Small Vessel Vasculitis for ABIM
Small Vessel Vasculitis for the American Board of Internal Medicine Exam
Overview of Small Vessel Vasculitis
Small vessel vasculitis (SVV) refers to a group of disorders that involve inflammation of the small blood vessels, including arterioles, capillaries, and venules.
Classification of Small Vessel Vasculitis
- ANCA-Associated Vasculitides (AAV): This group of vasculitides is characterized by antineutrophil cytoplasmic antibodies (ANCA) targeting neutrophil proteins.
- Granulomatosis with Polyangiitis (GPA): Formerly known as Wegener’s granulomatosis, GPA commonly affects the respiratory tract and kidneys.
- Microscopic Polyangiitis (MPA): Unlike GPA, MPA typically lacks granulomatous inflammation and primarily involves the kidneys and lungs.
- Eosinophilic Granulomatosis with Polyangiitis (EGPA): Also known as Churg-Strauss syndrome, EGPA is associated with asthma, eosinophilia, and multi-organ involvement.
- Immune Complex–Mediated Vasculitides:
- IgA Vasculitis (Henoch-Schönlein Purpura, HSP): Common in children, HSP involves IgA deposition and presents with palpable purpura, abdominal pain, and arthralgia.
- Cryoglobulinemic Vasculitis: Associated with cryoglobulins in serum, commonly linked to hepatitis C infection and causing skin ulcers, arthralgias, and renal involvement.
- Hypocomplementemic Urticarial Vasculitis: Rare, often associated with systemic lupus erythematosus, and presents with urticaria and low complement levels.
Pathophysiology
- ANCA-Associated Mechanisms:
- ANCAs target neutrophil proteins, primarily myeloperoxidase (MPO) and proteinase 3 (PR3), leading to neutrophil activation.
- Activated neutrophils adhere to vessel walls, causing direct damage and promoting inflammation.
- In GPA and MPA, ANCAs are positive in a significant proportion of patients, with PR3-ANCA commonly seen in GPA and MPO-ANCA in MPA.
- Immune Complex Deposition:
- In immune complex vasculitides, such as IgA vasculitis and cryoglobulinemic vasculitis, immune complexes deposit in vessel walls.
- The deposition activates complement pathways, resulting in inflammation and tissue damage.
- IgA vasculitis typically shows IgA-dominant immune deposits, while cryoglobulinemic vasculitis involves cryoglobulins that precipitate at low temperatures.
Clinical Presentation
- General Symptoms of SVV:
- Fever, fatigue, weight loss, and malaise are common constitutional symptoms across SVV.
- Skin lesions such as palpable purpura are characteristic of SVV due to vessel inflammation and leakage.
- Organ-specific symptoms vary by type and extent of involvement.
- Granulomatosis with Polyangiitis (GPA):
- Upper Respiratory Tract: Chronic sinusitis, nasal ulcers, and saddle-nose deformity due to septal destruction.
- Lungs: Nodules, cavitary lesions, and hemoptysis.
- Kidneys: Rapidly progressive glomerulonephritis (RPGN), leading to hematuria and proteinuria.
- Microscopic Polyangiitis (MPA):
- Similar to GPA but without granulomas.
- Renal Involvement: RPGN similar to GPA.
- Pulmonary Involvement: Alveolar hemorrhage and interstitial lung disease.
- Eosinophilic Granulomatosis with Polyangiitis (EGPA):
- Triad of asthma, eosinophilia, and vasculitis.
- Lungs: Asthma with transient pulmonary infiltrates.
- Nervous System: Mononeuritis multiplex, especially affecting peripheral nerves.
- Skin: Palpable purpura and subcutaneous nodules.
- IgA Vasculitis (Henoch-Schönlein Purpura):
- Commonly affects children; manifests with palpable purpura, often on lower extremities.
- Gastrointestinal Symptoms: Colicky abdominal pain and gastrointestinal bleeding.
- Renal Involvement: Hematuria and proteinuria, which can progress to nephropathy.
- Cryoglobulinemic Vasculitis:
- Commonly associated with hepatitis C.
- Skin: Palpable purpura, often on extremities.
- Renal: Membranoproliferative glomerulonephritis (MPGN), leading to hematuria and proteinuria.
- Neurologic: Peripheral neuropathy is common.
Diagnosis
- Laboratory Studies:
- ANCA Testing: Essential for diagnosing AAV; PR3-ANCA (c-ANCA) is associated with GPA, and MPO-ANCA (p-ANCA) with MPA and EGPA.
- Eosinophilia: Commonly seen in EGPA.
- Cryoglobulin Testing: Essential for cryoglobulinemic vasculitis, particularly in hepatitis C patients.
- Complement Levels: Reduced complement levels are seen in cryoglobulinemic vasculitis and hypocomplementemic urticarial vasculitis.
- Biopsy:
- Kidney Biopsy: Shows pauci-immune crescentic glomerulonephritis in AAV and immune complex deposits in IgA vasculitis and cryoglobulinemic vasculitis.
- Skin Biopsy: Confirms leukocytoclastic vasculitis in small vessel vasculitides with characteristic neutrophil infiltrates.
- Imaging:
- Chest X-Ray or CT: Evaluates lung involvement, particularly nodules or cavitary lesions in GPA and interstitial changes in MPA.
Treatment
- Glucocorticoids:
- First-line treatment for active disease to reduce inflammation.
- High-dose prednisone is commonly initiated, often followed by a taper based on disease response.
- Immunosuppressive Agents:
- Cyclophosphamide: Indicated for severe, life-threatening cases such as RPGN or alveolar hemorrhage.
- Methotrexate or Azathioprine: Used for maintenance therapy after induction of remission with cyclophosphamide.
- Rituximab: An anti-CD20 monoclonal antibody used as an alternative to cyclophosphamide, especially in relapsing disease.
- Plasma Exchange:
- Considered in severe cases with rapidly progressive glomerulonephritis or pulmonary hemorrhage in AAV.
- Specific Treatments for Underlying Conditions:
- Antiviral Therapy for Hepatitis C: Important in cryoglobulinemic vasculitis linked to hepatitis C infection.
- Avoidance of Cold: Recommended in cryoglobulinemic vasculitis to prevent cryoprecipitation.
Key Points
- Types: SVV includes ANCA-associated vasculitides (GPA, MPA, EGPA) and immune complex-mediated vasculitides (IgA vasculitis, cryoglobulinemic vasculitis).
- ANCA Association: GPA and MPA are often associated with PR3- and MPO-ANCA, respectively.
- Organ Involvement:
- GPA: Respiratory tract, kidneys.
- MPA: Kidneys, lungs.
- EGPA: Lungs, skin, and peripheral nerves.
- IgA Vasculitis: Skin, gastrointestinal tract, kidneys.
- Cryoglobulinemic Vasculitis: Skin, kidneys, nerves.
- Diagnosis: ANCA testing, cryoglobulin testing, eosinophil count, and complement levels aid in diagnosis; biopsy confirms the diagnosis in uncertain cases.
- Treatment:
- Glucocorticoids: Core component for inducing remission.
- Cyclophosphamide/Rituximab: Used for induction in severe cases.
- Maintenance Therapy: Methotrexate or azathioprine is used to maintain remission.
- Plasma Exchange: Used selectively for life-threatening manifestations in AAV.