Small Vessel Vasculitis for USMLE Step 1
Small Vessel Vasculitis for the USMLE Step 1 Exam
Overview of Small Vessel Vasculitis
Small vessel vasculitis (SVV) refers to a group of inflammatory disorders affecting small blood vessels, including arterioles, capillaries, and venules. SVV commonly affects multiple organ systems and may present with various symptoms based on the underlying type and the organs involved.
Classification of Small Vessel Vasculitis
- ANCA-Associated Vasculitides (AAV): Characterized by antibodies directed against neutrophil cytoplasmic proteins, causing vascular inflammation.
- Granulomatosis with Polyangiitis (GPA): Previously known as Wegener’s granulomatosis, GPA primarily involves the respiratory tract and kidneys and is associated with PR3-ANCA (c-ANCA).
- Microscopic Polyangiitis (MPA): Similar to GPA but without granulomas; primarily involves the kidneys and lungs and is often associated with MPO-ANCA (p-ANCA).
- Eosinophilic Granulomatosis with Polyangiitis (EGPA): Also known as Churg-Strauss syndrome, EGPA is characterized by asthma, eosinophilia, and multi-organ involvement; usually MPO-ANCA positive.
- Immune Complex–Mediated Vasculitides:
- IgA Vasculitis (Henoch-Schönlein Purpura, HSP): Frequently seen in children, presenting with palpable purpura, arthritis, and abdominal pain due to IgA deposition in vessel walls.
- Cryoglobulinemic Vasculitis: Often associated with chronic hepatitis C infection, this form involves cryoglobulin deposition, leading to skin ulcers and renal disease.
Pathophysiology
- ANCA-Associated Vasculitides (AAV):
- ANCAs (primarily anti-PR3 and anti-MPO) target neutrophil enzymes, causing neutrophil activation.
- Activated neutrophils adhere to and damage endothelial cells, triggering inflammation and vessel destruction.
- GPA is typically associated with c-ANCA (PR3-ANCA), while MPA and EGPA are associated with p-ANCA (MPO-ANCA).
- Immune Complex Vasculitides:
- Characterized by the deposition of immune complexes (e.g., IgA in IgA vasculitis or cryoglobulins in cryoglobulinemic vasculitis).
- These complexes activate the complement system, leading to inflammation and damage to vessel walls.
Clinical Presentation
- General Symptoms: Fever, weight loss, and malaise are common in most small vessel vasculitides. Palpable purpura is characteristic of SVV, often on the lower extremities.
- Granulomatosis with Polyangiitis (GPA):
- Upper Respiratory Tract: Sinusitis, nasal ulcers, saddle-nose deformity.
- Lower Respiratory Tract: Lung nodules, cavitary lesions, hemoptysis.
- Kidneys: Rapidly progressive glomerulonephritis (RPGN) leading to hematuria and proteinuria.
- Microscopic Polyangiitis (MPA):
- Similar presentation to GPA but lacks granulomas.
- Primarily involves kidneys (RPGN) and lungs (alveolar hemorrhage).
- Eosinophilic Granulomatosis with Polyangiitis (EGPA):
- Lungs: Asthma and transient pulmonary infiltrates.
- Peripheral Nervous System: Mononeuritis multiplex.
- Skin: Palpable purpura and nodules.
- IgA Vasculitis:
- Skin: Palpable purpura, typically on lower extremities.
- Gastrointestinal Tract: Abdominal pain, bleeding.
- Kidneys: Hematuria and mild proteinuria, potentially progressing to IgA nephropathy.
- Cryoglobulinemic Vasculitis:
- Often related to hepatitis C infection.
- Skin: Palpable purpura and ulcers.
- Kidneys: Membranoproliferative glomerulonephritis (MPGN) with hematuria.
Diagnosis
- Laboratory Testing:
- ANCA Testing: PR3-ANCA (c-ANCA) for GPA; MPO-ANCA (p-ANCA) for MPA and EGPA.
- Eosinophil Count: Elevated in EGPA.
- Complement Levels: Low in cryoglobulinemic vasculitis due to immune complex deposition.
- Biopsy:
- Skin or Renal Biopsy: Confirms leukocytoclastic vasculitis with neutrophil infiltration in small vessels.
- Renal Biopsy in AAV: Shows pauci-immune crescentic glomerulonephritis.
Key Points
- Types of SVV:
- ANCA-associated vasculitides (GPA, MPA, EGPA) and immune complex–mediated vasculitides (IgA vasculitis, cryoglobulinemic vasculitis).
- Distinct Features:
- GPA: Sinus, lung, and kidney involvement; PR3-ANCA (c-ANCA) positive.
- MPA: Lung and kidney involvement without granulomas; MPO-ANCA (p-ANCA) positive.
- EGPA: Associated with asthma, eosinophilia, and p-ANCA.
- IgA Vasculitis: IgA deposits; skin, GI, and kidney involvement.
- Diagnosis:
- ANCA testing, eosinophil count, and biopsy findings confirm diagnosis.
- Treatment Overview:
- Glucocorticoids for inflammation control.
- Cyclophosphamide or rituximab for severe AAV.