Small Vessel Vasculitis – Classification and Pathogenesis
Small vessel vasculitis refers to inflammation of blood vessels predominantly involving small intraparenchymal arteries, arterioles, capillaries, and venules.
In some conditions, medium-sized vessels may also be involved.
Classification
Based on the underlying mechanism, small vessel vasculitis is broadly classified into two groups:
- Immune complex-mediated vasculitis
- ANCA-associated vasculitis
The main difference between these two groups is the presence or absence of significant immunoglobulin and complement deposition in the affected vessel walls.
| Feature | Immune Complex Vasculitis | ANCA-Associated Vasculitis |
|---|---|---|
| Main mechanism | Immune complex deposition | ANCA-mediated neutrophil activation |
| Immunoglobulin deposition | Prominent | Little or absent |
| Complement deposition | Usually present | Little or absent |
| Immunopathological pattern | Immune complex-mediated | Pauci-immune |
1. Immune Complex-Mediated Vasculitis
In this type, antigen–antibody complexes are deposited in the vessel wall, leading to inflammation and vascular injury.
The basic mechanism involves:
- Formation of antigen–antibody complexes
- Deposition of immune complexes in vessel walls
- Activation of complement
- Recruitment and activation of neutrophils and monocytes
- Injury to the vessel wall
Immune complexes may be formed in the circulation or locally within the vessel wall.
Causes and Examples
Drug hypersensitivity: Certain drugs act as antigens or haptens, resulting in immune complex formation. Skin lesions are common, and withdrawal of the offending drug may lead to resolution.
Infections: Microbial antigens may form circulating immune complexes. Hepatitis B infection is an important example discussed in relation to polyarteritis nodosa.
Autoimmune disorders: Conditions such as systemic lupus erythematosus and rheumatoid arthritis may produce immune complex-mediated vascular injury.
Other important examples include IgA vasculitis and cryoglobulinemic vasculitis.
2. ANCA-Associated Vasculitis
ANCA stands for antineutrophil cytoplasmic antibody.
These are autoantibodies directed against antigens present mainly within neutrophil granules and monocyte lysosomes.
Two important types are:
- PR3-ANCA – directed against proteinase 3
- MPO-ANCA – directed against myeloperoxidase
Important Associations
| ANCA Type | Common Disease Association |
|---|---|
| PR3-ANCA | Granulomatosis with polyangiitis |
| MPO-ANCA | Microscopic polyangiitis |
| MPO-ANCA | Eosinophilic granulomatosis with polyangiitis |
Pathogenesis
During neutrophil activation, intracellular antigens such as PR3 and MPO become accessible on the cell surface.
ANCA binds to these antigens, resulting in further neutrophil activation.
Activated neutrophils release reactive oxygen species and proteolytic enzymes, which damage the vascular endothelium.
Why Is It Called Pauci-Immune Vasculitis?
Although autoantibodies are involved in the disease, there is little or no demonstrable immunoglobulin deposition in the vessel wall.
This pattern is called pauci-immune vasculitis.
Thus, the term pauci-immune describes the immunopathological appearance and does not mean that antibodies are unimportant.
Clinical Significance of ANCA
ANCA is important because it:
- Plays a role in the pathogenesis of vascular injury
- Serves as a useful diagnostic marker
- May help in assessing disease activity
Key Take-Home Points
- Small vessel vasculitis predominantly affects arterioles, capillaries, and venules.
- It is broadly classified into immune complex-mediated and ANCA-associated vasculitis.
- Immune complex vasculitis shows immunoglobulin or complement deposition in vessel walls.
- ANCA-associated vasculitis produces vascular injury through neutrophil activation.
- PR3-ANCA and MPO-ANCA are the two important antibody specificities.
- ANCA-associated vasculitis typically shows a pauci-immune pattern.
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