Chapter 8 - Xerostomia and salivary gland hypofunction

Chapter 8 Xerostomia and salivary gland hypofunction Professor Mahvash Navazesh, Herman Ostrow School of Dentistry of USC, LosAngeles, USA

Introduction Saliva plays a significant role in the maintenance of oral-pharyngeal health.

Subjective complaints of a dry mouth (xerostomia) and objective evidence of diminished salivary output (salivary gland hypofunction) are common conditions, particularly in medically compromised older adults. They can result in impaired food and beverage intake, a sundry of oral disorders, and diminished host defence and communication. Persistent salivary gland hypofunction can produce permanent oral and pharyngeal disorders and impair a person’s quality of life.

Global estimates of xerostomia and salivary gland hypofunction are difficult to ascertain due to limited study design, differences in study populations, usage of the terms xerostomia and salivary gland hypofunction interchangeably, utilisation of different diagnostic criteria and saliva collection methods, and limited sample sizes.

Overall, the prevalence of xerostomia and salivary gland hypofunction increases with age and affects approximately 30% of the population aged 65 years and older.

There are multiple causes of xerostomia and salivary gland hypofunction the most common being drug-induced, since most older adults are taking at least one medication that causes salivary gland hypofunction. It is difficult, however, to estimate the true prevalence of xerostomia in older adults taking medications. The prevalence of xerostomia is nearly 100% among patients with SjÜgren’s syndrome, an autoimmune exocrinopathy affecting between 1-4% of older adults. Radiation of the head and neck for the treatment of cancer causes permanent xerostomia, which has a 100% prevalence rate if the dose is >25 Gy, but the numbers affected are relatively small compared with those older adults susceptible to medicationinduced xerostomia. Estimates of the prevalence of xerostomia in adult ambulatory and nursing home populations range from 16-72%. Combining the prevalence of xerostomia-associated conditions with the percentage of adults with these conditions who complain of xerostomia yields the above-mentioned general estimate of approximately 30% xerostomia prevalence among adults 65 years and older.

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Approximately 80% of all persons over age 65 have at least one chronic condition and 50% have at least two. Hypertension and heart diseases, diabetes, arthritis and cancer are the most frequently occurring conditions among older adults.

These conditions, and the medications often prescribed for their management, could impact the structure and function of salivary glands leading to complaints of xerostomia or clinical evidence of salivary gland hypo-function. More than 400 medications list dry mouth as a potential adverse effect. In May 2011 the United States Food and Drug Administration (FDA) added dry mouth to its consumer health information.

Aetiology of xerostomia and salivary gland hypofunction: salivary gland pathology Intraoral sources of salivary gland pathology can be divided into three broad classifications: infectious, non-infectious, and neoplastic. Bacterial infections are more common in older adults who experience salivary gland hypofunction secondary to medications, head and neck radiation, systemic diseases, or dehydration. Acute parotitis was commonly seen before the antibiotic era in terminally ill and dehydrated patients and contributed to mortality by sepsis. Now, acute parotitis is observed infrequently. Chronic parotitis is not unusual and it follows obstruction of a parotid duct with subsequent bacterial colonisation and infection.

Signs and symptoms of bacterial salivary infections include swelling, purulence from the major salivary gland duct, and pain.

Viral infections occur in persons of all ages, particularly in immunocompromised patients, and preferentially involve parotid glands. Mumps is caused by paramyxovirus, and presents as bilateral parotid gland swelling in children.

Cytomegalovirus infections tend to be mild with non-specific findings, and are observed primarily in adults.

Non-infectious (reactive) causes of salivary pathology are most commonly due to obstruction of a salivary gland excretory duct and can be divided into acute and chronic conditions. Acute sialadenitis usually results from an immediate partial or complete ductal obstruction (i.e. sialolithiasis), whereas chronic recurrent sialadenitis occurs as a result of prior infection and/or ductal scarring.

Mucoceles are the most common reactive lesion of the lower lip and are caused by local trauma. When a minor salivary gland duct is severed mucin leaks into the surrounding connective tissue resulting in a smooth-surfaced painless nodule in the submucosal tissues. Mucous cysts of the sublingual gland, and, less frequently, the submandibular gland, are referred to as ranulas. They present as either unilateral

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circumscribed lesions (subsequent to ductal obstruction and cystic dilation) or plunging lesions (following extravasation of saliva herniating through the tissues of the floor of the mouth and the mylohyoid muscle). Both types of ranulas require surgical excision and possible marsupialization of the cyst.

Most calculi (sialoliths, stones) develop in the submandibular duct system and are caused by calcification of mucous plugs and cellular debris, typically as a result of dehydration and glandular inactivity. Sialoliths occur infrequently in the parotid duct system and are considered rare in the sublingual and minor salivary glands.

Most salivary gland tumours are benign, arising from epithelial tissues; however, neoplasms may originate from any adjacent tissue or structure (adipose, nerves, blood vessels, lymph nodes, lymphatics). The preponderance of benign salivary gland neoplasms occurs within the parotid gland, with the majority (80%) being pleomorphic adenomas. These tend to be unilateral and most commonly present as an asymptomatic mass in the tail of the parotid gland. They are slow growing, well delineated and encapsulated. Malignant salivary gland tumour incidence increases with age, and these tumours are more common in the submandibular and sublingual glands compared with the parotid gland. When epithelial neoplasms arise in the submandibular or sublingual glands, only 50% are benign.

Mucoepidermoid carcinoma is the most common malignant salivary gland tumour, followed by adenoid cystic carcinoma (cylindroma), acinic cell carcinoma, adenocarcinoma, squamous cell carcinoma, and carcinoma arising in a pleomorphic adenoma. The most commonly affected intraoral site is the palate followed by the upper lip. Adenoid cystic carcinomas are aggressive tumours that undergo perineural invasion. They have good 10-year survival rates, but long-term mortality is likely. The signs and symptoms of a malignant salivary gland tumour include a swelling with facial nerve paralysis, pain, or facial paresis.

Systemic diseases There are numerous systemic conditions that have been associated with xerostomia and salivary gland hypofunction, the most common being Sjögren’s syndrome, primarily a disease affecting women with a typical onset during the fourth or fifth decade of life. Clinically, Sjögren’s syndrome presents in either primary or secondary forms. Primary Sjögren’s syndrome is characterised by xerostomia and xerophthalmia (dry eyes) that are the result of a progressive loss of salivary and lacrimal gland function. Secondary Sjögren’s syndrome includes involvement of one or both of these exocrine sites in the presence of another connective tissue disease such as rheumatoid arthritis, systemic sclerosis, or systemic lupus erythematosus. Lymphocytic infiltrates of salivary glands increase as the inflammatory disease progresses, 66

ultimately producing acinar gland degeneration, necrosis, atrophy, and complete destruction of the salivary gland parenchyma. Diagnosis requires a combination of objective salivary, lacrimal, and serological criteria and subjective complaints of xerostomia or xerophthalmia.

Other autoimmune conditions associated with Sjögren’s syndrome and causing salivary gland hypofunction include rheumatoid arthritis, scleroderma, and lupus.

HIV+ infected individuals and those with AIDS frequently experience salivary gland hypofunction from lymphocytic destruction of the glands and as a sequela of medications. Diabetes may cause changes in salivary secretions, and associations have been made between poor glycemic control, peripheral neuropathies, and salivary hypofunction. Alzheimer’s disease, Parkinson’s disease, strokes, cystic fibrosis, Hepatitis C and dehydration will also inhibit salivary secretion.

It was previously thought that salivary function declined with greater age, yet it is now accepted that output from the major salivary glands does not undergo clinically significant decrements in healthy older adults. There are reports of agerelated decrements in several salivary constituents, whereas other studies report age-stable production of salivary electrolytes and proteins in the absence of major medical problems and medications. It is likely that numerous systemic diseases (e.g.

Sjögren’s syndrome) and their treatments (medications, head and neck radiation, chemotherapy) contribute significantly to salivary gland hypofunction in the elderly. It has been demonstrated that the salivary glands of older adults are more vulnerable to the deleterious effects of medications compared with those of younger individuals, confirming the finding of greater xerostomia prevalence among older adults, particularly those taking medications.

Medications The most common causes of salivary gland hypofunction and xerostomia are prescription and non-prescription medications. For example, 80% of the most commonly prescribed medications have been reported to cause xerostomia, with over 400 medications causing a side effect of salivary gland hypofunction. The intake of prescription medications increases with age, and more than 75% of persons over the age of 65 years take at least one prescription medication. Further, with the increased intake of prescription medications, there is an increase in xerostomia.

The most common types of medications causing salivary hypofunction have anticholinergic effects via inhibition of acetylcholine binding to muscarinic receptors on the acinar cells. This prevents initiation of the cascade of physiological events that ultimately result in water movement through acinar cells, into the ductal system, and ultimately into the mouth. Importantly, any medications that inhibit neurotransmitter 67

binding to acinar membrane receptors, or that interfere with ion transport pathways, may also adversely affect the quality and quantity of salivary output.

These medications include tricyclic antidepressants, sedatives and tranquilizers, antihistamines, antihypertensives (alpha and beta blockers, diuretics, calciumchannel blockers, angiotensin converting enzyme inhibitors), cytotoxic agents, anti Parkinsonian, and anti-seizure drugs.

Chemotherapy for cancer treatment has also been associated with salivary gland hypofunction. These changes appear to occur during and immediately after treatment. Most patients experience a return of salivary function to prechemotherapy levels, yet long-term changes have been reported. Finally, radioactive iodine (I131) used in treatment for cancers of the thyroid gland may cause parotid, but not submandibular, salivary gland hypofunction in a dosedependent fashion, since the salivary glands concentrate iodide to levels much higher than those in the blood.

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