Organ System Manifestations of Sjögren's Syndrome
Sjögren's syndrome is a systemic autoimmune disease that affects multiple organ systems beyond the classic sicca symptoms, with up to 80% of patients experiencing extraglandular manifestations that can significantly impact morbidity, mortality, and quality of life. 1
Glandular Manifestations
Ocular Involvement
- Dry eyes (keratoconjunctivitis sicca) - primary manifestation
- Symptoms: irritation, itching, pain, foreign body sensation, light sensitivity, blurry vision 1
- Signs: reduced tear film stability, abnormal ocular staining score, reduced tear production on Schirmer test
- Inflammatory ocular conditions: scleritis, sterile keratitis, uveitis 1
Oral Involvement
- Dry mouth (xerostomia) - primary manifestation
- Symptoms: need for liquids to swallow dry foods, frequent sipping of water, burning sensation 1
- Signs: reduced salivary flow rates (unstimulated ≤0.1 ml/minute)
- Oral complications: dental caries, oral candidiasis, gum inflammation 1
- Salivary gland enlargement: parotid and submandibular glands
Systemic Manifestations
Musculoskeletal System
- Arthralgia/arthritis (non-erosive)
- Myalgia
- Myositis (less common)
Cutaneous Manifestations
- Dry skin (xerosis)
- Vasculitic lesions
- Raynaud's phenomenon
- Annular erythema
- Diffuse vasculitis with ulcers (potentially life-threatening) 2
Respiratory System
- Xerotrachea (dry cough)
- Interstitial lung disease (10-20% of patients) 1
- Non-specific interstitial pneumonia
- Usual interstitial pneumonia
- Lymphoid interstitial pneumonitis
- Organizing pneumonitis
- Bronchiectasis
- Severe ILD with NYHA class III/IV (potentially life-threatening) 2
Renal Manifestations
- Tubulointerstitial nephritis
- Renal tubular acidosis
- Glomerulonephritis
- Rapidly progressive glomerulonephritis (potentially life-threatening) 2
Neurological Involvement
Peripheral nervous system:
Central nervous system:
Gastrointestinal System
- Dysphagia (reported in up to 80% of patients) 2
- Esophageal dysmotility
- Atrophic gastritis
- Pancreatitis
- Liver involvement (primary biliary cholangitis)
Hematological Manifestations
- Anemia
- Leukopenia
- Thrombocytopenia
- Severe cytopenias (potentially life-threatening) 2
- Lymphadenopathy
Cardiovascular System
- Pericarditis
- Raynaud's phenomenon
- Autonomic dysfunction
Endocrine System
- Autoimmune thyroid disease (frequently co-occurring)
- Hypergammaglobulinemic purpura
Reproductive System
- Vaginal dryness
- Dyspareunia
- Pregnancy complications:
- Congenital heart block in babies of anti-Ro positive mothers (requires monitoring with fetal echocardiography between 16-26 weeks) 1
Lymphoproliferative Disorders
- Increased risk of non-Hodgkin lymphoma (2-5% of patients) 2
- Risk factors: decreased C4 levels, cryoglobulinemia, persistent salivary gland enlargement 1
Laboratory Abnormalities
- Anti-SSA/Ro antibodies (most specific)
- Anti-SSB/La antibodies
- Antinuclear antibodies (most frequent)
- Rheumatoid factor
- Hypergammaglobulinemia
- Hypocomplementemia (prognostic marker)
- Cryoglobulinemia (prognostic marker)
Clinical Pearls and Pitfalls
- Important pitfall: Sjögren's syndrome may present with systemic manifestations before the onset of sicca symptoms ("occult" Sjögren's) 4
- Key consideration: Regular monitoring for lymphoma development is essential, particularly in patients with decreased C4 levels 1
- Diagnostic challenge: Extra-glandular manifestations can mimic other autoimmune diseases, requiring comprehensive evaluation 3
- Treatment consideration: Systemic immunomodulatory/immunosuppressive therapies should be restricted to patients with active systemic disease after careful organ-by-organ evaluation 2
Understanding the multi-system nature of Sjögren's syndrome is crucial for early diagnosis and appropriate management to prevent complications and improve quality of life.