Key points

Introduction

Sialadenitis is defined as inflammation of the salivary glands. The saliva they produce is essential for the normal functioning and health of the mouth. Sialadenitis in the pediatric population accounts for up to 10% of all salivary gland disease. Viral parotitis and juvenile recurrent parotitis (JRP) are the two most common causes.

Viral sialadenitis is most commonly caused by the paramyxovirus. Mumps should be distinguished from other causes of sialadenitis; however, the incidence has significantly declined as a result of vaccination. Infectious sialadenitis may also be the result of bacterial infections. Acute suppurative parotitis can develop from aerobic and anaerobic bacterial pathogens. Both are likely the result of diminished salivary flow with ascending infection from the oral cavity or transitory bacteremia, where contact is made with the ductal epithelium.

Less well characterized is obstructive and recurrent acute sialadenitis. JRP is the most commonly reported clinical entity. JRP is the subject of an increasing amount of research to adequately characterize its cause and reach a consensus on treatment. A variety of factors are thought to cause JRP, including genetic, immune, infection, dehydration, allergy, ductal abnormalities, and ductal obstruction. Presently, most authors favor a multifactorial cause. Salivary stones are the most common cause of chronic obstructive sialadenitis. Although common in the adult population, salivary stones are far less common in the pediatric population. Pediatric sialolithiasis is thought to occur in less than 5% of all reported cases.

Other systemic processes, including immune deficiency (IgA), autoimmune disease (Sjögren syndrome), viral infection (HIV), genetic factors (HLA B-27), and allergy have all been suggested as predisposing factors in the development of a form of chronic sialadenitis. There are scattered case series and case reports, without formal investigations to substantiate a strong association.

In the last 20 years, there has been a paradigm shift in the management of sialadenitis. Historically, open surgical and gland excision procedures were the treatment of choice for conservative management failures. Transition to gland preservation techniques has advanced nonsurgical, minimally invasive interventions, alone or in combination with other surgical approaches. Sialendoscopy was first reported more than two decades ago and has become the leading diagnostic technique and intervention for pediatric sialadenitis.

This article presents a comprehensive review of pathophysiology, clinical presentation, diagnosis, and treatment of pediatric sialadenitis.

Introduction

Sialadenitis is defined as inflammation of the salivary glands. The saliva they produce is essential for the normal functioning and health of the mouth. Sialadenitis in the pediatric population accounts for up to 10% of all salivary gland disease. Viral parotitis and juvenile recurrent parotitis (JRP) are the two most common causes.

Viral sialadenitis is most commonly caused by the paramyxovirus. Mumps should be distinguished from other causes of sialadenitis; however, the incidence has significantly declined as a result of vaccination. Infectious sialadenitis may also be the result of bacterial infections. Acute suppurative parotitis can develop from aerobic and anaerobic bacterial pathogens. Both are likely the result of diminished salivary flow with ascending infection from the oral cavity or transitory bacteremia, where contact is made with the ductal epithelium.

Less well characterized is obstructive and recurrent acute sialadenitis. JRP is the most commonly reported clinical entity. JRP is the subject of an increasing amount of research to adequately characterize its cause and reach a consensus on treatment. A variety of factors are thought to cause JRP, including genetic, immune, infection, dehydration, allergy, ductal abnormalities, and ductal obstruction. Presently, most authors favor a multifactorial cause. Salivary stones are the most common cause of chronic obstructive sialadenitis. Although common in the adult population, salivary stones are far less common in the pediatric population. Pediatric sialolithiasis is thought to occur in less than 5% of all reported cases.

Other systemic processes, including immune deficiency (IgA), autoimmune disease (Sjögren syndrome), viral infection (HIV), genetic factors (HLA B-27), and allergy have all been suggested as predisposing factors in the development of a form of chronic sialadenitis. There are scattered case series and case reports, without formal investigations to substantiate a strong association.

In the last 20 years, there has been a paradigm shift in the management of sialadenitis. Historically, open surgical and gland excision procedures were the treatment of choice for conservative management failures. Transition to gland preservation techniques has advanced nonsurgical, minimally invasive interventions, alone or in combination with other surgical approaches. Sialendoscopy was first reported more than two decades ago and has become the leading diagnostic technique and intervention for pediatric sialadenitis.

This article presents a comprehensive review of pathophysiology, clinical presentation, diagnosis, and treatment of pediatric sialadenitis.

Anatomy and pathophysiology

A review of the anatomy of the salivary gland network can aid in understanding the pathophysiology of sialadenitis. The function of the major salivary glands is to secrete saliva through a network of ducts. Saliva has numerous functions, including taste, digestion, lubrication, tooth integrity, and antibacterial activity, which maintain the health of the mouth. The paired major salivary glands consist of the submandibular, parotid, and sublingual glands. There are numerous minor salivary glands scattered along the lips, tongue, buccal mucosa, palate, and pharynx.

The parotid glands are the largest of the salivary glands. Stensen duct travels parallel and approximately 1 cm below the zygoma to exit opposite the second upper molar. The length of Stensen duct is 4 to 6 cm. The glossopharyngeal nerve provides autonomic innervation to the parotid gland for the secretion of saliva.

The submandibular glands are the second largest salivary glands. Wharton duct exits the floor of the mouth near the frenulum of the tongue. The length of Wharton duct is 4 to 5 cm. Autonomic fibers are carried through the facial and lingual nerve to innervate the submandibular gland.

The sublingual glands lie just deep to the mucosa of the floor of the mouth and, unlike the parotid and submandibular glands, lack a single dominant duct. They drain through multiple small ducts, which exit the gland and open along the floor of the mouth. Autonomic innervation of the sublingual gland follows the submandibular gland.

Minor salivary glands are scattered in the oral cavity and oral pharynx. They each have a single duct that secretes into the oral cavity and pharynx. Autonomic innervation primarily comes from the lingual nerve.

The salivary glands are made up of parenchyma and stroma. The parenchyma of the salivary glands is made up of the salivary acinus and associated ducts. Stroma consists of surrounding connective tissue. Salivary acini produce saliva, which is composed of organic and inorganic compounds. Saliva is secreted through a complex ductal system into the mouth and pharynx. Serous acini secrete watery saliva that is enzyme rich and contains IgA. Serous saliva aids in digestion, taste, antibacterial properties, and tooth integrity. Mucinous acini produce viscous saliva that contains higher amounts of IgA and other protective enzymes. Mucinous saliva facilitates lubrication, mastication, and swallowing. The parotid gland is composed of primarily serous acini. Both the submandibular and sublingual glands contain serous and mucinous acini. The submandibular gland, however, has more serous than mucinous acini. The sublingual gland is predominately mucinous. Two-thirds of constant salivation is produced by the submandibular gland, and reversed during periods of stimulation when two-thirds of salivation is produced by the parotid gland. The basal salivary flow rate in the parotid gland is considerably less than that of the submandibular gland.

A variety of factors are attributed to inflammation of the salivary glands. Viral or bacterial infections are thought to cause salivary gland inflammation. Some authors have suggested that genetics, immunologic diseases, congenital ductal abnormalities, dehydration, and allergy contribute to the pathology. As diagnostic technology has improved, additional predisposing factors have been reported, including salivary stones, mucus plugs, foreign bodies, and stenosis.

Viral or bacterial infections may result in sialadenitis from direct inoculation of the ductal epithelium or through ascending oral cavity infections. Retrograde infections can arise from a septic focus in the oral cavity. Alternatively, they may be the result of normal oral flora entering the salivary glands secondary to diminished salivary flow in the dehydrated, toxic, or debilitated patient. Transient bacteremia with direct ductal inoculation during a systemic illness, such as mumps parotitis, has also been suggested.

It has been difficult to identify one specific cause pertaining to recurrent acute sialadenitis. Histologic specimens of sialadenitis show dilated ducts (sialectases) and stromal lymphocytic infiltration. Conventional thought has been that infection is a primary event. The development of sialectases is considered a secondary change predisposing to chronic low-grade inflammation with acute exacerbations. Other clinicians advocate a sequence of events effecting a structural change, predisposing to recurrent acute inflammation. These authors suggested that decreased salivary flow leads to inflammation and tissue destruction. Tissue destruction exacerbates inflammation and salivary stasis, yielding mucus plugs/debris, stenosis, and postobstructive sialectases. Microscopic examination has shown that mucus plugs contain desquamated cells. The mucus plugs are secondary to inflammation but are also an obstruction. Other authors proposed that congenital ductal stenosis predisposes to recurrent episodes of inflammation.

Obstruction by salivary stones or foreign bodies can also result in sialadenitis. These obstructions cause inflammation, salivary stasis, postobstructive dilation, tissue damage, and remodeling that predispose to further inflammatory changes. Several theories describe the formation of a salivary stone. Salivary mucin, bacteria, and desquamated epithelial cells form an early organic nidus. Organic and nonorganic material is deposited around the nidus, which gradually expands. Another model suggests that infection (inflammation and tissue destruction) changes salivary composition (precipitation of proteins or changes in calcium solubility), which leads to stone formation. The retrograde theory for sialolithiasis describes how bacteria, nutrients, or a foreign body from the oral cavity pass into the salivary duct and become the nidus for stone formation.

The link between genetics, immunologic disease, and allergy and sialadenitis is not completely understood. Early studies excluded a relationship connecting these factors. Others have supported such an association based on cytologic and pathologic findings of inflammation, vasculitis, tissue destruction, and stenosis. IgA deficiency can predispose to infection, and genetic factors influence the overall immune response.

The general consensus is that sialadenitis is a multifactorial process. Recently, Jabbour and colleagues comprehensively described how multiple factors, independently or in combination, can result in acute, chronic, or recurrent salivary gland inflammation. The appropriately termed “salivary gland inflammatory cycle” is a sequence of events that includes decreased salivary flow, inflammation, ductal dysfunction and metaplasia, and increased mucinous saliva. Each component progresses serially to complete a full circle and return to decreased salivary flow. Predisposing factors of the inflammatory cycle include dehydration, infection, ductal abnormality, and/or immune factors. Additional components that can result from or add to the cycle include the precipitation of proteins with stone formation, and ductal stenosis resulting from chronic inflammation. Both further the inflammatory cycle through obstruction and decreased salivary flow. In the multifactorial cause proposed by Jabbour and colleagues, inflammation is the cause and result of the nonneoplastic inflammatory disease.

Although the inflammatory cycle is present in parotid and submandibular gland disease, there is a closer association between the parotid gland and an inflammatory or infectious process. Both bacterial and viral infections and idiopathic inflammation occur more commonly in the parotid gland, whereas sialolithiasis occurs most frequently in the submandibular gland. The parotid gland has a lower rate of secretion and a less mucinous salivary composition than the submandibular gland. Mucinous saliva confers greater antibacterial properties. Both increase the parotid glands susceptibility to infection and inflammation. Characteristic inflammatory changes, ductal stenosis, and sialectasis cause recurrent inflammation more commonly in the parotid gland. The submandibular gland is more likely to form salivary stones. The mucinous saliva is viscous and likely to form a nidus for stone formation (80%–90%).

Clinical presentation and diagnosis

The most common presenting symptoms of acute sialadenitis are swelling, pain, fever, and erythema overlying the affected glands. Symptoms are usually unilateral; in bilateral cases, symptoms are more prominent on one side. Pain is elicited with mastication and/or swallowing. Trismus can be present. The mouth of the duct is erythematous and edematous. Purulence and/or inspissated mucus may be expressed by manual palpation and gentle pressure applied over the salivary gland and duct. In severe cases of infectious sialadenitis, systemic complications can extend regionally into adjacent tissues, or systemically spread to distal sites. Clinical signs vary based on the site of inflammation and an acute or chronic presentation. Table 1 provides a complete list of sialadenitis etiologies.

Viral parotitis is generally caused by the paramyxovirus. Mumps, historically the most common infectious sialadenitis, has become much less common because of immunization efforts. The effectiveness of the vaccine approaches 90%. Clinicians should distinguish mumps from other causes of sialadenitis in the pediatric population, because outbreaks have occurred among highly vaccinated individuals. Mumps is a systemic illness that infects the salivary glands without producing purulence. Prodromal symptoms include fever, headache, and malaise, with subsequent gland involvement. Other exocrine glands can be affected, and systemic complications, such as encephalitis, are not uncommon. Serologic assays are useful in confirming the diagnosis. Other viruses are less commonly associated with salivary gland inflammation (see Table 1 ).

Bacterial sialadenitis most commonly occurs in the parotid gland. It is characterized by acute swelling of the cheek that extends to the angle of the mandible. In the submandibular gland, severe infection may result in floor of mouth edema and respiratory compromise. It is usually distinguished from other inflammatory diseases of the salivary glands by the presence of pus. In the absence of purulence, fever and leukocytosis support the diagnosis. The most common pathogens associated with acute bacterial parotitis are Staphylococcus aureus and Streptococcus species, and less commonly, anaerobic pathogens (see Table 1 ). Any purulence should be sent for aerobic/anaerobic Gram stain and culture. Antistaphylococcal penicillinase-resistant antibiotics should be started while awaiting culture results. Systemic manifestations, such as abscess formation, should be evaluated with imaging.

Chronic sialadenitis is commonly associated with chronic inflammation and obstruction of the salivary glands. Patients frequently present with repeated episodes of acute painful gland swelling, which can be complicated by a superimposed bacterial infection. Often, the symptoms are associated with eating and settle between meals. The main causes for chronic obstructive sialadenitis are salivary stones, mucus plugs, ductal stenosis, and foreign bodies.

Pediatric sialolithiasis is relatively uncommon and usually included within the adult literature. It occurs in less than 5% of all cases. Similar to adult sialolithiasis, stones are found in the submandibular gland in 80% to 90% of cases, followed by the parotid gland, and rarely the sublingual and minor salivary glands. Salivary stones in pediatric cases are smaller, occur distally within the duct, and present with shorter symptom duration.

There is little literature characterizing ductal stenosis or stricture in obstructive sialadenitis. Stenosis of the duct is more common in the parotid ductal system than in the submandibular gland based on endoscopic findings. Obstruction is primarily caused by inflammation in the salivary duct, leading to segments of stricture and dilation. The partial obstruction caused by stenosis is thought to be an important factor in the recurrence and persistence of sialadenitis and the formation of sialoliths. Although the incidence of mucus plugs, foreign bodies, and ductal stenosis was lacking in the past, advancements in diagnostic and therapeutic tools have allowed clinicians to confirm their presence in the development of chronic obstructive sialadenitis.

Chronic sialadenitis is also connected to immune deficiency and several autoimmune disorders, such as Sjögren syndrome, selective IgA deficiency, HIV, and HLA-B27 syndromes. Diagnostic salivary endoscopy suggests that chronic inflammation and tissue destruction lead to stricture formation and stenosis. Similarly, acute infection may complicate this chronic disease.

Sjögren syndrome is a chronic inflammatory disease of the exocrine glands with many extraglandular manifestations. The salivary glands are the main target. Dry mouth and dry eyes are common signs of Sjögren syndrome. Histopathologic changes include lymphocytic infiltration, sialectases, and tissue destruction. It is rare in children and as a result standardized criteria are lacking. However, acute inflammatory symptoms have been reported as the initial presentation in some cases. The presence of salivary gland inflammation has been used to increase the sensitivity of proposed pediatric criteria for Sjögren syndrome.

Reports have also described immune deficiency in association with sialadenitis. Several authors have reported IgA deficiency in patients presenting with recurrent parotitis through serology and immunoflorescence studies.

Salivary gland involvement in children with HIV is well recognized. Characteristically, one or both glands are firm, nontender, and chronically enlarged. Xerostomia may also be a presenting symptom. Infiltration of CD8-positive lymphocytes, possibly as a result of HIV, Epstein-Barr virus, or an interaction between the two, enlarges the gland. The diagnosis of HIV parotitis is usually clinical with typical findings of HIV.

JRP is a separate clinical entity, and thought to be the most common salivary disease involving children, after mumps. It is characterized by recurrent episodes of inflammation of the parotid gland. Symptoms include jaw swelling, pain, and redness, associated with fever and malaise. Most cases are unilateral; when bilateral cases occur, one side is usually dominant. The true incidence of JRP is unknown; most reports are case series. Studies show predominance in males, although the sex distribution is reversed when events continue into adulthood. The age distribution is biphasic, typically occurring between ages 2 and 6, and again at the start of puberty. The natural history is recurrence. However, most authors agree that this is a self-limited disease that resolves sometime after puberty, whereas rare cases extend into adulthood.

The diagnosis of JRP is made clinically in patients with a history of recurrence and physical examination findings. Ultrasonographic findings are consistently being used to make the clinical diagnosis. The minimum requirement for diagnosis is two episodes. Most patients are only diagnosed after multiple episodes have occurred. Hackett and colleagues reported an average of 4.7 episodes with a range between two and nine events. Typically, symptoms last 4 to 7 days. The interval between attacks varies individually, with episodes occurring every 3 to 4 months to 10 times per year. The measure of severity and thus treatment is based on the frequency of disease.

There are case reports that link JRP, immune deficiency, genetics, and allergy. No causality has been proved; in many early, large series of JRP, these conditions were not found to contribute to this diease. Autoimmune disease is not likely. Most consider JRP as self-limiting and autoantibodies are usually absent. Instead, clinicians should distinguish JRP from recurrent sialadenitis as a presenting sign of autoimmune disease. A clear cause is unknown, although a multifactorial approach is recognized as the leading hypothesis. Each attack may further tissue destruction and function of the gland. Early recognition of JRP and treatment of this pathology are of utmost importance.