Description

An inflammatory disorder of blood vessels

• Clinical features result from the destruction of blood vessel walls with subsequent thrombosis, ischemia, bleeding, and/or aneurysm formation.
• Vasculitis is a heterogeneous group of diseases classified by the size, type, and location of involved blood vessels.
  • Small-vessel vasculitis
    • Microscopic polyangiitis (MPA)
    • Granulomatosis with polyangiitis (GPA; formerly Wegener granulomatosis)
    • Eosinophilic GPA (EGPA; formerly Churg-Strauss syndrome)
    • Antiglomerular basement membrane (anti-GBM) disease
    • Cryoglobulinemic vasculitis
    • IgA vasculitis (formerly Henoch-Schönlein purpura [HSP])
    • Hypocomplementemic urticarial vasculitis
  • Medium-vessel vasculitis
    • Polyarteritis nodosa (PAN)
    • Kawasaki disease (KD)
  • Large-vessel vasculitis
    • Takayasu arteritis (TAK)
    • Giant cell arteritis (GCA)
• Vasculitis occurs as a primary disorder or secondary to infection, a drug reaction, malignancy, or connective tissue disease.
  • Variable vessel vasculitis
    • Behçet disease
    • Cogan syndrome
  • Single-organ vasculitis
    • Cutaneous leukocytoclastic angiitis
    • Cutaneous arteritis
    • Primary CNS vasculitis
  • Vasculitis associated with systemic disease
    • Lupus vasculitis
    • Rheumatoid vasculitis
    • Sarcoid vasculitis
  • Vasculitis associated with other etiology
    • Hepatitis C–associated cryoglobulinemic vasculitis
    • Hepatitis B–associated vasculitis
    • Syphilis-associated aortitis
    • Drug-induced immune complex vasculitis
    • Drug-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis
    • Cancer-associated vasculitis
• Protean features often delay definitive diagnosis.

Epidemiology

Highly variable, depending on the particular syndrome

• Hypersensitivity vasculitis is most commonly encountered in clinical practice.
• KD, IgA vasculitis, and dermatomyositis are more common in children.
• TAK is most prevalent in young Asian women. GPA, MPA, and EGPA are more common in middle-aged males.
• GCA occurs exclusively in those >50 years of age and is rare in the African-American population.

Incidence
Annual incidence in adults (unless otherwise specified)

• IgA vasculitis: 200 to 700/1 million in children <17 years of age
• GCA: 100 to 170/1 million in Caucasians aged >50 years
• KD: depends on race/age; ~200/1 million
• PAN: 2 to 33/1 million
• GPA: 4 to 15/1 million
• MPA: 1 to 24/1 million
• EGPA: 1 to 3/1 million
• TAK: 2/1 million
• Primary CNS vasculitis: 2/1 million in adults
• Hypersensitivity vasculitis: depends on drug exposure
• Viral-/retroviral-associated vasculitis: unknown; >90% of cases of cryoglobulinemic vasculitis are associated with hepatitis C.
• Connective tissue disorder–associated vasculitis: variable

Etiology and Pathophysiology

• Three major immunopathogenic mechanisms
  • Immune-complex formation: systemic lupus erythematosus (SLE), IgA vasculitis (HSP), and cryoglobulinemic vasculitis
  • ANCA autoantibodies: GPA, MPA, and EGPA
  • Pathogenic T-lymphocyte response: GCA and TAK
• Pathophysiology best understood where known drug triggers have been identified (e.g., antibiotics, sulfonamides, and hydralazine)

Genetics

• Mutation in CECR1 encoding adenosine deaminase 2 is associated with PAN.
• Behçet syndrome is associated with HLA-B*51.
• IgA vasculitis is associated with HLA-DQA1*01:01, HLA-DQB1*05:01, and HLA-DRB1*01:01.

Risk Factors

A combination of genetic susceptibility and environmental exposure likely triggers onset.

General Prevention

Early identification is the key to prevent irreversible organ damage in severe forms of systemic vasculitis.

Commonly Associated Conditions

Hepatitis C (cryoglobulinemic vasculitis), hepatitis B (PAN), cytomegalovirus (CMV), Epstein-Barr virus (EBV), HIV (viral-/retroviral-associated vasculitis), SLE, rheumatoid arthritis (RA), Sjögren syndrome, mixed connective tissue disease (MCTD), dermatomyositis, ankylosing spondylitis, Behçet disease, relapsing polychondritis (CTD-associated vasculitis), respiratory tract methicillin-resistant Staphylococcus aureus (MRSA) in GPA, levamisole-adulterated cocaine; medications: propylthiouracil, methimazole, hydralazine, minocycline; SARS-CoV-2 infection