What is Sjögren's (Sicca) syndrome?

What is Sicca Syndrome (Sjögren's Syndrome)?

Sicca syndrome, also known as Sjögren's syndrome, is a chronic systemic autoimmune disease characterized by lymphocytic infiltration and destruction of exocrine glands—primarily the lacrimal and salivary glands—resulting in severe dryness of the eyes (keratoconjunctivitis sicca) and mouth (xerostomia), with potential multiorgan involvement and approximately 5% risk of lymphoma development. 1, 2

Core Pathophysiology

The fundamental disease mechanism involves chronic inflammatory cellular infiltration of exocrine glands by lymphocytes, particularly T cells and B cells, leading to progressive glandular dysfunction 1, 3. This autoimmune process is triggered by the interplay of genetic susceptibility, environmental factors (particularly viral infections like Epstein-Barr virus, hepatitis C, and HTLV-1), and hormonal influences 3. The histological hallmark is focal lymphocytic sialadenitis with a focus score ≥1 foci/4 mm² on minor salivary gland biopsy 1, 3.

Clinical Presentation

Primary Sicca Symptoms

• Dry eyes (xerophthalmia): Sensation of foreign body, irritation, itching, pain, light sensitivity, and frequent need for eye drops 1
• Dry mouth (xerostomia): Need for liquids to swallow dry foods, frequent water sipping, burning sensation in mouth, angular cheilitis, frequent dental cavities, and gingivitis 1

Systemic Manifestations Beyond Dryness

• Musculoskeletal: Joint pain (arthralgias) and muscle pain (myalgias) 1
• Mucocutaneous: Vaginal dryness causing painful intercourse, dry skin with itchiness or flaking 1
• Neurological: Peripheral neuropathy with numbness, altered sensation, or burning pain in extremities 1
• Constitutional: Extreme fatigue 1
• Pulmonary: Dry nonproductive cough (xerotrachea) affecting 38% of patients, small airway disease, and interstitial lung disease 1

Epidemiology and Classification

• Prevalence: Affects approximately 0.4% of the general population with an annual incidence of 3.9-5.3 per 100,000 people 1
• Gender distribution: Overwhelming female predominance with a 20:1 female-to-male ratio 1, 3
• Primary Sjögren's syndrome: Occurs alone as a distinct entity 1
• Secondary Sjögren's syndrome: Occurs in association with other autoimmune diseases such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus 1, 2

Diagnostic Criteria (2016 ACR/EULAR Classification)

The diagnosis is based on a weighted scoring system where a total score of ≥4 meets criteria for primary Sjögren's syndrome 1:

• Anti-SSA/Ro antibody positivity: 3 points 1
• Focal lymphocytic sialadenitis with focus score ≥1 foci/4 mm²: 3 points 1
• Abnormal ocular staining score ≥5 or van Bijsterveld score ≥4: 1 point 1
• Schirmer test result ≤5 mm/5 minutes without anesthesia: 1 point 1
• Unstimulated salivary flow rate ≤0.1 ml/minute: 1 point 1

Critical Complications and Prognosis

Lymphoma Risk

• Approximately 5% of patients develop lymphoma, making primary Sjögren's syndrome the rheumatic disease most strongly associated with lymphoid malignancy 1, 4
• Decreased C4 levels at diagnosis are associated with higher lymphoma risk and warrant increased surveillance 1, 4

Other Serious Complications

• Potentially life-threatening vasculitic disorders 5
• Ocular complications including scleritis, sterile keratitis, and uveitis 1
• Progressive pulmonary involvement with interstitial lung disease (10% within first year, 20% after 5 years) 1

Distinction from Checkpoint Inhibitor-Induced Sicca Syndrome

An important clinical caveat: Checkpoint inhibitor (CPI)-induced sicca syndrome is distinct from classical Sjögren's syndrome 5. CPI-associated sicca syndrome predominantly affects men, presents mainly with dry mouth (often without dry eyes), has lower prevalence of autoantibodies (52% ANA, 20% Ro/SS-A versus higher rates in classical Sjögren's), and shows a predominant T-cell infiltrate with acinar destruction rather than the typical histological profile of idiopathic primary Sjögren's syndrome 5. This distinction is critical when evaluating patients on cancer immunotherapy 5.

Management Principles

First-line treatment for dryness should be symptomatic relief using topical therapies including artificial tears and ointments for dry eyes and saliva substitutes for dry mouth 5, 1. For mild systemic manifestations, antimalarials such as hydroxychloroquine and NSAIDs for joint pain should be considered 1. For severe, refractory systemic disease, sequential use of glucocorticoids, immunosuppressive agents, and biologics (particularly B-cell targeted therapies) may be necessary 5, 1.

Co-management with a rheumatologist is essential due to potential systemic complications, lymphoma risk, and need for immunosuppressive therapy monitoring 1, 4. Approximately 10% of patients with clinically significant dry eye have underlying Sjögren's syndrome, warranting a low threshold for serological workup when dry eye presents with systemic symptoms 1, 3.