Frederick B. Vivino
Vatinee Y. Bunya
• Sjögren’s syndrome is a chronic autoimmune disorder in which the body mistakenly attacks its own exocrine tear and salivary glands, leading to dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca).
• In addition, patients can have systemic features involving multiple systems throughout the body including the skin, lungs, liver, kidneys, gastrointestinal tract, vasculature, blood, and nervous system.
• 1.3 million patients with primary Sjögren’s in US (range 0.4–3.1 million)
• Prevalence rate 0.43% (0.13–1%)
• Females are affected 9 times more frequently than males.
• Onset usually fourth to sixth decade of life.
Familial predisposition possible, but no single gene has yet been identified.
Lymphocytic infiltration and destruction of the lacrimal and salivary glands likely triggered by a viral and/or environmental cue in a genetically susceptible individual.
Exact etiology unknown.
Commonly Associated Conditions
• Systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, systemic sclerosis, autoimmune thyroid disease, autoimmune liver disease, inflammatory muscle disease, and leukocytoclastic vasculitis.
• When sicca symptoms (dry eyes and mouth) develop in patients with established connective tissue disease, the diagnosis is considered secondary Sjögren’s syndrome.
• About 5% of patients develop non-Hodgkin B-cell lymphoma within 10 years of diagnosis.
• Symptoms of dry eye (burning, stinging, gritty feeling, artificial tear use)
• Symptoms of dry mouth
• History of rheumatic symptoms or severe fatigue
• Visual acuity
• Lid exam looking for coexisting meibomian gland disease or blepharitis
• Tear break-up time, abnormal if <10 seconds
• Staining of conjunctiva and cornea with lissamine green or rose bengal (note rose bengal may cause stinging and is less well-tolerated than lissamine green)
• Staining of conjunctiva and cornea with fluorescein
• Schirmer’s test
– Abnormal if unanesthetized and ≤5 mm at 5 minutes
– Unanesthetized test measures basal and reflex tear secretion
– With topical anesthetic, test measures basal tear secretion
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
• Anti-Ro/SS-A or Anti-La/SS-B positive in 40–60% of patients with primary Sjögren syndrome
• ANA and RF-positivity may be seen in up to 90%
Follow-up & special considerations
Low complement C4 and cryoglobulins may be markers for lymphomas.
• No ophthalmic diagnostic imaging indicated.
• Nuclear medicine salivary scintigraphy is useful in evaluation of xerostomia
• American–European Consensus Group Diagnostic Criteria (1)
• 6 criteria:
– Symptoms of aqueous tear insufficiency (dry eye for 3 months, foreign body sensation, artificial tear use > 3 × /d)
– Oral symptoms (dry mouth for 3 months, swollen salivary glands, need to drink liquids to swallow food)
– Ocular signs (unanesthetized Schirmer’s test ≤5 mm at 5 minutes, rose bengal staining >4 on van Bijsterveld scale),
– Van Bijsterveld scale sums amount of rose bengal staining in: Nasal conjunctiva, Temporal conjunctiva, and cornea. Each area is assigned a staining score of 0–3. Sum of scores equals total score (maximum score of 9).
– Oral signs (abnormal salivary scintography, parotid sialography, or unstimulated salivary flow <1.5 mL in 15 minutes)
– Minor salivary gland biopsy showing ≥1 conglomeration of >50 mononuclear cells in 4 mm2 of glandular tissue.
• Autoantibodies: Positive anti-Ro/SS-A or anti-La/SS-B
• Primary Sjögren’s syndrome is diagnosed in previously healthy individuals with sicca symptoms which arise de novo.
• Diagnosis of primary Sjögren’s requires at least 4 positive criteria, one of which has to be histopathology or serum autoantibodies.
• Diagnosis of secondary Sjögren’s requires at least 1 sicca symptom, an established connective tissue disease diagnosis, plus 3 signs of Sjögren’s (see criteria 3–5 above).
• Lacrimal gland biopsy shows focal and/or diffuse lymphocytic infiltration. Advanced disease can show fibrous or fatty replacement of glandular structures.
• Labial salivary gland biopsy shows similar changes and is less invasive than lacrimal biopsy.
• Age-related or medication-induced dry eye and dry mouth.
• Thyroid eye disease
• Lacrimal infiltrative disease (amyloidosis, sarcoidosis, lymphoma)
• Other causes of ocular irritation (blepharitis, eyelid malposition, trichiasis)
• Hypovitaminosis A
• Other causes of dry mouth (e.g., mouth-breathing, radiation-induced xerostomia)
• Artificial tears (preservative-free if used more than 4x/day)
• Topical cyclosporine 0.05–1% 1 drop OU 2x/day (2)[A]
• Cyclosporine drops often burn on instillation; this usually improves with continued use.
• 10% N-acetylcysteine 1 drop 4x/day for filamentary keratitis.
• Topical steroids (monitor for intraocular pressure elevation and cataract formation)
• Topical autologous serum drops
• Systemic immunomodulatory therapy including oral steroids, hydroxychloroquine, azathioprine, cyclophosphamide, methotrexate, and IV rituximab are used for systemic disease. Usually managed in consultation with a rheumatologist.
• Muscarinic agonists (pilocarpine PO 5 mg 3–4x/day or cevimeline 30mg PO 3x/day)
Avoid prescribing medications with anti-cholinergic side effects that can exacerbate sicca symptoms.