What is Sjögren syndrome and what are its common comorbidities?

Sjögren Syndrome: Definition and Key Comorbidities

What is Sjögren Syndrome?

Sjögren syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands, resulting in severe dryness of mucosal surfaces—primarily dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia)—with potential for significant systemic organ involvement and increased mortality risk. 1

Core Pathophysiology

• The disease involves infiltration of exocrine glands with lymphocytes, leading to secondary compromise of gland function and systemic immune dysfunction 1
• Abnormal B cell and T cell responses to autoantigens Ro/SSA and La/SSB drive the destruction of glandular epithelium 2

Epidemiology

• Affects approximately 0.4% of the general population with an annual incidence of 3.9-5.3 per 100,000 people 1
• Women are disproportionately affected with a female-to-male ratio of 20:1 1
• Predominantly affects middle-aged women but can occur in children, men, and the elderly 2

Classification

• Primary Sjögren syndrome occurs as an independent disease entity 1
• Secondary Sjögren syndrome occurs in association with other autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma 1, 3

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Most Relevant Comorbidities

Lymphoproliferative Disorders (Highest Mortality Risk)

Approximately 5% of patients with Sjögren syndrome will develop lymphoma, making this the most critical comorbidity requiring vigilant monitoring. 1, 3

• Primary Sjögren syndrome is the rheumatic disease most strongly associated with lymphoid malignancy development, with a meta-analysis showing an incidence rate of 18.9% (95% CI, 9.4–37.9) 4
• Most commonly marginal zone B-cell lymphomas develop 5
• Decreased C4 complement levels at diagnosis are a key prognostic marker associated with higher lymphoma risk 1, 4, 3
• Regular monitoring for signs of lymphoma development is mandatory 1, 3

Pulmonary Manifestations

Respiratory involvement is common and progressive, affecting up to 38% of patients and requiring systematic evaluation. 1

Upper Airway Disease

• Chronic cough (>8 weeks duration) affects approximately 38% of patients 1
• Xerotrachea causing persistent dry cough is common 1
• Laryngopharyngeal reflux occurs frequently 1
• Vocal cord cystic lesions ("bamboo nodules") represent a rare but significant complication 1
• Obstructive sleep apnea is a potential complication 1

Progressive Lower Airway Disease

• Bronchiolitis (small airway disease) with neutrophilic, lymphocytic, or eosinophilic inflammation 1
• Bronchiectasis with chronic sputum production 1
• Reactive airway disease and obstructive lung disease 1

Interstitial Lung Disease (ILD)

• ILD prevalence increases over time: 10% within the first year, 20% after 5 years 1
• Presents with dyspnea ranging from minimal exertion-related to severe respiratory compromise 1
• Annual pulmonary function tests are recommended for patients with respiratory symptoms 1
• High-resolution CT chest with expiratory views is indicated when respiratory symptoms are present 1

Neurological Complications

Neurological involvement requires immediate co-management with neurology and can significantly impact morbidity. 1

• Peripheral neuropathy manifesting as numbness, altered sensation, or burning pain in extremities 1
• Myopathy with significant weakness limiting mobility or self-care requires immediate neurology consultation 1
• Central nervous system involvement can occur 2
• Pulse corticosteroids (methylprednisolone 1-2 mg/kg IV) should be used for acute severe neurological involvement 1

Other Autoimmune Diseases

• Thyroid dysfunction or autoimmune thyroiditis is commonly associated 3
• Primary biliary cholangitis occurs in 8% of cases, particularly in those positive for anti-centromere antibodies 3
• Screening for other autoimmune conditions is warranted 1, 3

Vasculitic Complications

• Cutaneous vasculitis presenting as palpable and nonpalpable purpura 6
• Systemic vasculitis can be life-threatening and requires aggressive immunosuppression 1
• Certain skin findings confer increased risk for multisystem vasculitis and non-Hodgkin lymphoma 6

Multisystem Organ Involvement

• Renal involvement including glomerulonephritis 7
• Hepatic involvement 2, 7
• Musculoskeletal manifestations including arthralgia and myalgia 1, 3
• Vaginal dryness causing painful intercourse 1
• Dry skin (xeroderma) causing itchiness or flaking 1, 6

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Critical Management Implications

Mandatory Co-Management

Co-management with a rheumatologist is essential—not optional—due to the numerous systemic complications and increased mortality risk. 1, 4, 3

Monitoring Requirements

• Regular screening for lymphoma development, particularly in patients with decreased C4 levels 1, 4, 3
• Annual pulmonary function tests for patients with respiratory symptoms 1
• Comprehensive evaluation for systemic manifestations including pulmonary, neurological, and renal involvement 1

Key Diagnostic Pitfall

• Unexplained chronic cough with dry eyes led to Sjögren diagnosis in 36% of previously undiagnosed patients—maintain high clinical suspicion 1
• About 10% of patients with clinically significant dry eye have underlying Sjögren syndrome 1

Impact on Quality of Life and Mortality

• Sjögren syndrome is a serious disease with excess mortality, mainly related to systemic involvement and lymphoma development 2
• The disease has a very substantial impact on patients' quality of life and daily activities 5
• Two types exist: a benign disease affecting quality of life, and a systemic syndrome with increased morbidity and mortality requiring close follow-up 7