Volume 20, No.

2
Original Articles
Xerostomia: Clinical Aspects and Treatment
Sandra F. Cassolato and Robert S. Turnbull
Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Canada M5G 1G6
Abstract
Xerostomia or dry mouth is a condition that is frequently encountered in dental practice. The most common
cause is the use of certain systemic medications, which make the elderly at greater risk because they are
usually more medicated. Other causes include high doses of radiation and certain diseases such as Sjgrens
syndrome. Xerostomia is associated with difficulties in chewing, swallowing, tasting or speaking. This
results in poor diet, malnutrition and decreased social interaction. Xerostomia can cause oral discomfort,
especially for denture wearers. Patients are at increased risk of developing dental caries. A thorough intra-
oral and extra-oral clinical examination is important for diagnosis. Treatment may include the use of
salivary substitutes (Biotene), salivary stimulants such as pilocarpine, ongoing dental care, caries prevention,
a review of the current prescription drug regimen and possible elimination of drugs having anticholinergic
effects. Because of the ageing population, and the concomitant increase in medicated individuals, dentists
can expect to be presented with xerostomia in an increasing number of patients in the coming years and
therefore should be familiar with its diagnosis and treatment. Therefore, the purpose of this review is to
outline for clinicians the common aetiologies, clinical identification, and routine therapeutic modalities
available for individuals with xerostomia.
Keywords: xerostomia, saliva, pilocarpine, saliva substitutes, salivary stimulants
Introduction
Xerostomia is a condition associated with both a
decrease in the amount of saliva produced and an
alteration in its chemical composition, therefore
causing dry mouth. This can have a deleterious
effect on many aspects of oral function and general
well being. It can cause a significant decline in
quality of life by decreasing taste sensation and
impairing chewing ability. Furthermore, it may
alter regular eating patterns, reducing the pleasure
of eating due to impaired or diminished taste
sensation. Patients with xerostomia often report an
avoidance of some foods, such as dry foods (bread)
and sticky foods (peanut butter), due to the inability
to chew or swallow effectively. Also, xerostomia
may impair a patients ability to speak, cause cracks
and fissures in the oral mucosa and halitosis. It
can cause denture wearing to be very
uncomfortable, exacerbating chewing difficulties.
This is mainly due to a reduced surface tension
between the dry mucosa and the denture. This all
can lead to poor diet. Indeed, xerostomia has been
shown to be a contributing factor to the high
prevalence of geriatric malnutrition in the United
States
1
. Moreover, it can pose problems for patients
socially by impairing their ability or willingness
to talk, Xerostomia can affect numerous aspects
of oral function, contributing to pain, caries and
oral infections. It also may deter a patient from air
travel because of decreased humidity in airplanes
2
.
Saliva
Ninety percent of saliva is produced by the major
salivary glands: the parotid, submandibular and
sublingual glands. The remaining 10% is produced
by minor salivary glands, which are important as
Volume 20, No. 2
65 Sandra F. Cassolato and Robert S. Turnbull
they lie beneath all of the oral mucosa with the
exception of the gingiva and the dorsum of the
tongue. These minor glands can be grouped into
lingual, labial, buccal, palatine and glossopalatine
3
.
Each of the above mentioned glands produces its
own secretion which varies in composition. Saliva
is composed of mainly water; the other components
are divided into inorganic and organic factors
4
.
These components all act to influence bacteria in
the oral environment.
Saliva has two major secretions. The first is a
serous fluid produced mainly by the parotid (20-
25% of total) and submandibular glands (70-75%
of total)
5
. This fluid is a protein-rich secretion
containing bactericidal substances such as
proteolytic enzymes and antibodies. Histologically,
serous cells are basophilic and contain many dense
secretory granules. The second salivary secretion
is mucous which is produced predominantly by the
submandibular and sublingual glands. The
secretions of the minor salivary glands are also
purely mucous. Mucous cells, which produce
secretions rich in glycoconjugates, contain water
and mucin, making them significant in lubrication
and preventing epithelial dehydration.
Histologically, mucous cells are lightly stained, and
their granules tend to fuse into a single mass.
Saliva serves a number of functions. Firstly, it
acts as the first defence against mechanical,
chemical and infectious attacks by protecting
against numerous oral bacteria and fungus. By
providing local antimicrobial activity through
enzymes such as immunoglobulin A, lysozyme,
lactoperoxidase and histatins, saliva aids in
reducing oral infections. Furthermore, it acts as a
vehicle for nutrients and digestive enzymes and
assists in the preparation of the food bolus. It also
functions to maintain tooth integrity from dental
decay by supporting ongoing remineralization of
teeth. It does so by providing a reservoir of calcium
and phosphate ions and forming the glycoprotein
pellicle. It also physically protects teeth from
harmful substances by coating them with
glycoproteins and mucoids. This also assists in oral
lubrication. In addition, saliva functions in
maintaining a neutral oral pH through bicarbonate
and phosphate buffer systems. Chewing,
swallowing and speech are all facilitated by
saliva
5,6
.
Reduced saliva, either qualitatively or
quantitatively, may negatively impact on oral
health. Research indicates that there is a loss of
salivary parenchymal acinar cells which occurs in
ageing
7
. These effects are often unrecognised as
the parotid gland is capable of maintaining function
without obvious changes in amount, composition
or variability
8
.
Saliva is thought to be secreted by a two-stage
mechanism
9
. Acinar cells produce an osmotic
gradient that is mediated by a co-transporter loop
in the basolateral membrane
10
.

This osmotic
gradient results in the production of salivary fluid.
The saliva of patients with xerostomia becomes
more viscous and foamy, losing its lubricating
ability and adhering to teeth and mucous
membranes. This thick saliva causes food and
bacteria to adhere to the teeth, resulting in a build-
up of plaque, which may ultimately contribute to
periodontal disease. It is the decline in production
of mucin that results in xerostomia.
Epidemiology
Xerostomia is frequently described as a symptom
of middle-aged and elderly individuals; however,
it may develop in any person of any age. If ignored,
it can result in serious oral consequences.
A study by Nederfors et al
11
interviewed 3,313
randomly selected individuals aged 20 to 80 years
in Sweden and found that the prevalence of
perceived xerostomia was 21.3% for men and
27.3% for women. This difference in gender was
found to be statistically significant. In addition, this
study reported that individuals who are taking any
medication report a higher prevalence of
xerostomia (32.5% for males and 28.4% for
females) than individuals who are not medicated
(18.8% for males and 14.6% for females). Also,
they found that the prevalence of xerostomia
increases with age, continuation of medication, and
the number of medications taken.
In a study conducted in Rochester, New York,
from a convenience sample of 710 American adults
ranging in age from 19 to 88 years, using a
standardized oral health questionnaire and oral
examination, Billings et al
12
observed that 24% of
females and 18% of males suffered from
xerostomia. They found that xerostomia was
associated with the use of medications with
hyposalivatory side-effects, difficulty consuming
dry foods, cracked lips, dry eyes, difficulty
swallowing, and in males, cigarette smoking.
A Maryland study by Hochberg et al
13
asked
2,520 non-institutionalized community dwelling
persons aged 65-84 years if they suffer from dry
mouth and 17% answered positive. They found that
the prevalence of dry mouth symptoms increased
with age, was more common in women than men
and was greater in whites than blacks.
A study in Florida by Gilbert et al
14
of 600
Volume 20, No. 2
Xerostomia: Clinical Aspects and Treatment 66
community-dwelling elderly people, with a mean
age of 78 years, found that 39% reported having
dryness of their mouth. Of these, 79% had at least
one medical condition, 57% were taking at least
one prescribed or over-the-counter medication and
33% were taking at least one potentially xerogenic
medication. Along with xerogenic medications,
age, diabetes, arthritis, perceived medical health,
and dependence in physical functioning were
significantly associated with the condition.
Individuals with xerostomia were also more likely
to have reported signs and symptoms of dental
disease, sensory changes, and other oral symptoms.
Ikebe et al
15
investigated the prevalence of
perceived dry mouth among a group of
independently living elderly people in Japan. They
found that 37.8% reported oral dryness on waking,
yet only 9.1% of them noticed a subjective feeling
of dry mouth during eating. A total of 41% of
subjects had at least one of these symptoms.
An interview of 368 elderly individuals in
Helsinki, Finland by Narhi
16
showed that 46% had
subjective symptoms of xerostomia and 12%
reported continuous oral dryness. Xerostomia was
found to be associated with the female gender,
mouth breathing and the use of systemic
medications.
In a study by Locker
17
, almost 20% of a
population of older adults reported xerostomia and
it was found to be the single most common of 22
symptoms and complaints listed. A logistic
regression analysis found that income, taking
prescribed medications and experiencing a stressful
life change within the previous six months all had
a significant effect.
A study by Pajukoski et al
18
of home-living
elderly patients (mean age 82 years), hospitalized
because of sudden worsening of their general
health, revealed the prevalence of complaints of
dry mouth to be 63% in hospitalized patients and
57% in out-patients.
Loesche et al
19
analysed the relationship between
complaints of xerostomia and food avoidance in
geriatric patients in a veteran affairs clinic and
retirement home. Among 529 subjects older than
56 years, 72% reported that they experience
xerostomia sometime during the day and 55% of
these said they use one or more medications for it.
The authors found that subjects with xerostomia
had difficulty chewing and in starting to swallow.
Sheiham et al
20
reported that patients with
xerostomia were significantly more likely to avoid
crunchy foods like vegetables, dry foods like bread,
and sticky foods such as peanut butter.
Furthermore, they found associations with
statistical significance between xerostomia and
food avoidance and the following medications: the
inhalants ipratropium and triamcinolone and the
systemic agents oxybutynin and triazolam. Another
study of 284 highly medicated (mean 3.6 drugs
per individual) institutionalized elderly by
Thomson et al
21
asked subjects, how often does
your mouth feel dry? Only patients taking
anticholinergic medication reported a higher
prevalence of xerostomia.
In a Scottish study by Samaranayake et al
22
, the
oral problems of 147 elderly patients in five long-
term care hospital wards were investigated and
35% complained of dry mouth. Moore et al
23
showed that subjects with Type 1 diabetes reported
symptoms of dry mouth more frequently than a
control group. Salivary flow rates were also
impaired in Type 1 diabetics. Sreebny et al
24
examined the prevalence of xerostomia in a group
of 40 ambulatory diabetic patients not taking
medications causing xerostomia. They found that
43% complained of dry mouth, 82% of which were
women. In this population, xerostomia was not
related to age or the type and duration of diabetes.
These patients suffered more symptoms of water
loss and oropharyngeal, ocular and vaginal dryness
than an age and gender-matched healthy non-
diabetic control. Also, the salivary flow rates of
the diabetic subjects were consistently lower than
the controls. Amongst a group of patients with
rheumatoid arthritis, Russell et al
25
found that 42%
showed symptoms of xerostomia. The literature
also suggests that xerostomia is more commonly
associated with HIV+ patients
26
. Xerostomia is
found in 30% of patients dying from cancer,
increasing in severity with advanced disease
27
.

A
controlled study of healthy persons across all ages
found no statistically significant difference in an
individuals ability to make parotid saliva, either
stimulated or unstimulated
28
.

Recent literature
suggests that symptoms of xerostomia start when
there is a decrease of 45% in normal salivary flow
29
.
In summary, most studies show that salivary
gland hypofunction is not a normal part of ageing.
Cross-sectional and longitudinal studies report that
parotid salivary gland function in healthy
individuals is predominantly age-independent
30,31
.
Salivary flow changes are associated with medical
conditions and medications that tend to be more
common in middle-aged and older individuals.
Xerostomia in the geriatric population is generally
due to medications, systemic diseases and head and
neck radiotherapy. Not only is there a relationship
between number of drugs and subjective dryness
of the mouth, there is also an important relationship
Volume 20, No. 2
between subjective dryness and number of
identified diseases in an individual. Overall, the
prevalence of xerostomia increases with age and
accounts for approximately 30% of the population
aged 65 and older
32
.
Aetiology
The aetiology of xerostomia can be either
temporary or chronic. Temporary hyposalivation
affects only resting salivary secretion and patients
maintain their ability to react to both gustatory and
olfactory stimulation. In patients with chronic
hyposalivation, both resting and stimulated
secretion rates are reduced, but more importantly,
dental and oral mucosal disease are more
prevalent
33
. This contributes to a reduced response
to treatment. The most pronounced salivary
dysfunction occurs in patients who have received
therapeutic irradiation for head and neck
malignancies and those with Sjgrens
syndrome
34,35
.
Medications
The most common aetiology of xerostomia amongst
patients in a dental practice is use of certain systemic
medications
11,36
. These drugs, used individually, or
in combination can affect salivary function.
Complaints of dry mouth in a geriatric population
are usually related to their increased use of
medications causing xerostomia and not due to
changes in the function of the major salivary
glands
37
.

Nederfors et al
11
found a strong
association of xerostomia with increasing age and
continuing pharmacotherapy. Furthermore, in
healthy persons, salivary function is well preserved
throughout life.
Medication usage is the most common cause of
reduced salivary output and alteration of salivary
composition
36
. Over 500 medications exist that
may cause xerostomia
4
. The most common
medications are presented in Table 1. The main
mechanism of these drugs is by inhibiting
signalling pathways within salivary tissue and
reducing fluid output of the gland. Most of these
have a less pronounced effect, affecting a small
proportion of patients depending on the number
of prescription drugs they are taking
36,38,39
.
A patients drug regimen should be regularly
reviewed to identify drugs that may contribute to
the patients xerogenic symptoms. Discussing the
causal drugs with the prescriber may identify an
alternative drug that may have less effect on
salivary flow.
Radiation
Xerostomia is one of the major side effects of
radical radiation therapy for head and neck
malignancies. It may be related to the disease, or
as a result of the irradiation volume to the salivary
glands
40
. As radiation treatment progresses, the
destruction of the parenchyma of the salivary
glands and their vascular supply produces
xerostomia
37
. The degree of destruction of
glandular tissue depends largely on the dose of
radiation administered and is most often
permanent. The level of radiation necessary to
destroy malignant cells ranges from 40-70 Gy. The
salivary tissue is extremely sensitive to radiation
and dosages greater than 30 Gy are sufficient to
change salivary function permanently
41
. Unless the
whole gland has undergone high doses of radiation,
partial recovery of the gland is likely to occur,
taking 6-12 months.
Xerostomia may be prevented by shielding the
Table 1. Category of xerogenic medications and examples.
Drug Category Example
Anorexiant phentermine, phendimetrazine
Anti-anxiety hydroxyzine, lorazepam, prazepam, diazepam
Anticholinergics dicyclomine, mepenzolate
Anticonvulsant felbamate, gabapentin
Antidepressants
Tricyclic amitriptyline, imipramine, doxepin
Selective serotonin reuptake inhibitors sertraline, paroxetine, fluoxetine
Anti-emetics meclizine, bucilzine
Antihistamines fexofenadine, azelastine, loratadine
Antihypertensives clonidine, methyldopa, prazosin
Antiparkinsonian biperiden, selegiline
Antipsychotic clozapine, chlorpromazine
Bronchodilator ipratopium, albuterol, metaproterenol
Decongestant pseudoephedrine
Diuretic spirnolactone, chlorothiazide, furosemide
Muscle relaxant cyclobenzaprine, baclofen
Narcotic analgesic meperidine, morphine
Sedative flurazapam, triazolam, temazepam
67 Sandra F. Cassolato and Robert S. Turnbull
Volume 20, No. 2
salivary glands during radiotherapy or modulation
of the intensity of radiation when possible
34
.
Particular chemotherapeutic agents may also
alter salivary buffering capacity
38
. In addition,
drugs used to treat cancer can cause a thickening
of saliva inducing a dry feeling and contributing
to impairment of salivary functions.
Sjgrens syndrome
Nutritional deficiencies and various diseases are
sometimes accompanied by a reduced salivary flow
rate. It should be emphasized that the relationship
between these two factors and dry mouth is poorly
documented in the literature, except for Sjgrens
syndrome. Sjgrens syndrome is an autoimmune
disorder primarily affecting the salivary and
lachrymal glands where clusters of infiltrating
lymphocytes replace the parenchyma of the glands
and there is a subsequent loss of secretory epithelial
cells
42
. As a consequence, major changes occur in
both the salivary flow rate and composition.
Sjgrens syndrome is reported to have a female
to male ratio of 9:1. The disease typically affects
middle-aged and elderly white women but may
occur in persons of all ages and ethnic
backgrounds.
Primary Sjgrens syndrome occurs when
xerostomia and keratoconjunctivitis sicca develop
as isolated clinical entities, whereas secondary
Sjgrens syndrome is when there is a complication
of pre-existing connective tissue disease
42
.
Approximately 25% of patients with rheumatoid
arthritis manifest evidence of secondary Sjgrens
syndrome. Other common causes of secondary
Sjgrens syndrome include systemic lupus
erythematosus, scleroderma and other connective
tissue diseases
43
.
Sjgrens syndrome can be detected by a reduced
sublingual salivary pool, unexplained dental caries,
complaints of dry mouth, keratoconjunctivitis
sicca, vaginal dryness, joint pain and fatigue
43,44
.
More diverse presentations include unexplained
diarrhoea, renal tubular acidosis, severe muscle
weakness and unusual haematologic changes. A
dentist should refer the patient to his or her family
physician for further investigation and perhaps a
subsequent referral to a rheumatologist.
Several tests to objectively evaluate the oral
component of Sjgrens syndrome are available.
One of the most common tests is a labial salivary
gland biopsy, which is typically a biopsy taken
from the minor salivary glands, unless a
malignancy is suspected
45
. The specimen is
examined histologically by a pathologist for
infiltration of periductular inflammatory cells, and
a depletion in the number of the secretory units,
namely acini and ducts, which are both important
evidence of Sjgrens syndrome
46
.

Eighty percent
of the inflammatory infiltrate is composed of T-
lymphocytes. The remaining cells are B-
lymphocytes and plasma cells. Histopathologic
results are graded on a scale depending on the
number of inflammatory foci per 4 mm
2
with a
single focus being equal to a cluster of 50 or more
lymphocytes. The diagnosis of Sjgrens syndrome
is made when at least one focus per 4 mm
2
is found,
provided other diagnostic criteria are satisfied
47
.
Serologic studies are important to definitively
diagnose suspected cases of Sjgrens syndrome
48
.
The presence of non-specific markers of
autoimmunity such as antinuclear antibodies,
rheumatoid factor, increased serum
immunoglobulin and total protein levels and an
increase in erythrocyte sedimentation rate are
obtained. Specific autoantibodies, such as anti
Ro/SSA or anti-La/SSB, are also significant
49
.
No single serologic marker however, is
characteristically found in all cases of Sjgrens
syndrome
48
.
A number of other diagnostic tests can be used
for objective evaluation of the oral component of
Sjgrens syndrome. These diagnostic tests include
sialometry, contrast sialography, sequential
salivary gland scintigraphy and ultrasonography
42
.
The evidence for the involvement of specific
viruses in Sjgrens syndrome is conflicting and
presently remains unknown. Some of the viruses
that have been implicated in the development of
Sjgrens syndrome are cytomegalovirus, Epstein-
Barr virus, hepatitis C virus, retroviruses (human
T cell leukaemia/lymphoma virus-1 (HTLV) and
human immunodeficiency virus type I (HIV-I),
human retrovirus 5)
42,50
. No direct correlation
however, has been established between these
viruses and Sjgrens syndrome.
The occurrence of salivary gland non-Hodgkins
lymphoma is a major complication of Sjgrens
syndrome
51
. Most of the lymphomas that occur in
patients with Sjgrens syndrome are low-grade
marginal zone B cell lymphomas which encompass
both mucosa-associated lymphoid tissue (MALT)
lymphomas and their nodal counterpart which are
monocytoid B cell lymphomas (MBCL)
52
.
There is a strong epidemiological association
between Sjgrens syndrome and Hepatitis C virus
(HCV) infection. Even though only 10% of HCV-
infected patients will have symptomatic
xerostomia, 77% of patients will have evidence of
Sjgrens syndrome after diagnostic testing
53
.
Sarcoidosis is another chronic inflammatory
disease that alters salivary gland function causing
Xerostomia: Clinical Aspects and Treatment 68
Volume 20, No. 2
xerostomia. In this disease, non-caseating
granulomas are formed, contributing to the
destruction of the glands
54
.
Miscellaneous
A study by Moore et al
23
reported that dry-mouth
was associated with the use of cigarettes, dysgeusia
and more frequent snacking behaviour. In this
study, medications causing xerostomia and
elevated fasting blood glucose concentrations were
significantly associated with decreased salivary
flow.
Other factors that may contribute to xerostomia
include poorly controlled diabetes
42
, chronic graft
versus host disease
55
, thyroid disorders
56
, hepatitis
C infection
42
, Milkuliczs disease
4
, surgical
removal of the salivary glands, dehydration and
psychogenic conditions such as fear, anxiety,
depression, mouth breathing and nasal obstruction.
Also, patients that have had an injury to the head
and neck can damage the nerves that innervate the
salivary glands and thus produce xerostomia
57
.
Oral candidiasis can be associated with
xerostomia and antifungal drugs may be necessary.
Patients that wear dentures should be advised to
remove them before using topical antifungal
agents. Dentures must also be disinfected by
soaking them in a fungicidal substance overnight
and then rinsing them before insertion.
Diagnosis
Assessing the entire oral cavity is critical in the
diagnosis of xerostomia. This involves careful
evaluation of signs and symptoms. Clinical
techniques of assessment that can be used include
extra-oral and intra-oral examinations, proper
investigation of salivary gland function by
calculating resting and stimulated flow rates, and
a biopsy of salivary glands
54
. In addition to a
clinical investigation, a detailed inquiry about
medications and systemic conditions is critical.
During the intra-oral examination, the
practitioner should first visually examine the
opening of the duct in the parotid and
submandibular glands. Following this, gentle extra-
oral pressure should be applied to each gland to
observe the viscosity of saliva. Normal parotid and
submandibular glands are not palpable because
they are softer than their surrounding tissues. If
there is pathology and the glands are palpable,
when palpating the parotid gland, the practitioner
must distinguish the masseter muscle from its
superficial location over the mandibular ramus.
When palpating the submandibular glands, the
practitioner should place an index finger in the floor
of the distal aspect of the mouth and another finger
should be placed on the skin extra-orally medial
to the mandibular angle
36
.

Clinically, the dentist
may have increased difficulty in stimulating saliva
from the ducts of the major salivary glands as the
patients tongue is often fissured and lobulated on
its dorsal side.
Upon clinical examination, depending on the
cause of dry mouth, a variety of signs and
complications are visible that can vary in severity.
It is important to first determine a differential
diagnosis and to ensure that other conditions are
not present simultaneously. It is possible for
example, that a patient suffering from burning
mouth syndrome may have no obvious aetiology
accompanying the dry mouth and hence this may
mask the true diagnosis
41
. An intra-oral
examination should identify the lubricity of the
mucosa and the presence and location of dental
decay.
Measuring salivary flow under resting or
stimulated secretions is a critical step in evaluating
dry mouth and helping to make an accurate
diagnosis. Navazesh et al
58
reported that
unstimulated whole salivary flow rate below 0.12
to 0.16 ml/min shows a higher incidence of
abnormalities of the soft and hard tissues. In order
to ensure reproducibility, and give a quantitative
assessment of salivary production, techniques used
in salivary flow measurement must be
standardized
54
.
According to Daniels et al
36
, because measuring
salivary flow rates is not a common practice in
most dental surgeries due to its time consuming
nature, it may be difficult to standardize. Four
clinical formulae to assist in predicting the presence
or absence of salivary hypofunction were identified
by Navazesh et al
58
. They used the following four
methods as their clinical measures: dryness of the
buccal mucosa, absence of saliva expressible from
the ducts, the total number of decayed, missing
and filled teeth, and dryness of the lips.
Clinical manifestations
The xerogenic patient characteristically has
mucosa that is dry and sticky, and saliva with a
stringy or foamy consistency. The normally moist,
glistening appearance of the oral cavity is often
replaced with a thin, pale, cracked appearance that
is more susceptible to gingivitis and bleeding.
Saliva that is normally found on the floor of the
mouth is usually absent
54
.
Patients often complain of a sticky, dry sensation
in the mouth. They encounter increased problems
with chewing, swallowing, tasting or speaking.
There is often difficulty with normal eating habits
due to changes in taste and difficulty eating spicy
69 Sandra F. Cassolato and Robert S. Turnbull
Volume 20, No. 2
or acidic food. Due to the lack of saliva, patients
may develop cracked lips, a dry irritated tongue,
numerous mouth sores and periodontal disease.
Halitosis is a common problem and the dryness of
the mouth and lips can cause discomfort ranging
from mild irritation to a severe burning sensation
59
.
Patients with significantly decreased salivary
output due to prolonged xerostomia have an
increased risk of developing dental caries
60
. This
is a result of the decrease in pH of saliva and the
proliferation of cariogenic bacteria, namely
Streptococcus mutans and Lactobacillus species.
The decay is most often recurrent or primary and
located at sites generally not usually susceptible
to caries such as the cervical margins, incisal
margins or the tips of teeth
54.
Furthermore, since
the normal balance of oral flora is altered and
bacteria and fungus can flourish, patients are more
prone to oral and oesophageal infections
2
.
Patients with xerostomia may have oral mucosa
that appears erythematous. This discolouration is
most commonly on the dorsal surface of the tongue,
the hard or soft palate, the commissures of the
mouth and under removable prostheses
5,54
. It is
identified clinically by erythematous and atrophied
filiform papillae on the dorsal tongue, appearing
smooth and cobblestone-like, or fissured.
Pseudomembranous candidiasis may occasionally
occur, presenting as a removable white plaque that
can be found on any mucosal surface. Angular
cheilitis may be another complication, usually
occurring in the presence of intraoral candidiasis,
presenting as cracking or fissuring of the
commissures. It is frequently associated with
Candida albicans, but may be caused by
Staphylococcus aureus. Some patients are
susceptible to mucositis and ulceration because the
dry mucosa is more vulnerable to trauma
61
.
Patients with post-irradiation xerostomia may
produce little or no saliva and frequently
experience oral discomfort and pain as well as the
other classic symptoms of xerostomia previously
discussed. Taste perception is significantly altered
often resulting in nutritional problems
62
. In
addition, they have an increased incidence of dental
caries and oral infections. This is due to the loss of
bactericidal components and of the self-cleansing
actions of saliva that leads to the accumulation of
dental plaque that ultimately changes the normal
oral microflora.
Patients with systemic diseases, such as
Sjgrens syndrome and HIV infection, may
develop enlarged parotid glands and
submandibular glands. In a study by Daniels et al
36
,
between one-third and one-half of patients with
Sjgrens syndrome develop enlargement of major
salivary glands. In Sjgrens and HIV patients, the
enlarged glands are most often bilateral, firm and
non-tender, usually affecting most or the entire
gland. It is important however, in the presence of
persistent and significantly enlarged salivary
glands and neck lymph nodes, to rule out
malignancies such as lymphoma
32
. Computerized
tomography and needle aspiration to determine
cytologic and flow cytometric analyses, can be
beneficial in the diagnosis.
Patients with xerostomia often experience sleep
disturbances due to the need to wake up and quench
their dry mouth. Long-time denture-wearers with
xerostomia frequently experience tissue friability
due to lack of lubrication and often require frequent
sips of water
40
.
In addition to these oral symptoms,
patients with dry mouth develop other symptoms
that include dry throat, nose, skin, scalp, dry or
burning eyes, decreased ability to smell, heartburn,
constipation, vaginal itching
42
and fungal
infections
24
.
Treatment
Caries prevention and comprehensive dental care
With the diminished salivary output xenogenic
patients are more prone to caries, and therefore
diligent oral hygiene and regular dental care are
essential. It is also important to instruct patients
on the role of dietary sugars in the development of
caries and the need to avoid cariogenic snacks.
Antibacterial mouthwashes such as 0.12%
chlorhexidine are useful to inhibit the development
of dental plaque and gingivitis since patients with
xerostomia tend to have a greater susceptibility.
The use of topical fluorides should be based on
the severity of the patients condition as well as
individual caries risk
33
. Fluoride is known as the
single most important intervention of radiation-
induced damage. For low risk patients, the
recommended regimen is regularly applied topical
fluorides plus a daily rinse with 0.05% sodium
fluoride
36
. For more severely affected patients, high
concentration fluoride solutions in a tray such as
1.23% acidulated phosphate fluoride gel for four
minutes is recommended four times per year.
Fluoride varnish is also beneficial and should be
considered as a possibility. Denture wearing can
be very uncomfortable for patients with xerostomia
due to reduced oral lubrication, often making
chewing difficult and painful. Relining dentures
may improve the fit and significantly affect patient
comfort, general appearance and self-esteem.
Biotene Denture Grip is a moisturizing adhesive
that may be recommended to patients.
Xerostomia: Clinical Aspects and Treatment 70
Volume 20, No. 2
Saliva substitutes
Moistening the oral mucosa with artificial saliva
substitutes has been shown to give relief
63
. Since
saliva is a complex secretion with a variety of
functions, it is difficult to mimic through artificial
methods. One of the most frequently used saliva
substitutes is water. Patients should understand that
dry mouth is rarely associated with systemic
dehydration and that consuming large quantities
of water does not overcome xerostomia; however,
frequent intake of water will assist in reducing
symptoms. Milk also contains many chemical and
physical properties suitable as a saliva substitute.
It acts by moisturizing and lubricating dehydrated
tissues, buffering oral acids, decreasing the risk of
enamel demineralisation, and it also contributes
to remineralization due to its calcium and
phosphate content
64
.
The most commonly prescribed saliva substitutes
are the artificial salivas. Unfortunately they are
usually not effective for more than a few hours.
These products are commonly used by patients at
their bedside, when they awake during the night,
or when talking. They can be categorized based
on their contents: glycerine and lemon or
carboxymethylcellulose and mucin. They include
remineralising contents such as calcium,
phosphate, fluoride and sugar alcohols (e.g.
sorbitol), which have a low cariogenic potential
65
.
They are important lubrication for the mucosa and
throat and help to clean teeth from bacteria and
debris. The lemon-based saliva substitutes
however, if used frequently, are potentially erosive
to enamel
63
.
Saliva substitutes provide a critical means of
maintaining some physiological function in
patients with impaired salivary flow and can help
to reduce the incidence of dental decay and dental
erosion
63
. However, they need to be used frequently
and over a long period of time. Saliva substitutes
are available as lozenges, rinses, sprays, swab
sticks and as reservoirs in dentures
66
. It is important
to select a product with low erosive potential to
prevent the demineralisation of enamel and
subsequent dental decay. The entire oral mucosa
should be covered and a small pool left under the
patients tongue. Patients should be advised not to
rinse their mouth following administration.
Salivary substitutes may provide an allergic
potential in patients who are sensitive to some of
the preservatives present in the artificial saliva
products
41
.
Biotene and Oralbalance
Biotene is available as a sugar-free chewing gum,
an alcohol-free mouthwash and a toothpaste, while
Oralbalance is available as a moisturizing gel.
Biotene and Oralbalance (Laclede Professional
Products, Rancho Dominguez, CA US) contain
three primary enzymes: lactoperoxidase, lysozyme,
glucose oxidase and one protein that is naturally
found in human saliva called lactoferrin. This
enzyme system acts to penetrate the cell wall of
plaque-forming bacteria, helping to maintain a
healthy balance of oral flora
40
. The goal of the
various enzymes is to replace the missing salivary
enzyme activity absent or decreased in patients
with xerostomia, reducing harmful organisms,
while not harming beneficial ones
67
Candida
species are sensitive to this enzyme system
68
.
Lactoferrin acts to deprive bacteria of iron. Biotene
is naturally sweetened with xylitol. Oral Balance
helps moisturize the oral mucosa, soothing and
relieving oral dryness. Multiple co-factors such as
hydrogen peroxide and halides, enable the
efficiency of the anti-microbial activity.
As outlined on the product package, Biotene
mouthwash is indicated for individuals
experiencing dry mouth or having oral irritations.
Directions for use of Biotene mouthwash are to
use approximately one tablespoon whenever
desired. Patients are to swish thoroughly for 30
seconds and expectorate. For the best results, it is
recommended to use Biotene mouthwash in
conjunction with Biotene toothpaste, especially at
bedtime.
Biotene toothpaste is a non-foaming, mild
toothpaste claiming not to irritate sore tissues. It is
recommended in place of regular toothpastes, after
each meal or as directed by a dentist or physician.
Patients with normal salivary gland function do
not benefit from Biotene toothpaste, however,
studies have shown that in xerostomic patients, a
lactoperoxidase-system containing toothpaste such
as Biotene can improve gingival health compared
to a control toothpaste
69
. In patients with
xerostomia, by combining the use of Biotene
toothpaste with a lactoperoxidase-containing gel,
such as Oralbalance, research shows that gingival
inflammation is significantly improved
70
.
Oralbalance should be applied onto the tongue
or directly to the affected areas and spread
thoroughly. The manufacturer claims that this
product quickly relieves dry mouth, protects
against irritations and burning sensations for
several hours and promotes healing of
inflammation. It is also recommended for use under
dentures.
There have been two clinical studies published
in the literature that examine the efficacy of
Biotene. A 1999 study by Epstein
68
compared the
71 Sandra F. Cassolato and Robert S. Turnbull
Volume 20, No. 2
use of Oralbalance gel and Biotene toothpaste
against a control of carboxymethylcellulose gel and
a commercial toothpaste. This study examined 19
patients receiving head and neck radiation
treatment for advanced cancer. Patients using
Oralbalance and Biotene reported these two
products to be more effective than the controls
(p=0.04). These patients also reported less dry
mouth upon waking (p=0.05).
A study by Warde
40
involved 28 patients with
post-irradiation xerostomia due to treatment for
head and neck cancer. These patients were given a
two-month supply of Biotene toothpaste,
mouthwash, chewing gum and Oralbalance gel.
They were given full instructions on how to use
these products. They were told to brush with
Biotene toothpaste in the morning, after eating, and
at bedtime. The Biotene chewing gum, mouthwash
and Oralbalance gel were to be used as desired to
relieve symptoms of xerostomia. After two months
of treatment, 54% of patients reported an
improvement in intraoral dryness, 36% of which
experienced a major improvement. Also, 46% said
there was an improvement in their ability to eat
normally and 61% said there was an improvement
in oral discomfort; however, only 10 patients said
they would continue using the products.
Furthermore, this study did not evaluate the
placebo effect, but did state that further research
is needed to examine placebo influences.
From these preliminary studies, it appears that
Biotene helps patients with xerostomia, however,
as Warde et al
40
state, a randomized phase III study
is needed. They also say that although pilocarpine,
Biotene and Oralbalance work by different
mechanisms, using them in combination may be
more effective.
Salivary stimulants
The secretion of saliva is largely controlled by the
parasympathetic nervous system. Therefore,
salivary flow can be stimulated by a variety of
factors such as stimulating the receptors within the
salivary glands in the oral cavity (afferent
pathways) or, alternatively, to act directly on
parasympathetic nerves (efferent pathways).
One of the most productive ways to combat
xerostomia is to stimulate oral receptors by
physiological or pharmacological means and hence
stimulate salivary function. Atkinson et al
5
reported
that reduced mastication would exacerbate atrophy
of the salivary glands. For this reason, research
indicates the importance of physiologically
stimulating these glands by masticatory or
gustatory stimuli such as chewing xylitol gum
71
or
sucking sugar-free hard candies
36
. Consumption of
foods that require active chewing will assist in
stimulating salivation and will decrease the
incidence of taste abnormalities. Also, patients
should be informed that dry and spicy foods should
be avoided as they tend to irritate mucosal
tissues
33,59,71
.
Additionally, organic acids such as ascorbic acid,
malic acid and citric acid increase salivation.
However, due to their acidity, these substances also
have a tendency to demineralise and erode enamel
resulting in dental caries, thus, they are not
recommended for long-term relief of xerostomia.
Some of the marketed salivary stimulants such
as Salix saliva stimulating lozenge, contain
sorbitol (Scandinavian Formulas, Perkasie, PA
US). The manufacturer claims that Salix
increases salivation of a reduced salivary gland
function through physiological stimulation of the
taste buds. There are side effects of salivary
stimulants containing sorbitol. Sorbitol is an
osmotic laxative agent which can induce
gastrointestinal symptoms such as diarrhoea, due
to its osmotic potential
72
.
Numerous studies have shown that gum chewing
stimulates salivary flow in patients with
xerostomia
73
. This is mainly because the act of
chewing is, in itself, associated with enhanced
salivation through effects on oral baroreceptors.
In addition, stimulation of taste receptors may also
contribute to the enhanced salivary response.
Pilocarpine HCl (Salagen, Pharmacia Canada Inc.)
In patients suffering from severe xerostomia,
systemic cholinergic stimulants such as pilocarpine
may be prescribed if no contraindications exist.
The salivary-stimulative effects of orally ingested
pilocarpine hydrochloride have been reported since
the late 1960s
74
. The mechanisms responsible for
the effects of pilocarpine on salivary flow
stimulation are both local and direct cellular
stimulation. The parasympathetic action of
pilocarpine induces water and electrolyte flow in
saliva. Research also has shown that pilocarpine
stimulates the production of mucin and of several
other salivary constituents
75
.
The usual dosage in adults is one or two 5.0 mg
tablets three or four times daily
33
, not to exceed 30
mg per day
41
. Patients should be treated for a
minimum of 90 days for optimum results. The
lowest dose that is tolerated and effective should
be used for maintenance. Several weeks must
elapse before the symptomatic improvement
becomes apparent because the reversal of the
atrophic and desiccated changes induced by
salivary deprivation does not occur immediately
after using pilocarpine. The time required to
Xerostomia: Clinical Aspects and Treatment 72
Volume 20, No. 2
increase salivation once pilocarpine has been taken
orally is 15 minutes, peaking at 60 minutes and
has a duration of two or three hours
76
.
The most frequent side effect of patients taking
5.0 mg three times a day of pilocarpine is
perspiration. Additional dose-dependent adverse
effects experienced by patients include nausea,
rhinitis, chills, frequent urination, dizziness,
headache, facial blushing, increased lacrimation,
and pharyngitis
41,62
. Pilocarpine is considered to be
a cholinergic parasympathomimetic drug that
exhibits potent muscarinic-stimulating properties
77
.
Because pilocarpine is a parasympathomimetic
drug, there is some risk of cardiovascular and
pulmonary side-effects and thus, it is only available
by prescription
36
. In 1966, Dawes
74
showed that
pilocarpine stimulation fails to reproduce the
normal combined sympathetic and
parasympathetic balance, thus leading to changes
in salivary composition.
Pilocarpine is only approved for use as a
sialogogue in patients undergoing radiation
therapy
78
, in patients who have Sjgrens
syndrome
79
and for drug-induced xerostomia
80
. In
such patients, products such as oral rinses, saliva
substitutes, salivary stimulants and sipping water
frequently usually are not adequate
62
. Pilocarpine
tablets should be administered with caution and
under close medical supervision to patients with
significant cardiovascular disease (hypotension,
hypertension, bradycardia, and tachycardia) and
pulmonary disease (e.g. controlled asthma, chronic
bronchitis, or chronic obstructive pulmonary
disease). Contraindications for pilocarpine include
patients with narrow-angle glaucoma, patients with
uncontrolled asthma
41
, and patients with gastric
ulcers
77
.
Evidence regarding its efficacy following
radiation is not definite; various reports indicate
that approximately 50% of patients may benefit
from its use
81
. In 1993, Johnson et al
78
examined
207 patients undergoing head and neck radiation
therapy and taking pilocarpine for symptoms of
xerostomia. Their research showed that 44% of
patients reported improved salivation while on a
dose of 5.0 mg three times a day. They concluded
that pilocarpine could improve many symptoms
associated with post-irradiation xerostomia such
as oral dryness, discomfort and speaking difficulty.
The success rate of pilocarpine is often variable
and hence patients may also require additional care
such as fluoride supplements and salivary
substitutes to prevent radiation-induced caries.
When a dentist is considering using pilocarpine,
it is suggested to also consult with the patients
physician
41
. Close monitoring of the patient is
recommended because of the possible significant
cholinergic side effects. The interaction of
pilocarpine with other medications such as beta-
adrenergic antagonists, and drugs with
parasympathomimetic effects, may preclude its use
in many patients with medication induced salivary
dysfunction. There have been no formal drug
interaction studies performed for pilocarpine. It is
advised that when a patient is on sialogogue
medication, they ingest approximately 1,900 ml
of water daily
82
.
Other systemic sialogogues are also available
such as anetholtrithion (Sialor, Paladin Labs Inc)
and cevimeline hydrochloride (Evoxac, Daiichi
Pharmaceutical Corporation). Fife et al
83
studied
the efficacy of cevimeline HCl in treating
xerostomia in 75 patients with Sjgrens syndrome
in a double-blind, randomized, placebo-controlled
trial. Their study reported that treatment with
cevimeline HCl, 30 mg three times daily, was well
tolerated and provided significant relief of
xerostomia for up to six weeks. They found that
although 60 mg three times daily provided similar
symptomatic improvement, there was an increase
in the occurrence of adverse effects, especially
gastrointestinal tract disorders. Further work to
determine the long-term efficacy and safety of
cevimeline HCl was suggested.
Other treatments
In the absence of a known cause of Sjgrens
syndrome, a suggested preventive treatment of
lymphoproliferations is to decrease the
hyperactivation of autoreactive B cells when
present. Immunosuppressive drugs such as
methotrexate or tumour necrosis factor alpha
antagonists have been investigated
52
.
Research indicates that highly active
antiretroviral therapy (HAART) has been
associated with a reduction in morbidity and
mortality in HIV-infected patients
84
. The
frequencies of HIV-associated periodontal disease,
Kaposis sarcoma, and other oral lesions, such as
xerostomia were found to be reduced following
HAART
85
.
A Phase II double-blind study comparing four
doses of oral interferon alpha (IFN) revealed that
150 units of IFN lozenges three times a day for
twelve weeks in subjects with primary Sjgrens
syndrome resulted in salivary flow improvement
and reduced symptoms of xerostomia
86
.
Conclusions
Xerostomia is a condition that can be very
debilitating for patients. With the ageing population
it is likely to be increasingly encountered in a dental
73 Sandra F. Cassolato and Robert S. Turnbull
Volume 20, No. 2
office and dental practitioners should be cognizant
of its diagnosis and treatment.
References
1. Rhodus N L, Brown J. The association of
xerostomia and inadequate intake in older adults. J
Am Diet Assoc 1990; 90: 1688-1692.
2. Iwamoto R R. A nursing perspective on
radiation-induced xerostomia. Oncology 1996; 10
(suppl): 12-15.
3. Provenza D V, Oral Histology. Philadelphia:
Lippincott , 1964.
4. Carranza F A, Newman M G, Takei T T.
Carranzas Clinical Periodontology. Philadelphia:
W.B. Saunders Company, 2002.
5. Atkinson J L, Wu A J. Salivary gland
dysfunction: causes, symptoms and treatment. J Am
Dent Assoc 1994; 125: 409-416.
6. Locker D. Xerostomia in older adults: a
longitudinal study. Gerodontology 1995; 12: 18-25.
7. Drummond J R, Newton J P, Abel R W.
Tomographic measurements of age changes in the
human parotid gland. Gerodontology 1995; 12: 26-
30.
8. Wu A J, Atkinson J C, Fox P C, et al. Cross-
sectional and longitudinal analyses of stimulated
parotid salivary constituents in healthy different aged
subjects. J Gerontol Med Sci 1993; 48: M219-224.
9. Thaysen J H, Thorn N A, Schwartz I L.
Excretion of sodium, potassium, chloride and carbon
dioxide in human parotid saliva. Am J Physiol 1954;
178: 155-159.
10. Turner R J. Mechanisms of fluid secretion by
salivary glands. Ann NY Acad Sci 1993; 694: 24-35.
11. Nederfors T, Isaksson R, Morestad H, et al.
Prevalence of perceived symptoms of dry mouth in
an adult Swedish population: relation to age, sex and
pharmacotherapy. Community Dent Oral Epidemiol
1997; 25: 211-216.
12. Billings R J, Proskin H M, Moss M E.
Xerostomia and associated factors in a community-
dwelling adult population. Community Dent Oral
Epidemiol 1996; 24: 312-316.
13. Hochberg M C, Tielsch J, Munoz B, et al.
Prevalence of symptoms of dry mouth and their
relationship to saliva production in community
dwelling elderly: the SEE project. Salisbury Eye
Evaluation. J Rheumatol 1998; 25: 486-491.
14. Gilbert G H. Heft M W, Duncan R P. Mouth
dryness as reported by older Floridians. Community
Dent Oral Epidemiol 1993; 21: 390-397.
15. Ikebe K, Nokubi T, Sajima H, et al. Perception
of dry mouth in a sample of community-dwelling
older adults in Japan. Spec Care Dent 2001; 21: 52-
59.
16. Narhi T O. Prevalence of subjective feelings
of dry mouth in the elderly. J Dent Res 1994; 73: 20-
25.
17. Locker D. Subjective reports of oral dryness
in an older adult population. Community Dent Oral
Epidemiol 1993; 21: 165-168.
18. Pajukoski H, Meurman J H, Halonen P, et
al. Prevalence of subjective dry mouth and burning
mouth in hospitalized elderly patients and outpatients
in relation to saliva, medication, and systemic
diseases. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2001; 92: 641-649.
19. Loesche W J, Bromberg J, Terpenning M S,
et al. Xerostomia, xerogenic medications and food
avoidances in selected geriatric groups. J Am Geriatr
Soc 1995; 43: 401-407.
20. Sheiham A, Steele J G, Marcenes W, et al.
The impact of oral health on stated ability to eat
certain foods; findings from the National Diet and
Nutrition Survey of Older People in Great Britain.
Gerodontology 1999; 16: 11-20.
21. Thomson W M, Brown R H, Williams S M.
Medication and perception of dry mouth in a
population of institutionalized elderly people. NZ Med
J 1993; 106: 219-21.
22. Samaranayake L P, Wilkieson C A, Lamey P
J, et al. Oral disease in the elderly in long-term
hospital care. Oral Dis 1995; 1: 147-151.
23. Moore P A, Guggenheimer J, Etzel K R, et
al. Type 1 diabetes mellitus, xerostomia, and salivary
flow rates. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2001; 92: 281-291.
24. Sreebny L M, Yu A, Green A, et al. Xerostomia
in diabetes mellitus. Diabetes Care 1992; 15: 900-
904.
25. Russell S, Reisine S. Investigation of
xerostomia in patients with rheumatoid arthritis. J Am
Dent Assoc 1998; 129: 733-739.
26. Schiodt M. Less common oral lesions
associated with HIV infection: prevalence and
classification. Oral Dis 1997; 3(Suppl 1): 208-13.
27. Addington-Hall J, McCarthy M. Dying from
cancer: results of a national population-based
investigation. Palliat Med 1995; 9: 295-305.
Xerostomia: Clinical Aspects and Treatment 74
Volume 20, No. 2
28. Heft M W, Baum B J. Unstimulated and
stimulated parotid salivary flow rate in individuals
of different ages. J Dent Res 1984; 63: 1182-1185.
29. Ghezzi E M, Lange L A, Ship J A.
Determination of variation of stimulated salivary flow
rates. J Dent Res 2000; 79: 1874-1878.
30. Baum B J. Evaluation of stimulated parotid
saliva flow rate in different age groups. J Dent Res
1981; 60: 1292-1296.
31. Ship J A, Nolan N, Puckett S. Longitudinal
analysis of parotid and submandibular salivary flow
rates in healthy, different aged adults. J Gerontol Med
Sci 1995; 50A: M285-289.
32. Ship J A, Pillemer S R, Baum B J. Xerostomia
and the geriatric patient. J Am Geriatr Soc 2003; 50:
535-543.
33. Fox P C. Management of dry mouth. Dent Clin
North Am 1997; 41: 863-875.
34. Atkinson J C, Baum B J. Salivary
Enhancement: Current Status and Future Therapies.
J Dent Educ 2001; 65: 1096-1101.
35. Longman L P, Higham S M, Rai K, et al.
Salivary gland hypofunction in elderly patients
attending a xerostomia clinic. Gerodontology 1995;
12: 67-72.
36. Daniels T E, Wu A J. Xerostomia - clinical
evaluation and treatment in general practice. J Can
Dent Assoc 2000; 28: 933-941.
37. Baum BJ . Salivary gland fluid secretion during
ageing. J Am Geriatr Soc 1989; 37: 453.
38. McDonald E, Marion C. Dry mouth:
Diagnosing and treating its multiple causes.
Geriatrics 1992; 46: 61-63.
39. Sreebny L M, Schwartz S S. A reference guide
to drugs and dry mouth - 2nd edition. Gerodontology
1997; 14: 33-47.
40. Warde P, Kroll B, OSullivan B, et al. A phase
II study of Biotene in the treatment of postradiation
xerostomia in patients with head and neck cancer.
Support Care Cancer 2000; 8: 203-208.
41. Wynn R L, Meiller T F. Artificial saliva
products and drugs to treat xerostomia. Gen Dent
2000; 48: 630-636.
42. Al-Hashimi I. The management of Sjgrens
syndrome in dental practice. J Am Dent Assoc 2001;
132: 1409-1417.
43. Rostron J, Rogers S, Longman L, et al.
Health-related quality of life in patients with primary
Sjgrens syndrome and xerostomia: a comparative
study. Gerodontology 2002; 19: 53-59.
44. Fox R I, Konttinen Y, Fisher A. Short
analytical review use of muscarinic agonists in the
treatment of Sjgrens syndrome. Clin Immunol 2001;
101: 249-263.
45. Fox R I, Stern M, Michelson P. Update in
Sjgrens syndrome. Curr Opin Rheumatol 2000; 12:
391-398.
46. Edgar W M, OMullane D M. Saliva and
dental health. London: British Dental Association,
1990.
47. Vivino F B, Katz W A. Sjgrens syndrome:
clinical picture and diagnostic tests. J Musculoskel
Med 1995; 12: 40-52.
48. Fox P C, Brennan, Pillemer S, et al. Sjgrens
syndrome: a model for dental care in the 21st century.
J Am Dent Assoc 1998; 129: 719-728.
49. Ben-Chetrit E, Fox R I, Tan E M. Dissociation
of immune responses to the SS-A (Ro) 52-kd and 60-
kd polypeptides in systemic lupus erythematosus and
Sjgrens syndrome. Arthritis Rheumatol 1990; 33:
349-355.
50. Venables P J, Rigby SP . Viruses in the
etiopathogenesis of Sjgrens syndrome. J Rheumatol
1997; 24(suppl. 50): 3-5.
51. Royer B, Cazals-Hatem D, Sibilia J, et al.
Lymphomas in patients with Sjgrens syndrome and
marginal zone B-cell neoplasms, arise in diverse
extranodal and nodal sites, and are not associated with
viruses. Blood 1997; 90: 766-775.
52. Mariette X. Lymphomas complicating
Sjgrens syndrome and hepatitis C virus infection
may share a common pathogenesis: chronic
stimulation of rheumatoid factor B cells. Ann Rheum
Dis, 2001; 60: 1007-1010.
53. Mayo M , Kaplan N M. Extrahepatic
manifestations of hepatitis C infection. Am J Med Sci
2003; 325: 135-148.
54. Greenspan B. Xerostomia: Diagnosis and
Management. Oncology 1996; 10 (Suppl): 7-11.
55. Nagler R, Marmary Y, Krausz Y, et al. Major
salivary gland dysfunction in human acute and
chronic graft-versus-host disease (GVHD). Bone
Marrow Transplant 1996; 17: 219-224.
56. Tenovuo, J O. Human Saliva: Clinical
Chemistry and Microbiology vol 1. Florida: CRC
Press Inc., 1989.
57. Navazesh M, Brightman V J, Pogoda J M.
Relationship of medical status, medications, and
salivary flow rates in adults of different ages. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1996;
81: 172-176.
75 Sandra F. Cassolato and Robert S. Turnbull
Volume 20, No. 2
58. Navazesh M, Christensen C, Brightman V.
Clinical criteria for the diagnosis of salivary gland
hypofunction. J Dent Res 1992; 71: 1363-1369.
59. Garg A K, Malo M. Manifestations and
treatment of xerostomia and associated oral effects
secondary to head and neck radiation therapy. J Am
Dent Assoc 1997; 128: 1128-1133.
60. Mersel A. Oral health status and dental needs
in a geriatric institutionalized population in Paris.
Gerodontology 1989; 8: 47-51.
61. Atkinson J C, Fox P C. Salivary gland
dysfunction. Clin Geriatr Med 1992; 8: 499-511.
62. Jacobs C, Van der Pas M. A multicenter
maintenance study of oral pilocarpine tablets for
radiation-induced xerostomia. Oncology 1996; 10
(Suppl): 16-20.
63. Smith G, Smith A J, Shaw L, et al. Artificial
saliva substitutes and mineral dissolution. J Oral
Rehabil 2001; 28: 728-731.
64. Herod G I. The use of milk as a saliva
substitute. J Public Health Dent 1994; 54: 184-189.
65. Kielbassa A M, Parichereh Shohadai A,
Schulte-Monting J. Effect of saliva substitutes on
mineral content of demineralized and sound dental
enamel. Support Care Cancer 2000; 9: 40-47.
66. Sinclair C F, Frost P M, Walter J D. New
design for an artificial saliva reservoir for the
mandibular complete denture. J Pros Dent 1996; 75:
276-280.
67. Epstein J B, Scully C. The role of saliva in
oral health and causes and effects of xerostomia. J
Can Dent Assoc 1992; 58: 217-221.
68. Epstein J B, Emerton S, Stevenson-Moore
P. A double-blind crossover trial of Oral Balance gel
and Biotene toothpaste versus placebo in patients with
xerostomia following radiation therapy. Oral Oncol
1999; 35: 132-137.
69. Van Steenberghe D, Van den Eynde E,
Jacobs R, et al. Effect of a lactoperoxidase containing
toothpaste in radiation-induced xerostomia. Int Dent
J 1994; 44: 133-138.
70. Banoczy J B, Dombi C, Czegledly A, et al. A
clinical study with lactoperoxidase-containing gel and
toothpaste in patients with dry mouth syndrome. J
Clin Dent 1994; 5: 65-69.
71. Odusola F. Chewing gum as an aid in treatment
of hyposalivation. NY State Dent J 1991; 57: 28-31.
72. Ratnaike R N. Mechanisms of drug-induced
diarrhoea in the elderly. Drugs & Ageing 1998; 13:
245-253.
73. Davies A N. A comparison of artificial saliva
and chewing gum in the management of xerostomia
in patients with advanced cancer. Palliat Med 2000;
14: 197-203.
74. Dawes C. The composition of human saliva
secreted in response to a gustatory stimulus and to
pilocarpine. J Physiol 1966; 183: 360-368.
75. Zimmerman R P, Mark R J, Tran L M, et al.
Concomitant pilocarpine during head and neck
irradiation is associated with decreased post-treatment
xerostomia. Int J Radiat Oncol Biol Phys 1997; 37:
571-575.
76. Fox P C, Atkinson J C, Macynski A A, et al.
Pilocarpine treatment of salivary gland hypofunction
and dry mouth (xerostomia). Arch Intern Med 1991;
151: 1479-1152.
77. Bernardi R, Perin C, Becker F L, et al. Effect
of pilocarpine mouthwash on salivary flow. Braz J
Med Biol Res 2002; 35: 105-110.
78. Johnson J T, Ferretti G A, Nethery W J, et
al. Oral pilocarpine for post-irradiation xerostomia
in patients with head and neck cancer. New Eng J
Med 1993; 329: 390-395.
79. Vivino F B, Al-Hashimi I, Khan Z. Pilocarpine
tablets for the treatment of dry mouth and dry eye
symptoms in patients with Sjgrens syndrome: a
randomized, placebo-controlled, fixed dose,
multicenter trial. Arch Intern Med 1999; 159: 174-
181.
80. Compendium of Pharmaceuticals and
Specialities (CPS). 36th ed. Toronto (ON): Webcom
Limited; 2001. P1203.
81. Rieke J W, Hafermann M D, Johnson J J, et
al. Oral pilocarpine for radiation-induced xerostomia:
integrated efficacy and safety results from two
prospective randomized clinical trials. Int J Radiat
Oncol Biol Phys 1995; 31: 661-669.
82. Zunt S L. Lecture entitled: Diagnosis and
management of dry mouth/xerostomia/salivary gland
hypofunction. Presented at Faculty of Dentistry,
University of Toronto, Nov. 2002.
83. Fife R S, Chase W F, Dore R K, et al.
Cevimeline for the treatment of xerostomia in patients
with Sjgren syndrome: a randomized trial. Arch
Intern Med 2002; 162: 1293-1300.
84. Brodt H R, Kamps B S, Gute P, et al.
Changing incidence of AIDS-defining illnesses in the
era of antiretroviral combination therapy. AIDS 1997;
11: 1731-1738.
Xerostomia: Clinical Aspects and Treatment 76
Volume 20, No. 2
85. Ramirez-Amador V, Esquivel-Pedraza L,
Sierra-Madero J, et al. The changing clinical
spectrum of human immunodeficiency virus (HIV)-
related oral lesions in 1, 000 consecutive patients: a
12-year study in a referral center in Mexico. Medicine
2003; 82: 39-50.
86. Ship J A, Fox P C, Michalek J E, et al.
Treatment of primary Sjgrens syndrome with low-
dose natural human interferon-alpha administered by
the oral mucosal route: a phase II clinical trial. IFN
Protocol Study Group. J Interferon Cytokine Res
1999; 19: 943-951.
77 Sandra F. Cassolato and Robert S. Turnbull
Address of correspondence:
Professor Robert S. Turnbull
Discipline of Periodontics
Faculty of Dentistry, University of Toronto
124 Edward Street
Toronto, Ontario Canada M5G 1G6
Tel: 416-979-4928
Fax: 416-979-4936
e-mail: robert.turnbull@utoronto.ca