Sialadenitis


Sialadenitis is inflammation of salivary glands, usually the major ones, the most common being the parotid gland, followed by submandibular and sublingual glands. It should not be confused with sialadenosis which is a non-inflammatory enlargement of the major salivary glands.
Sialadenitis can be further classed as acute or chronic. Acute sialadenitis is an acute inflammation of a salivary gland which may present itself as a red, painful swelling that is tender to touch. Chronic sialadenitis is typically less painful but presents as recurrent swellings, usually after meals, without redness.
Causes of sialadenitis are varied, including bacterial, viral and autoimmune conditions.

Types

Acute

;Predisposing factors
;Clinical features
  • painful swelling
  • reddened skin
  • edema of the cheek, periorbital region and neck
  • low-grade fever
  • malaise
  • raised ESR, CRP, leucocytosis
  • purulent exudate from duct punctum

    Chronic

;Clinical features
  • unilateral
  • mild pain / swelling
  • common after meals
  • duct orifice is reddened and flow decreases
  • may or may not have visible/palpable stone.
  • Parotid gland
  • * recurrent painful swellings
  • Submandibular gland
  • * usually secondary to sialolithiasis or stricture

    Signs and symptoms

Sialadenitis is swelling and inflammation of the parotid, submandibular, or sublingual major salivary glands. It may be acute or chronic, infective or autoimmune.

Acute

  • Acute sialadenitis secondary to obstruction is characterised by increasingly, painful swelling of 24–72 hours, purulent discharge and systemic manifestations.

    Chronic

  • Chronic sialadenitis causes intermittent, recurrent periods of tender swellings. Chronic sclerosing sialadenitis is commonly unilateral and can mimic a tumour.

    Autoimmune

  • Autoimmune sialadenitis causes unilateral or bilateral painless swellings unless there is a secondary infection.

    Infection

  • The most common salivary gland infection is mumps. It is characterised by bilateral swelling of the parotid glands; however, other major salivary glands may also be affected in around 10% of cases. The swelling persists for about a week, along with low-grade fever and general malaise.
  • Recurrent parotitis of childhood is characterised by periods of pain and swelling in the parotid gland accompanied by a fever.

    Complications

Causes

Sialadenitis can be caused by cancer, autoimmune conditions, viral and bacterial infections, idiopathic causes or stones formed mainly from calculus. It was thought that morphological characteristics of the salivary ducts could also be a contributing factor, as stagnation of saliva due to these could perhaps cause an increased incidence of sialadenitis. However, one study found no statistically significant difference between the length of ducts or the angles they incorporate within them and the likelihood of developing sialadenitis, although this study only had a small sample size of 106. The study also confirmed that age, gender, side of face and degree of sialadenitis had no impact on the length of the ducts or the angles formed within the ducts.
Viral pathogens more commonly cause sialadenitis in comparison to bacterial pathogens. Mumps is the most common virus that affects the parotid and submandibular glands, with the parotid gland affected most often out of these two. Other viruses that have been shown to cause sialadenitis in both these glands include HIV, coxsackie, and parainfluenza. Classically, HIV parotitis is either asymptomatic or a non-painful swelling, which is not characteristic of sialadenitis. Some common bacterial causes are S. aureus, S. pyogenes, viridans streptococci and H. influenzae.
Autoimmune conditions that can cause sialadenitis include Sjögren's syndrome, sarcoidosis, and granulomatosis with polyangiitis. Sjögren's syndrome and sarcoidosis are the most common causes of chronic sialadenitis and are often closely associated with it, and in many cases are believed to be the primary cause, although often with other contributing factors present also. One well known form of sarcoidosis is known as Heerfordt's syndrome which is characterized by facial nerve palsy, enlargement of the parotid and anterior uveitis. One study came to the conclusion that the presence of salivary calculi is the main indicator for the removal of the submandibular gland in patients where neoplasia is absent. This was because 82% of glands removed in an ENT department in Stockholm were found to have salivary calculi within them and all of these cases but one had chronic sialadenitis. A mucous retention cyst was found in one patient, but this was not considered to have contributed to the sialadenitis in this case.
The duration of the sialadenitis was found to be closely linked to atrophy, fibrosis and the degree of the inflammation in another study, which looked primarily at microliths found in the ducts and glands. Liths were also found to be related to the duration that the individual had symptoms of sialadenitis, whereas microliths were found in normal glands and varied with age. Microliths could possibly form reservoirs, thus allowing infection to ascend further towards the glands but this could not be confirmed due to the liths and microliths being distinct in this study. However, many glands did show only very minimal variations, which could allow the opportunity for more conservative treatment instead of the surgical removal of the affected gland in the future.

Histopathology

The initial stage of acute bacterial sialadenitis involves the accumulation of bacteria, neutrophils and inspissated fluid in lumen of ductal structures. Damage to ductal epithelium results in sialodochitis, accumulation of neutrophils in glandular stroma, followed by acini necrosis with microabscesses formation. Recurrent episodes result in the chronic stage, which involves the establishment of periductal lymph follicles and further destruction of salivary acini.

Infective sialadenitis

Generally, in acute bacterial and viral sialadenitis cases, the lobular architecture of the gland is maintained or may be slightly expanded. Areas of liquefaction, indicating presence of abscess, may also be seen microscopically.
In acute bacterial sialadenitis, acinar destruction with interstitial neutrophil infiltrates is observed. Small abscesses with necrosis are common.
In viral sialadenitis, vacuolar changes are seen in the acini with lymphocytic and monocytic infiltrate found in the interstitium.
Cytomegalovirus sialadenitis may show no gross symptoms.
Chronic sialadenitis presents with 50% of which are monoclonal by PCR while mucosa-associated lymphoid tissue lymphoma has ducts surrounded by broad coronas of monocytoid cells, infiltration of interfollicular region by monocytoid cells or atypical plasma cells containing Dutcher bodies, monoclonality by immunohistochemistry or flow cytometry, and monocytoid infiltrates in regional lymph nodes.
Histologically, chronic sialadenitis can appear from unremarkable to a firm tan with expansion or atrophy of the lobular structure depending on the degree of inflammation and chronicity. Salivary stones may be evident with cystic dilation of the salivary ducts and periductal fibrosis. Mucus extravasation may also be observed.
Common observations of chronic sialadenitis include chronic inflammatory infiltrate, fibrosis, acinar atrophy, and mucous cell metaplasia of the ductal system is observed.
In sialoithiasis, concomitant squamous metaplasia may be observed in the salivary ducts with dark calcific stone fragments.

Chronic sialadenitis

has various degrees of inflammation that can include focal lymphocytic sialadenitis to widespread salivary gland cirrhosis with obliteration of acini. This can be a result of obstruction of salivary ducts by microliths, or a result of immune reaction with the formation of secondary lymph follicles. Chronic sclerosing sialadenitis is characterised by presence of three major criteria of dense lymphoplasmacytic infiltrate, storiform pattern of fibrosis and obliterative phlebitis. Minor criteria include phlebitis without obliteration of the lumen and increased numbers of eosinophils. There are two features relatively inconsistent with diagnosis of IgG4-related disease which are the presence of epithelioid cell granulomas and a prominent neutrophilic infiltrate.
Sclerosing polycystic sialadenitis histologically resembles sclerosing adenosis/fibrocystic change of breast tissue. It composes of acini and ductal elements embedded in dense sclerotic stroma, and has a characteristic finding of large acinar cells present with abundant eosinophilic cytoplasmic granules. In addition, it may also present ductal epithelial proliferation which could range from hyperplasia, atypia to DCIS-like. Its stroma may show focal adipose tissue with myxoid change and variable radial scar. At present, there are immunohistochemical studies of limited value only. It is cytologically difficult to diagnose this type of sialadenitis due to the rarity of this condition and the presence of variable cell types in a cystic background.
In autoimmune sialadenitis, activation of T and B cells that infiltrate the interstitium occurs due to a response to an unidentified antigen present in the salivary gland parenchyma. This response then results in acini destruction and the formation of epimyoepithelial islands.

Autoimmune sialadenitis

Most histological appearance of autoimmune sialadenitis is similar to that of myoepithelial sialadenitis. In general, a diffuse to multinodular expansion is observed in myoepithelial sialadenitis. A distinguishing feature is the presence of epithelial-myoepithelial islands infiltrated by lymphocytes. Germinal centers may form with the progression of lymphoid infiltrate resulting in acinar atrophy. Proliferation of ductal epithelium-myoepithelium arises causing the obliteration of ductal lumina causing the formation of the epithelial-myoepithelial islands.
Granulomatosis with polyangiitis may have areas of liquefaction necrosis caused by vasculitis. A triad of vasculitis, necrosis and granulomatous inflammation may be observed.
In secondary Sjögren’s syndrome, periglandular fibrosis with the absence of inflammation may also be observed in addition to that of myoepithelial sialadenitis from the progressive systemic sclerosis.
Sarcoid has tight epithelioid granulomas and lymphoid infiltrate.
Chronic sclerosing sialadenitis has periductal fibrosis with a dense lymphoplasmacytic infiltrate with lymphoid follicles. Eosinophils may be seen.