Medium & Variable-Sized Vasculitis for ABIM
Medium & Variable-Sized Vasculitis for the American Board of Internal Medicine Exam
Medium and Variable-Sized Vessel Vasculitis
Medium and variable-sized vessel vasculitis includes several conditions primarily affecting medium-sized arteries but can also involve vessels of varying sizes. The main types are Polyarteritis Nodosa (PAN), Kawasaki Disease, Thromboangiitis Obliterans (Buerger’s Disease), and Behçet’s Disease.
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Polyarteritis Nodosa (PAN)
- Definition:
- PAN is a systemic necrotizing vasculitis affecting medium-sized arteries, sparing smaller arterioles and venules.
- It can affect multiple organs but has a strong predilection for the renal, gastrointestinal, and peripheral nervous systems.
- Epidemiology:
- Occurs in adults, with a slight male predominance.
- Though rare, it is sometimes associated with hepatitis B virus (HBV) infection.
- Pathophysiology:
- Immune-mediated, necrotizing inflammation of medium-sized arteries leads to vessel wall destruction and microaneurysm formation.
- Damage occurs in the muscular layer of the vessel wall, causing ischemia and organ infarction.
- Clinical Presentation:
- Systemic Symptoms: Fever, weight loss, and malaise.
- Renal: Hypertension due to renal ischemia and infarction, but usually no glomerulonephritis.
- Neurologic: Mononeuritis multiplex, presenting as asymmetric sensory and motor neuropathies.
- Gastrointestinal: Abdominal pain (often postprandial), nausea, and vomiting; can lead to mesenteric ischemia and bowel infarction.
- Dermatologic: Livedo reticularis, subcutaneous nodules, and ulcerations.
- Diagnosis:
- Laboratory Tests: Elevated ESR, CRP, and sometimes hepatitis B surface antigen (HBsAg) in HBV-associated cases.
- Tissue Biopsy: Demonstrates transmural inflammation with fibrinoid necrosis of medium-sized arteries.
- Angiography: Useful to identify microaneurysms in mesenteric or renal arteries, often described as “beading” due to segmental involvement.
- Management:
- Corticosteroids: Mainstay treatment, typically high-dose prednisone.
- Immunosuppressive Agents: Cyclophosphamide may be used in severe cases.
- Antiviral Therapy: In HBV-associated PAN, antiviral therapy combined with corticosteroids is recommended.
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Kawasaki Disease
- Definition:
- Kawasaki disease is an acute, self-limited vasculitis that primarily affects children, involving medium-sized arteries, especially the coronary arteries.
- It is the leading cause of acquired heart disease in children in developed countries.
- Epidemiology:
- Primarily affects children under 5, with a higher incidence in Asian populations.
- Pathophysiology:
- Exact etiology is unknown but may involve an abnormal immune response to infection in genetically susceptible individuals.
- Vascular inflammation targets coronary arteries, leading to aneurysms and myocardial infarction in severe cases.
- Clinical Presentation:
- Diagnosis is clinical and based on prolonged fever (>5 days) with at least four of the following criteria:
- Bilateral Conjunctival Injection: Non-exudative conjunctivitis.
- Oral Mucosal Changes: Strawberry tongue, red cracked lips.
- Polymorphous Rash: Maculopapular or erythematous rash.
- Peripheral Extremity Changes: Erythema or desquamation of hands and feet.
- Cervical Lymphadenopathy: Often unilateral, >1.5 cm.
- Complications:
- Coronary artery aneurysms can develop, potentially leading to myocardial infarction and ischemic heart disease if untreated.
- Diagnosis:
- Primarily clinical; however, elevated ESR and CRP are common, and thrombocytosis may occur in the subacute phase.
- Echocardiography: Performed at diagnosis and during follow-up to assess for coronary aneurysms.
- Management:
- Intravenous Immunoglobulin (IVIG): Given within 10 days of symptom onset to reduce risk of coronary aneurysms.
- Aspirin: High-dose during the acute phase, followed by a lower dose to prevent thrombosis in coronary aneurysms.
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Thromboangiitis Obliterans (Buerger’s Disease)
- Definition:
- Thromboangiitis obliterans is a non-atherosclerotic, segmental vasculitis affecting small- and medium-sized arteries and veins in the extremities.
- Strongly associated with tobacco use.
- Epidemiology:
- Primarily affects young men, often under 45, who are heavy smokers.
- Pathophysiology:
- Inflammatory and thrombotic occlusions develop in distal vessels of the hands and feet.
- Tobacco exposure is thought to trigger an immune response that damages the endothelium of these vessels.
- Clinical Presentation:
- Extremity Ischemia: Claudication, rest pain, ulcerations, and gangrene of fingers or toes.
- Raynaud’s Phenomenon: Secondary Raynaud’s phenomenon with episodic pallor, cyanosis, and redness in the digits.
- Migratory Superficial Thrombophlebitis: Red, tender cords along superficial veins.
- Diagnosis:
- Clinical diagnosis based on history, especially with heavy tobacco use.
- Angiography: Shows “corkscrew” collaterals and segmental occlusions in affected vessels.
- Management:
- Smoking Cessation: Absolute requirement to prevent progression; no effective pharmacologic treatment if smoking continues.
- Symptomatic Management: Includes analgesics for pain, wound care, and sometimes amputation for severe ischemic damage.
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Behçet’s Disease
- Definition:
- Behçet’s disease is a variable vessel vasculitis affecting vessels of all sizes and types, including arteries, veins, and capillaries.
- It is characterized by recurrent oral and genital ulcers, uveitis, and systemic inflammation.
- Epidemiology:
- Most common in the Middle East and East Asia, typically affecting adults aged 20-40.
- Pathophysiology:
- Exact cause is unknown but thought to involve aberrant immune responses triggered by environmental factors in genetically susceptible individuals.
- Affects multiple organs due to systemic vasculitis, including the skin, eyes, joints, and central nervous system.
- Clinical Presentation:
- Oral Ulcers: Painful, recurrent aphthous ulcers, usually the first sign.
- Genital Ulcers: Similar to oral ulcers but deeper and often scarring.
- Ocular Involvement: Uveitis, which can lead to vision loss.
- Skin Lesions: Erythema nodosum, acneiform lesions.
- Vascular Involvement: Thrombosis, especially in large veins (e.g., deep vein thrombosis, pulmonary artery aneurysm).
- Neurological Involvement: Meningoencephalitis, seizures.
- Diagnosis:
- Clinical criteria, including recurrent oral ulcers plus two of the following: genital ulcers, uveitis, skin lesions, or a positive pathergy test (skin hypersensitivity test).
- Pathergy Test: Pricking the skin causes a papular or pustular lesion within 48 hours, indicating abnormal immune response.
- Management:
- Corticosteroids: Used for acute flares.
- Immunosuppressive Therapy: Azathioprine, TNF inhibitors, or cyclosporine for chronic and severe cases, especially with ocular or neurological involvement.
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Key Points
- Polyarteritis Nodosa (PAN):
- Affects medium-sized arteries, sparing small vessels; associated with HBV in some cases.
- Causes ischemia in kidneys, nerves, and the GI tract; diagnosed with biopsy or angiography.
- Treated with corticosteroids and immunosuppressive agents, and antivirals if HBV-associated.
- Kawasaki Disease:
- Affects children under 5, presenting with prolonged fever, rash, conjunctivitis, and mucosal changes.
- Risk of coronary aneurysms if untreated; treated with IVIG and high-dose aspirin.
- Thromboangiitis Obliterans (Buerger’s Disease):
- Affects young smokers, leading to ischemia in the hands and feet; smoking cessation is essential.
- Presents with claudication, ulcers, and superficial thrombophlebitis.
- Behçet’s Disease:
- Variable vessel vasculitis causing oral and genital ulcers, uveitis, skin lesions, and venous thrombosis.
- Managed with corticosteroids for acute flares and immunosuppressive agents for systemic involvement.