Sjogren syndrome

**Pathophysiology:** Autoimmune lymphocytic infiltration (mainly CD4+ T cells, plus B cells and plasma cells) of exocrine glands causes gland destruction and fibrosis. It is a type IV hypersensitivity process with a prominent autoantibody component. Primary Sjögren is isolated. Secondary Sjögren occurs with another autoimmune disease, most often rheumatoid arthritis, and also with SLE or systemic sclerosis.

**Epidemiology:** Women are affected about 9:1, usually ages 40–60. There are HLA associations (HLA-DR3, HLA-DRw52).

**Clinical features:** - Classic triad: dry eyes (keratoconjunctivitis sicca: burning, gritty sensation, corneal damage), dry mouth (xerostomia: dysphagia, dental caries, difficulty with dry foods, oral candidiasis), and arthritis (non-erosive). - Bilateral parotid (or other salivary) gland enlargement. - Mnemonic: "Can't see, can't spit, can't pee, can't climb a tree" (dry eyes, dry mouth, dry vagina/urethra, arthritis). - Extraglandular features: - Raynaud phenomenon. - Interstitial lung disease. - Interstitial nephritis, causing distal (type 1) renal tubular acidosis. - Palpable purpura/vasculitis. - Peripheral neuropathy. - Autoimmune thyroiditis. - Neonatal lupus with congenital heart block can occur in infants of anti-Ro-positive mothers.

**Diagnosis:** - Autoantibodies: anti-SSA (anti-Ro) and anti-SSB (anti-La). ANA is often positive, and rheumatoid factor is positive in many patients (even without RA). Polyclonal hypergammaglobulinemia is common. - Schirmer test shows decreased tear production (<5 mm in 5 min). Rose bengal or lissamine green staining shows corneal damage. - Minor salivary gland (lip) biopsy shows focal lymphocytic sialadenitis. This is the key confirmatory test. - Anti-SSA/SSB are not specific; they are also found in SLE.

**Complications:** - Increased risk of non-Hodgkin B-cell lymphoma, especially marginal zone (MALT) lymphoma of the parotid. Suspect it with persistent or enlarging parotid swelling, new lymphadenopathy, or falling complement/cryoglobulinemia. - Dental caries and oral candidiasis. - Corneal ulceration.

**Treatment:** - Symptomatic: artificial tears, sialogogues (pilocarpine or cevimeline, both muscarinic agonists), good oral hygiene, and sugar-free gum. - Systemic disease may need hydroxychloroquine or other immunosuppressants.

**Differential for parotid enlargement and dry mouth:** - Sarcoidosis (Mikulicz/Heerfordt syndrome). - IgG4-related disease. - Mumps. - HIV (diffuse infiltrative lymphocytosis syndrome). - Bulimia. - Anticholinergic drugs.

**High-yield pearls:** - Sjögren is one of the classic associations with anti-Ro/La antibodies. - Think of it in a middle-aged woman with dry eyes, dry mouth, and parotid enlargement. - Biopsy shows lymphocytic infiltrate of the glands. - The major long-term complication is lymphoma.