Q5 LONG ANSWER 10M ★ High-yield

Classify vasculitis. Describe the important large, medium and small vessel vasculitides.

Pathology · 2nd Professional — Para-Clinical

Definition and Classification

Vasculitis is inflammation of blood vessel walls, causing ischaemia of the tissues supplied, and often accompanied by systemic features.

Mechanism	Examples
Immune complex mediated	Henoch–Schonlein purpura, cryoglobulinaemic vasculitis (hepatitis C), drug-induced, polyarteritis nodosa associated with hepatitis B
ANCA associated	Granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis
Direct infection	Aspergillus, mucormycosis, syphilis, rickettsia
Cell mediated	Giant cell arteritis, Takayasu arteritis, transplant rejection

Large Vessel Vasculitis

Disease	Features	Key points
Giant cell (temporal) arteritis	Over 50 years; temporal headache, scalp tenderness, jaw claudication, visual loss; associated with polymyalgia rheumatica	ESR very high. Granulomatous inflammation with giant cells and fragmented internal elastic lamina; skip lesions mean a long biopsy segment is needed. Start steroids immediately to prevent blindness — do not wait for the biopsy
Takayasu arteritis	Young ASIAN women under 40; aortic arch and its branches	"pulseless disease" — absent upper limb pulses, unequal blood pressures, bruits, visual disturbance. Relatively common in India

Medium Vessel Vasculitis

Disease	Features	Key points
Polyarteritis nodosa	Young adults; renal, gastrointestinal, cardiac, peripheral nerves; spares the lung	Segmental transmural necrotising inflammation with fibrinoid necrosis; lesions of different ages coexist. Nodular aneurysms give a "beads on a string" angiogram. About 30% are hepatitis B associated. ANCA negative
Kawasaki disease	Children under 5; fever over 5 days, conjunctivitis, rash, cervical lymphadenopathy, strawberry tongue, desquamation of the hands and feet	Coronary artery aneurysms — the reason it matters; treated with intravenous immunoglobulin and aspirin
Buerger disease (thromboangiitis obliterans)	Young male smokers; distal limb arteries and veins	Severe pain, claudication, ulceration, gangrene; segmental thrombosing inflammation with microabscesses. Stopping smoking is the only effective treatment. Common in India and the Middle East

Small Vessel Vasculitis

Disease	ANCA	Features
Granulomatosis with polyangiitis (Wegener)	C-ANCA (anti-PR3)	The triad — necrotising granulomas of the upper respiratory tract (sinusitis, saddle-nose deformity), lung (cavitating nodules), and necrotising glomerulonephritis
Microscopic polyangiitis	P-ANCA (anti-MPO)	Pulmonary–renal syndrome with haemoptysis and rapidly progressive glomerulonephritis; NO granulomas; all lesions of the same age
Eosinophilic granulomatosis (Churg–Strauss)	P-ANCA in about 40%	Asthma, eosinophilia and vasculitis; granulomas with eosinophils; neuropathy
HENOCH–schonlein purpura	Negative — IgA immune complexes	Children after an upper respiratory infection; palpable purpura on buttocks and legs, abdominal pain, arthralgia, IgA nephropathy

CLINICAL PEARL

Polyarteritis nodosa and microscopic polyangiitis are separated by three things. Polyarteritis affects medium vessels, is ANCA negative, spares the lung, and shows lesions of different ages. Microscopic polyangiitis affects small vessels, is p-ANCA positive, involves the lung, and shows lesions all of the same age. That last point reflects a single precipitating insult rather than repeated ones.

General Clinical Features and Investigation

Suspect vasculitis in unexplained fever, weight loss and fatigue with palpable purpura, mononeuritis multiplex, glomerulonephritis, haemoptysis, or multisystem disease with a raised ESR
Palpable purpura is the classic sign, and is palpable because the inflamed vessel wall makes the lesion raised — unlike thrombocytopenic purpura
Mononeuritis multiplex — asymmetrical involvement of named nerves; highly suggestive
Investigations — ESR and CRP, urinalysis for casts and protein, ANCA, complement, hepatitis B and C serology, cryoglobulins, angiography, and biopsy of an affected organ
Urinalysis is the cheapest and most valuable test, since renal involvement is common, silent and determines prognosis

General Morphology and Immunopathogenesis

Feature	Significance
Fibrinoid necrosis of the vessel wall	The hallmark of necrotising vasculitis; bright eosinophilic material replacing the wall
Transmural inflammatory infiltrate	Neutrophils early, then mononuclear cells
Leucocytoclasis	Fragmented neutrophil nuclei ("nuclear dust") — characteristic of small vessel vasculitis
Granulomas	Present in giant cell arteritis, Takayasu, granulomatosis with polyangiitis and eosinophilic granulomatosis; absent in polyarteritis nodosa and microscopic polyangiitis
Destruction of the internal elastic lamina	Leads to aneurysm formation, as in polyarteritis nodosa and Kawasaki disease
Healing by fibrosis	Causes stenosis and occlusion — the pulseless disease of Takayasu

ANCA are thought to be pathogenic, not merely markers — they activate primed neutrophils directly, causing them to degranulate against the endothelium

Applied Aspects

Giant cell arteritis is a medical emergency — visual loss is sudden, painless and irreversible, so steroids are started on clinical suspicion and the biopsy done within a week
Takayasu arteritis is relatively common in India and should be considered in a young woman with hypertension, absent pulses or unequal blood pressures
Buerger disease is entirely preventable — and no treatment works if the patient continues to smoke, including bidis
ANCA-associated vasculitis requires urgent immunosuppression with steroids and cyclophosphamide or rituximab; untreated, one-year mortality exceeds 80%
Kawasaki disease must be treated within 10 days to prevent coronary aneurysms, and is the commonest cause of acquired heart disease in children in developed countries
Always exclude infection and malignancy before immunosuppressing, since both mimic vasculitis and both are made much worse by it — and in India, tuberculosis in particular
Henoch–Schonlein purpura is usually self-limiting in children, but renal function must be followed, since nephritis may appear or progress later
Cryoglobulinaemic vasculitis warrants hepatitis C testing, since treating the virus treats the vasculitis
Relapse is common in ANCA-associated disease, so maintenance immunosuppression and long-term follow-up are needed; a rising ANCA titre may precede clinical relapse
The distinction between primary vasculitis and a secondary vasculitis of connective tissue disease matters, since the latter is managed by treating the underlying disease
Pneumocystis prophylaxis is given with prolonged high-dose immunosuppression, since opportunistic infection is a major cause of death in treated vasculitis
Cyclophosphamide causes infertility and haemorrhagic cystitis, so fertility preservation is discussed and mesna given; rituximab is now often preferred in the young
Temporal artery biopsy remains worthwhile even after starting steroids, since the histology persists for a week or two — treatment should never be delayed for it
Bone protection is started with the steroids, since these are prolonged high-dose courses in elderly patients
Polymyalgia rheumatica and giant cell arteritis overlap — up to half of patients with arteritis have polymyalgic symptoms, and every such patient should be asked about headache and visual change at each visit
Vasculitis mimics are important — cholesterol embolism, atrial myxoma, infective endocarditis and antiphospholipid syndrome all produce multisystem ischaemia without vessel inflammation
Biopsy before treatment wherever possible, since immunosuppression obscures the histology and the diagnosis then becomes very hard to establish

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