Sjogren syndrome

Sjogren syndrome is a chronic inflammatory autoimmune disease that occurs mainly in middle-aged women. The cause of primary Sjogren syndrome is unknown, whereas secondary Sjogren syndrome is associated with underlying autoimmune diseases (e.g., rheumatoid arthritis). As the immune system mainly attacks lacrimal and salivary glands, patients typically present with xerophthalmia (dry eyes) and xerostomia (dry mouth), the combination of which is also known as sicca syndrome. The disease may also involve the skin, joints, internal organs, and nervous system. It is diagnosed via the detection of autoantibodies (anti-SSA/Ro, ANA) and salivary gland biopsy. Management focuses on supportive measures and, in more severe cases, immunosuppressants.

• Sex: : ♀ > ♂ (∼ 9:1) ^[1]
• Age of onset: : typically 40–60 years ^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Primary Sjogren syndrome: idiopathic (association with HLA-DR52) ^[2]
• Secondary Sjogren syndrome
  • Autoimmune connective tissue diseases: rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis
  • Primary biliary cirrhosis (PBC)
  • Association with viral infections: hepatitis C, HIV, EBV, human T-cell lymphotropic virus (HTLV)

Glandular symptoms ^[3]

• Inflammation of the salivary glands: decreased production of saliva → xerostomia (dry mouth)
  • Dysphagia
  • Increased formation of dental caries and tendency to oral infections
  • Parotid gland enlargement, often bilateral
  • Tongue fissures
• Inflammation of the lacrimal glands (chronic dacryoadenitis): decreased secretion of tears → xerophthalmia (dry eyes) → keratoconjunctivitis sicca
  • Redness, itching, burning of eyes
  • Sensation of sand or foreign body in the eyes
  • Blurred vision
• Sicca syndrome: : combination of dry mouth and dry eyes
• Nasal dryness: leads to chronic rhinitis, nosebleeds
• Pharyngeal, tracheal, and bronchial dryness: persistent, dry cough
• Vaginal dryness: dyspareunia and increased risk of infections

Extraglandular symptoms ^[4][5]

• General symptoms: : fatigue and arthralgias (∼ 70% of cases)
• Skin manifestations: xerosis ; Raynaud phenomenon (∼ 15–30% of cases)
• Vasculitis (∼ 10% of cases)
  • Palpable purpura of the legs
  • Recurrent urticaria, skin ulcerations
  • Glomerulonephritis
• Neurological and psychiatric manifestations
  • Depression
  • Variety of focal and/or diffuse findings (e.g., impaired gross motor control, paresis, seizures, peripheral neuropathy)
• Pulmonary manifestation: interstitial lung disease
• Gastrointestinal manifestations: e.g., dyspepsia, reflux esophagitis

The classical presentation is a middle-aged woman with dry eyes and a dry mouth, accompanied by rheumatoid arthritis or systemic lupus erythematosus

Sjogren syndrome is diagnosed based on the typical clinical features and is confirmed via detection of specific antibodies and a pathologically low tear production. Biopsy of the salivary gland is the most accurate test, but is not needed to establish the diagnosis.

Laboratory tests ^[6]

• Blood tests
  • Nonspecific findings: ↑ ESR, normocytic anemia, leukopenia, eosinophilia, hypergammaglobulinemia
  • Immunological findings (for additional information, see antibody diagnosis of autoimmune diseases)
    • Anti-Ro/SSA antibody and anti-La/SSB antibody ; (∼ 70% of cases): target ribonucleoprotein antigens (Ro/La) of epithelial cells, especially of the salivary glands
    • Antinuclear antibodies (ANAs; positive in up to 97% of cases)
    • Rheumatoid factor (RF)
• Urinalysis: possible signs of glomerulonephritis or interstitial nephritis (e.g., proteinuria, red cell casts)

Eye examination

• Schirmer test: : shows decreased tear production
• Slit lamp examination
  • Rose Bengal stain : shows damaged epithelium of the cornea and conjunctiva
  • Reduced tear break-up time

Biopsy

• Method: usually taken from the labial salivary glands
• Findings
  • Destruction of minor salivary glands (fibrosis, parenchymal atrophy)
  • Sialadenitis with dense focal lymphocytic infiltrations

Ultrasound of the parotid gland

• Findings
  • Honeycomb or cloud-like structure of the glandular parenchyma
  • Alternating hypoechoic areas and band-like hyperechoic septa and cysts

• Secondary Sjogren syndrome: treat the underlying disease
• For dry mouth
  • Regular dental care
  • Adequate hydration and foods that stimulate salivary flow (e.g., dried fruit slices)
  • In moderate/severe disease: artificial saliva; , muscarinic agonists; , and immunosuppression (e.g., hydroxychloroquine)
• For dry eyes
  • Avoid dry environments (e.g., shield eyes from wind, keep air humid)
  • Artificial tears
  • In moderate disease: topical immunosuppression (e.g., cyclosporine); , lubricants
• Treatment of extraglandular disease: depends on the specific manifestation
  • Arthralgia may be managed with NSAIDs or hydroxychloroquine.
  • Neurological manifestations may require aggressive immunosuppression.

• Risk of developing associated conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis)
• Corneal scarring, ulcer, rupture, and infection
• B-cell lymphomas, such as MALT lymphoma (may manifest with parotid swelling)
• Renal tubular acidosis type 1 ^[7]
• Pregnancy: fetal loss, infant with neonatal lupus syndrome and associated complete heart block

Individuals with Sjogren syndrome have an increased risk of developing MALT lymphoma.

References:^[1]

We list the most important complications. The selection is not exhaustive.