CLINICAL REVIEW Section 1 Epidemiology and aetiology
Sjogren's syndrome (SS) is a relatively under diagnosed cause for
dry eyes (xerophthalmia) and mouth (xerostomia), and the diagnosis
is often delayed for months to years.
The presence of xerostomia and xerophthalmia is also called sicca
syndrome. It is considered one of the commonest autoimmune
connective tissue disorders, with a prevalence of 0.5-3 per cent in
the adult population and is similar in most racial groups
Like most autoimmune conditions, it tends to affect mainly women,
with a female-to-male ratio of 9:1. Although it can affect all age
groups, its peak age of onset is in the fourth and fifth decades.
The syndrome is a multisystem autoimmune disorder affecting
primarily the exocrine glands in the body. The lesion in this
disorder starts with lymphocytic infiltration of the salivary glands
leading to inflammatory symptoms including swelling and pain. Later,
the glandular tissues atrophy and progressively disappears leading to
The disease process is not limited to salivary glands and may
affect virtually all organs, including lungs, nervous, system and
Although there is evidence for genetic (HLA-DR3)2 and
environmental (viral infections) associations,3 their exact
contribution to the disease process is still unknown.
Approximately half of all cases of the syndrome are primary cases
while the remainder (secondary SS) are associated with autoimmune
conditions, including systemic lupus erythematosus (SLE), rheumatoid
arthritis (RA), and thyroiditis.
Both primary and secondary SS are similar in symptoms and signs,
although primary SS tends to have more prominent sicca symptoms while
secondary SS is less associated with anti-Ro and anti-La
Salivary gland swelling
The disease process is not limited to salivary glands alone and
may affect virtually all organs, including lungs, nervous system and
As the disease affects exocrine glands primarily, the earliest
symptoms are of reduced tear and saliva production. Patients often
present complaining of a burning, sandy sensation under the eyelids
along with itching and redness, difficulty in swallowing dry foods
or speaking continuously, a burning sensation in the mouth or an
increase in dental caries.
In 60 per cent of primary SS, there may be salivary gland
enlargement. This may be unilateral initially but becomes bilateral.
In addition, other exocrine glands in the body may also be involved,
leading to hoarseness, dry skin and loss of vaginal secretions.
SS is a systemic disease and patients with primary SS often
report general constitutional symptoms such as fatigue, low-grade
fever and myalgias.
Half of patients also report arthritis, which may be deforming
due to periarticular tissue damage with no signs of erosions on x-
rays (Jaccoud's arthropathy) asopposedtothe erosive disease seen in
Skin signs include Raynaud's phenomenon and purpura secondary to
Primary SS may also present with major organ involvement. Nervous
system involvement may manifest as a mononeuritis multiplex as a
consequence of small vessel vasculitis.
Liver abnormalities including hepatomegaly and elevated alkaline
phosphatase may be found in primary SS, often associated with anti-
mitochondrial antibodies. Renal involvement is found in 5 per cent
of SS, often as glomerulonephritis, and SS may also be associated
with a sterile interstitial cystitis, leading to nocturia and pain.
SS may affect the entire respiratory airway leading to a dry
cough, airway obstruction and rarely interstitial lung disease.
The sicca syndrome needs to be confirmed by simple objective
clinical tests that assess gland secretion. A Schirmer's tear test
can be easily performed in clinic (see box left).
Unstimulated whole saliva sialometry, used to assess saliva
production (see box right), can also be carried out in a clinical
With the results of the two clinical tests, the main
investigations to consider include biopsy of a minor salivary gland
(usually of the lower lip) and the presence of autoantibodies.
Anti-Ro and anti-La antibodies are found in 60 per cent and 40
per cent of primary SS respectively. Rheumatoid factor is also found
in 60 per cent of primary SS with no underlying diagnosis of RA.
General blood results may include elevated inflammatory markers,
leukopaenia and hypergammaglobulinaemia on serum electrophoresis in
80 per cent of cases.
The probability of SS is high with a history of sicca syndrome
for at least three months confirmed with either Schirmer's test or
sialometry along with anti-Ro and/or anti-La positivity. If the
suspicion of SS is high despite negative results, a salivary gland
biopsy will be required.
Other investigations including sialography to assess the salivary
gland ductsystem, rose bengal staining of the cornea and
scintigraphy for salivary gland function may provide additional
SCHIRMER'S TEAR TEST
1. Bend the Schirmer's test strip at the indentation and place
the shorter end under the lower eyelid.
2. Leave test strip for five minutes.
3. Measure how much of the test strip is wet from the
4. A healthy person wets >/=15mm after 5 minutes. A positive
result for xerophthalmia occurs when
Periartlcular tissue damage may cause arthritis symptoms in SS
UNSTIMULATED WHOLE SAUVA SIALOMETRY
1. Use a container/beaker used for measuring volume.
2. Over 15 minutes, collect all saliva produced by spitting into
the container. Instruct patient not to swallow during this time.
3. A positive result for xerostomia occurs when
IVIG helps reverse the whole disease if treated early
Dry eyes should be lubricated regularly with artificial tears.
There are various preparations of eye lubricants but the more
viscous drops should be used before bedtime as they are longer
lasting but can cause blurringofvision.
It is important to avoid factors that may exacerbate dry eyes,
including windy environments, cigarette smoking and drugs such as
In severe disease, where lubricants are ineffective, surgical
treatments including punctual cauterisation or lateral tarsorrhaphy
may be used.
Sugar-free lemon drops or flavoured lozenges are often used as
first-line treatment to stimulate the production of saliva for
xerostomia. These stimulants need to be sugar-free, because the risk
of dental caries is high inSSandoralhygieneshouldbe emphasised to
patients. Some patients may prefer the use of artificial saliva as
an alternative, particularly at bedtime.
In severe cases, pilocarpine may be helpful in stimulating
salivary secretion but sideeffects such as flushing may limit its
Hydroxychloroquine is effective for most general constitutional
symptoms of SS but particularly arthralgias and myalgias.5
Severe organ involvement including interstitial lung disease,
nervous system involvement and vasculitis will require systemic
corticosteroids and other immunosuppressive agents, including
cyclophosphamide and azathioprine. These agents are usually
initiated and monitored by a specialist secondary care unit.
Pregnant women with SS who are positive for anti-Ro and/ or anti-
La antibodies require an early appointment with a secondary
obstetric service. These antibodies are associated with the
development of permanent congenital heart block (CHB) as well as a
transient neonatal lupus rash.6
The risk of CHB requires regular fetal echocardiograms. Any signs
of heart block will require immunosuppressive treatments.
Rose bengal: a pink dye used In the eye to show damage to the
Section 4 Prognosis and complications
Primary SS in most cases has a long benign course. Some large,
long-term follow-up studies have found no increased mortality among
patients with primary SS compared to the background population.
However, there are factors that may increase the morbidity and
mortality rate in a subgroup of SS patients (see box below right).
Patients with primary SS have a 44 times higher risk of
developing lymphoma than the general population.7
These lymphomas tend to be of B-cell origin, which may produce
rheumatoid factor. They are usually extranodal and in over half of
cases, are found in salivary glands.
The physician should always be alert to patients who complain of
persistent, painful parotid gland enlargement, which may be
bilateral. In this situation, a referral for an urgent biopsy may be
Signs and symptoms
Other signs associated with lymphoma include splenomegaly and
lymphadenopathy. Physicians should also be alert to a history of
persistent fever, unexplained weight loss and night sweats. The
severity of the malignancy varies widely, but some of the lymphomas
may be of low histological grade and may go into remission
spontaneously or with immunosuppressive treatments given for
systemic SS alone.
The mortality and morbidity figures for secondary SS are strongly
influenced by the associated autoimmune rheumatic disease. In SS
associated with RA, the development of SS usually occurs many years
after the diagnosis of RA and is usually mild. The symptoms are
primarily from the sicca syndrome and systemic features of SS are
The clinical picture is much more complicated when SS is
associated with connective tissue diseases such as SLE, since these
disorders have similar disease features to SS.
All cases of suspected SS should be referred to secondary
specialist care initially.
Primary SS will require investigations for potential systemic or
major organ involvement while secondary SS will require management
of the associated autoimmune disorder.
Patients with primary SS have a 44 times higher risk of
developing lymphoma than the general population
Sjogren's syndrome: dry tongue due to the wasting of salivary