The differential diagnosis for “rare” parotid gland diseases is broad and encompasses infectious, neoplastic, autoimmune, metabolic, and iatrogenic etiologies. The body of knowledge of parotid gland diseases has grown owing to advances in imaging and pathologic analysis and molecular technology. This article reviews rare parotid diseases, discussing the respective disease’s clinical presentation, diagnosis, imaging, pathogenesis, treatment, and prognosis.
Key points
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The majority of nonneoplastic disorders of the parotid gland can be categorized based on clinical history and physical examination.
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Classification of the parotid gland disease process helps to direct treatment and prognosis.
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Diagnosis of autoimmune and granulomatous conditions often requires special laboratory tests and salivary gland biopsy.
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The possibility of underlying neoplastic disorders must be considered while treating nonneoplastic disease processes.
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Newer minimally invasive surgical, medical, and diagnostic options such as sialendoscopy, botulinum toxin injection, and ultrasonography should be considered to complement traditional treatment algorithms.
Clinical presentation
The clinical presentation and history varies for uncommon parotid gland disorders. Swelling is present in nearly all clinical entities and is either nonpainful or painful. Conditions can range from chronic to acute and aggravating factors like eating can direct the differential in a specific way. Other key historical details include constitutional symptoms, unilateral versus bilateral symptoms, history of radioactive iodine treatment, history of measles, mumps, rubella vaccination, and history of autoimmune disease.
Sialadenosis
Sialadenosis (sialosis) is a chronic, bilateral, diffuse, noninflammatory, nonneoplastic swelling of the major salivary glands that primarily affects the parotid glands. Sialadenosis can be painless or in some instances tender. Sialadenosis is associated with nutritional and hormonal disturbances, particularly chronic malnutrition, obesity, alcoholism, acromegaly, diabetes insipidus, diabetes mellitus, hypothyroidism, liver disease, uremia, and eating disorders. Many medications have been implicated in sialadenosis, most commonly antihypertensives. Some cases of sialadenosis have no underlying cause.
Sialadenosis affects 10% to 50% of patients with bulimia nervosa ( Fig. 1 ). Other nutritional deficiencies include beriberi, gastrointestinal disease, malnutrition, Chagas disease, pellagra, and vitamin A deficiency. Diabetes is also an important cause of sialadenosis. In some cases, parotid gland swelling and enlargement precede the diagnosis of diabetes. Some research suggests working up patients for diabetes who present with parotid gland swelling of unknown origin. Sialadenosis is also seen in patients with alcoholism and alcoholic cirrhosis with an estimated incidence of 30% to 86%.
The pathogenesis of sialadenosis is not well-established. It may involve a neuropathic process of the autonomic innervations of the parotid gland in the setting of systemic demyelinating polyneuropathy. Autonomic neuropathies are noted in patients with alcoholism, nonalcoholic liver diseases, and diabetes. Dysfunction of autonomic regulation leads to an imbalance of acinar protein synthesis and protein secretion. Sialadenosis treatment targets the underlying condition with variable resolution of parotid gland symptoms.
Bacterial Sialadenitis
Acute sialadenitis is a bacterial infection of the parotid gland. High bacterial loads in the oral cavity provide opportunity for infection of the glands. Normal salivary flow is protective against retrograde colonization and overgrowth of bacteria in the salivary ducts and parenchyma. Saliva has antimicrobial properties owing to the presence of lysosomes, immunoglobulin (Ig)A antibodies, and sialic acid. The current incidence of acute sialadenitis has been reported at 0.02% of hospital admissions, with the parotid gland being most commonly affected.
Salivary stasis, reduced flow, and obstruction can be precipitating events for acute sialadenitis. Acute sialadenitis most frequently occurs in sixth or seventh decades of life. A decrease in saliva production can be caused by multiple medical conditions. Examples include Sjögren syndrome, diuretic therapy for hypertension, osmotic diuresis from diabetes mellitus, and postoperative fluid shift, especially after gastrointestinal procedures.
The classic presentation of acute suppurative parotitis is the sudden onset of diffuse enlargement of the involved gland with associated induration and tenderness ( Fig. 2 ). Staphylococcus aureus has been attributed as the causative microbe in up to 90% of cases of suppurative sialadenitis. Other aerobic organisms implicated include Streptococcus pneumoniae , Escherichia coli , and Haemophilus influenzae . Initial treatment consists of antibiotics, warm compresses, gland massage, and sialagogues. Empiric treatment with penicillinase-resistant antistaphylococcal antibiotic should be initiated while awaiting cultures. Computed tomography or ultrasound imaging is useful if an abscess or regional spread of infection is suspected. Sialography and sialendoscopy are contraindicated. In the event of abscess formation, incision and drainage is indicated.
Viral Sialadenitis
Mumps
The most common cause of acute viral infection of the parotid gland is mumps. Before the release of the mumps vaccine in 1967, the incidence of mumps in the United States was as high as 300,000 cases per year and it was the most common cause of parotid swelling. Subsequent to the development of a vaccine, the demographics of mumps shifted from being a disease of childhood to affecting young adults.
Prodromal symptoms include fever, malaise, myalgia, and anorexia. The onset of parotitis usually occurs within 24 hours but may follow up to a week later. Parotitis is generally bilateral, but may be unilateral. The submandibular gland and sublingual gland are involved less frequently.
The diagnosis is made by confirmation of antibodies to the mumps S and V antigens. Amylase can elevate during mumps infection and it is helpful to examine subtypes to distinguish mumps parotitis (amylase-S) and pancreatitis (amylase-P) Diagnosis can also be made by isolating the virus from the cerebrospinal fluid during the first 3 days of clinical symptoms for patients presenting with aseptic meningitis. The mumps virus is also present in the saliva for approximately 1 week starting 2 to 3 days before onset of parotitis. Viral cultures of urine will also be possible for the first 2 weeks of illness. Polymerase chain reaction or viral cultures can also be used to detect the virus. Treatment is symptoms based. Chronic obstructive sialadenitis may develop many years after the acute episode of mumps.
Human immunodeficiency virus
Viral infection with more generalized signs and symptoms as associated with human immunodeficiency virus (HIV) can also cause a focal sialadenitis that may not be appreciated in the acute phase. Diffuse gradual enlargement of the parotid glands may be seen and has been termed HIV-associated salivary gland disease ( Fig. 3 ). These findings may be seen at any time in the HIV disease process and may be the presenting symptom. Since the introduction of highly active antiretroviral therapy in the mid 1990s, there has been a decline in the prevalence of oral manifestations of HIV infection. However, the incidence of HIV-associated salivary gland diseases, mostly involving the parotid glands, has remained the same. Parotid gland enlargement reportedly occurs in 1% to 10% of HIV-infected patients. Etiologies of parotid enlargement specific to HIV-seropositive patients include hyperplastic lymphadenopathy, benign lymphoepithelial cysts, and diffuse infiltrative lymphocytosis syndrome. Benign lymphoepithelial cysts occur in 3% to 6% of HIV-positive adults and in 1% to 10% of HIV-positive children, and often presents early in the course of HIV infection with slowly progressive but asymptomatic parotid gland enlargement. A known adverse effect of protease inhibitors is fat accumulation in various parts of the body. Protease inhibitors have been suggested to cause fatty infiltration of the parotid gland or parotid lipomatosis, resulting in glandular swelling.
Other viral causes
Other viral infections have been implicated in acute viral parotitis including hepatitis C virus, cytomegalovirus, Coxsackie A and B viruses, echoviruses, parainfluenza, adenovirus, and influenza A. Treatment of all viral infections is symptomatic. Added antimicrobial therapy is indicated in the presence of superimposed infections.
Obstructive Sialadenitis
Chronic sialadenitis is characterized by recurrent inflammation and pain in the parotid gland. Factors include the triad of stasis, obstruction, and reduced salivary flow rate. Sialolithiasis, salivary duct stricture, external duct compression, systemic disease, or stasis may be causative. Repeated glandular infection results in permanent damage to the salivary gland characterized by sialectasia, ductal ectasia, and progressive acinar destruction combined with lymphocytic infiltrate. The structural changes with chronic repeated infections result in reduced function. Thus, xerostomia develops in up to 80% of patients.
Patients with chronic sialadenitis present with a history of recurrent painful swelling of the affected parotid gland that is exacerbated with eating. Physical examination confirms asymmetric, firm, and occasionally tender glands. Examination of the oral cavity assesses for xerostomia, quality and consistency of the saliva, patency of the duct opening at the papilla, and bimanual palpation of the glands. Ultrasonography is a valuable adjunct to physical examination and can help to detect salivary stones that are not palpable clinically as well as assess for neoplasms and strictures.
Computed tomography is the preferred diagnostic imaging modality to evaluate for calculi or neoplasms within the gland. Sialography may be useful to detect ductal abnormalities such as ectasia or strictures. A specialized MRI protocol to evaluate the salivary gland ducts, named MR sialography, is a noninvasive technique to evaluate the ductal system. Initial treatment for chronic sialadenitis includes sialogogues, hydration, massage, and antibiotics during an acute exacerbation. When conservative management is insufficient or in cases of sialolithiasis, sialendoscopy can be both diagnostic and therapeutic.
Granulomatous infections of the parotid glands
Tuberculosis of the Parotid Gland
Tuberculosis is a rare cause of parotid enlargement. It is often mistaken for a parotid tumor. Older children and adults are affected most commonly. Parotid involvement is most common with primary Mycobacterium tuberculosis infection, whereas in disseminated pulmonary infections, the submandibular gland is more commonly involved. Most cases of primary tuberculosis of the parotid gland are believed to arise from a focus of infection in the tonsil or teeth.
The presentation is that of an enlarging firm parotid mass that is identical to a neoplasm on imaging. Clinically, it may mimic acute inflammatory sialadenitis and diagnosis requires positive acid-fast salivary stain and purified protein derivative test. Fine needle aspiration can reveal caseous necrosis in some cases. Polymerase chain reaction of the fine needle aspirate is highly sensitive but difficult to obtain. Treatment is the same as for any tuberculosis infection, requiring multidrug therapy. In resistant cases, excision may be necessary and is curative.
Nontuberculous Mycobacterial Infections
Nontuberculous mycobacterial infections are rare in the parotid gland. M kansasii , M scrofulaceum , and M avium are the most commonly encountered nontuberculous mycobacterial infections and are common in soil, water, and food. These infections are most commonly encountered in children younger than 5 years old. The typical presentation is tender induration in the region of the salivary gland that fails antibiotic therapy. The overlying skin develops thinning and adherence to the infected gland, with a characteristic violaceous hue. Fine needle aspiration biopsy carries a risk of fistula formation. Antibiotic treatment with clarithromycin or other antibiotics can be attempted, but often results in prolonged treatment during which the patient remains symptomatic and fistulization or repeated abscess formation occurs. Thus, recommended treatment is complete gland excision.
Cat-Scratch Disease
Cat-scratch disease is caused by the gram-negative bacillus Bartonella henselae . A local infection at the scratch site is followed 1 to 2 weeks later by lymphadenopathy in the draining lymph nodes. Parotid lymph nodes may be involved. Lymph node enlargement progresses over 1 to 2 weeks and can persist for 2 to 3 months. Abscess formation may develop. Reassurance and observation for lymphadenopathy resolution is usually sufficient. If the patient is highly symptomatic, antibiotics like erythromycin, azithromycin, gentamicin, and rifampin are all therapeutic.
Sarcoidosis
Sarcoidosis is a granulomatous disorder with many systemic manifestations encompassing nearly all organ systems. Parotid gland involvement has been reported in 6% to 30% of patients with sarcoidosis. One notable presentation is that of uveoparotid fever, also known as Heerfordt syndrome, which is characterized by uveitis, parotid enlargement, and facial paralysis. This syndrome has been reported to affect 0.3% of patients with sarcoidosis. Parotid swelling can last months to years and eventually resolves spontaneously. Biopsy of the minor salivary glands may establish the diagnosis. Corticosteroids are effective, especially in the acute phase and for the management of facial paralysis.
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