OSCE Question: Vasculitis

CLINICAL SCENARIO

• Recurrent episodes of bloody nasal discharge and nasal crusting
• Productive cough with occasional haemoptysis
• Facial pain and bilateral sinus congestion
• Progressive swelling and frothy urine noticed over the past 2 weeks
• On examination: saddle-nose deformity, palpable purpuric papules on both lower limbs, bilateral wheeze, and periorbital oedema
• BP: 152/96 mmHg | Temperature: 37.8°C | Urine dipstick: 3+ blood, 2+ protein

• Hb: 9.2 g/dL (normocytic)
• WBC: 11,200/μL
• Creatinine: 2.4 mg/dL (baseline 0.9 one year ago)
• Urine microscopy: dysmorphic RBCs + RBC casts
• CXR: bilateral pulmonary nodules with central cavitation
• ANCA serology: c-ANCA positive, anti-PR3 antibody: strongly positive
• Renal biopsy: pauci-immune crescentic glomerulonephritis

QUESTIONS (Marks as indicated)

MODEL ANSWER

(a) Diagnosis (2 marks)

The triad of upper respiratory involvement (sinusitis, nasal crusting, saddle-nose), lower respiratory involvement (cavitating nodules, haemoptysis), and renal involvement (rapidly progressive glomerulonephritis) combined with strongly positive c-ANCA/anti-PR3 is diagnostic.

• Dermatology 2-Volume Set 5e, Table 24.7

(b) Classification (3 marks)

1. Microscopic Polyangiitis (MPA) - p-ANCA/anti-MPO positive, pauci-immune GN without granulomas
2. Eosinophilic Granulomatosis with Polyangiitis (EGPA) - formerly Churg-Strauss syndrome; associated with asthma, eosinophilia, and paranasal sinusitis

The three AAVs are characterised by vasculitis of small-to-medium vessels, presence of ANCAs, and overlapping yet distinguishable organ involvement. New ACR-EULAR classification criteria have been proposed for these diseases.

• Dermatology 2-Volume Set 5e, p. 521

(c) Classic Clinical Triad of GPA (3 marks)

1. Necrotising granulomatous inflammation of the upper respiratory tract - bloody/purulent rhinorrhoea, nasal crusting, saddle-nose deformity, sinusitis, subglottic stenosis, conductive/sensorineural hearing loss
2. Necrotising granulomatous inflammation of the lower respiratory tract - pulmonary nodules (may cavitate), haemoptysis, diffuse alveolar haemorrhage
3. Necrotising pauci-immune crescentic glomerulonephritis - haematuria, proteinuria, RBC casts, rapidly progressive renal failure

GPA is an autoimmune necrotising vasculitis characterised by granulomata of upper and lower respiratory tracts and kidneys; it can be fatal if not treated promptly.

• Scott-Brown's Otorhinolaryngology, Block 13

(d) Pathogenesis (4 marks)

1. Priming - Infections or inflammatory cytokines (e.g., TNF-α, IL-8) prime circulating neutrophils, causing surface expression of PR3 (proteinase-3) and MPO (myeloperoxidase) antigens.
2. ANCA binding - Circulating c-ANCA (anti-PR3) binds surface-expressed PR3 on primed neutrophils, leading to neutrophil activation via Fc-receptor cross-linking.
3. Neutrophil-mediated endothelial injury - Activated neutrophils undergo respiratory burst, degranulate, and release proteolytic enzymes (elastase, proteinase-3), reactive oxygen species, and neutrophil extracellular traps (NETs), directly damaging the vascular endothelium.
4. Pauci-immune inflammation - The process results in fibrinoid necrosis of vessel walls with little to no immune complex deposition (hence "pauci-immune") - distinguishing AAV from immune-complex-mediated vasculitis.

Recent data suggest classification by ANCA specificity (PR3-ANCA vs MPO-ANCA) is clinically more informative than grouping by traditional disease category.

• Fishman's Pulmonary Diseases, Block 15; Dermatology 2-Volume Set 5e, p. 521

(e) Investigations (4 marks)

• ANCA panel: c-ANCA/anti-PR3 (GPA), p-ANCA/anti-MPO (MPA/EGPA)
• Anti-GBM antibody (to exclude Goodpasture's syndrome)
• ANA, dsDNA, complement (C3, C4) - to exclude SLE-associated vasculitis
• Hepatitis B and C serology (secondary vasculitis)
• ESR, CRP (disease activity)
• FBC, renal function, LFTs, serum protein electrophoresis

• 24-hour urine protein
• Urine microscopy (dysmorphic RBCs, RBC casts confirm GN)

• High-resolution CT chest (cavitating nodules, pulmonary haemorrhage)
• CT sinuses (mucosal thickening, erosions, septal perforation)
• Echocardiogram if cardiac involvement suspected

• Renal biopsy (gold standard) - pauci-immune crescentic GN with focal necrosis and few/no immune deposits on immunofluorescence
• Nasal/sinus biopsy if renal biopsy contraindicated - shows necrotising granulomatous vasculitis
• Bronchoscopy with BAL if diffuse alveolar haemorrhage suspected (sequential bloody BAL returns)

(f) Induction Treatment and Role of Plasma Exchange (4 marks)

• Rituximab is preferred in relapsing disease, younger patients, and those at risk of cyclophosphamide toxicity
• Cyclophosphamide (pulse IV preferred over oral due to lower cumulative dose and bladder toxicity)
• Steroids tapered over 3-6 months following clinical response

1. Severe rapidly progressive GN (creatinine >5.8 mg/dL or dialysis-dependent)
2. Diffuse alveolar haemorrhage with respiratory failure
3. Pulmonary-renal syndrome

Treatment approach uses glucocorticoids (GC) as backbone; rituximab (RTX) and cyclophosphamide (CYC) for ANCA-associated vasculitis induction; plasma exchange (LCY) reserved for life-threatening organ involvement.

• Fitzpatrick's Dermatology, General Approach to Treatment of Systemic Vasculitis

(g) Maintenance Therapy (2 marks)

• Rituximab 500 mg IV every 6 months (preferred) OR Azathioprine 2 mg/kg/day (alternative)
• Low-dose oral prednisolone is continued during early maintenance and gradually tapered
• Duration: at least 24 months (minimum); many guidelines recommend 4-5 years given high relapse risk (50-70% at 5 years with GPA)
• Monitor ANCA titres - rising titres may predict relapse but treatment decisions should be based on clinical assessment, not titres alone
• Co-trimoxazole (trimethoprim-sulfamethoxazole) added for Pneumocystis jirovecii prophylaxis during immunosuppression

(h) Serious Complications of Untreated Disease (2 marks)

1. End-Stage Renal Disease (ESRD) - rapidly progressive crescentic GN can lead to dialysis dependence within weeks; 5-year renal survival without treatment approaches 0%
2. Diffuse Alveolar Haemorrhage (DAH) - life-threatening pulmonary haemorrhage from pulmonary capillaritis; presents with haemoptysis, progressive hypoxia, and anaemia; has a reported mortality of up to 50% without prompt treatment

EXAMINER'S KEY POINTS

OSCE Question: Vasculitis

CLINICAL SCENARIO

QUESTIONS

ANSWERS

1. Upper respiratory tract - sinusitis, nasal crusting, saddle-nose deformity
2. Lower respiratory tract - cavitating pulmonary nodules, haemoptysis
3. Renal - pauci-immune crescentic glomerulonephritis (haematuria, proteinuria, renal failure)

1. Urine microscopy - dysmorphic RBCs + RBC casts (confirms glomerulonephritis)
2. Renal biopsy - pauci-immune crescentic GN (minimal/no immune deposits on immunofluorescence)

• High-dose corticosteroids (IV methylprednisolone, then oral prednisolone)
• Rituximab OR Cyclophosphamide (pulse IV preferred)

Add plasma exchange if creatinine >5.8 mg/dL or diffuse alveolar haemorrhage is present.