Sjögren Syndrome, Scleroderma, Polyarteritis Nodosa

1. Sjögren’s syndrome

Immune-mediated destruction of the lacrimal and salivary glands → dry eyes (keratoconjunctivitis sicca) + dry mouth (xerostomia).

• Forms: primary (isolated “sicca syndrome”) or secondary (with SLE/RA).
• Pathogenesis: CD4⁺ T cells against ductal epithelial antigens + systemic B-cell hyperreactivity; autoantibodies anti-SSA/Ro and anti-SSB/La (against ribonucleoprotein); certain MHC-II alleles predispose.
• Morphology: intense lymphocytic + plasma-cell infiltration of glands (may form germinal centers) → gland destruction; extraglandular involvement (CNS, skin, kidney). Consequences: corneal drying/ulceration, oral mucosal atrophy/fissuring, nasal septal perforation, bronchitis/pneumonitis.
• Clinical: women 40–60 years; salivary gland enlargement; ~40× increased risk of (MALT/non-Hodgkin) lymphoma.

2. Systemic sclerosis (Scleroderma)

Intensive fibrosis of skin, GI tract, kidney, heart, lung, muscle. Two forms:

Diffuse	Limited (CREST)
Widespread skin, rapid, early GI/organ involvement	Skin of face/fingers only; later course
Anti-Scl-70 (topoisomerase I) → pulmonary fibrosis	Anti-centromere → benign course, pulmonary HTN

CREST = Calcinosis, Raynaud, Esophageal dysmotility, Sclerodactyly, Telangiectasia.

• Pathogenesis (3 interrelated): autoimmune response (CD4 T cells → TGF-β, IL-13, PDGF → collagen), vascular damage (endothelial injury → intimal fibrosis → ischemia), excess collagen deposition.
• Morphology: skin — sclerotic atrophy starting at fingers → claw hands, mask-like face; GI — esophageal fibrosis (“inflexible rubber tube”) → GERD/Barrett, malabsorption; lung — interstitial fibrosis + pulmonary HTN → cor pulmonale; kidney — vessel wall thickening, fibrinoid necrosis → renal crisis/failure (treat with ACE inhibitor); heart — myocardial fibrosis.
• Clinical: 50–60 years, female:male 3:1; Raynaud in nearly all (white→blue→red); dysphagia, dyspnea.

3. Polyarteritis nodosa (PAN)

Polyarteritis = many vessels; nodosa = segmental. Necrotizing inflammation of vessel walls (non-infectious necrotizing vasculitis), often immune-complex driven; ~30% HBV-associated (HBsAg complexes).

• Morphology: segmental transmural necrotizing inflammation of small–medium arteries (esp. branch points), spares the lungs. Acute: mixed infiltrate + fibrinoid necrosis + thrombosis → microaneurysms; chronic: fibrous wall thickening. Impaired perfusion → infarction, ulceration, ischemic atrophy, hemorrhage.
• Clinical: men >50 (any age); episodic with symptom-free intervals. Ischemia affects:
  • Renal → hypertension, oliguria, renal failure (most common cause of death).
  • GI → abdominal pain, malabsorption, melena.
  • Nerves → mononeuritis multiplex.
  • Skin → livedo reticularis, nodules, ulcers, gangrene.
  • Heart → coronary involvement.
• Diagnosis: biopsy / angiography (microaneurysms). Spares glomeruli (renal artery involvement, unlike SLE).

💡 High-yield: Sjögren = anti-SSA/SSB, dry eyes + mouth, ↑ lymphoma risk. Scleroderma = fibrosis + Raynaud; diffuse = anti-Scl-70, limited/CREST = anti-centromere; renal crisis → ACE inhibitor. PAN = medium-artery necrotizing vasculitis, spares lungs, HBV-linked, mononeuritis multiplex; spares glomeruli (vs SLE).