What are the causes of vasculitis?

Causes of Vasculitis

Vasculitis is primarily caused by inflammation of blood vessels that can be categorized as primary inflammatory processes or secondary processes due to underlying diseases, with the most common causes being autoimmune disorders, infections, and medications.

Classification Based on Vessel Size

• Large-vessel vasculitis affects the aorta and its first- and second-order branches, including:

  • Giant cell arteritis (Takayasu's disease) - typically affecting older patients (>50 years) 1
  • Behçet's syndrome 1
  • Relapsing polychondritis 1
  • Vasculitis associated with arthropathies 1

• Medium-vessel vasculitis involves main visceral arteries and their initial branches, including:

  • Polyarteritis nodosa 1
  • Temporal arteritis (a form of giant cell arteritis) 1
  • Granulomatosis with polyangiitis (formerly Wegener's) 1
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) 1
  • Kawasaki disease 1

• Small-vessel vasculitis affects intraparenchymal vessels and microvessels, including:

  • ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis) 2
  • Immune complex vasculitis 2
  • Vasculitis associated with systemic disorders (rheumatoid arthritis, systemic lupus erythematosus, serum sickness) 1

Etiological Categories

Primary (Idiopathic) Vasculitis

• Occurs without a well-known underlying cause 3
• Includes conditions like granulomatosis with polyangiitis and microscopic polyangiitis 1
• Often associated with genetic predisposition and environmental triggers 2

Secondary Vasculitis

Infection-Related Causes

• Infections are considered the most common cause of secondary vasculitis 3

• Direct vascular damage mechanisms:

  • Staphylococcus species 3
  • Streptococcus species 3
  • Salmonella species 3
  • Treponema species 3
  • Rickettsia species 3
  • Cytomegalovirus 3
  • Herpes Simplex Virus 1 and 2 3

• Indirect immune-mediated mechanisms:

  • Mycobacterium tuberculosis 3
  • Mycobacterium leprae 3
  • Hepatitis B virus 3
  • Human Immunodeficiency Virus 3
  • Molecular mimicry leading to cross-reactive immune responses 3

Drug-Induced Vasculitis

• One of the most common forms of vasculitis 4
• Withdrawal of the offending agent is often sufficient to resolve clinical manifestations 4
• Differential diagnosis between drug-induced and idiopathic vasculitis may be difficult 4

Vasculitis Associated with Systemic Diseases

• Rheumatoid arthritis 1
• Systemic lupus erythematosus 1
• Serum sickness 1
• Other connective tissue or autoimmune diseases 1

Degenerative and Dysplastic Disorders

• Collagen abnormalities (Marfan and Ehlers-Danlos syndromes) 1
• Erdheim's cystic medial necrosis 1
• Arteriomegaly 1
• Neurofibromatosis 1
• Fibromuscular dysplasia (FMD) - most common dysplastic disease affecting arteries 1

Thrombotic and Embolic Causes

• Primary prothrombotic diseases:

  • Clotting system abnormalities (protein C, protein S, antithrombin III deficiencies) 1
  • Factor V Leiden or prothrombin mutations 1
  • Hyperhomocysteinemia 1
  • Lupus anticoagulant or anticardiolipin antibody 1
  • Prothrombotic states associated with malignancies and inflammatory bowel disease 1

• Thromboembolic arterial occlusive disease:

  • Macroemboli from cardiac sources 1
  • Microemboli from cardiac or arterial sources 1

Vasospastic Disorders

• Migraine headache 1
• Cerebral vasospasm associated with intracranial bleeding 1
• Prinzmetal's angina 1
• Raynaud's phenomenon (primary or secondary) 1
• Ergot toxicity 1

Pathophysiological Mechanisms

• Immune complex-mediated inflammation 5
• ANCA-associated neutrophil activation 1
• Direct vascular wall damage by infectious agents 3
• Molecular mimicry between microbial and self-antigens 3
• Defective neutrophil apoptosis or impaired clearance of apoptotic cell fragments 1

Clinical Implications and Management Considerations

• Diagnosis often requires a combination of clinical presentation, biopsy, and surrogate markers 1
• Imaging plays a crucial role in diagnosing vasculitis, especially for large and medium vessels 1
• Treatment approaches vary based on the type, severity, and extent of vasculitis 1
• Without treatment, severe vasculitis can lead to significant morbidity and mortality 2
• Regular monitoring of disease activity, treatment toxicity, and infection is essential 2

Common Pitfalls and Caveats

• Vasculitis can present with a broad variety of signs and symptoms, making diagnosis challenging 6
• Different vasculitides with similar clinical presentations may have quite different prognoses and treatments 6
• Overlap between vessel size categories exists; for example, large-vessel vasculitis can also affect medium and small vessels 1
• Withdrawal of potential causative agents should be considered before initiating immunosuppressive therapy in suspected drug-induced vasculitis 4
• Ethnic and regional differences in incidence, prevalence, and clinical characteristics should be recognized 7