Sjögren Syndrome

A 38 year old female presents to her primary care physician with complaints of dry eyes and dry mouth for the past 6 months. She reports burning, itching, and a gritty sensation in both eyes and uses artificial tear drops frequently. She also has difficulty swallowing dry foods and needs to drink water frequently while eating. Examination reveals non-tender bilateral parotid gland enlargement. She has a history of rheumatoid arthritis diagnosed 2 years ago and is taking methotrexate once weekly with folinic acid. Vital signs are within normal limits. Serology shows positive ANA, rheumatoid factor, anti-SSA (Ro), and anti-SSB (La) antibodies. Schirmer test shows reduced tear production. Minor salivary gland biopsy demonstrates focal lymphocytic sialadenitis. Diagnosis?

Diagnosis is Secondary Sjögren syndrome.

1. Definition

Sjögren syndrome is a systemic autoimmune disease characterized by sicca symptoms, especially dry eyes and dry mouth, due to immune-mediated inflammation of the lacrimal and salivary glands. It may occur as primary or secondary disease.

2. Classification

1. Primary Sjögren syndrome occurs in isolation
2. Secondary Sjögren syndrome occurs with another autoimmune disease such as rheumatoid arthritis or systemic lupus erythematosus

3. Pathophysiology

1. Lymphocytic infiltration of exocrine glands
2. Characteristic lesion is focal lymphocytic sialadenitis
3. Leads to reduced tear and saliva production
4. B cell activation produces autoantibodies such as anti-SSA (Ro) and anti-SSB (La)
5. Chronic B cell activation increases risk of MALT lymphoma

4. Clinical Features

4.1 Glandular Features

1. Keratoconjunctivitis sicca causing dry, gritty eyes
2. Xerostomia causing dry mouth and difficulty swallowing
3. Parotid gland enlargement
4. Dental caries, tooth decay, and oral infections

4.2 Other Dryness

1. Vaginal dryness with dyspareunia
2. Dry skin
3. Dryness of the respiratory tract

4.3 Extraglandular Manifestations

1. Fatigue
2. Arthralgia or arthritis
3. Raynaud phenomenon
4. Cutaneous vasculitis
5. Interstitial lung disease
6. Renal involvement such as tubulointerstitial nephritis or renal tubular acidosis
7. Peripheral neuropathy or CNS involvement
8. Cryoglobulinemia and hypergammaglobulinemia

5. Diagnosis

5.1 Serology

1. ANA often positive but nonspecific
2. Rheumatoid factor may be positive
3. Anti-SSA (Ro) is the most diagnostically useful antibody
4. Anti-SSB (La) may also be present

5.2 Ocular Testing

1. Schirmer test ≤ 5 mm in 5 minutes indicates decreased tear production
2. Slit lamp examination with vital dye staining confirms keratoconjunctivitis sicca

5.3 Salivary Assessment

1. Unstimulated salivary flow ≤ 0.1 mL per minute is abnormal
2. Salivary gland ultrasonography is a useful noninvasive tool

5.4 Histopathology

1. Minor salivary gland biopsy is the most specific single test
2. Shows focal lymphocytic sialadenitis with focus score ≥ 1 per 4 mm²

6. Complications

1. Corneal damage and possible vision loss
2. Dental caries and tooth loss
3. Interstitial lung disease
4. Renal tubular acidosis
5. Peripheral neuropathy
6. Increased risk of B cell non-Hodgkin lymphoma, especially MALT lymphoma

7. Management

7.1 Dry Eyes

1. Preservative-free artificial tears
2. Nighttime lubricating gels or ointments
3. Topical cyclosporine or tacrolimus in selected cases
4. Punctal plugs for severe dryness

7.2 Dry Mouth

1. Frequent water intake
2. Sugar-free gum or lozenges
3. Saliva substitutes
4. Strict oral hygiene and regular dental care

7.3 Secretagogues

1. Pilocarpine
2. Cevimeline

7.4 Systemic Therapy

1. Not required for isolated sicca symptoms
2. Hydroxychloroquine, glucocorticoids, or immunosuppressive agents for extraglandular disease
3. Options include methotrexate, azathioprine, mycophenolate mofetil, or leflunomide
4. Rituximab may be used in severe cases

8. Key Clinical Insight

Dry eyes + dry mouth + parotid enlargement + anti-SSA positivity + focal lymphocytic sialadenitis = Sjögren syndrome

Association with rheumatoid arthritis confirms secondary Sjögren syndrome.

9. Exam Level Pearls

1. Anti-SSA (Ro) is the most useful antibody
2. Minor salivary gland biopsy is the most specific test
3. Schirmer test provides objective evidence of dry eyes
4. Up to 50 percent of patients develop extraglandular manifestations
5. Markedly increased risk of non-Hodgkin lymphoma
6. Persistent parotid enlargement, low C4, and cryoglobulinemia suggest higher lymphoma risk