Vasculitis — Symptoms, Causes & Treatment | MyMedicPlus

Vasculitis refers to a heterogeneous group of diseases characterised by inflammation and necrosis of blood vessel walls — causing vessel wall thickening, luminal narrowing, aneurysm formation, and thrombosis, ultimately leading to tissue ischaemia and end-organ damage. The clinical manifestations depend primarily on the size of vessels affected, the organs involved, and the extent and severity of vascular damage. Vasculitis is classified by vessel size according to the 2012 Chapel Hill Consensus Conference nomenclature: large-vessel vasculitis (affecting the aorta and its major branches) — includes giant cell arteritis (GCA, affecting adults over 50) and Takayasu's arteritis (affecting young women, predominantly the aortic arch and branches); medium-vessel vasculitis (affecting the main visceral arteries and their branches) — includes polyarteritis nodosa (PAN) and Kawasaki disease (children); and small-vessel vasculitis (affecting arterioles, capillaries, and venules) — includes ANCA-associated vasculitis (AAV): granulomatosis with polyangiitis (GPA, formerly Wegener's), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss); and immune complex-mediated: IgA vasculitis (Henoch-Schönlein purpura — the most common vasculitis in children), cryoglobulinaemic vasculitis, and anti-GBM disease (Goodpasture's syndrome). Vasculitis is rare — GCA has the highest incidence at approximately 150-200 per 100,000 persons over 50; ANCA-associated vasculitis affects approximately 20 per 100,000.

ANCA-associated vasculitis (AAV): autoantibodies — anti-neutrophil cytoplasmic antibodies targeting either proteinase-3 (PR3-ANCA, cytoplasmic c-ANCA pattern, strongly associated with GPA) or myeloperoxidase (MPO-ANCA, perinuclear p-ANCA pattern, associated with MPA and EGPA) — bind to primed neutrophils, activating them to degranulate and damage vessel walls through release of reactive oxygen species and lytic enzymes. IFN-gamma, IL-17, and complement pathways amplify the inflammatory cascade. The mechanism for ANCA induction remains unclear — environmental factors, microbial antigens (Staphylococcus aureus nasal carriage in GPA), and genetic susceptibility (HLA-DPB1*04:01 for PR3-ANCA) are implicated. Drug-induced ANCA vasculitis: propylthiouracil (PTU — used for hyperthyroidism), hydralazine, minocycline, levamisole-adulterated cocaine, and anti-TNF biologics can induce MPO-ANCA and cause drug-induced AAV — reverses with drug cessation. Large-vessel vasculitis: GCA and Takayasu's arteritis are driven by CD4+ helper T-cells (Th1 and Th17 pathways) and macrophages causing granulomatous inflammation in the vessel adventitia and media — the trigger is unknown but infectious aetiology is suspected; IL-6 is a major mediator (explaining the efficacy of tocilizumab). Infective causes: hepatitis B surface antigen-antibody immune complexes cause polyarteritis nodosa (PAN); hepatitis C-associated cryoglobulinaemia (mixed cryoglobulinaemia) causes immune-complex-mediated small-vessel vasculitis — treating hepatitis C with DAAs achieves vasculitis remission. Kawasaki disease: unknown trigger (likely infectious — Yersinia pseudotuberculosis, coronavirus) causing acute self-limited large-vessel vasculitis in children under 5.

Constitutional (all types): fever, weight loss, fatigue, arthralgia. Renal (small-vessel): haematuria, proteinuria, rapidly progressive glomerulonephritis (RPGN) — oliguria, rising creatinine. Pulmonary (GPA, MPA, EGPA): haemoptysis, cavitating pulmonary nodules (GPA), pulmonary haemorrhage and respiratory failure. Skin: palpable purpura predominantly on lower limbs (small-vessel vasculitis), livedo reticularis, digital ischaemia, and skin ulceration. Nervous system: mononeuritis multiplex (PAN — foot drop, wrist drop). GCA: temporal headache, scalp tenderness, jaw claudication, sudden visual loss (ischaemic optic neuropathy — ophthalmological emergency requiring immediate steroids). Upper respiratory tract (GPA): saddle-nose deformity from nasal septal destruction, chronic rhinosinusitis with nasal crusting and epistaxis, subglottic stenosis causing stridor. EGPA: asthma (severe, pre-existing, often refractory), peripheral eosinophilia above 1.5 × 10^9/L, eosinophilic myocarditis. IgA vasculitis (Henoch-Schönlein purpura — predominantly children): palpable purpura on buttocks and legs, colicky abdominal pain, arthritis, and haematuria. Takayasu's arteritis: asymmetric blood pressure between arms (above 10 mmHg difference), absent radial pulse, and bruits over carotid or subclavian arteries.

ANCA serology: c-ANCA/PR3 (GPA — sensitivity above 85% in active disease), p-ANCA/MPO (MPA, EGPA — often with peripheral eosinophilia). ANA (SLE vasculitis), anti-GBM antibodies (Goodpasture's — combined pulmonary haemorrhage and RPGN). CBC (eosinophilia above 1.5 × 10^9/L — EGPA), CRP/ESR. Urinalysis with microscopy (RBC casts — pathognomonic of necrotising glomerulonephritis). Renal biopsy: pauci-immune necrotising crescentic GN (ANCA-AAV). Skin, nerve, or muscle biopsy for confirmation. Temporal artery biopsy (GCA — skip lesions require sample length above 2 cm; perform within 1-2 weeks of starting steroids). PET-CT (large vessel vasculitis activity — GCA, Takayasu). CT or MR angiography (CTA/MRA): demonstrates vessel wall thickening, stenosis, and aneurysms in large-vessel vasculitis without invasive catheterisation. Conventional angiography (PAN, Takayasu — microaneurysms, stenoses in medium vessels). Complement levels (C3, C4): reduced in immune complex vasculitides (SLE, cryoglobulinaemia, IgA vasculitis). Cryoglobulins: types II and III associated with hepatitis C-related vasculitis. Echocardiogram: for Kawasaki disease (coronary aneurysms), GCA (aortic root dilatation).

ANCA-AAV induction: IV methylprednisolone 500-1000 mg x3 days plus cyclophosphamide (IV pulses 15 mg/kg every 3 weeks — Eurolupus protocol) or rituximab 375 mg/m^2 weekly x4 (preferred for relapsing disease, renal-limited disease, or in women of childbearing age — RAVE and RITUXVAS trials demonstrate non-inferiority). Rituximab is now the preferred induction agent per EULAR 2024 guidelines. ANCA-AAV maintenance (18-24 months): rituximab 500 mg every 6 months or azathioprine 2 mg/kg/day. GCA induction: prednisolone 60 mg/day; tocilizumab 162 mg weekly SC (IL-6 receptor inhibitor — GiACTA trial) added for relapsing or resistant GCA — allows significant steroid dose reduction. Kawasaki disease: IVIG 2 g/kg single infusion plus aspirin (reduces coronary aneurysm incidence from 20% to below 5% when given within 10 days of fever onset). Plasma exchange (plasmapheresis): for severe ANCA-AAV with pulmonary haemorrhage or serum creatinine above 500 μmol/L at presentation. Avacopan (Tavneos — complement C5a receptor inhibitor): FDA and EMA approved adjunct to rituximab or cyclophosphamide for severe ANCA-AAV — reduces cumulative prednisolone exposure. PAN: corticosteroids plus cyclophosphamide; hepatitis B-associated PAN requires concurrent antiviral therapy (tenofovir or entecavir) as essential treatment to eliminate the immune complex trigger.

End-stage renal disease (ANCA vasculitis with RPGN — 20-30% at 5 years without prompt treatment). Pulmonary hemorrhage (GPA, MPA — life-threatening respiratory failure). Vision loss (GCA — ischemic optic neuropathy; permanent if not treated within hours-days). Aortic aneurysm (GCA, Takayasu). Coronary artery aneurysms (Kawasaki disease — risk of MI in young adults). Treatment complications: cyclophosphamide-related hemorrhagic cystitis, malignancy (bladder cancer — MESNA prophylaxis), infections (Pneumocystis jiroveci prophylaxis with co-trimoxazole), and osteoporosis from long-term steroids. Rituximab infusion reactions, secondary immunodeficiency with opportunistic infections (PCP pneumonia, herpes zoster reactivation), and treatment-related haematological toxicity require vigilant monitoring throughout the entire duration of immunosuppressive therapy for vasculitis.

No primary prevention for idiopathic vasculitis — the autoimmune or granulomatous trigger is unknown and not modifiable. Secondary prevention and relapse risk reduction: treat hepatitis B infection (tenofovir or entecavir) and hepatitis C infection (direct-acting antivirals — sofosbuvir plus velpatasvir) promptly to eliminate immune complex-mediated vasculitis triggers; avoid or withdraw causative drugs (propylthiouracil, hydralazine, minocycline, levamisole-adulterated cocaine — a detailed drug history is essential in all new ANCA vasculitis presentations). Regular disease activity monitoring using validated tools: BVAS (Birmingham Vasculitis Activity Score) at every clinic visit for ANCA-AAV; serial ESR, CRP, and ANCA titres; eGFR and urine dipstick with microscopy at every review — microhaematuria or red cell casts are the earliest indicators of renal relapse. Steroid-related harm prevention (mandatory given the very high cumulative prednisolone doses in vasculitis): calcium 1200 mg daily plus vitamin D 800 IU daily plus oral bisphosphonate (alendronate 70 mg weekly or risedronate 35 mg weekly) from the first day of high-dose corticosteroid therapy; baseline and annual DEXA scan for fracture risk stratification. Pneumocystis jiroveci pneumonia (PCP) prophylaxis: co-trimoxazole 480 mg three times weekly throughout the induction phase and for at least 6 months during maintenance — mandatory with cyclophosphamide; recommended with rituximab when CD4 lymphocytes fall below 200 cells/microlitre. Vaccinations: annual influenza, pneumococcal (PCV13 then PPSV23), and COVID-19 booster vaccinations are safe and important in all immunosuppressed vasculitis patients; live vaccines (MMR, yellow fever, varicella, live zoster vaccine) are contraindicated on rituximab, cyclophosphamide, or high-dose corticosteroids — offer recombinant zoster vaccine (Shingrix) instead.

Seek emergency care (call 999/112 or go to A&E immediately) for: sudden visual loss or blurred vision in a patient over 50 with temporal headache or jaw claudication — possible giant cell arteritis causing ischaemic optic neuropathy which causes permanent blindness within hours if untreated; start high-dose corticosteroids (prednisolone 60-80 mg/day) immediately — do not wait for biopsy confirmation; rapidly progressive renal failure (oliguria, rising creatinine over days) with haematuria and frothy urine (RPGN from ANCA vasculitis — renal function can be permanently lost within days without urgent treatment including plasma exchange and immunosuppression); massive haemoptysis in a known vasculitis patient (pulmonary haemorrhage from GPA or MPA — life-threatening); and suspected vasculitis in a child with prolonged fever, rash, and coronary aneurysm risk (Kawasaki disease — IVIG must be given within 10 days of fever onset to prevent coronary artery aneurysms). See a rheumatologist urgently for: new symptoms of organ involvement (haematuria, neuropathy, skin purpura, systemic symptoms) in a patient with known vasculitis — possible relapse requiring treatment escalation; and any person with multi-system symptoms (renal + pulmonary + skin + systemic) suggesting new-onset vasculitis. Vasculitis is rare but rapidly organ-threatening — do not delay referral if suspected.