Extraglandular Manifestations of Sjögren's Syndrome
The extraglandular manifestations among the options listed are: (a) cutaneous purpuric vasculitis, (d) glomerulonephritis, and (e) interstitial nephritis. Xerostomia, xerophthalmia, and parotid gland enlargement are glandular manifestations, not extraglandular.
Understanding the Classification
Sjögren's syndrome manifestations are divided into two distinct categories based on the tissue involvement:
Glandular Manifestations (NOT extraglandular):
- Xerostomia (dry mouth) and xerophthalmia (dry eyes) result from lymphocytic infiltration of salivary and lacrimal glands 1
- Parotid gland enlargement represents direct exocrine gland involvement 2
- These are the defining features of the disease itself, not extraglandular complications
Extraglandular Manifestations (the correct answers):
The extraglandular features occur in 40-50% of patients and fall into two pathophysiologic categories 3, 4:
Category 1: Epithelial lymphocytic invasion
- Interstitial nephritis - results from lymphocytic infiltration of renal epithelial tissues 3, 4
- Lung involvement (interstitial pneumonitis)
- Liver involvement
Category 2: Immune complex-mediated disease
- Cutaneous purpuric vasculitis - leukocytoclastic or cryoglobulinemic vasculitis occurring in 5-10% of patients 5
- Glomerulonephritis - immune complex deposition in glomeruli 3
- Peripheral neuropathy
- These manifestations are associated with cryoglobulins, low C4 levels, and carry worse prognosis with higher lymphoma risk 3, 4
Clinical Significance
Patients with vasculitis, glomerulonephritis, palpable purpura, low C4 levels, and cryoglobulinemia represent a high-risk subset with increased morbidity, mortality, and lymphoma development risk (approximately 5% overall lymphoma risk) 3, 4. These patients require aggressive immunosuppression, typically glucocorticoids combined with synthetic immunosuppressives (cyclophosphamide, azathioprine, methotrexate) or rituximab for refractory cases 6, 5.
Key Pitfall to Avoid:
Do not confuse the primary sicca symptoms (xerostomia/xerophthalmia) and salivary gland enlargement as "extraglandular." These are the core glandular features that define the disease. The term "extraglandular" specifically refers to involvement of organs and tissues outside the exocrine glands 7, 4.