Systemic Vasculitides
A boards-focused tour of the systemic vasculitides organized by Chapel Hill vessel size, pairing each disease with its antibody, buzzwords, and imaging. It drills the high-yield next-best-step decisions—steroids-before-biopsy in giant cell arteritis and rituximab-based induction in ANCA-associated disease.
Framework: classify by vessel size
Systemic vasculitides are immune-mediated inflammation of vessel walls, producing three kinds of damage: luminal narrowing (ischemia), wall weakening (aneurysm/rupture), and downstream organ infarction. The Boards' organizing principle is the Chapel Hill classification by vessel size, because size predicts the antibody, the imaging, and the clinical picture.
- Large vessel: giant cell (temporal) arteritis, Takayasu arteritis
- Medium vessel: polyarteritis nodosa (PAN), Kawasaki disease
- Small vessel — ANCA-associated: GPA, MPA, EGPA
- Small vessel — immune-complex: IgA vasculitis (HSP), cryoglobulinemic (HCV), anti-GBM (Goodpasture)
Shared red flags of any systemic vasculitis: palpable purpura, mononeuritis multiplex, glomerulonephritis, constitutional symptoms (fever, weight loss), and high ESR/CRP. When a vignette pairs multi-organ ischemia + elevated inflammatory markers + no infection, think vasculitis.
- Giant cell arteritis (GCA): age >50, female; new temporal headache, jaw claudication, scalp tenderness, amaurosis fugax → permanent vision loss from arteritic anterior ischemic optic neuropathy. ESR often 50–100+. Associated with polymyalgia rheumatica (~40–50%).
- Takayasu ('pulseless disease'): Asian women <40; absent/asymmetric pulses, arm-to-arm BP discrepancy, bruits, limb claudication. Aorta + major branches.
- Polyarteritis nodosa (PAN): medium vessel; Hepatitis B–associated; SPARES the lungs; mononeuritis multiplex, mesenteric/renal ischemia, renovascular HTN, livedo reticularis. Renal damage is from arterial ischemia/infarction, not glomerulonephritis. ANCA-negative. Angiography = microaneurysms ('string of beads/rosary').
- Kawasaki disease: children <5; risk of coronary artery aneurysms; treat IVIG + aspirin (a rare pediatric aspirin indication).
ANCA-associated (pauci-immune GN, no immune deposits):
- GPA (Wegener): c-ANCA / anti-PR3. Triad = upper airway (sinusitis, epistaxis, saddle-nose), lung (cavitary nodules, hemoptysis), kidney (RPGN).
- MPA: p-ANCA / anti-MPO. Like GPA but no granulomas, no nasopharyngeal destruction; most common cause of the pulmonary–renal syndrome.
- EGPA (Churg-Strauss): p-ANCA / anti-MPO (~40%); asthma + eosinophilia + granulomas, mononeuritis multiplex.
Immune-complex (deposits present on IF):
- IgA vasculitis (HSP): child after URI; palpable purpura (buttocks/legs), arthralgia, abdominal pain, IgA nephropathy. Usually self-limited.
- Cryoglobulinemic: Hepatitis C; palpable purpura, arthralgia, low C4.
- Anti-GBM (Goodpasture): hemoptysis + RPGN; linear IgG on immunofluorescence.
Comparison — vessel, antibody, clue, first-line
| Vasculitis | Vessel | Antibody / marker | Classic clue | First-line Tx |
|---|---|---|---|---|
| Giant cell arteritis | Large | ESR↑↑, no autoAb | Jaw claudication, vision loss, age >50 | Steroids NOW |
| Takayasu | Large | ESR↑ | Pulseless, arm BP diff, <40 | Steroids |
| PAN | Medium | HBsAg; ANCA– | Spares lungs; string-of-beads | Steroids ± cyclophosphamide (HBV: antiviral) |
| Kawasaki | Medium | — | Coronary aneurysm, child <5 | IVIG + aspirin |
| GPA | Small | c-ANCA / PR3 | Sinus + lung + kidney, saddle nose | Steroids + rituximab |
| MPA | Small | p-ANCA / MPO | Pulmonary-renal, no granuloma | Steroids + rituximab |
| EGPA | Small | p-ANCA / MPO (~40%) | Asthma + eosinophilia | Steroids; +CYC/rituximab if severe; mepolizumab (anti–IL-5) if refractory |
| IgA vasculitis (HSP) | Small | IgA deposits | Purpura + abd pain, child | Supportive |
Vignette: A 72-year-old woman reports 3 weeks of new right-sided temporal headache, scalp tenderness when combing her hair, and pain in the jaw while chewing. This morning she had transient monocular vision loss. ESR 92 mm/hr, CRP elevated.
- Diagnosis: Giant cell (temporal) arteritis.
- Next best step: Start high-dose glucocorticoids IMMEDIATELY — do not wait for biopsy. With any visual symptoms, give IV methylprednisolone.
- Confirm with temporal artery biopsy (granulomatous inflammation, giant cells, skip lesions) within ~1–2 weeks — biopsy findings persist for weeks and a negative biopsy (skip lesions) does not exclude the diagnosis. Temporal artery ultrasound ('halo sign') supports the dx.
- Tocilizumab (IL-6 inhibitor) is a steroid-sparing adjunct.
Board trap: delaying steroids to get the biopsy → preventable, irreversible blindness.
Vignette: A 48-year-old man has months of chronic sinusitis and epistaxis, now with hemoptysis and dark urine. Exam shows a saddle-nose deformity. Labs: hematuria with RBC casts, rising creatinine; CXR: cavitary lung nodules. c-ANCA / anti-PR3 positive.
- Diagnosis: Granulomatosis with polyangiitis (GPA).
- Next best step: Obtain biopsy to confirm — necrotizing granulomatous vasculitis; renal biopsy = pauci-immune crescentic GN.
- Induction: high-dose glucocorticoids + rituximab (or cyclophosphamide). Add plasma exchange only in selected severe disease (e.g., severe renal impairment or alveolar hemorrhage) — not routine after PEXIVAS.
Contrast: MPA gives the same pulmonary-renal picture but is p-ANCA/MPO and lacks granulomas and upper-airway destruction.
Diagnostic workflow & management principles
Work-up, in order:
- ESR/CRP — elevated in active disease.
- ANCA panel — c-ANCA/PR3 (GPA) vs p-ANCA/MPO (MPA, EGPA). ANCA is negative in large-/medium-vessel and immune-complex disease.
- Urinalysis every time — dysmorphic RBCs / RBC casts signal glomerulonephritis and upstage urgency.
- Imaging: angiography (CTA/MRA) for large/medium vessel — Takayasu stenoses/occlusion, PAN microaneurysms; temporal artery US for GCA.
- Biopsy = tissue gold standard, but must not delay sight- or organ-saving therapy.
Management principles:
- Steroids are the backbone of nearly all; start empirically when organ/vision-threatening.
- ANCA vasculitis: induction = steroids + rituximab or cyclophosphamide, then maintenance.
- Treat the driver: HBV (PAN) and HCV (cryoglobulinemia) need antivirals; Kawasaki needs IVIG + aspirin.
- Kawasaki — 'CRASH and Burn' (need fever ≥5 days + ≥4 of): Conjunctivitis (bilateral, nonexudative), Rash (polymorphous), Adenopathy (cervical), Strawberry tongue/mucositis, Hands/feet (edema, then desquamation); Burn = fever.
- GPA — 'ELK': Ears/nose/sinus, Lungs, Kidneys (the classic triad).
- PAN Passes (spares) the lungs — pulmonary sparing separates it from ANCA vasculitis.
- ANCA pairing: c-ANCA = PR3 (GPA); p-ANCA = MPO (MPA, EGPA).
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