Rheumatology: Vasculitis, GCA and PMR

• Basics: Classifying Vasculitis | When to Suspect Vasculitis | Investigating Suspected Vasculitis
• Large vessels and PMR: Polymyalgia Rheumatica | Giant Cell Arteritis — Features | Giant Cell Arteritis — Diagnosis | Giant Cell Arteritis — Treatment | Takayasu Arteritis
• Medium and small vessels: Polyarteritis Nodosa | ANCA-associated Vasculitis — Overview | GPA, MPA and EGPA | Treating ANCA-associated Vasculitis | Anti-GBM Disease | IgA Vasculitis | Cryoglobulinaemic and Other Small-vessel Vasculitis | Behçet's Disease
• Revision: Vasculitis at a Glance | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🩺 Vasculitis, GCA and PMR — page 5 of the Rheumatology chapter. Vasculitis means inflammation of blood vessel walls, causing narrowing, blockage, aneurysms or bleeding in whatever organs those vessels supply. It is rare, but giant cell arteritis can blind and ANCA vasculitis can destroy the kidneys and lungs within days, so early recognition saves organs and lives. Polymyalgia rheumatica is common in older people and closely linked to GCA. Kawasaki disease is in the Paediatrics chapters; aortic aneurysm surgery is on the Vascular Surgery page.
Your four questions for every patient: Could this be vasculitis — fever, weight loss and multi-organ symptoms with high inflammatory markers? What size of vessel is involved? Which organs are threatened right now — eyes, kidneys, lungs, nerves, gut? Have infection, cancer, endocarditis and drugs been excluded before giving high-dose immunosuppression?

Classifying Vasculitis

(Chapel Hill Consensus Conference 2012 nomenclature.)

When to Suspect Vasculitis

• Systemic illness — fever, sweats, weight loss, fatigue, arthralgia, myalgia, with high CRP and ESR, anaemia and thrombocytosis.
• Plus multi-organ features:
  • Skin — palpable purpura (raised, non-blanching, usually on the legs), ulcers, nodules, livedo, digital infarcts, splinter haemorrhages.
  • Kidneys — haematuria and proteinuria, rapidly rising creatinine (rapidly progressive glomerulonephritis), hypertension.
  • Lungs — haemoptysis, cough, breathlessness, nodules or cavities, infiltrates, asthma (EGPA).
  • ENT — chronic sinusitis, crusting, nosebleeds, deafness, saddle nose, subglottic stenosis.
  • Nerves — mononeuritis multiplex (e.g. sudden foot drop or wrist drop), sensory neuropathy.
  • Eyes — scleritis, retinal vasculitis, orbital mass, visual loss (GCA).
  • Gut — abdominal pain after eating, bleeding, perforation.
• Mimics to exclude — infective endocarditis (blood cultures, echo), other infections (TB, hepatitis B and C, HIV, syphilis), cancer (lymphoma, paraneoplastic), cholesterol emboli (after angiography — livedo, eosinophilia, AKI), drugs, atrial myxoma, antiphospholipid syndrome, calciphylaxis.

⚠️ Safety Pearl — pulmonary–renal syndrome (lung haemorrhage with rapidly progressive kidney failure) is a medical emergency. Send ANCA and anti-GBM urgently (same-day results), and involve renal and rheumatology teams immediately.

Investigating Suspected Vasculitis

• Bloods — FBC (anaemia, eosinophilia, platelets), CRP and ESR, U&E, LFTs, bone profile, CK.
• Urine — dipstick for blood and protein, microscopy (red cell casts = glomerulonephritis), protein–creatinine ratio. A normal urine dip is important information.
• Immunology — ANCA (with PR3 and MPO specificity), anti-GBM, ANA, ENA, anti-dsDNA, complement (C3, C4 — low in cryoglobulinaemia and SLE), cryoglobulins (sample kept warm), RF, immunoglobulins and protein electrophoresis, antiphospholipid antibodies.
• Infection screen — blood cultures, hepatitis B and C, HIV, syphilis, TB (IGRA, chest X-ray); echocardiogram if endocarditis possible.
• Imaging:
  • Chest X-ray and CT — nodules, cavities, haemorrhage.
  • CT sinuses, ENT examination.
  • Vascular ultrasound (temporal and axillary arteries — GCA), CT or MR angiography, PET-CT (large vessel vasculitis).
  • Mesenteric angiography (PAN — microaneurysms).
• Biopsy — the most affected accessible tissue: kidney (pauci-immune necrotising crescentic glomerulonephritis in ANCA vasculitis; linear IgG in anti-GBM; IgA deposits in IgA vasculitis), skin, nasal mucosa, nerve and muscle, temporal artery, lung.
• Nerve conduction studies — mononeuritis multiplex.
• Disease activity — BVAS (Birmingham Vasculitis Activity Score); damage — VDI.

Polymyalgia Rheumatica

• Inflammatory condition of older people (almost always over 50, usually over 60; women more than men) causing pain and stiffness of the shoulder and hip girdles.
• Features:
  • Bilateral shoulder pain and stiffness (± hip girdle and neck), morning stiffness over 45 minutes, for at least 2 weeks.
  • Difficulty getting out of bed, dressing, combing hair; pain on moving the shoulders, but power is normal (pain-limited).
  • Systemic symptoms — fatigue, low-grade fever, weight loss, low mood.
  • Sometimes peripheral arthritis, carpal tunnel syndrome, distal swelling.
• Tests — raised ESR and/or CRP (a normal result makes PMR less likely but doesn't exclude it); CK normal (unlike myositis).
• Before diagnosing, exclude mimics (BSR) — FBC, U&E, LFTs, bone profile, protein electrophoresis (myeloma), TFTs, CK, RF and anti-CCP (late-onset RA), urine dipstick, vitamin D; chest X-ray (malignancy, infection).
• Differential diagnosis — late-onset RA, myeloma and other cancers, infection (endocarditis, septic arthritis), shoulder problems (rotator cuff, frozen shoulder, OA), hypothyroidism, myositis, statin myopathy, Parkinson's disease, fibromyalgia, CPPD (crowned dens), vasculitis, immune checkpoint inhibitor PMR.
• Ask about GCA symptoms at every visit — about 15–20% of PMR patients develop GCA.
• Treatment (BSR/EULAR):
  • Prednisolone 12.5–25 mg daily (usually 15 mg) — expect a dramatic response within days (about 70% improvement within a week, with normalising inflammatory markers within 4 weeks).
  • No response to 15–20 mg — reconsider the diagnosis.
  • Slow taper — e.g. to 10 mg by about 4–8 weeks, then reduce by 1 mg every 4–8 weeks; usual total course 1–2 years; relapses are common (increase back to the last effective dose).
  • Bone protection (bisphosphonate, calcium and vitamin D), steroid card, monitor glucose and BP.
  • Steroid-sparing — methotrexate for relapsing disease or high steroid risk; IL-6 inhibitors (tocilizumab, sarilumab) for refractory disease (specialist).
• Refer to rheumatology — atypical features (age under 60, normal markers, peripheral arthritis, systemic features suggesting other disease), poor response, relapse, need for long-term steroids, or GCA symptoms (urgent).

Giant Cell Arteritis — Features

• Giant cell arteritis (GCA) — granulomatous vasculitis of large and medium arteries, especially the branches of the external carotid (temporal artery), the ophthalmic and posterior ciliary arteries, and the aorta and its branches.
• Who — age over 50 (mean about 72), women 2–3 times more than men, northern European descent; often with PMR.
• Cranial features:
  • New headache — usually temporal, may be occipital; constant.
  • Scalp tenderness (pain on combing hair or lying on a pillow).
  • Jaw claudication — pain in the jaw muscles on chewing (the most specific symptom); tongue claudication.
  • Visual symptoms — sudden painless loss of vision (anterior ischaemic optic neuropathy — pale swollen disc), amaurosis fugax, diplopia, visual field loss; loss of vision is usually permanent, and the other eye may follow within days.
  • Abnormal temporal arteries — thickened, tender, nodular, reduced or absent pulse.
• Systemic features — fever, weight loss, fatigue, night sweats, PMR symptoms; sometimes just pyrexia of unknown origin in an older person.
• Large-vessel GCA — arm claudication, absent arm pulses, BP difference between arms, subclavian and axillary bruits; later thoracic aortic aneurysm and dissection.
• Stroke — vertebrobasilar territory (rare but serious).

Giant Cell Arteritis — Diagnosis

• Suspected GCA is a medical emergency — start steroids immediately (before tests), then refer the same day to a fast-track GCA pathway (BSR 2020).
• Bloods — ESR and CRP (raised in over 95% — normal results make GCA unlikely but not impossible), FBC (anaemia, high platelets), LFTs (raised ALP).
• Confirm the diagnosis (don't let steroids delay the tests — but do them quickly):
  • Temporal and axillary artery ultrasound — "halo sign" (wall thickening), non-compressible artery; ideally within 1 week of starting steroids.
  • Temporal artery biopsy — over 1 cm length, ideally within 2 weeks of steroids; skip lesions mean a negative biopsy doesn't exclude GCA; risks — facial nerve injury, scalp necrosis.
  • PET-CT, CT or MR angiography — large-vessel involvement.
• Same-day ophthalmology for any visual symptoms.
• Other causes of headache and high ESR in older people — myeloma, infection (sinusitis, endocarditis), cancer, intracranial lesion, cervical spondylosis, trigeminal neuralgia.

Giant Cell Arteritis — Treatment

• No visual loss — prednisolone 40–60 mg daily (often 1 mg/kg up to 60 mg) started immediately.
• Visual loss or amaurosis — IV methylprednisolone 500 mg–1 g daily for 3 days (or high-dose oral prednisolone 60 mg) plus urgent ophthalmology; the aim is to protect the other eye — lost vision rarely recovers.
• Tapering (BSR) — continue the starting dose until symptoms and markers settle (2–4 weeks), then reduce gradually (e.g. by 10 mg every 2 weeks to 20 mg, then slower) — total course often 12–18 months or longer.
• Tocilizumab (IL-6 receptor antagonist) — reduces relapses and steroid exposure (GiACTA trial) — NICE recommends it for relapsing or refractory GCA (for up to 1 year); note it suppresses CRP, so monitor symptoms closely.
• Methotrexate — a steroid-sparing option.
• Supportive — bone protection (bisphosphonate from the start), PPI if GI risk, steroid card and sick day rules, monitor glucose and BP, vaccinations; aspirin is not routinely recommended (unless otherwise indicated for CVD).
• Relapse — headache, PMR symptoms, rising markers — increase steroids to the last effective dose (or higher with ischaemic symptoms); consider tocilizumab.
• Long-term — monitor for aortic aneurysm (chest X-ray, imaging per local policy, especially with large-vessel disease); steroid side effects.
• Driving — visual loss may mean the patient must inform the DVLA (visual acuity and field standards).

Takayasu Arteritis

• Large-vessel vasculitis of the aorta and its main branches in young women (under 40), more common in Asia.
• Early — fever, weight loss, arthralgia, fatigue ("pre-pulseless" phase).
• Later — "pulseless disease": arm claudication, absent or weak pulses, BP difference over 10 mmHg between arms, bruits (subclavian, carotid, abdominal), renovascular hypertension, dizziness and stroke, aortic regurgitation, aneurysms.
• Diagnosis — CRP and ESR, CT or MR angiography, PET-CT.
• Treatment — steroids with methotrexate, azathioprine or mycophenolate; anti-TNF or tocilizumab for refractory disease; angioplasty or bypass for fixed narrowings when the disease is quiet; BP control (measure in the leg if both arms are affected).

Polyarteritis Nodosa

• Necrotising vasculitis of medium-sized arteries, ANCA-negative, with no glomerulonephritis (kidney damage is from infarcts and renal artery aneurysms instead).
• Association — hepatitis B (less common now with vaccination); also hairy cell leukaemia; DADA2 (genetic, young people with strokes).
• Features:
  • Fever, weight loss, myalgia, arthralgia.
  • Mononeuritis multiplex (foot drop, wrist drop).
  • Skin — tender nodules, livedo racemosa, ulcers, digital gangrene.
  • Kidneys — hypertension (renal artery involvement), kidney infarcts, haematuria (without casts).
  • Gut — post-prandial abdominal pain, bleeding, bowel infarction and perforation.
  • Testicular pain (orchitis), heart (MI, heart failure).
• Diagnosis — biopsy (skin, nerve, muscle) or angiography showing microaneurysms (kidneys, liver, gut — "beading").
• Treatment — steroids ± cyclophosphamide (severe); hepatitis B-associated PAN — antivirals with short-course steroids and plasma exchange (avoid long-term immunosuppression).
• Cutaneous PAN — skin-limited (nodules and livedo on the legs), often after streptococcal infection; milder.

ANCA-associated Vasculitis — Overview

• Small-vessel necrotising vasculitis with few immune deposits ("pauci-immune") and anti-neutrophil cytoplasmic antibodies (ANCA).
• Three diseases:
  • Granulomatosis with polyangiitis (GPA) — usually PR3-ANCA (c-ANCA).
  • Microscopic polyangiitis (MPA) — usually MPO-ANCA (p-ANCA).
  • Eosinophilic granulomatosis with polyangiitis (EGPA) — MPO-ANCA in only about 40%.
• Who — older adults (peak 60–70), men and women.
• Organs — kidneys (rapidly progressive glomerulonephritis with crescents), lungs (nodules, cavities, haemorrhage), ENT, skin, nerves, eyes.
• ANCA-negative disease occurs (especially localised GPA and EGPA) — biopsy is key.
• Drug-induced ANCA vasculitis — hydralazine, propylthiouracil, minocycline, levamisole (contaminant of cocaine — purpura of the ears, very high-titre MPO and PR3), anti-TNF.
• Prognosis — untreated, most die within a year; with treatment, most survive, but relapses (especially PR3), infections, kidney failure and CV disease are major risks.

GPA, MPA and EGPA

• EGPA phases — asthma and rhinitis (often for years) → eosinophilia (eosinophilic pneumonia, gastroenteritis) → vasculitis; check eosinophils in adult-onset or worsening asthma with systemic features.
• Treatment of EGPA — steroids; mepolizumab (anti-IL-5) for relapsing or refractory disease; cyclophosphamide or rituximab for organ-threatening disease.

Treating ANCA-associated Vasculitis

• Treat organ-threatening disease urgently (kidney, lung haemorrhage, eye, nerve) in a specialist centre.
• Induction of remission (BSR, KDIGO, EULAR):
  • Glucocorticoids — IV methylprednisolone pulses for severe disease, then oral prednisolone with a reduced-dose taper (PEXIVAS showed lower doses are as effective with fewer infections).
  • Plus rituximab (preferred in many — especially relapsing PR3 disease, younger patients, fertility concerns) or IV cyclophosphamide.
  • Avacopan (oral C5a receptor antagonist) — allows faster steroid reduction (NICE TA).
  • Plasma exchange — considered in very severe kidney disease (e.g. creatinine over 500) or with anti-GBM antibodies; no overall survival benefit in PEXIVAS.
  • Non-severe disease — methotrexate or mycophenolate with steroids.
• Maintenance — rituximab every 6 months (preferred) or azathioprine; usually for at least 2–4 years; low-dose steroids tapered off where possible.
• Prevent complications:
  • Co-trimoxazole (PJP prophylaxis) during induction.
  • Bone protection, PPI, vaccinations (before rituximab), check immunoglobulins.
  • Cardiovascular risk management; bladder cancer and infertility monitoring after cyclophosphamide.
  • Nasal care (saline douching, treat Staphylococcus aureus carriage — linked with GPA relapse).
• Monitor — symptoms, urine (haematuria), creatinine, CRP, ANCA levels (a rising ANCA alone is not a reason to treat).
• Kidney failure — dialysis and later transplant (once in remission).

Anti-GBM Disease

• Anti-glomerular basement membrane disease (Goodpasture's disease) — antibodies against type IV collagen in the kidney and lung basement membranes.
• Who — two peaks: young men (lung and kidney) and older women (kidney); smoking, inhaled hydrocarbons and lung infections increase lung haemorrhage.
• Features — rapidly progressive glomerulonephritis (AKI over days, haematuria) ± pulmonary haemorrhage (haemoptysis, breathlessness, falling Hb, raised TLCO from blood in the alveoli).
• Diagnosis — anti-GBM antibodies (urgent test); kidney biopsy — linear IgG deposition along the basement membrane, crescents; about 30% are also ANCA positive ("double positive" — relapse like ANCA vasculitis).
• Treatment — emergency:
  • Plasma exchange (removes antibodies) daily.
  • High-dose steroids and cyclophosphamide.
  • Dialysis; stop smoking.
• Prognosis — kidney recovery is unlikely if dialysis-dependent with 100% crescents at presentation (unless lung haemorrhage needs treatment anyway); relapse is rare (unlike ANCA disease).
• Other causes of pulmonary–renal syndrome — ANCA vasculitis (commonest), SLE, cryoglobulinaemia, IgA vasculitis, thrombotic microangiopathy, severe pneumonia (Legionella) with AKI, pulmonary oedema with kidney failure.

IgA Vasculitis

• IgA vasculitis (Henoch–Schönlein purpura) — the commonest vasculitis in children; less common but more severe in adults.
• Often follows an upper respiratory infection.
• Features:
  • Palpable purpura on the legs and buttocks (non-blanching).
  • Arthralgia or arthritis (knees, ankles).
  • Abdominal pain, GI bleeding, intussusception (children).
  • Kidney involvement — haematuria, proteinuria (IgA nephritis) — more frequent and serious in adults.
  • Orchitis.
• Diagnosis — clinical; skin biopsy (IgA deposits on immunofluorescence); kidney biopsy if significant proteinuria or kidney dysfunction; platelets are normal (distinguishes from thrombocytopenic purpura).
• Management:
  • Most cases (especially children) settle within weeks — rest, analgesia (avoid NSAIDs if kidney involvement).
  • Monitor urine and BP (children — for 6–12 months).
  • Steroids for severe gut or joint disease; immunosuppression for significant nephritis (adults).
• IgA nephropathy — kidney-only relative (visible haematuria 1–2 days after a sore throat) — see the Renal chapters.

Cryoglobulinaemic and Other Small-vessel Vasculitis

• Cryoglobulinaemic vasculitis — immunoglobulins that clump in the cold, blocking small vessels:
  • Hepatitis C is the main cause (mixed cryoglobulinaemia — types II and III); also Sjögren's, SLE, lymphoma, myeloma (type I — hyperviscosity).
  • Features — purpura (legs), arthralgia, weakness (Meltzer's triad); neuropathy, membranoproliferative glomerulonephritis, leg ulcers, Raynaud's.
  • Tests — cryoglobulins (sample transported warm), very low C4, positive RF, hepatitis C serology.
  • Treatment — treat hepatitis C with direct-acting antivirals; rituximab; plasma exchange in severe disease.
• Hypocomplementaemic urticarial vasculitis — urticarial wheals that last over 24 hours, burn rather than itch, and leave bruising; low complement (anti-C1q); linked with SLE.
• Cutaneous small-vessel (leukocytoclastic) vasculitis — palpable purpura limited to the skin, usually triggered by drugs (antibiotics — penicillins, NSAIDs), infections, or no cause; usually settles; always check urine and look for systemic disease.
• Vasculitis with connective tissue disease — RA (rheumatoid vasculitis), SLE, Sjögren's.
• Paraneoplastic vasculitis — haematological cancers (especially), solid tumours.

Behçet's Disease

• Variable vessel vasculitis affecting arteries and veins of any size; most common along the old Silk Road (Turkey, Middle East, Iran, Japan); HLA-B51; young adults (20–40); men often more severe.
• Features:
  • Recurrent painful mouth ulcers (at least 3 times a year — nearly all patients).
  • Genital ulcers (scrotum, vulva — often scar).
  • Eye disease — uveitis (anterior, posterior or panuveitis), retinal vasculitis — can blind.
  • Skin — erythema nodosum, acne-like pustules, pathergy (a pustule forming 24–48 hours after a needle prick).
  • Vascular — venous thrombosis (DVT, superficial thrombophlebitis, Budd–Chiari, cerebral venous sinus thrombosis), pulmonary artery aneurysms (massive haemoptysis), arterial aneurysms.
  • Neuro-Behçet's — brainstem lesions, meningoencephalitis.
  • Gut — ileocaecal ulcers (mimics Crohn's).
  • Arthritis — non-erosive oligoarthritis.
• Diagnosis — clinical (International Criteria for Behçet's Disease); no specific blood test.
• Treatment:
  • Mouth and genital ulcers — topical steroids, colchicine, apremilast.
  • Skin and joints — colchicine.
  • Eye, vascular, neuro or gut disease — steroids with azathioprine, anti-TNF (infliximab, adalimumab), interferon-alpha.
  • Venous thrombosis is treated mainly with immunosuppression (inflammation drives the clot); anticoagulation is used cautiously (check for pulmonary artery aneurysms first — bleeding risk).
• UK Centres of Excellence for Behçet's (London, Birmingham, Liverpool).

Vasculitis at a Glance

Spot the Diagnosis