S j ö g ren S y n d ro m e a n d

Ot h er C au s es o f Sic ca in
Older A dults
a,b, b
Alan N. Baer, MD *, Brian Walitt, MD, MPH

KEYWORDS
 Sjögren syndrome  Dry eye  Aging  Salivary hypofunction  Xerostomia

KEY POINTS
 Symptoms of dry eyes and dry mouth are common in the elderly and most often relate to
medication side effects.
 Sjögren syndrome is the prototypic illness that causes dry eyes and dry mouth and is an
important diagnostic consideration in older individuals presenting with dry eye and mouth
symptoms.
 The diagnosis of Sjögren syndrome requires the presence of anit- Sjögren Syndrome A
(SSA) and/or anti-Sjögren syndrome B (SSB) antibodies, or a minor salivary gland biopsy
showing at least 1 tightly aggregated periductal lymphocytic aggregate per 4 mm2 of glan-
dular tissue section (focal lymphocytic sialadenitis with a focus score 1).
 Management of Sjögren syndrome requires attention to both the glandular (ocular and oral
dryness, glandular enlargement) and extraglandular manifestations (eg, arthritis, pneumonitis,
nephritis, vasculitis).

INTRODUCTION

Symptoms of dryness of the eyes, mouth, and vagina (in women) are common among
the elderly and have a substantial impact on life quality. The prevalence of these symp-
toms increases with age and reaches up to 30% in persons more than the age of
65 years, particularly in women.1–5 Objective evidence of diminished tear or saliva pro-
duction is much less frequent,4–6 indicating the weak association between dryness
symptoms and objective measures. There are many potential causes for mucosal dry-
ness in the elderly, and multiple factors can contribute in a single individual.

Disclosure: Dr A.N. Baer reports consulting fees from Bristol-Myers Squibb and Novartis.
This article was supported in part by the Intramural Research Program of the NIH, NIDCR.
a
Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Med-
icine, 5200 Eastern Avenue, Suite 4000, Mason Lord Center Tower, Baltimore, MD 21224, USA;
b
National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Cen-
ter Drive, Bethesda, MD 20892, USA
* Corresponding author. 5200 Eastern Avenue, Suite 4000, Mason Lord Center Tower, Baltimore,
MD 21224.
E-mail address: alanbaer@jhmi.edu

Clin Geriatr Med 33 (2017) 87–103

http://dx.doi.org/10.1016/j.cger.2016.08.007 geriatric.theclinics.com
0749-0690/17/ª 2016 Elsevier Inc. All rights reserved.
88 Baer & Walitt

Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by

dry eyes and dry mouth, arising from autoimmune-induced inflammation of the
lacrimal and salivary glands. It primarily affects perimenopausal and postmenopausal
women and is a prime diagnostic consideration in older patients with mucosal dry-
ness. It can occur in a primary form or in association with another systemic autoim-
mune disease (termed secondary SS). The reported prevalence of primary SS in
population-based studies ranges from 0.01% to 0.09%.7 SS is present in up to
17% of patients with rheumatoid arthritis,8,9 a disease whose prevalence reaches
1.1% in the United States.10 Thus, the overall prevalence is higher, making SS the sec-
ond most common systemic rheumatic disease.
This article reviews the clinical manifestations, differential diagnosis, and medical
evaluation of elderly patients with dry eyes and mouth, as well as the approach to
the diagnosis and management of SS.

DRY EYE

Dry eye manifests most often with ocular irritation, including burning, stinging, sore-
ness, and a foreign body sensation. The symptoms are aggravated by exposure to
low humidity, wind, or air drafts, as well as prolonged visual attention, including
reading. Less frequent symptoms include blurred vision, excess tearing, and
blepharospasm.
Dry eye is generally caused by diminished tear production or by excessive tear
evaporation11 (Box 1). The former is most often caused by lacrimal gland disease
but can result from lacrimal gland duct obstruction or reflex hyposecretion related
to corneal sensory loss. Excessive evaporation from meibomian gland dysfunction
and other forms of blepharitis is more common. Other causes of dryness include
incomplete lid closure during sleep, allergic conjunctivitis, and trachoma.
Tear production and lipid content have been shown to diminish with age12,13 as a
result of changes in lacrimal and meibomian glands, a decreased density of conjunc-
tival goblet cells, and somatosensory nerve impairments.14 In addition, the elderly
frequently have conditions contributing to dry eye, such as the use of medications
with anticholinergic side effects, past refractive or cataract surgery,15 lagophthalmos,
blink abnormalities, and conjunctivochalasis.16

Box 1
Common causes of dry eye in the elderly
Aqueous Tear Deficiency Evaporative Tear Deficiency
 SS  Meibomian gland dysfunction (posterior
 Age-related dry eye blepharitis)
 Systemic medications (eg, antihistamines,  Exophthalmos, poor lid apposition, lid
b-blockers, antispasmodics, diuretics) deformity
 Lacrimal gland duct obstruction (eg, cicatricial  Low blink rate
pemphigoid, mucous membrane pemphigoid,  Ocular surface disorders (eg, vitamin A
trachoma, erythema multiforme, burns) deficiency, toxicity from topical drugs/
 Ocular sensory loss leading to reflex preservatives, contact lens wear)
hyposecretion (eg, diabetes mellitus, corneal  Ocular surface disease (eg, allergic
surgery, contact lens wear, trigeminal nerve conjunctivitis)
injury)
 Lacrimal gland infiltration (eg, sarcoid,
lymphoma, graft vs host disease, AIDS,
IgG4-related disease)
Abbreviations: AIDS, acquired immunodeficiency syndrome; Ig, immunoglobulin.
 Sjögren Syndrome 89

The assessment of dry eye requires multiple tests (Box 2). The Schirmer test mea-
sures tear production17 and can be reliably performed by a geriatrician in a clinic
setting. A sterile rectangular strip of filter paper, rounded and notched at the proximal
end, is folded over the lower eyelid at the midpoint between the middle and lateral
fornix of each eye. The patient is then asked to close the eyes gently during the 5-min-
ute duration of the test. The extent of tear wicking or wetting is recorded in millimeters
and is normally greater than 5 mm in both eyes. The Schirmer test can be performed
with or without anesthesia to measure basal and reflex tear secretion, respectively.
This test is imperfect in the elderly, because the results decline with age. In 2
population-based surveys of elderly individuals (65 years or older), the prevalence
of an abnormal Schirmer test ranged from 12% to 58%.2,4
Ocular surface staining with vital dyes allows slit lamp visualization of devitalized
conjunctival cells and corneal epithelial defects. Lissamine green is most commonly
used to stain the conjunctiva and fluorescein the cornea. The extent of ocular surface
staining is a measure of dryness-induced ocular surface damage, is one of the
classification criteria for SS, and can be scored using methods described by van
Bijsterveld18 and by the Sjögren International Collaborative Clinical Alliance
(SICCA).18–20
The tear breakup time is used to assess the stability of the tear film21 and is typically
abnormal in meibomian gland dysfunction. Tear osmolarity measurement22,23 is the
best for predicting dry eye severity.23

XEROSTOMIA AND SALIVARY HYPOFUNCTION

Symptoms of dry mouth, termed xerostomia, include burning, dry lips, alteration of
taste, and a sense of having an inadequate amount of saliva. There also may be diffi-
culty speaking, swallowing, and wearing dentures. The need to sip water to swallow
dry food is an important marker of reduced salivary function.24 Halitosis, painful
tongue fissures, mucosal ulcers, and pain with ingestion of spicy or acidic foods are
common discomforts that may stem from candidal overgrowth on the oral mucosa.
The relation between salivation and xerostomia is complex. Dawes25 showed that
healthy patients report dry mouth symptoms when their baseline salivary flow is
reduced by 50%, even if the residual salivary flow level remains within the broad range
of normal.

Box 2
Tests used to assess dry eye disease
Test Abnormal Value Significance of Abnormal Test
Schirmer <5 mm/5 minute in either eye Inadequate tear production
Ocular surface staining Score 4 (van Bijsterveld)18 Damage to the ocular surface
Score 3 (SICCA)19
Tear break up time <10 seconds Poor tear film stability, as seen in
meibomian gland dysfunction
Tear osmolarity 308 mOsm/L in either eye Excessive tear evaporation,
lacrimal gland disease, or ocular
surface inflammation
Abbreviation: SICCA, Sjögren’s International Collaborative Clinical Alliance.
Data from van Bijsterveld OP. Diagnostic tests in the sicca syndrome. Arch Ophthalmol
1969;82(1):10–4; and Whitcher JP, Shiboski CH, Shiboski SC, et al. A simplified quantitative
method for assessing keratoconjunctivitis sicca from the Sjögren’s syndrome International
Registry. Am J Ophthalmol 2010;149(3):405–15.
90 Baer & Walitt

Saliva is produced by the major (parotid, submandibular, sublingual) and myriad

submucosal minor salivary glands. The parotid glands only produce saliva on gusta-
tory or olfactory stimulation. Saliva is continually secreted by the sublingual, subman-
dibular, and minor salivary glands. This basal secretion is crucial for maintaining oral
health.
Both unstimulated and stimulated salivary flow rates are measured. Saliva that
pools in the mouth without stimulation can be collected for 5 to 15 minutes, providing
a measure of so-called whole saliva production in a clinic setting (Box 3). It is consid-
ered the most relevant measure of oral health. Stimulated whole salivary flow rates can
be measured with the patient chewing gum or preweighed gauze and are not generally
affected by medication use. With special research techniques, stimulated (eg, with
lemon juice on the tongue) and unstimulated saliva flow rates can be measured
from the individual parotid glands or sublingual/submandibular glands.
Human salivary glands undergo atrophy with age (Fig. 1). In morphometric studies,
aging was associated with acinar loss and replacement with fat and connective tis-
sue.26,27 Whole unstimulated saliva flow rates decline with age, which may contribute
to the age-dependent increase in dental caries.28 However, this is not true for stimu-
lated parotid saliva flow rates.29
There are multiple potential causes for xerostomia and salivary hypofunction in the
elderly (Box 4).6 Side effects from medications commonly used in the geriatric popu-
lation are the most common.

VAGINAL DRYNESS

Vaginal dryness, dyspareunia, and vulvar pruritus are common symptoms among
postmenopausal women. These symptoms relate to menopause-related decreases
in the levels of estrogen and other sex steroids but can also have other causes. In
2014, 2 international societies recommended that the range of symptoms and signs
associated with menopause be termed the genitourinary syndrome of menopause.30
These symptoms include genital dryness, burning, irritation, inadequate lubrication,
dyspareunia, urinary urgency, dysuria, and recurrent urinary tract infections. Similar
symptoms are also seen with infectious vaginitis, irritant or allergic vulvitis or vaginitis,

Box 3
Measurement of unstimulated whole salivary flow rate
Unstimulated whole saliva collection measures saliva production under resting or basal condi-
tions. The patient should not have had anything to eat or drink for 90 minutes before the pro-
cedure. The use of a parasympathomimetic should be discontinued for 12 hours before the
procedure, and the use of artificial saliva should be stopped 3 hours before. During the collec-
tion procedure, the patient is instructed to minimize actions that can stimulate saliva (talking,
increased orofacial movement) and should not swallow. At time 0, any saliva present in the
mouth is cleared by swallowing. For the subsequent 5 minutes, any saliva collected in the
mouth is emptied into a preweighed tube every minute (ie, 5 times). This collecting tube
then is weighed to determine a postcollection weight. The difference between the precollec-
tion and postcollection weight is determined, and this represents the unstimulated whole
saliva production for 5 minutes. To convert to a volume of saliva from the weight of saliva,
an assumption is made that saliva is similar to water, with 1 g of water/saliva at 4 C equaling
1 mL of saliva/water.
Less than 0.100 mL/min is considered a reduced unstimulated salivary flow rate.

From Wu AJ. Optimizing dry mouth treatment for individuals with Sjögren’s syndrome. Rheum
Dis Clin North Am 2008;34(4):1004; with permission.
 Sjögren Syndrome 91

Fig. 1. Histopathology of minor labial salivary glands. The sections are from biopsies of a 28-
year-old woman (A) and a 65-year-old woman (B), shown at the same magnification. Neither
had Sjögren syndrome. (A) This histopathologic section shows normal tissue, with confluent
mucous acini and normal-sized intralobular ducts. (B) In contrast, this section shows exten-
sive acinar loss, interstitial fibrosis, ductal dilatation, and fatty replacement. These changes
are often seen to varying degrees in older patients (H&E stain, original magnification 100).

vulvovaginal dermatoses, hypertonic pelvic floor muscle dysfunction, painful bladder

syndrome/interstitial cystitis, vulvodynia, and pudendal neuralgia.30
In women affected by SS, vaginal dryness can be severe and affect sexual ability
and pleasure.31 There is scant information regarding the cause of this dryness. One
hypothesis is that the Skene and related glands of the vaginal introitus are affected
in the same manner as exocrine glands found elsewhere.32 There has been no histo-
pathologic confirmation of this to date.

SJÖGREN SYNDROME

SS is the prototypic illness of dryness of the eyes and mouth. It is a systemic autoim-
mune disease characterized by lymphocytic infiltration of the salivary and lacrimal
glands. This chronic inflammatory process gradually leads to glandular injury and
related dysfunction over the course of years, eventually causing the cardinal symp-
toms of dry eyes and mouth. Keratoconjunctivitis sicca is the term coined by Henrik
Sjögren33 in 1933 to describe the dry eye component of this syndrome. Key features
are shown in Box 5.
SS disease onset is uncommon after the age of 65 or 70 years.40,41 Older patients with
SS, compared with younger ones, have a lower frequency of serologic abnormalities,

Box 4
Common causes of dry mouth in the elderly

 Medications, including antidepressants, anticholinergics, antispasmodics, antihypertensives,

antihistamines, sedatives, and diuretics
 SS
 Diabetes mellitus
 Head and neck irradiation
 Dehydration
 Parkinson disease
92 Baer & Walitt

Box 5
Key clinical features of Sjögren syndrome

 Predominant involvement of women, with female to male ratios more than 10:1.
 Diagnosis most commonly established in the fifth and sixth decades of life, although
symptoms of dryness may precede the diagnosis by many years.
 Affects individuals across the age spectrum, including children, but most commonly women
in the perimenopausal years of life.
 Extraglandular manifestations in approximately 50% of patients, including constitutional
symptoms (eg, fatigue and mild cognitive impairment) and other systemic manifestations,
with involvement of diverse organ systems.
 Presence of anti-SSA/Ro and anti-SSB/La in 60% to 80% of patients.34–37
 Increased risk of B-cell non-Hodgkin lymphoma, particularly MALT and diffuse B-cell
lymphoma. The relative risk of non-Hodgkin lymphoma ranges from 4.8 for primary to 9.6
for secondary SS,38 with an estimated lifetime risk of 5% to 10%.39

Abbreviation: MALT, mucosa-associated lymphoid tissue.

Data from Refs.34–39

such as anti-SSA, anti-SSB, rheumatoid factor, and hyperglobulinemia.42 Parotid

enlargement, arthralgia, and Raynaud phenomenon are also less common, although
higher frequencies of lung involvement and anemia have been noted.41 A distinct subset
of older patients with SS with anticentromere antibodies is characterized by Raynaud
phenomenon, overlap features of limited systemic sclerosis, and more severe salivary
and lacrimal gland dysfunction.43
The clinical presentation of SS is varied, but is most often that of mucosal dryness
(Box 6).
SS is associated with a variety of systemic manifestations (Box 7). Some are direct
manifestations of the disease, whereas others represent coincidental autoimmune
diseases. Apart from symptoms of fatigue, joint pain, and mild cognitive impairment
(often termed brain fog), the prevalence of these organ-specific manifestations is
each less than 20%.44
The natural history is generally one of stability, with a slow decline in lacrimal and
salivary gland function. It is not characterized by the types of disease flares seen in
systemic lupus or rheumatoid arthritis, but patients may report periods of worsening
sicca or fatigue. There is no increase in overall mortality according to a recent

Box 6
Modes of presentation of Sjögren syndrome

 Symptoms or signs of dry eyes and mouth

 Episodic or persistent salivary gland enlargement
 Sudden increase in dental caries
 An established connective tissue disease complicated by dry eyes or mouth
 Extraglandular disease (eg, annular erythema, cryoglobulinemia, peripheral neuropathy, or
interstitial pneumonitis)
 Abnormal serologic test, such as anti-SSA and/or anti-SSB antibodies
 MALT lymphoma of a salivary gland
 Sjögren Syndrome 93

Box 7
Systemic manifestations of Sjögren syndrome
Organ Involvement Manifestation
Constitutional Fatigue
Mild cognitive disturbance
Musculoskeletal Arthritis/arthralgia
Myositis (especially inclusion body myositis)
Cutaneous Annular erythema
Xerosis
Palpable purpura
Pulmonary Interstitial pneumonitis
Follicular bronchiolitis
Vascular Raynaud
Vasculitis
Gastrointestinal Atrophic gastritis
Primary biliary cirrhosis
Endocrine Autoimmune thyroid disease
Cardiac Pericarditis
Renal Interstitial nephritis with renal tubular acidosis
Membranoproliferative glomerulonephritis
Hematologic Leukopenia, neutropenia
Thrombocytopenia
Anemia
Monoclonal gammopathy
Cryoglobulinemia
Lymphoproliferative Lymphoma
Neurologic Peripheral neuropathy
Ataxic ganglionopathy
Myelitis (including neuromyelitis optica)

meta-analysis, but patients with specific extraglandular manifestations, including

those with vasculitis, cryoglobulinemia, pulmonary disease, and lymphoma, have
been identified as having higher mortalities.45,46

DIAGNOSIS OF SJÖGREN SYNDROME

The diagnosis requires evidence of autoimmune-induced inflammation targeting the

salivary or lacrimal glands. Two sets of classification criteria are currently in use: the
2002 American-European Criteria Group (Box 8) and the 2012 American College of
Rheumatology provisional classification criteria (Box 9).47,48 Both require that the pa-
tient have either anti-SSA and/or anti-SSB antibodies or a minor salivary gland biopsy
showing focal lymphocytic sialadenitis with a focus score greater than or equal to 1.
These 2 sets of criteria have good concordance.49 However, both criteria sets have lim-
itations, and thus a new set of international consensus criteria is in development. The
authors use these current classification criteria as a general guide, and establish the
diagnosis if a patient has an objective measure of ocular and/or oral dryness or charac-
teristic imaging abnormalities (eg, by ultrasonography, magnetic resonance [MR], or
computed tomography [CT]), coupled with anti-SSA antibodies or a positive lip biopsy.
For practicing geriatricians, the authors recommend that patients suspected of
having SS be evaluated as follows:
 History, seeking a history of persistent symptoms of dry eyes and/or mouth. Vali-
dated screening questions are included in the American-European Classification
Criteria (see Box 8)
94 Baer & Walitt

Box 8
American-European Consensus Group Revised International Classification Criteria for Sjögren
syndrome

1. Ocular symptoms: a positive response to at least 1 of the following questions:

a. Have you had daily, persistent, troublesome dry eyes for more than 3 months?
b. Do you have a recurrent sensation of sand or gravel in the eyes?
c. Do you use tear substitutes more than 3 times a day?
2. Oral symptoms: a positive response to at least 1 of the following questions:
a. Have you had a daily feeling of dry mouth for more than 3 months?
b. Have you had recurrently or persistently swollen salivary glands as an adult?
c. Do you frequently drink liquids to aid in swallowing dry food?
3. Ocular signs: objective evidence of ocular involvement, defined as a positive result for at
least 1 of the following 2 tests:
a. Schirmer test, performed without anesthesia (<5 mm in 5 min)
b. Rose Bengal score or other ocular dye score (>4 according to van Bijsterveld scoring
system)
4. Histopathology: in minor salivary glands (obtained through normal-appearing mucosa)
focal lymphocytic sialoadenitis, evaluated by an expert histopathologist, with a focus
score greater than 1, defined as several lymphocytic foci (which are adjacent to normal-
appearing mucous acini and contain more than 50 lymphocytes) per 4 mm2 of glandular
tissue.
5. Salivary gland involvement: objective evidence of salivary gland involvement defined by a
positive result for at least 1 of the following diagnostic tests:
a. Unstimulated whole salivary flow (<1.5 mL in 15 min)
b. Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary, or
destructive pattern), without evidence of obstruction in the major ducts
c. Salivary scintigraphy showing delayed uptake, reduced concentration, and/or delayed
excretion of tracer
6. Autoantibodies: presence in the serum of the following autoantibodies:
a. Antibodies to Ro(SSA) or La(SSB) antigens, or both
For primary SS
In patients without any potentially associated disease, primary SS may be defined as follows:
a. The presence of any 4 of the 6 items indicates primary SS, as long as either item IV
(histopathology) or VI (serology) is positive
b. The presence of any 3 of the 4 objective criteria items (ie, items III, IV, V, VI)
c. The classification tree procedure represents a valid alternative method for classification,
although it should be more properly used in clinical-epidemiologic survey
For secondary SS
In patients with a potentially associated disease (eg, another well-defined connective tissue
disease), the presence of item I or item II plus any 2 from among items III, IV, and V may be
considered to indicate secondary SS
Exclusion criteria: past head and neck radiation treatment; hepatitis C infection; acquired
immunodeficiency disease (eg, AIDS); preexisting lymphoma; sarcoidosis; graft-versus-host
disease; use of anticholinergic drugs (since a time shorter than 4-fold the half-life of the
drug)

From Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren’s syndrome: a
revised version of the European criteria proposed by the American-European Consensus Group.
Ann Rheum Dis 2002;61(6):557; with permission.
 Sjögren Syndrome 95

Box 9
American College of Rheumatology provisional criteria for classification of Sjögren syndrome

The classification of SS, which applies to individuals with signs/symptoms that may be
suggestive of SS, is met in patients who have at least 2 of the following 3 objective features:
1. Positive serum anti-SSA/Ro and/or anti-SSB/La or (positive rheumatoid factor and
antinuclear antibody (ANA) titer greater than or equal to 1:320)
2. Labial salivary gland biopsy showing focal lymphocytic sialadenitis with a focus score greater
than or equal to 1 focus/4 mm2
3. Keratoconjunctivitis sicca with ocular staining score greater than or equal to 3 (assuming
that individual is not currently using daily eye drops for glaucoma and has not had
corneal surgery or cosmetic eyelid surgery in the last 5 years)
Prior diagnosis of any of the following conditions excludes participation in SS studies or
therapeutic trials because of overlapping clinical features or interference with criteria tests:
 History of head and neck radiation treatment
 Hepatitis C infection
 AIDS
 Sarcoidosis
 Amyloidosis
 Graft-versus-host disease
 IgG4-related disease

From Shiboski SC, Shiboski CH, Criswell L, et al. American College of Rheumatology classification
criteria for Sjögren’s syndrome: a data-driven, expert consensus approach in the Sjögren’s Inter-
national Collaborative Clinical Alliance cohort. Arthritis Care Res (Hoboken) 2012;64(4):484;
with permission.

 Examination, seeking signs of salivary hypofunction and of a systemic rheumatic

disease
 Oral examination
- Is there enlargement of the lacrimal or major salivary glands? What is the

texture of the major salivary glands? Are there discrete nodules or masses?
- Does saliva pool under the elevated tongue when observed over the course

of 1 minute?
- Does the tongue have deep fissures, a hyperlobulated appearance, or

absence of filiform papillae on its surface?

 General examination
- Look for sclerodactyly, palpable purpura, synovitis, basilar pulmonary rales

 Laboratory testing
 Screen for ANA (tested by immunofluorescence assay), anti-SSA (Ro), and
anti-SSB (La), and rheumatoid factor. Anti-SSA and anti-SSB antibodies can
be present despite a negative ANA test.
 A complete blood count, urinalysis, and chemistry profile may reveal abnor-
malities supportive of SS, including leukopenia and neutropenia, hyperglobu-
linemia, renal impairment, and proteinuria.
 Ophthalmologic examination
 Schirmer testing is an appropriate initial test. A formal ophthalmologic exami-
nation serves not only to confirm the diagnosis of dry eye but also to define the
contributing causes, such as meibomian gland dysfunction and conjunctivo-
chalasis. Guidelines for this evaluation can be found at https://sicca-online.
ucsf.edu/documents/eye-exam-SOP.pdf
 Sialometry
 Documentation of salivary hypofunction is only necessary if the eye examina-
tion does not show dry eye disease (see Box 3).
96 Baer & Walitt

 Labial gland biopsy

 A labial gland biopsy, best performed by an oral surgeon, is required for diag-
nosis if the patient lacks anti-SSA and/or anti-SSB antibodies. The biopsy also
has value in excluding alternative diagnoses (eg, sarcoid, amyloid, mucosa-
associated lymphoid tissue lymphoma, and immunoglobulin [Ig] G4–related
disease). Guidelines for its performance can be found at https://sicca-online.
ucsf.edu/documents/Oral-Saliva-SOP.pdf.
 Imaging (Fig. 2)
 Salivary gland ultrasonography is favored because of its low cost and lack of
ionizing radiation. The presence of multiple ovoid hypoechoic lesions, often
bounded by hyperechoic bands, correlates with markers of more severe dis-
ease. These imaging abnormalities have high specificity for the diagnosis,
but only moderate sensitivity.50–54

Fig. 2. Imaging techniques in Sjögren syndrome. This patient has bilateral symmetric parotid
gland enlargement, seen best on the T2 fat-suppressed MR images (A). Note the multiple
T2-hyperintense foci scattered throughout both glands, a characteristic finding. With ultra-
sonography (B), multiple hypoechoic rounded lesions with convex borders are noted
throughout the glandular parenchyma. In normal parotid gland tissue, the parenchyma
has a homogeneous appearance with ultrasonography.
 Sjögren Syndrome 97

 CT imaging is not recommended because of the radiation exposure. However,

the presence of multiple punctate calcifications within the parotid glands has
high specificity.55
 MRI of the parotid glands may reveal heterogeneity of signal intensity on both
T1-weighted and T2-weighted images, with both hypointense and hyperin-
tense foci measuring 1 to 4 mm in diameter.56
Be aware of certain common pitfalls in the diagnostic evaluation. Antibodies to SSA
and SSB are not specific. They are found in systemic lupus and inflammatory myopathies
and are seen in up to 0.9% of healthy women in the US population.57 Labial gland bi-
opsies of older adults are also subject to misinterpretation. The histopathology of the mi-
nor salivary gland, termed focal lymphocytic sialadenitis, is characterized by lymphocytic
aggregates that surround intralobular salivary ducts (Fig. 3) and are adjacent to normal-
appearing mucus-secreting acini. The number of these lymphocytic aggregates per
4 mm2 of glandular tissue section equates to the focus score. A score greater than or
equal to 1 is a criterion for the classification of SS and has been validated as the best cut-
off value differentiating SS from non-SS controls.58 Because chronic inflammation of the
salivary gland can also arise from ductal obstruction and other forms of glandular injury,
care must be taken to exclude from the focus score lymphocytic aggregates in areas of
severe acinar loss, ductal dilatation, and fibrosis (Fig. 4).
In elderly patients, the differential diagnosis of SS primarily includes alternative
causes of sicca symptoms, salivary and/or lacrimal gland enlargement, and the char-
acteristic serologic abnormalities.
 Sicca complex in the elderly: age-related interstitial fibrosis, acinar atrophy, and
nonspecific chronic inflammation in the labial gland biopsy may be misinter-
preted as indicating SS (see Fig. 4).
 Salivary and/or lacrimal gland enlargement: in elderly patients, particular atten-
tion should be paid to the possibility of lymphoma. IgG-4 related disease is
most common in elderly men. It may present as unilateral submandibular gland
enlargement (Küttner tumor) or parotid and lacrimal gland enlargement. Other
diagnostic possibilities include amyloid infiltration, sarcoidosis, human immuno-
deficiency virus infection, bulimia, and hyperlipoproteinemia.

Fig. 3. Focal lymphocytic sialadenitis. This section of a labial minor salivary gland biopsy
shows the typical features of focal lymphocytic sialadenitis. Note the tightly aggregated
lymphocytes surrounding ducts and adjacent to normal-appearing mucous acini. At least
3 foci are evident (H&E stain, original magnification 100).
98 Baer & Walitt

Fig. 4. Potential misinterpretation of labial gland biopsies. (A) The lymphocytic focus is
typical of that seen in focal lymphocytic sialadenitis, being centered on a duct and adjacent
to normal-appearing mucus-secreting acini. (B) In contrast, the lymphocytic focus here is
present within a gland lobule marked by interstitial fibrosis, ductal dilatation, and marked
acinar loss. This focus should not be interpreted as representative of Sjögren syndrome (H&E
stain, original magnification 100).

 Serologic abnormalities: antinuclear antibodies, rheumatoid factor, and mono-

clonal proteins are more prevalent in the elderly population.57 Thus, positive tests
must be interpreted cautiously when they coincide with symptoms or signs of
oral or ocular dryness.

MANAGEMENT OF SJÖGREN SYNDROME

Most patients only require topical and systemic treatments directed at alleviating their
ocular, oral, and vaginal dryness; preventing dental decay; and managing oral
candidiasis. Patients with systemic manifestations, including those with joint pain,
skin lesions, and internal organ involvement, may benefit from immunomodulatory
treatments. All patients with SS require monitoring for disease complications, espe-
cially lymphoma.
Management of ocular dryness depends on its severity and the patient’s response
to therapy.59 Avoidance of wind and smoke, and the use of protective eyewear, can be
helpful for all patients. Artificial tears with a demulcent (eg, methylcellulose, propylene
glycol, and glycerin) are a mainstay of treatment. Patients should use preservative-free
drops if drops are instilled 4 or more times a day. Use of thicker ocular gels and oint-
ments before bed can help with dryness that occurs during sleep. Supplementation of
the diet with omega-3 essential fatty acids has been shown to be of benefit. Use of
topical cyclosporine and steroid solutions can be useful in a variety of dry eye condi-
tions but should be undertaken in consultation with an ophthalmologist. Punctal plugs
to preserve tears are often used in moderate to severe dry eye. Patients with more se-
vere dry eye disease may require the use of moisture chamber spectacles, autologous
serum tears, contact lenses, or scleral prostheses.
Prevention of oral dryness includes maintaining good hydration and avoiding
medications that worsen dryness. Patients should be counseled to be more aware
of factors that can aggravate dryness, such as low-humidity environments and mouth
breathing. Frequent sips of oral solutions can be helpful, with options ranging from
water to artificial saliva. Sucking on sugar-free hard candies helps stimulate saliva
flow. Oral hygiene and dental care are essential in preserving dentition in persons
with pathologic oral dryness.
 Sjögren Syndrome 99

Muscarinic agonists, such as pilocarpine and cevimeline, can substantially increase

saliva and, to a lesser extent, tear flow. However, overall tolerance of these agents
may be hampered by cholinergic side effects of excessive sweating, increased urinary
frequency, flushing, chills, rhinitis, nausea, and diarrhea. Care must be taken when
these medications are prescribed to the elderly.
Vaginal moisturizers and lubricants, including olive and vitamin E oils, are initial
treatment options for vaginal dryness. Vitamin E capsules can be opened and the
oil used in and around the vagina. A suppository containing hyaluronic acid, vitamin
E, and vitamin A, used once daily for 14 days, then once every other day for the
next 2 weeks, can be effective.60 Obtaining these suppositories requires a compound-
ing pharmacist. Topical estrogen cream may help if symptoms do not improve with
these other measures.
Hydroxychloroquine is commonly used for the management of joint pain and/or fa-
tigue. However, clinical trials with this drug have shown mixed results, with none
showing major clinical improvements.61–63 The effect of immunosuppressive therapies
on the glandular manifestations has been disappointing to date. The effect of rituxi-
mab on SS dryness is still being evaluated, with potential benefit being observed in
a small, double-blind, placebo-controlled trial64 but not in a larger one.65 Prolonged
therapy may be required for benefit.66

SUMMARY

Dryness of the eyes and mouth is a prevalent symptom among the elderly, most
often related to the side effects of medications. However, there is a broad differen-
tial diagnosis for each symptom, and careful evaluation is important to define the
cause and correct treatment. SS is the prototypic disease that leads to these symp-
toms and primarily affects perimenopausal women. The diagnosis requires demon-
stration of an autoimmune disease underlying the sicca manifestations, either
serologically or pathologically. Management can involve both topical and systemic
therapies.

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