What are the causes of small vessel vasculitis (inflammation of small blood vessels)?

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From the Guidelines

Small vessel vasculitis is primarily caused by autoimmune mechanisms, with the main causes including ANCA-associated vasculitis, immune complex deposition, and drug-induced vasculitis, as supported by the most recent evidence from 1. The causes of small vessel vasculitis can be broken down into several key categories:

  • ANCA-associated vasculitis, which includes granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, as described in 1 and 1
  • Immune complex deposition, such as IgA vasculitis/Henoch-Schönlein purpura and cryoglobulinemic vasculitis, as mentioned in 1
  • Drug-induced vasculitis, which can be triggered by medications such as hydralazine, propylthiouracil, and minocycline, as well as illicit drugs, as noted in 1 and 1 Infections can also trigger vasculitis through molecular mimicry, where pathogens share structural similarities with self-antigens, causing cross-reactive immune responses, as discussed in 1. Genetic factors play a role in susceptibility, with certain HLA types associated with increased risk, as highlighted in 1. Environmental triggers like silica exposure and underlying conditions such as hepatitis B and C infections, connective tissue diseases, and malignancies can also cause secondary small vessel vasculitis, as mentioned in 1, 1, and 1. The pathophysiology involves neutrophil activation, endothelial cell damage, and inflammatory cytokine release, leading to vessel wall inflammation, tissue ischemia, and organ dysfunction, as described in 1 and 1. Early diagnosis and treatment targeting the underlying cause are essential to prevent permanent organ damage, as emphasized in 1 and 1.

From the Research

Causes of Small Vessel Vasculitis

The causes of small vessel vasculitis are varied and can be attributed to several factors, including:

  • Unknown causes, as stated in 2
  • Immunopathologic basis, with classification by vessel size 2
  • Autoimmune processes, such as antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) 3, 4, 5, 6
  • Genetic background and pathophysiology, which can differ between ANCA-positive and ANCA-negative patients 4
  • Eosinophilic granulomatosis with polyangiitis (EGPA), a rare form of AAV characterized by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia 3, 4, 6
  • Microscopic polyangiitis (MPA), a small vessel vasculitis defined by necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels 5

Types of Small Vessel Vasculitis

Some of the types of small vessel vasculitis include:

  • ANCA-associated vasculitis (AAV), which includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) 3, 4, 5, 6
  • Eosinophilic granulomatosis with polyangiitis (EGPA), characterized by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia 3, 4
  • Microscopic polyangiitis (MPA), defined by necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels 5
  • Granulomatous vasculitides, characterized by intramural, predominantly lymphohistiocytic infiltrates with the formation of giant cells, including giant cell arteritis (GCA) and Takayasu arteritis (TAK) 6

Pathophysiology and Clinical Manifestations

The pathophysiology and clinical manifestations of small vessel vasculitis can vary depending on the type and severity of the disease, including:

  • Necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels 5
  • Granulomatous inflammation, mainly affecting the upper and/or lower respiratory tract, in EGPA with eosinophilic infiltrates 3, 4, 6
  • Eosinophilic infiltration and inflammation, resulting in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy 3
  • ANCA-positive and ANCA-negative patients, with different genetic background, pathophysiology, and clinical manifestations 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Small vessel vasculitis.

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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