Systemic vasculitides in the elderly

Definition and classification. Inflammation of blood-vessel walls causing ischaemia, necrosis and organ damage. The Chapel Hill Consensus classifies by vessel size: large-vessel (giant cell arteritis, Takayasu arteritis); medium-vessel (polyarteritis nodosa, Kawasaki disease); small-vessel ANCA-associated (granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis); and small-vessel immune-complex (IgA vasculitis, cryoglobulinaemic, anti-GBM disease).

Which vasculitides matter in old age. Giant cell arteritis (GCA) is the commonest primary systemic vasculitis in adults and occurs almost exclusively over the age of 50, with peak incidence in the seventies. ANCA-associated vasculitis — especially microscopic polyangiitis — peaks at 65–75 years. Drug-induced and malignancy-associated (paraneoplastic) vasculitis are proportionally commoner in the elderly.

GCA — clinical features. New-onset temporal headache, scalp tenderness, jaw claudication (the most specific symptom), amaurosis fugax or sudden painless visual loss (anterior ischaemic optic neuropathy), a tender, thickened or pulseless temporal artery, constitutional symptoms, and overlap with polymyalgia rheumatica. Large-vessel GCA causes aortitis, thoracic aortic aneurysm, limb claudication and unequal pulses. GCA should be considered in any older patient with cerebrovascular or vertebrobasilar symptoms.

GCA — investigation and treatment. Markedly raised ESR (often >75 mm/h) and CRP, normochromic anaemia, thrombocytosis, raised alkaline phosphatase. Temporal artery biopsy — take a 1–2 cm segment because of skip lesions; or temporal artery ultrasound showing the "halo sign" and a positive compression sign; CT/MR angiography or PET-CT for large-vessel disease. Start prednisolone 40–60 mg daily immediately — IV methylprednisolone if there is visual loss — without waiting for the biopsy, which remains positive for up to 2 weeks. Add low-dose aspirin, bone protection and gastroprotection.

ANCA-associated vasculitis — clinical features. A subacute constitutional illness (fever, weight loss, malaise, arthralgia) evolving into a pulmonary–renal syndrome. GPA — upper airway disease (epistaxis, nasal crusting, sinusitis, saddle-nose deformity, subglottic stenosis), lung nodules and cavities, and rapidly progressive glomerulonephritis. MPA — RPGN and alveolar haemorrhage without granulomas. EGPA — late-onset asthma, eosinophilia, mononeuritis multiplex and cardiac involvement.

ANCA — investigations. c-ANCA / anti-PR3 (GPA) and p-ANCA / anti-MPO (MPA, EGPA). Urinalysis and microscopy showing dysmorphic red cells and red-cell casts is the single most important bedside test — never omit it. Rising creatinine, CXR and HRCT, ENT and ophthalmic assessment, nerve conduction studies, and renal biopsy showing pauci-immune necrotising crescentic glomerulonephritis.

Treatment of ANCA-associated vasculitis. Remission induction — glucocorticoids plus rituximab or cyclophosphamide; rituximab is preferred in older adults and in relapsing disease because it avoids cyclophosphamide's bladder toxicity, infertility and malignancy risk. Plasma exchange is reserved for severe alveolar haemorrhage and the most severe renal disease. Maintenance — rituximab or azathioprine (or methotrexate/mycophenolate) for 2–4 years. All doses of cyclophosphamide and rituximab must be reduced for age and renal function.

Mimics and differential diagnosis in the elderly. Infective endocarditis (fever, splinter haemorrhages, glomerulonephritis, positive ANCA in some), atrial myxoma, cholesterol embolisation (livedo reticularis, blue toes, eosinophilia and AKI after an arterial procedure), antiphospholipid syndrome, malignancy (myeloma, lymphoma, myelodysplasia), and drug-induced vasculitis (hydralazine, propylthiouracil, minocycline, levamisole-adulterated cocaine — typically very high-titre MPO-ANCA). Chronic infections — tuberculosis, hepatitis B and C, HIV — must be excluded before immunosuppression, particularly in India.

Geriatric-specific issues. Presentation is frequently non-specific — pyrexia of unknown origin, weight loss, anaemia, raised inflammatory markers, delirium or unexplained functional decline. Treatment toxicity, not the vasculitis, is the main cause of death in older patients — infection is a commoner cause of death than active disease. Therefore: PJP prophylaxis with co-trimoxazole, bone protection, glucose and blood-pressure monitoring, gastroprotection, hepatitis B and TB screening, and vaccination before rituximab are all mandatory.

Monitoring and prognosis. Follow CRP, creatinine, urinalysis and ANCA titre (an imperfect guide to activity); score activity with the Birmingham Vasculitis Activity Score (BVAS) and accumulated damage with the Vasculitis Damage Index (VDI). Increasing age predicts worse renal and overall survival; relapse is frequent after treatment withdrawal, and end-stage renal disease is the major long-term morbidity in MPA.

GCA — upadacitinib. The phase 3 SELECT-GCA trial (NEJM 2025) showed that upadacitinib 15 mg once daily with a 26-week steroid taper achieved sustained remission in 46.4% versus 29.0% with placebo plus a 52-week taper, with roughly halved cumulative glucocorticoid exposure; FDA approval followed in April 2025, making it the second approved drug for GCA after tocilizumab. The 2025/2026 EULAR recommendations now require referral of suspected GCA within 24 hours and advise adding tocilizumab or upadacitinib in refractory or relapsing disease or where steroid toxicity risk is high.

ANCA-associated vasculitis — steroid minimisation. Avacopan, an oral C5a receptor antagonist, is approved as an adjunct in severe AAV on the basis of the ADVOCATE trial, allowing substantial glucocorticoid reduction with better renal recovery; and the PEXIVAS-informed reduced-dose glucocorticoid regimen (with restriction of plasma exchange) is now standard. Both are especially valuable in older patients, in whom steroid toxicity and infection drive mortality.