Small Vessel Vasculitis for USMLE Step 2
Small Vessel Vasculitis for the USMLE Step 2 Exam
Overview of Small Vessel Vasculitis
Small vessel vasculitis (SVV) encompasses a group of disorders that cause inflammation in small blood vessels, including capillaries, venules, and arterioles. These conditions can involve multiple organs, with a wide range of symptoms influenced by the type of vasculitis and the organs affected.
Classification of Small Vessel Vasculitis
- ANCA-Associated Vasculitides (AAV): Marked by the presence of antineutrophil cytoplasmic antibodies (ANCA), which target neutrophil proteins and cause vascular inflammation.
- Granulomatosis with Polyangiitis (GPA): Formerly called Wegener’s granulomatosis, GPA is commonly associated with PR3-ANCA (c-ANCA) and affects the respiratory tract and kidneys.
- Microscopic Polyangiitis (MPA): Lacks granulomas and commonly involves the kidneys and lungs; often associated with MPO-ANCA (p-ANCA).
- Eosinophilic Granulomatosis with Polyangiitis (EGPA): Also known as Churg-Strauss syndrome, EGPA presents with asthma, eosinophilia, and vasculitis, and is associated with MPO-ANCA (p-ANCA).
- Immune Complex–Mediated Vasculitides:
- IgA Vasculitis (Henoch-Schönlein Purpura, HSP): Common in children, IgA vasculitis features IgA deposits in vessel walls and presents with palpable purpura, abdominal pain, and arthralgia.
- Cryoglobulinemic Vasculitis: Often associated with hepatitis C infection, this vasculitis presents with palpable purpura, arthralgia, and kidney involvement due to cryoglobulin deposition in vessels.
Pathophysiology
- ANCA-Associated Mechanisms:
- ANCA autoantibodies target neutrophil enzymes, primarily PR3 and MPO, leading to neutrophil activation and vascular damage.
- GPA is typically associated with PR3-ANCA (c-ANCA), while MPA and EGPA are linked with MPO-ANCA (p-ANCA).
- Immune Complex Deposition:
- In IgA vasculitis, IgA immune complexes deposit in small vessels, activating the complement system and triggering inflammation.
- Cryoglobulinemic vasculitis involves cryoglobulins that precipitate at low temperatures, resulting in immune complex-mediated vascular inflammation.
Clinical Presentation
- Common Features:
- Constitutional symptoms like fever, malaise, and weight loss are frequent in SVV.
- Palpable purpura is a hallmark of SVV, seen especially on the lower extremities due to small vessel involvement.
- Granulomatosis with Polyangiitis (GPA):
- Respiratory Tract: Chronic sinusitis, nasal ulcers, and saddle-nose deformity due to cartilage destruction.
- Lungs: Pulmonary nodules, cavitary lesions, and hemoptysis.
- Kidneys: Rapidly progressive glomerulonephritis (RPGN) with hematuria and proteinuria.
- Microscopic Polyangiitis (MPA):
- Similar to GPA but without granulomas.
- Kidneys: RPGN similar to GPA.
- Lungs: Alveolar hemorrhage causing cough and hemoptysis.
- Eosinophilic Granulomatosis with Polyangiitis (EGPA):
- Lungs: Asthma with 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 proteinuria, sometimes leading to IgA nephropathy.
- Cryoglobulinemic Vasculitis:
- Linked to hepatitis C.
- Skin: Palpable purpura, often on extremities.
- Kidneys: Membranoproliferative glomerulonephritis (MPGN) causing hematuria and proteinuria.
- Neurological: Peripheral neuropathy is common.
Diagnosis
- Laboratory Studies:
- ANCA Testing: PR3-ANCA (c-ANCA) is associated with GPA; MPO-ANCA (p-ANCA) is associated with MPA and EGPA.
- Eosinophil Count: Elevated in EGPA.
- Cryoglobulin Testing: Essential in cryoglobulinemic vasculitis, especially in patients with hepatitis C.
- Complement Levels: Reduced in cryoglobulinemic vasculitis due to immune complex consumption.
- Biopsy:
- Skin or Renal Biopsy: Demonstrates leukocytoclastic vasculitis in SVV.
- Kidney Biopsy: Shows pauci-immune glomerulonephritis in ANCA-associated vasculitides and immune deposits 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).
- Organ Involvement:
- GPA: Respiratory tract, kidneys.
- MPA: Kidneys and lungs.
- EGPA: Asthma, eosinophilia, nervous system.
- IgA Vasculitis: Skin, GI tract, kidneys.
- Diagnosis: ANCA testing, eosinophil count, cryoglobulin levels, and biopsy findings aid in diagnosis.
- Treatment Overview:
- Glucocorticoids: Core treatment for inflammation control.
- Cyclophosphamide/Rituximab: Used for severe AAV.