Vasculitis

Constitutional features (across all vasculitides): fever, malaise, weight loss, night sweats, myalgia, and arthralgia. Multi-system inflammatory illness not fitting a single diagnosis should always raise vasculitis as a differential.

Takayasu arteritis: young women with limb claudication, blood pressure asymmetry between arms, absent or reduced pulses, vascular bruits, dizziness, and visual or cerebrovascular symptoms.

Polyarteritis nodosa: constitutional features with renal disease (infarction and renovascular hypertension, NOT glomerulonephritis), GI (mesenteric ischaemia, abdominal pain, perforation), neurological (mononeuritis multiplex - asymmetric, painful, affecting named nerves), skin (livedo reticularis, nodules, ulceration, gangrene), MSK (myalgia, arthralgia), and testicular pain. ANCA-negative. Lungs spared.

Kawasaki disease (paediatric): fever for 5 or more days plus at least 4 of bilateral non-purulent conjunctivitis, oral mucosal change, polymorphous rash, peripheral changes (palmar/plantar erythema, desquamation), and cervical lymphadenopathy. Coronary artery aneurysms drive long-term morbidity.

Granulomatosis with polyangiitis: upper airways (~90% - nasal crusting, epistaxis, septal perforation, saddle-nose deformity, sinusitis, otitis, subglottic stenosis); lower airways (~90% - pulmonary nodules with cavitation, diffuse alveolar haemorrhage); kidneys (~80% - RPGN with active urinary sediment); also peripheral neuropathy, ocular disease (scleritis, orbital pseudotumour), and skin involvement.

Microscopic polyangiitis: dominant renal RPGN with pulmonary capillaritis and diffuse alveolar haemorrhage; no upper airway disease. Pulmonary-renal syndrome is classic.

EGPA: three sequential phases - allergic (late-onset asthma, rhinitis), eosinophilic (peripheral eosinophilia, eosinophilic pneumonia or GI infiltration), and vasculitic (purpura, mononeuritis multiplex, eosinophilic myocarditis, glomerulonephritis). Cardiac involvement is the leading cause of EGPA death - echocardiography and cardiac MRI are essential at diagnosis.

IgA vasculitis: palpable non-thrombocytopenic purpura over lower limbs and buttocks, abdominal pain (intussusception risk in children), non-deforming arthritis (knees, ankles), and nephritis (haematuria, proteinuria - the most important long-term complication). Usually self-limiting in children; adults have a more severe course.

Behcet's: recurrent oral and genital ulcers, anterior or posterior uveitis (sight-threatening), skin lesions, and a positive pathergy test (papule or pustule at a sterile needle prick).

MSK and SEM relevance: PMR mimics rotator cuff disease (bilateral, raised inflammatory markers, dramatic steroid response distinguishes); vasculitic mononeuritis multiplex mimics entrapment neuropathy (painful, multifocal, named-nerve, progressive); jaw claudication in GCA mimics TMJ dysfunction (relieved by rest, ischaemic, raised markers in an older adult).

Strategy depends on the suspected vessel size; urgency is paramount. Do not delay treatment for pulmonary haemorrhage, RPGN, or GCA while awaiting investigations.

Blood tests: FBC (normocytic anaemia, thrombocytosis; marked eosinophilia in EGPA; normal platelets in IgA vasculitis), ESR and CRP (almost always raised in active disease; ~4-5% of biopsy-proven GCA has normal markers), renal function with urinalysis (the single most important bedside test - active sediment with blood, protein, and red cell casts indicates RPGN until proven otherwise).

ANCA testing follows a standard two-step pathway: indirect immunofluorescence followed by PR3 and MPO ELISA. c-ANCA/anti-PR3 strongly associates with GPA; p-ANCA/anti-MPO with MPA, and EGPA positive in ~40%. ANCA is negative in PAN, GCA, Takayasu, Kawasaki, and IgA vasculitis. A negative ANCA does not exclude AAV when clinical and histological features are compelling. Request ANCA urgently for RPGN or pulmonary haemorrhage.

Other blood work: complement (normal in AAV, low in immune-complex vasculitis); hepatitis B serology in suspected PAN; hepatitis C in cryoglobulinaemia; cryoglobulins and serum protein electrophoresis when cryoglobulinaemic vasculitis is suspected; IgA levels (supportive only in IgA vasculitis).

Imaging: HRCT thorax for pulmonary nodules, cavitation, and alveolar haemorrhage; CT or MR angiography for large-vessel disease (Takayasu, large-vessel GCA aortitis) and for PAN microaneurysms (mesenteric or renal angiography); PET-CT detects active large-vessel inflammation; echocardiography and cardiac MRI are essential in EGPA.

Tissue biopsy is the gold standard for definitive diagnosis: renal biopsy (pauci-immune crescentic glomerulonephritis in AAV; IgA deposition in IgA vasculitis), skin biopsy with immunofluorescence (leukocytoclastic vasculitis with or without IgA), nerve or muscle biopsy in mononeuritis multiplex (necrotising vasculitis of vasa nervorum), nasal or sinus biopsy in GPA, and temporal artery biopsy for GCA.

Principle: induce remission rapidly, then maintain remission long-term while minimising toxicity. Treatment delay can be fatal. BSR/BHPR guidelines and NICE technology appraisals frame UK practice. GCA is covered on the PMR/GCA page and only summary points appear here.

ANCA-associated vasculitis (GPA, MPA, EGPA):

Induction of remission for organ- or life-threatening disease (RPGN, pulmonary haemorrhage, severe systemic involvement):

• •Rituximab (anti-CD20; NICE TA308) OR cyclophosphamide, both combined with high-dose corticosteroids (IV methylprednisolone followed by oral taper). Rituximab is increasingly preferred for less gonadotoxicity and lower malignancy risk.
• •Avacopan (complement C5a receptor inhibitor; NICE TA880) as adjunct for up to 12 months to reduce cumulative glucocorticoid exposure.
• •Plasma exchange may be considered for severe renal vasculitis or pulmonary haemorrhage.

Limited (non-organ-threatening) disease: methotrexate or mycophenolate with corticosteroids may suffice (especially in limited GPA without renal involvement).

Maintenance of remission: rituximab (preferred per NICE TA308) at typical 6-monthly infusions, or azathioprine or methotrexate, for 24-48 months individualised by relapse risk. Steroid tapering throughout. Co-trimoxazole for PJP prophylaxis according to the immunosuppressive regimen, glucocorticoid dose, and local protocol.

EGPA-specific: corticosteroids for mild disease; cyclophosphamide or rituximab for organ-threatening disease; mepolizumab (NICE TA769) and benralizumab target the IL-5 pathway for relapsing or refractory EGPA. Cardiac involvement drives mortality - cardiology input is essential.

Polyarteritis nodosa: corticosteroids for mild disease; cyclophosphamide plus corticosteroids for severe disease. Hepatitis B-associated PAN requires antiviral therapy (entecavir or tenofovir) alongside short-course immunosuppression.

IgA vasculitis: usually self-limiting in children with supportive care; corticosteroids for severe abdominal pain or significant nephritis; renal monitoring (urinalysis, blood pressure) for at least 6 months. Adults often require immunosuppression for significant renal disease.

Behcet's: colchicine for mucocutaneous disease; immunosuppression (azathioprine, ciclosporin, mycophenolate) for organ involvement; TNF inhibitors (infliximab, adalimumab) and apremilast for refractory disease.

Takayasu: high-dose corticosteroids first-line; steroid-sparing with methotrexate, azathioprine, or mycophenolate; biologic therapy (TNF inhibitors, tocilizumab) for refractory disease; vascular surgery or angioplasty for critical stenoses.

General principles across all vasculitides: bone protection on long-term steroids per NICE NG223/NOGG; cardiovascular risk management; vaccinations up to date with live vaccines contraindicated during immunosuppression; screening for latent TB, hepatitis B and C, and HIV before rituximab; ongoing relapse monitoring with clinical assessment, inflammatory markers, urinalysis, renal function, and FBC.

Rehabilitation manages the consequences of disease and treatment - corticosteroid side effects (proximal myopathy, osteoporosis, weight gain, metabolic syndrome), deconditioning, fatigue, peripheral neuropathy, and psychological impact. Exercise is safe and beneficial in stable, treated disease and improves cardiovascular fitness, fatigue, strength, and mood.

Steroid-related complications: progressive strengthening for proximal myopathy (quadriceps, hip abductors, core); weight-bearing exercise and falls prevention alongside pharmacological bone protection; FRAX assessment. Differentiate steroid myopathy (insidious, CK normal) from active vasculitic myalgia.

Mononeuritis multiplex rehabilitation: physiotherapy for weakness and sensory loss, orthotics for foot drop (AFO), and neuropathic pain management per NICE CG173. Nerve recovery may be incomplete.

Fatigue management: exercise (paradoxically beneficial), pacing, energy conservation, sleep hygiene, and treatment of contributors (anaemia, depression, hypothyroidism). Supervised cardiovascular rehabilitation when cardiac involvement is present (EGPA). Psychological support is important given anxiety about relapse, treatment side effects, and prognosis. Vasculitis UK is a key patient support organisation to signpost.

• •Chapel Hill 2012 consensus classification - the modern vessel-size framework for systemic vasculitis.
• •BSR/BHPR guidelines for ANCA-associated vasculitis - induction with rituximab or cyclophosphamide plus steroids; maintenance with rituximab or azathioprine.
• •NICE TA308 - rituximab for AAV induction and maintenance.
• •NICE TA880 - avacopan as adjunct in GPA/MPA induction, reducing glucocorticoid exposure for up to 12 months.
• •NICE TA769 - mepolizumab for relapsing or refractory EGPA.
• •2022 ACR/EULAR vasculitis classification criteria (GCA, Takayasu, GPA, MPA, EGPA) - weighted clinical, laboratory, and imaging domains.

• •Chapel Hill 2012 classifies vasculitides by predominant vessel size.
• •GPA: c-ANCA/PR3, upper + lower airways + kidneys. MPA: p-ANCA/MPO, kidneys + lungs, no upper airway.
• •EGPA: asthma + eosinophilia + vasculitis; cardiac involvement drives mortality.
• •PAN: hepatitis B-associated; microaneurysms; no lungs, no GN; ANCA-negative.
• •IgA vasculitis: paediatric purpura tetrad; renal monitoring for at least 6 months.
• •AAV induction: rituximab or cyclophosphamide plus steroids; rituximab maintenance per NICE TA308.