Residency · Residency · Internal Medicine
Vasculitis: Pattern Recognition and Urgent Management
Introduction
Vasculitis encompasses a group of disorders characterized by inflammation and destruction of blood vessel walls. The clinical presentation depends on the size and distribution of the affected vessels. Early recognition is critical because untreated vasculitis can lead to irreversible organ damage and death. The internist must recognize clinical patterns, initiate appropriate workup, and begin treatment while awaiting rheumatology consultation.
Classification by Vessel Size
| Vessel Size | Disease | Key Features | ANCA/Serology |
|---|---|---|---|
| Large | Giant cell arteritis (GCA) | Age >50, temporal headache, jaw claudication, vision loss | Negative |
| Large | Takayasu arteritis | Young women, limb claudication, BP differential | Negative |
| Medium | Polyarteritis nodosa (PAN) | Renal/mesenteric ischemia, livedo, neuropathy; HBV association | ANCA-negative |
| Small (ANCA) | GPA | Upper/lower respiratory, renal; saddle nose, cavitary lung lesions | c-ANCA/PR3 |
| Small (ANCA) | MPA | Renal (RPGN), pulmonary hemorrhage | p-ANCA/MPO |
| Small (ANCA) | EGPA | Asthma, eosinophilia, neuropathy, cardiac | p-ANCA/MPO (~40%) |
| Small (Immune complex) | IgA vasculitis (HSP) | Palpable purpura, arthritis, abdominal pain, nephritis | IgA deposits |
| Small (Immune complex) | Cryoglobulinemic | Purpura, arthralgia, GN; HCV associated | Cryoglobulins, low C4 |
Large-Vessel Vasculitis
- Giant cell arteritis (GCA): temporal artery and aortic branches; age > 50
- Takayasu arteritis: aorta and major branches; typically young women
Medium-Vessel Vasculitis
- Polyarteritis nodosa (PAN): renal, mesenteric, and peripheral arteries; NOT associated with ANCA
- Kawasaki disease: coronary arteries; pediatric population
Small-Vessel Vasculitis (ANCA-Associated)
- Granulomatosis with polyangiitis (GPA): upper/lower respiratory tract, kidneys; c-ANCA/PR3
- Microscopic polyangiitis (MPA): kidneys, lungs; p-ANCA/MPO
- Eosinophilic granulomatosis with polyangiitis (EGPA): asthma, eosinophilia, neuropathy; p-ANCA/MPO in ~40%
Small-Vessel Vasculitis (Immune Complex)
- IgA vasculitis (Henoch-Schonlein purpura): palpable purpura, arthritis, abdominal pain, nephritis
- Cryoglobulinemic vasculitis: associated with hepatitis C; purpura, arthralgia, glomerulonephritis
Giant Cell Arteritis
Clinical Features
- Age > 50; most common primary systemic vasculitis in older adults
- New-onset headache (temporal), scalp tenderness, jaw claudication
- Visual symptoms: amaurosis fugax, diplopia, irreversible vision loss if untreated
- Constitutional symptoms: fever, weight loss, fatigue
- Polymyalgia rheumatica (PMR) coexists in 40-60% of GCA patients
Diagnosis
- ESR and CRP: almost always markedly elevated; normal values make GCA unlikely
- Temporal artery biopsy: gold standard; obtain within 2 weeks of starting steroids (inflammation persists)
- Biopsy should be >= 1 cm; skip lesions can cause false negatives; consider bilateral biopsy
- Temporal artery ultrasound: halo sign; increasingly used as non-invasive alternative
Management
- Do NOT wait for biopsy to start treatment if clinical suspicion is high
- Prednisone 60 mg daily for uncomplicated GCA; taper over 12-24 months
- IV methylprednisolone (1 g daily for 3 days) if visual symptoms present
- Tocilizumab: steroid-sparing agent; FDA-approved for GCA; enables faster taper
- Low-dose aspirin for vascular event prevention
ANCA-Associated Vasculitis
Granulomatosis with Polyangiitis (GPA)
- Classic triad: upper airway disease (sinusitis, nasal crusting, saddle-nose deformity), pulmonary involvement (nodules, cavitary lesions, diffuse alveolar hemorrhage), glomerulonephritis
- Associated with c-ANCA (anti-PR3 antibodies)
- Can present with subglottic stenosis, orbital pseudotumor, mononeuritis multiplex
Microscopic Polyangiitis (MPA)
- Rapidly progressive glomerulonephritis and pulmonary capillaritis/alveolar hemorrhage
- Associated with p-ANCA (anti-MPO antibodies)
- No granulomatous inflammation (distinguishes from GPA)
- Renal biopsy shows pauci-immune crescentic glomerulonephritis
Diagnosis
- ANCA testing: c-ANCA/PR3 for GPA; p-ANCA/MPO for MPA
- Urinalysis: dysmorphic RBCs, RBC casts, proteinuria
- Renal biopsy: pauci-immune crescentic GN is characteristic
- CT chest: nodules, cavitary lesions, ground-glass opacities
- Tissue biopsy when possible for definitive diagnosis
Urgent Management
- Organ-threatening disease (pulmonary hemorrhage, RPGN): pulse IV methylprednisolone + rituximab or cyclophosphamide
- Rituximab is preferred for induction in most cases (RAVE trial: noninferior to cyclophosphamide)
- Plasma exchange: consider in severe renal disease (creatinine > 5.7 mg/dL) or diffuse alveolar hemorrhage (PEXIVAS trial showed mortality benefit uncertain but used in practice)
- Avacopan (complement C5a receptor inhibitor): approved as adjunctive therapy; may reduce glucocorticoid exposure
Maintenance Therapy
- Rituximab every 6 months or azathioprine: for remission maintenance
- Duration: minimum 2 years; relapse is common, especially in PR3-positive disease
- Monitor ANCA titers, renal function, and urinalysis regularly
Polyarteritis Nodosa
- Medium-vessel vasculitis; ANCA-negative
- Associated with hepatitis B in some cases
- Mesenteric ischemia, renal artery aneurysms, mononeuritis multiplex, livedo reticularis, skin nodules
- No glomerulonephritis or pulmonary capillaritis (distinguishes from ANCA-associated vasculitis)
- Diagnosis: angiography showing microaneurysms; tissue biopsy
- Treatment: corticosteroids +/- cyclophosphamide; treat hepatitis B if associated
When to Suspect Vasculitis
- Multisystem disease without a unifying diagnosis
- Unexplained constitutional symptoms with end-organ damage
- Palpable purpura, mononeuritis multiplex, unexplained renal failure with active sediment
- Pulmonary-renal syndrome (alveolar hemorrhage + glomerulonephritis)
- New headache or visual symptoms in a patient > 50 with elevated inflammatory markers
Key Clinical Pearls
- Start high-dose corticosteroids immediately for suspected GCA with visual symptoms; do not wait for biopsy
- ANCA-associated vasculitis presenting with pulmonary-renal syndrome is a medical emergency
- PAN is ANCA-negative and does not cause glomerulonephritis or pulmonary capillaritis
- Rituximab is noninferior to cyclophosphamide for ANCA-associated vasculitis induction and is preferred for most patients
- Always check urinalysis and creatinine in suspected vasculitis; silent renal involvement is common
References
- Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1-11.
- Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis (RAVE). N Engl J Med. 2010;363(3):221-232.
- Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30-47.
- Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33(8):1122-1128.