IgG4-related disease¶

Pathophysiology¶

• Exact aetiology unknown, likely autoimmune in nature
• Characterised by:
  • Lymphoplasmacytic infiltration with IgG4-positive plasma cells
  • Storiform fibrosis
  • Obliterative phlebitis
• Elevated serum IgG4 levels (>135 mg/dL) in 60-70% of patients
• T helper 2 (Th2) and regulatory T (Treg) cell responses play a crucial role

Demographics¶

• Predominantly affects middle-aged to elderly males
• Male to female ratio approximately 3:1
• Peak incidence in the sixth and seventh decades of life
• Increasing recognition worldwide, but true prevalence unknown

Diagnosis¶

• Comprehensive diagnostic criteria include:
  1. Characteristic clinical features
  2. Elevated serum IgG4 levels
  3. Histopathological findings
• Organ-specific diagnostic criteria exist for some manifestations (e.g., autoimmune pancreatitis)
• Differential diagnosis includes malignancy, other autoimmune conditions, and infection

• Tissue biopsy often required for definitive diagnosis

• Head, neck and CNS manifestations relevant to neuroradiology:

  • Hypertrophic pachymeningitis: focal or diffuse dural thickening and enhancement, T2-hypointense (fibrosis)
  • Hypophysitis: thickened, enhancing pituitary stalk and gland, often with diabetes insipidus
  • Orbital disease: enlarged lacrimal glands, infraorbital nerve and extraocular muscles; orbital "pseudotumour"
  • Bilateral symmetrical salivary and lacrimal gland enlargement (Mikulicz disease); perineural spread along the trigeminal branches
• Systemic clues: "sausage-shaped" pancreas (autoimmune pancreatitis), biliary strictures and periaortic "coated aorta"

Treatment¶

• Corticosteroids first-line, with rituximab for relapsing or refractory disease; usually steroid-responsive