The Systemic Vasculitides — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr David Chen is a 56-year-old engineer presenting with a three-month history of progressive nasal crusting, epistaxis and bilateral conductive hearing loss, followed over the past two weeks by haemoptysis and a rising creatinine to 340 micromol per litre from a baseline of 80. He has lost 5 kg and is profoundly fatigued. He has no significant past medical history, takes no regular medications, and is a non-smoker. He is married with two teenage children and has been unable to work for the past month. [1]

c-ANCA is strongly positive with anti-PR3 specificity. Anti-GBM antibody is negative. Renal biopsy shows pauci-immune necrotising crescentic glomerulonephritis with 60 per cent crescents. Chest CT shows multiple cavitating pulmonary nodules. Blood cultures and echocardiogram are normal. [1]

My problem list is: (1) granulomatosis with polyangiitis presenting as a pulmonary-renal syndrome — an organ- and life-threatening presentation requiring immediate immunosuppression; (2) rapidly progressive glomerulonephritis with 60 per cent crescents and a creatinine of 340; (3) pulmonary involvement with cavitating nodules and probable alveolar haemorrhage; (4) upper airway disease with nasal crusting and conductive hearing loss; (5) constitutional features with 5 kg weight loss; (6) treatment-related risks including infection, cyclophosphamide or rituximab toxicity, and glucocorticoid side effects; and (7) the psychosocial impact of a new diagnosis of a serious chronic illness on a working man with a family. [1]

This is a medical emergency. My immediate management is admission and same-day initiation of IV methylprednisolone and rituximab, with concurrent exclusion of mimics and involvement of nephrology, respiratory and rheumatology." [1]

Examiner probing questions and model answers

Examiner: Walk me through your immediate management plan in detail. [1]

"I would admit Mr Chen to hospital under the joint care of nephrology and rheumatology. My immediate management is: [1]

First, glucocorticoid induction — intravenous methylprednisolone 1 g daily for three days, followed by oral prednisolone 1 mg/kg daily (approximately 60 to 80 mg), with a planned taper to 5 mg daily by 4 to 5 months. The PEXIVAS trial showed that a reduced-dose glucocorticoid regimen is non-inferior to standard high-dose regimens and reduces serious infections, so I would discuss a reduced-dose approach with my team [6][7].

Second, rituximab — 375 mg per square metre weekly for four weeks, or 1 g on days 1 and 15. Rituximab is now the preferred induction agent for organ-threatening ANCA-associated vasculitis based on the RAVE trial, which showed non-inferiority to cyclophosphamide, and the RITUXVAS trial, which confirmed this in renal vasculitis. Rituximab is preferred in relapsing disease and in patients who may wish to preserve fertility [3][4].

Third, before or concurrently with immunosuppression, I would exclude the key mimics — anti-GBM antibody for overlap syndrome, blood cultures and echocardiogram for endocarditis and myxoma, ANA and anti-dsDNA for lupus, and hepatitis serology. Treating endocarditis with rituximab instead of antibiotics would be catastrophic. [1]

Fourth, I would consider plasma exchange. The indications are anti-GBM overlap, dialysis-dependent renal disease, or severe diffuse alveolar haemorrhage. The MEPEX trial showed short-term renal recovery benefit with plasma exchange in severe renal vasculitis, but the larger PEXIVAS trial did not show benefit on the composite of death or end-stage kidney disease, so I would discuss this with my team and with the patient [5][6].

Finally, supportive care — oxygen and ventilatory support if needed, renal support with nephrology input (dialysis if indicated), co-trimoxazole for pneumocystis prophylaxis, bone protection, and gastric protection." [1]

Examiner: How confident are you in the diagnosis? What would change your approach? [1]

"The diagnosis is secure — the triad of ENT disease, pulmonary nodules with haemoptysis, and pauci-immune crescentic glomerulonephritis, combined with c-ANCA/PR3 positivity, is pathognomonic for GPA. The 2022 ACR/EULAR classification criteria for GPA use a scored system and this patient clearly exceeds the threshold [7].

What would change my approach is a positive anti-GBM antibody — this would indicate an overlap syndrome requiring mandatory plasma exchange in addition to rituximab and steroids, because anti-GBM disease causes pulmonary haemorrhage and rapidly progressive GN that is fatal without antibody removal. I would also reconsider if endocarditis were present — the treatment would be antibiotics and surgical source control, not immunosuppression." [1]

Examiner: What is your maintenance plan once remission is achieved? [1]

"After three to six months of successful induction, I would switch to maintenance therapy. My first choice is rituximab maintenance — 1 g every four months for 24 to 36 months. Rituximab is preferred for maintenance, particularly in PR3-ANCA disease, which relapses at roughly twice the rate of MPO-ANCA disease. Alternatives are azathioprine 2 mg/kg daily (check TPMT first), mycophenolate mofetil 2 g daily, or methotrexate 20 to 25 mg weekly. [1]

I would continue low-dose prednisolone at 5 mg daily or less for the first four to six months, then taper if possible. I would monitor ANCA titre, inflammatory markers, renal function and urinalysis every three months, with regular full blood count and immunoglobulins to detect rituximab-related hypogammaglobulinaemia. Total maintenance duration is typically 18 to 24 months after sustained remission, then cautious withdrawal with relapse monitoring [7]."

Examiner: What is the prognostic discussion you would have with Mr Chen and his family? [1]

"I would frame GPA as a serious but treatable chronic relapsing disease. The good news is that sustained remission is achievable with modern therapy — the RAVE and RITUXVAS trials showed remission rates of 64 to 76 per cent at 6 to 12 months with rituximab. The challenges are the treatment burden — immunosuppression carries infection risk, rituximab can cause hypogammaglobulinaemia, and prolonged steroids cause osteoporosis, diabetes and mood effects. [1]

The renal outcome depends on his response to induction — with a creatinine of 340 and 60 per cent crescents, there is a real risk of chronic kidney disease or end-stage renal disease if remission is not achieved quickly. Relapse is common, particularly in PR3-ANCA disease, so lifelong monitoring is essential. [1]

I would address the practical impact — time off work, financial pressure, the need for regular infusions and blood tests, and the anxiety of a new serious diagnosis. I would involve a clinical psychologist and connect him with the Vasculitis Foundation support resources." [1]

Examiner: What about giant cell arteritis? How does the approach differ? [1]

"GCA is a large-vessel vasculitis in patients over 50, and the urgency is visual loss rather than renal failure. The key differences are: first, the dose of steroids is lower — 40 to 60 mg orally for GCA without visual symptoms, versus 1 g IV for organ-threatening AAV. Second, the steroid-sparing agent is tocilizumab, not rituximab — the GiACTA trial showed that subcutaneous tocilizumab with a steroid taper achieved sustained glucocorticoid-free remission in over 50 per cent at 52 weeks. Third, the diagnosis is confirmed by temporal artery biopsy or ultrasound halo sign, not by renal biopsy. And fourth, GCA does not require cyclophosphamide or rituximab in most cases — the management is steroids plus or minus tocilizumab [2]."

Short Case Viva — Palpable purpura and mononeuritis multiplex

Examination instruction

"Examine this patient's skin and perform a focused neurological examination of the limbs." [1]

Systematic examination routine

1. Inspect the skin — describe the purpura: palpable, non-blanching, distributed on the lower limbs and dependent areas, size from pinpoint to several millimetres, presence of ulceration, necrosis, livedo reticularis, or digital infarcts. Note any surgical scars (previous biopsy sites).
2. Examine the hands and arms — splinter haemorrhages, nailfold changes, digital ulcers, subcutaneous nodules, pulse character and rhythm.
3. Examine for mononeuritis multiplex — test wrist extension (radial nerve, wrist drop), foot dorsiflexion (peroneal nerve, foot drop), median nerve sensation (median), ulnar nerve sensation, and peroneal and sural nerve sensation. Mononeuritis multiplex is the simultaneous or sequential infarction of peripheral nerves in distinct territories — it is a red-flag finding indicating vasculitic neuropathy.
4. Examine for associated systemic features — blood pressure in both arms (Takayasu, GCA large-vessel), abdominal bruits (PAN, Takayasu), oral and genital ulcers (Behcet), saddle-nose deformity and septal perforation (GPA), episcleritis or scleritis (GPA), strawberry tongue (Kawasaki — paediatric), and livedo reticularis (PAN, cryoglobulinaemia, cholesterol emboli). [1]

Presentation template

"This patient has palpable non-blanching purpura on the lower limbs consistent with a small-vessel leukocytoclastic vasculitis. There is also evidence of mononeuritis multiplex with a right foot drop and sensory loss in the left ulnar and right peroneal nerve distributions, which together suggest a vasculitic neuropathy. [1]

The vessel-size distribution is small vessel, and the differential is between ANCA-associated vasculitis (GPA, MPA, EGPA) and immune complex vasculitis (cryoglobulinaemic, IgA vasculitis, lupus). Given the (specify — ENT disease pointing to GPA, asthma and eosinophilia pointing to EGPA, hepatitis C and low complement pointing to cryoglobulinaemia, recent drug exposure pointing to hypersensitivity vasculitis), the most likely diagnosis is (specify). [1]

I would confirm with a skin biopsy for light microscopy and immunofluorescence, a combined sural nerve and muscle biopsy given the neuropathy, and the following laboratory panel: ANCA by both indirect immunofluorescence and anti-PR3 and anti-MPO ELISA, complement C3 and C4, cryoglobulins collected warm, rheumatoid factor, hepatitis B and C serology, ANA and anti-dsDNA, urinalysis and urine microscopy, and a full drug history." [1]

Discussion questions

Examiner: What is the significance of mononeuritis multiplex? [1]

"Mononeuritis multiplex is the simultaneous or sequential infarction of two or more peripheral nerves in separate territories, from vasculitis of the vasa nervorum. It is a classic presentation of systemic vasculitis, particularly PAN, MPA, EGPA and cryoglobulinaemic vasculitis. It is a red-flag finding because it indicates active, organ-threatening disease that requires urgent diagnosis and treatment. The investigation of choice is a combined sural nerve and muscle biopsy, which has the highest diagnostic yield. Treatment is high-dose glucocorticoids with cyclophosphamide or rituximab, depending on the underlying diagnosis." [1]

Examiner: How would you distinguish PAN from microscopic polyangiitis at the bedside? [1]

"PAN is a medium-vessel vasculitis that causes mononeuritis multiplex, renovascular hypertension, mesenteric ischaemia and microaneurysms on angiography — but crucially does NOT cause glomerulonephritis and does NOT involve the lungs. If a patient has medium-vessel features with glomerulonephritis or pulmonary involvement, it is not PAN — it is microscopic polyangiitis. MPA is a small-vessel ANCA-associated vasculitis with p-ANCA/MPO positivity, pauci-immune crescentic glomerulonephritis, and alveolar haemorrhage or interstitial lung disease. The key discriminator is the presence or absence of renal (glomerulonephritis) and pulmonary involvement — their presence rules out PAN and points to MPA [1]."

Examiner: What about the complement level — how does it help? [1]

"The complement level is the key discriminator between immune complex and ANCA-associated small-vessel vasculitis. Low complement (particularly low C4) points to cryoglobulinaemic vasculitis, IgA vasculitis or lupus. Normal complement points to ANCA-associated vasculitis or PAN. In this patient, I would request C3 and C4 alongside the ANCA panel. A low C4 with a positive rheumatoid factor and palpable purpura would strongly suggest cryoglobulinaemic vasculitis, and I would then check for cryoglobulins (sample kept warm) and hepatitis C serology." [1]