What is small vessel vasculitis?

Small Vessel Vasculitis

Small vessel vasculitis is a group of diseases characterized by necrotizing inflammation of small blood vessels (arterioles, capillaries, and venules) that can lead to serious health consequences including organ damage and failure if not properly diagnosed and treated. 1, 2

Classification and Types

• Small vessel vasculitis affects intraparenchymal vessels (arterioles, capillaries, and venules), though medium or large vessels may occasionally also be involved 3, 1

• Small vessel vasculitides are primarily divided into two major categories based on immunopathological features:

  • ANCA-associated vasculitis (pauci-immune): characterized by little or no immune complex deposition 3, 4
  • Immune complex vasculitis: characterized by significant immune complex deposition 1, 4

• ANCA-associated vasculitis includes three main subtypes:

  • Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) 3, 1
  • Microscopic polyangiitis (MPA) 3, 1
  • Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) 3, 1

• Immune complex vasculitides include:

  • IgA vasculitis (formerly Henoch-Schönlein purpura) 1, 4
  • Cryoglobulinemic vasculitis 1, 4
  • Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis) 4
  • Anti-glomerular basement membrane disease 4

Pathophysiology

• In ANCA-associated vasculitis, autoantibodies target neutrophil cytoplasmic components (primarily proteinase 3 or myeloperoxidase), leading to neutrophil activation, degranulation, and release of tissue-damaging enzymes and reactive oxygen species 4, 5

• In immune complex vasculitis, deposition of immune complexes in vessel walls activates complement and recruits inflammatory cells, causing vessel damage 2, 4

• Genetic factors play a significant role in disease susceptibility, with specific HLA associations identified for different vasculitis subtypes 4, 5

• Environmental triggers such as infections, drugs, and other exposures may initiate disease in genetically predisposed individuals 4, 5

Clinical Manifestations

• Clinical presentations vary widely depending on the vessels and organs involved, ranging from isolated skin involvement to life-threatening multi-organ disease 2, 6

• Common manifestations include:

  • Skin: palpable purpura, urticaria, ulcers, and nodules 2, 6
  • Kidney: glomerulonephritis with hematuria, proteinuria, and declining renal function 3, 6
  • Respiratory tract: sinusitis, epistaxis, pulmonary infiltrates, and potentially life-threatening diffuse alveolar hemorrhage 3, 6
  • Nervous system: mononeuritis multiplex, peripheral neuropathy, or central nervous system involvement 6

• Pulmonary-renal syndrome (simultaneous lung and kidney injury) is a serious manifestation that should raise concern for vasculitis 3

Diagnosis

• Diagnosis relies on a combination of clinical findings, laboratory tests, and often histopathology 2, 6

• Laboratory evaluation should include:

  • ANCA testing (both immunofluorescence patterns and specific ELISA for PR3-ANCA and MPO-ANCA) 3, 6
  • Complement levels (may be low in immune complex vasculitis) 6
  • Renal function tests and urinalysis 3, 6
  • Complete blood count and inflammatory markers 6
  • Specific tests for associated conditions (e.g., hepatitis B and C serologies for cryoglobulinemic vasculitis) 6

• Histopathologic examination typically shows:

  • Leukocytoclastic vasculitis with fibrinoid necrosis of vessel walls 2
  • Neutrophilic infiltration around blood vessels 2
  • Presence or absence of immune deposits (distinguishing immune complex from pauci-immune vasculitis) 3, 2

• Tissue biopsy from an affected organ is often necessary for definitive diagnosis, with preference for targeted biopsies of recent active lesions 2

Treatment

• Treatment goals include inducing remission, preventing relapse, and minimizing treatment toxicity 1, 7

• Treatment intensity is determined by disease severity and extent of organ involvement 1

• For ANCA-associated vasculitis:

  • Induction therapy for severe disease typically includes high-dose corticosteroids combined with either cyclophosphamide or rituximab 3, 1, 7
  • Maintenance therapy usually continues for 18-24 months with less toxic agents such as azathioprine, methotrexate, or rituximab 3, 1
  • In cases of diffuse alveolar bleeding with hypoxemia, plasma exchange may be considered in addition to standard therapy 3

• For immune complex vasculitis, treatment depends on the specific type and severity, but often includes corticosteroids and immunosuppressants 1

• Infection prophylaxis with trimethoprim-sulfamethoxazole is recommended during immunosuppressive therapy 1

• Regular monitoring of disease activity, treatment toxicity, and infection is essential 1

Prognosis and Complications

• Without treatment, severe small vessel vasculitis can lead to significant morbidity and mortality, particularly with kidney and lung involvement 3, 7

• With appropriate treatment, remission can be achieved in most patients, though relapse is common 7

• Long-term complications include chronic kidney disease, pulmonary fibrosis, and treatment-related toxicities 7

• Cardiovascular risk factors, osteoporosis prevention, and infection risk require careful monitoring 1

Special Considerations

• Pregnancy requires modification of treatment regimens to avoid teratogenic medications 1

• A multidisciplinary approach involving specialists based on organ involvement is recommended for optimal management 1

• Regular assessment of disease activity using validated tools helps guide treatment decisions 1