What is vasculitis?

Vasculitis: Definition and Classification

Vasculitis is an inflammatory process affecting blood vessel walls, leading to their compromise or destruction with subsequent hemorrhagic and ischemic events that can damage organs and tissues. 1 This inflammation can affect vessels of any size, type, and location, resulting in a broad spectrum of clinical syndromes.

Classification of Vasculitis

Vasculitis is primarily classified based on the size of the predominantly affected blood vessels:

Large Vessel Vasculitis

• Examples: Giant cell arteritis (GCA) and Takayasu arteritis
• Vessels affected: Aorta and its major branches
• Clinical features:
  • GCA affects older patients (>50 years), involving supra-aortic vessels
  • Takayasu arteritis affects young women (≤40 years), involving the aorta and main branches 1

Medium Vessel Vasculitis

• Examples: Polyarteritis nodosa (PAN) and Kawasaki disease
• Vessels affected: Main visceral arteries and their branches
• Clinical features:
  • PAN can be cutaneous (limited to skin) or systemic (affecting visceral vessels)
  • Kawasaki disease is self-limiting, acute, and often involves coronary arteries 1

Small Vessel Vasculitis

• Examples: ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis), IgA vasculitis (Henoch-Schönlein purpura)
• Vessels affected: Arterioles, capillaries, and venules
• Clinical features: Often presents as palpable purpura or infiltrated erythema 1, 2

Pathophysiology

The pathophysiology of vasculitis is largely autoimmune, though the exact mechanisms vary by type:

• ANCA-associated vasculitis: Antineutrophil cytoplasmic antibodies (ANCA) bind to and activate neutrophils, causing release of oxygen radicals, lytic enzymes, and inflammatory cytokines 2
• Immune complex-mediated: Deposition of immune complexes in vessel walls activates complement and attracts inflammatory cells
• Granulomatous inflammation: Characteristic of certain types like granulomatosis with polyangiitis
• Infectious triggers: Some forms may be triggered by infections (e.g., Staphylococcus aureus has been implicated in granulomatosis with polyangiitis) 2

Clinical Presentation

Vasculitis can present with:

1. Constitutional symptoms: Fever, fatigue, weight loss, myalgias
2. Organ-specific manifestations:
   • Skin: Palpable purpura, nodules, ulcers, livedo racemosa
   • Kidneys: Hematuria, proteinuria, rapidly declining renal function
   • Lungs: Cough, hemoptysis, pulmonary infiltrates, alveolar hemorrhage
   • Nervous system: Mononeuritis multiplex, peripheral neuropathy
   • Eyes: Scleritis, episcleritis, uveitis
   • ENT: Sinusitis, otitis, hearing loss, nasal crusting 2

Diagnosis

Diagnosis of vasculitis requires:

1. Clinical assessment: Detailed history and physical examination
2. Laboratory tests:
   • Complete blood count, inflammatory markers (ESR, CRP)
   • Autoantibodies (ANCA, anti-GBM)
   • Urinalysis and kidney function tests 2
3. Imaging:
   • CT/CTA, MRI/MRA for large and medium vessel vasculitis
   • FDG-PET/CT for assessment of disease activity 1
4. Biopsy: Essential for definitive diagnosis, especially in ANCA-negative cases
   • Skin biopsy should extend to subcutis from the most tender or purpuric lesion
   • Direct immunofluorescence helps distinguish IgA-associated from IgG/IgM-associated vasculitis 1, 3

Treatment Approach

Treatment depends on the type and severity of vasculitis:

1. Mild disease:

   • NSAIDs for symptomatic relief
   • Colchicine or dapsone for persistent/recurrent disease 1

2. Moderate to severe disease:

   • Systemic corticosteroids
   • Immunosuppressants (azathioprine, methotrexate, cyclophosphamide) 1, 4

3. Severe or life-threatening disease:

   • Combination of corticosteroids and cyclophosphamide or rituximab
   • Treatment divided into induction (3-6 months) and maintenance phases (18+ months) 2, 1

4. Refractory disease:

   • Plasma exchange
   • Intravenous immunoglobulin
   • Biologic therapies (rituximab, tocilizumab) 1, 3

Common Pitfalls in Diagnosis and Management

• Delayed diagnosis: Early diagnosis and treatment are essential for improving survival
• Underestimating systemic involvement: Cutaneous manifestations may be the first sign of systemic disease
• Misdiagnosis of vasculitis mimics: Thrombotic disorders can present with similar findings
• Failure to recognize ANCA-negative vasculitis: Approximately 10% of patients with clinical features of small-vessel vasculitis are ANCA-negative 1

Vasculitis represents a complex group of disorders requiring prompt recognition and appropriate management to prevent permanent organ damage and improve patient outcomes.