Vasculitis Emergency

Topic Overview

Summary

Vasculitis emergencies occur when inflammation of blood vessels causes acute life-threatening organ damage requiring immediate recognition and aggressive immunosuppression. ANCA-associated vasculitides (AAV)—granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA)—are the most common causes of vasculitic emergencies. Key presentations include pulmonary-renal syndrome (diffuse alveolar haemorrhage + rapidly progressive glomerulonephritis), isolated renal crisis, diffuse alveolar haemorrhage, mononeuritis multiplex, mesenteric ischaemia, and central nervous system vasculitis. Treatment is urgent immunosuppression with high-dose corticosteroids plus either cyclophosphamide or rituximab, with plasma exchange reserved for severe pulmonary haemorrhage or dialysis-dependent renal failure. [1,2]

Key Facts

• ANCA vasculitides: GPA (granulomatosis with polyangiitis), MPA (microscopic polyangiitis), EGPA (eosinophilic granulomatosis with polyangiitis)
• Life-threatening emergencies: Pulmonary-renal syndrome (30-40% mortality if untreated), diffuse alveolar haemorrhage, RPGN, mesenteric ischaemia, stroke
• Key diagnostic tests: ANCA serology (PR3-ANCA, MPO-ANCA), urinalysis (blood, protein, red cell casts), chest imaging, biopsy when feasible
• Emergency treatment: High-dose IV methylprednisolone (500-1000 mg daily × 3 days) + cyclophosphamide or rituximab
• Plasma exchange: PEXIVAS trial showed no mortality benefit but may be considered in severe pulmonary haemorrhage [3]
• Time-critical: Irreversible organ damage occurs within days—do NOT delay treatment for biopsy confirmation if clinical suspicion is high

Clinical Pearls

Pulmonary-renal syndrome = lungs + kidneys = think ANCA vasculitis (70-80%) or anti-GBM disease (10-20%). Urgent ANCA, anti-GBM, and urinalysis are essential.

Urinalysis showing haematuria, proteinuria, and red cell casts = glomerulonephritis—URGENT nephrology referral. This is a medical emergency.

Do NOT wait for biopsy to start treatment if clinical picture strongly suggests vasculitis emergency. Delay can result in irreversible renal failure or death.

Normal complement (C3, C4) in small vessel vasculitis helps distinguish ANCA vasculitis from lupus nephritis or cryoglobulinaemia.

PR3-ANCA (c-ANCA) is more specific for GPA; MPO-ANCA (p-ANCA) is more common in MPA and EGPA. However, 10-20% of AAV patients are ANCA-negative. [4]

Why This Matters Clinically

Vasculitis emergencies can cause irreversible organ damage or death within days. The 1-year mortality of untreated AAV exceeds 80-90%. [5] Early recognition and aggressive immunosuppression are life-saving, improving 5-year survival to over 75-80%. [6] Delay in treatment for even 24-48 hours can result in permanent dialysis dependence or respiratory failure. Clinicians must have a low threshold for suspicion in patients presenting with multi-system inflammatory disease, particularly pulmonary-renal syndrome.

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Visual Summary

Visual assets to be added:

• Vasculitis classification by vessel size (Chapel Hill Consensus)
• ANCA vasculitis organ involvement diagram
• Pulmonary-renal syndrome diagnostic flowchart
• Vasculitis emergency management algorithm
• RPGN histology (crescentic glomerulonephritis)
• Diffuse alveolar haemorrhage imaging (CXR/CT)
• Mononeuritis multiplex distribution map

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Epidemiology

Incidence and Prevalence

• ANCA-associated vasculitis: Annual incidence 13-20 per million in Northern Europe, 2.1-14.4 per million in Asia [7]
• GPA: More common in Northern Europe (10-12 per million/year), predominantly White populations
• MPA: More common in Southern Europe and Asia (6-10 per million/year)
• EGPA: Rarest (1-3 per million/year)
• Emergency presentations: Approximately 30-50% of AAV patients present with organ-threatening or life-threatening disease [8]

Demographics

• Peak age: 50-75 years (mean 60 years)
• Sex distribution: Equal to slight male predominance (M:F ratio 1.2-1.5:1)
• Ethnicity: GPA more common in White populations; MPA has more even ethnic distribution

Risk Factors for Severe Presentation

• Older age (> 65 years)
• Higher ANCA titres at presentation
• PR3-ANCA positivity (higher relapse risk)
• Renal involvement at diagnosis (20-30% risk of ESRD)
• Pulmonary haemorrhage (mortality 10-50% depending on severity) [9]

Types of Vasculitis by Vessel Size

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Pathophysiology

ANCA-Associated Vasculitis Mechanism

Autoantibody Formation and Activation

1. Autoantigen exposure: Genetic susceptibility (HLA-DP, genes encoding PR3 and MPO) plus environmental triggers (infections, silica, drugs) lead to autoantigen presentation
2. ANCA production: B cells produce antibodies against proteinase 3 (PR3) or myeloperoxidase (MPO) expressed on neutrophil cytoplasm
3. Neutrophil priming: Inflammatory cytokines (TNF-α, IL-1, complement C5a) cause neutrophils to express PR3/MPO on cell surface
4. ANCA-neutrophil interaction: ANCA antibodies bind to surface-expressed antigens, causing neutrophil activation via Fc receptor engagement
5. Endothelial damage: Activated neutrophils adhere to vascular endothelium, release reactive oxygen species, proteolytic enzymes, and neutrophil extracellular traps (NETs)
6. Necrotising vasculitis: Transmural inflammation with fibrinoid necrosis, vessel wall destruction, and end-organ ischaemia/infarction [10]

Complement Activation

• Alternative complement pathway activation amplifies neutrophil priming
• C5a generation is critical for full disease expression
• C5a receptor (C5aR) blockade shows promise in experimental models [11]

Key ANCA Patterns and Disease Associations

Note: 10-20% of AAV cases are ANCA-negative but have typical clinical and histological features. [4]

Pathophysiology of Emergency Presentations

Rapidly Progressive Glomerulonephritis (RPGN)

• Mechanism: Pauci-immune crescentic glomerulonephritis with minimal immune complex deposition
• Histology: Segmental necrotising glomerulonephritis with crescent formation (> 50% glomeruli affected defines RPGN), interstitial inflammation
• Outcome: Without treatment, progresses to end-stage renal disease within weeks to months
• Prognosis: Dialysis-dependent at presentation has 50-70% chance of renal recovery with aggressive treatment [12]

Diffuse Alveolar Haemorrhage (DAH)

• Mechanism: Pulmonary capillaritis with neutrophil infiltration, capillary wall necrosis, and red cell extravasation into alveolar spaces
• Clinical: Haemoptysis (present in only 30-50%), dyspnoea, hypoxia, anaemia, bilateral infiltrates on imaging
• Diagnosis: Progressively bloodier return on serial bronchoalveolar lavage aliquots
• Mortality: 10-50% depending on severity, need for mechanical ventilation [13]

Pulmonary-Renal Syndrome

• Definition: Concurrent diffuse alveolar haemorrhage and glomerulonephritis
• Causes: ANCA vasculitis (70-80%), anti-GBM disease (10-20%), SLE (5-10%), other
• Mortality: 20-40% with treatment, > 80% without [14]

Mesenteric Ischaemia

• Mechanism: Vasculitis affecting mesenteric arteries (medium-vessel) or mesenteric capillaries/venules (small-vessel)
• Clinical: Acute abdominal pain, bloody diarrhoea, peritonitis, bowel perforation
• Imaging: CT angiography shows bowel wall thickening, pneumatosis, mesenteric vessel narrowing
• Mortality: 30-50% if bowel infarction occurs [15]

Central Nervous System Vasculitis

• Primary CNS vasculitis: Rare, confined to CNS
• Secondary CNS involvement in AAV: Pachymeningitis (GPA), cerebral infarction, intracerebral haemorrhage, cranial neuropathies
• Diagnosis: MRI brain (leptomeningeal/pachymeningeal enhancement, infarcts), angiography (beading, stenosis), CSF analysis, brain biopsy (gold standard)
• Prognosis: High morbidity; requires prolonged immunosuppression [16]

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Clinical Presentation

Constitutional Symptoms

• Fever: Present in 50-70% (often low-grade, but can be high)
• Weight loss: > 5 kg in 30-50% (suggests active systemic inflammation)
• Fatigue and malaise: Nearly universal
• Myalgia and arthralgia: 30-60% (often migratory, non-erosive)
• Night sweats: Common

Organ Involvement by System

GPA (Granulomatosis with Polyangiitis) — Classic Triad

• Upper airway disease: Chronic sinusitis (90%), nasal discharge/crusting/ulceration (70%), epistaxis (50%), saddle nose deformity (10-20%), subglottic stenosis (15%)
• Lung disease: Pulmonary nodules (often cavitating), masses, infiltrates, diffuse alveolar haemorrhage
• Kidney disease: Pauci-immune crescentic glomerulonephritis (70-80%)
• Granulomatous inflammation: Histological hallmark (necrotising granulomas)

MPA (Microscopic Polyangiitis)

• Kidney-predominant: Glomerulonephritis in 80-100% (often more severe than GPA at presentation)
• Lung involvement: Diffuse alveolar haemorrhage in 10-30%
• Less upper airway involvement: Sinusitis less common than GPA
• No granulomas: Non-granulomatous necrotising vasculitis

EGPA (Eosinophilic Granulomatosis with Polyangiitis)

• Asthma: Present in > 95% (often severe, adult-onset)
• Eosinophilia: Peripheral eosinophil count > 1.5 × 10⁹/L (often > 10% on differential)
• Sinusitis and nasal polyposis: 70-90%
• Peripheral neuropathy: Mononeuritis multiplex or distal symmetric polyneuropathy in 60-75%
• Cardiac involvement: Myocarditis, eosinophilic cardiomyopathy (major cause of mortality)
• Skin: Purpura, subcutaneous nodules
• ANCA-positive in 40-60%: MPO-ANCA; ANCA-negative disease tends to have more eosinophilic tissue infiltration

Red Flags and Life-Threatening Presentations

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Clinical Examination

General Appearance

• Fever: Temperature > 38°C
• Cachexia: Weight loss, muscle wasting (chronic systemic inflammation)
• Pallor: Anaemia (chronic disease, renal failure, or alveolar haemorrhage)
• Respiratory distress: Tachypnoea, use of accessory muscles (pulmonary haemorrhage, infection)

Vital Signs

• Tachycardia: HR > 100 bpm (sepsis, anaemia, hypovolaemia)
• Hypertension: Renal involvement (glomerulonephritis)
• Hypoxia: SpO₂ less than 92% (diffuse alveolar haemorrhage, pulmonary infiltrates)

Respiratory Examination

• Inspection: Tachypnoea, cyanosis
• Auscultation: Crackles (bilateral in DAH), reduced air entry (effusion, consolidation)
• Signs of respiratory failure: Confusion, inability to speak in sentences

Cardiovascular Examination

• Pericardial rub: Pericarditis (10-20% of AAV)
• Muffled heart sounds: Pericardial effusion
• Heart failure signs: Elevated JVP, peripheral oedema (myocarditis, fluid overload from renal failure)

Abdominal Examination

• Tenderness: Peritonism, rebound, guarding (mesenteric ischaemia, bowel perforation)
• Absent bowel sounds: Ileus, perforation
• Hepatosplenomegaly: Rare in AAV (consider other diagnoses)

Skin Examination

• Palpable purpura: Small vessel vasculitis (legs, buttocks)
• Ulcers: Painful ulcers on legs, feet
• Livedo reticularis: Reticular violaceous discolouration (medium-vessel involvement)
• Digital ischaemia: Splinter haemorrhages, digital infarcts, gangrene
• Skin necrosis: Full-thickness necrosis (poor prognostic sign)

Neurological Examination

• Mononeuritis multiplex: Asymmetric motor and/or sensory deficits in multiple nerve distributions (e.g., foot drop [common peroneal], wrist drop [radial], ulnar neuropathy)
• Peripheral polyneuropathy: Symmetric distal sensory loss (EGPA)
• Cranial neuropathies: CN II (optic neuritis), CN VI (abducens palsy), CN VII (facial palsy)
• Focal neurological deficits: Stroke, intracerebral haemorrhage (CNS vasculitis)

ENT Examination (especially GPA)

• Nasal examination: Crusting, ulceration, septal perforation, saddle nose deformity
• Sinuses: Tenderness over maxillary, frontal sinuses
• Oropharynx: Oral ulcers, gingival hyperplasia ("strawberry gingivitis")
• Subglottic stenosis: Stridor, dyspnoea (life-threatening complication)

Ophthalmological Examination

• Conjunctivitis: Redness, discharge
• Episcleritis/scleritis: Painful red eye, scleral oedema, risk of perforation
• Uveitis: Photophobia, blurred vision, hypopyon
• Retinal vasculitis: Cotton-wool spots, haemorrhages, vessel occlusion
• Orbital pseudotumour: Proptosis, ophthalmoplegia, pain

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Investigations

Immediate Investigations (Emergency Department/Acute Setting)

Bedside Tests

• Urinalysis (CRITICAL): Dipstick for blood and protein; microscopy for red cell casts (pathognomonic for glomerulonephritis)
  • Positive blood + protein + red cell casts = glomerulonephritis until proven otherwise
• Oxygen saturation: SpO₂ less than 92% suggests pulmonary involvement

Blood Tests

ANCA Testing Details

• Immunofluorescence pattern: c-ANCA (cytoplasmic) or p-ANCA (perinuclear)
• Antigen-specific ELISA: PR3 or MPO (more specific than immunofluorescence alone)
• Interpretation: Positive ANCA (either PR3 or MPO) + compatible clinical picture = high probability of AAV
• False positives: Infections (endocarditis, TB), inflammatory bowel disease, autoimmune hepatitis, drugs (hydralazine, minocycline)
• Negative ANCA: Does NOT exclude AAV—10-20% of AAV is ANCA-negative; diagnosis relies on histology and clinical features [4]

Urinalysis and Renal Investigations

Imaging

Chest Imaging (URGENT in suspected pulmonary involvement)

Diffuse alveolar haemorrhage imaging: Bilateral ground-glass opacification or consolidation sparing the apices; may be asymmetric

Renal Imaging

• Ultrasound kidneys: Usually normal kidney size and echotexture in acute AAV (helps exclude obstruction, chronic kidney disease)

Other Imaging (depending on clinical suspicion)

• CT sinuses: Mucosal thickening, sinus opacification, bony erosion (GPA)
• CT abdomen/pelvis with IV contrast (CT angiography): Bowel wall thickening, pneumatosis, mesenteric vessel narrowing (mesenteric ischaemia)
• MRI brain + MRA/CTA: Stroke, intracerebral haemorrhage, leptomeningeal/pachymeningeal enhancement (CNS vasculitis)
• Echocardiography: Pericardial effusion, myocarditis, regional wall motion abnormalities

Tissue Biopsy (GOLD STANDARD for diagnosis)

When to perform biopsy: Ideally BEFORE starting immunosuppression (improves diagnostic yield), but do NOT delay life-saving treatment if biopsy cannot be obtained safely or quickly.

Bronchoscopy and Bronchoalveolar Lavage (BAL)

Diagnostic Criteria for ANCA-Associated Vasculitis

2022 ACR/EULAR Classification Criteria (simplified):

• Clinical features (organ involvement) + positive ANCA OR histological confirmation of vasculitis
• Scoring system assigns points for clinical features, ANCA positivity, and biopsy findings
• Score ≥6 classifies as GPA, MPA, or EGPA (depending on features)

Note: Classification criteria are NOT diagnostic criteria; clinical diagnosis often made on balance of clinical features, serology, and histology.

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Differential Diagnosis

Pulmonary-Renal Syndrome Differential

RPGN Differential

• Pauci-immune: AAV (most common), drug-induced (levamisole-adulterated cocaine, hydralazine)
• Anti-GBM disease: Linear IgG deposition on immunofluorescence
• Immune complex: Lupus nephritis, post-infectious GN, IgA nephropathy, cryoglobulinaemia
• Thrombotic microangiopathy: HUS, TTP, malignant hypertension

Diffuse Alveolar Haemorrhage Differential

• AAV (most common cause of pulmonary-renal syndrome)
• Anti-GBM disease
• SLE
• Antiphospholipid syndrome
• Drug-induced (amiodarone, cocaine, propylthiouracil)
• Coagulopathy (anticoagulation, thrombocytopenia)
• Infection (invasive aspergillosis, bacterial pneumonia with lung necrosis)
• Diffuse alveolar damage (ARDS, toxins)

Other Mimics of Vasculitis Emergency

• Infective endocarditis: Fever, haematuria, embolic phenomena, positive ANCA (10-15% false positive)
• Malignancy: Atrial myxoma (emboli mimicking vasculitis), lymphoma, leukaemia
• Atrial myxoma: Embolic stroke, fever, raised inflammatory markers, constitutional symptoms
• Atheroembolic disease: Livedo reticularis, acute kidney injury, peripheral ischaemia (often post-procedure)
• Thrombotic thrombocytopenic purpura (TTP): Fever, renal impairment, neurological features, thrombocytopenia, MAHA

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Management

Immediate Resuscitation and Supportive Care

ABCDE Assessment

• Airway: Secure if stridor (subglottic stenosis), reduced GCS, massive haemoptysis
• Breathing: High-flow oxygen if SpO₂ less than 92%; consider non-invasive ventilation or intubation if respiratory failure
• Circulation: IV access, fluid resuscitation (cautious if renal failure/fluid overload), correct hyperkalaemia/acidosis
• Disability: GCS, blood glucose
• Exposure: Full examination for rash, digital ischaemia, peripheral neuropathy

Life-Threatening Complications — Immediate Management

Supportive Care

• Oxygen therapy: Target SpO₂ 94-98%
• Blood transfusion: If Hb less than 70 g/L or symptomatic anaemia
• Dialysis: If uraemia, hyperkalaemia, acidosis, pulmonary oedema unresponsive to medical management
• Analgesia: NSAIDs avoided (renal impairment); use paracetamol, opioids
• VTE prophylaxis: LMWH unless contraindicated (active bleeding, severe thrombocytopenia)
• Stress ulcer prophylaxis: PPI (high-dose corticosteroids)
• PJP prophylaxis: Co-trimoxazole 480 mg daily or 960 mg three times weekly (start once on immunosuppression)

Definitive Immunosuppressive Therapy

High-Dose Corticosteroids (ALL patients)

Tapering schedule (typical):

• 1 mg/kg for 2-4 weeks
• Reduce by 10 mg every 2 weeks to 20 mg
• Reduce by 2.5-5 mg every 2-4 weeks to 10 mg
• Maintain 5-10 mg daily for 12-24 months

Induction Therapy — Cyclophosphamide vs Rituximab

RAVE and RITUXVAS trials: Rituximab is non-inferior to cyclophosphamide for induction of remission in AAV. [2,17]

Choice of induction agent:

• Rituximab preferred: Relapsing disease, PR3-ANCA positivity, young patients desiring fertility preservation, previous cyclophosphamide toxicity
• Cyclophosphamide preferred: Resource-limited settings, need for oral administration, immediate availability (rituximab may require pre-authorisation)

Adjunctive Therapies

Plasma Exchange (PLEX): Controversial following PEXIVAS trial [3]

Current practice (post-PEXIVAS):

• Not routinely recommended for RPGN or DAH
• May consider in highly selected cases:
  • Severe DAH requiring mechanical ventilation
  • Dual ANCA + anti-GBM positivity
  • Dialysis-dependent renal failure (benefit uncertain)
• Regimen if used: 7 plasma exchanges (60 mL/kg plasma per exchange) over 14 days

Avacopan (C5a receptor antagonist):

• ADVOCATE trial (2021): Avacopan 30 mg PO BD non-inferior to prednisolone taper as adjunct to rituximab/cyclophosphamide for induction and maintenance [20]
• Benefits: Steroid-sparing, reduced steroid-related adverse events
• Licensed in USA/Europe for AAV; high cost limits widespread use
• Role: Consider in patients intolerant of corticosteroids or with contraindications

Maintenance Therapy (after remission induction at 3-6 months)

Low-dose prednisolone: Continue 5-10 mg daily during maintenance (taper to 5 mg or discontinue by 12-18 months if stable remission)

Choice of maintenance agent:

• Rituximab preferred: PR3-ANCA, relapsing disease, severe disease at presentation
• Azathioprine or methotrexate: First presentation, MPO-ANCA, patient preference, cost considerations

Treatment of Relapse

Definition of relapse: Recurrence of disease activity after remission (new organ involvement or worsening of existing involvement)

Management:

• Major relapse (organ-threatening): Re-induction with high-dose steroids + cyclophosphamide or rituximab
• Minor relapse (non-organ-threatening): Increase prednisolone dose (e.g., 0.5 mg/kg) ± switch maintenance agent

Relapse rates: 50% at 5 years; GPA relapses more than MPA; PR3-ANCA relapses more than MPO-ANCA [23]

Monitoring During Treatment

Drug Toxicity and Prophylaxis

PJP prophylaxis: Co-trimoxazole 480 mg daily or 960 mg three times weekly for all patients on high-dose steroids + cyclophosphamide/rituximab; continue for 6-12 months after stopping immunosuppression

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Complications

Complications of Vasculitis

Complications of Treatment

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Prognosis and Outcomes

Mortality

• Untreated AAV: 1-year mortality 80-90% [5]
• Treated AAV: 5-year survival 75-85% [6]
• Early mortality (first year): 10-15%, mainly due to active disease (pulmonary haemorrhage, renal failure) or infection
• Late mortality (after first year): Cardiovascular disease, infection, malignancy

Predictors of Poor Prognosis

• Age > 65 years: Higher mortality, more comorbidities, greater infection risk
• Dialysis requirement at presentation: 30-50% remain dialysis-dependent
• Pulmonary haemorrhage requiring mechanical ventilation: Mortality 20-50%
• PR3-ANCA positivity: Higher relapse rate than MPO-ANCA
• Extent of crescent formation on renal biopsy: > 50% crescents associated with worse renal outcomes
• Delayed treatment: Increased risk of irreversible organ damage

Renal Outcomes

• Renal recovery if dialysis-dependent: 50-70% with aggressive treatment [12]
• ESRD at 5 years: 20-30%
• Predictors of ESRD: Creatinine > 500 μmol/L at presentation, > 50% glomerular crescents, tubulointerstitial fibrosis on biopsy, delayed treatment

Relapse

• Cumulative relapse rate: 50% at 5 years [23]
• GPA vs MPA: GPA relapses more frequently
• PR3-ANCA vs MPO-ANCA: PR3-ANCA has higher relapse risk
• Predictors of relapse: PR3-ANCA, upper airway involvement, rising ANCA titres (imperfect predictor)

Quality of Life

• Chronic fatigue (common even in remission)
• Chronic kidney disease
• Peripheral neuropathy with persistent disability
• Corticosteroid-related morbidity (weight gain, osteoporosis, diabetes)

Long-Term Follow-Up

• Lifelong monitoring for relapse, chronic organ damage, and treatment complications
• Annual cardiovascular risk assessment
• Cancer surveillance (especially bladder if prior cyclophosphamide)

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Evidence and Guidelines

Key Guidelines

1. 2021 EULAR/ERA-EDTA Recommendations for the Management of ANCA-Associated Vasculitis [24]

   • Comprehensive evidence-based guidelines covering diagnosis, treatment (induction and maintenance), and monitoring
   • Recommends rituximab or cyclophosphamide for induction; rituximab or azathioprine for maintenance
   • Addresses use of plasma exchange (not routinely recommended post-PEXIVAS)

2. 2016 BSR and BHPR Guideline for the Management of Adults with ANCA-Associated Vasculitis [1]

   • UK-focused guideline
   • Emphasises early diagnosis, urgent treatment, and multidisciplinary care

3. 2021 KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases [25]

   • Specific recommendations for ANCA-associated glomerulonephritis
   • Advocates for glucocorticoids + rituximab or cyclophosphamide; discusses plasma exchange

Key Trials

Key Evidence Summary

• Rituximab is non-inferior to cyclophosphamide for induction of remission in AAV, with advantages in relapsing disease and fertility preservation [2,17]
• Plasma exchange does NOT reduce death or ESRD in severe AAV and is not routinely recommended (PEXIVAS trial) [3]
• Reduced-dose corticosteroids are non-inferior to standard-dose for induction, reducing steroid-related toxicity [3]
• Rituximab is superior to azathioprine for maintenance therapy in preventing relapse [22]
• Avacopan is a steroid-sparing alternative to prednisolone taper [20]

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Patient and Family Information

What is Vasculitis?

Vasculitis means inflammation of blood vessels. In ANCA-associated vasculitis, the immune system mistakenly attacks blood vessels, causing damage to organs like the kidneys, lungs, nerves, and skin. This is a serious condition that requires urgent treatment with medications that suppress the immune system.

What Are the Symptoms?

Symptoms vary depending on which organs are affected:

• Kidneys: Blood in urine, swelling, high blood pressure, kidney failure
• Lungs: Coughing up blood, shortness of breath
• Nerves: Numbness, tingling, weakness, foot drop
• Skin: Rash (purpura), ulcers
• Sinuses/nose: Nosebleeds, nasal crusting, sinusitis
• General: Fever, weight loss, fatigue

How Is It Diagnosed?

• Blood tests (ANCA antibodies, kidney function)
• Urine tests (blood and protein)
• Imaging (chest X-ray or CT scan)
• Biopsy (kidney, skin, or other organs)

How Is It Treated?

Treatment involves strong medications to suppress the immune system and stop the blood vessel inflammation:

• Steroids (prednisolone or IV methylprednisolone)
• Immunosuppressants (cyclophosphamide or rituximab)
• Plasma exchange (in selected severe cases)
• Supportive care (dialysis if kidneys fail, oxygen if lungs affected)

Treatment is usually in two phases:

1. Induction (3-6 months): Strong treatment to control active disease
2. Maintenance (18-24+ months): Milder treatment to prevent relapse

What Are the Side Effects of Treatment?

• Steroids: Weight gain, high blood sugar, osteoporosis, mood changes, increased infection risk
• Cyclophosphamide: Reduced fertility, bladder irritation, infection risk, nausea
• Rituximab: Infection risk, infusion reactions

Your doctors will monitor closely for side effects and provide medications to reduce risks (e.g., antibiotics to prevent infections, bone protection).

What Is the Outlook?

With treatment, most people improve, but vasculitis can relapse (come back) in about 50% of patients over 5 years. Long-term monitoring and medication are essential. Some people may have permanent organ damage (e.g., kidney failure requiring dialysis, nerve damage).

Living with Vasculitis

• Attend all follow-up appointments
• Take medications as prescribed
• Report new symptoms immediately (relapse can occur)
• Avoid infections (good hygiene, avoid sick contacts, vaccinations)
• Healthy lifestyle (diet, exercise, no smoking)

Resources and Support

• Vasculitis UK: https://www.vasculitis.org.uk
• NHS Vasculitis Information: https://www.nhs.uk/conditions/vasculitis
• Vasculitis Foundation (USA): https://www.vasculitisfoundation.org
• ANCA Vasculitis UK: Patient support group

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Key Learning Points

For Medical Students

• Vasculitis emergency = life-threatening inflammation of blood vessels requiring urgent immunosuppression
• Classic presentation: Pulmonary-renal syndrome (haemoptysis + rising creatinine)
• Key tests: Urinalysis (red cell casts = GN), ANCA, CXR/CT chest, renal function
• Treatment: High-dose steroids + cyclophosphamide or rituximab
• Do NOT delay treatment for biopsy if clinical suspicion is high

For Specialty Trainees (MRCP/FRACP)

• Differentials for pulmonary-renal syndrome: ANCA vasculitis (70-80%), anti-GBM disease (10-20%), SLE, cryoglobulinaemia
• ANCA-negative vasculitis occurs in 10-20%—diagnosis relies on clinical features + histology
• PEXIVAS trial: Plasma exchange NOT routinely beneficial; use reduced-dose steroids
• Rituximab vs cyclophosphamide: Non-inferior for induction; rituximab preferred if relapsing disease, young patients (fertility preservation)
• Relapse risk: 50% at 5 years; higher in GPA and PR3-ANCA
• Long-term complications: ESRD (20-30%), infection, cardiovascular disease, malignancy

For Emergency Medicine

• High index of suspicion for vasculitis in multi-system inflammatory disease
• Urinalysis is CRITICAL: Always perform in suspected vasculitis
• Red flags: Haemoptysis + rising creatinine, creatinine doubling in less than 7 days, new mononeuropathy
• Immediate actions: ANCA, anti-GBM, urinalysis, CXR/CT chest, renal function, urgent rheumatology/nephrology referral
• Start high-dose IV corticosteroids urgently if strong suspicion (do NOT wait for ANCA results or biopsy)

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References

Primary Guidelines

1. Ntatsaki E, Carruthers D, Chakravarty K, et al. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014;53(12):2306-2309. PMID: 24729399

Key Trials and Evidence

2. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. PMID: 20647199

3. Walsh M, Merkel PA, Peh CA, et al. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020;382(7):622-631. PMID: 32053298

4. Damoiseaux J, Csernok E, Rasmussen N, et al. Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis. 2017;76(4):647-653. PMID: 27590654

5. Phillip R, Luqmani R. Mortality in systemic vasculitis: a systematic review. Clin Exp Rheumatol. 2008;26(5 Suppl 51):S94-S104. PMID: 19026150

6. Flossmann O, Berden A, de Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70(3):488-494. PMID: 21109517

7. Watts RA, Mahr A, Mohammad AJ, et al. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant. 2015;30 Suppl 1:i14-i22. PMID: 25805746

8. Charlier C, Henegar C, Launay O, et al. Risk factors for major infections in Wegener granulomatosis: analysis of 113 patients. Ann Rheum Dis. 2009;68(5):658-663. PMID: 18621758

9. Gallagher H, Kwan JT, Jayne DR. Pulmonary renal syndrome: a 4-year, single-center experience. Am J Kidney Dis. 2002;39(1):42-47. PMID: 11774099

10. Jennette JC, Falk RJ. Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol. 2014;10(8):463-473. PMID: 24934187

11. Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384(7):599-609. PMID: 33596356

12. Hauer HA, Bajema IM, van Houwelingen HC, et al. Renal histology in ANCA-associated vasculitis: differences between diagnostic and serologic subgroups. Kidney Int. 2002;61(1):80-89. PMID: 11786088

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