Chapter 375: The Vasculitis Syndromes¶
Chapter 375 | Part 11: Immune-Mediated, Inflammatory, and Rheumatologic Disorders
KEY CLINICAL POINTS¶
- Vasculitis syndromes are a heterogeneous group of disorders characterized by inflammation and damage to blood vessels, with varied etiologies including immune complexes, ANCA, and T-cell responses.
- Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are classified as ANCA-associated vasculitides.
- Diagnosis requires integration of clinical features, laboratory tests (e.g., ANCA, ESR, CRP), and biopsy findings, with imaging playing a key role in assessing vascular involvement.
- Treatment varies by syndrome: GPA/MPA often use cyclophosphamide/rituximab, GCA requires glucocorticoids, and Takayasu arteritis may need surgical intervention.
- Prognosis depends on disease severity, organ involvement, and response to therapy, with significant morbidity and mortality in severe cases.
1. DEFINITION & OVERVIEW¶
Vasculitis syndromes are a group of disorders characterized by inflammation and damage to blood vessels, leading to ischemia and organ dysfunction. They can be primary (e.g., GPA, MPA, EGPA) or secondary to infections, malignancies, or autoimmune diseases. The pathogenesis involves immune-mediated mechanisms such as immune complex deposition, ANCA, or T-cell responses.
Table 375-1: Vasculitis Syndromes¶
| Primary Vasculitis Syndromes | Secondary Vasculitis Syndromes |
|---|---|
| Granulomatosis with polyangiitis | Vasculitis associated with probable etiology |
| Microscopic polyangiitis | Drug-induced vasculitis |
| Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) | Hepatitis C virus–associated cryoglobulinemic vasculitis |
| IgA vasculitis (Henoch-Schönlein) | Hepatitis B virus–associated vasculitis |
| Cryoglobulinemic vasculitis | Polyarteritis nodosa |
| Kawasaki disease | Cancer-associated vasculitis |
| Giant cell arteritis | Vasculitis associated with systemic disease |
| Takayasu arteritis | Lupus vasculitis |
| Behçet’s disease | Rheumatoid vasculitis |
| Sarcoid vasculitis | Others |
Table 375-2: Potential Mechanisms of Vessel Damage¶
| Mechanism | Associated Syndromes |
|---|---|
| Pathogenic immune-complex formation | IgA vasculitis, Lupus vasculitis, Hepatitis C cryoglobulinemic vasculitis |
| Production of antineutrophilic cytoplasmic antibodies | Granulomatosis with polyangiitis, Microscopic polyangiitis, EGPA |
| Pathogenic T lymphocyte responses and granuloma formation | Giant cell arteritis, Takayasu arteritis |
| Serum sickness and cutaneous vasculitis syndromes | Serum sickness-like reactions |
| Hepatitis B virus–associated vasculitis | Hepatitis B virus–associated vasculitis |
1.1 Classification Systems¶
Vasculitis syndromes are classified based on vessel size and pathogenic mechanisms. The 2012 Chapel Hill Consensus Nomenclature categorizes them into small-vessel (e.g., MPA, EGPA), medium-vessel (e.g., GCA, Takayasu arteritis), and large-vessel (e.g., polyarteritis nodosa) vasculitides.
1.2 Key Syndromes¶
Key syndromes include GPA (granulomatous vasculitis with neutrophilic infiltration), MPA (pauci-immune glomerulonephritis), EGPA (asthma, eosinophilia, granulomas), GCA (inflammation of large vessels), and Takayasu arteritis (inflammation of aortic arch branches).
2. EPIDEMIOLOGY¶
Vasculitis syndromes have varying prevalence and demographics. GPA has an estimated prevalence of 3/100,000, with a male-to-female ratio of 1:1. MPA is less common, with an incidence of 3–5/100,000. GCA is most common in individuals >50 years, with higher prevalence in women. Takayasu arteritis is more common in young women in Asia.
2.1 Incidence and Prevalence¶
GPA: 3/100,000; MPA: 3–5/100,000; GCA: 6.9–32.8/100,000 in individuals ≥ 50 years; Takayasu arteritis: 1.2–2.6/1,000,000.
2.2 Risk Factors¶
Infections (e.g., hepatitis B/C), autoimmune diseases (e.g., lupus), malignancies, and genetic factors (e.g., HLA-DRB1*04).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Pathogenesis involves immune-mediated mechanisms: immune complex deposition, ANCA (e.g., anti-MPO, anti-PR3), and T-cell responses. GPA and MPA are associated with ANCA, while GCA involves T-cell-mediated inflammation. Viral infections (e.g., hepatitis C) can trigger cryoglobulinemic vasculitis.
3.1 Immune Complexes¶
Immune complexes deposit in vessel walls, triggering inflammation. Hepatitis C-associated cryoglobulinemia is a classic example.
3.2 ANCA-Associated Vasculitis¶
Anti-MPO and anti-PR3 antibodies drive inflammation in GPA and MPA. These autoantibodies activate neutrophils, leading to vasculitis.
3.3 T-Cell Mediated Pathways¶
T-cell responses and granuloma formation are central to granulomatous vasculitis (e.g., GPA, EGPA).
4. CLINICAL FEATURES¶
Clinical manifestations vary by syndrome. GPA presents with sinusitis, lung nodules, and renal involvement. MPA is characterized by glomerulonephritis and pulmonary capillaritis. EGPA features asthma, eosinophilia, and granulomas. GCA presents with headache, jaw claudication, and visual loss.
Table 375-5: Clinical Manifestations of GPA¶
| Manifestation | Percentage at Disease Onset | Percentage Throughout Course |
|---|---|---|
| Kidney | 18% | 77% |
| Ear/Nose/Throat | 73% | 92% |
| Sinusitis | 51% | 85% |
| Nasal disease | 36% | 68% |
| Lung | 45% | 85% |
| Pulmonary infiltrates | 25% | 66% |
| Pulmonary nodules | 24% | 58% |
| Hemoptysis | 12% | 30% |
| Eye involvement | 52% | 85% |
4.1 GPA¶
Classic triad: sinusitis, lung nodules, and renal involvement. Subglottic stenosis and saddle nose deformity may occur.
4.2 MPA¶
Renal involvement (pauci-immune glomerulonephritis) and pulmonary capillaritis are common. Skin purpura and gastrointestinal vasculitis may occur.
4.3 EGPA¶
Asthma, eosinophilia, granulomas, and vasculitis. Mononeuritis multiplex and pulmonary infiltrates are common.
4.4 GCA¶
Headache, jaw claudication, visual changes, and polymyalgia. Ischemic optic neuropathy is a feared complication.
5. DIFFERENTIAL DIAGNOSIS¶
Differential diagnoses include infections (e.g., syphilis, tuberculosis), malignancies (e.g., lymphoma), and non-vasculitic conditions (e.g., lupus, rheumatoid arthritis). For GCA, differential diagnoses include temporal arteritis mimics (e.g., migraines, meningitis).
5.1 Infections¶
Bacterial endocarditis, syphilis, and fungal infections (e.g., histoplasmosis) can mimic vasculitis.
5.2 Neoplasms¶
Lymphoma, sarcoidosis, and other malignancies may present with vasculitis.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic workup includes ANCA testing (cANCA/pANCA), imaging (e.g., MRI, CT), and biopsy. Renal biopsy confirms pauci-immune glomerulonephritis in MPA. Arteriography is critical for Takayasu arteritis.
Table 375-3: Conditions Mimicking Vasculitis¶
| Category | Examples |
|---|---|
| Infectious Diseases | Bacterial endocarditis, syphilis, histoplasmosis |
| Coagulopathies | Antiphospholipid syndrome, thrombotic thrombocytopenic purpura |
| Neoplasms | Lymphoma, atrial myxoma |
| Drug Toxicity | Cocaine, levamisole |
| Other | Sarcoidosis, atheroembolic disease |
6.1 Laboratory Tests¶
Elevated ESR, CRP, and ANCA (anti-MPO, anti-PR3). Hypocomplementemia in cryoglobulinemic vasculitis.
6.2 Imaging¶
MRI/CT for CNS vasculitis, arteriography for large-vessel involvement, and ultrasound for peripheral arteries.
6.3 Biopsy¶
Skin, renal, or vessel biopsy confirms vasculitis. Granulomatous inflammation is characteristic of GPA.
7. MANAGEMENT & TREATMENT¶
Treatment is tailored to syndrome severity. GPA/MPA use cyclophosphamide/rituximab, GCA requires glucocorticoids, and Takayasu arteritis may need surgical intervention. Supportive care includes anticoagulation and infection prophylaxis.
Table 375-4: Toxic Side Effects of Vasculitis Drugs¶
| Drug | Major Toxicities |
|---|---|
| Glucocorticoids | Osteoporosis, diabetes, avascular necrosis |
| Cyclophosphamide | Bone marrow suppression, cystitis, bladder cancer |
| Methotrexate | Bone marrow suppression, hepatotoxicity |
| Rituximab | Infections, hypogammaglobulinemia |
| Drug | Major Toxicities |
|---|---|
| Azathioprine | Bone marrow suppression, hepatotoxicity |
7.1 Induction Therapy¶
Cyclophosphamide (2 mg/kg/day) or rituximab (375 mg/m²) with glucocorticoids for severe disease. Avacopan is an emerging option for severe GPA/MPA.
7.2 Maintenance Therapy¶
Azathioprine, methotrexate, or mycophenolate mofetil. Rituximab is preferred for long-term maintenance in ANCA-associated vasculitis.
7.3 Special Considerations¶
Avoid cyclophosphamide in pregnancy. Monitor for infections, bone loss, and renal function during treatment.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis varies by syndrome. GPA/MPA have high mortality if untreated, but remission is achievable with aggressive therapy. GCA requires prompt treatment to prevent blindness. Complications include renal failure, cardiovascular events, and secondary infections.
8.1 Mortality¶
Untreated GPA/MPA: 50–70% mortality. GCA: 10–20% mortality with untreated disease.
8.2 Long-Term Risks¶
Renal failure, aortic aneurysm rupture, and opportunistic infections. Chronic corticosteroid use leads to osteoporosis and diabetes.
9. SPECIAL CONSIDERATIONS¶
Pregnancy requires careful management to avoid teratogenic drugs (e.g., cyclophosphamide). Pediatric vasculitis (e.g., Henoch-Schönlein purpura) often has a better prognosis. Elderly patients face higher risks of infections and drug toxicity.
9.1 Pregnancy¶
Avoid cyclophosphamide; use methotrexate or rituximab cautiously. Monitor for fetal growth and maternal complications.
9.2 Pediatrics¶
Henoch-Schönlein purpura is common in children. Treatment is usually supportive, with corticosteroids for severe cases.
10. KEY POINTS & CLINICAL PEARLS¶
- ANCA testing is critical for diagnosing GPA, MPA, and EGPA. 2. Early treatment with glucocorticoids and cyclophosphamide/rituximab improves outcomes in GPA/MPA. 3. GCA requires prompt treatment to prevent visual loss. 4. Vasculitis in pregnancy necessitates careful drug selection. 5. Monitor for infections and drug toxicity during long-term therapy.