Vasculitis Syndromes

Vasculitis is inflammation of blood vessel walls leading to ischaemia, necrosis and aneurysm formation. The dominant exam framework is size-based classification (Chapel Hill consensus), which links each syndrome to a characteristic vessel calibre, demographic, ANCA status and a signature clinical clue. Master the size-demographic-ANCA triad and most questions answer themselves.

Classification (Chapel Hill nomenclature)

Vasculitides are grouped by the predominant vessel size involved. This single axis drives both the clinical picture and the answer to most MCQs.

Vessel size	Syndromes	Hallmark vessels
Large vessel	Takayasu arteritis, Giant cell (temporal) arteritis	Aorta + major branches
Medium vessel	Polyarteritis nodosa (PAN), Kawasaki disease	Main visceral arteries (renal, coronary, mesenteric)
Small vessel — ANCA-associated	GPA (Wegener), EGPA (Churg-Strauss), MPA	Arterioles, capillaries, venules
Small vessel — immune complex	IgA vasculitis (HSP), cryoglobulinaemic, anti-GBM, hypocomplementaemic urticarial	Capillaries, post-capillary venules
Variable vessel	Behçet disease, Cogan syndrome	Any size, arteries + veins

High-yield: Large-vessel vasculitis classically causes granulomatous inflammation; ANCA-associated small-vessel vasculitis causes pauci-immune necrotising inflammation (few/no immune deposits); immune-complex small-vessel vasculitis shows deposits on immunofluorescence.

A useful first branch point: age. Takayasu and Kawasaki affect the young; GCA and PAN affect older adults; HSP is the commonest childhood vasculitis.

Large-vessel vasculitis

Takayasu arteritis ("pulseless disease")

• Granulomatous panarteritis of the aorta and its major branches, classically the subclavian and carotid.
• Demographics: young Asian females (< 40 years). The most stereotyped exam stem.
• Phases: early systemic (fever, malaise, arthralgia) → late occlusive (ischaemic).
• Clinical features: absent/asymmetric upper-limb pulses, >10 mmHg inter-arm BP difference, subclavian/carotid bruits, claudication of limbs, renovascular hypertension, visual disturbance, aortic regurgitation.
• Investigation of choice: CT/MR angiography showing long, smooth segmental stenoses ("rat-tail" tapering), occlusions and aneurysms. Conventional angiography is the historic gold standard.
• ESR/CRP raised in active disease. No diagnostic autoantibody.
• Management: high-dose corticosteroids; steroid-sparers (methotrexate, azathioprine, tocilizumab, TNF inhibitors). Angioplasty/bypass for critical stenosis once inflammation controlled.

High-yield: Takayasu = young Asian female + absent radial pulse + BP difference between arms. Diagnosis confirmed by angiography, not biopsy.

Giant cell arteritis (temporal arteritis)

• Granulomatous large/medium vessel arteritis of the extracranial carotid branches, especially the temporal artery.
• Demographics: age > 50 years (often > 70), commonest primary vasculitis in adults; strong association with polymyalgia rheumatica (PMR).
• Clinical features: new-onset temporal/throbbing headache, scalp tenderness, jaw claudication (most specific symptom), thickened/tender/pulseless temporal artery, constitutional symptoms.
• Feared complication: anterior ischaemic optic neuropathy → sudden, painless, irreversible monocular blindness from posterior ciliary artery involvement.
• Investigation: ESR markedly raised (>50 mm/hr), CRP raised; temporal artery biopsy is confirmatory — shows granulomatous inflammation, multinucleate giant cells, fragmented internal elastic lamina. Biopsy a long segment (>1–2 cm) because of skip lesions.
• Management flow: Suspect GCA → start high-dose prednisolone IMMEDIATELY (do not wait for biopsy) → biopsy within 1–2 weeks (steroids do not erase findings quickly) → add IV methylprednisolone if visual symptoms → taper over months → tocilizumab as steroid-sparing agent → low-dose aspirin to reduce ischaemic events.

High-yield: In suspected GCA, steroids first, biopsy later — vision loss is irreversible. ESR >50, jaw claudication and age >50 are the classic triad.

Feature	Takayasu	Giant cell arteritis
Typical age	< 40 yrs	> 50 yrs
Sex/ethnicity	Asian females	Older adults, both sexes
Vessel	Aorta + branches	Temporal/cranial branches
Signature clue	Absent pulse, BP gap	Jaw claudication, blindness
Diagnosis	Angiography	Temporal artery biopsy
Associated	—	Polymyalgia rheumatica

Medium-vessel vasculitis

Polyarteritis nodosa (PAN)

• Necrotising arteritis of medium-sized muscular arteries causing aneurysms ("beads on a string"), thrombosis and infarction. Spares the lungs and is NOT associated with ANCA or glomerulonephritis (it causes renal infarcts/renovascular hypertension, not GN).
• Association: Hepatitis B (immune-complex driven); also hairy cell leukaemia.
• Clinical features: fever, weight loss, myalgia; mononeuritis multiplex (e.g. foot drop), skin (livedo reticularis, nodules, ulcers), abdominal angina/mesenteric ischaemia, orchitis (testicular pain is a classic clue), renovascular hypertension.
• Investigation of choice: conventional/CT angiography of renal and mesenteric vessels showing microaneurysms; biopsy of affected nerve/muscle/skin shows necrotising arteritis with fibrinoid necrosis. Check HBsAg.
• Management: corticosteroids ± cyclophosphamide for severe disease. HBV-associated PAN: antiviral therapy + short steroids + plasma exchange (avoid prolonged immunosuppression which worsens viral replication).

High-yield: PAN spares the lung and is ANCA-negative; presence of glomerulonephritis or pulmonary haemorrhage points away from PAN towards microscopic polyangiitis. Testicular pain + mononeuritis multiplex + HBV = PAN.

Kawasaki disease

• Acute self-limiting medium-vessel vasculitis of childhood (usually < 5 yrs); leading cause of acquired heart disease in children due to coronary artery aneurysms.
• Diagnostic criteria — fever ≥ 5 days plus ≥ 4 of 5 (mnemonic "CRASH and burn"):
  • Conjunctivitis (bilateral, non-exudative, limbal sparing)
  • Rash (polymorphous)
  • Adenopathy (cervical, unilateral, > 1.5 cm)
  • Strawberry tongue / mucositis, cracked red lips
  • Hand/foot changes (oedema, erythema, later periungual desquamation)
  • burn = fever ≥ 5 days
• Investigation: clinical diagnosis; echocardiography to detect coronary aneurysms (baseline and follow-up). Raised ESR/CRP, thrombocytosis (2nd week).
• Management: IVIG + high-dose aspirin within 10 days reduces aneurysm risk. (Kawasaki is one of the few paediatric indications for aspirin.)

High-yield: Kawasaki — fever ≥ 5 days + CRASH; treat with IVIG + aspirin; complication = coronary artery aneurysm, monitored by echo.

Small-vessel vasculitis — ANCA-associated (AAV)

These share pauci-immune necrotising inflammation and a tendency for pulmonary-renal syndrome (alveolar haemorrhage + rapidly progressive glomerulonephritis).

Syndrome	ANCA	Antigen	Distinguishing clue
GPA (Wegener)	c-ANCA	PR3	Upper + lower airway + kidney; saddle-nose, granulomas
EGPA (Churg-Strauss)	p-ANCA (~40%)	MPO	Asthma + eosinophilia, allergic history
MPA (microscopic polyangiitis)	p-ANCA	MPO	Pulmonary-renal, no granulomas, no asthma

Granulomatosis with polyangiitis (GPA / Wegener)

• Necrotising granulomatous vasculitis of upper airway, lung and kidney.
• Triad: upper respiratory tract (sinusitis, otitis, nasal crusting, saddle-nose deformity from septal destruction, subglottic stenosis) + lower respiratory (cavitating lung nodules, haemoptysis) + necrotising glomerulonephritis.
• Eyes (scleritis, proptosis from retro-orbital mass), skin, nerves.
• Marker: c-ANCA (anti-PR3) — highly specific.
• Investigation: ANCA serology; biopsy (lung/kidney/nasal) showing granulomatous necrotising vasculitis; CXR/CT — cavitating nodules. Urine for active sediment.

High-yield: Saddle-nose + cavitating lung nodules + haematuria + c-ANCA/PR3 = GPA.

Eosinophilic granulomatosis with polyangiitis (EGPA / Churg-Strauss)

• Three phases: allergic (asthma, allergic rhinitis) → eosinophilic (eosinophilia, pulmonary infiltrates) → vasculitic (mononeuritis multiplex, cardiac, GI).
• Hallmarks: long-standing asthma + peripheral eosinophilia + p-ANCA (anti-MPO). Cardiac involvement is the leading cause of death.
• Leukotriene-receptor antagonist exposure historically linked (likely unmasking).

Microscopic polyangiitis (MPA)

• Pauci-immune small-vessel vasculitis with necrotising GN and pulmonary capillaritis but NO granulomas and NO asthma — distinguishes it from GPA and EGPA. p-ANCA (anti-MPO) positive. The "great mimic" of PAN, but MPA affects small vessels, involves the lung, and is ANCA-positive.

Management of ANCA-associated vasculitis

Induction: glucocorticoids + (cyclophosphamide OR rituximab). Add plasma exchange for severe alveolar haemorrhage or severe renal failure. Maintenance: lower-dose steroids + rituximab / azathioprine / methotrexate. EGPA-specific: mepolizumab (anti-IL-5) for relapsing/refractory disease.

High-yield: Rituximab is now first-line (with steroids) for induction in severe GPA/MPA, especially relapsing or PR3-positive disease.

Small-vessel vasculitis — immune complex

IgA vasculitis (Henoch-Schönlein purpura, HSP)

• Commonest vasculitis of childhood, often post-upper-respiratory infection; IgA immune-complex deposition.
• Classic tetrad:
  1. Palpable purpura over buttocks and extensor lower limbs (symmetrical, dependent)
  2. Arthralgia/arthritis (knees, ankles)
  3. Abdominal pain (risk of intussusception — typically ileoileal)
  4. IgA nephropathy (haematuria, proteinuria) — determines long-term prognosis
• Investigation: clinical; skin biopsy → leukocytoclastic vasculitis with IgA deposition on immunofluorescence; urinalysis to track renal involvement. Normal platelet count (purpura is non-thrombocytopenic).
• Management: largely supportive (self-limiting); corticosteroids for severe abdominal pain or nephritis; monitor BP and urine.

High-yield: HSP = palpable purpura on buttocks/legs + abdominal pain + arthritis + haematuria, with normal platelets and IgA deposits. Watch for intussusception.

Cryoglobulinaemic vasculitis

• Hepatitis C is the leading cause (type II mixed cryoglobulinaemia). Palpable purpura, arthralgia, neuropathy, membranoproliferative GN, low C4. Treat underlying HCV ± rituximab.

Variable-vessel: Behçet disease

• Recurrent oral + genital aphthous ulcers, uveitis, skin lesions, and the classic pathergy test (sterile pustule at needle-prick site). Associated with HLA-B51; high prevalence along the Silk Route (Turkey, Middle East). Can involve veins (thrombosis) and arteries (pulmonary artery aneurysm).

Diagnostic approach — putting it together

1. Confirm vasculitis (raised inflammatory markers, ischaemia, multisystem involvement).
2. Define vessel size from organ pattern (pulse loss/aorta = large; coronary/renal infarct = medium; purpura/GN/alveolar haemorrhage = small).
3. Order serology: ANCA (PR3 → GPA; MPO → MPA/EGPA), HBsAg (PAN), HCV/cryoglobulins, complement, eosinophil count.
4. Confirm with the right test: biopsy for small-vessel and GCA; angiography for large-vessel and PAN.
5. Treat: steroids are the backbone across all; add cyclophosphamide/rituximab for organ-threatening AAV; IVIG+aspirin for Kawasaki; antivirals for HBV-PAN/HCV-cryo.

Key differentials

• Pulmonary-renal syndrome: GPA, MPA, anti-GBM (Goodpasture) disease, SLE. Anti-GBM shows linear IgG on IF (vs pauci-immune AAV).
• Palpable purpura + abdominal pain: HSP vs cryoglobulinaemia vs drug-induced leukocytoclastic vasculitis.
• Sudden monocular blindness in elderly: GCA vs central retinal artery occlusion vs non-arteritic AION (GCA has high ESR/CRP).
• Mimics of true vasculitis: infective endocarditis, cholesterol emboli, atrial myxoma, antiphospholipid syndrome — always exclude before immunosuppressing.

Complications

• GCA: irreversible blindness, aortic aneurysm/dissection.
• Takayasu: stroke, renovascular hypertension, aortic regurgitation.
• PAN: bowel infarction/perforation, renal infarcts.
• Kawasaki: coronary aneurysm, MI, sudden death.
• AAV: ESRD, alveolar haemorrhage, subglottic stenosis (GPA), cardiac death (EGPA).
• HSP: chronic kidney disease (from IgA nephropathy), intussusception.

Recently asked / exam angle

• Young Asian woman, unequal arm BP, absent radial pulse → Takayasu; best test = MR/CT angiography.
• Elderly patient, jaw claudication, ESR 90, sudden visual loss → GCA; start steroids before biopsy.
• Asthma + eosinophilia + mononeuritis multiplex + p-ANCA → EGPA (Churg-Strauss).
• Saddle-nose + cavitating lung nodule + haematuria + c-ANCA → GPA.
• Child with fever ≥ 5 days, strawberry tongue, peeling fingertips → Kawasaki; treat IVIG + aspirin, complication coronary aneurysm.
• Child with buttock purpura, abdominal pain, normal platelets → HSP; biopsy IF shows IgA.
• HBsAg-positive man with mononeuritis multiplex, testicular pain, renal microaneurysms → PAN.
• Match-the-following ANCA: PR3 = c-ANCA = GPA; MPO = p-ANCA = MPA/EGPA.
• First-line induction for severe GPA → steroids + rituximab (or cyclophosphamide); add plasma exchange for alveolar haemorrhage.

Rapid revision

• Takayasu = young Asian female, pulseless, BP gap >10 mmHg, diagnose by angiography.
• GCA = age >50, jaw claudication, ESR >50, temporal artery biopsy (skip lesions); steroids before biopsy to save vision.
• PAN = medium vessels, HBV-associated, ANCA-negative, spares lung, microaneurysms on angiography, testicular pain.
• Kawasaki = fever ≥5 days + CRASH; IVIG + aspirin; complication = coronary aneurysm.
• GPA (Wegener) = c-ANCA/PR3, saddle-nose, cavitating nodules, GN — the "ELK" (ENT, Lung, Kidney).
• EGPA (Churg-Strauss) = p-ANCA/MPO, asthma + eosinophilia, cardiac death; treat refractory with mepolizumab.
• MPA = p-ANCA/MPO, pulmonary-renal, no granuloma, no asthma.
• HSP = commonest childhood vasculitis, palpable purpura on buttocks/legs, normal platelets, IgA deposits, watch intussusception.
• Cryoglobulinaemia = Hepatitis C, low C4, MPGN.
• Behçet = oral + genital ulcers, uveitis, HLA-B51, positive pathergy test.
• Steroids are the backbone of all vasculitis treatment; organ-threatening AAV adds rituximab/cyclophosphamide.
• Pulmonary-renal syndrome: think GPA, MPA, anti-GBM (linear IgG), SLE.