Pathophysiology

Despite the various agents that cause parotitis, involvement of the gland occurs mainly by three mechanisms. The most common mechanism is a localized infection limited to the gland and surrounding structures. Parotitis may be a manifestation of a systemic infection, as in mumps, or rarely may develop secondary to hematogenous seeding during periods of transient bacteremia. Several common contributing factors and pathophysiologic mechanisms lead to swelling of the gland. The parotid is well encapsulated and consists of superficial and deep lobes separated by the facial nerve. The parotid duct (Stensen duct) traverses the buccal soft tissue anteriorly and exits opposite the second upper molar. Thin, watery secretions from the parotid gland cleanse the ductal system and have some bacteriostatic properties, preventing accumulation of bacteria and debris. Factors that predispose individuals to the development of parotitis include side effects of certain drugs and diseases that lead to dehydration, xerostomia, or ductal obstruction ( Box 13.1 ). Decreased salivary flow allows retrograde migration of bacteria. Stasis in the ductal system, caused by ductal ectasia, inflammation, calculi, or strictures, allows proliferation of bacteria and inflammation within the gland.

Etiology

Infectious parotitis may be caused by aerobes, anaerobes, mycobacteria, and viruses ( Box 13.2 ). In all age groups, Staphylococcus aureus is the organism most commonly associated with suppurative parotitis. Gram-negative pathogens (e.g., Escherichia coli and Klebsiella and Pseudomonas spp.) also may cause suppurative parotitis, particularly in neonates and debilitated or hospitalized patients. The role of anaerobic organisms in this infection has become apparent, especially when poor oral hygiene and oral pathology are associated features. In cases of recurrent parotitis of childhood, Streptococcus spp. are the bacteria most commonly isolated. Granulomatous parotitis most often is caused by Mycobacterium tuberculosis and may occur in the absence of systemic or disseminated tuberculous disease. Other causes of granulomatous parotitis include Mycobacterium avium-intracellulare , Actinomyces spp., and gram-negative intracellular organisms ( Francisella tularensis and Brucella spp.).

In the postvaccine era, the most common viral cause of parotitis still is the paramyxovirus mumps virus. coxsackieviruses, Epstein-Barr virus, influenza A virus, parainfluenza viruses, adenovirus, human herpesvirus–6, herpes simplex virus, cytomegalovirus, and lymphocytic choriomeningitis virus all have been implicated in cases of parotitis.

Clinical Presentation and Diagnosis

A detailed history and physical examination are crucial in assisting the clinician in determining the most likely etiology of parotid gland swelling. One should determine the onset and duration of symptoms, their periodicity, and the character of salivary secretions. In addition, the presence of a systemic disease must be excluded. Examination of the parotid gland is achieved best by simultaneous palpation of the intraoral and extraoral salivary structures. Gentle external pressure should be applied to the gland, and the parotid duct should be examined for evidence of purulent secretions or surrounding erythema.

Suppurative parotitis occurs most commonly in neonates or patients with dehydration, poor oral hygiene, malnutrition, immunosuppression, oral trauma, sepsis, or any medication or disease that decreases salivary secretions. Usually, the disease is unilateral; however, bilateral suppurative parotitis may occur in 17% of cases. The disease is characterized by acute onset of pain, swelling, warmth, and induration of the involved gland and purulent discharge from the Stensen duct. Associated physical findings include fever, trismus, malaise, and cervical adenitis. In suppurative parotitis, Gram stain and culture (aerobic and anaerobic) of purulent material from the duct can provide a specific microbiologic diagnosis. In addition, elevation of the white blood cell count with a neutrophil predominance may help differentiate this form of parotitis from viral parotitis and parotid disease of a noninfectious etiology.

Mumps is the most common form of viral parotitis and is characterized by a prodrome of fever, malaise, anorexia, and headache. Usually, the following day, unilateral or bilateral earache and parotid tenderness develop. The gland or glands enlarge during the subsequent 2 to 3 days, and the orifice of the Stensen duct is erythematous and swollen, yet secretions from the duct are clear. At the point of maximal swelling, the angle of the jaw is obliterated and the earlobe is lifted upward and outward. The other salivary glands are involved in 10% of cases. Rare systemic manifestations of mumps infection include epididymo-orchitis, meningitis, meningoencephalitis, and oophoritis. More recent outbreaks of confirmed and probable mumps emphasize that this infection may occur in highly immunized populations. In 2006, the United States had the largest mumps epidemic in two decades, involving more than 6000 patients. Most cases occurred in Midwestern states (Iowa, Kansas, Wisconsin, Illinois, Nebraska, and South Dakota). The highest incidence was among college-aged students, most of whom had received two doses of measles-mumps-rubella (MMR) vaccine. The largest U.S. mumps outbreak since 2006 began at a summer camp in New York in June 2009. This outbreak included 1521 cases. Vaccination status was known for 1115, of which 976 (88%) had received at least one dose of mumps-containing vaccine. Other viral agents may produce similar clinical manifestations and can be differentiated from mumps only by culture and hemagglutination inhibition, complement fixation, or enzyme-linked immunosorbent assay serology. In viral parotitis, the white blood cell count may be normal, slightly elevated, or depressed, with a lymphocytic predominance.

Granulomatous parotitis typically manifests as a painless, slowly enlarging mass without surrounding inflammation. It may be misdiagnosed as a slow-growing tumor until the correct diagnosis is made by biopsy and culture. M. tuberculosis and M. avium-intracellulare may cause infection in the parenchyma of the gland or in intraglandular or periglandular lymph nodes. Clinical evidence of systemic tuberculous disease usually is absent. Parotitis has been observed as an extension of nontuberculous cervical adenitis. Actinomycosis of the parotid gland causes a slowly enlarging, nodular, nontender gland; associated oral or cervicofacial infection usually is present. Fistulas draining yellow or white material with sulfur granules are common findings.

Recurrent parotitis of childhood is rare, with onset typically occurring before the child reaches 10 years of age and a peak incidence at approximately 6 years of age. Some authors hypothesize that an underlying congenital abnormality, such as sialectasis, is a common predisposing feature. Others suggest that selective IgA deficiency may be a contributing variable. Clinically, these children experience repeated episodes of fever, pain, and unilateral swelling of the parotid gland. Purulent material can be expressed from the Stensen duct and, when cultured, often yields streptococcal organisms. Sialography and ultrasound reveal multiple areas of sialectasis throughout the parotid glands bilaterally, even if only one side is symptomatic. The frequency of attacks varies, and each episode of parotitis may last 2 weeks, when it resolves spontaneously. Several authors have noted that recurrences become less frequent with increasing age and that the disease tends to cease at the onset of puberty or early adulthood.

Human Immunodeficiency Virus and Parotid Enlargement

Salivary gland enlargement has been recognized as a common finding in children infected with HIV since before the era of highly active antiretroviral therapy (HAART). The prevalence of this manifestation in HIV-infected individuals is 0% to 58%. More recently, in a retrospective report of oral lesions in a cohort of HIV-infected children from Brazil, Miziara and colleagues noted the prevalence of parotid gland enlargement to be 7.6%. Although parotid enlargement occurred more commonly in children older than 5 years of age, the prevalence did not differ between children who were receiving antiretroviral therapy without protease inhibitors and children who were receiving HAART.

The exact pathophysiology is unknown, but proposed mechanisms include lymphoepithelial cysts, lymph node enlargement within the gland, cytomegalovirus or Epstein-Barr virus infection, and diffuse infiltrative lymphocytosis syndrome of the gland. This entity in HIV-positive children possibly is associated with the HLA-DR5 and HLA-DR11 phenotypes, but the significance of this finding is unclear. Bilateral parotid enlargement frequently is seen as part of diffuse infiltrative lymphocytosis syndrome, which is characterized by proliferation of CD8 ⁺ lymphocytes within the circulation and is of unclear etiology. Growth of the parotid is secondary to infiltration of CD8 lymphocytes into the gland, follicular hyperplasia of intraparotid lymphoid tissue (as occurs in lymph nodes throughout the body in HIV infection), and development of diffuse intraparotid, lymphoepithelial cysts. Epstein-Barr virus has been proposed as an impetus for CD8 lymphoproliferation because the virus has been isolated from parotid tissue of some affected patients. The absence of positive serology for the virus renders it an unlikely causative agent, however. HIV, which may be the inciting agent, has been detected in dendritic cells, macrophages, and lymphocytes isolated from the parotid glands of affected patients.

Parotid enlargement may be present in 20% to 50% of children with HIV infection and acquired immunodeficiency syndrome (AIDS). The median time from birth to development of parotid enlargement is 4.6 years, and often it is the first manifestation of HIV infection acquired during the perinatal period in an otherwise healthy older child. HIV-positive children with enlarged parotid glands tend to have a slower progression to death than do HIV-positive children with oral herpes or candidiasis. Usually, both parotid glands are involved, and an affected patient presents with enlarged, tender parotid glands, xerostomia, and increased serum amylase level. Severity of pain and size of the gland tend to fluctuate without apparent cause. This manifestation of HIV infection and AIDS is still commonly seen in developing countries where access to antiretroviral therapy is limited.

The differential diagnoses for parotid enlargement in an HIV-positive patient include viral and bacterial parotitis. Some patients have preexisting xerostomia that may increase their susceptibility to parotitis. In addition, the immunocompromised state of patients with AIDS may predispose them to development of infection of the parotid gland with other agents, such as cytomegalovirus, Epstein-Barr virus, bacteria, mycobacteria, and fungi. Noninfectious etiologies, such as non-Hodgkin lymphoma or Kaposi sarcoma, also should be included in the differential diagnosis of parotid gland enlargement in an HIV-infected patient, although these manifestations usually are observed in adults.