Vasculitis Classification by Vessel Size
Vasculitis is best organized by the caliber of vessel involved, because vessel size predicts the clinical presentation, the affected demographic, and the diagnostic workup. Large-vessel disease affects the aorta and its major branches (claudication, pulse deficits); medium-vessel disease strikes muscular arteries (aneurysms, organ infarction); and small-vessel disease damages arterioles, capillaries, and venules (purpura, glomerulonephritis). Anchoring each vasculitis to its vessel size lets you rapidly narrow the differential and choose the right diagnostic test.
Large-Vessel Vasculitis (GCA, Takayasu Arteritis)
Large-vessel vasculitis targets the aorta and its major branches, producing claudication and pulse deficits. Giant cell arteritis (GCA, temporal arteritis) is the most common systemic vasculitis in adults, occurring almost exclusively in patients over 50, more often women, with Northern European ancestry. Look for new temporal headache with scalp tenderness, jaw claudication (highly specific), and visual symptoms (amaurosis fugax, diplopia, permanent vision loss); about half have associated polymyalgia rheumatica. ESR is markedly elevated (often >50, can be >100) with elevated CRP; temporal artery biopsy shows granulomatous inflammation with giant cells and skip lesions (may be falsely negative), and ultrasound/MRI may reveal a 'halo sign.' Start high-dose glucocorticoids immediately—before biopsy—because preventing blindness is the priority; biopsy stays positive for up to 2 weeks after steroids. Tocilizumab is a steroid-sparing option. Takayasu arteritis ('pulseless disease') affects young women under 40, more commonly of Asian ancestry, causing diminished/absent pulses, limb claudication, hypertension (renal artery stenosis), and bruits. Diagnose with CT or MR angiography, which classically shows long-segment stenoses, arterial wall thickening, occlusions, and occasionally aneurysms of the aorta and its major branches; treat with glucocorticoids plus steroid-sparing agents (methotrexate, azathioprine, mycophenolate) and vascular intervention for critical stenosis.
Medium-Vessel Vasculitis (PAN, Kawasaki Disease)
Medium-vessel vasculitis affects muscular arteries, producing aneurysms and organ infarction. Polyarteritis nodosa (PAN) occurs in adults and spares capillaries and venules—so there is NO glomerulonephritis; instead, renal involvement is renovascular hypertension. Features span systemic symptoms (fever, weight loss, myalgias), skin (livedo reticularis, nodules, ulcers), neurological (mononeuritis multiplex—asymmetric neuropathy), GI (abdominal pain, bowel ischemia), and cardiac (coronary arteritis). About 20% of cases are associated with hepatitis B, so check HBsAg. Angiography reveals microaneurysms in a 'string of beads' pattern, biopsy shows necrotizing arteritis of medium vessels, and crucially PAN is ANCA negative. Treat with glucocorticoids plus cyclophosphamide for severe disease, and antiviral therapy if hepatitis B is present. Kawasaki disease is the medium-vessel vasculitis of children under 5, presenting with fever ≥5 days plus mucocutaneous changes: non-purulent conjunctival injection, strawberry tongue, lip fissuring, rash, and palm/sole erythema with desquamation, along with cervical lymphadenopathy. The dreaded complication is coronary artery aneurysm. Diagnosis is clinical (fever plus 4 of 5 mucocutaneous features); treat with IVIG plus aspirin to reduce coronary aneurysm risk, and monitor coronaries with echocardiography.
Small-Vessel Vasculitis (GPA, MPA, EGPA, IgA Vasculitis)
Small-vessel vasculitis attacks arterioles, capillaries, and venules, producing palpable purpura and glomerulonephritis. GPA, MPA, and EGPA are grouped as the 'ANCA-associated' vasculitides and share pauci-immune crescentic glomerulonephritis on renal biopsy (few immune deposits) when the kidney is involved, but the strength of the ANCA association differs sharply among them. GPA (granulomatosis with polyangiitis) causes upper respiratory disease (sinusitis, nasal septal perforation, 'saddle nose'), lower respiratory disease (pulmonary nodules, cavitary lesions, diffuse alveolar hemorrhage), and rapidly progressive glomerulonephritis; it is ANCA positive in roughly 80–90% of cases, classically c-ANCA (anti-PR3). MPA (microscopic polyangiitis) resembles GPA but has NO granulomas and NO upper respiratory involvement, with rapidly progressive GN plus pulmonary hemorrhage as the classic combination; it is ANCA positive in roughly 80–90% of cases, classically p-ANCA (anti-MPO). EGPA (eosinophilic granulomatosis with polyangiitis, formerly Churg-Strauss) features a history of asthma/allergies, high peripheral eosinophilia, mononeuritis multiplex, and eosinophilic myocarditis (its leading cause of death); it progresses through allergic, eosinophilic, and vasculitic phases. Importantly, EGPA is ANCA positive in only about 30–60% of cases—when present, ANCA is typically p-ANCA (anti-MPO) and correlates with vasculitic manifestations such as glomerulonephritis and neuropathy, whereas ANCA-negative EGPA tends to have more prominent cardiac and pulmonary eosinophilic infiltrate disease. A negative ANCA therefore does not exclude EGPA. IgA vasculitis (Henoch-Schönlein purpura) is a small-vessel vasculitis with IgA immune-complex deposition (NOT ANCA-associated), classically presenting with palpable purpura on the lower extremities, arthralgias, abdominal pain, and IgA nephropathy. Diagnose ANCA-associated disease with ANCA testing plus tissue biopsy for definitive confirmation. Induction is glucocorticoids plus cyclophosphamide or rituximab; maintenance uses rituximab, azathioprine, or methotrexate; and plasmapheresis is reserved for severe renal failure or pulmonary hemorrhage.
High-yield
- Vessel size predicts presentation: large = claudication/pulse deficits; medium = aneurysms/organ infarction; small = purpura/glomerulonephritis.
- GCA occurs in patients >50; Takayasu affects young women (<40).
- In a patient >50 with new headache, jaw claudication, or visual symptoms, start steroids before biopsy—preventing blindness is the priority.
- GCA temporal artery biopsy remains positive for up to 2 weeks after starting steroids.
- PAN is ANCA negative and spares the glomeruli (renovascular hypertension, not GN); ~20% associated with hepatitis B.
- Kawasaki disease: fever ≥5 days + mucocutaneous features in a child <5; coronary artery aneurysm is the feared complication; treat with IVIG + aspirin.
- ANCA-associated vasculitides (GPA, MPA, EGPA) can cause pulmonary-renal syndromes: c-ANCA (PR3) → GPA; p-ANCA (MPO) → MPA. EGPA, when ANCA positive, is usually p-ANCA (MPO).
- GPA and MPA are ANCA positive in ~80–90% of cases, but EGPA is ANCA positive in only ~30–60%—a negative ANCA does not exclude EGPA.
- Renal biopsy in ANCA-associated vasculitis shows pauci-immune crescentic glomerulonephritis.
- EGPA three phases: asthma/allergy → eosinophilia → vasculitis; eosinophilic myocarditis is the leading cause of death, and ANCA-negative EGPA skews toward cardiac/pulmonary infiltrate disease.
- 'String of beads' microaneurysms on angiography point to PAN (also classically seen in fibromuscular dysplasia of the renal artery); Takayasu instead shows long-segment stenoses, wall thickening, and occlusions.
Pitfalls
- Confusing PAN with small-vessel disease—PAN spares capillaries/venules, causes NO glomerulonephritis, and is ANCA negative.
- Assuming a normal temporal artery biopsy excludes GCA; skip lesions cause false negatives, and steroids should never be delayed for biopsy.
- Mixing up GCA and Takayasu demographics—GCA is >50 years, Takayasu is young women <40.
- Forgetting that MPA lacks granulomas and upper respiratory involvement, unlike GPA.
- Assuming a negative ANCA rules out EGPA—only ~30–60% of EGPA is ANCA positive, and ANCA-negative EGPA is a recognized phenotype with more cardiac/pulmonary infiltrate disease.
- Missing hepatitis B testing (HBsAg) in a patient with suspected PAN.
- Overlooking eosinophilic myocarditis in EGPA—it is the leading cause of death and must be evaluated urgently.
- Attributing Kawasaki's renal or vascular findings to glomerulonephritis; the danger in Kawasaki is coronary artery aneurysm.
- Attributing a 'string of beads' microaneurysm pattern to Takayasu—that pattern belongs to PAN and fibromuscular dysplasia, whereas Takayasu shows long smooth stenoses, wall thickening, and occlusions.
Clinical pearls
- Jaw claudication is a highly specific clue for giant cell arteritis.
- Takayasu is 'pulseless disease'—diminished pulses and bruits over major arteries in a young woman, with long-segment stenoses on angiography.
- Mononeuritis multiplex (asymmetric neuropathy) is a shared clue for both PAN and EGPA.
- Saddle-nose deformity and nasal septal perforation point to GPA.
- Rapidly progressive GN + pulmonary hemorrhage is the classic pairing of microscopic polyangiitis.
- When EGPA is ANCA positive, expect p-ANCA (anti-MPO) and more vasculitic (renal/neurologic) disease; ANCA-negative EGPA tilts toward cardiac and pulmonary infiltrate.
- Start IVIG and aspirin promptly in Kawasaki disease to reduce coronary aneurysm risk.
Frequently asked
How does vessel size help me quickly categorize a vasculitis?
Match the clinical picture to vessel caliber: large-vessel disease (aorta and branches) causes claudication and pulse deficits; medium-vessel disease (muscular arteries) causes aneurysms and organ infarction; small-vessel disease (arterioles, capillaries, venules) causes palpable purpura and glomerulonephritis.
Why do we start steroids before biopsy in suspected GCA?
Because GCA can cause irreversible blindness, preventing vision loss is the priority. High-dose glucocorticoids are started immediately, and the temporal artery biopsy remains positive for up to 2 weeks after steroids are begun, so treatment does not compromise diagnosis.
How do I distinguish PAN from small-vessel vasculitis?
PAN is a medium-vessel vasculitis that spares capillaries and venules, so it does NOT cause glomerulonephritis (renal involvement is renovascular hypertension) and it is ANCA negative. Angiography shows 'string of beads' microaneurysms, and ~20% of cases are associated with hepatitis B.
What are the classic angiographic findings in PAN versus Takayasu arteritis?
PAN produces medium-vessel microaneurysms in a 'string of beads' pattern (a finding also classically taught for fibromuscular dysplasia of the renal artery). Takayasu arteritis, a large-vessel vasculitis, instead shows long-segment stenoses, arterial wall thickening, occlusions, and occasionally aneurysms of the aorta and its major branches—not a 'string of beads' pattern.
What ANCA pattern goes with which small-vessel vasculitis, and how reliable is ANCA?
c-ANCA (anti-PR3) is associated with GPA; p-ANCA (anti-MPO) is associated with MPA. GPA and MPA are ANCA positive in ~80–90% of cases. EGPA is ANCA positive in only ~30–60% of cases and, when positive, is usually p-ANCA (anti-MPO); a negative ANCA does not exclude EGPA. Tissue biopsy confirms the diagnosis, with renal biopsy showing pauci-immune crescentic glomerulonephritis when the kidney is involved.
How do GPA and MPA differ?
GPA has granulomas and prominent upper respiratory involvement (sinusitis, nasal septal perforation, saddle-nose), along with lower respiratory disease and rapidly progressive GN, and is classically c-ANCA (anti-PR3) positive. MPA is similar but has NO granulomas and NO upper respiratory involvement; its classic presentation is rapidly progressive GN plus pulmonary hemorrhage, and it is classically p-ANCA (anti-MPO) positive.
What are the diagnostic criteria and key complication of Kawasaki disease?
Kawasaki disease is diagnosed clinically in children under 5 by fever ≥5 days plus 4 of 5 mucocutaneous features (conjunctival injection, strawberry tongue/lip fissuring, rash, palm/sole erythema with desquamation, cervical lymphadenopathy). The dreaded complication is coronary artery aneurysm; treat with IVIG plus aspirin and monitor coronaries with echocardiography.
What are the three phases of EGPA and how does ANCA status relate to its presentation?
EGPA (formerly Churg-Strauss) progresses through an allergic phase (asthma, allergic rhinitis), an eosinophilic phase (peripheral eosinophilia and tissue infiltration), and a vasculitic phase (neuropathy, cardiac, renal involvement). Only about 30–60% of patients are ANCA positive; ANCA (typically p-ANCA/anti-MPO) tends to accompany vasculitic features such as glomerulonephritis and neuropathy, while ANCA-negative disease skews toward cardiac and pulmonary eosinophilic infiltrate. Eosinophilic myocarditis is the leading cause of death and warrants immediate cardiac evaluation.
Turn this into reasoning you can use on exam day — practice Vasculitis Classification by Vessel Size on branching cases where your decisions shape the patient.