Sjögren Syndrome
BASICS
- Definition:
- Chronic autoimmune disorder, lymphocytic infiltration of exocrine glands (especially lacrimal/salivary), causing decreased gland function.
- Presents with sicca symptoms: dry eyes (xerophthalmia), dry mouth (xerostomia), parotid enlargement
- Extraglandular manifestations: arthralgia, myalgia, Raynaud, pulmonary/GI disease, cytopenias, lymphadenopathy, vasculitis, renal tubular acidosis, lymphoma, CNS & PNS involvement
- Variants:
- Primary: Not associated with other disease (HLA-DRB10301, 1501)
- Secondary: With another autoimmune disorder (RA most common, also SLE, scleroderma)
EPIDEMIOLOGY
- Annual incidence: ~4/100,000
- Female:Male = 9:1
- Onset: 4th–5th decade
- US prevalence: 1–4 million
ETIOLOGY & PATHOPHYSIOLOGY
- Unknown etiology; viral trigger (EBV, HCV, HTLV-1) suspected in genetically predisposed
- Pathology: CD4+ T-cell infiltration → cytokine production → B-cell dysregulation → autoantibody production, chronic inflammation, increased B-cell malignancy
- Genetics: Familial tendency, HLA-DR associations
RISK FACTORS
- No known modifiable risk factors
PREVENTION
- No prevention; early diagnosis/treatment prevents complications
- Oral health providers are key in early detection/management
COMMONLY ASSOCIATED CONDITIONS
- Secondary SS: RA, SLE, scleroderma, MCTD, PBC, autoimmune thyroiditis, polymyositis, hepatitis C, HIV, vasculitis, cryoglobulinemia, chronic active hepatitis
DIAGNOSIS
2016 ACR/EULAR Criteria (≥4 points from below + symptoms):
- +Serum anti-SSA/Ro Ab: 3 points
- Labial salivary gland biopsy with focus score ≥1 foci/4 mm²: 3 points
- Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4: 1 point
- Schirmer test ≤5 mm/5 min: 1 point
- Unstimulated salivary flow rate ≤0.1 mL/min: 1 point
Exclusion: Prior head/neck radiation, active hepatitis C (PCR+), AIDS, sarcoidosis, amyloidosis, GVHD
HISTORY
- Ocular: dry, burning, scratchy eyes, sandy/gritty sensation, frequent use of artificial tears
- Oral: dry mouth, difficulty swallowing, dental caries, tongue sticking to depressor, parotid swelling
- Systemic: arthralgias, myalgias, fatigue, Raynaud, vasculitis, pulmonary/GI/renal/CNS involvement
- Gynecologic: vaginal dryness, dyspareunia
PHYSICAL EXAM
- Eyes: decreased tear pool, keratoconjunctivitis sicca, filamentary keratosis
- Mouth: dry mucosa, reduced saliva, caries (incisor/cervical), dark red tongue
- Glands: parotid/submandibular enlargement
- Skin: vasculitic purpura
DIFFERENTIAL DIAGNOSIS
- Dry eyes: hypovitaminosis A, age, blepharitis, Parkinson, Bell’s palsy, gland infiltration (lymphoma, sarcoid), low estrogen
- Dry mouth: meds (anticholinergics, antihistamines, antidepressants), dehydration, anxiety, sialadenitis, hepatitis C/HIV, head/neck radiation
- Salivary swelling: obstruction, infection, neoplasm, IgG4 disease, alcoholism, cirrhosis, DM, anorexia, viral infection
DIAGNOSTIC TESTS
- Schirmer test (<5 mm/5 min = abnormal)
- Rose Bengal test: ocular staining/TBUT
- Minor salivary gland biopsy: gold standard
- Autoantibodies: ANA+ (95%), RF+ (75%), anti-SSA (56%), anti-SSB (30%)
- Imaging: salivary scintigraphy, parotid sialography (not in acute), MRI, salivary US (nonhomogeneity = most useful)
- Labs: CBC, ESR, CRP, urinalysis, ANA, RF, anti-Ro/SSA, anti-La/SSB
TREATMENT
Goals
- Symptom relief, improved QOL, manage systemic disease
General
- Avoid meds worsening dryness (anticholinergics, antidepressants)
- Oral hygiene, dental care, fatigue management
Dry Mouth (Xerostomia)
- Nonpharmacologic: gustatory/mechanical stimulants (sugar-free, xylitol gum/lozenges), fluoride mouthwashes, artificial saliva
- Pharmacologic: cevimeline (Evoxac), pilocarpine (Salagen)
- Not recommended: routine immunosuppressives, HCQ, oral glucocorticoids, rituximab
Dry Eyes (Keratoconjunctivitis Sicca)
- Nonpharmacologic: preservative-free artificial tears, gels/ointments (night), humidifiers
- If severe/unresponsive: topical NSAIDs, corticosteroids, cyclosporine (ophthalmology guidance)
MSK Pain
- Inflammatory: HCQ 1st line
- Acute pain: short course acetaminophen/NSAID (<7–10 days)
- If refractory: MTX, short-term corticosteroids, cyclosporine (if severe)
Other
- Gynecologic dryness: lubricants, moisturizers; vaginal estrogen if refractory
- Fatigue: exercise; DHEA not effective above placebo
- Severe extraglandular: cyclophosphamide, mycophenolate, azathioprine
Procedures
- Punctal plugs: if refractory dry eyes
- Surgery: rare, for extraglandular severe complications
REFERRALS
- Rheumatology: systemic/complex disease
- Ophthalmology: severe ocular symptoms
- Dental: annual exam + 2x cleanings/year
COMPLEMENTARY & ALTERNATIVE
- Acupuncture may help xerostomia
ONGOING CARE
- Monitor for systemic complications, lymphoma, parotid tumor
- Adjust frequency based on severity
DIET
- Reduce sugar, avoid non-water drinks between meals, nothing but water 1 hour before bed
PATIENT EDUCATION
- Most symptoms managed with nonpharmacologic measures (water intake, humidifier, gum, artificial tears, dental care)
- Smoking cessation
PROGNOSIS
- Extraglandular involvement = ↓QOL, ↑mortality
- Primary SS: ↑ risk lymphoma, thyroid cancer
COMPLICATIONS
- Dental caries, gum disease, dysphagia, sialolithiasis, keratitis, conjunctivitis, ocular surface scarring
ICD-10
- M35.01: Sjögren syndrome w/ keratoconjunctivitis
- M35.03: Sjögren syndrome w/ myopathy
- M35.00: Sjögren syndrome, unspecified
CLINICAL PEARLS
- Many symptoms can be treated with artificial tears, sugar-free lozenges, lifestyle mods.
- Coordinate care: rheumatology, ophthalmology, dentistry.
- Suspect in unexplained lung disease + ANA+.
- ↑ risk of lymphoma, celiac disease.