What is Sjogren syndrome, particularly in middle-aged women?

What is Sjögren Syndrome

Sjögren syndrome is a chronic autoimmune disease characterized by lymphocytic infiltration and destruction of exocrine glands—particularly the salivary and lacrimal glands—resulting in severe dry mouth (xerostomia) and dry eyes (xerophthalmia), with a striking 20:1 female-to-male predominance affecting primarily middle-aged women. 1

Core Pathophysiology

• The fundamental mechanism involves chronic inflammatory cellular infiltration of exocrine glands by lymphocytes, leading to progressive glandular dysfunction and the characteristic sicca (dryness) symptoms 1, 2
• The disease is caused by the interplay of genetic susceptibility, environmental triggers (particularly viral infections like Epstein-Barr virus, hepatitis C, and HTLV-1), and hormonal factors 2
• Abnormal B cell and T cell responses to autoantigens Ro/SSA and La/SSB drive the destruction of glandular epithelium 3
• The histological hallmark is focal lymphocytic sialadenitis with a focus score ≥1 foci/4 mm² on minor salivary gland biopsy 1, 2

Epidemiology and Demographics

• Women are overwhelmingly affected with a 20:1 female-to-male ratio, strongly implicating hormonal influences 1, 2
• Annual incidence is approximately 3.9-5.3 per 100,000 people, with a prevalence of 92.8 cases per 100,000 1
• The disease affects approximately 0.4% of the general population 1
• Typical onset occurs in middle-aged and postmenopausal women, though the disease can occur in children, men, and the elderly 3, 4

Classification

• Primary Sjögren syndrome occurs alone as a distinct entity without other autoimmune diseases 1
• Secondary Sjögren syndrome occurs in association with other autoimmune diseases such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus 1, 5

Clinical Manifestations

Primary Sicca Symptoms

• Dry mouth (xerostomia) manifests as needing liquids to swallow dry foods, frequent water sipping, burning mouth sensation, angular cheilitis (painful sores at mouth corners), frequent dental cavities, and gingivitis 1
• Dry eyes (keratoconjunctivitis sicca) presents with foreign body sensation, eye irritation, itchiness, pain, light sensitivity, and frequent need for eye drops 1

Systemic Manifestations

• Joint pain (arthralgias) and muscle pain (myalgias) are common musculoskeletal symptoms 1
• Vaginal dryness causing painful intercourse and dry skin with itchiness or flaking affect mucous membranes 1
• Peripheral neuropathy causing numbness, altered sensation, or burning pain in extremities 1
• Extreme fatigue is a prominent constitutional symptom 1

Pulmonary Involvement

• Chronic cough (>8 weeks duration) affects approximately 38% of patients 1
• Dry, nonproductive cough (xerotrachea) and small airway disease can develop 1
• Bronchiolitis, bronchiectasis, and interstitial lung disease may occur, with ILD prevalence increasing to 10% within the first year and 20% after 5 years 1

Serious Complications

• Approximately 5% of patients develop lymphoma, representing a 320 cases per 100,000 patient-years increased incidence—the highest lymphoma risk among all rheumatic diseases 1, 6, 3
• Decreased C4 complement levels at diagnosis are associated with higher lymphoma risk 1, 6
• Other serious manifestations include scleritis, sterile keratitis, uveitis, and potentially life-threatening vasculitic or lymphoproliferative disorders 1

Diagnostic Criteria

• The latest classification criteria use a weighted scoring system where ≥4 points meets criteria for primary Sjögren syndrome 1
• Anti-SSA/Ro antibody positivity scores 3 points (most specific marker) 1, 2
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm² scores 3 points 1
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4 scores 1 point 1
• Schirmer test result ≤5 mm/5 minutes without anesthesia scores 1 point 1
• Unstimulated salivary flow rate ≤0.1 ml/minute scores 1 point 1

Management Approach

First-Line Symptomatic Treatment

• Artificial tears and lubricating ointments are primary therapy for dry eyes, with topical cyclosporine 0.05% for moderate to severe inflammatory dry eye 1
• Saliva substitutes provide first-line relief for xerostomia 1
• Pilocarpine 5 mg orally three to four times daily can be used if inadequate response to topical measures, though adverse effects include sweating (68% at 30 mg/day), nausea (15%), rhinitis (14%), and diarrhea (7%) 1, 7
• Cevimeline is an alternative cholinergic agent with similar efficacy 8, 9

Systemic Disease Management

• Hydroxychloroquine 200-400 mg daily may be considered for mild systemic manifestations such as joint pain, though evidence for dry eye improvement is weak 1
• NSAIDs can be used for joint pain and inflammation 1
• For severe, refractory systemic disease, B-cell targeted therapies may be considered, following sequential use of glucocorticoids, immunosuppressive agents, and biologics 1

Essential Co-Management

• Co-management with a rheumatologist is mandatory due to potential systemic complications, particularly the 5% lifetime lymphoma risk 1, 6
• Regular monitoring for signs of lymphoma development is essential, especially in patients with decreased C4 levels 1, 6
• Annual pulmonary function tests are recommended for patients with respiratory symptoms 1
• Neurology consultation is mandatory when neurological symptoms develop 1

Critical Clinical Considerations

• Approximately 10% of patients with clinically significant aqueous deficient dry eye have underlying primary Sjögren syndrome, warranting a low threshold for serological workup 1, 2
• Maintain high suspicion when dry eye occurs with systemic symptoms like fatigue, arthralgia, or recurrent parotid swelling 2
• The disease is associated with excess mortality, mainly related to systemic involvement and lymphoma development 3
• Despite its autoimmune nature, evidence for immunosuppressive agents remains limited for glandular manifestations 9