Pathophysiology Salivary Glands

Pathophysiology of
salivary glands
PRODI KG FK UMY
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Salivary glands - Anatomy

Minor salivary glands
n
p
Hundreds throughout mouth
Major salivary glands (3 on each side of

face)
n
p
p
Parotid Gland (cheek)

Submandibular gland (under angle of the
jaw)
Sublingual gland (under tongue)
Minor salivary glands

o
The minor salivary glands are shown to be

organs whose function is decisively involved in
symptoms such as xerostomia, stomatodynia,
and what is known as "denture intolerance".
o Moreover, proper secretion of the palatine
glands is of crucial importance for the physical
retention of maxillary full dentures.
o There are no connections between secretory
rates of major and minor salivary glands.
o The effect of certain drugs on salivary
production and thus on the symptoms of
hyposalivation seems to be considerable.
Parotid Gland
n
n
Largest salivary gland

Most prone to bacterial sialadenitis
p
p
p
Facial nerve bisects gland

p
p
Superficial lobe
Deep lobe
Lies over maxillary bone

p
p
Neonatal sialadenitis
Acute bacterial sialadenitis
Chronic sialadenitis
Superior to mandible
Anterior to angle of jaw and auricle
Stensen's Duct (Parotid Papilla)

p
p
Opens out adjacent to maxillary second molar

Milking parotid gland will expel drop at duct
Gl. parotis
Submandibular gland
n
n
Second largest salivary gland

Located within submandibular triangle
p
p
p
Recessed immediately below mandible

Overlies hypoglossus muscle
Hypoglossal and lingual nerves overly gland
Wharton's Duct
p
Opens adjacent to lingual frenulum
Gl. submandibularis
Physiology and Function

Saliva function
n
p
p
Controls oral pH
Assists with food intake
n
n
Lubricates food bolus

Contains amylase for carbohydrate
digestion
Mouth cleansing and oral hygiene

n
n
Saliva limits oral pathogen growth

Reduces oral odor (halitosis)
Saliva content
o Water 99,4%
o Organic compounds mucin, amylase,
lysozym, immunoglobulin A
o Anorganic compounds HCO3-, I, K, Cl,
Na, Ca, phosphates and others.
Saliva production
n
Differential saliva production by glands

p
Unstimulated salivation (Salivary gland at

rest)
n
n
1.5 Liters produced per day (basal rate)

Major salivary glands: 90% of saliva
produced
Submandibular and sublingual glands: 70%
of saliva
Stimulated salivation
n
n
Saliva production increases 5 fold

Parotid gland produces majority of saliva
Regulation of secretion
n
Innervation
p
Parasympathetic innervation to major

salivary glands
n
n
Otic ganglion fibers supply Parotid Gland

Submandibular ganglion supplies other
major glands
Sympathetic innervation promotes saliva

flow
n
Stimulates muscle contractions at salivary

ducts
Testing of saliva production

The kach test
o Unstimulated production collection of saliva
into container during 15 min
o Stimulated production collection of saliva
during 15 min of chewing parafine gum
o Measuring of both amounts during 2x15 min
o Normal levels: greater than 8-10 ml
o Pathologic levels: under 8 ml
Xerostomia
o
Definition
n
Decreased saliva production
Physiology: Saliva plays vital role

in dental health
n
n
n
n
Re-mineralizes enamel
Buffers cariogenic acids
Removes food residue
Inhibits bacterial growth
Causes of Xerostomia
Medications (anticholinergic affect)
n
p
p
p
p
p
p
p
p
p
p
p
Tricyclic Antidepressants
Antispasmodics
Neuroleptics
MAO inhibitors
Antiparkinsonian agents
Lithium
Central Adrenergic Agonists (antihypertensives)
Diuretics
Decongestants
Antihistamines
Bronchodilators
Other causes
p
p
p
p
p
p
p
p
Radiation therapy to head and neck

Salivary Gland surgery
Sjogren's Syndrome
Amyloidosis
Human Immunodeficiency Virus (HIV Infection)
Diabetes Mellitus
Major Depression
Granulomatous Disease
n
n
n
Sarcoidosis
Tuberculosis
Leprosy
Other diseases
o Sjgren's sy
o Felty's sy
o Diabetes, hyperthyreosis, anemia,
avitaminosis B, hepatopatia
Sjgren's sy
o
Sjgren's syndrome (SS) is a relatively common

autoimmune connective tissue disorder. It is
most frequent in middle-aged women. About
30% of patients with autoimmune disorders
such as RA, SLE, scleroderma, vasculitis,
mixed connective tissue disease, Hashimoto's
thyroiditis, primary biliary cirrhosis, or chronic
autoimmune hepatitis develop SS. Genetic
associations have been found (eg, HLA-DR3
antigens in whites with primary SS).
Pathophysiology
o Salivary, lacrimal, and other exocrine glands become
infiltrated with CD4+ T cells and with some B cells. The T

cells produce inflammatory cytokines (eg, IL-2,
-interferon). Salivary duct cells also produce cytokines,
eventually damaging the secretory ducts. Atrophy of the
secretory epithelium of the lacrimal glands causes
desiccation of the cornea and conjunctiva
(keratoconjunctivitis sicca). Lymphocytic infiltration and
intraductal cellular proliferation in the parotid gland cause
luminal narrowing and in some cases formation of
compact cellular structures termed myoepithelial islands;
atrophy of the gland can result. Dryness and GI mucosal
or submucosal atrophy and diffuse infiltration by plasma
cells and lymphocytes may cause symptoms (eg,
dysphagia).
Symptoms and Signs

o SS often affects the eyes or mouth initially and
sometimes exclusively. Dry eyes can produce irritation

and photosensitivity. In advanced cases, the cornea is
severely damaged, epithelial strands hang from the
corneal surface (keratitis filiformis), and vision can be
impaired. Diminished saliva (xerostomia) results in
difficulty chewing, swallowing, secondary Candida
infection, tooth decay, and calculi in the salivary ducts.
Taste and smell may be diminished. Dryness may also
develop in the skin and in mucous membranes of the
nose, throat, larynx, bronchi, vulva, and vagina. Dryness
of the respiratory tract may produce cough or lung
infections. Alopecia may occur. Parotid glands enlarge in
13 of patients and are usually firm, smooth, and mildly
tender. Chronic salivary gland enlargement is rarely
painful.
o Arthritis occurs in about 13 of patients and is similar in
distribution and character to RA.

o Other common extraglandular manifestations include
generalized lymphadenopathy, Raynaud's phenomenon,
parenchymal lung involvement (which is common but
infrequently serious), and vasculitis that can occasionally
affect the peripheral nerves or CNS or cause skin rashes
(including purpura), glomerulonephritis, or mononeuritis
multiplex. Kidney involvement can produce renal tubular
acidosis, impaired concentrating ability, kidney stones, or
interstitial nephritis. Pseudolymphoma, malignant
lymphoma, or Waldenstrm's macroglobulinemia can
develop; patients develop non-Hodgkin lymphoma at 40
times the normal rate and require careful follow-up.
Chronic hepatobiliary disease, pancreatitis (exocrine
pancreatic tissue is similar to that of salivary glands), and
fibrinous pericarditis may also occur.
Diagnosis
o
SS should be suspected in patients with

scratchy or dry eyes or dry mouth, enlarged
salivary glands, purpura, or renal tubular
acidosis. Such patients should receive
diagnostic tests that can include evaluation of
the eyes and salivary glands and serologic
tests. Diagnosis is based on 6 criteria: eye
symptoms, oral symptoms, eye tests, salivary
gland involvement, autoantibodies, and
histopathology. SS is probable if 3 criteria
(including objective criteria) are positive and
definite if 4 criteria are positive.
o Eye symptoms consist of 3 mo of
either dry eyes or use of tear substitutes

3 times/day; slit-lamp examination may
also confirm dry eyes. Oral symptoms
consist of > 3 mo of daily dry mouth
sensation, daily use of liquids to aid in
swallowing, or swollen salivary glands.
Ceratoconjunctivitis sicca
Candidasis oralis
The Schirmer test measures the quantity of

tears secreted in 5 min after irritation from a
filter paper strip placed under each lower eyelid.
A young person normally moistens 15 mm of
each paper strip. Most people with SS moisten
< 5 mm, although about 15% of test results are
false-positive and 15% are false-negative.
Ocular staining with an eyedrop of rose bengal
or lissamine green solution is highly specific.
Slit-lamp examination showing a fluorescein
tear breakup in < 10 sec is also suggestive.
o Salivary gland involvement can be confirmed by
abnormally low saliva production ( 1.5 mL/15
min) as measured by salivary flow, sialography,
or salivary scintiscanning, although these tests
are less often used.
Serologic criteria have limited sensitivity and

specificity. They include antibodies to Ro (SSA) or to nuclear antigens (termed La or SS-B
autoantibodies), antinuclear antibodies, or an
elevated level of antibodies against -globulin.
Rheumatoid factor is present in > 70% of
patients. ESR is elevated in 70%, 33% have
anemia, and up to 25% have leukopenia.
o Biopsy of minor salivary glands in the buccal
mucosa should be performed if diagnosis is not
clear. Histopathologic involvement is confirmed
if labial minor salivary glands show multiple
large foci of lymphocytes with atrophy of acinar
tissue.
Haematoxylin and eosin stained section of a labial gland from a patient with
Sjogren's syndrome showing (A) a periductal focus and (B) an area of more
extensive lymphocytic infiltration associated with a proliferating duct.
Mason, G I et al. Mol Pathol 2003;56:52-59
Copyright 2003 BMJ Publishing Group Ltd.
Prognosis and Treatment

o
The disease is chronic, and death may

occasionally result from pulmonary infection
and, rarely, from renal failure or lymphoma.
Other connective tissue disorders usually
worsen prognosis. There is no specific
treatment for the basic process.
o Dry eyes should be treated with OTC lubricating
eyedrops qid and prn. Skin and vaginal dryness
can be treated with lubricants.
Mouth dryness may be avoided by sipping

fluids throughout the day, chewing sugarless
gum, and using a saliva substitute containing
carboxymethylcellulose as a mouthwash. Drugs
that decrease salivary secretion (eg,
antihistamines, antidepressants, other
anticholinergics) should be avoided. Fastidious
oral hygiene and regular dental visits are
essential. Stones must be promptly removed,
preserving viable salivary tissue. The pain of
suddenly enlarged salivary glands is generally
best treated with warm compresses and
analgesics. Pilocarpine, 5 mg po tid to qid, or
cevimeline HCl, 30 mg po tid, can stimulate
salivary production but should be avoided in
patients with bronchospasm and closed-angle
glaucoma.
Felty sy
o
o
o
o
o
o
o
o
o
Young people
RA
Splenomegaly
Lymphadenopathy
Anemia
Thrombocytopenia
Neutropenia
Fever, loos of weight, tiredness
Gramm/positive infections
Management of xerostomia
o
Management
Consider stopping offending medication
Commercial Saliva substitute
Fluoride Supplementation
n
n
n
p
p
Use 1.1% Fluoride gel daily

Fluoride toothpaste
Scrupulous dental care is essential
Ptyalism
o
Pathophysiology
Normal Submandibular Saliva production 0.100.15 ml/min
Ptyalism may result in 1-2 L/day of Saliva loss
Mechanisms of excessive Saliva
n
n
p
p
p
p
Decreased Saliva swallowing and clearance

Excessive Saliva production
Neuromuscular disease
Anatomic abnormalities
Causes
o
Saliva Overproduction
Pregnancy (Ptyalism Gravidarum)
n
p
Hyperemesis Gravidarum
Excessive starch intake

Gastrointestinal causes
n
n
p
p
p
p
p
Gastric distention or irritation

Gastroesophageal Reflux
Acute Gastritis or Gastric Ulcer
Pancreatitis
Liver disease
Medications and toxins

p
p
p
p
p
p
p
p
p
p
p
Clozapine (Clozaril)
Potassium Chlorate
Pilocarpine
Mercury Poisoning
Copper
Arsenic poisoning
Antimony (used to treat parasitic infections)
Iodide
Bromide
Aconite (derived from Aconitum napellus root)
Cantharides
Stomatitis and localized oral lesions

p
p
p
p
p
Aphthous Ulcers
Oral chemical burns
Oral suppurative lesions
Alveolar abscess
Epulis
Oral infectious Lesions

p
p
p
p
p
Dental Caries
Diphtheria
Syphilis
Tuberculosis
Small Pox
Difficulty Swallowing Saliva

Infections
n
p
p
p
p
p
p
p
Tonsillitis
Retropharyngeal Abscess
Peritonsillar Abscess
Epiglottitis
Mumps
Chancre
Actinomycosis
Bone Lesions
n
p
p
p
Jaw fracture or dislocation

Ankylosis of the temporomandibular joint
Sarcoma of the jaw
Neuromuscular disorders
p
p
p
p
p
p
p
p
p
p
Cerebral Palsy
Mental retardation
Bulbar Paralysis
Pseudobulbar paralysis
Bilateral Facial Nerve Palsy
Cerebrovascular Accident
Myasthenia Gravis
Hypoglossal Nerve palsy
Rabies
Botulism
Miscellaneous Causes
p
p
p
Radiation therapy
Macroglossia
Dental malocclusion
Management
o
n
n
Non-specific
Treat specific causes as below
General measures to reduce Saliva
p
p
Tooth brushing and mouthwash has drying effect

Reduce starch intake from diet
Orthodontic appliances that aid swallowing
n
p
Upper plate to cover palate with movable beads

n
n
Aids lip closure

Directs Saliva toward pharynx
Anticholinergic Medications (if refractory to above)
n
p
Glycopyrrolate
n
n
n
Adults: 0.5 to 2 mg PO qd to tid prn

Children: 0.04 mg/kg PO qd to tid prn
Scopolamine Patch 1.5 mg applied every 72 hours prn
Advanced procedures in severe and refractory

cases
p
Botulinum toxin A Salivary Gland injection

n
n
Radiation therapy
n
Performed under ultrasound guidance

Porta (2001) Psychiatry 70:538-40
Borg (1998) Int J Radiat Oncol Biol Phys 41:11139
Surgery
n
n
n
Submandibular Gland excision or duct relocation

Parotid duct relocation or ligation
Salivary denervation (transtympanic neurectomy)
o
n
n
n
Specific measures
Treat Nausea with Antiemetics
Treat Gastroesophageal Reflux
Neuromuscular causes
p
p
p
p
Speech pathology (e.g. swallowing mechanism)

Occupational therapy (e.g. head-back wheelchair)
Neurology consultation
Biofeedback
Oral diseases including dental malocclusion
n
p
Dentist or orthodontist
Macroglossia or Tonsillar Hypertrophy
n
p
Otolaryngology
Sialadenitis
o Acute viral and bacterial infection
o Chronic bacterial, fibroproductive,
post-actnic, specific (actinomycosis,

syfylis, TBC), immunosialadenitis
Acute viral sialadenitis

o Parotitis acuta
o Paramyxovirus
o Neurotrophic effect n.VIII
o Affection of gonadal tissues, pancreas,
central nervous systm

o Incubation: 18 days
o Whole life immunity
Acute bacterial sialadenitis

o Ascendent ductal infection
o Dehydratation, diabetes, renal diseases,
wrong dental hygiene, inflammation in

mouth and pharynx
Chronic bacterial parotitis

o Predisposition ectasy of salivary ducts
congenital, postinfectious, obstructive,

immunopatological
o Sialography
Chronic fibroproductive
sialoadenitis of submandibulary
gland
o Known as Kttner tumor
o Periductal sclerosis
o Extirpation of submandibular gland and
histological verification
Sialolithiasis
o
Stones composed of Ca salts often obstruct

salivary glands, causing pain, swelling, and
sometimes infection. Diagnosis is made
clinically or with CT, ultrasound, or sialogram.
Treatment involves stone expression with saliva
stimulants, manual manipulation, a probe, or
surgery.
Eighty percent of stones originate in the

submandibular glands and obstruct Wharton's
duct. Most of the rest originate in the parotid
glands and block Stensen's duct. Only about
1% originate in the sublingual glands. Multiple
stones occur in about 25% of cases.
o Most salivary stones are composed of Ca
phosphate with small amounts of Mg and
carbonate. Patients with gout may have uric
acid stones. Stone formation requires a nidus
on which salts can precipitate plus salivary
stasis. Stasis occurs in patients who are
debilitated, dehydrated, have reduced food
intake, or take anticholinergics. Persisting or
recurrent stones predispose to infection of the
involved gland (sialadenitis).
Symptoms, Signs, and

Diagnosis
o Stones cause glandular swelling and pain, particularly after
eating, which stimulates saliva flow. Symptoms may subside

after a few hours. Relief may coincide with a gush of saliva.
Some stones cause intermittent or no symptoms. If a stone is
lodged distally, it may be visible or palpable at the duct's outlet.
o If a stone is not apparent on examination, the patient can be
given a sialagogue (eg, lemon juice, hard candy, or some other
substance that triggers saliva flow). Reproduction of symptoms
is almost always diagnostic of a stone.
o CT, ultrasound, and sialography are highly sensitive and are
used if clinical diagnosis is equivocal. Contrast sialography may
be performed through a catheter inserted into the duct and can
differentiate between stone, stenosis, and tumor. This technique
is occasionally therapeutic.
o Because 90% of submandibular calculi are radiopaque and
90% of parotid calculi are radiolucent, plain x-rays are not
always accurate. MRI is not indicated.
Treatment
o Analgesics, hydration, and massage can relieve
symptoms. Antistaphylococcal antibiotics can be used to

prevent acute sialadenitis if started early. Stones may
pass spontaneously or when salivary flow is stimulated
by sialagogues; patients are encouraged to suck a lemon
wedge or sour candy every 2 to 3 h.
o Stones right at the duct orifice can sometimes be
expressed manually by squeezing with the fingertips.
Dilation of the duct with a small probe may facilitate
expulsion.
o Surgical removal of stones succeeds if other methods
fail. Stones at or near the orifice of the duct may be
removed transorally, whereas those in the hilum of the
gland often require complete excision of the salivary
gland
Enlargement of salivary glands

o
Causes
Unilateral Salivary enlargement
n
p
p
p
p
Salivary Gland Tumor

Bacterial Sialadenitis
Chronic Sialadenitis
Sialolithiasis
Bilateral Salivary enlargement with

hypofunction
p
p
p
Viral Sialadenitis
Sjogren's Syndrome
Human Immunodeficiency Virus (HIV
Infection or AIDS)
Chronic granulomatous disease
n
n
n
Sarcoidosis
Tuberculosis
Leprosy
Sialadenosis (asymptomatic parotid

enlargement)
p
p
p
p
Eating disorder (Anorexia, Bulimia)

Cirrhosis
Chronic Pancreatitis
Endocrine Disorder
n
n
n
Acromegaly
Diabetes Mellitus
Gonadal hypofunction
Case report Bulimia nervosa (BN)

o case of a 22-year-old woman with BN
who had bilateral parotid gland swelling,

serum electrolyte alteration and no
dental stigmata. Her principal concern
was the associated cosmetic deformity.
From the time of onset, the parotid gland

swelling was persistent, painless and did not
fluctuate in size. Palpation confirmed that the
enlarged parotid glands were painless and
normal in tone. We did not see any cervical
lymphadenopathy. Intraorally, the mucosa was
normally moist. All salivary ducts were patent
with a clear and adequate salivary flow exiting
from each parotid orifice when the gland was
manually milked. The patient was caries-free,
and no restorations were present. There were
no signs of enamel erosion or periodontal
abnormalities. The patient was excellent at
following an oral hygiene regimen.
Because she became increasingly alarmed

about the parotid gland swellings, she sought
medical care in June 2002, without admitting to
the emetic problem. A computerized
tomography, or CT, scan was performed, and
she was told that the parotid glands were
enlarged and denser for unknown reasons but
that no pathology was present. She was not
offered any medical treatment.
Figure 1. A. Right parotid

gland swelling (arrow). B. Left
parotid gland swelling (arrow).
Figure 2. Computerized
tomography scan with contrast
of moderately enlarged parotid
glands (arrows).
In December 2002, she visited another

physician, who performed a serology
evaluation. The patients serum potassium level
was abnormally low (3.2 millimolar per liter;
normal = 3.55.5 mmol/L).
o Hypokalemia was the only abnormality
uncovered by the physician. At this point, the
patient told her physician that she had BN.
o After potassium replacement therapy, she was
referred to a psychiatrist and prescribed the
antidepressant paroxetine hydrochloride.
o Bilateraland occasionally unilateralparotid gland
swelling is not unusual in people with BN; the incidence

of parotid gland swelling has been reported to occur in 10
to 15 percent of people with BN.The submandibular
salivary gland is involved infrequently. The exact
pathogenesis has not been determined.
o However, it generally is accepted that multiple emetic
episodes cause an autonomic neuropathy. With

sympathetic nerve impairment, individual acinar cells
enlarge because of zymogen granule engorgement.
o One explanation is that the sympathetic nerve supply to
the secreting acinar cell is concerned with the production

and secretion of zymogen, the precursor of amylase.
Because of sympathetic nerve dysfunction, there may be
an increase in zymogen storage in the cell, owing to
increased production, decreased secretion of the
granules or both
Benign tumors
n
Benign
p
Mixed Tumor (Pleomorphic adenoma)

n
n
n
n
n
p
p
Most Common benign Salivary Gland tumor

May affect major Salivary Glands
May also affect minor Salivary Glands (esp.
palate)
Slow growing, nonulcerated painless tumor
Occurs most commonly in women aged 30
to 60 years
Monomorphic Adenoma
Warthin's Tumor
Malignant tumors
n
Malignant
p
Mucoepidermoid carcinoma (ages 20 to 50

years)
Adenoid cystic carcinoma (age over 50
years)
Locations: May affect any of

Salivary Glands
Parotid Gland
Sublingual Gland
Submandibular Gland
Minor Salivary Glands
n
n
n
n
p
p
Especially on posterolateral Hard Palate

Buccal mucosa and lips may also be
affected
Diagnosis
n
n
n
Slow growing, painless mass

Palpation reveals enlargement
CT or MRI scan diagnostic
Management
n
Surgical biopsy
Prognosis
n
Mucoepidermoid carcinoma
p
Five year survival dependent on grading:
50-90%
Adenoid cystic carcinoma
p
Five year survival: 65%
p
Twenty year survival: 15%

Pathophysiology Salivary Glands

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Pathophysiology of

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Salivary glands - Anatomy

Hundreds throughout mouth

Major salivary glands (3 on each side of

Parotid Gland (cheek)

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Minor salivary glands

The minor salivary glands are shown to be

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Largest salivary gland

Facial nerve bisects gland

Lies over maxillary bone

Stensen's Duct (Parotid Papilla)

Opens out adjacent to maxillary second molar

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Second largest salivary gland

Recessed immediately below mandible

Opens adjacent to lingual frenulum

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Physiology and Function

Lubricates food bolus

Mouth cleansing and oral hygiene

Saliva limits oral pathogen growth

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Differential saliva production by glands

Unstimulated salivation (Salivary gland at

1.5 Liters produced per day (basal rate)

Saliva production increases 5 fold

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Parasympathetic innervation to major

Otic ganglion fibers supply Parotid Gland

Sympathetic innervation promotes saliva

Stimulates muscle contractions at salivary

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Testing of saliva production

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Decreased saliva production

Physiology: Saliva plays vital role

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Radiation therapy to head and neck

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Sjgren's syndrome (SS) is a relatively common

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infiltrated with CD4+ T cells and with some B cells. The T

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Symptoms and Signs

sometimes exclusively. Dry eyes can produce irritation

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o Arthritis occurs in about 13 of patients and is similar in

distribution and character to RA.

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SS should be suspected in patients with

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o Eye symptoms consist of 3 mo of

either dry eyes or use of tear substitutes

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