What are the different types of autoimmune vasculitis?

Types of Autoimmune Vasculitis

Autoimmune vasculitis is classified primarily by vessel size into large, medium, and small vessel vasculitis, with ANCA-associated vasculitis (AAV) representing the most clinically significant small vessel category, comprising granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). 1, 2, 3

Classification by Vessel Size

Large Vessel Vasculitis

• Giant cell arteritis (GCA) affects the aorta and its major branches, typically occurring in patients over 50 years old 3
• Takayasu arteritis (TAK) similarly affects large vessels and the aorta 3

Medium Vessel Vasculitis

• Polyarteritis nodosa (PAN) affects main visceral arteries and their initial branches 3, 4
• Can present with necrotizing inflammation of small and medium-sized arteries 4

Small Vessel Vasculitis (ANCA-Associated)

The three primary ANCA-associated vasculitides are distinguished by their pathologic features, ANCA serotype, and clinical presentation:

Granulomatosis with Polyangiitis (GPA, formerly Wegener's granulomatosis)

• Characterized by necrotizing granulomatous inflammation plus vasculitis affecting small to medium vessels 1, 2
• 80-90% are PR3-ANCA positive with cytoplasmic ANCA (C-ANCA) pattern 1, 2
• Commonly presents with upper and lower respiratory tract involvement, with persistent bleeding, crusting, nasal obstruction, and potential septal perforation 1

Microscopic Polyangiitis (MPA)

• Characterized by vasculitis without granulomatous inflammation, affecting small vessels 1, 2
• Most commonly MPO-ANCA positive with perinuclear ANCA (P-ANCA) pattern, though 20-40% can be PR3-ANCA positive 1, 2
• Frequently presents with pauci-immune focal and segmental necrotizing crescentic glomerulonephritis 1

Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly Churg-Strauss syndrome)

• Characterized by eosinophilic tissue infiltration plus vasculitis affecting small to medium vessels 2, 3
• Only 40% are ANCA-positive (35% PR3-ANCA, 35% MPO-ANCA), making it distinct from GPA and MPA 1, 2
• Typically develops in patients with adult-onset asthma and chronic rhinosinusitis with eosinophilic nasal polyps 1
• Often includes middle ear disease 1

Small Vessel Vasculitis (Immune Complex-Mediated)

• Cryoglobulinemic vasculitis (often associated with hepatitis C virus infection) 1, 3
• IgA vasculitis (Henoch-Schönlein purpura) characterized by IgA immune complex deposition 3, 5

Key Diagnostic Features

ANCA Testing

• High-quality antigen-specific immunoassays for MPO-ANCA and PR3-ANCA are the preferred screening method, with approximately 90% of patients with small-vessel vasculitis having detectable ANCA 2
• PR3-directed c-ANCA is present in 80-90% of GPA cases 1
• MPO-directed p-ANCA is found in 35% of EGPA cases 1

Histopathologic Confirmation

• Biopsy showing necrotizing vasculitis, granulomatous inflammation, or pauci-immune glomerulonephritis is the gold standard for diagnosis 2
• Pauci-immune vasculitis is characterized by little or no deposition of immune complexes in the vessel wall 1

Critical Diagnostic Pitfalls to Avoid

• Do not delay treatment in ANCA-positive patients with compatible clinical presentation while awaiting biopsy, particularly in rapidly deteriorating patients with pulmonary-renal syndrome 1, 2
• Do not use ANCA subtype alone for classification, as up to 30% of MPA patients are PR3-ANCA positive without typical GPA features 2
• Do not overlook drug-induced vasculitis: cocaine and levamisole (a common cocaine adulterant) can cause ANCA-positive vasculitis 1
• Recognize that nasal biopsies in GPA often lack specific diagnostic features, and biopsies from other involved organs may be required 1
• Remember that ANCA can be negative in localized GPA, especially when disease is limited to the sinonasal tract 1