- Email: [email protected]
Acute Suppurative Parotitis
A c u t e Su p p u r a t i v e P a ro t i t i s Michael Rhodes,
MD
a
, Bradley J. Benson,
MD
b,
*
KEYWORDS Parotitis Parotid gland Acute suppurative parotitis Sialolithiasis Sialadenitis
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Parotitis is an inflammatory process of the parotid gland caused by an infectious or rheumatologic process. 2. Obstruction of the Stensen duct by a sialolith or a foreign body is the most common cause of acute inflammation. 3. Acute suppurative parotitis (ASP) is most commonly a result of static salivary flow and migration of oral microbes up the Stensen duct. 4. In the past, ASP was a severe complication of abdominal surgery, but in the modern era of improved hydration, oral hygiene, and antibiotics it is rare. 5. Bacterial ASP is typically polymicrobial, with high rates of Staphylococcus aureus and anaerobic organisms. Patients with prolonged illnesses or frequent contact with the health care system are at risk for health care–associated ASP infection caused by methicillin resistant S aureus or Pseudomonas. 6. Management of ASP is focused on relieving parotid obstruction with sialagogues or parotid massage, appropriate rehydration, antibiotic therapy, and optimization of medical comorbidities. 7. Admission to the hospital should be considered if the patient appears systemically ill with concern for sepsis or severe dehydration. 8. Consultation from an ear, nose, and throat specialist should be considered in cases in which a discrete palpable mass is present. 9. Ultrasonography is an effective imaging modality to assess for parotid inflammation, sialoliths, cystic lesions, or abscesses. CONTINUED
Conflicts of interest: The authors have no conflicts of interest to disclose. a Departments of Internal Medicine and Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA; b Division of General Internal Medicine, University of Minnesota Medical School, D653 Mayo Memorial Bldg, 420 Delaware St. SE, MMC 741, Minneapolis, MN 55455, USA * Corresponding author. E-mail address: [email protected] Hosp Med Clin 4 (2015) 191–204 http://dx.doi.org/10.1016/j.ehmc.2014.12.006 2211-5943/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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CONTINUED
10. The differential for parotitis beyond acute bacterial infection includes viral infection, benign lymphoepithelial cysts associated with human immunodeficiency virus, rheumatologic disease, endocrine disease, mycobacterial or fungal infections, and medication effects.
What is parotitis? Parotitis is defined as an inflammatory process of the parotid gland. Sialadenitis is the inflammation or infection of a salivary gland, and parotitis is the specific term for parotid gland inflammation. Common causes are bacterial, viral, or rheumatologic. What are the pertinent anatomic features of the parotid gland? The parotid glands are paired salivary glands located lateral to the masseter muscle extending posteriorly to the sternocleidomastoid muscle in the region over the ramus of the mandible (Fig. 1).1,2 The parotids are the largest of the more than 500 salivary glands in the oral mucosa.1 The parotid glands secrete saliva into the oral cavity through the Stensen duct. The Stensen duct enters the oral cavity near the second maxillary molar transecting the buccinators muscle into the buccal mucosa. The significant structures that run through or are adjacent to the parotid gland include the facial nerve, external carotid artery, retromandibular vein, and multiple lymph nodes.1 An estimated 500 to 1500 mL of saliva are excreted daily from the parotid glands, submandibular glands, and the minor salivary glands.2 What is acute suppurative parotitis (ASP)? ASP is a bacterial infection of the parotid gland. The first clinical description of ASP is attributed to Cruveilhier in 1836. The pathophysiologic basis of ASP is static flow of saliva leading to migration of oral flora up the Stensen duct. The reduced flow of saliva may be caused by duct stricture, obstruction (most commonly from sialoliths), or decreased saliva production secondary to illness or medication.3 The decline in saliva flow creates stasis, which potentiates bacterial growth, and leads to the loss of saliva’s bacteriostatic effects, contributing to an oral environment that is more prone to bacterial infection. What predisposes patients to develop ASP and how can it be prevented? In the past, epidemiologic studies have shown a higher incidence of ASP in patients with trauma and those who have recently undergone abdominal surgery.4 Other known factors that contribute to risk of ASP include dehydration, starvation, debilitation, advanced age, immunosuppression, oral neoplasm, tracheostomy, and known ductal obstruction.5–8 Diabetes is a common comorbidity in these patients, presumably because of the dehydration and immunosuppression associated with hyperglycemia. Drugs that decrease saliva production, especially anticholinergic agents, also predispose patients to develop ASP (Box 1).3 Before the modern antibiotic era, ASP carried a mortality of w50%, making it a serious postoperative complication. President James Garfield died in 1881 of secondary ASP infection 11 weeks after surviving a gunshot wound to the abdomen.3,7 The dehydration and malnutrition that occurs with severe illness or abdominal trauma likely accounted for the high historical
Acute Suppurative Parotitis
Fig. 1. Dissection drawings of the salivary glands and the facial nerve. (From Gray H. Anatomy of the human body. 20th edition. Philadelphia: Lea & Febiger; 1918.)
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Box 1 Factors that decrease salivary flow, and thus increase risk of ASP Ductal obstruction Dehydration Nerve damage Irradiation to the gland area Medications; specifically anticholinergic medications Chronic disease Diabetes mellitus Renal failure Cystic fibrosis Hypothyroidism Sjo¨gren syndrome Malnutrition Tracheotomy Periodontal disease
mortality of ASP, as in President Garfield’s case. Current perioperative attention to adequate hydration, nutrition, and oral hygiene has led to a profound decline in the rates of ASP in modern hospitals.7 How often are people hospitalized for ASP? Bacterial infections of the salivary glands account for 0.01% to 0.02% of hospital admissions and less than 0.1% of postoperative patients.5,7 Patients are more likely to be hospitalized for an exacerbation of a chronic condition, and ASP is a secondary diagnosis. The role of the hospitalist is as much about appropriate management of the chronic conditions with attention to preventive measures, including rehydration and oral hygiene, as it is about treatment of ASP. What history is important to assess in patients with ASP? A comprehensive history is essential when evaluating a patient with ASP. Patients often have multiple comorbid chronic disease conditions contributing to development of ASP. The patients are typically middle aged to elderly, with medical history of recent surgery, chronic disease, and/or polypharmacy.9 The chronicity of the parotid inflammation is essential in establishing a diagnosis of ASP versus a chronic parotitis (symptoms>1 month), which is more likely to have architectural damage to the gland and abscess formation that may require surgical drainage. A complete review of systems is essential to assess for signs of toxicity and/or dehydration. Reports of prandial pain separate from trismus may indicate obstructive process and sialolithiasis.7 What are the characteristic examination findings in patients with ASP? On examination there is typically generalized swelling over the parotid, likely unilateral, with erythema, tenderness, induration, trismus, and fever. The expression of pus from
Acute Suppurative Parotitis
the Stensen duct by milking of the parotid gland is considered a pathognomonic finding.4 Because of the dense fibrous capsule over the parotid gland, rarely does pus drain externally.2,10 If there is bilateral parotid swelling, then a systemic nonbacterial cause should be considered. If there is a discrete mass noted in the parotid, then consider neoplasm or large abscess, and imaging will be needed to better define the mass. In these cases, consultation from an ear, nose, and throat (ENT) specialist is appropriate for consideration of either biopsy or drainage (Fig. 2). What are the initial studies in evaluation when suspecting ASP? Evaluation is similar to other infectious processes: complete blood count with differential, basic metabolic panel, and Gram stain and cultures of the suppurative discharge. Although cultured pus from the Stensen duct may be helpful, it has a high likelihood of being contaminated by normal oral flora.4 Direct aspiration of any significant abscess that is identified or aspiration of the parotid is more likely to identify a causative pathogen.10 Which bacteria cause ASP? The pathologic microbes most commonly migrate from the oral space into the parotid through the Stensen duct. Staphylococcus aureus is the most common individual organism isolated from parotitis specimens, but the anaerobic oral flora comprises a large percentage of cases as a class. One study of parotid gland infections identified S aureus in 18% of cases, whereas at least 1 anaerobic bacterium was noted in 54%
Fig. 2. Algorithm of evaluation and management of parotid swelling. CT, computed tomography; IV, intravenous; US, ultrasonography.
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of cases.10 A similar study found 64% of isolates containing anaerobic bacteria.6 The presumption is that, in many clinical settings, anaerobic organisms are not identified more often because of inadequate anaerobic sample handling and culture techniques. The study notably found that 51% of cases grew a b-lactamase–producing organism, which has implications for antibiotic selection.6 The patient’s medical history and recent exposure to nosocomial organisms play an important role in determining what organism is infecting the parotid gland. As emphasized previously, salivary flow through the Stensen duct is essential to prevent migration of bacteria into the parotid. In saliva there is a high concentration of fibronectin, to which Staphylococcus species have a high adherence. Therefore, a previously healthy person who has a decrease in saliva flow is more likely to have gram-positive ASP. Deficiency in fibronectin has been noted in chronically ill patients and patients with cystic fibrosis. Studies have shown that a lack of fibronectin favors adherence of Pseudomonas and/or Escherichia coli.11 Regardless, it should be assumed that, given the diversity of flora in the oral cavity, the antimicrobial choice for parotitis should be broad enough to cover both aerobic and anaerobic organisms. If the patient is or was recently hospitalized, antibiotics should cover resistant organisms like methicillinresistant S aureus (MRSA) or Pseudomonas.7 What is the role of imaging in ASP? Initial plain films of the mouth and jaw, specifically panoramic views, can be helpful in identifying a sialolith that may be causing obstruction. Sialography is not recommended in ASP given the risk for duct rupture, spreading bacteria into tissues, and intense pain associated with the study.12 Ultrasonography by a skilled operator can be the safest, most accurate, and least expensive tool for diagnosing inflammatory parotid disease. Sialoliths are frequently identified with ultrasonography. Doppler ultrasonography is highly accurate at identifying the cystic nature of lesions versus abscesses.13 Noncontrast computed tomography (CT) is helpful when ultrasonography cannot identify a sialolith but stone obstruction is suspected. Noncontrast CT potentially can also help delineate the extent of stone burden. Contrast-enhanced CT is indicated when abscess is suspected and ultrasonography is unable to fully define the lesion. In addition, contrast-enhanced CT can aid when there is a question of dental infections or abscess contributing to or mimicking parotitis.13 MRI is not necessarily better than CT or ultrasonography at identifying sialoliths, but it is less invasive compared with conventional sialography. MRI is most useful in assessment of the parenchymal changes of the gland and identification of atrophy that may be associated with Sjo¨gren syndrome (Figs. 3 and 4).13 What is the recommended treatment of ASP? Treatment of ASP is focused on rehydration (intravenous or oral), broad antibiotic coverage, stabilization of underlying acute and chronic conditions, and minimizing medications that cause xerostomia. Treatments that may increase salivary flow are also helpful, including warm compresses, sialagogues, and/or parotid massage. Empiric antibiotics should broadly cover polymicrobial oral flora including aerobes, anaerobes, and b-lactamase–producing bacteria. In patients with risk factors for nosocomial infection, coverage for MRSA and Pseudomonas is appropriate. Box 2 summarizes acceptable empiric regimens. Antibiotics may be tailored to match sensitivities of predominant organisms identified on culture, but clinicians must be confident that
Acute Suppurative Parotitis
Fig. 3. CT image of patient with unilateral parotid and Stensen duct swelling.
appropriate specimen handling and culture techniques were used to reliably isolate anaerobes because they are notoriously difficult to isolate.6 If there is no improvement with medical therapy, causes of obstruction to saliva flow should be reconsidered, including tumor or ductal salivary stones (see Box 2). Most cases do not require imaging but, if abscess formation is suspected, ENT consultation is appropriate to determine the need for imaging to guide drainage (Box 3). What is chronic bacterial parotitis? A history of recurrent or prolonged (>1 month) bacterial parotitis may result in parenchymal and/or ductal changes that lead to disrupted saliva flow, saliva stasis, and recurrent infections.7,12 The fibrotic and cystic changes from the chronic infections are easily seen on ultrasonography.12 Patients are often middle aged with a long history of intermittent exacerbations of unilateral parotid swelling, with asymptomatic periods in between exacerbations.4 The periods of illness may last weeks or even
Fig. 4. Sialolith in the right Stensen duct. There is only mild parotid swelling in this patient.
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Box 2 Parenteral antibiotic regimes for ASP Immunocompetent with no MRSA risk factors Nafcillin with clindamycin or metronidazole First-generation cephalosporin with clindamycin or metronidazole Ampicillin-sulbactam Macrolide with metronidazole MRSA risk factors Vancomycin or linezolid with metronidazole Immunocompromised or recent hospitalization Vancomycin or linezolid with piperacillin-tazobactam or imipenem, meropenem or cefepime and metronidazole Data from Brook I. Aerobic and anaerobic microbiology of suppurative sialadenitis. J Med Microbiol 2002;51:526–9; and Carlson ER. Diagnosis and management of salivary gland infections. Oral Maxillofacial Surg Clin North Am 2009;21:293–312.
months at a time with a spectrum of severity.4 In contrast with ASP, the facial swelling and erythema are generally less severe. During initial exacerbations, patients may have systemic symptoms of fever and malaise, but patients are less likely to be toxic. There is generally less pain with eating and less purulent drainage noted.7 What is the treatment of chronic bacterial parotitis? In cases of chronic parotitis, sialographic imaging with CT or MRI is recommended to define the degree of stricture or dilatation of the Stensen duct.7 Conservative management includes measures to improve salivary flow: warm compresses, lozenges, and appropriate medication management. Systemic steroids have been reported as helpful at reducing inflammation, but they should not be used when the patient is acutely infected.6 Sialoendoscopy can be performed to lavage the Stensen duct and perform balloon dilation and/or stenting of the areas of stricture. Sialoendoscopy is not performed for ASP, because it potentially spreads bacterial further into the gland. Over time, the flares can worsen and a larger chronic abscess may form that can mimic a more toxic presentation of ASP and should be treated as such.7 The recurrent
Box 3 Severe complications of ASP Sepsis with or without shock Extending soft tissue infection into neck, face, mediastinum Osteomyelitis of the mandible Septic thrombophlebitis of the jugular vein (Lemierre syndrome) Airway obstruction Invasion of the external auditory canal Facial nerve palsy; this is more common with parotid malignancy
Acute Suppurative Parotitis
infections cause structural damage to the parotid, and eventually surgical removal of the gland may be required.4 What is chronic recurrent juvenile parotitis? This is a less described disease process and likely represents a variety of entities. Congenital abnormalities of the parotid gland ducts likely contribute to some cases. The ducts have a large diameter and poor sphincter function, which leads to easier migration of materials from the oral cavity. Children are generally aged 3 to 6 years when symptoms present, and symptoms often resolve by the teenage years. Treatment is usually a prolonged course of antibiotics.7,12 Does Mycobacterium cause parotitis? Mycobacterium tuberculosis is an uncommon cause of parotitis, even in areas with endemic tuberculosis (TB).14 Although mycobacterial granulomas can be seen in the parotid glands of patients with TB, it is more likely that the lymph nodes residing with the parotids are infected rather than the gland itself. On examination, tuberculous parotitis presents with a discrete, slow-growing mass that is more likely to be confused with a neoplasm than an acute bacterial infection.7,14 The mass is typically unilateral and associated with matted lymph nodes.15 A detailed social history assessing for TB risk factors is essential to determine how high M tuberculosis should be in the differential. If tuberculosis is suspected, skin testing (or an interferon-gamma release assay) and chest radiography should be obtained. Fine-needle aspiration may be helpful, but often this is equivocal and surgical excision, histology assessing for granulomas, and acid-fast bacilli culture are required.15 Nontuberculous mycobacterial parotid disease may be seen in children or immunocompromised adults. Mycobacterium kansasii, Mycobacterium avium-intracellulare, and Mycobacterium scrofulaceum are the most common organisms. Clinically these organisms cause a rapidly enlarging parotid mass that is nonresponsive to antibiotic therapy. A violaceous discoloration of the overlying skin has been described and is a clue to these disorders. Surgical removal of the gland is likely to be required.7 What is acute viral parotitis? The most frequent viral cause for parotitis is mumps (paramyxovirus). This vaccinepreventable disease is most common in children aged 4 to 6 years when most of the population is unvaccinated. Mumps is present worldwide, and in unvaccinated populations tends to have epidemics every 3 to 5 years.16 Before the vaccination era, essentially the entire population was exposed to mumps before adulthood. Mumps vaccination was introduced in the United States in 1967, creating a 99.8% reduction in cases.16 Recent declining trends in vaccination rates have led to a return of mumps epidemics in North America. In 2006, the United States had an outbreak of 6584 cases of mumps, predominantly in young adults aged 18 to 23 years; the majority had been vaccinated in childhood.16 It is thought that the immunity of these young adults had waned since their vaccination, and, unlike in their parents’ generation, they were not intermittently exposed to the mumps virus in the community during their adolescence.16 A clinical mumps infection is preceded by an incubation period of 7 to 21 days during which patients are asymptomatic. Patients are contagious for the 7 days before symptoms and 7 days after symptoms develop.16 The virus is spread in respiratory
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airborne droplets and fomites. Clinically, ill patients have bilateral (75%) or unilateral (25%) swelling of the parotid glands with pain, tenderness to palpation, erythema, malaise, and fever. Patients often complain of pain with speech, swallowing, and eating.16 Trismus may be present if there is inflammation involving the pterygoid muscles. Beyond parotitis, mumps can cause epididymo-orchitis (15%–30% in male patients), mastitis, oophoritis (5% in female patients), meningitis (1%–10%), encephalitis (0.1%), thyroiditis, hepatitis, pancreatitis, and myocarditis (3%–14%). In the past, laboratory studies have been of limited use in suspected mumps cases because this has been primarily a clinical diagnosis. Given the public health implications of an outbreak, the US Centers for Disease Control and Prevention now recommends that a buccal or oral swab specimen and a blood sample be obtained from all patients with clinical features consistent with mumps. State health departments may require notification and are an excellent resource for specific testing and specimen handling.17 Note that the highest yield is from specimens collected from throat swabs.14 Other viral causes that may cause parotitis include:
Coxsackie A virus Cytomegalovirus Epstein-Barr virus Influenza A Parainfluenza virus type 3 Lymphocytic choriomeningitis Human herpes virus 6 Echovirus
What is the treatment of viral parotitis? Viral parotitis is a self-limited condition with low mortality. Management is directed at symptomatic relief and monitoring for severe forms of the disease, such as meningitis and encephalitis. It is estimated that 13% of men experience diminished lifelong fertility if there is unilateral orchitis, and 30% to 87% if there is bilateral orchitis.16 No similar phenomenon has been noted in women, though data are limited because w5% of women have oophoritis. There is no evidence to support use of immune globin in treatment or prevention of mumps.16 How does human immunodeficiency virus (HIV) infection affect the parotid gland? Patients with HIV infection are at increased risk for ASP because of immunosuppression and debility. In addition, they are at risk for HIV-associated salivary gland disease (HIV-SGD). HIV-SGD leads to development of benign lymphoepithelial cysts (BLEC) in the parotid gland. Estimates are that 1% to 10% of individuals infected wit HIV develop parotid enlargement from BLEC.18 The pathogenesis is thought to be a reaction of glandular tissue to the HIV virus rather than direct damage from the HIV virus.12 Symptoms include painless, slow-growing, multifocal, and bilateral (80%) parotid enlargement, often with xerostomia.18 The finding of multiple cysts on parotid gland imaging is highly suspicious for HIV-related BLEC. BLEC is so uncommon outside of HIV infection that finding cystic enlargement of the parotid gland should prompt testing for HIV. Initial treatment consists of symptom control and antiretroviral therapy. More extensive cases may require sclerosing, radiation, or surgical treatments.18 The increased use of antiretroviral therapy over the last decade has led to a decline in incidence of BLEC.18 BLEC is a slowly progressing process, therefore if there is a rapid
Acute Suppurative Parotitis
enlargement of the parotid gland then evaluation for infection or lymphoma is warranted.18 RHEUMATOLOGIC CONDITIONS ASSOCIATED WITH PAROTITIS
Does sarcoidosis cause parotitis? The parotid is affected in less than 10% of cases of sarcoidosis. Clinically, sarcoidosis can cause a bilateral painless enlargement of the parotids that has a diffuse or multinodular character. Before establishing the diagnosis of sarcoidosis, lymphoma must be ruled out. The diagnosis is predominantly made by exclusion with confirmation of histologic findings of noncaseating granulomas in the parotid along with chest radiograph findings consistent with sarcoidosis. Heerfordt syndrome, also known as uveoparotid fever, is the constellation of parotid enlargement, bilateral uveitis, and facial nerve palsy.13,19 Identifying Heerfordt syndrome in a patient is considered pathognomonic for sarcoidosis.13 Does granulomatosis with polyangiitis present as parotitis? Salivary gland involvement is uncommon, but parotitis has been reported as a presenting sign of granulomatosis with polyangiitis (GPA; previously known as Wegener granulomatosis).20 GPA is a vasculitis of small and medium-sized vessels that leads to aseptic necrotizing granulomas.20 The cause and serologic confirmation of the disease is circulating cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA), but many cases do not test positive for C-ANCA at the time of initial presentation. The classic triad of GPA is disease in the upper and lower respiratory tract with associated kidney disease.20 Clinical symptoms commonly consist of sinusitis, epistaxis, cough, hemoptysis, and generalized systemic symptoms of arthralgia, fever, malaise, and weight loss.20 When parotitis is part of GPA, the patients tend to be more than 40 years of age and present with 2 to 6 weeks of either unilateral or bilateral parotid enlargement. Imaging identifies a mass in the parotid, possibly with central necrosis. This mass is often assumed to be malignancy or atypical infection and the diagnosis of GPA is delayed until a second organ system becomes affected. The consequences of delayed diagnosis of GPA can be disastrous. Therefore it is essential to consider multisystem disease early when cases of acute or subacute parotitis do not seem to be improving as anticipated. Laboratory investigations testing for inflammatory markers and ANCA (serially if the initial investigation is negative) in combination with biopsy assessing for vasculitis with granulomas are warranted in the evaluation for GPA. How is Sjo¨gren syndrome related to parotitis? Sjo¨gren syndrome does not cause acute parotitis but it does greatly increase the risk of developing ASP caused by xerostomia. Sjo¨gren syndrome is a systemic autoimmune disease characterized by chronic inflammation of the exocrine glands caused by progressive lymphocytic infiltration and destruction of the glandular tissue. The salivary and lacrimal glands are affected in particular, especially the parotid glands. Patients are classically women in their 40s or 50s.2 The resulting clinical presentation is xerostomia and keratoconjunctivitis. Sjo¨gren syndrome often causes enlargement of the parotids that is painless, but the decline in salivary flow potentiates upstream migration of bacteria, causing acute parotitis.
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What is drug-induced parotitis? Medication-induced xerostomia is commonly implicated in the development of parotitis. However, inflammation of the parotid directly attributable to medications is an uncommon and poorly understood phenomenon. Brooks and Thompson21 completed a literature review in 2012 and could not find consistent causal relationships of specific medications and parotitis. Despite this, many cases of parotitis associated with medications have been reported over the decades, most notably so-called iodide mumps and anesthesia mumps (Box 4).22 Iodide-related parotitis has been noted in patients with renal failure after receiving iodine-based contrast medium. These patients developed painless, bilateral parotid enlargement, which resolved over the following week with no long-term complications.22 Anesthesia mumps is a heterogeneous phenomenon that has no clear cause. Postulations have included head positioning during anesthesia creating pneumoparotitis, medications causing decreased Stensen duct sphincter tone, parasympathetic nerve stimulation causing parotid hyperemia, and inflammatory reaction to the anesthetic itself.22 If crepitus is noted on examination of the parotids, then pneumoparotitis is likely. The parotid enlargement of anesthesia mumps is self-limited and generally no treatment is required. CLINICAL GUIDELINES
To our knowledge, there are no published clinical guidelines on the evaluation or management of parotitis.
Box 4 Medications and toxins associated with parotitis L-Asparaginase
Cytarabine H2-blockers Angiotensin-converting enzyme inhibitors Calcium channel blockers Phenothiazine antipsychotics Promazine Thioridazine Clozapine Antiretroviral therapies Antibiotics Doxycycline Minocycline Nitrofurantoin Sulfadiazine Trimethoprim/sulfamethoxazole Organophosphate poisoning
Acute Suppurative Parotitis
PERFORMANCE IMPROVEMENT
ASP is most commonly encountered by hospitalists in patients admitted for surgery or decompensation of a chronic condition, and ASP develops as the patients become dehydrated and have declining saliva flow. Areas of quality improvement in ASP are focused on preventive measures. These measures include close attention to hydration; good oral hygiene; optimal management of the patients’ comorbidities, such as diabetes; and avoidance of medications causing xerostomia. In patients diagnosed with ASP, timely identification of the condition and initiation of appropriate antibiotic therapy may be useful quality indicators. REFERENCES
1. Beale T, Madani G. Anatomy of the salivary glands. Semin Ultrasound CT MR 2006;27:436–9. 2. Butt F. Chapter 18. Benign diseases of the salivary glands. In: Lalwani AK, editor. CURRENT diagnosis & treatment in otolaryngology—head & neck surgery. 3rd edition. New York: McGraw-Hill; 2012. Available at: http://accessmedicine.mhmedical. com/content.aspx?bookid5386&Sectionid539944053. Accessed February 10, 2015. 3. Grey H. Anatomy of the human body. 20th edition. Philadelphia: Lea & Febiger; 1918. 4. Mandel L. Differentiating acute suppurative parotitis from acute exacerbations of a chronic parotitis: case reports. J Oral Maxillofac Surg 2008;66:1964–8. 5. Fattahi TT, Lyu PE, Van Sickels JE. Management of acute suppurative parotitis. J Oral Maxillofac Surg 2002;60:446–8. 6. Brook I. Aerobic and anaerobic microbiology of suppurative sialadenitis. J Med Microbiol 2002;51:526–9. 7. Carlson ER. Diagnosis and management of salivary gland infections. Oral Maxillofacial Surg Clin North Am 2009;21:293–312. 8. Gilbert DN, Chambers HF, Eliopoulos GM, et al, editors. The Sanford guide to antimicrobial therapy. 44th edition. Sperryville (VA): Antimicrobial Therapy; 2014. 9. Armstrong MA, Turturro MA. Salivary gland emergencies. Emerg Med Clin North Am 2013;31:481–99. 10. Brook I. Acute bacterial suppurative parotitis: microbiology and management. J Craniofac Surg 2003;149(1):37–40. 11. Katz J, Fisher D, Leviner E, et al. Bacterial colonization of the parotid duct in xerostomia. Int J Oral Maxillofac Surg 1990;19:7–9. 12. Cascarini L, McGurk M. Epidemiology of salivary gland infections. Oral Maxillofacial Surg Clin North Am 2009;21:353–7. 13. Madani G, Beale T. Inflammatory conditions of the salivary glands. Semin Ultrasound CT MR 2006;27:440–51. 14. Iseri M, Aydiner O, Celik L, et al. Tuberculosis of the parotid gland. J Laryngol Otol 2005;119:311–3. 15. Holmes S, Gleeson MJ, Cawson RA. Mycobacterial disease of the parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:292–8. 16. Rubin S, Carbone KM. Chapter 194. Mumps. In: Longo DL, Fauci AS, Kasper DL, et al, editors. Harrison’s principles of internal medicine. 18th edition. New York: McGraw-Hill; 2012. Available at: http://accessmedicine.mhmedical.com/content. aspx?bookid5331&Sectionid540726953. Accessed February 10, 2015. 17. Mumps. Centers for Disease Control and Prevention website. 2014. Available at: http://www.cdc.gov/mumps/. Accessed October 30, 2014.
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18. Shanti RM, Aziz SR. HIV-associated salivary gland disease. Oral Maxillofacial Surg Clin North Am 2009;21:339–43. 19. Wasfi YS, Wasfi YS, Fontenot AP. Chapter 12. Sarcoidosis. In: Hanley ME, Welsh CH, editors. CURRENT diagnosis & treatment in pulmonary medicine. New York: McGraw-Hill; 2003. Available at: http://accessmedicine.mhmedical.com/content. aspx?bookid5346&Sectionid539883260. Accessed February 10, 2015. 20. Barrett AW. Wegener’s granulomatosis of the major salivary glands. J Oral Pathol Med 2012;41:721–7. 21. Brooks KG, Thompson DF. A review and assessment of drug-induced parotitis. Ann Pharmacother 2012;46:1688–98. 22. Mandel L, Surattanont F. Bilateral parotid swelling: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:221–37.
MD
a
, Bradley J. Benson,
MD
b,
*
KEYWORDS Parotitis Parotid gland Acute suppurative parotitis Sialolithiasis Sialadenitis
HOSPITAL MEDICINE CLINICS CHECKLIST
1. Parotitis is an inflammatory process of the parotid gland caused by an infectious or rheumatologic process. 2. Obstruction of the Stensen duct by a sialolith or a foreign body is the most common cause of acute inflammation. 3. Acute suppurative parotitis (ASP) is most commonly a result of static salivary flow and migration of oral microbes up the Stensen duct. 4. In the past, ASP was a severe complication of abdominal surgery, but in the modern era of improved hydration, oral hygiene, and antibiotics it is rare. 5. Bacterial ASP is typically polymicrobial, with high rates of Staphylococcus aureus and anaerobic organisms. Patients with prolonged illnesses or frequent contact with the health care system are at risk for health care–associated ASP infection caused by methicillin resistant S aureus or Pseudomonas. 6. Management of ASP is focused on relieving parotid obstruction with sialagogues or parotid massage, appropriate rehydration, antibiotic therapy, and optimization of medical comorbidities. 7. Admission to the hospital should be considered if the patient appears systemically ill with concern for sepsis or severe dehydration. 8. Consultation from an ear, nose, and throat specialist should be considered in cases in which a discrete palpable mass is present. 9. Ultrasonography is an effective imaging modality to assess for parotid inflammation, sialoliths, cystic lesions, or abscesses. CONTINUED
Conflicts of interest: The authors have no conflicts of interest to disclose. a Departments of Internal Medicine and Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA; b Division of General Internal Medicine, University of Minnesota Medical School, D653 Mayo Memorial Bldg, 420 Delaware St. SE, MMC 741, Minneapolis, MN 55455, USA * Corresponding author. E-mail address: [email protected] Hosp Med Clin 4 (2015) 191–204 http://dx.doi.org/10.1016/j.ehmc.2014.12.006 2211-5943/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
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10. The differential for parotitis beyond acute bacterial infection includes viral infection, benign lymphoepithelial cysts associated with human immunodeficiency virus, rheumatologic disease, endocrine disease, mycobacterial or fungal infections, and medication effects.
What is parotitis? Parotitis is defined as an inflammatory process of the parotid gland. Sialadenitis is the inflammation or infection of a salivary gland, and parotitis is the specific term for parotid gland inflammation. Common causes are bacterial, viral, or rheumatologic. What are the pertinent anatomic features of the parotid gland? The parotid glands are paired salivary glands located lateral to the masseter muscle extending posteriorly to the sternocleidomastoid muscle in the region over the ramus of the mandible (Fig. 1).1,2 The parotids are the largest of the more than 500 salivary glands in the oral mucosa.1 The parotid glands secrete saliva into the oral cavity through the Stensen duct. The Stensen duct enters the oral cavity near the second maxillary molar transecting the buccinators muscle into the buccal mucosa. The significant structures that run through or are adjacent to the parotid gland include the facial nerve, external carotid artery, retromandibular vein, and multiple lymph nodes.1 An estimated 500 to 1500 mL of saliva are excreted daily from the parotid glands, submandibular glands, and the minor salivary glands.2 What is acute suppurative parotitis (ASP)? ASP is a bacterial infection of the parotid gland. The first clinical description of ASP is attributed to Cruveilhier in 1836. The pathophysiologic basis of ASP is static flow of saliva leading to migration of oral flora up the Stensen duct. The reduced flow of saliva may be caused by duct stricture, obstruction (most commonly from sialoliths), or decreased saliva production secondary to illness or medication.3 The decline in saliva flow creates stasis, which potentiates bacterial growth, and leads to the loss of saliva’s bacteriostatic effects, contributing to an oral environment that is more prone to bacterial infection. What predisposes patients to develop ASP and how can it be prevented? In the past, epidemiologic studies have shown a higher incidence of ASP in patients with trauma and those who have recently undergone abdominal surgery.4 Other known factors that contribute to risk of ASP include dehydration, starvation, debilitation, advanced age, immunosuppression, oral neoplasm, tracheostomy, and known ductal obstruction.5–8 Diabetes is a common comorbidity in these patients, presumably because of the dehydration and immunosuppression associated with hyperglycemia. Drugs that decrease saliva production, especially anticholinergic agents, also predispose patients to develop ASP (Box 1).3 Before the modern antibiotic era, ASP carried a mortality of w50%, making it a serious postoperative complication. President James Garfield died in 1881 of secondary ASP infection 11 weeks after surviving a gunshot wound to the abdomen.3,7 The dehydration and malnutrition that occurs with severe illness or abdominal trauma likely accounted for the high historical
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Fig. 1. Dissection drawings of the salivary glands and the facial nerve. (From Gray H. Anatomy of the human body. 20th edition. Philadelphia: Lea & Febiger; 1918.)
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Box 1 Factors that decrease salivary flow, and thus increase risk of ASP Ductal obstruction Dehydration Nerve damage Irradiation to the gland area Medications; specifically anticholinergic medications Chronic disease Diabetes mellitus Renal failure Cystic fibrosis Hypothyroidism Sjo¨gren syndrome Malnutrition Tracheotomy Periodontal disease
mortality of ASP, as in President Garfield’s case. Current perioperative attention to adequate hydration, nutrition, and oral hygiene has led to a profound decline in the rates of ASP in modern hospitals.7 How often are people hospitalized for ASP? Bacterial infections of the salivary glands account for 0.01% to 0.02% of hospital admissions and less than 0.1% of postoperative patients.5,7 Patients are more likely to be hospitalized for an exacerbation of a chronic condition, and ASP is a secondary diagnosis. The role of the hospitalist is as much about appropriate management of the chronic conditions with attention to preventive measures, including rehydration and oral hygiene, as it is about treatment of ASP. What history is important to assess in patients with ASP? A comprehensive history is essential when evaluating a patient with ASP. Patients often have multiple comorbid chronic disease conditions contributing to development of ASP. The patients are typically middle aged to elderly, with medical history of recent surgery, chronic disease, and/or polypharmacy.9 The chronicity of the parotid inflammation is essential in establishing a diagnosis of ASP versus a chronic parotitis (symptoms>1 month), which is more likely to have architectural damage to the gland and abscess formation that may require surgical drainage. A complete review of systems is essential to assess for signs of toxicity and/or dehydration. Reports of prandial pain separate from trismus may indicate obstructive process and sialolithiasis.7 What are the characteristic examination findings in patients with ASP? On examination there is typically generalized swelling over the parotid, likely unilateral, with erythema, tenderness, induration, trismus, and fever. The expression of pus from
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the Stensen duct by milking of the parotid gland is considered a pathognomonic finding.4 Because of the dense fibrous capsule over the parotid gland, rarely does pus drain externally.2,10 If there is bilateral parotid swelling, then a systemic nonbacterial cause should be considered. If there is a discrete mass noted in the parotid, then consider neoplasm or large abscess, and imaging will be needed to better define the mass. In these cases, consultation from an ear, nose, and throat (ENT) specialist is appropriate for consideration of either biopsy or drainage (Fig. 2). What are the initial studies in evaluation when suspecting ASP? Evaluation is similar to other infectious processes: complete blood count with differential, basic metabolic panel, and Gram stain and cultures of the suppurative discharge. Although cultured pus from the Stensen duct may be helpful, it has a high likelihood of being contaminated by normal oral flora.4 Direct aspiration of any significant abscess that is identified or aspiration of the parotid is more likely to identify a causative pathogen.10 Which bacteria cause ASP? The pathologic microbes most commonly migrate from the oral space into the parotid through the Stensen duct. Staphylococcus aureus is the most common individual organism isolated from parotitis specimens, but the anaerobic oral flora comprises a large percentage of cases as a class. One study of parotid gland infections identified S aureus in 18% of cases, whereas at least 1 anaerobic bacterium was noted in 54%
Fig. 2. Algorithm of evaluation and management of parotid swelling. CT, computed tomography; IV, intravenous; US, ultrasonography.
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of cases.10 A similar study found 64% of isolates containing anaerobic bacteria.6 The presumption is that, in many clinical settings, anaerobic organisms are not identified more often because of inadequate anaerobic sample handling and culture techniques. The study notably found that 51% of cases grew a b-lactamase–producing organism, which has implications for antibiotic selection.6 The patient’s medical history and recent exposure to nosocomial organisms play an important role in determining what organism is infecting the parotid gland. As emphasized previously, salivary flow through the Stensen duct is essential to prevent migration of bacteria into the parotid. In saliva there is a high concentration of fibronectin, to which Staphylococcus species have a high adherence. Therefore, a previously healthy person who has a decrease in saliva flow is more likely to have gram-positive ASP. Deficiency in fibronectin has been noted in chronically ill patients and patients with cystic fibrosis. Studies have shown that a lack of fibronectin favors adherence of Pseudomonas and/or Escherichia coli.11 Regardless, it should be assumed that, given the diversity of flora in the oral cavity, the antimicrobial choice for parotitis should be broad enough to cover both aerobic and anaerobic organisms. If the patient is or was recently hospitalized, antibiotics should cover resistant organisms like methicillinresistant S aureus (MRSA) or Pseudomonas.7 What is the role of imaging in ASP? Initial plain films of the mouth and jaw, specifically panoramic views, can be helpful in identifying a sialolith that may be causing obstruction. Sialography is not recommended in ASP given the risk for duct rupture, spreading bacteria into tissues, and intense pain associated with the study.12 Ultrasonography by a skilled operator can be the safest, most accurate, and least expensive tool for diagnosing inflammatory parotid disease. Sialoliths are frequently identified with ultrasonography. Doppler ultrasonography is highly accurate at identifying the cystic nature of lesions versus abscesses.13 Noncontrast computed tomography (CT) is helpful when ultrasonography cannot identify a sialolith but stone obstruction is suspected. Noncontrast CT potentially can also help delineate the extent of stone burden. Contrast-enhanced CT is indicated when abscess is suspected and ultrasonography is unable to fully define the lesion. In addition, contrast-enhanced CT can aid when there is a question of dental infections or abscess contributing to or mimicking parotitis.13 MRI is not necessarily better than CT or ultrasonography at identifying sialoliths, but it is less invasive compared with conventional sialography. MRI is most useful in assessment of the parenchymal changes of the gland and identification of atrophy that may be associated with Sjo¨gren syndrome (Figs. 3 and 4).13 What is the recommended treatment of ASP? Treatment of ASP is focused on rehydration (intravenous or oral), broad antibiotic coverage, stabilization of underlying acute and chronic conditions, and minimizing medications that cause xerostomia. Treatments that may increase salivary flow are also helpful, including warm compresses, sialagogues, and/or parotid massage. Empiric antibiotics should broadly cover polymicrobial oral flora including aerobes, anaerobes, and b-lactamase–producing bacteria. In patients with risk factors for nosocomial infection, coverage for MRSA and Pseudomonas is appropriate. Box 2 summarizes acceptable empiric regimens. Antibiotics may be tailored to match sensitivities of predominant organisms identified on culture, but clinicians must be confident that
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Fig. 3. CT image of patient with unilateral parotid and Stensen duct swelling.
appropriate specimen handling and culture techniques were used to reliably isolate anaerobes because they are notoriously difficult to isolate.6 If there is no improvement with medical therapy, causes of obstruction to saliva flow should be reconsidered, including tumor or ductal salivary stones (see Box 2). Most cases do not require imaging but, if abscess formation is suspected, ENT consultation is appropriate to determine the need for imaging to guide drainage (Box 3). What is chronic bacterial parotitis? A history of recurrent or prolonged (>1 month) bacterial parotitis may result in parenchymal and/or ductal changes that lead to disrupted saliva flow, saliva stasis, and recurrent infections.7,12 The fibrotic and cystic changes from the chronic infections are easily seen on ultrasonography.12 Patients are often middle aged with a long history of intermittent exacerbations of unilateral parotid swelling, with asymptomatic periods in between exacerbations.4 The periods of illness may last weeks or even
Fig. 4. Sialolith in the right Stensen duct. There is only mild parotid swelling in this patient.
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Box 2 Parenteral antibiotic regimes for ASP Immunocompetent with no MRSA risk factors Nafcillin with clindamycin or metronidazole First-generation cephalosporin with clindamycin or metronidazole Ampicillin-sulbactam Macrolide with metronidazole MRSA risk factors Vancomycin or linezolid with metronidazole Immunocompromised or recent hospitalization Vancomycin or linezolid with piperacillin-tazobactam or imipenem, meropenem or cefepime and metronidazole Data from Brook I. Aerobic and anaerobic microbiology of suppurative sialadenitis. J Med Microbiol 2002;51:526–9; and Carlson ER. Diagnosis and management of salivary gland infections. Oral Maxillofacial Surg Clin North Am 2009;21:293–312.
months at a time with a spectrum of severity.4 In contrast with ASP, the facial swelling and erythema are generally less severe. During initial exacerbations, patients may have systemic symptoms of fever and malaise, but patients are less likely to be toxic. There is generally less pain with eating and less purulent drainage noted.7 What is the treatment of chronic bacterial parotitis? In cases of chronic parotitis, sialographic imaging with CT or MRI is recommended to define the degree of stricture or dilatation of the Stensen duct.7 Conservative management includes measures to improve salivary flow: warm compresses, lozenges, and appropriate medication management. Systemic steroids have been reported as helpful at reducing inflammation, but they should not be used when the patient is acutely infected.6 Sialoendoscopy can be performed to lavage the Stensen duct and perform balloon dilation and/or stenting of the areas of stricture. Sialoendoscopy is not performed for ASP, because it potentially spreads bacterial further into the gland. Over time, the flares can worsen and a larger chronic abscess may form that can mimic a more toxic presentation of ASP and should be treated as such.7 The recurrent
Box 3 Severe complications of ASP Sepsis with or without shock Extending soft tissue infection into neck, face, mediastinum Osteomyelitis of the mandible Septic thrombophlebitis of the jugular vein (Lemierre syndrome) Airway obstruction Invasion of the external auditory canal Facial nerve palsy; this is more common with parotid malignancy
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infections cause structural damage to the parotid, and eventually surgical removal of the gland may be required.4 What is chronic recurrent juvenile parotitis? This is a less described disease process and likely represents a variety of entities. Congenital abnormalities of the parotid gland ducts likely contribute to some cases. The ducts have a large diameter and poor sphincter function, which leads to easier migration of materials from the oral cavity. Children are generally aged 3 to 6 years when symptoms present, and symptoms often resolve by the teenage years. Treatment is usually a prolonged course of antibiotics.7,12 Does Mycobacterium cause parotitis? Mycobacterium tuberculosis is an uncommon cause of parotitis, even in areas with endemic tuberculosis (TB).14 Although mycobacterial granulomas can be seen in the parotid glands of patients with TB, it is more likely that the lymph nodes residing with the parotids are infected rather than the gland itself. On examination, tuberculous parotitis presents with a discrete, slow-growing mass that is more likely to be confused with a neoplasm than an acute bacterial infection.7,14 The mass is typically unilateral and associated with matted lymph nodes.15 A detailed social history assessing for TB risk factors is essential to determine how high M tuberculosis should be in the differential. If tuberculosis is suspected, skin testing (or an interferon-gamma release assay) and chest radiography should be obtained. Fine-needle aspiration may be helpful, but often this is equivocal and surgical excision, histology assessing for granulomas, and acid-fast bacilli culture are required.15 Nontuberculous mycobacterial parotid disease may be seen in children or immunocompromised adults. Mycobacterium kansasii, Mycobacterium avium-intracellulare, and Mycobacterium scrofulaceum are the most common organisms. Clinically these organisms cause a rapidly enlarging parotid mass that is nonresponsive to antibiotic therapy. A violaceous discoloration of the overlying skin has been described and is a clue to these disorders. Surgical removal of the gland is likely to be required.7 What is acute viral parotitis? The most frequent viral cause for parotitis is mumps (paramyxovirus). This vaccinepreventable disease is most common in children aged 4 to 6 years when most of the population is unvaccinated. Mumps is present worldwide, and in unvaccinated populations tends to have epidemics every 3 to 5 years.16 Before the vaccination era, essentially the entire population was exposed to mumps before adulthood. Mumps vaccination was introduced in the United States in 1967, creating a 99.8% reduction in cases.16 Recent declining trends in vaccination rates have led to a return of mumps epidemics in North America. In 2006, the United States had an outbreak of 6584 cases of mumps, predominantly in young adults aged 18 to 23 years; the majority had been vaccinated in childhood.16 It is thought that the immunity of these young adults had waned since their vaccination, and, unlike in their parents’ generation, they were not intermittently exposed to the mumps virus in the community during their adolescence.16 A clinical mumps infection is preceded by an incubation period of 7 to 21 days during which patients are asymptomatic. Patients are contagious for the 7 days before symptoms and 7 days after symptoms develop.16 The virus is spread in respiratory
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airborne droplets and fomites. Clinically, ill patients have bilateral (75%) or unilateral (25%) swelling of the parotid glands with pain, tenderness to palpation, erythema, malaise, and fever. Patients often complain of pain with speech, swallowing, and eating.16 Trismus may be present if there is inflammation involving the pterygoid muscles. Beyond parotitis, mumps can cause epididymo-orchitis (15%–30% in male patients), mastitis, oophoritis (5% in female patients), meningitis (1%–10%), encephalitis (0.1%), thyroiditis, hepatitis, pancreatitis, and myocarditis (3%–14%). In the past, laboratory studies have been of limited use in suspected mumps cases because this has been primarily a clinical diagnosis. Given the public health implications of an outbreak, the US Centers for Disease Control and Prevention now recommends that a buccal or oral swab specimen and a blood sample be obtained from all patients with clinical features consistent with mumps. State health departments may require notification and are an excellent resource for specific testing and specimen handling.17 Note that the highest yield is from specimens collected from throat swabs.14 Other viral causes that may cause parotitis include:
Coxsackie A virus Cytomegalovirus Epstein-Barr virus Influenza A Parainfluenza virus type 3 Lymphocytic choriomeningitis Human herpes virus 6 Echovirus
What is the treatment of viral parotitis? Viral parotitis is a self-limited condition with low mortality. Management is directed at symptomatic relief and monitoring for severe forms of the disease, such as meningitis and encephalitis. It is estimated that 13% of men experience diminished lifelong fertility if there is unilateral orchitis, and 30% to 87% if there is bilateral orchitis.16 No similar phenomenon has been noted in women, though data are limited because w5% of women have oophoritis. There is no evidence to support use of immune globin in treatment or prevention of mumps.16 How does human immunodeficiency virus (HIV) infection affect the parotid gland? Patients with HIV infection are at increased risk for ASP because of immunosuppression and debility. In addition, they are at risk for HIV-associated salivary gland disease (HIV-SGD). HIV-SGD leads to development of benign lymphoepithelial cysts (BLEC) in the parotid gland. Estimates are that 1% to 10% of individuals infected wit HIV develop parotid enlargement from BLEC.18 The pathogenesis is thought to be a reaction of glandular tissue to the HIV virus rather than direct damage from the HIV virus.12 Symptoms include painless, slow-growing, multifocal, and bilateral (80%) parotid enlargement, often with xerostomia.18 The finding of multiple cysts on parotid gland imaging is highly suspicious for HIV-related BLEC. BLEC is so uncommon outside of HIV infection that finding cystic enlargement of the parotid gland should prompt testing for HIV. Initial treatment consists of symptom control and antiretroviral therapy. More extensive cases may require sclerosing, radiation, or surgical treatments.18 The increased use of antiretroviral therapy over the last decade has led to a decline in incidence of BLEC.18 BLEC is a slowly progressing process, therefore if there is a rapid
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enlargement of the parotid gland then evaluation for infection or lymphoma is warranted.18 RHEUMATOLOGIC CONDITIONS ASSOCIATED WITH PAROTITIS
Does sarcoidosis cause parotitis? The parotid is affected in less than 10% of cases of sarcoidosis. Clinically, sarcoidosis can cause a bilateral painless enlargement of the parotids that has a diffuse or multinodular character. Before establishing the diagnosis of sarcoidosis, lymphoma must be ruled out. The diagnosis is predominantly made by exclusion with confirmation of histologic findings of noncaseating granulomas in the parotid along with chest radiograph findings consistent with sarcoidosis. Heerfordt syndrome, also known as uveoparotid fever, is the constellation of parotid enlargement, bilateral uveitis, and facial nerve palsy.13,19 Identifying Heerfordt syndrome in a patient is considered pathognomonic for sarcoidosis.13 Does granulomatosis with polyangiitis present as parotitis? Salivary gland involvement is uncommon, but parotitis has been reported as a presenting sign of granulomatosis with polyangiitis (GPA; previously known as Wegener granulomatosis).20 GPA is a vasculitis of small and medium-sized vessels that leads to aseptic necrotizing granulomas.20 The cause and serologic confirmation of the disease is circulating cytoplasmic antineutrophil cytoplasmic antibody (C-ANCA), but many cases do not test positive for C-ANCA at the time of initial presentation. The classic triad of GPA is disease in the upper and lower respiratory tract with associated kidney disease.20 Clinical symptoms commonly consist of sinusitis, epistaxis, cough, hemoptysis, and generalized systemic symptoms of arthralgia, fever, malaise, and weight loss.20 When parotitis is part of GPA, the patients tend to be more than 40 years of age and present with 2 to 6 weeks of either unilateral or bilateral parotid enlargement. Imaging identifies a mass in the parotid, possibly with central necrosis. This mass is often assumed to be malignancy or atypical infection and the diagnosis of GPA is delayed until a second organ system becomes affected. The consequences of delayed diagnosis of GPA can be disastrous. Therefore it is essential to consider multisystem disease early when cases of acute or subacute parotitis do not seem to be improving as anticipated. Laboratory investigations testing for inflammatory markers and ANCA (serially if the initial investigation is negative) in combination with biopsy assessing for vasculitis with granulomas are warranted in the evaluation for GPA. How is Sjo¨gren syndrome related to parotitis? Sjo¨gren syndrome does not cause acute parotitis but it does greatly increase the risk of developing ASP caused by xerostomia. Sjo¨gren syndrome is a systemic autoimmune disease characterized by chronic inflammation of the exocrine glands caused by progressive lymphocytic infiltration and destruction of the glandular tissue. The salivary and lacrimal glands are affected in particular, especially the parotid glands. Patients are classically women in their 40s or 50s.2 The resulting clinical presentation is xerostomia and keratoconjunctivitis. Sjo¨gren syndrome often causes enlargement of the parotids that is painless, but the decline in salivary flow potentiates upstream migration of bacteria, causing acute parotitis.
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What is drug-induced parotitis? Medication-induced xerostomia is commonly implicated in the development of parotitis. However, inflammation of the parotid directly attributable to medications is an uncommon and poorly understood phenomenon. Brooks and Thompson21 completed a literature review in 2012 and could not find consistent causal relationships of specific medications and parotitis. Despite this, many cases of parotitis associated with medications have been reported over the decades, most notably so-called iodide mumps and anesthesia mumps (Box 4).22 Iodide-related parotitis has been noted in patients with renal failure after receiving iodine-based contrast medium. These patients developed painless, bilateral parotid enlargement, which resolved over the following week with no long-term complications.22 Anesthesia mumps is a heterogeneous phenomenon that has no clear cause. Postulations have included head positioning during anesthesia creating pneumoparotitis, medications causing decreased Stensen duct sphincter tone, parasympathetic nerve stimulation causing parotid hyperemia, and inflammatory reaction to the anesthetic itself.22 If crepitus is noted on examination of the parotids, then pneumoparotitis is likely. The parotid enlargement of anesthesia mumps is self-limited and generally no treatment is required. CLINICAL GUIDELINES
To our knowledge, there are no published clinical guidelines on the evaluation or management of parotitis.
Box 4 Medications and toxins associated with parotitis L-Asparaginase
Cytarabine H2-blockers Angiotensin-converting enzyme inhibitors Calcium channel blockers Phenothiazine antipsychotics Promazine Thioridazine Clozapine Antiretroviral therapies Antibiotics Doxycycline Minocycline Nitrofurantoin Sulfadiazine Trimethoprim/sulfamethoxazole Organophosphate poisoning
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PERFORMANCE IMPROVEMENT
ASP is most commonly encountered by hospitalists in patients admitted for surgery or decompensation of a chronic condition, and ASP develops as the patients become dehydrated and have declining saliva flow. Areas of quality improvement in ASP are focused on preventive measures. These measures include close attention to hydration; good oral hygiene; optimal management of the patients’ comorbidities, such as diabetes; and avoidance of medications causing xerostomia. In patients diagnosed with ASP, timely identification of the condition and initiation of appropriate antibiotic therapy may be useful quality indicators. REFERENCES
1. Beale T, Madani G. Anatomy of the salivary glands. Semin Ultrasound CT MR 2006;27:436–9. 2. Butt F. Chapter 18. Benign diseases of the salivary glands. In: Lalwani AK, editor. CURRENT diagnosis & treatment in otolaryngology—head & neck surgery. 3rd edition. New York: McGraw-Hill; 2012. Available at: http://accessmedicine.mhmedical. com/content.aspx?bookid5386&Sectionid539944053. Accessed February 10, 2015. 3. Grey H. Anatomy of the human body. 20th edition. Philadelphia: Lea & Febiger; 1918. 4. Mandel L. Differentiating acute suppurative parotitis from acute exacerbations of a chronic parotitis: case reports. J Oral Maxillofac Surg 2008;66:1964–8. 5. Fattahi TT, Lyu PE, Van Sickels JE. Management of acute suppurative parotitis. J Oral Maxillofac Surg 2002;60:446–8. 6. Brook I. Aerobic and anaerobic microbiology of suppurative sialadenitis. J Med Microbiol 2002;51:526–9. 7. Carlson ER. Diagnosis and management of salivary gland infections. Oral Maxillofacial Surg Clin North Am 2009;21:293–312. 8. Gilbert DN, Chambers HF, Eliopoulos GM, et al, editors. The Sanford guide to antimicrobial therapy. 44th edition. Sperryville (VA): Antimicrobial Therapy; 2014. 9. Armstrong MA, Turturro MA. Salivary gland emergencies. Emerg Med Clin North Am 2013;31:481–99. 10. Brook I. Acute bacterial suppurative parotitis: microbiology and management. J Craniofac Surg 2003;149(1):37–40. 11. Katz J, Fisher D, Leviner E, et al. Bacterial colonization of the parotid duct in xerostomia. Int J Oral Maxillofac Surg 1990;19:7–9. 12. Cascarini L, McGurk M. Epidemiology of salivary gland infections. Oral Maxillofacial Surg Clin North Am 2009;21:353–7. 13. Madani G, Beale T. Inflammatory conditions of the salivary glands. Semin Ultrasound CT MR 2006;27:440–51. 14. Iseri M, Aydiner O, Celik L, et al. Tuberculosis of the parotid gland. J Laryngol Otol 2005;119:311–3. 15. Holmes S, Gleeson MJ, Cawson RA. Mycobacterial disease of the parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:292–8. 16. Rubin S, Carbone KM. Chapter 194. Mumps. In: Longo DL, Fauci AS, Kasper DL, et al, editors. Harrison’s principles of internal medicine. 18th edition. New York: McGraw-Hill; 2012. Available at: http://accessmedicine.mhmedical.com/content. aspx?bookid5331&Sectionid540726953. Accessed February 10, 2015. 17. Mumps. Centers for Disease Control and Prevention website. 2014. Available at: http://www.cdc.gov/mumps/. Accessed October 30, 2014.
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18. Shanti RM, Aziz SR. HIV-associated salivary gland disease. Oral Maxillofacial Surg Clin North Am 2009;21:339–43. 19. Wasfi YS, Wasfi YS, Fontenot AP. Chapter 12. Sarcoidosis. In: Hanley ME, Welsh CH, editors. CURRENT diagnosis & treatment in pulmonary medicine. New York: McGraw-Hill; 2003. Available at: http://accessmedicine.mhmedical.com/content. aspx?bookid5346&Sectionid539883260. Accessed February 10, 2015. 20. Barrett AW. Wegener’s granulomatosis of the major salivary glands. J Oral Pathol Med 2012;41:721–7. 21. Brooks KG, Thompson DF. A review and assessment of drug-induced parotitis. Ann Pharmacother 2012;46:1688–98. 22. Mandel L, Surattanont F. Bilateral parotid swelling: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:221–37.