Small Vessel Vasculitis for USMLE Step 3
Small Vessel Vasculitis for the USMLE Step 3 Exam
Overview of Small Vessel Vasculitis
Small vessel vasculitis (SVV) includes a group of disorders involving inflammation in small blood vessels, including capillaries, venules, and arterioles. These diseases often present with a range of systemic symptoms and multi-organ involvement.
Classification of Small Vessel Vasculitis
- ANCA-Associated Vasculitides (AAV): Characterized by the presence of antineutrophil cytoplasmic antibodies (ANCA), which target neutrophil enzymes and induce vascular inflammation.
- Granulomatosis with Polyangiitis (GPA): Formerly Wegener’s granulomatosis, GPA often affects the respiratory tract and kidneys and is associated with PR3-ANCA (c-ANCA).
- Microscopic Polyangiitis (MPA): Primarily involves the kidneys and lungs without granulomas; commonly linked to MPO-ANCA (p-ANCA).
- Eosinophilic Granulomatosis with Polyangiitis (EGPA): Also known as Churg-Strauss syndrome, EGPA presents with asthma, eosinophilia, and systemic vasculitis and is usually associated with MPO-ANCA (p-ANCA).
- Immune Complex–Mediated Vasculitides:
- IgA Vasculitis (Henoch-Schönlein Purpura, HSP): Predominantly seen in children, IgA vasculitis involves IgA deposits and presents with palpable purpura, abdominal pain, and arthralgia.
- Cryoglobulinemic Vasculitis: Often associated with hepatitis C infection, presenting with palpable purpura, arthralgias, and kidney involvement due to cryoglobulin deposition.
Pathophysiology
- ANCA-Associated Mechanisms:
- ANCAs, primarily anti-PR3 and anti-MPO, target neutrophil enzymes, leading to neutrophil activation.
- Activated neutrophils adhere to the vessel endothelium, causing damage and inflammation.
- PR3-ANCA (c-ANCA) is typical for GPA, while MPO-ANCA (p-ANCA) is seen in MPA and EGPA.
- Immune Complex Deposition:
- IgA vasculitis involves IgA immune complex deposition in small vessels, which activates the complement system, promoting inflammation.
- Cryoglobulinemic vasculitis involves cryoglobulins that precipitate in cooler temperatures, leading to immune complex–mediated damage, especially in patients with chronic hepatitis C.
Clinical Presentation
- General Symptoms:
- Common symptoms include fever, malaise, weight loss, and palpable purpura, often on the lower extremities.
- Granulomatosis with Polyangiitis (GPA):
- Upper Respiratory Tract: Chronic sinusitis, nasal ulcers, saddle-nose deformity from cartilage destruction.
- Lungs: Nodules, cavitary lesions, and hemoptysis.
- Kidneys: Rapidly progressive glomerulonephritis (RPGN), causing hematuria and proteinuria.
- Microscopic Polyangiitis (MPA):
- Similar to GPA but without granulomas.
- Kidneys: RPGN with hematuria and proteinuria.
- Lungs: Alveolar hemorrhage presenting with hemoptysis.
- Eosinophilic Granulomatosis with Polyangiitis (EGPA):
- Lungs: Asthma with transient pulmonary infiltrates.
- Nervous System: Mononeuritis multiplex, affecting peripheral nerves.
- Skin: Palpable purpura and subcutaneous nodules.
- IgA Vasculitis:
- Skin: Palpable purpura, typically on the legs and buttocks.
- GI Tract: Abdominal pain, possible GI bleeding.
- Kidneys: Hematuria and mild proteinuria, potentially leading to IgA nephropathy.
- Cryoglobulinemic Vasculitis:
- Commonly related to hepatitis C infection.
- Skin: Palpable purpura, often on extremities.
- Kidneys: Membranoproliferative glomerulonephritis (MPGN) with hematuria and proteinuria.
- Neurologic: Peripheral neuropathy, presenting with numbness and weakness.
Diagnosis
- Laboratory Studies:
- ANCA Testing: PR3-ANCA (c-ANCA) for GPA, MPO-ANCA (p-ANCA) for MPA and EGPA.
- Eosinophil Count: Elevated in EGPA.
- Cryoglobulin Levels: Useful in cryoglobulinemic vasculitis, especially in patients with hepatitis C.
- Complement Levels: Low in cryoglobulinemic vasculitis due to immune complex deposition.
- Biopsy:
- Skin or Renal Biopsy: Shows leukocytoclastic vasculitis in SVV.
- Kidney Biopsy: Indicates pauci-immune crescentic glomerulonephritis in AAV and immune complex deposition in IgA or cryoglobulinemic vasculitis.
Key Points
- Types: SVV includes ANCA-associated vasculitides (GPA, MPA, EGPA) and immune complex–mediated vasculitides (IgA vasculitis, cryoglobulinemic vasculitis).
- Distinctive Features:
- GPA: Upper respiratory tract, lung, and kidney involvement with c-ANCA positivity.
- MPA: Lung and kidney involvement without granulomas, associated with p-ANCA.
- EGPA: Associated with asthma, eosinophilia, and peripheral neuropathy; linked to p-ANCA.
- IgA Vasculitis: IgA deposits; primarily affects skin, GI tract, and kidneys.
- Diagnosis: ANCA testing, eosinophil count, cryoglobulin levels, and biopsy confirm diagnosis.
- Treatment:
- Glucocorticoids: Key for inflammation control.
- Cyclophosphamide/Rituximab: Used for severe cases of AAV.