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Home , Parotid duct, Parotid gland, Parotitis, Saliva, Salivary gland, Sialadenitis

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Shankar Haran, MBBS; Presentation is key to diagnosing Saniya Kazi, MBBS, FRACP; Saliya Caldera, MBBS, BSc, FRCS (ORL-HNS) salivary disorders Departments of Otolaryngology and Paediatrics, Townsville Hospital, Queensland, Australia Initial offer the best guide to next Shankar.haran01@gmail steps in assessment, testing, and treatment, plus any .com

The authors reported no needed referral or multidisciplinary care. potential conflict of interest relevant to this article.

aking a diagnosis of a disorder can be PRACTICE difficult. Common presentations, such as a painful RECOMMENDATIONS or swollen gland, can be caused by numerous disor- ❯ Use ultrasonography M ders of strikingly variable severity and consequences, includ- for initial imaging of a ing inflammatory, infectious, and neoplastic conditions, for salivary gland. A which treatment can differ significantly, and referral for spe- ❯ Refer patients with the cialty care is sometimes necessary. following findings for further Yet it is the patient’s presentation that can aid you in mak- specialty evaluation: abscess, ing the diagnosis that will guide management. Consider that unresponsive to medical care, recurrent or acute symptoms often result from , for example, and chronic symptoms, suspected chronic or recurrent symptoms are caused more often by ob- (for excision), and structive or nonobstructive inflammatory conditions and suspected . A . Diagnosis of an apparent neoplasm, prompted by clinical findings, is made using imaging and fine-needle -as Strength of recommendation (SOR) piration (FNA) . Acute infection usually resolves with A Good-quality patient-oriented evidence and supportive management; calculi that cause B Inconsistent or limited-quality persistent symptoms warrant referral for consideration of patient-oriented evidence stone or gland removal; and malignant neoplasms usually re-  C Consensus, usual practice, opinion, disease-oriented quire excision as well as dissection and or evidence, case series radiotherapy, or both—calling for multidisciplinary care. In this article, we clarify what can be an imprecise and per- plexing path from the presentation to diagnosis to treatment of disorders of the salivary . To begin, see “Geography of the salivary glands,” on page E3, for an overview of the location, struc- ture, and corresponding ducts of the component salivary glands (parotid, submandibular, sublingual, and minor glands).

Presentation helps establish the differential Dx Ask: Are the glands swollen? Painless salivary gland swelling has a variety of causes, includ- ing neoplasm, sialadenosis, and the eating disorders bulimia and anorexia nervosa. There is significant overlap of presenta- tions among those causes (FIGURE). accompanying swell- ing is uncommon but not unheard of. CONTINUED

MDEDGE.COM/FAMILYMEDICINE VOL 68, NO 8 | OCTOBER 2019 | THE JOURNAL OF FAMILY PRACTICE E1 ❚ Neoplasms. Tumors of the salivary . Features of a tumor that gland are relatively uncommon, constitut- raise concern of malignancy include6: ing approximately 2% of head and neck • rapid growth neoplasms; most (80%) occur in the parotid • pain gland, and most of those are benign.1 Al- • tethering to underlying structures or though benign and malignant salivary gland overlying skin neoplasms do not usually present with pain, • firm mass pain can be associated with a neoplasm sec- • associated cervical ondary to suppuration, hemorrhage into a • facial- palsy. mass, or infiltration of a malignancy into ad- jacent tissue. The workup of a malignant tumor is Benign tumors. The majority of benign the same as it is for a benign neoplasm: tumors are pleomorphic adenomas of the US-guided FNA, essential for diagnosis, and parotid, accounting for approximately 60% of contrast-enhanced CT or MRI to delineate salivary gland neoplasms.1,2 Tumors localized the tumor. to the are often (in 50% Malignant salivary gland neoplasms of cases) malignant, however.3 usually require excision as well as neck dis- Benign tumors are typically slow- section and chemotherapy or radiotherapy, growing and, generally, painless. On ex- or both, necessitating a multidisciplinary ap- Ultrasonography amination, they are well-circumscribed, proach. Also, there is potential for squamous- is an excellent mobile, and nontender. Patients present- cell carcinoma and melanoma of the head to initial imaging ing late with a large tumor might, however, metastasize to salivary gland nodes; it choice for experience pain secondary to stretching of is important, therefore, to examine for, and investigating a the parotid capsule or compression of local elicit any history of, cutaneous malignancy of possible salivary structures. the scalp or face. gland tumor. Ultrasonography (US) is an excellent ❚ Sialadenosis presents with asymp- initial imaging choice for investigating a tomatic bilateral hypertrophy of the salivary possible salivary gland tumor; US is com- glands—more commonly the parotids and bined with FNA, which is safe and highly rarely the submandibular glands. Swelling is reliable for differentiating neoplastic and persistent, symmetrical, painless, and of nor- non-neoplastic disorders.4 (Avoid open bi- mal tone on palpation. opsy of a neoplasm because of the risk of Causes of sialadenosis include alcohol- tumor spillage.) In patients with suspected ism and, less commonly, mellitus neoplasm, contrast-enhanced computed to- and malnutrition; some cases are idiopathic. mography (CT) or magnetic resonance imag- An autonomic neuropathy, causing excessive ing (MRI) should also be performed, because salivary acinar synthesis or failure of both modalities allow delineation of the tu- adequate secretion, or both, is common to al- mor mass and demonstration of any infiltra- coholism, diabetes, and malnutrition.7 Sub- tion of surrounding structures. sequent engorgement of acinar cells leads to Treatment of benign neoplasms involves clinical parotid hypertrophy. complete excision because, with some tu- Diagnosis is based on history and exami- mors, particularly pleomorphic adenomas, nation, as well as on the findings of US or CT, there is risk of malignant transformation over which will reveal bilateral gland enlargement time. Superficial is the most and increased density. The glands appear common procedure, because most benign dense because adipose cells are displaced by tumors occur in the superficial lobe of the pa- acinar cell hypertrophy; however, end-stage rotid gland. Delicate dissection of the facial changes can result in the opposite appearance: nerve is integral to the operation, although a lucent enlargement caused by fatty infiltra- temporary palsy will still occur in tion.2 FNA is unnecessary, unless there is suspi- 5% to 10% of patients undergoing superficial cion of neoplasm, as there would be in patients parotidectomy for a benign tumor, with per- with asymmetrical parotid enlargement, pain, manent injury occurring in fewer than 1%.5 enlargement, or facial-nerve in-

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Geography of the salivary glands

Parotid

Parotid gland

Sublingual gland

Submandibular gland

The salivary glands comprise the major paired parotid, submandibular, and sublingual glands, as well as minor salivary glands that line the oropharyngeal mucosa. Secretion of is modulated by both autonomic and humoral factors.

z The sits between the mastoid process, the ramus of the , and the styloid process, extend- ing from the external auditory meatus superiorly to below the and into the neck inferiorly. The gland is surrounded by a tough capsule. Embedded within the gland is the facial nerve, which divides into its 5 branches within the substance of the gland. The parotid (Stensen’s) duct passes anteriorly before turning medially to pierce the , opening onto the of the opposite the second upper .

z The submandibular gland comprises (1) a large superficial part that fills the space between the mandible and the IMAGE: ©STOCKTREKIMAGES/SCIENCESOURCE floor of the and (2) a small deep part that wraps around the posterior border of the . The submandibular (Wharton’s) duct runs anteriorly to open onto the floor of the mouth, alongside the frenulum.

z The , the smallest of the major salivary glands, lies anteriorly in the floor of the mouth, with many small ducts opening either into the submandibular duct or directly into the mouth.

z Basic secretory units of salivary glands are clusters of cells, each called an . These cells secrete a fluid that contains , , mucous, and , all of which flow out of the acini into collecting ducts. The saliva produced by the parotid is mainly serous; by the submandibular gland, mixed; and by the sublingual and minor salivary glands, mucoid.

volvement. In patients with sialadenosis, in ❚ Bulimia and anorexia nervosa. Bulimia contrast, acinar cell hypertrophy alone will be nervosa, the induction of after binge present. eating, can be associated with bilateral or occa- Treatment of sialadenosis is best aimed sionally unilateral parotid swelling. Anorexia, a at rectifying the underlying medical condi- form of self-starvation, can occur in association tion, which might, over time, lead to some with bulimia, with patients also presenting with reduction in the size of the gland. There is no parotid swelling. Associated parotid swelling is specific effective therapy for elimination of similar to what is seen in sialadenosis: painless, glandular swelling. persistent, and of nonpathologic consistency. CONTINUED

MDEDGE.COM/FAMILYMEDICINE VOL 68, NO 8 | OCTOBER 2019 | THE JOURNAL OF FAMILY PRACTICE E3 The pathophysiology of bulimia- and lar duct stone, bimanual palpation might re- anorexia-associated parotid-gland swelling is veal its position if it is located distally in the identical to what is seen in sialadenosis: dys- floor of the mouth; a proximal stone might regulation of acinar cell sympathetic nerve not be palpable. supply that leads to enlargement of individu- Although US is operator-dependent, it is al parenchymal cells.8 Contrast-enhanced CT the imaging modality of choice for identifying can reveal increased vascularity associated sialolithiasis10 because it can identify gland with active bulimia. FNA and CT, however, architecture, duct dilation, and both radio- are required only in patients in whom the lucent and radiopaque stones. For patients diagnosis is not clear and when neoplasm is in whom US findings are normal despite a suspected. convincing clinical presentation of sialolithi- Treatment includes correcting electro- asis, CT should be performed because small lyte abnormalities and, more importantly, stones can be missed on US.11 addressing underlying emotional issues to Supportive measures for sialolithiasis stop purging episodes. Psychiatric input and are listed in the TABLE. Reserve antibiotics social support are invaluable. Parotid gland for patients who have signs or symptoms of swelling generally improves with cessation of infection, including pyrexia, , and vomiting episodes. malaise. A beta-lactam , such as amoxicillin–clavulanate, 875 mg orally bid, For a Ask: Is the patient in pain? or a cephalosporin, such as cephalexin, 500 submandibular Causes of salivary gland pain include sialoli- mg orally qid, are appropriate first-line op- duct stone, thiasis, , and recurrent of tions. , 300 mg orally tid, or met- bimanual childhood. Pain occurs secondary to stretch- ronidazole, 500 mg orally tid, are acceptable palpation might ing of the fibrous capsule in which the parotid alternatives. When signs or symptoms are reveal its position or submandibular gland is surrounded, com- persistent or recurrent, refer the patient for a if it’s located pression of pain fibers by an expanding mass, surgical opinion. distally in the floor or infiltration of by neoplasia. Stones located in the floor of the mouth of the mouth; a ❚ Sialolithiasis. Sialolithiasis, or salivary are usually excised through an intraoral ap- proximal stone stones, are primarily carbonate con- proach. In the past, gland excision was ad- might not be centrations within the salivary ductal system. vocated when a sialolith was found more palpable. More than 80% occur in the submandibular proximally within the gland parenchyma. gland or duct9 as a result of production of More recently, however, sialendoscopy, in- mixed mucoid and serous saliva and a tortu- volving insertion of a small, semirigid endo- ous duct path. scope into the salivary duct, has been shown Patients usually present with a history of safe and effective for removing a stone; suc- intermittent swelling and pain of the involved cessful removal, in as many as 80% of cases, gland associated with eating. Increased pro- increases to 90% when performed using a duction of saliva during meals, which then minimally invasive surgical technique.12 Al- passes through a partially obstructed salivary though sialendoscopy is effective, the tech- duct, leads to salivary retention and glandu- nique cannot always treat the underlying lar swelling. Thus, a recurring pattern can abnormality of the salivary gland; gland ex- develop, with varying periods of remission,7 cision is therefore warranted in some cases. eventually leading to an acute suppurative Last, extracorporeal shock wave thera- process or sialadenitis (described below). py is aimed at fragmenting salivary stones Chronic salivary disease can also be caused before retrieval. Results are variable, how- by stricture of a duct or, rarely, external com- ever, and treatment should be guided by an pression by a tumor mass. otolaryngologist.13,14 Examination often reveals an enlarged ❚ Sialadenitis (bacterial and viral and often tender gland; conversely, chronic infection). Acute suppurative sialadenitis oc- disease can lead to gland . Usually, curs secondary to retrograde ductal bacterial only minimal saliva is able to be expressed infection. The parotid gland is most frequently from an obstructed duct. For a submandibu- involved,15 although submandibular sialadeni-

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No

• Alcohol • Anorexia • Type 2 DM Type • Sialadenosis: Sialadenosis: Treat Treat underlying cause Bilateral History of dry mouth Yes

Consider No stone identified syndrome and systemic causes Test for ANA, RF, ACE, Anti SSA/Ro ACE, for ANA, RF, Test and SSB/La antibodies. Imaging of the chest (if sarcoidosis is suspected). Refer to otolaryngologist + rheumatologist. with saliva Treat and sialogogues, substitutes, muscarinic cholinergic stimulators ) (eg, such as Sjögren's No or sialectasia. Possible stricture Possible CT +/- Arrange uncertain, consider uncertain, If diagnosis remains ultrasound

Refer to otolaryngologist

Stone identified ) AND refer Yes gland) Stone involving commonly Chronic Palpable BOX Sialolith (most submandibular to otolaryngologist for definitive management. If patient develops or trismus, , commence malaise, amoxicillin/ antibiotics: clavulanate or clindamycin Conservative management. (see No

Yes Yes ) AND , Arrange bacterial to confirm Recurrent? sialography sialadenitis. sialadenitis. Likely chronic Likely BOX systemic upset Yes antibiotics: amoxicillin/ antibiotics: clavulanate or clindamycin. If not improving with conservative refer management, to otolaryngologist for consideration of gland excision Conservative management. (see No Painful?

Unilateral No (cervical swelling Salivary glandSalivary favor malignancy) Possible neoplasm Possible lymphadenopathy or Requires further investigation including ultrasound + FNA. If investigation is suspicious for neoplasm, arrange contrast- enhanced CT and urgent referral to otolaryngologist facial nerve involvement

Viral Bilateral sialadenitis Supportive care: analgesia, analgesia, Supportive care: attention to hydration, If not improved after consider chronic 6 weeks, causes No improvement Refer to otolaryngologist ). BOX No Conservative management: management: Conservative (see If patient develops fever, or malaise, trismus, commence antibiotics: amoxicillin/clavulanate or clindamycin Acute commonly involving Acute sialolith (most sound scan indicated submandibular gland). submandibular gland). Stone may be palpable

clinically, otherwise ultra - clinically, Yes No improvement Inpatient management: IV Ultrasound, review antibiotics, by otolaryngologist for potential drainage unwell? Febrile or Febrile systemically Yes ) AND No gland) trismus? BOX Sialogogues: lemon drops, sugar-free lollipops sugar-free lemon drops, Sialogogues: (commonly sialadenitis Warm compress and gland massage  Warm naproxen)  Anti-inflammatories (eg, or significant Unilateral Acute bacterial Fluctuant mass, Fluctuant mass, BOX gland disorders: management of salivary Conservative 1.  2. 3. involving parotid Conservative management (see antibiotics: amoxicillin/ clavulanate or clindamycin significantly unwell, significantly unwell, FIGURE you? take A swollen will salivary the workup Where gland: rheumatoid factor; SSA/Ro, Sjögren's-syndrome computed tomography; DM, diabetes mellitus; FNA, fine-needle aspiration; RF, ACE, angiotensin-converting ; ANA, antinuclear antibody; CT, related A; SSB/La, Sjögren's-syndrome type B antigen/ La protein.

MDEDGE.COM/FAMILYMEDICINE VOL 68, NO 8 | OCTOBER 2019 | THE JOURNAL OF FAMILY PRACTICE E5 TABLE as diabetes mellitus or intravenous drug use, Checklist of supportive measures or in patients residing in an area of substantial for sialolithiasis incidence of methicillin-resistant S aureus. In • Hydration those cases, substitute vancomycin or linezolid for nafcillin.18 • Gland massage (“milk” the gland toward the duct papillae) Less commonly, abscess can form, with • Warm compresses (heat a damp towel, squeeze out excess water, and the patient presenting as systemically unwell place it over the gland) with a fluctuant mass. If the diagnosis is unclear • Sialagogues (eg, gum, lemon drops, sugar-free lollipops) or the patient does not improve, abscess can • Nonsteroidal anti-inflammatory drugs (eg, ibuprofen, diclofenac, be confirmed by US. Expedient surgical review naproxen) and inpatient admission can then be arranged. • Good oral hygiene (brush and floss teeth, use a chlorhexidine 0.2% Unlike bacterial sialadenitis, causes of mouthwash at least twice a day). viral sialadenitis are often bilateral. (a paramyxovirus) is the most common tis is not uncommon. Patients usually present viral cause, affecting primarily children with sudden-onset unilateral, painful swelling. < 15 years.19 The parotid glands are most of- Pathophysiology involves or ten involved, with inflammation and decreased oral intake leading to salivary sta- causing significant pain because of increas- sis and subsequent bacterial migration into ing intraparotid pressure as expansion of the In sialolithiasis, the gland. Medically debilitated and postop- gland is limited by its tense fibrous capsule. reserve erative patients are therefore at greater risk; Complications of mumps include orchitis, antibiotics for so are patients with diabetes mellitus, poor meningitis, pancreatitis, and oophoritis. patients who oral hygiene, Sjögren’s syndrome, hypothy- Mumps is highly contagious; it is spread have signs roidism, or renal failure.16 Certain medica- through contact with airborne saliva drop- or symptoms tions, including , can also lets, with viral entry through the nose or of infection, predispose to hyposalivation.17 mouth, followed by proliferation in the sali- including pyrexia, (As discussed, sialolithiasis and stricture vary glands or on surface of the trismus, and of salivary ducts can also cause acute bacte- respiratory tract.7 Diagnosis is confirmed by malaise. rial infection; in such cases, however, the typi- viral serology. A positive test of serum im- cal presentation is one of chronic or recurrent munoglobulin M confirms the diagnosis, infection.) but this test should not be performed until Examination might reveal an exquisitely 3 days after onset of symptoms because a tender, indurated, and inflamed gland; can false-negative result is otherwise possible.20 often be expressed from the respective intraoral Immunoglobulin G serologic testing can fur- orifice. Any expressed pus should be sent for ther aid diagnosis; the titer is measured ap- culture to guide antibiotic therapy. proximately 4 days after onset of symptoms Treatment should focus on hydration, oral and again 2 to 3 weeks later. A 4-fold rise in hygiene, and antibiotics, while reversing or titer confirms mumps. minimizing any underlying contributing medi- Other viral that can cause si- cal condition. Warm compresses applied to aladenitis include Epstein-Barr , cyto- the involved gland, massage, and sialagogues, megalovirus, immunodeficiency virus, such as lemon drops or sugar-free lollipops, can , and influenza. Treatment is stimulate salivary flow and prevent stasis. supportive: analgesia, hydration, oral hygiene, More than 80% of infections are caused and rest. Inflammation might take weeks to by Staphylococcus aureus17; anaerobic and resolve, but expect complete resolution. For a mixed infections have also been recognized. patient who has significant trismus, poor oral A beta-lactam , such as amoxicillin- intake, or a potentially threatened airway, in- clavulanate, is the antibiotic of choice. A patient patient care should be provided. who is systemically unwell should be treated as ❚ Recurrent parotitis of childhood is an an inpatient with nafcillin and metronidazole. inflammatory condition that usually affects Methicillin-resistant S aureus must also be con- one, but at times both, parotid glands. It is sidered in patients with comorbid disease, such characterized by episodes of painful swell-

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ing. Incidence peaks at 3 to 6 years of age.7 Episodes can be frequent, occurring 1 to References 5 times a year and lasting 3 to 7 days— 1. de Oliveira FA, Duarte EC, Taveira CT, et al. Salivary gland tumor: a review of 599 cases in a Brazilian population. Head Neck Pathol. sometimes longer—and usually resolving 2009;3:271-275. without treatment. 2. Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986;8:177-184. The precise etiology of recurrent paroti- 3. Bova R. A guide to salivary gland disorders. Medicine Today. tis of childhood is unclear; possibly, saliva 2006;7:44-48. 4. Zhang S, Bao R, Bagby J, et al. Fine needle aspiration of salivary aggregates to form obstructive mucous plugs, glands: 5-year experience from a single academic center. Acta thus causing stasis and swelling of the gland. Cytol. 2009;53:375-382. 5. Bova R, Saylor A, Coman WB. 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Updated S2K AWMF guideline for the diagnosis and follow-up of obstructive sial- and malaise warrant treatment with oral an- adenitis—relevance for radiologic imaging. Rofo. 2014;186: tibiotics. Sialadenoscopy, which can be con- 843-846. Pus can often be 11. Schwarz D, Kabbasch C, Scheer M, et al. Comparative analysis of sidered in children with frequent episodes, sialendoscopy, sonography, and CBCT in the detection of sialoli- expressed from can decrease the frequency and severity of thiasis. Laryngoscope. 2015;125:1098–1101. the respective 21 12. Atienza G, López-Cedrún JL. Management of obstructive sali- episodes. The condition usually resolves vary disorders by sialendoscopy: a systematic review. Br J Oral intraoral orifice spontaneously at puberty. Maxillofac Surg. 2015;53:507-519. in sialadenitis. 13. Escudier MP, Brown JE, Putcha V, et al. 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Differentiating acute suppurative parotitis from acute exacerbation of a chronic parotitis: case reports. J Oral Maxillofac Treatment of xerostomia includes saliva Surg. 2008;66:1964-1968. substitutes, sialagogues, and, for oral candi- 18. Chow AW. Suppurative parotitis in adults. UpToDate.com. www. uptodate.com/contents/suppurative-parotitis-in-adults. Accessed diasis, antifungals. Muscarinic cholinergic September 25, 2019. stimulators, such as pilocarpine, 5 mg qid 19. Katz SL, Gershon AA, Hotez PJ. Infectious Diseases of Children. New York, NY: Mosby Year Book; 1998:280-289. 22 have been used with some success ; patients 20. Krause CH, Molyneaux PJ, Ho-Yen DO, et al. Comparison of should be advised of potential adverse effects mumps-IgM ELISAs in acute infection. J Clin Virol. 2007;38: 153-156. with these agents, including sweating, uri- 21. Quenin S, Plouin-Gaudon I, Marchal F, et al. Juvenile recurrent nary frequency, flushing, and chills. JFP parotitis: sialendoscopic approach. Arch Otolaryngol Head Neck Surg. 2008;134:715-719. 22. Papas AS, Sherrer YS, Charney M, et al. Successful treatment CORRESPONDENCE of dry mouth and dry eye symptoms in Sjögren’s syndrome Shankar Haran, MBBS, ENT Department, Townsville Hospital, patients with oral pilocarpine: a randomized, placebo- 100 Angus Smith Dr, Douglas, Queensland, Australia 4814; controlled, dose-adjustment study. J Clin Rheumatol. 2004;10: [email protected]. 169-177.

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