Vasculitis & Vascular Pathology

Vasculitis is inflammation of vessel walls, classified primarily by the size of vessel involved, which is the single most exam-tested axis. This note also folds in atherosclerosis pathogenesis, aneurysms, and Mönckeberg sclerosis — the high-yield non-inflammatory vascular pathology that NEET PG loves to pair with ANCA tables.

Classification by vessel size (the master framework)

The Chapel Hill Consensus classifies vasculitides by the dominant calibre of vessel affected. Memorising this table is worth several marks because almost every MCQ asks either "which vessel?" or "which ANCA?".

Vessel size	Diseases	Classic clue
Large (aorta + major branches)	Takayasu arteritis, Giant cell (temporal) arteritis	Pulse loss, BP discrepancy, headache + jaw claudication
Medium (muscular arteries)	Polyarteritis nodosa (PAN), Kawasaki disease	Microaneurysms (rosary), coronary aneurysm in a child
Small (arterioles, capillaries, venules)	Granulomatosis with polyangiitis (GPA/Wegener), Eosinophilic GPA (Churg-Strauss), Microscopic polyangiitis (MPA), Henoch-Schönlein purpura (HSP/IgA vasculitis), Cryoglobulinaemic vasculitis	Palpable purpura, glomerulonephritis, ANCA

High-yield: The single most repeated NEET PG stem is "vessel size–disease pairing." Large → Takayasu/GCA; Medium → PAN/Kawasaki; Small → GPA/EGPA/MPA/HSP. Lock this in first.

High-yield: ANCA-associated vasculitides (AAV) are all small-vessel: GPA, EGPA, MPA. PAN is classically ANCA-negative and HBV-associated.

Large-vessel vasculitis

Giant cell (temporal) arteritis (GCA)

The commonest vasculitis in adults > 50 years, strongly associated with polymyalgia rheumatica (PMR).

• Clinical: new-onset temporal headache, scalp tenderness, jaw claudication (most specific symptom), and the feared complication — anterior ischaemic optic neuropathy → sudden painless monocular blindness from ophthalmic/posterior ciliary artery involvement.
• Investigation: markedly raised ESR (often > 50–100 mm/hr) and CRP. Temporal artery biopsy is the gold standard — but lesions are segmental (skip lesions), so a long (1.5–2 cm) segment is needed; a negative biopsy does not exclude.
• Histology: granulomatous inflammation of media with multinucleate giant cells, fragmentation of the internal elastic lamina.
• Management: start high-dose corticosteroids immediately — do NOT wait for biopsy — to save vision. Tocilizumab (anti-IL-6) is steroid-sparing.

High-yield: Jaw claudication is the most specific symptom; sudden blindness is the most feared complication. Treat first, biopsy later.

Takayasu arteritis ("pulseless disease")

Granulomatous large-vessel vasculitis of the aorta and arch branches in young Asian women < 40 years.

• Clinical: absent/weak upper-limb pulses, BP discrepancy between arms, carotid bruits, claudication, hypertension (renal artery stenosis).
• Investigation: angiography (CT/MR or conventional) shows long smooth stenoses and occlusions of the aortic arch branches; raised ESR.
• Histology: granulomatous panarteritis identical to GCA — distinguished by age and vessel territory.
• Management: corticosteroids; surgical/endovascular revascularisation for critical stenosis.

High-yield: Takayasu = young Asian woman + unequal arm BP + absent radial pulse. GCA = old patient + temporal headache + raised ESR. Same histology, opposite demographics.

Medium-vessel vasculitis

Polyarteritis nodosa (PAN)

Necrotising vasculitis of medium muscular arteries, classically spares the lungs and is NOT ANCA-associated.

• Associations: ~30% linked to Hepatitis B (HBsAg); also hairy cell leukaemia.
• Clinical: systemic — fever, weight loss, mononeuritis multiplex, abdominal angina, renal involvement (renin-mediated hypertension, NOT glomerulonephritis), skin nodules/livedo. Lungs spared (key discriminator from GPA/MPA).
• Pathology: segmental transmural fibrinoid necrosis → weakening → microaneurysms ("rosary/string-of-beads" on angiography). Lesions of different ages coexist (acute + healed) in the same vessel — a classic exam fact.
• Investigation: mesenteric/renal angiography shows microaneurysms; biopsy of affected organ; check HBsAg.
• Management: corticosteroids + cyclophosphamide; antivirals (e.g. entecavir) + plasma exchange if HBV-associated.

High-yield: PAN spares the lungs, is ANCA-negative, causes renin-driven HTN (not GN), and links to Hepatitis B. Lesions of different ages = pathognomonic.

Kawasaki disease

Acute febrile vasculitis of medium arteries in children < 5 years, the leading cause of acquired heart disease in children via coronary artery aneurysms.

Diagnosis needs fever ≥ 5 days + 4 of 5 (mnemonic CRASH and burn):

• C — Conjunctivitis (bilateral, non-exudative)
• R — Rash (polymorphous)
• A — Adenopathy (cervical, often unilateral)
• S — Strawberry tongue / mucosal changes, cracked lips
• H — Hand/foot erythema, oedema, later periungual desquamation
• (burn) — fever ≥ 5 days

Stepwise approach: Fever ≥5 days → meet CRASH criteria → baseline echocardiography → IVIG + high-dose aspirin → repeat echo to surveil coronary aneurysms.

High-yield: Kawasaki is the one time aspirin is given to a child (Reye's risk accepted) — IVIG + aspirin within 10 days reduces coronary aneurysm risk from ~25% to < 5%.

Small-vessel vasculitis & ANCA

This is the densest exam region. Two ANCA patterns matter:

Feature	c-ANCA (PR3-ANCA)	p-ANCA (MPO-ANCA)
Target antigen	Proteinase-3	Myeloperoxidase
IF pattern	Cytoplasmic	Perinuclear
Main disease	GPA (Wegener)	MPA, EGPA (Churg-Strauss)

Granulomatosis with polyangiitis (GPA / Wegener)

Triad of upper airway + lung + kidney, with c-ANCA / anti-PR3.

• Clinical: chronic sinusitis, nasal septal perforation → saddle-nose deformity, otitis; lung cavitating nodules, haemoptysis; rapidly progressive (crescentic) glomerulonephritis.
• Histology: necrotising granulomatous inflammation + small-vessel vasculitis; pauci-immune GN (scanty immune deposits on IF).
• Management: induction with corticosteroids + rituximab (or cyclophosphamide).

Eosinophilic GPA (Churg-Strauss / EGPA)

Asthma + eosinophilia + vasculitis, with p-ANCA / anti-MPO (positive in ~40%).

• Clinical phases: allergic rhinitis/asthma → blood and tissue eosinophilia → necrotising vasculitis with granulomas; mononeuritis multiplex and cardiac involvement (a leading cause of death).
• Investigation: raised eosinophils, raised IgE.

Microscopic polyangiitis (MPA)

Pauci-immune necrotising small-vessel vasculitis, p-ANCA / anti-MPO, presenting as pulmonary–renal syndrome (alveolar haemorrhage + RPGN) but — unlike GPA — no granulomas and no nasopharyngeal destruction.

High-yield: GPA = c-ANCA (PR3) + granulomas + saddle nose. MPA = p-ANCA (MPO) + NO granulomas. EGPA = p-ANCA + asthma + eosinophilia. All cause pauci-immune crescentic GN.

Henoch-Schönlein purpura (IgA vasculitis / HSP)

The commonest childhood vasculitis, immune-complex mediated with IgA deposition, typically following an upper-respiratory infection.

• Tetrad: palpable purpura (extensor legs/buttocks) + arthralgia + abdominal pain (risk of intussusception) + IgA nephropathy (haematuria).
• Pathology: leukocytoclastic vasculitis; IgA + C3 in mesangium on immunofluorescence — same deposits as Berger disease.
• Management: mostly supportive/self-limiting; steroids for severe gut/renal disease.

High-yield: HSP = child + palpable purpura on buttocks/legs + abdominal pain + IgA mesangial deposits. ANCA-negative (immune-complex, not pauci-immune).

Buerger disease (thromboangiitis obliterans)

A special segmental thrombosing vasculitis of small/medium arteries and veins of the extremities in heavy young male smokers.

• Clinical: instep claudication, migratory superficial thrombophlebitis, Raynaud's, digital ulceration/gangrene.
• Management: absolute smoking cessation is the only proven treatment that prevents amputation.

High-yield: Buerger disease in a young male smoker — corkscrew collaterals on angiography; quitting tobacco is curative-grade therapy.

Atherosclerosis — pathogenesis

The dominant non-inflammatory vascular pathology and a perennial MCQ source.

Risk factors: non-modifiable (age, male, family history/genetics) and modifiable — dyslipidaemia (↑LDL, ↓HDL), hypertension, smoking, diabetes. The most important is hyperlipidaemia.

"Response-to-injury" hypothesis (flow): Endothelial injury (LDL, HTN, smoking, haemodynamic stress at branch points) → LDL accumulation & oxidation in intima → monocyte adhesion & migration → macrophages engulf oxidised LDL → foam cells → fatty streak → smooth-muscle cell migration (PDGF, FGF) + ECM synthesis → fibrous cap over a necrotic lipid core = atheroma.

• Fatty streak is the earliest visible lesion (even in children) — composed of lipid-laden foam cells.
• Vulnerable plaque has a thin fibrous cap, large lipid core, many macrophages → prone to rupture → thrombosis → MI/stroke.
• Sites: abdominal aorta > coronary > popliteal > internal carotid > circle of Willis.

High-yield: Foam cells = macrophages (and SMCs) laden with oxidised LDL. Plaque vulnerability depends on cap thickness and inflammation, not absolute size.

Arteriolosclerosis & Mönckeberg sclerosis

Distinguish the three "sclerosis" patterns — a classic two-line MCQ.

Type	Vessel	Pathology	Setting
Hyaline arteriolosclerosis	Arterioles	Pink hyaline wall thickening	Benign HTN, diabetes
Hyperplastic arteriolosclerosis	Arterioles	"Onion-skin" concentric SMC + fibrinoid necrosis	Malignant HTN
Mönckeberg medial sclerosis	Medium muscular arteries	Medial calcification, lumen spared	Age > 50, does NOT narrow lumen

High-yield: Mönckeberg = ring-like medial calcification of muscular arteries that is clinically harmless (lumen patent), unlike atherosclerosis which is intimal and obstructive.

Aneurysms

An aneurysm is an abnormal localised vessel dilatation. True aneurysm involves all three wall layers; false (pseudo) aneurysm is a contained haematoma communicating with the lumen.

Aneurysm	Location/cause	Exam pearl
Abdominal aortic aneurysm (AAA)	Infra-renal aorta; atherosclerosis	Pulsatile mass; rupture = triad of pain, hypotension, mass. Repair at ≥ 5.5 cm
Thoracic aortic aneurysm	Ascending aorta; cystic medial degeneration	Marfan, hypertension, tertiary syphilis (tree-bark aorta)
Berry (saccular) aneurysm	Circle of Willis, anterior communicating artery	Rupture → subarachnoid haemorrhage; assoc. ADPKD, Ehlers-Danlos
Aortic dissection	Intimal tear, blood enters media	Tearing interscapular chest pain; HTN, Marfan; Stanford A vs B
Mycotic aneurysm	Infective (endocarditis) weakening	Septic emboli
Charcot-Bouchard microaneurysm	Lenticulostriate vessels	Hypertensive intracerebral haemorrhage

High-yield: Berry aneurysm rupture = sudden "worst headache of life" → subarachnoid haemorrhage; associated with adult polycystic kidney disease. Charcot-Bouchard ≠ berry — it causes deep hypertensive brain bleeds.

High-yield: Syphilitic (tertiary) aortitis → vasa vasorum endarteritis → ascending aortic aneurysm + tree-bark intima + aortic regurgitation. AAA is atherosclerotic and infra-renal.

Key differentials & discriminators

Quick "which one?" resolvers:

1. Lung + kidney + sinuses, c-ANCA → GPA. Asthma + eosinophilia → EGPA. Lung–kidney, no granuloma, p-ANCA → MPA.
2. Renal involvement but lung-spared, ANCA-negative, HBV → PAN.
3. Child + palpable purpura + abdominal pain → HSP.
4. Child + fever ≥5 days + coronary aneurysm → Kawasaki.
5. Old + temporal headache + blindness → GCA. Young Asian woman + pulseless → Takayasu.
6. Young male smoker + digital gangrene → Buerger.

Recently asked / exam angle

• Vessel-size–disease pairing in match-the-following format (large/medium/small) — near-guaranteed.
• ANCA antigen pairing: c-ANCA = PR3 = GPA; p-ANCA = MPO = MPA/EGPA — direct one-liners.
• PAN features: "Which is true about PAN?" → lung-sparing, HBV link, ANCA-negative, microaneurysms, lesions of different ages.
• Kawasaki: drug of choice / complication (coronary aneurysm) / CRASH criteria.
• GCA: investigation of choice (temporal artery biopsy, skip lesions) and immediate management (steroids before biopsy).
• Sclerosis triad: hyaline (DM/benign HTN) vs hyperplastic onion-skin (malignant HTN) vs Mönckeberg (medial, lumen spared).
• Aneurysm associations: berry–ADPKD, thoracic–Marfan/syphilis, AAA–atherosclerosis, Charcot-Bouchard–hypertensive bleed.
• Atherosclerosis: earliest lesion (fatty streak), foam-cell origin (macrophage), most common site (abdominal aorta).
• Buerger disease: corkscrew collaterals, smoking cessation as treatment.

Rapid revision

1. Large vessel → Takayasu (young Asian woman, pulseless) + GCA (old, temporal headache, blindness); both granulomatous.
2. Medium vessel → PAN (lung-sparing, HBV, ANCA-neg, microaneurysms) + Kawasaki (child, coronary aneurysm).
3. Small vessel + ANCA → GPA, EGPA, MPA; immune-complex → HSP, cryoglobulinaemia.
4. c-ANCA = PR3 = GPA; p-ANCA = MPO = MPA & EGPA.
5. GCA: treat with steroids immediately, biopsy shows skip lesions + giant cells + fragmented internal elastic lamina.
6. PAN: lesions of different ages coexist; renin-mediated HTN, NOT glomerulonephritis.
7. Kawasaki: IVIG + aspirin; CRASH + fever ≥ 5 days; coronary artery aneurysm is the dreaded complication.
8. GPA: saddle-nose, cavitating lung nodules, pauci-immune crescentic GN.
9. HSP: child, palpable purpura on buttocks, IgA mesangial deposits, abdominal pain (intussusception).
10. Atherosclerosis: fatty streak earliest; foam cell = lipid-laden macrophage; abdominal aorta most affected.
11. Mönckeberg: medial calcification of muscular arteries, lumen patent, harmless; hyperplastic onion-skin = malignant HTN.
12. Aneurysms: berry–ADPKD/SAH, thoracic–Marfan/syphilis (tree-bark), AAA–atherosclerosis (repair ≥ 5.5 cm), Charcot-Bouchard–hypertensive ICH.