Pulmonary vasculitis and diffuse alveolar haemorrhage in ICU

Also known as ANCA-associated vasculitis · Granulomatosis with polyangiitis · GPA · Microscopic polyangiitis · MPA · Diffuse alveolar haemorrhage · DAH · Pulmonary renal syndrome

Pulmonary vasculitis with diffuse alveolar haemorrhage (DAH): ANCA-associated vasculitides (GPA — Wegener's, MPA, EGPA — Churg-Strauss) cause capillaritis → alveolar bleeding. Pulmonary-renal syndrome: DAH + rapidly progressive glomerulonephritis. Clinical: haemoptysis, dyspnoea, hypoxia, falling Hb, diffuse infiltrates on imaging + AKI, haematuria, proteinuria. Diagnosis: ANCA (PR3/c-MPO), renal biopsy (pauci-immune crescentic GN), bronchoalveolar lavage (macroscopically bloody or haemosiderin-laden macrophages). Treatment: high-dose glucocorticoids (e.g. IV methylprednisolone 3000 mg as in MEPEX) plus cyclophosphamide OR rituximab (RAVE/RITUXVAS), plasma exchange for severe DAH/RPGN (MEPEX renal recovery; PEXIVAS no death/ESKD benefit). Other DAH causes: anti-GBM (Goodpasture), SLE, coagulopathy, drug-induced, idiopathic pulmonary haemosiderosis.

high19 referencesUpdated 26 July 202622 min readVerification in progress

Practise this topic

8 MCQs

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Management of suspected pulmonary vasculitis with DAH

Recognise — haemoptysis + dyspnoea + falling Hb + diffuse infiltrates + AKI (pulmonary-renal syndrome). Haemoptysis is absent in up to one-third of DAH patients — a falling Hb with diffuse infiltrates is the clue. Hypoxia may be severe
Resuscitate — ABC. Oxygen (may need intubation/ventilation for hypoxia). Transfusion for anaemia. Treat as a time-critical syndrome: respiratory failure and end-stage renal failure can occur rapidly
Investigations — (a) ANCA (PR3/c-MPO), anti-GBM. (b) Renal: U&E, creatinine, urinalysis (RBC casts). (c) Bronchoscopy + BAL (macroscopically bloody returns or haemosiderin-laden macrophages = DAH). (d) CT chest (nonspecific alveolar filling — ground-glass/consolidation). (e) Renal biopsy (necrotising crescentic GN; linear IgG if anti-GBM)
IMMUNOSUPPRESSION — do not delay in the unstable patient: (1) High-dose glucocorticoids (e.g. IV methylprednisolone 3000 mg, the MEPEX comparator regimen). (2) Rituximab 375 mg/m² weekly × 4 (RAVE) OR cyclophosphamide 2 mg/kg/day (RAVE control arm) — EULAR 2022 recommends high-dose glucocorticoids plus rituximab or cyclophosphamide for life- or organ-threatening AAV
Plasma exchange — may be considered for rapidly progressive glomerulonephritis (EULAR 2022); standard in anti-GBM disease. MEPEX: 7 exchanges improved dialysis-independence at 3 months (69% vs 49%) in AAV presenting with creatinine over 500 µmol/L (5.8 mg/dL); PEXIVAS: no reduction in death or ESKD
Supportive ICU — lung-protective ventilation, renal replacement therapy, transfusion, PJP prophylaxis with trimethoprim-sulfamethoxazole during immunosuppression
Maintenance — after induction: rituximab is the EULAR-recommended maintenance for GPA/MPA (MAINRITSAN: 500 mg days 0 and 14, then months 6, 12, 18); azathioprine and methotrexate are alternatives

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SAQ — ANCA-associated vasculitis with pulmonary-renal syndrome

10 minutes · 10 marks

A 58-year-old man presents to the emergency department with a 3-week history of malaise, low-grade fever, arthralgia, and two episodes of small-volume haemoptysis, now with worsening dyspnoea. Over the past 4 days he has noticed his urine is dark and frothy. On examination: T 37.9 degrees C, RR 28, SpO2 90 per cent on room air, BP 168/96, HR 102, coarse bilateral inspiratory crackles. No rash, no synovitis. Investigations: haemoglobin 78 g/L (was 132 four months ago), WCC 14.2, platelets 280, creatinine 386 micromol/L (baseline 90), urea 28, CRP 142, INR 1.0, APTT 32. Urinalysis shows blood 3+, protein 2+, and microscopy reveals red cell casts. Chest X-ray shows bilateral diffuse perihilar airspace opacities. PR3-ANCA strongly positive (high titre); MPO-ANCA negative; anti-GBM antibody negative. Bronchoscopy returns progressively bloodier lavage aliquots from the right middle lobe. CT chest shows bilateral ground-glass and consolidative change, sparing the periphery.

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SAQ — Goodpasture syndrome (anti-GBM disease) with massive haemoptysis

10 minutes · 10 marks

A 24-year-old previously well man presents with a 10-day history of progressive dyspnoea and a 2-day history of frank haemoptysis (around 200 mL over 12 hours), now requiring intubation for severe hypoxaemia (PaO2/FiO2 90). On examination he is pale, tachycardic (HR 128) and hypotensive (BP 96/58). Haemoglobin 64 g/L, creatinine 410 micromol/L (baseline 80), urea 32, potassium 6.0 mmol/L. Urinalysis: blood 3+, protein 2+, red cell casts on microscopy. Chest X-ray shows bilateral diffuse alveolar infiltrates. Anti-GBM antibody strongly positive (44 EU/mL; normal less than 20). PR3-ANCA and MPO-ANCA negative. Renal biopsy shows linear IgG deposition along the glomerular basement membrane with crescent formation in 80 per cent of glomeruli.

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Clinical pearls

High-yield pulmonary vasculitis/DAH points for CICM/FFICM exam

Diffuse alveolar haemorrhage (DAH) may have NO haemoptysis (absent in up to one-third). Symptoms and imaging are nonspecific; recognition often requires BAL. Falling haemoglobin + diffuse pulmonary infiltrates + dyspnoea = DAH until proven otherwise. Don't be reassured by absence of haemoptysis.^[12] }
Pulmonary-renal syndrome = diffuse alveolar haemorrhage + glomerulonephritis. The diseases most commonly implicated are ANCA-positive small-vessel vasculitis and anti-GBM disease. Prompt recognition is required — respiratory failure and end-stage renal failure can occur rapidly. ALWAYS check renal function and urinalysis in DAH.^[13] }
ANCA-associated vasculitis (AAV) — the big three: (1) GPA (Wegener's): PR3-ANCA, upper respiratory (sinusitis, epistaxis, saddle nose), lower respiratory (cavitating nodules), renal. (2) MPA: renal predominant, DAH, neuropathy (ANCA positive in 93% of the Lauque MPA-alveolar-haemorrhage series). (3) EGPA (Churg-Strauss): asthma, eosinophilia, neuropathy. Necrotising GN on biopsy (Lauque: focal segmental necrotising glomerulonephritis in 27 of 29).^[2] }
Anti-GBM disease (Goodpasture) must be excluded. Anti-GBM antibodies against the NC1 domain of alpha-3 type IV collagen attack the glomerular AND alveolar basement membranes — crescentic GN with LINEAR IgG on immunofluorescence. Treated with plasma exchange + prednisolone + cyclophosphamide (the Levy regimen, given to all 71 patients). DIFFERENT from AAV, where plasma exchange is selective (EULAR 2022: may be considered in RPGN).^[5] }^[15] }
Bronchoalveolar lavage (BAL) diagnosis of DAH. DAH is diagnosed when BAL is macroscopically bloody or contains haemosiderin-laden macrophages, in the absence of lung infection or pulmonary oedema (Lauque criteria). Sequential returns becoming progressively bloodier indicate ongoing alveolar bleeding. BAL also excludes infection — a key differential in the immunosuppressed.^[2] }^[12] }
High-dose glucocorticoids are first-line for life- or organ-threatening AAV/DAH — combined with either rituximab or cyclophosphamide (EULAR 2022). MEPEX used 3000 mg IV methylprednisolone as the comparator adjunct; taper to a target of 5 mg prednisolone-equivalent/day within 4-5 months. Steroids alone are not the whole answer — induction includes rituximab or cyclophosphamide.^[14] }^[4] }
Cyclophosphamide vs rituximab — RAVE trial. RAVE (2010, 197 patients): rituximab 375 mg/m² weekly × 4 vs cyclophosphamide 2 mg/kg/day — remission without prednisone at 6 months 64% vs 53% (non-inferior), SUPERIOR in relapsing disease (67% vs 42%), and as effective in alveolar haemorrhage and major renal disease; no significant difference in adverse events.^[3] }
Plasma exchange (PLEX) for severe AAV — two landmark trials. MEPEX (2007, creatinine over 500 µmol/L / 5.8 mg/dL): 7 exchanges vs 3000 mg IV methylprednisolone — dialysis-independence at 3 months 69% vs 49%, ESRD at 12 months 19% vs 43%. PEXIVAS (2020, 704 patients, eGFR under 50 or diffuse pulmonary haemorrhage): 7 exchanges within 14 days did NOT reduce death or ESKD (28.4% vs 31.0%, HR 0.86, P=0.27). Use selectively: RPGN (EULAR: may be considered) and anti-GBM disease.^[4] }^[8] }^[14] }
DAH vs ARDS on imaging — both cause diffuse infiltrates. DAH imaging is nonspecific and similar to other acute alveolar filling processes; haemoptysis may be absent; anaemia (mean Hb 8.1 g/dL in the Lauque series) and ANCA positivity support DAH. ARDS has an identified trigger. Bronchoscopy (bloody BAL or siderophages) distinguishes.^[12] }^[2] }
PJP prophylaxis during immunosuppression. Serious opportunistic and non-opportunistic infections are especially common in AAV, peaking in the first year post-diagnosis; trimethoprim-sulfamethoxazole significantly reduces the incidence of Pneumocystis jirovecii pneumonia and is the standard prophylactic agent.^[19] }
Maintenance therapy after induction. EULAR 2022 recommends rituximab for remission maintenance in GPA/MPA; azathioprine and methotrexate are alternatives. MAINRITSAN (2014): rituximab 500 mg on days 0 and 14 then months 6, 12, 18 vs daily azathioprine — major relapse at month 28: 5% vs 29%.^[14] }^[18] }
Imaging in DAH is nonspecific. Radiographic changes resemble other acute alveolar filling processes (ground-glass opacities and consolidation); DAH cannot be diagnosed on imaging alone — BAL and the clinical context (falling Hb, ANCA) do the work.^[12] }
Rituximab: B-cell depleting therapy. Anti-CD20 monoclonal antibody. Induction dose 375 mg/m² weekly × 4 (RAVE, RITUXVAS); maintenance dose 500 mg days 0 and 14 then 6-monthly (MAINRITSAN). Recommended for both induction (with high-dose glucocorticoids) and maintenance by EULAR 2022 and by the 2021 ACR/Vasculitis Foundation guideline.^[3] }^[18] }^[14] }^[16] }
Relapse prevention. Maintenance rituximab halves relapse risk versus azathioprine (MAINRITSAN: 5% vs 29% major relapse at month 28; HR 6.61). RAVE showed rituximab superior to cyclophosphamide for re-induction in relapsing disease (67% vs 42% remission). EULAR 2022: rituximab is the maintenance of choice for GPA/MPA.^[18] }^[3] }^[14] }

References19Show

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