Submandibular Sialadenitis/Sialadenosis

The salivary glands serve numerous functions, including lubrication; enzymatic degradation of food substances; production of hormones, antibodies, and other blood group–reactive substances; mediation of taste; and antimicrobial protection. The regulation of salivary flow is primarily through the autonomic system and, most importantly, the parasympathetic division. In the case of the submandibular gland, this is mediated through the submandibular ganglion. Presynaptic fibers are derived from the superior salivatory nucleus and carried by the chorda tympani nerve, which joins the lingual nerve traveling towards the ganglion. Postsynaptic fibers extend from the ganglion to the gland itself.

Saliva is produced in the glandular subunit. The fluid component of the saliva is derived from the perfusing blood vessels in proximity to the gland, while the macromolecular composition is derived from secretory granules within the acinar cells. The saliva is produced in the acinus. Myoepithelial cells, containing contractile elements, are located along the periphery of the acinus. Upon contraction of these myoepithelial cells, the saliva is secreted into the ductal system.

The exact mechanism of salivary secretion is not completely understood but is believed to be under the influence of a cyclic AMP (adenosine 3,'5'-cyclic monophosphate) and a calcium-activated phosphorylation mechanism. The salivary secretions are then modified by a variety of cell types along a series of ducts, including the striated, intercalated, and excretory ducts, before finally being excreted through the Wharton duct into the oral cavity.

The concentration of mucus is higher in the submandibular gland, accounting for the viscous nature of its secretions relative to the other salivary glands. This increased viscosity, and subsequent relatively slower flow, contributes to the propensity for salivary gland calculi and stasis in certain disease states.

Frequency

United States

The exact frequency of submandibular sialadenitis is unclear. The incidence of acute suppurative parotitis has been reported at 0.01-0.02% of all hospital admissions. The submandibular gland is suggested to account for approximately 10% of all cases of sialadenitis of the major salivary glands. Extrapolation would suggest an incidence of 0.001-0.002%, but this is unconfirmed.

Race

No race predilection per se exists.

Sex

No sex predilection per se exists.

Age

Although no obvious age predilection exists, per se, sialadenitis as a whole tends to occur in the older, debilitated, or dehydrated patient.[3]

Submandibular sialadenitis takes several forms. The diagnostic workup of any submandibular enlargement begins with a thorough history. This should include onset, duration of symptoms, recurrence, recent operative history, recent dental work, and thorough drug history, immunization history (specifically measles , mumps , rubella [MMR] vaccine), past medical (specifically autoimmune) history, past surgical history, and history of radiation therapy. Inquire as to associated fever or chills, weight loss, presence of a mass, bilaterality or unilaterality, skin changes, lymphadenopathy, keratitis , shortness of breath, oral discharge, dental pain, or skin discharge.

Physical examination should begin with the gland itself. The gland should be palpated for the presence of calculi. Examine the ductal opening for purulence. Palpation should extend into the floor of mouth as well as the soft tissue of the tongue, cheek, and neck. Lingual papillary atrophy should be looked for, as well as loss of enamel from the tooth surface (the latter may be associated with bulimia ). All of the major salivary glands should be examined for masses, symmetry, and the presence of discharge. The presence of lymphadenopathy should be noted. The eyes should be examined for any presence of interstitial keratitis. A quick cranial nerve examination should be conducted with particular attention to cranial nerves VII and XII. The lungs should be examined and a chest radiograph ordered if suspected pulmonary involvement exists.

Acute sialadenitis

Acute sialadenitis is an acute inflammation of a salivary gland.

Patients typically present with erythema over the area, pain, tenderness upon palpation, and swelling. Frank cellulitis and induration of adjacent soft tissues may be present. Purulent material may be observed being expressed from the Wharton duct, particularly upon milking the gland. Rarely, a cutaneous fistula may occur, with spontaneous drainage of purulent material. The inflammation is secondary to an infectious process.

The most common organism is Staphylococcus aureus. Other bacterial organisms include Streptococcus viridans, Haemophilus influenzae, Streptococcus pyogenes, and Escherichia coli. The infection is often the result of dehydration with overgrowth of the oral flora. The most common causes are postoperative dehydration, radiation therapy, and immunosuppression (eg, diabetes mellitus, organ transplant, chemotherapy, human immunodeficiency virus).

Of note, infection of the submandibular gland is rare in the neonate and prepubescent child. When it does occur, similar pathogens have been identified, including Pseudomonas aeruginosa and group B streptococci. Physical examination, in addition to the symptoms described above, includes failure to thrive and irritability. Progression may occur, involving the contralateral gland. The etiology of this entity is unclear.

Although less common than bacteria, several viruses have been implicated in submandibular sialadenitis. These include the mumps virus, which typically affects the parotid gland but can affect the submandibular gland as well. Other viruses include HIV, coxsackievirus, parainfluenza types I and II, influenza A, and herpes.

A study by Naylor et al indicated that risk factors for acute sialadenitis after skull base surgery, though poorly understood, “may include extreme flexion and/or rotation of the head and neck.”[4]

Infection of the submandibular gland can result in the formation of a submandibular abscess. In this state, the patient may appear toxic, with features similar to acute submandibular sialadenitis. Spiking fevers are not uncommon. This is a serious condition requiring strict attention because of the possibility that the abscess may spread to involve other deep neck spaces of the neck. Trismus may be indicative of parapharyngeal involvement. Progression to Ludwig angina, a life-threatening infection of the submental and sublingual spaces, although rare, can occur.

Chronic sialadenitis

Chronic sialadenitis, in contrast, is typically less painful and is associated with recurrent enlargement of the gland (often following meals) typically without erythema. The chronic form of the disease is associated with conditions linked to decreased salivary flow, rather than dehydration. These conditions include calculi, salivary stasis, and a change in the fluid and electrolyte composition of the gland.

Sialolithiasis

Salivary calculi (sialolithiasis) relate to the formation and deposition of concretions within the ductal system of the gland.

Eighty percent of all salivary calculi occur in the submandibular gland, with approximately 70% of these demonstrable as radio-opacities on routine plain radiography consisting of intraoral occlusal radiographs.

The calculi vary in size and may be single or multiple. The formation of calculi is associated with chronic sialadenitis, and in particular, the recurrent nature of the problem.

The exact mechanism of stone formation is unclear, but it appears to be related to the following conditions:

• Salivary stagnation

• Epithelial injury along the duct resulting in sialolith formation, which acts as a nidus for further stone formatio

• Precipitation of calcium salts

The stones themselves are typically composed of calcium phosphate or calcium carbonate in association with other salts and organic material such as glycoproteins, desquamated cellular residue, and mucopolysaccharides.

Patients most often present with a colicky postprandial swelling of the gland. The course of the disease is typically relapsing and remitting until a final definitive treatment, usually in the form of surgery, is undertaken.

Autoimmune sialadenitis

Autoimmune diseases, in particular Sjögren syndrome, can be associated with sialadenitis. Although preferentially affecting the parotid gland, the submandibular and minor salivary glands are also affected. The disease, which is associated with keratoconjunctivitis sicca, xerostomia, salivary gland enlargement, and lingual papillary atrophy, is confirmed through biopsy of the minor salivary glands of the lip. Numerous laboratory tests are also used to confirm the diagnosis, such as autoantibodies Sjögren syndrome A (SS-A) and Sjögren syndrome B (SS-B), rheumatoid factor, and antinuclear antibodies.

Sialadenosis

Sialadenosis refers to nonneoplastic noninflammatory swelling in association with acinar hypertrophy and ductal atrophy.

Etiologies fall into 5 major categories.

• Nutritional (eg, vitamin deficiency, bulimia)

• Endocrine (eg, diabetes mellitus, hypothyroidism)

• Metabolic (eg, obesity, cirrhosis, malabsorption)

• Inflammatory/autoimmune (eg, Sjögren disease, Heerfordt syndrome)

• Drug induced (eg, thiourea)

Physical examination shows a nontender swelling that is often bilateral and symmetric but can be unilateral and asymmetric.

See the list below:

• In evaluating the patient with sialadenitis, steps should be taken in the following order: history, physical examination, culture, laboratory investigation, radiography, and if indicated, fine-needle aspiration biopsy (see History and Physical).

• Laboratory investigations should begin with culture of the offending gland (if possible, prior to the administration of antibiotics).

• Blood cultures should be obtained in the patient exhibiting bacteremia or sepsis.

• As a rule, needle aspiration of a suspected abscess is not indicated.

• Routine electrolytes and complete blood cell count with differential should be obtained to assess for any evidence of dehydration or systemic infection.

• If a diagnosis of autoimmunity is entertained, serum analysis for antinuclear antibody, SS-A, SS-B, and erythrocyte sedimentation rate should be conducted.

Numerous radiologic techniques are available in submandibular imaging. Deciding which study to obtain first is often difficult. Examination selection should be based in part on the suspected cause of the problem. The authors' institution tends to begin with plain radiography, followed by the use of computed tomography scanning with combined sialography.

Radiography

Of all the radiologic examinations available, one of the simplest is conventional plain radiography.[5] Anteroposterior, lateral, and oblique intraoral occlusal views are used. This technique is particularly valuable in evaluating the presence of calculi, which are radio-opaque in approximately 70% of cases. These radiographs are limited in that they do not provide any information about the ductal system or soft tissues.

Sialography

Sialography can be used to evaluate sialolithiasis or other obstructive entities, as well as inflammatory and neoplastic disease. In this technique, a water-soluble medium such as meglumine diatrizoate is injected into the Wharton duct and lateral, oblique, and anteroposterior plain radiographs are obtained in order to assess the ductal arborization. Contraindications for this test are iodine allergy and acute sialadenitis.

Any filling defects (eg, calculi), retained secretions (eg, chronic sialadenitis), stricture formation (eg, inflammation), extravasation (eg, Sjögren disease), or irregularly contoured borders (eg, neoplasm) are noted.

Ultrasonography

Ultrasonography can be used to differentiate between solid versus cystic lesions of the gland. It can also be used to differentiate intrinsic from extrinsic disease and can be helpful in identification of abscess formation. A 2009 study by Bozzato et al determined that application of ascorbic acid (vitamin C) as a contrast agent can aid in the ultrasound assessment of obstructive sialadenitis of the parotid and submandibular glands.[6, 7]

A study by Omotehara et al indicated that ultrasonography is effective in the diagnosis of immunoglobulin G4–related sclerosing sialadenitis (IgG4-SS), with ultrasonography showing the submandibular gland to have a significantly greater longitudinal diameter and thickness in patients with IgG4-SS than in controls. In addition, a rough contour to the gland was found in 62.9% of the patients, versus 8.3% of the controls. Moreover, in an examination of internal echo textures, patients showed multiple hypoechoic nodule patterns or diffuse hypoechoic patterns, in contrast to controls, who were found to have only homogeneous echo textures. Additionally, significantly higher color Doppler signaling was observed in cases of IgG4-SS than in controls.[8, 9]

In an examination of the parotid and submandibular glands, a study by Li et al suggested that ultrasonography may also be helpful in posttreatment follow-up of IgG4 sialadenitis, finding that the treated glands decreased significantly in volume and that their internal echoes showed greater homogeneity.[10]

A study by Larson et al indicated that in terms of identifying sialoliths intraoperatively in patients with chronic obstructive sialadenitis, surgeon-performed ultrasonography has positive and negative predictive values of are 94% and 91%, respectively.[11]

CT scanning

Computed tomography (CT) scanning is an excellent modality in differentiating intrinsic versus extrinsic glandular disease. It is also extremely valuable in defining abscess formation versus phlegmon. It is limited in evaluating the ductal system unless combined with simultaneous sialography.

MRI

Magnetic resonance imaging (MRI) is of little utility in sialadenitis or sialadenosis. It does not allow evaluation of the ductal system, and it is not helpful in defining calcifications. It is an excellent tool for soft tissue definition and is invaluable in instances of suspected neoplasia.

PET/CT scanning

A retrospective cohort study by Takano et al indicated that 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) scanning may, when combined with serologic and clinical evaluation, be able to diagnose IgG4-SS. The investigators found that in 98% of patients with IgG4-SS, FDG uptake was increased in the submandibular gland. The diagnostic sensitivity, specificity, and accuracy of high FDG uptake by the submandibular gland in combination with a serum IgG4 level of 135 mg/dL or higher were reported to be 96.9%, 90.0%, and 86.4%, respectively.[12]

See the list below:

• Fine-needle aspiration and biopsy

  • Open biopsy of the lip should be considered when the diagnosis of Sjögren disease is contemplated.

  • If suspicion of a solid neoplasm masquerading as sialadenitis is significant, a fine-needle aspiration with biopsy should be undertaken. The management and differential diagnosis of submandibular neoplasms is beyond the scope of the current discussion.

Management of submandibular sialadenitis and sialadenosis involves a wide range of approaches, from conservative medical management to more aggressive surgical intervention.

One management scheme is as follows:

• Acute sialadenitis

  • Medical management - Hydration, antibiotics (oral versus parenteral), warm compresses and massage, sialogogues[2]

  • Surgical management - Consideration of incision and drainage versus excision of the gland in cases refractory to antibiotics, incision and drainage with abscess formation, gland excision in cases of recurrent acute sialadenitis

• Salivary calculi

  • Medical management - Hydration, compression and massage, antibiotics for the infected gland

  • Surgical management - Duct cannulation with stone removal, gland excision in recurrent case

• Sjögren disease

  • Medical management - Hydration, dental hygiene, rheumatology and dental referral

  • Surgical management - Gland excision not usually needed unless recurrent acute sialadenitis

• Sialadenosis

  • Medical management - Treatment of underlying cause

  • Surgical management - Not indicated

A prospective study by Choi et al indicated that following salivary stimulation therapy, patients with radioactive iodine (RAI)-induced sialadenitis may undergo a subjective reduction in symptoms but will not experience significant improvement in salivary gland function. The study involved 61 patients who were diagnosed with chronic RAI-induced sialadenitis following thyroidectomy and RAI treatment. After salivary stimulation with pilocarpine, significant improvement was seen in the patients’ subjective symptom scores; however, salivary flow rates and salivary gland scintigraphy parameters, as measured in the parotid and submandibular glands, were not significantly different from their prestimulation values.[13]

A study by Kim et al of 33 patients (58 salivary glands) with chronic obstructive sialadenitis indicated that intraductal irrigation can relieve symptoms of the condition. As assessed using a numeric rating scale, a set of 3-5 visits for intraductal irrigation reduced the average symptom severity score from 6.0 to 3.3. However, irrigation was not associated with a change in ductal width.[14]

Medical management of submandibular sialadenitis and sialadenosis centers on eliminating the causative factor.

• Acute sialadenitis

  • In cases of acute sialadenitis, adequate hydration should be ensured and electrolyte imbalances corrected.

  • Patients are most often treated on an outpatient basis, with the administration of a single dose of parenteral antibiotics in an emergency department, followed by oral antibiotics for a period of 7-10 days. Clindamycin (900 mg IV q8h or 300 mg PO q8h) is an excellent choice and provides good coverage against typical organisms.

  • Patients who exhibit significant morbidity, are significantly dehydrated, or are septic should be admitted to hospital. In this latter group of patients, CT scanning of the area should be performed. If a large abscess is noted, incision and drainage should be considered. Small abscesses typically respond to conservative methods.

  • In cases refractory to antibiotics, viral and atypical bacterial causes should be considered.

• Sialolithiasis

  • Patients with sialolithiasis should be initially treated with hydration, warm compresses, and gland massage.

  • Antibiotics are indicated in patients exhibiting infection.

• Sjögren disease

  • In those patients with Sjögren disease, hydration and prevention of complications should be undertaken.

  • Dental hygiene should be strictly maintained in order to prevent carries, and dental and rheumatology consults should be sought. Gland excision is rarely indicated.

• Sialadenosis: Sialadenosis should be managed expectantly. Treatment should be directed towards managing the underlying problem and achieving homeostasis. Gland excision is not indicated.

Acute sialadenitis

Patients who exhibit significant morbidity, are significantly dehydrated, or are septic should be admitted to hospital. In this latter group of patients, CT scanning of the area should be performed. If a large abscess is noted, incision and drainage should be considered. Small abscesses typically respond to conservative methods.

In patients with recurrent acute attacks, gland excision during a period of quiescence should be considered. Serial CT scanning is often useful.

Endoscopic management of sialadenitis frequently obviates the need for gland removal. Results follow a learning curve.[15]

Chronic sialadenitis

A retrospective study described sialendoscopy as a safe and effective means of treating children with recurrent or chronic sialadenitis. Semensohn et al examined the medical records of 12 pediatric patients who underwent diagnostic and therapeutic sialendoscopy for recurrent parotitis (nine patients) or chronic submandibular sialadenitis (three patients). During follow-up, which averaged 16.5 months, only one patient needed additional surgery (salvage parotidectomy), due to repeated recurrences.[16]

Sialolithiasis

In patients with calculi in proximity of the opening of the Wharton duct, the duct can be cannulated, dilated, and the stone removed via a transoral approach.

Patients with deep intraparenchymal stones or multiple stones should have their glands excised on an elective basis. Ultrasonic lithotripsy is rarely effective and is not offered at the authors' institution.

A study by Kopeć et al indicated that sialendoscopy and sialendoscopy-assisted surgery are effective treatments for lithiasis of the submandibular glands. The study found that of 175 patients with submandibular gland stones, complete stone removal was achieved in 149 of them, through either sialendoscopy alone (82 patients) or sialendoscopy with surgery (67 patients). The procedures were also effective in the treatment of lithiasis of the parotid glands.[17, 18]

Similarly, a prospective study by Aubin-Pouliot et al indicated that sialendoscopy-assisted salivary duct surgery is an effective treatment for chronic obstructive sialadenitis, especially that caused by sialolithiasis. In the study’s 40 patients (54 glands), the overall mean score on the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire improved by 22.6 points, falling from 36.1 preoperatively to 13.5 at 3 months postoperatively. For submandibular gland patients specifically, the mean score fell from 38.1 preoperatively to 10.3, while for parotid gland patients the mean score fell from 32.6 to 19.0. The investigators found the greatest COSS score improvement in patients whose condition was caused by sialolithiasis, as opposed to those with radioactive iodine– or inflammatory-related sialolithiasis.[19]

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Class Summary

Therapy must cover all likely pathogens in the context of this clinical setting.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

See the list below:

• For patients with acute sialadenitis not requiring admission, follow-up visit should be 3 days from the first visit and then 1 week later (with improvement).

• Patients with chronic sialadenitis/sialolithiasis and autoimmune sialadenitis or sialadenosis should be seen on a regular basis and if acute exacerbation of the problem occurs.

See the list below:

• Patients requiring inpatient management should be monitored on a daily basis and preferably twice daily.

• In order to ascertain the progression or improvement of acute sialadenitis, serial CT scanning may be warranted.

• Patients with sialolithiasis should be treated conservatively during the acute exacerbation stage and should be monitored after discharge for definitive surgical intervention.

See the list below:

• In addition to the antibiotics, patients may be treated with any form of nonsteroidal anti-inflammatory medications. Narcotics may be needed in severe cases, and increasing pain refractory to medications is often an indication for admission for further evaluation.

• In addition, medications predisposing to xerostomia should be avoided where possible. These include antiparkinsonian, antiemetics, antinauseants, over-the-counter and prescription cold medications, antidepressants, antihypertensive agents, diuretics, anticholinergics, antianxiety agents, and decongestants.

See the list below:

• The most serious complication of acute sialadenitis is the formation of an abscess. Management is described above.

• Complications of chronic sialadenitis and autoimmune sialadenitis are most often dental in nature because of the decreased function of the gland and the protective effect provided against caries.

• Chronic inflammation of the gland with or without calculi often renders the gland difficult to excise because of the loss of normal tissue planes.

See the list below:

• The prognosis of acute sialadenitis is very good. Most cases are easily treated with conservative medical management, and admission is the exception, not the rule. Acute symptoms resolve within 1 week; however, edema in the area may last several weeks.

• Postsurgery, patients are often already admitted with appropriate intravenous antibiotics. These patients have a similar prognosis.

• Patients with chronic sialadenitis often have a relapsing and remitting course. Prognosis is dependent on the etiology.

• Patients with sialolithiasis require definitive surgical treatment in most cases, which results in an excellent prognosis.

• Patients with Sjögren or other autoimmune diseases are likely to have a protracted course related to systemic involvement.

• Patients with sialadenosis have a good prognosis, if their underlying problem is adequately controlled. Even if control is attained, bilateral swelling may be persistent.

See the list below:

• Patients with any form of sialadenitis should be educated as to the value of hydration and excellent oral hygiene. This lessens the severity of the attacks and prevents dental complications. Patients with sialadenosis should be educated regarding the mechanism of their underlying pathology and methods of maintaining control over them.

• For excellent patient education resources, visit eMedicineHealth's Oral Health Center.