Write a short note on the vasculitides, with emphasis on granulomatosis with polyangiitis.

Definition & Classification

Vasculitis is inflammation of blood vessel walls, causing destruction, stenosis, aneurysm formation and downstream ischaemia. The Chapel Hill Consensus classifies by the size of the predominant vessel involved:

Features Suggesting Vasculitis

Any multisystem illness with constitutional symptoms (fever, weight loss, fatigue) plus raised inflammatory markers and one or more of: palpable purpura, mononeuritis multiplex, glomerulonephritis with active urinary sediment, pulmonary infiltrates or haemorrhage, unexplained ischaemia in a young patient, or episcleritis/scleritis. The combination of lung and kidney involvement — the pulmonary-renal syndrome — is a classic vasculitic presentation.

Anca and its Interpretation

ANCA supports but never replaces the diagnosis: it may be negative in limited disease and positive in infection (endocarditis, tuberculosis), inflammatory bowel disease and drug reactions (hydralazine, propylthiouracil, cocaine adulterated with levamisole).

Granulomatosis with Polyangiitis (wegener's)

A necrotising granulomatous vasculitis of small and medium vessels, classically affecting the upper airway, lung and kidney — the "ELK" triad (Ear-nose-throat, Lung, Kidney).

Clinical features:

• Upper respiratory tract (most common initial site): persistent nasal crusting, epistaxis, sinusitis unresponsive to antibiotics, nasal septal perforation with saddle-nose deformity, otitis media, hearing loss, and subglottic stenosis causing stridor.
• Lower respiratory tract: cough, haemoptysis, dyspnoea, pleuritic pain; CT shows nodules that cavitate, and diffuse alveolar haemorrhage in severe disease.
• Renal: pauci-immune, rapidly progressive crescentic glomerulonephritis with haematuria, red cell casts, proteinuria and rising creatinine — the manifestation that determines survival.
• Eye: scleritis, episcleritis, orbital pseudotumour with proptosis.
• Skin: palpable purpura, ulcers, nodules.
• Nervous system: mononeuritis multiplex, cranial neuropathy.
• Constitutional: fever, weight loss, arthralgia, malaise.

Investigations:

• c-ANCA/anti-PR3
• raised ESR and CRP
• urinalysis with microscopy for dysmorphic red cells and casts (mandatory at every visit)
• renal function
• CT chest and sinuses
• biopsy for definitive diagnosis — renal biopsy shows pauci-immune necrotising crescentic glomerulonephritis (little or no immune deposit on immunofluorescence), and lung or nasal biopsy shows necrotising granulomatous inflammation.

Management — two phases:

• Remission induction: high-dose corticosteroids combined with cyclophosphamide or rituximab (rituximab is at least as effective and preferred in young patients concerned about fertility, and in relapsing disease). Plasma exchange is considered for severe renal disease or diffuse alveolar haemorrhage.
• Remission maintenance for at least 2 years: azathioprine, methotrexate or rituximab, with a slowly tapering low-dose steroid.
• Supportive and preventive: *Pneumocystis jirovecii* prophylaxis with co-trimoxazole during intensive immunosuppression; bone protection; vaccination; monitoring for cyclophosphamide toxicity — haemorrhagic cystitis (prevented with mesna and hydration), infertility, and bladder malignancy; and screening for infection, which causes much of the mortality.
• Monitor for relapse — ANCA titres, urinalysis, renal function and inflammatory markers; relapse is common.