IGG-4 RELATED DISEASE
WHAT?
• A chronic, immune-mediated fibroinflammatory disease with tumefactive infiltration of IgG4+ plasma cells and lymphocytes.
• Characterized by:
- Storiform fibrosis
- Organ inflammation
- Organ enlargement
- Organ dysfunction
PATHOPHYSIOLOGY
• Immune basis: Th2 & Treg cell-mediated
• Key Features:
- Tumefactive lesions
- IgG4+ plasma cell infiltration
- Storiform fibrosis
- Obliterative phlebitis
- Chronic inflammation -> progressive organ dysfunction
• Serum IgG4 elevated in ~70% (not specific)
COMMON CLINICAL PRESENTATIONS (BY ORGAN)
• Pancreas: Type 1 AIP (Autoimmune Pancreatitis), mass effect, painless jaundice; mass: "sausage shaped" pancreas
• Biliary Tract: IgG4-Sclerosing Cholangitis - mimics PSC; often with AIP
• Salivary/Lacrimal Glands: Mikulicz disease (bilateral swelling), Küttner tumor (Submandibular glands), dacryoadenitis
• Orbit: Dacryoadenitis, orbital pseudotumor, proptosis
• Retroperitoneum: Retroperitoneal fibrosis (Ormond disease); may obstruct ureters
• Aorta: Inflammatory aortitis, mimics vasculitis
• Kidneys: Tubulointerstitial nephritis (TIN), membranous nephropathy, proteinuria
• Lungs: Nodules, interstitial changes
• Hypertrophic pachymeningitis: Dura mater (intracranial/meninges)
• Lymphocytic hypophysitis: Pituitary gland
• Others: Thyroid (Riedel's), CNS, prostate, breast, skin
DIAGNOSIS
• Essential Criteria: Clinical/radiologic evidence of mass or organ enlargement
• Histopathology:
- Dense lymphoplasmacytic infiltrate
- 30-50 IgG4+ plasma cells/HPF
- Storiform fibrosis
- Obliterative phlebitis
• Exclusion of Mimics: Infectious, malignant, or other autoimmune diseases
• Supportive Labs:
- ↑ Serum IgG4 (~66%) - not specific
- ↑ IgE, ↓ complement
• Classification: 2019 ACR/EULAR Criteria (>= 20 points): stepwise approach with mimics excluded
MANAGEMENT
• First-Line:
- Prednisone: 0.6 mg/kg/day, tapered over 2 months
• Refractory or Steroid-Dependent:
- Rituximab: 1 g IV x2 doses, 2 weeks apart
- Inebilizumab: 300 mg IV x2 doses
• Other options:
- Azathioprine: 2 mg/kg/day
- Mycophenolate mofetil: 2-2.5 g/day
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