Clinics in Dermatology (2017) 35, 468–476

Etiology, evaluation, and management

of xerostomia
Jillian W. Millsop, MD, MS, Elizabeth A. Wang, BS, Nasim Fazel, MD, DDS ⁎
Department of Dermatology, University of California, Davis School of Medicine, Sacramento, CA

Abstract Xerostomia is defined as the complaint of oral dryness. It is a condition that primarily affects older
adults and can have a significant negative effect on one’s quality of life. Patients with xerostomia often do
not have objective signs of hyposalivation. The underlying etiology of xerostomia includes a variety of
systemic diseases and local factors. Our aim is to provide a comprehensive review of the differential
diagnosis, evaluation, and management of xerostomia. Prompt diagnosis and management can alleviate
the clinical manifestations of this debilitating condition.
© 2017 Elsevier Inc. All rights reserved.

Introduction Differential diagnosis for causes of xerostomia

Xerostomia is defined as the complaint of oral dryness.1
Xerostomia occurs in 5.5% to 46% of the population, and most
commonly in older adults.2 Xerostomia is also more common
in women than in men.3 It can occur due to inadequate salivary
secretion secondary to abnormal function of the salivary
glands, which is categorized as “true” xerostomia4; however,
most patients with xerostomia often do not have objective
signs of hyposalivation. “Symptomatic” xerostomia or “pseu-
do” xerostomia refers to oral dryness despite normal salivary
gland function.4 Patients with xerostomia can have clinical
manifestations of difficulty in swallowing, chewing, and/or
speaking and can present with burning mouth, halitosis, al-
tered taste, dry buccal mucosa, glossitis, cracked and peeled
lips, oral candidiasis, and dental caries despite good oral hy-
giene (Table 1).1,5,6 As a result, xerostomia can lead to a poor
quality of life for affected individuals.
⁎ Corresponding author. Tel.: +1-916-734-6876; fax: +1-916-442-5702.
E-mail address: nfazel@ucdavis.edu (N. Fazel).
The underlying etiology of xerostomia may be divided into two
broad categories: systemic diseases and local factors (Table 2).
Systemic diseases that can cause xerostomia include, but are
not limited to, endocrine, autoimmune, infectious, and
granulomatous diseases. The more common systemic diseases
are reviewed here. Local factors that can cause xerostomia
include medications, head and neck radiation therapy, and
lifestyle factors.
Systemic diseases
Endocrine diseases
Diabetes mellitus is a condition that occurs due to insuffi-
cient production of insulin. Type 1 diabetes mellitus occurs
when there is a definite lack of insulin secretion due to genetic
and autoimmune factors, leading to hyperglycemia.7 Type 2
diabetes mellitus leads to hyperglycemia due to insulin resis-
tance and relative insulin shortage.8 A common symptom of
uncontrolled diabetes mellitus is dry mouth, likely due to

http://dx.doi.org/10.1016/j.clindermatol.2017.06.010
0738-081X/© 2017 Elsevier Inc. All rights reserved.
Xerostomia: Work-up and Management 469

Table 1 Clinical manifestations of xerostomia Table 2 Differential diagnosis for the underlying etiology of
xerostomia
Functional difficulties
• Difficulty swallowing Systemic factors Local factors
• Difficulty chewing • Endocrinologic causes: • Medications (most common
• Difficulty speaking ○ Diabetes mellitus categories listed here):
• Altered taste ○ Autoimmune thyroid ○ Anticholinergic agents
Morphologic findings and consequences diseases ○ Antiparkinsonian
• Burning mouth (eg, Grave disease medications
• Halitosis and autoimmune ○ Antidepressants
• Dry buccal mucosa thyroiditis) ○ Antipsychotics
• Glossitis • Autoimmune causes: ○ Antihistamines
• Cracked and peeled lips ○ Sjögren syndrome ○ Antihypertensives
• Oral candidiasis ○ Rheumatoid arthritis ○ Sedative agents
• Dental caries ○ Systemic lupus ○ Anti-HIV drugs
erythematosus ○ Cytotoxic drugs
○ Scleroderma ○ Antineoplastic drugs
○ Primary biliary cirrhosis ○ Opioids
dehydration and polyuria.7 Xerostomia has been reported in
• Infectious causes: • Head and neck radiation
38% of children and 53% of adolescents with type 1 diabetes ○ Actinomycosis • Lifestyle factors:
mellitus9,10 and in 14% to 62% of type 2 diabetes mellitus ○ Human immunodeficiency ○ Tobacco use
patients.10–12 virus ○ Alcohol use
Autoimmune thyroid diseases are conditions in which pa- ○ Hepatitis C virus ○ Caffeinated
tients have serum antibodies against thyroid antigens such as ○ Human T-lymphotropic beverage consumption
thyroid-stimulating hormone receptor and thyroglobulin. virus type 1 virus ○ Dehydration
Many patients with thyroid disease have been found also to ○ Cytomegalovirus ○ Heavy snoring
have Sjögren syndrome, which is characterized by dry mouth, ○ Epstein-Barr virus ○ Mouth breathing
suggesting there may be a similar pathogenic mechanism • Granulomatous causes: ○ Upper respiratory
between the two conditions.13 ○ Tuberculosis tract infections
○ Sarcoidosis
• Other systemic causes:
Autoimmune diseases ○ Chronic graft-versus-host
Sjögren syndrome is the most recognized autoimmune dis- disease after stem
ease associated with hyposalivation leading to dry mouth. In cell transplantation
this condition, the salivary glands are targeted by the immune ○ End-stage renal disease
system. The salivary glands are infiltrated by a combination of ○ Hemochromatosis
macrophages, mast cells, B cells, T cells, and plasma cells.14 ○ Amyloidosis
The plasma cells produce autoantibodies anti-Ro and anti-La, ○ Parkinson disease
which target the muscarinic 3 receptor, leading to atrophy of ○ Ectodermal dysplasia
the glands.14–16 ○ The aging process
Systemic lupus erythematosus is a debilitating connective
tissue disease. More than 75% of patients with this condition
have reported xerostomia.1 An association has been found Primary biliary cirrhosis is a progressive cholestatic disease
between a decreased unstimulated salivary flow rate and characterized by destruction of bile ducts. Xerostomia, dys-
systemic lupus erythematosus.17 One-third of patients with phagia, fatigue, and jaundice are clinical manifestations of
lupus also have Sjögren syndrome.1 the condition.21 An estimated 47% to 73% of patients with pri-
Rheumatoid arthritis (RA) is an autoimmune disease mary biliary cirrhosis have clinical manifestations consistent
affecting the connective tissues. Salivary immune system is with Sjögren syndrome.22,23
impaired in RA patients with xerostomia. Compared with
nonxerostomic RA patients, the xerostomic patients with RA Infections
had decreased peroxidase activity, decreased saliva and Bacterial and viral infections are associated with xerosto-
protein, and a lower specific content of secretory immunoglob- mia. With regard to bacterial infections, actinomycosis is a
ulin A and peroxidase.18 Sjögren syndrome most commonly gram-positive, anaerobic bacterial infection that infiltrates the
occurs concomitantly with RA.19 parotid and submandibular gland ducts and can form abscess-
Scleroderma, or progressive systemic sclerosis, is a connec- es.24,25 Viral infections associated with xerostomia include
tive tissue disease characterized by chronic fibrosis of the skin HIV, human T-lymphotropic virus type 1, hepatitis C virus
and connective tissues. A common oral manifestation of this (HCV), cytomegalovirus, and Epstein-Barr virus.
disease is fibrosis of excretory ducts, acini of lacrimal and sal- In HIV infection, xerostomia is related to the infiltration of
ivary glands, and capillaries resulting in xerostomia.20 CD8+ cells in the salivary glands.26 In addition, the side effects
470
of antiretroviral medications, such as didanosine and protease
inhibitors, can also cause xerostomia.26 Between 1.2% to 40%
of HIV patients have xerostomia.26–31 Like HIV, human T-
lymphotropic virus type 1 triggers autoimmune disease by in-
fecting immunocompetent cells. Anti–human T-lymphotropic
virus type 1 antibodies can be found in the peripheral blood of
between 3.8% and 36.7% of Sjögren syndrome patients.32–35
In HCV infection, between 5% and 55% of patients may
experience xerostomia.36–39 HCV has also been found to be
associated with Sjögren syndrome1 where interferon and
ribavirin therapies commonly administered for HCV manage-
ment can induce dry mouth.40,41
Cytomegalovirus and Epstein-Barr virus infections are also
associated with xerostomia. In cytomegalovirus infection,
immunologic destruction of salivary and lacrimal gland ductal
cells leads to xerostomia.42 Epstein-Barr virus is associated
with many autoimmune conditions, including Sjögren
syndrome, and it is believed to be the inciting factor of Sjögren
syndrome, resulting in xerostomia.1 The inflammatory effects
on the exocrine glands are thought to be due to a combination
of autoimmunity and Epstein-Barr virus infection.1
Granulomatous diseases
Tuberculosis is a granulomatous disease caused by myco-
bacterial infection. Though it is widely known that tuberculo-
sis infiltrates lung tissue, it may also affect the salivary glands.
Affected patients may experience granuloma formation in the
salivary glands, resulting in edema of the glands.43 Patients
with tuberculosis may also report xerostomia.43
Sarcoidosis is a granulomatous disease that affects mainly
the lungs and lymph nodes. Coexistence of histologic and
clinical features between sarcoidosis and Sjögren syndrome
is known.44 Patients with sarcoidosis have been found to have
parotid salivary gland enlargement, submandibular gland
edema, and xerostomia.44
Other systemic causes
Chronic graft-versus-host disease is an immune-mediated
disease involving many organs that occurs after hematopoietic
stem cell transplantation. Xerostomia is one of the more
common oral clinical manifestations of graft-versus-host
disease after stem cell transplantation, with as many as 53%
of patients experiencing this symptom.45 These findings may
be due to fibrosis, lymphocytic infiltration, and destruction
of the salivary gland tissue from immune recognition of
antigenic disparities between donor and recipient.46
End-stage renal disease is a term used to describe late-stage
chronic kidney disease, in which there is irreversible loss of re-
nal function for which dialysis or kidney transplantation is
needed. Because the kidneys are unable to reabsorb sodium,
patients experience polyuria and dehydration, and subsequent
xerostomia ensues.47,48 Xerostomia has been reported in 28%
to 59% of end-stage renal disease patients.47,48
Xerostomia is also a symptom found in two systemic depo-
sition disorders, hemochromatosis and amyloidosis. Hemo-
chromatosis is a condition of iron overload in various
J.W. Millsop et al.
organs. Xerostomia in hemochromatosis occurs due to iron
deposition in salivary glands, leading to decreased salivary
flow rate.49 Amyloidosis is a disorder of amyloid deposition
in a variety of organs. Xerostomia, oral amyloid nodules,
and macroglossia are reported findings in amyloidosis due to
the destruction and infiltration of the salivary glands by
amyloid.50
Parkinson disease is a progressive neurologic disorder.
Xerostomia occurs due to decreased salivary production, with
one study correlating impaired salivary production with levo-
dopa administration, a mainstay therapy for Parkinson disease,
and female gender.51 Other antiparkinsonian medications that
can cause xerostomia are amantadine, benztropine, bromocrip-
tine, carbidopa, entacapone, pramipexole, rasagiline, ropinir-
ole, selegiline, and trihexyphenidyl.52
Ectodermal dysplasia is a genetic disorder of ectodermal
tissue. Xerostomia occurs due to hypoplasia or aplasia of the
salivary glands.53 A decreased salivary flow rate has also been
found in patients with ectodermal dysplasia.54
Although aging would not be considered a systemic disease
as such, salivary gland function is often impaired. With age,
there is approximately 30% loss of acinar salivary gland cells,
and fibrous and adipose tissue replaces the cells.55 In the elder-
ly, there are alterations in the levels of various substances that
form saliva, including lysozyme, lactoferrin, immunoglobulin
A, sodium, potassium, and proline-rich protein.56,57 Studies
have found a decreased salivary flow rate in the elderly
compared with younger adults.58,59
Local factors
Medication inducement is a common underlying etiology.
It is estimated that more than 400 medications affect the sali-
vary gland function and lead to hyposalivation.60,61 Medica-
tions with anticholinergic activity can cause hyposalivation
by decreasing acetylcholine released by parasympathetic
nerves.52 The common offenders of xerostomia include
antiparkinsonian medications; antipsychotic agents, including
haloperidol; antidepressant medications, including selective
serotonin reuptake inhibitors, tricyclic antidepressants, and
atypical antidepressants; sedative agents, including benzodiaz-
epines; antihistamines, including first- and second-generation
agents; anti-HIV agents; opioids; cytotoxic agents such as
interferon, ribavirin, and antineoplastic agents; and antihyper-
tensive medications, including angiotensin-converting
enzyme inhibitors, calcium channel blockers, diuretics,
α-agonists, and beta blockers.52,62
Head and neck radiation commonly results in hyposaliva-
tion and xerostomia. Radiation may cause destruction of the
acinar and stem cells of the salivary glands, leading to glandu-
lar atrophy and fibrosis.52 Destruction and apoptosis occurs
with exposure of 60 Gray (Gy) or higher of radiation.52
Lifestyle factors also contribute to dry mouth. Smoking, al-
cohol use, and drinking caffeinated beverages can lead to oral
dryness. Alcohol use can include rinsing with mouthwash, as
well as consuming alcoholic beverages.3 Heavy snoring, along
Xerostomia: Work-up and Management
with such temporary factors as dehydration, mouth breathing,
and upper respiratory tract infections, can cause xerostomia.63
Evaluation and workup for xerostomia
The diagnosis of xerostomia begins with taking a thorough
medical history. Patients should be asked about difficulty
swallowing, chewing, and speaking, as well as altered taste.
Patients with salivary gland abnormalities may report difficul-
ty wearing dentures, in addition to difficulty in eating crunchy,
hard, acidic, or spicy foods.64 A review of the patient’s medi-
cations, medical history, including head and neck radiation,
and social history are all needed to determine underlying
causes of dry mouth (Table 2).
Many formal questionnaires have been devised to identify
and rate the severity of xerostomia.65–69 Perhaps the most re-
cent concise questionnaire to measure xerostomia is the Sum-
mated Xerostomia Inventory—Dutch Version. This
summated rating scale asks patients to rate five statements
regarding dry mouth clinical manifestations, using one of three
response options (“Never,” scoring 1; “Occasionally,” 2; and
“Often,” 5). The responses are then scored and summed to give
a single score, with higher scores representing more severe
clinical manifestations (Table 3).70
After a comprehensive medical history, a thorough oral
examination should follow. Signs of hyposalivation and xeros-
tomia71 include glassy oral mucosa, smoothed gingiva, loss of
papillae of the dorsal tongue, fissured or lobulated tongue
(Figure 1A and B), foamy saliva, no or minimal salivary
accumulation in the floor of the mouth, more than two cervical
caries, mucosal debris on the oral palate, and sticking of a
dental mouth mirror to the tongue or buccal mucosa.
Salivary flow rates can also be counted for an objective di-
agnosis of hyposalivation. They are measured at least 5 mi-
nutes after fasting overnight or 2 hours after a meal.71
Sialometric tests include measuring the stimulated salivary
flow rate, unstimulated salivary flow rate, and parotid and pal-
atal secretion. Normal salivary flow rate, when stimulated, is
between 1.5 to 2.0 mL/min and when unstimulated the flow
rate is 0.3 to 0.4 mL/min.5,72 Hyposalivation refers to a stimu-
lated salivary flow rate of ≤0.5 to 0.7 mL/min, and unstimu-
lated salivary flow rate is b0.1 mL/min, which is measured
while the patient is sitting upright.5,73 The diagnosis of xeros-
tomia secondary to hyposalivation is made when the salivary
Table 3 The Summated Xerostomia Inventory—Dutch
Version70
1 My mouth feels dry when eating a meal.
2 My mouth feels dry.
3 I have difficulty in eating dry foods.
4 I have difficulties swallowing certain foods.
5 My lips feel dry.
471
flow rate is less than the oral mucosal fluid absorption rate in
addition to the oral fluid evaporation rate.74
Saliva can be collected through the “draining method,” in
which saliva is constantly drained from the lower lip for 15 mi-
nutes into a graduated cylinder,75 or by placing a graduated ab-
sorbent strip on the floor of the mouth with measurements
taken at 1,2, and 3 minutes.76 Stimulated salivary production
can also be obtained by having a patient chew unflavored
gum base or paraffin wax for 1 minute77 or by placing 2%
citric acid solution on the sides of the tongue every 30 seconds
for 5 minutes. 2 Salivary gland flow can be measured with a
micropipette and absorbent filter paper.2
A diagnosis of salivary gland dysfunction can also be made
with imaging including sialography, scintigraphy with
technetium-99m, and computed tomography scan or magnetic
resonance imaging of the salivary glands.4 Laboratory tests
can be obtained to determine if the underlying cause is related
to a systemic disease. For instance, to evaluate for Sjögren syn-
drome, anti-Ro and anti-La antibodies can be tested.
A minor salivary gland biopsy can also be performed, par-
ticularly for cases of suspected Sjögren syndrome. The biopsy
is generally obtained from the lower lip. In this disease, histo-
pathologic testing indicates at least one area of dense infiltrate
of at least 50 lymphocytes/4 mm2 (Figure 2).78
Management
Preventative measures are key to managing xerostomia. Pa-
tients should be counseled regarding maintaining hydration with
adequate water consumption. Good oral hygiene with regular
dental visits and topical fluorides are also necessary for identifi-
cation of signs of xerostomia and for the prevention of dental
caries, respectively. Increasing humidity in the evening and
avoiding crunchy, spicy, acidic, or hard foods may also be help-
ful.2 Medical management of underlying diseases may im-
prove clinical manifestations, as will lifestyle modifications.
Discontinuing medications that cause dry mouth or switch-
ing them to alternative agents should be considered if it is safe
and necessary for the patient. Emerging preventive measures
for xerostomia include administration of botulinum toxin79
or systemic growth factors,80,81 producing regenerative sali-
vary gland tissue through transplantation or gene therapy,82
and use of tempol, a radioprotective agent,83 but all require
further studies.
Systemic agents
Treatment of the clinical manifestations of xerostomia can
be divided into two categories: systemic sialogogues and top-
ical agents (Table 4). The two systemic agents that are ap-
proved therapies for xerostomia by the US Food and Drug
Administration are oral pilocarpine and cevimeline. Pilocar-
pine is a nonselective muscarinic agonist and parasympathetic
agent. The recommended starting dose is 5 mg daily for a
472
Fig. 1 A, Dry, chapped lips secondary to chronic xerostomia.
(Permission granted by Dermatology Online Journal to reprint.) B,
Dry appearance of the tongue with evidence of fissuring. (Permission
granted by Dermatology Online Journal to reprint.)
maximum of 30 mg daily.84 Patients are typically instructed to
take 5 mg three times daily for at least 3 months.85 Pilocarpine
specifically can diminish dry mouth in patients who have un-
dergone radiation therapy to the head and neck. Optimal effect
in patients with head and neck radiation occurs between 2 and
3 months after initiating the medication.86 Side effects include
vision changes, hiccups, bradycardia, hypotension, broncho-
constriction, hyperhidrosis, nausea, vomiting, diarrhea, cuta-
neous vasodilation, and increased frequency of urination.2 It
J.W. Millsop et al.
Fig. 2 Histopathologic examination indicating focal chronic lympho-
cytic inflammatory infiltrate with plasma cells in Sjögren syndrome.
should be used with caution in patients with cardiovascular
and pulmonary diseases and is contraindicated in patients with
iritis and narrow-angle glaucoma.2
Cevimeline is a muscarinic agonist that is selective for M1
and M3 receptors, which are located in the lacrimal and sali-
vary glands.62 It has fewer side effects than pilocarpine, be-
cause it does not affect M2 receptors.62 Standard dosing is
30 mg three times daily for at least 3 months.2 It is also longer
acting than pilocarpine.62 Its most common side effect is dys-
pepsia.62 Both cevimeline and pilocarpine are contraindicated
in patients with chronic pulmonary disease and uncontrolled
asthma, as well as those taking β-adrenergic blockers.2 These
agents should also be used cautiously in patients with uncon-
trolled hypertension and active gastric ulcers.2
Other systemic sialogogues include bethanechol, anethole
trithione, and yohimbine. Bethanechol is a carbamic ester of
β-methylcholine resistant to cholinesterase, and it affects the
M3 receptors.62 It is beneficial in patients with dry mouth after
head and neck radiation and can increase their salivary flow
rate.87 The recommended dose is 25 mg three times daily.62
Side effects include diarrhea and nausea.62 A clinical trial of
anethole trithione, a cholagogue and bile secretion–
stimulating medication, produced improvement in dry mouth
and increased salivary flow.88 Yohimbine, an α2-
adrenoceptor antagonist, may be effective for xerostomia in
patients taking psychotropic medications, according to one
small study.89
Intraoral topical agents
Topical medications are the first-line treatments recom-
mended for xerostomia. The more commonly used agents
can be categorized into chewing gums or candies and salivary
stimulants and saliva substitutes. Chewing gums and candies
should be sugar-free to prevent dental caries. They can often
stimulate saliva secretion and reduce friction of the oral muco-
sa.90 Salivary stimulants and substitutes, including tooth-
pastes, mouthwashes, and gels, can improve salivary gland
function. Saliva substitutes resemble natural saliva and in-
crease salivary viscosity.91 Saliva substitutes commonly con-
tain carboxymethylcellulose, xanthan gum, mucins,
hydroxyethylcellulose, polyethylene oxide, or linseed oil.92,93
Xerostomia: Work-up and Management 473

Table 4 Therapeutic options for xerostomia

FDA-approved systemic sialogogues
Medication Dosing recommendations Side effects and contraindications
Pilocarpine • Initial dose: 5 mg daily • Side effects:
• Maximum dose: 30 mg daily ○ Vision changes
• Typical dose: 5 mg three times daily for at least 3 months ○ Hiccups
○ Bradycardia
○ Hypotension
○ Bronchoconstriction
○ Hyperhidrosis
○ Nausea, vomiting, diarrhea
○ Cutaneous vasodilation
○ Increased urinary frequency
• Contraindications:
○ Iritis and narrow-angle glaucoma
○ Cardiovascular disease
○ Chronic pulmonary disease
including uncontrolled asthma
○ Patients taking β-adrenergic blockers
○ Active gastric ulcers
Cevimeline • 30 mg three times daily for at least 3 months • Side effects:
○ Dyspepsia
• Contraindications:
○ Chronic pulmonary disease including
uncontrolled asthma
○ Uncontrolled hypertension
○ Patients taking β-adrenergic blockers
○ Active gastric ulcers
Other systemic sialogogues Intraoral topical agents Emerging medical therapies
Bethanechol Chewing gums and candies Acupuncture
Anethole trithione Salivary stimulants Electrostimulation
Yohimbine Salivary substitutes For head and neck radiation patients:
• Amifostine
• Hyperbaric oxygen
• Intensity-modified radiation therapy
FDA, US Food and Drug Administration.

Sprays have been used for the treatment of xerostomia. A
sialogogue spray, composed of 1% malic acid, has produced
benefit in antihypertensive- and antidepressant-induced xeros-
tomia, but it has a potential risk for enamel loss.94,95 An
intraoral lubricant spray, oxygenated glycerol triester, has
had increased efficacy for xerostomia compared with a com-
mercially available saliva substitute in one study.96 Mucin
sprays, tablets, and lozenges may be using in reducing the
findings in dry mouth.2,97–100 Other topical products, contain-
ing xylitol, betaine, and olive oil, have also been effective
against medication-induced dry mouth.101
Emerging forms of management
Other reported treatments for xerostomia include acupunc-
ture102 and intraoral electrostimulation.103 Hyperbaric oxygen
for patients who have undergone radiation has been reported to
increase salivary function.104 Patients who have undergone
head and neck radiation may also find relief with amifostine, a
cytoprotective agent, or intensity-modified radiation therapy.105
Conclusions
Xerostomia can be a debilitating condition and may be due
to a variety of underlying etiologies, including systemic dis-
eases, medications, head and neck radiation, and modifiable
lifestyle factors. Taking a thorough medical history, including
the patient’s medication list, and social history is of utmost
importance for the diagnosis of dry mouth. Clinical signs of
dry mouth, identified during a physical examination, include
glossy oral mucosa, altered gingiva, fissured tongue or loss
of lingual papillae, and foamy saliva. Once a diagnosis is made
and an underlying etiology is identified, there are many
therapeutic options for management that can help alleviate
the clinical manifestations of xerostomia.
474
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