ABSTRACT: Xerostomia, or dry mouth, is a common complaint that may be caused by several conditions, which include side effects of a wide variety of drugs, such as antidepressants, therapeutic radiation to the head and neck, dehydration, diabetes, and diseases involving salivary glands, such as Sjgren's syndrome. The complaint of dry mouth may or may not be associated with decreased salivary gland function. Individuals with xerostomia complain of problems with eating, speaking, swallowing, and wearing dentures. Some people also complain of salivary gland enlargement or changes in taste. Lack of saliva may predispose one to oral infections, such as candidiasis, and increase the risk of dental caries. Management of the individual patient with xerostomia includes assessment of salivary gland function, replacement therapy, and prevention of caries and oral candidiasis. Early recognition and management of xerostomia may prevent devastating dental disease and help to improve the quality of life. [ONCOLOGY 10(Suppl):7-11, 1996]
Xerostomia, or dry mouth, is a fairly common finding and may be related to a variety of conditions including systemic disease, radiation therapy involving the salivary glands, and drug therapy. Individuals with a dry mouth may have complaints that are due to changes in quality as well as quantity of saliva and also may not be related to the degree of salivary dysfunction. Without the protective functions of saliva that include antimicrobial activity, control of pH, and removal of food debris from the oral cavity, the risk for developing Candida infection and dental caries increases . Diagnosis of xerostomia requires careful evaluation of signs and symptoms, with clinical extra-oral and intra-oral exami- nations, assessment of salivary gland function by measurement of resting and stimulated flow rates, and, in some cases, biopsy of minor salivary glands.
Examination of the entire oral cavity is an important part of the assessment. In an individual with xerostomia, the mucosa may be dry and sticky, with the saliva appearing stringy or foamy. There may be little or no pooled saliva in the floor of the mouth, and it may be difficult to express saliva from the ducts of the major salivary glands. Dental caries may be found at the cervical margin (neck of the teeth), the incisal margins, or the tips of the teeth. These may be recurrent or primary caries and may occur at the margin of existing restorations. This type of caries may be rapid and is particularly devastating in those with severe, permanent xerostomia.
The oral mucosa may appear erythematous, with areas of the dorsal tongue sometimes becoming atrophic. The redness may represent erythematous candidiasis due to an overgrowth of Candida albicans. The erythematous patches commonly affect the hard or soft palate and dorsal surface of the tongue. Occasionally, pseudomembranous candidiasis occurs, which presents as removable white plaque that can be found on any mucosal surface. Angular cheilitis presents as cracking or fissuring at the commissures and can occur either alone or with intra-oral candidiasis. Angular cheilitis is commonly associated with C albicans, but may be caused by Staphylococcus aureus. Individuals with oral candidiasis may complain of a burning sensation and changes in taste. Some individuals are susceptible to oral ulceration because of trauma to the dry mucosa. Patients with systemic disease, such as Sjgren's syndrome and human immunodeficiency virus (HIV) infection, may have enlarged parotid glands and even submandibular glands.
Individuals with xerostomia complain of problems with eating, speaking, swallowing, and wearing dentures. They may experience difficulty in eating dry foods, wearing dentures for a long period of time, or speaking without taking frequent sips of water. Interference with eating may occur because of changes in taste and difficulty eating spicy or acidic food.
Many conditions can cause a reduction in salivary flow. Some produce reversible or temporary dryness, while others result in changes that are essentially permanent. Complaints of dry mouth in a geriatric population are more likely to be related to medications than to changes in the salivary glands. Temporary conditions include use of certain drugs, viral infections, dehydration and psychogenic causes, such as fear. Many different types of drugs have been associated with dry mouth. These include drugs to prevent motion sickness, antihistamines, antidepressants, anti-psychotics, antianxiety agents, antiparkinsonism drugs, antihypertensives, decongestants, diuretics and the narcotic, meperidine. Many of these drugs, including the antihistamines, antidepressants, antipsychotics, antianxiety medications, and decongestants, cause dryness because of their anticholinergic action.
Some drugs affect fluid and electrolyte balance. The antihypertensive medication methyldopa causes dryness because it is metabolized to methyl-norepinephrine in the brain. This causes stimulation of alpha-2-adrenergic receptors in the brainstem. Dryness in the elderly appears to be related to medication use or systemic disease rather than to changes directly attributable to age [2-5].
Chronic inflammatory disease, such as Sjgren's syndrome, sarcoidosis, and amyloidosis, cause xerostomia because of changes in the salivary glands. Sjgren's syndrome is an autoimmune disease in which marked infiltration of exocrine glands, notably, the lachrymal and salivary glands, occurs. The lachrymal gland infiltrate causes dry eyes (keratoconjunctivitis sicca). The infiltrate, consisting predominantly of CD4 lymphocytes, as well as a small number of plasma cells and macrophages, replaces the gland acinar or secretory cells.
The disease occurs in two forms. Primary Sjgren's syndrome is mostly confined to the salivary and lachrymal glands. Secondary Sjgren's syndrome is associated with rheumatoid arthritis and other autoimmune diseases, including systemic lupus erythematosus. Autoantibodies may be found that react against ANA, SS-A(Ro), and SS-B(La). The etiology of Sjgren's syndrome is unclear but probably includes viral, genetic and immunological factors. Diagnosis of Sjgren's syndrome is made from clinical and laboratory assessments, including histopathology of labial salivary gland biopsy.
Sarcoidosis is another chronic inflammatory disease that causes xerostomia because of changes in salivary glands that include granulomatous inflammation with Langhans' type giant cells and epithelioid macrophages, forming noncaseating granulomas. In amyloidosis, deposits of amyloid occur in the salivary glands with the consequent development of xerostomia.
Some individuals infected with HIV experience salivary gland enlargement and xerostomia. HIV-salivary gland disease is similar, in some ways, to Sjgren's syndrome, with xerostomia and enlargement of the parotid glands and, occasionally, the submandibular glands. However, dry eyes are not a common complaint. In HIV-salivary gland disease the T-lymphocytic infiltrate is comprised predominantly of CD8+ cells, whereas CD4+ cells predominate in Sjgren's syndrome. HIV-salivary gland disease is more common in children but is occasionally seen also in adults. Other systemic diseases that can cause xerostomia include diabetes, if uncontrolled, and cystic fibrosis.
Almost all patients who undergo radiation therapy to the head and neck develop xerostomia. Radiation causes changes to the secretory cells, particularly the serous cells, resulting in a reduction in salivary output and a change in the viscosity of the saliva. Thick or sticky saliva is a common early complaint. The degree of permanent xerostomia depends upon the volume of salivary gland included in the fields of radiation and the total radiation dose. Even low doses of radiation6 can cause changes in the quantity and quality of saliva. When the total radiation dose exceeds 5,200 cGy, salivary flow diminishes, the mouth feels extremely dry, and little or no saliva is expressible from the salivary ducts. These changes are essentially permanent, with little or no recovery of salivary gland function .
Some patients undergoing chemotherapy have reported dryness during therapy, but these changes are usually temporary . Xerostomia may also be a feature of graft-vs-host disease. Changes occur when donor lymphocytes proliferate and infiltrate the recipient tissues, including salivary glands, in a pattern and with clinical results resembling those seen in Sjgren's syndrome.
Xerostomia may be evident from examination of the oral mucosa. Complaints of dryness should be further evaluated by careful questioning. Problems with eating and swallowing have been shown to have a close association with xerostomia .
Salivary flow measurement (sialometry) is an important part of the evaluation of dry mouth. It can be used to investigate and establish the diagnosis of xerostomia. The efficacy of interventive regimens, such as discontinuing medications or the use of sialagogues, can be evaluated by repeated salivary flow measurements. Standardized techniques must be used. These have the advantage of being relatively easy to perform, are reproducible, and give a quantitative assessment of salivary production.
Measurement of resting, or unstimulated, whole saliva is an easy way to evaluate complaints of dryness. Resting flow may be reduced in association with fear or anxiety, depression, and diabetes , and with the use of certain drugs. Reduced flow usually correlates with complaints of dryness. Normal resting flow during the day is about 0.3 mL/min .
Salivary flow rates from the parotid gland or the submandibular/sublingual glands can be assessed by the use of collection devices placed over the duct orifices. Saliva is stimulated with citric acid. The normal flow rate from the parotid gland is usually within the range of 0.4 to 1.5 mL/min/gland [11,12]. Reduced parotid flow is seen in diseases such as Sjgren's syndrome, following radiation therapy, and with some medications. Reduced flow may not always be associated with complaints of dryness.
Imaging techniques may provide additional important information in some cases, although they may not be useful in assessing salivary gland function. Sialography involves the injection of a radio-opaque material into the salivary glands. It may be useful in identifying salivary gland stones and salivary gland masses. Sometimes the contrast medium can cause damage and can be retained in people with xerostomia, because the material is not cleared from the gland.
Scintigraphy of the major glands using sodium pertechnetate can be helpful in assessing salivary gland function. Biopsy of minor labial salivary glands is used in the diagnosis of Sjgren's syndrome, HIV-salivary gland disease, sarcoidosis, amyloidosis, and graft-vs-host disease. Biopsy of major glands should be reserved for investigation of salivary gland enlargement when malignancy is suspected.
1. Korsten MA, Rosman AS, Fishbein S, et al: Chronic xerostomia
increases esophageal acid exposure and is associated with esophageal
injury. Am J Med 90:701-706, 1991.
2. Wu AJ, Ship JA: A characterization of major salivary gland
flow rates in the presence of medications and systemic diseases.
Oral Surg Oral Med Oral Path 76:301-306, 1993.
3. Sreebny LM, Yu A, Green A, et al: Xerostomia in diabetes mellitus.
Diabetes Care 15:900-904, 1992.
4. Sreebny LM: Recognition and treatment of salivary induced conditions.
Int Dent J 39:197-204, 1989.
5. Gilbert GH, Heft MW, Duncan RP: Mouth dryness as reported by
older Floridians. Community Dent Oral Epidemiol 21:390-397, 1993.
6. Dreizen S, Brown LR, Handler S, et al: Radiation-induced xerostomia
in cancer patients: Effect on salivary and serum electrolytes.
Cancer 38:273-278, 1976.
7. Franzen L, Funegard U, Ericson T, et al: Parotid gland function
during and following radiotherapy of malignancies in the head
and neck: A consecutive study of salivary flow and patient discomfort.
Eur J Cancer 28:457-462, 1992.
8. Schubert MM, Izzutsu KT: Iatrogneic causes of salivary gland
dysfunction. J Dent Res 66:680-688, 1987.
9. Fox PC, Busch KA, Baum BJ: Subjective reports of xerostomia
and objective measures of salivary gland performance. J Am Dent
Assoc 115:581-584, 1987.
10. Sreebny LM, Yu A, Green A, et al: Xerostomia in diabetes mellitus.
Diabetes Care 15:900-904, 1992.
11. Daniels TE, Silverman S Jr., Michalski JP, et al: The oral
component of Sjögren's syndrome. Oral Surg Oral Med Oral
Path 39:875-885, 1985.
12. Wu AJ, Ship JA: A characterization of major salivary gland
flow rates in the presence of medications and systemic diseases.
Oral Surg Oral Med Oral Path 76:301-306, 1993.
13. Epstein JB, Burcheu JL: A clinical trial of bethanechol in
patients with xerostomia after radiation therapy: A pilot study.
Oral Surg Oral Med Oral Path 77:610-614, 1994.
14. Fox PC, Atkinson JC, Macynski AA, et al: Pilocarpine treatment
of salivary gland hypofunction and dry mouth (xerostomia). Arch
Intern Med 151:1149-1152, 1991.
15. Greenspan D, Daniels TE: Effectiveness of pilocarpine in postradiation
xerostomia. Cancer 59:1123-1125, 1987.
16. Ferguson MM: Pilocarpine and other cholinergic drugs in the
management of salivary gland dysfunction. Oral Surg Oral Med Oral
Path 75:186-191, 1993.
17. Wiseman LR, Faulds D: Oral pilocarpine: A review of its pharmacological
properties and clinical potential in xerostomia. Drug Evaluation
18. Valdez IH, Wolff A, Atkinson JC, et al: Use of pilocarpine
during head and neck radiation therapy to reduce xerostomia and
salivary dysfunction. Cancer 71:1848-1851, 1993.
19. Johnson JT, Ferretti GA, Nethery WJ, et al: Oral pilocarpine
for post-irradiation xerostomia in patients with head and neck
cancer. N Engl J Med 329:390-395, 1993.
20. LeVeque FG, Montgomery M, Potter D, et al: A multicenter,
randomized, double-blind, placebo-controlled, dose-titration study
of oral pilocarpine for treatment of radiation-induced xerostomia
in head and neck cancer patients. J Clin Oncol 11:1124-1131, 1993.
21. Epstein JB, Schubert MM: Synergistic effect of sialagogues
in management of xerostomia after radiation therapy. Oral Surg
Oral Med Oral Path 64:179-182, 1987.
22. Stefler M, Chou L, Daniels TE: Electrical stimulation of salivary
flow in patients with Sjögren's syndrome. J Dent Res 67:1334-1337,
23. Talal N, Quinn JH, Daniels TE: The clinical effects of electrostimulation
on salivary function of Sjögren's syndrome patients: A placebo-controlled
study. Rheumatol Int 12:43-45, 1992.
24. Meyerowitz C, Featherstone JD, Billings RJ, et al: Use of
an intraoral model to evaluate 0.05% sodium fluoride mouth rinse
in radiation-induced hyposalivation. J Dent Res 70:894-898, 1991.
25. Epstein JB, McBride BC, Stevenson-Moore P, et al: The efficacy
of chlorhexidine gel in reduction of Streptococcus mutans and
Lactobacillus species in patients treated with radiation therapy.
Oral Surg Oral Med Oral Path 71:172-178, 1991.