prompt the clinician to test the patient's HIV status. The presence of hairy leukoplakia is significantly associated with an HIV viral load of at least 3000 copies/mul.

Recently, EBV has been detected in aggressive periodontal lesions more often than in less diseased periodontal tissues, and has also been detected in periapical lesions. The significance of these findings is unclear.

Primary CMV infection is usually asymptomatic in patients who are immunocompetent. The virus is shed by glandular secretions, including saliva. It occasionally is shed in urine. Primary CMV infection can be asymptomatic, but it can also mimic mononucleosis. Clinical disease is more common in neonates and in patients who are immunosuppressed than in other individuals.

CMV can persist indefinitely in the host. Reactivation of latent infection can occur in patients who are immunosuppressed, including most patients who have undergone organ transplantation and as many as 90% of patients with AIDS. Latent CMV infection may cause esophagitis, which is occasionally accompanied by oral ulcerations or erythema. The disease can also affect many other body systems, including the colon, eyes, liver, lungs, or brain. The oral ulcerations are clinically nonspecific, and a biopsy is required for definitive diagnosis. A patient with HIV infection who develops CMV oral ulcerations is at high risk for progression to AIDS.

Congenital CMV infection affects 0.5-2.2% of newborns. It is frequently asymptomatic, but oral manifestations may include enamel hypoplasia of the primary teeth.

HHV-7 infection has been associated with roseola infantum, acute hemiplegia of childhood, respiratory tract infections, and hepatitis. It has also been linked to seizures in children with febrile illnesses. HHV-7 has been identified in the saliva of adults, and this is most likely where the virus persists chronically.

DNA sequences of HHV-8 have been identified in persons with KS. HHV-8, also termed KS-associated herpesvirus, may be important in causing and/or maintaining KS lesions. KS in oral cavity follows the same disease pattern as KS in other body sites, and, initially, the lesion may appear as a red, purple, or dusky patch that enlarges into a plaque and later progresses into a tumorous mass. It is observed most frequently in immunosuppressed patients and rarely occurs in children. In the oral cavity, early KS may mimic an amalgam tattoo. The palate is the initial site of intraoral KS in approximately half the cases; other favored sites include the gingiva, the tongue, and the tonsillar area.

Differentials

Workup

Radiography of suspected early KS may be useful to differentiate it from an amalgam tattoo. In many amalgam tattoos, the amalgam is visible as discrete radiopaque particles.

Diagnosis is often made based on the clinical findings alone, especially for HHV-1, HHV-2, and HHV-3. A smear of an intact viral vesicle may be helpful to confirm the clinical diagnosis. Smear results may reveal virally altered epithelial cells. Direct immunofluorescence antibody tests and culturing help identify the causative virus. Biopsy is usually required to confirm a diagnosis of KS, and it may be required to confirm the diagnosis of other conditions.

Standard hematoxylin and eosin staining may reveal virally laden epithelial cells. Immune staining may differentiate between various viral types.

KS is typically a neoplastic spindle cell proliferation with erythrocytes in slitlike spaces and extravasation between the neoplastic cells.

Medical care

Establishing the diagnosis is important because the differential diagnoses include diseases that are conventionally treated with immunosuppressive agents. Immunosuppressive therapy may not be prudent for an active herpetic infection because it could promote dissemination.

Herpesvirus infections may trigger erythema multiforme. If recurrences are common and debilitating, long-term suppressive antiviral therapy may reduce the recurrence of herpes and thus erythema multiforme.

The goals of treatment are to make the patient comfortable and to prevent secondary infections or worsening systemic illness. The patient should maintain fluid intake and a balanced diet with the use of liquid food replacement if necessary. Analgesics, such as acetaminophen, may make the patient more comfortable. Aspirin should be avoided in pediatric patients because of the possibility of Reye syndrome. Topical anesthetics and coating agents may make the patient more comfortable and may aid in the consumption of food; however, they do not speed healing.

In order to limit the emergence of resistant strains, the US Food and Drug Administration (FDA) recommends that systemic antivirals be reserved for the treatment of oral herpetic lesions only in patients who are immunocompromised. Topical antivirals may reduce viral shedding and decrease patient discomfort.

Patients should be advised about the potential for autoinoculation if they touch the herpetic lesion and then touch a mucous membrane or an eye. Controlling autoinoculation can be a challenge if the patient is a young child.

Some patients find that sunburn triggers the recurrence of labial lesions. Sun avoidance by the use of hats or shading or the application of a sunscreen or sunblock may reduce the frequency of recurrences.

If the decision is made to use systemic antiviral treatment, it should be initiated as early as possible in the prodromal stage to reduce the size, severity, and duration of the lesions. Topical antiviral medications are minimally useful in treating recurrent HHV-1 infection in healthy patients. Emollient preparations may make the patient more comfortable. Systemic prophylactic antiviral medication may be indicated for patients who experience 6 or more recurrences a year or for patients who experience repeated bouts of erythema multiforme induced by herpes.

Antiviral therapy is most effective in limiting the area of involvement and the duration of the symptoms if instituted within the first 48-72 hours. Acyclovir may control the size of the lesions, but it is less effective than valacyclovir or famciclovir in reducing pain and in lessening the risk of postherpetic neuralgia. Postherpetic neuralgia is especially common in older patients, and it may be appropriately managed with short-term, high-dose corticosteroid prophylaxis in conjunction with or following antiviral therapy. The pain of postherpetic neuralgia can also be managed with anticonvulsants, antidepressants, painkillers, or topical anesthetics.

Topical tretoin gel may be used to manage oral hairy leukoplakia, but it often is not necessary. Management of the underlying immunosuppressed status may be a more useful strategy.

Consultations

Patients with ocular lesions should immediately be referred to an ophthalmologist.

Patients with KS are commonly referred to an appropriate subspecialist for treatment.

Patients with confirmed hairy leukoplakia or KS should undergo a thorough investigation of their immune status.

Medication

Medical/legal pitfalls

Background

HPVs are members of the Papovaviridae family, which are small icosahedral viruses that contain circular DNA. The term papova is derived from the first 2 letters of their common clinical features, as follows: papillomatous lesions, polyomas (varied tumor induction), and vacuolization of infected cells.

At least 106 types of HPV have been discovered. The infectivity of HPV is incompletely understood. Some types of HPV may act in concert with cofactors such as diminished immunity or sun exposure.

Although the magnitude of its risk is not completely clear, HPV is currently considered to be an independent risk factor for the development of oral squamous cell carcinoma. Odds ratios range in various studies from 2.0 to 5.4, and variation is in part associated with the method of viral detection. Certain HPV types have been more strongly associated with malignancies of the tonsils, anus, genital tract, and other areas.

Pathophysiology

HPV is a 50-nm virus composed of double-stranded DNA with no envelope. The virus penetrates the mucosal epithelium and invades the cells of the basal layer, where the viral circular DNA inserts into the host DNA.

Frequency

HPV has been detected in the oral cavity of approximately 6-10% of children and adolescents. The rate of HPV in the oral cavity of healthy adults is estimated at 5-80%. Persistent oral HPV infection in one spouse appears to predict similar infection in the other spouse, regardless of oral sex habits.

HPV-16 has been linked to the development of dysplasia and carcinoma of the uterine cervix. Oral HPV-16 detection is more common in women with HPV-associated cervical dysplasia. Oral HPV-16 detection is much less common in children than in adolescents and adults. However, persistence of HPV-16 and other high-risk HPV types is more common in infants of parents with persistent oral HPV infections and high-risk behaviors.

Oral HPV may also be more common in renal dialysis patients. Recent development of effective HPV vaccines may in the future have a significant impact on these rates.

Mortality/morbidity

Most oral lesions caused by HPV are benign. Lesions are usually painless and not ulcerated, although they may be secondarily ulcerated by trauma. Lesions may be more common and severe in immunocompromised patients than in other patients.

Clinical history

Verruca vulgaris, or common warts (HPV-2; HPV-4; occasionally HPV-1, HPV-3, HPV-27, HPV-29, and HPV-57), are more common on the skin than in the oral cavity. On the oral mucosa, the warts are usually sessile, verrucous, and white; solitary or multiple; and elevated with discrete borders. The lesions most commonly occur on the lips, hard palate, or gingiva. Verruca plana is similar but less elevated. Warts are commonly observed on the digits of patients with oral infection.

Condyloma acuminata, or genital warts (HPV-6, HPV-11), may also affect the oral mucosa. These lesions are usually cerebriform, pink, and sessile and solitary or multiple; they occur more commonly on nonkeratinized mucosa than on keratinized mucosa. Patients infected with HPV-6 or HPV-11 and their sexual partners may have genital lesions, and the lesions have presumably been spread to the oral cavity via oral-genital contact.

Focal epithelial hyperplasia, or Heck disease (HPV-13, HPV-32), may appear as an epidemic in young adults in small communities. This condition was first described in native North American people. Heck disease typically manifests as multiple, smooth, sessile nodules, often on the mucosal surface of the lower lip or on the buccal mucosa. Lesions may regress spontaneously after several months.

HPV may have a role in oral premalignancy and malignancy in humans. HPV-16 in particular (but also HPV-18, HPV-33, HPV-35, and others) have been associated with verruciform proliferations in the oral cavity, oral premalignant lesions, and oral squamous cell carcinoma. HPVs may interfere with the normal function of regulatory proteins, such as p53, p16, and pRb, and they may have a promoter effect.

Differentials

Workup

The typing of HPV, if deemed necessary, may be performed by immunohistochemical detection of HPV structural proteins. This analysis has a low sensitivity. Enzyme-linked immunosorbent assay and polymerase chain reaction DNA amplification are more sensitive techniques for HPV detection.

Diagnosis is usually achieved with biopsy results. Excisional biopsy is commonly performed, and it has a high success rate as a treatment of these lesions.

Carbon dioxide laser treatment is not generally recommended because viral DNA has been detected in the laser plume. Such laser treatment is considered potentially infectious to surgical personnel. However, HPV DNA was absent in the laser plume of the Er:YAG laser in one study.

When the production of viral DNA and structural proteins begins, koilocytosis also develops, with dark shrunken nuclei and cytoplasmic vacuolization of infected cells.

Verruca vulgaris typically exhibits a verrucous epithelial proliferation with hyperkeratosis. Koilocytes are frequently noted in the upper stratum spinosum and stratum corneum. Collarette formation may be observed. The thin connective-tissue papillae may contain T lymphocytes.

Condyloma acuminata may exhibit acanthosis but not as much keratosis as verrucae. Collarette formation, basilar hyperplasia, increased mitoses (even high level), and koilocytes in the stratum spinosum are all variable features. However, epithelial dysplasia is not a feature of oral condylomata.

Focal epithelial hyperplasia (Heck disease) exhibits acanthosis of the spinous layer and thickened, fused rete pegs. The epithelial cells may exhibit intracellular edema. Slight parakeratosis is usually present.

Medical care

Oral lesions are usually treated with excisional biopsy. After the lesions have been removed and the diagnosis is confirmed by biopsy results, they usually do not recur unless reinfection occurs. To prevent reinfection, the source of infection (eg, digits, lesions on sexual partners) should be determined and treated if possible.

Topical agents are sometimes used. Cidofovir is an antiviral agent that is a nucleotide analog of deoxycytidine monophosphate. The antiviral agent cidofovir is approved for intravenous administration in patients with AIDS who have CMV retinitis. Topical administration of this medication (1% cream or gel) has been used for refractory condyloma acuminata and recurrent genital herpes. Cidofovir is occasionally used for oral lesions. It may cause nephrotoxicity, uveitis, and numerous other adverse effects when used systemically.

Intralesional injections may be used in refractory cases, but they are not recommended for the primary treatment of oral lesions. Bleomycin is a cytotoxic polypeptide that inhibits DNA synthesis in cells and viruses. Adverse effects include pain with injection, local urticaria, Raynaud phenomenon, and possible tissue necrosis. Bleomycin should be considered a third-line treatment when standard therapies have failed. Interferon alfa (IFN-A) is a naturally occurring cytokine with antiviral, antibacterial, anticancer, and immunomodulatory effects. Intralesional administration of IFN-A is associated with mild flulike symptoms. Treatments may be required for several weeks to months before beneficial results are observed. IFN-A should be considered a third-line treatment to be used after standard therapies have failed.

Systemic agents, such as retinoids or synthetic vitamin A analogs, may be used to treat extensive lesions in patients who are immunocompromised or immunosuppressed. They may be used in conjunction with other treatments. Adverse effects may include liver function abnormalities, increased serum lipid levels, and teratogenicity. Some clinicians have used podophyllin, but it is not approved by the FDA for this purpose.

Medication

Follow-up

Consult an obstetrician/gynecologist (for females) or a urologist (for males) for patients with condyloma acuminata (and their sexual partners) to detect, diagnose, and treat any coexistent lesions of the anogenital lesion, which may be premalignant.

If the initial therapy is inadequate or lesions recur, evaluation of the patient for underlying immunosuppression may be warranted.

Educate the patient concerning the etiology and the route of transmission to prevent reinfection.

Medical/legal pitfalls

Background

The coxsackieviruses belong to the Picornaviridae family and, more specifically, to the Enterovirus genus. Enteroviruses are further divided into 4 subgroups: polioviruses, group A coxsackieviruses, group B coxsackieviruses, and echoviruses. Group A coxsackieviruses comprise 23 serotypes, and group B coxsackieviruses comprise 6 serotypes.

Coxsackieviruses cause 3 conditions that can manifest in the oral cavity: hand-foot-and-mouth disease, herpangina, and acute lymphonodular pharyngitis. Hand-foot-and-mouth disease is usually caused by coxsackievirus A16 and, less commonly, by types A5, A7, A10, B2, and B5 and Enterovirus 71 (EV 71). EV 71 outbreaks are often associated with more serious manifestations, including meningitis. Herpangina outbreaks and individual cases are mainly associated with coxsackieviruses A1-6, A8, A10, and A22. Acute lymphonodular pharyngitis is associated with the A10 subgroup.

Pathophysiology

Enteroviruses infect humans mainly via the fecal-oral route. Spread of the disease can also occur via direct contact with nasal and throat secretions from individuals who are infected.

The virus attaches and replicates in susceptible areas of the pharynx or in the distal part of the GI tract. After multiplying in the submucosal lymphoid tissues, enteroviruses move to the regional lymph nodes (cervical and mesenteric) and produce a minor viremia that is transient and undetectable. Most infections are subclinical, and viral replication stops or is halted by host defense mechanisms. Oral and cutaneous lesions result from secondary infection of the small blood vessels during the viremia stage. The incubation period is 2 days to 2 weeks but is generally 3-5 days. A patient who is infected sheds the virus several days before symptoms appear and can continue to excrete the virus several weeks after the illness.

Frequency

In the United States, most cases (individual and outbreaks) occur in the summer and early fall.

Internationally, major outbreaks of hand-foot-and-mouth disease related to EV 71 occurred in Malaysia in 1997 and in Taiwan in 1998.

In the United States, illness usually occurs as summer outbreaks, peaking between August and October. Infections occur with higher frequency in younger age groups, in people who live in crowded areas, and in people who are economically disadvantaged. Under these conditions, the rate of infection with 1 or more enteroviruses can be more than 50%.

Mortality/morbidity

Oral symptoms, such as mild pharyngitis and erythema of the oral mucosa, occur with hand-foot-and-mouth disease, herpangina, and acute lymphonodular pharyngitis. In hand-foot-and-mouth disease, an accompanying rash also occurs. Other than the oral discomfort and general malaise that accompanies herpangina, acute lymphonodular disease, and most forms of hand-foot-and-mouth disease, mortality and morbidity rates are low.

Hand-foot-and-mouth disease caused by EV 71 is often accompanied by more life-threatening manifestations, such as respiratory distress and aseptic meningitis.

A major outbreak of hand-foot-and-mouth disease was reported in Taiwan in 1998; this outbreak resulted in a number of deaths. The etiologic agent implicated was EV 71, which is 1 of 2 possible agents implicated in hand-foot-and-mouth disease. Most patients who were hospitalized developed rapid cardiopulmonary failure and died soon afterward. This event is the third known EV 71 outbreak leading to rapid deterioration and death in children. Previous outbreaks in young children occurred in Bulgaria in 1975 and in Malaysia from April through June in 1997.

Race

Sex

Age

Hand-foot-and-mouth disease most often occurs in children younger than 5 years. Herpangina most frequently occurs in children aged 3-10 years. Acute lymphonodular pharyngitis also most frequently occurs in children.

Clinical history

After an incubation period of 3-6 days, a mild fever usually occurs, accompanied by malaise, anorexia, and a sore mouth. Oral vesicular lesions usually follow after 1-2 days. Skin lesions follow oral lesions in approximately 75% of children who are infected, whereas only 10% of adults who are infected present with a cutaneous rash. The infection usually lasts 5-8 days. Oral lesions generally occur in groups of 5-10 vesicles that soon rupture and often coalesce, resulting in shallow ulcerations surrounded by erythematous halos. Involved sites include the anterior buccal mucosa, the tongue, and the soft palate.

Accompanying skin lesions occur on the dorsal or lateral aspects of the hands and feet and on the fingers and toes. Skin lesions are approximately 3-7 mm in diameter and consist of a mixture of papules and clear vesicles with a surrounding zone of erythema.

In herpangina, the sudden onset of infection is characterized by fever, sore throat, and painful swallowing. These symptoms manifest several hours to a day prior to the appearance of vesicular lesions on the posterior aspect of the pharynx. Other symptoms include headache, anorexia, vomiting, and abdominal pain. The fever usually subsides in 2-4 days, but ulcers may be present for as long as 1 week. Most cases of herpangina are mild and resolve spontaneously.

The oral lesions begin as punctate macules that evolve over a 24-hour period into 2- to 4-mm erythematous papules. Vesicular change and central ulceration follow, with the development of peripheral zones of erythema. The lesions usually occur in groups of 2-6 and are moderately painful. They occur on the soft palate, usually between the tonsils and the uvula. The lesions are less frequently observed on the tonsils, on the posterior aspect of the pharyngeal wall, or on the buccal mucosa.

Acute lymphonodular pharyngitis is considered a variant of herpangina. The pattern of distribution of oral lesions is similar to that observed in herpangina. The main difference is that in acute lymphonodular pharyngitis, the pharyngeal lesions remain papular without progression to vesicles and ulcers.

Differentials

Workup

The diagnosis for each of the 3 entities can usually be established based on the clinical symptoms. However, if laboratory confirmation is necessary, viral isolation via cell culturing, polymerase chain reaction, or serologic testing can be used. Cell culturing is the most widely used method for confirming the diagnosis.

Genomic sequencing of the virus is likely to be used for confirmation in the future.

Swabs can be taken from the oral lesions or from the stool samples submitted for viral testing.

Initially, intracellular and intercellular edema occurs with formation of an intraepithelial vesicle. As the vesicle becomes larger and involves the basal cell layer, a subepithelial vesicle forms, followed by ulceration. A mixed lymphocytic and neutrophilic inflammatory cell infiltrate is often present.

Medical care

Medical care is not usually necessary. The goals of treatment are to make the patient comfortable and to prevent secondary infections or worsening systemic illness. The patient should maintain fluid intake and a balanced diet with the use of liquid food replacement if necessary. Analgesics, such as acetaminophen, may make the patient more comfortable. Aspirin should be avoided in pediatric patients because of the possibility of Reye syndrome. Topical anesthetics and coating agents may make the patient more comfortable and may aid in the consumption of food; however, they do not speed healing.

Medication

Background

Mumps, also known as epidemic parotitis, is an acute generalized infection observed in children aged 5-15 years. The viral agent belongs to the Paramyxoviridae family. The parotid glands are usually affected, whereas the submandibular and sublingual glands are generally spared. Meningitis and epididymo-orchitis are the 2 most important but less common features of this disease.

Pathophysiology

The mumps virus is a member of the Paramyxoviridae family and of the Rubulavirus genus. This genus includes the mumps virus; Newcastle disease virus; and human parainfluenza virus types 2, 4a, and 4b. Transmission of the mumps virus occurs via direct contact, via droplets, or via fomites, and it enters through the nose or mouth. More intimate contact is necessary for the spread of mumps than for measles or varicella. During the incubation period (approximately 16-18 d), the virus proliferates in the upper respiratory tract and regional lymph nodes. Viremia follows with secondary spread to the glandular and neural tissues. Inflammation of infected tissues leads to the manifestations of parotitis and aseptic meningitis. Patients are most contagious 1-2 days before the onset of parotitis.

Frequency

In the United States, prior to the use of the live attenuated mumps vaccine in 1967, epidemics occurred every 2-5 years. The outbreaks were more frequent between January and May. Since the introduction of the mumps vaccine, a decline of more than 99% has occurred in the annual incidence of mumps in the United States. In 1986 and 1987, a resurgence of mumps occurred, with 12,848 cases reported in 1987. Most cases affected children aged 10-19 years who were born prior to the institution of recommendations for routine mumps vaccination. More recently, in 1996, approximately 750 cases were reported to the US Centers for Disease Control and Prevention (CDC).

Mortality/morbidity

Deaths related to mumps are rare; more than half the deaths occur in individuals older than 19 years. Fetal deaths are increased when mumps infection occurs during the first trimester. Approximately one third of the people infected with the mumps virus are asymptomatic. Although as many as 50% of patients with mumps demonstrate inflammation of the CNS, less than 10% present with manifestations of CNS infection. Adults are at higher risk of aseptic meningitis. A common complication of mumps infection is orchitis, but sterility is rare. Other less common complications include pancreatitis and deafness.

Race

Sex

Age

Mumps is uncommon in infants younger than 1 year because of passive immunity acquired via placental transfer of maternal antibodies. Before the vaccine was instituted in 1967 and during the initial period of vaccination, most cases occurred in children aged 5-9 years, with 90% of cases in children younger than 15 years. In the late 1980s, a shift toward older individuals aged 5-19 years occurred. Recently, the number of cases in infants and elderly persons has increased.

Clinical history

Prodromal symptoms include a low-grade fever, malaise, lack of appetite, and headache. A day after the initial symptoms appear, reports of earache and tenderness of the parotid glands are common. One parotid gland often enlarges a few days after the other, and unilateral involvement is observed in one fourth of patients with salivary gland involvement. Once maximum parotid gland swelling has occurred, the pain, fever, and tenderness quickly diminish. The affected parotid gland returns to its normal size within 1 week. Complications of parotitis are uncommon. Recurrent acute and chronic sialadenitis are potential complications of parotitis.

Physical findings

Parotitis results in enlargement and tenderness of involved parotid glands, and it is observed in 30-40% of individuals who are infected. At its most severe stage, the earlobe on the affected side lifts upward and outward. Enlarged parotid glands can also be observed when viewing the patient from behind. The enlarged parotid gland may obscure the angle of the mandible, in contrast to cervical lymphadenopathy, which does not hide this structure.

Intraorally, enlargement and redness of the opening of the Stensen duct of the affected gland occur. Trismus can lead to difficulty in eating and in speaking. Involvement of the submandibular glands may accompany parotitis but rarely occurs as the sole manifestation of mumps. Submandibular gland involvement is similar in presentation to that of anterior cervical lymphadenopathy. Sublingual gland involvement is least likely to occur in comparison with the other major salivary glands. Submandibular and sublingual gland involvement is usually bilateral and accompanied by swelling of the tongue.

Causes

Epidemics related to the mumps paramyxovirus have occurred in military populations and other communities, including prisons, boarding schools, ships, and remote islands. The spread of mumps in a community is also postulated to occur via children in schools and via those who secondarily infect their family members. In spite of vaccination, past outbreaks of mumps may be related to vaccine failure by using a single dose of the vaccine.

Differentials

Infections - Parainfluenza 3 virus, coxsackievirus, influenza A virus, CMV, Staphylococcus aureus (suppurative parotitis), or HIV-related parotitis

Other - Mikulicz syndrome, uveoparotid fever (Heerfordt syndrome), or Sjögren Syndrome

Workup

The diagnosis of mumps is usually established on the basis of the clinical symptoms, particularly the constitutional symptoms and the swelling and tenderness of the parotid gland.

Definitive diagnosis of mumps depends on serologic studies or viral isolation from clinical specimens, including saliva, urine, and cerebrospinal fluid (CSF). The virus is present in the saliva from 2-3 days before until 4-5 days after the onset of parotitis; saliva specimens should be obtained during this period.

A number of serologic tests are available, including complement fixation, hemagglutination inhibition, neutralization, enzyme immunoassay (EIA), and radial hemolysis antibody tests. EIA is one of the more sensitive tests and is widely used to detect immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. IgM antibody levels are increased in the first few days of infection, and they peak after 1 week. If IgG antibody titers increase between the acute initial phase and the later convalescent phase (collect 2 specimens), mumps infection is suggested. Past infection is demonstrated by EIA or neutralization test results.

The salivary gland tissue is relatively spared of inflammatory involvement during early infection. Diffuse interstitial edema and an inflammatory infiltrate occur and consist of macrophages and lymphocytes. Neutrophils and necrotic debris often occupy the ductal lumens with degeneration of ductal epithelium. Inflammation may spread to the glandular areas in severe cases.

Medical care

Patients should be referred to an appropriate physician for care. Symptomatic and supportive therapy is recommended for mumps parotitis. Analgesic antipyretics reduce fever and relieve pain related to salivary gland inflammation (see Medication). Warm or cold packs applied to the face also may be helpful. Cases of meningitis or pancreatitis require appropriate medical attention.

The mumps vaccine (Jeryl-Lynn strain) is a live attenuated vaccine that was licensed in 1967. The mumps vaccine may be administered alone or in combination with the rubella and measles vaccines. This vaccine is known as the measles, mumps, and rubella, or MMR, vaccine. More than 97% of individuals who are vaccinated develop measurable antibodies to the mumps virus. Immunity from vaccination is estimated to last more than 25 years and is believed to be lifelong in many vaccinated individuals.

Two doses of mumps vaccine are routinely recommended in all children. Doses should be administered at least 1 month apart. The first dose is usually administered on or after the child's first birthday. A second dose is administered to ensure immunity in those who do not respond to the first dose. The second dose may be administered in children aged 4-6 years. Individuals born after 1957 should show documentation of at least 1 dose of the MMR vaccine. If this documentation is not available, a single dose of the MMR vaccine should be administered.

Diet

Avoidance of citric fruit juices is recommended for patients with mumps because discomfort usually ensues when these substances are consumed.

Medication

Analgesic antipyretics may be recommended to reduce pain and discomfort from parotitis. See Medication.

Follow-up

In the CNS, aseptic meningitis is a relatively common complication that does not cause symptoms in 50-60% of patients. Aseptic meningitis manifests with symptoms of headache and stiff neck in approximately 15% of patients. Resolution occurs in 3-10 days.

Orchitis (testicular inflammation) is one of the most common complications of mumps infection. It occurs in approximately 20-50% of postpubertal males, usually after the onset of parotitis. Symptoms include testicular swelling and tenderness, nausea, vomiting, and fever. Pain and swelling diminish after 1 week, but tenderness may continue for several weeks. Testicular atrophy occurs in 50% of patients with orchitis, but sterility is uncommon.

Pancreatitis is an uncommon complication and may manifest in the absence of parotitis. Hyperglycemia is temporary and reversible. Infection with the mumps virus has been suggested to be related to type 1 diabetes mellitus; however, studies have not been conclusive thus far.

Mumps-related deafness is one of the major causes of acquired sensorineural deafness in children. This complication is estimated to occur in 1 in 20,000 patients with mumps.

Children who are infected with mumps should not attend school or daycare centers until 9 days after the onset of parotitis.

When attempting to control outbreaks, schools should exclude susceptible students from attending affected schools. The susceptible students may return to school after immunization. Students who are exempt from mumps vaccination for medical, religious, or other reasons should avoid affected schools for at least 26 days after the onset of parotitis in the last person who was infected.

Background

Measles, also known as rubeola, is an acute, infectious, highly contagious disease that frequently occurs in children. In the United States, the incidence of measles has dramatically decreased as a result of the measles vaccine; however, it remains a significant problem in developing countries.

Pathophysiology

The measles virus is a paramyxovirus belonging to the Morbillivirus genus. The paramyxovirus can survive for as long as 2 hours in the air and on surfaces. Measles is spread by direct contact via droplets from respiratory secretions in patients who are infected. It is considered one of the most communicable infectious diseases.

The initial site of infection is the respiratory epithelium. Multiplication of the measles virus in the respiratory epithelium and regional lymph nodes is followed by a primary viremia with spread to the reticuloendothelial system. A secondary viremia occurs upon breakdown and necrosis of the reticuloendothelial cells, and the virus infects the leukocytes. During secondary viremia, infection may spread to the thymus, the spleen, the lymph nodes, the liver, the skin, and the lungs.

Frequency

In the United States, measles generally occurs in late winter and spring. Prior to the use of the measles vaccine in 1963, approximately 500,000 cases and 500 deaths were reported each year. Epidemic cycles occurred every 2-3 years. More than 50% of the population had measles by age 6 years, and more than 90% were reported to have had it by age 15 years. After licensure of the vaccine in 1963, the number of reported cases of measles dropped by more than 98%, and the 2- to 3-year epidemic cycles no longer prevailed.

From 1989-1991, the incidence of measles rose significantly, with approximately 55,000 cases reported in this 3-year period. The highest number of cases occurred in children younger than 5 years. These cases were prevalent in Hispanic and African American populations. This prevalence was determined to be a result of low vaccination rates among preschool-aged children in these groups. The incidence of measles decreased after this period, and since 1993, fewer than 500 cases have been observed in most years.

From 2001-2003, state and local health departments reported annual totals of confirmed measles cases as 116, 44, and 56, respectively, with a total of 216 cases. In 2002, a record low measles rate of 0.15 cases per million individuals was reported, representing a 59% decrease from the rate reported in 2000, which was the lowest previously noted.

Persons who are at higher risk for measles are unvaccinated individuals in colleges and postsecondary institutions because of large concentrations of susceptible persons. Others who are at risk of exposure to measles are those who work in medical facilities, regardless of whether they are medical or nonmedical staff. Others at high-risk are those who have refused vaccination for personal or religious reasons. Individuals who are traveling outside the United States are also at increased risk of being exposed to measles.

In March 2004, the Iowa Department of Public Health informed the CDC that a 19-year-old student had flown from India to the United States during an infectious stage of measles. Because of nonmedical exemption, the students at this Iowa college were not vaccinated and 6 of them were infected with measles during a trip to India. The measles infection in these students while traveling abroad demonstrates how transmissible measles is in unvaccinated individuals.

Since 1993, the largest outbreaks in the United States occurred in certain communities in Nevada, Utah, Missouri, and Illinois. These outbreaks occurred in groups of individuals who refused vaccination.

Mortality/morbidity

Recently, in the United States, the number of deaths caused by measles has been approximately 1-2 per 1000 cases. Young children and adults are at higher risk of death. Pneumonia accounts for approximately 60% of measles-related deaths. In children with measles, pneumonia-related deaths are most common, whereas in adults, encephalitis-related deaths are more common. Measles-related fatalities are increased in children with leukemia or HIV infection who are immunocompromised.

Developing countries have higher rates of measles in children younger than 1 year. Malnourishment, particularly vitamin A deficiency, is a factor that influences the severity of measles. The mortality rate due to measles in populations with malnutrition can be as high as 25%.

Complications have occurred in as many as 30% of patients with measles. The complications are more severe in young children and adults. The most commonly reported complication from 1985-1992 was diarrhea, followed by otitis media and pneumonia.

Race

Sex

Age

Prior to the routine administration of the measles vaccine, measles affected school-aged children. After that, other groups were affected, including preschool-aged children younger than 5 years and adults older than 20 years.

Clinical history

The incubation period for measles is the time from exposure to the prodrome. This period is approximately 10-14 days and is longer in adults than in children.

The prodrome phase lasts for several days and likely coincides with the secondary viremia phase. It is manifested by malaise, fever, anorexia, conjunctivitis, and respiratory symptoms. Toward the end of the prodrome and just prior to the appearance of the rash, Koplik spots are observed. The skin eruption of measles lasts approximately 5-6 days. The period of uncomplicated illness from the late prodrome to disappearance of skin lesions and fever lasts 7-10 days.

Physical findings

The fever in affected individuals can peak as high as 103-105°F. Patients also experience respiratory symptoms, such as cough and coryza (runny nose), which may resemble a severe upper respiratory tract infection.

Koplik spots are pathognomonic for measles. They are located on the buccal mucosa in the premolar and/or molar area. Occasionally, in severe cases of measles, several areas of the oral cavity may be affected by the enanthem. The intraoral lesions may persist for several days and begin to slough with the onset of the rash.

Koplik spots consist of bluish-gray specks against an erythematous background. They have been compared to grains of sand. As few as 1 spot and as many as 50 spots may occur. The lesions are plaquelike or nodular and oval or round. The measles rash often begins near the hairline and then involves the face and the neck; over the next few days, it progresses to the extremities and finally to the palms and the soles. The rash is erythematous and maculopapular and may become confluent as it progresses. It lasts approximately 5 days and resolves in the same order it appeared, from the face and the neck to the extremities.

Differentials

Workup

All specimens collected for viral culture in cases suggestive of measles should be sent to the nearest state public health laboratory or to the CDC. The measles virus can be isolated from blood, urine, or nasopharyngeal secretions. Clinical specimens and serologic specimens should be obtained at the same time and preferably within 7 days of the onset of the rash. The easiest method that aids in confirming the diagnosis is to test for IgM antibody levels in a single specimen from an individual who is infected. A person who is infected or has received the vaccine initially has an IgM response followed by an IgG response. IgM antibodies are present for 1-2 months after exposure to the measles virus, and IgG antibodies are present for many years.

IgG tests (eg, enzyme-linked immunoabsorbent assay, hemagglutination inhibition, indirect fluorescent antibody tests) are conducted on 2 specimens. The first specimen is obtained during the acute phase (within 4 d of the start of the rash), and the second specimen is collected during the convalescent phase (2-4 wk later). Positive results show increased levels of IgG in the convalescent specimen.

Oral and cutaneous lesions show necrosis of the superficial aspects of the epithelium with an inflammatory infiltrate that consists of neutrophils. Multinucleated giant cells, known as Warthin-Finkeldey cells, may be present in lymphoid tissue and lungs.

Medical care

Patients should be referred to an appropriate physician for care. Supportive treatment is recommended. Appropriate antibiotic therapy is necessary for secondary bacterial infections.

The World Health Organization has recommended that vitamin A supplementation be provided for children with measles living in areas that have a documented vitamin A deficiency problem.

Recently, intravenous and aerosol administration of ribavirin has been used to treat severe cases of measles in patients who are immunocompromised; however, the FDA has not approved this drug for the treatment of measles.

The measles vaccine currently used in the United States is a live attenuated Enders-Edmonston strain (formerly called the Moraten strain). This vaccine is combined with the rubella and mumps vaccines and is administered as the MMR vaccine. Antibodies to measles virus develop in approximately 95% of children vaccinated at age 12 months and in 98% of children vaccinated at age 15 months. The vaccine induces long-term, if not lifelong, immunity to measles in 99% of individuals who receive 2 doses. Two doses of the measles vaccine in the form of MMR are recommended for all children. Individuals born before 1957 should be able to show documentation of immunity either via vaccination or via history of disease. In an individual who has been exposed to measles, administration of the live vaccine within 72 hours can provide long-term immunity.

Follow-up

No oral complications are reported from measles. Diarrhea, otitis media, and pneumonia are the more common complications encountered from measles infection.

One case of acute encephalitis occurs in every 1000-2000 cases of measles. Acute encephalitis begins 6 days after the onset of the rash; symptoms include high-grade fever, headache, stiff neck, convulsions, and coma. The fatality rate is approximately 15%.

Subacute sclerosing panencephalitis is a previously unexplained CNS disease that occurs months to years after the initial measles infection. Progressive deterioration of intellect, convulsive seizures, motor abnormalities, and, eventually, death characterize subacute sclerosing panencephalitis.

When measles infection occurs during pregnancy, the likelihood of early labor, spontaneous abortion, and low birth weight increases. Whether birth defects are caused by measles infection is questionable.

Background

Rubella, also known as German measles, is an acute exanthematous viral infection that is similar in appearance to mild measles (rubeola) infections. It occurs in children and adults. The major potentially serious manifestations are observed in fetuses infected with rubella, resulting in various congenital defects.

Pathophysiology

The rubella virus is an RNA virus belonging to the Togavirus family and the Rubivirus genus. It is related to the group A arboviruses, specifically Eastern and Western encephalitis viruses. The rubella virus is unstable and is killed by lipid solvents, trypsin, formalin, ultraviolet light, and extremes in temperature and pH. The virus is spread via respiratory droplets from individuals who are infected. The virus replicates in the nasopharyngeal tissues and lymph nodes. A viremia results 5-7 days after initial exposure to other areas of the body. Patients are believed to be contagious when the rash is emerging. The virus may also be shed from the throat from 10 days before to 15 days after the onset of the rash. In congenital rubella infections, transplacental spread of virus occurs in the viremia stage. Infants with congenital rubella syndrome (CRS) shed large amounts of rubella virus in their body secretions for many months.

Rubella is moderately contagious. It is most transmissible when the rash begins. Infants with CRS shed large amounts of the virus and can spread rubella to caregivers vulnerable to rubella infection.

Outbreaks continue to occur in populations that are susceptible to rubella infections, including those exposed to certain individuals who have religious or philosophic beliefs regarding personal exemption to vaccination. Other recent outbreaks have occurred in workplaces with employees who were born in countries outside of the United States that do not advocate routine immunizations, including Latin American and Caribbean countries.

Frequency

In the United States, the incidence of rubella infections is higher in late winter and spring.

Prior to the licensure of the rubella vaccine in 1969, the number of cases of rubella was high. The largest annual number was 57,686 cases in 1969. After 1969, the incidence of rubella dropped significantly. Fewer than 1000 cases per year were reported after 1983.

In 1988, the number of cases of rubella in the United States fell to an all time low of 223. However, in 1989, the number of cases nearly doubled from the previous year to 396. This was thought to have occurred with the rise in measles cases as a result of failure of timely vaccination of preschool children. After this resurgence, the number of cases of rubella fell steadily.

The demographics of rubella cases in the United States changed in the 1990s. It now occurs more frequently in foreign-born Hispanic adults who are unvaccinated or in those who have unknown vaccination status. Furthermore, rubella infection continues to occur in women of childbearing age who were born outside the United States.

Since 2001, the annual numbers of rubella cases in the United States have been the lowest in recorded history. Twenty-three cases were reported in 2001, 18 in 2002, 7 in 2003, and 9 in 2004. Approximately half of these cases occurred in persons born outside the United States, of whom most were born outside the Western Hemisphere.

Prior to the recommendations for the rubella vaccine, epidemics of rubella occurred every 6-9 years. The last major epidemic occurred in the United States in 1964-1965.

Mortality/morbidity

Complications of rubella infection occur more frequently in adults than in children.

Arthritis and/or arthralgias occur in as many as 70% of adult women who are infected with rubella. Joint involvement occurs at the same time as the rash and may last as long as 1 month.

Encephalitis is observed in 1 in 5000 cases and more often in adults than in children. Deaths rates related to encephalitis in the setting of rubella range from 0-50%.

Hemorrhagic complications occur in approximately 1 in 3000 cases and manifest more often in children than in adults. Thrombocytopenic purpura is common and likely due to low levels of platelets and vascular damage. GI and cerebral hemorrhage may also occur.

In 1964, 12.5 million cases of rubella were reported, with 20,000 infants born with CRS. In early pregnancy, rubella infection can lead to serious complications, including fetal death, premature delivery, and congenital defects. Spontaneous abortions and stillbirths are common. As many as 85% of fetuses infected during the first trimester are affected. Complications are rare when rubella infection occurs after the 20th week of pregnancy.

All organ systems may be affected in CRS. Some investigators have reported developmental defects, including enamel hypoplasia and delayed eruption of deciduous teeth; however, other groups have debated the validity of such findings in CRS. Deafness is the most common manifestation and, occasionally, the only one of congenital rubella infection. Ocular defects, such as glaucoma, cataracts, and retinopathy, are possible sequelae. Cardiac defects, including patent ductus arteriosus, ventricular septal defect, pulmonary stenosis, and coarctation of the aorta, may be observed. Neurologic manifestations, such as microcephaly and mental retardation, are other potential complications.

Race

Sex

Age

Rubella is considered a childhood disease; however, it can affect adolescents and adults.

Clinical history

The incubation period is approximately 12-23 days. A prodrome is observed more often in older children and adults than in others; it lasts 1-5 days. Symptoms include low-grade fever, swollen glands, malaise, and upper respiratory tract symptoms. The rash of rubella follows the prodrome and lasts approximately 3 days. Lymphadenopathy can be observed as long as 1 week before the onset of the rash and up to several weeks later.

Physical findings

Symptoms are often mild, and 30-50% of patients are asymptomatic or subclinical. The major manifestation of rubella is the presence of lymphadenopathy involving the postauricular, posterior cervical, and suboccipital lymph nodes. The rash of rubella begins on the face and progresses down the body. The rash consists of erythematous macules and, at times, small papules.

Intraorally, an enanthem consisting of petechial lesions, known as the Forchheimer sign, is observed in approximately 20% of patients. Clinically, these dark red papules are observed on the soft palate. These lesions may arise at the onset of the rash. Palatal petechiae are also occasionally observed. The Forchheimer sign is not pathognomonic of rubella infection.

Other manifestations of rubella infection include conjunctivitis, orchitis, and arthritis.

Differentials

Calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia (CREST) syndrome

Workup

The rubella virus can be isolated from various secretions, including nasal, throat, blood, urine, and CSF specimens. The virus should be isolated in all cases suggestive of rubella or CRS. Serologic analysis is the most common means of confirming the diagnosis of rubella exposure.

Enzyme-linked immunoabsorbent assay is a readily available and easily performed test. It is used to detect IgM antibodies early in infection or IgG antibodies during the postinfection and/or vaccination period. Positive IgM test results for rubella imply recent postnatal infection or congenital infection. False-positive results for rubella IgM have been documented in patients with positive rheumatoid factor, parvovirus infections, and positive heterophile testing for infectious mononucleosis.

Medical care

Treatment for rubella is supportive care. Patients should be referred to an appropriate physician for care. Individuals with rubella infection should be isolated from places, such as school and work, for 7 days after the onset of the rash. No specific treatment is indicated for the oral manifestations of rubella.

The currently used rubella vaccine is a live attenuated virus. The rubella vaccine can be administered as a single agent or in combination with the measles and mumps vaccines as the MMR vaccine. Of individuals who are vaccinated, 90% or more are protected against clinical rubella for at least 15 years. A single dose of the vaccine likely provides long-term immunity. Immunizing postpubertal males and females is recommended. The goal of rubella vaccination is to prevent CRS.

The prognosis is guarded in CRS, depending on the severity of the manifestations.

Drug Category: Local anesthetics

These agents stabilize the neuronal membrane and prevent the initiation and transmission of nerve impulses.

Drug Name	Lidocaine (Xylocaine)
Description	Topical anesthetic for mucous membranes of mouth and pharynx that binds selectively to sodium channels, thus blocking entry of sodium ions into axon. Depolarization and progression of action potential is prevented.
Adult Dose	1 tbsp (15 mL) or less undiluted solution, swish in mouth then expectorate; alternatively, apply up to 1 tbsp of solution to affected area with a cotton-tipped applicator; do not repeat more frequently than q3h; not to exceed 8 doses/d
Pediatric Dose	<3 years: Not established >3 years with lean body mass and normal body development: Maximum dosage is calculated according to weight or age; based on weight, 1.5-2 mg/lb is recommended
Contraindications	Documented hypersensitivity
Interactions	Potential for increased toxicity with class I antiarrhythmic drugs (eg, tocainamide, mexiletine); effects are additive
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Reduce dose in children and patients who are debilitated, elderly, or acutely ill based on age, weight, and physical condition; patients who use topical anesthetics may experience impaired swallowing and increased risk of aspiration (avoid consumption of food for 60 min after oral application); numbness of tongue or buccal mucosa may increase risk of biting trauma

Drug Category: Analgesics

These agents ensure patient comfort, promote pulmonary toilet, and have sedating properties.

Drug Category: Nonsteroidal anti-inflammatory drugs

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may also exist, including inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Drug Category: Antihistamines

Antihistamines are type 1 histamine receptor blockers that act to block the action of histamine after its release from mast cells and basophils. They are most effective when used prophylactically. The 2 classes of antihistamines are sedating and nonsedating. Typically, the sedating antihistamines are stronger and have more adverse anticholinergic effects.

Viral Infections of the Mouth

AUTHOR AND EDITOR INFORMATION

INTRODUCTION

HUMAN HERPESVIRUS

Background

Pathophysiology

Frequency

Mortality/morbidity

Age

Clinical history

Differentials

Workup

Medical care

Consultations

Medication

Medical/legal pitfalls

HUMAN PAPILLOMAVIRUS

Background

Pathophysiology

Frequency

Mortality/morbidity

Clinical history

Differentials

Workup

Medical care

Medication

Follow-up

Medical/legal pitfalls

COXSACKIEVIRUS

Background

Pathophysiology

Frequency

Mortality/morbidity

Race

Sex

Age

Clinical history

Differentials

Workup

Medical care

Medication

MUMPS

Background

Pathophysiology

Frequency

Mortality/morbidity

Race

Sex

Age

Clinical history

Physical findings

Causes

Differentials

Workup

Medical care

Diet

Medication

Follow-up

MEASLES (RUBEOLA)

Background

Pathophysiology

Frequency

Mortality/morbidity

Race

Sex

Age

Clinical history

Physical findings

Differentials

Workup

Medical care

Follow-up

RUBELLA

Background

Pathophysiology

Frequency

Mortality/morbidity

Race

Sex

Age