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]."