Goodpasture's syndrome (Anti GBM disease)

Related Subjects: |Granulomatosis with Polyangiitis GPA (Wegener's) |Goodpasture's syndrome (Anti GBM disease) |Respiratory Failure |Acute Kidney Injury |Haemodialysis |

⚡ The prognosis of Goodpasture’s syndrome depends heavily on early diagnosis and early treatment. 🧪 Many labs can rapidly test for Anti-GBM and ANCA antibodies → early suspicion should trigger immediate renal consultation. Delay = risk of irreversible renal failure. Test in any simultaneous haemoptysis and renal failure.

About 📖

• Goodpasture's Syndrome (Anti-GBM Disease): Rare autoimmune pulmonary - renal syndrome
• A combination of rapidly progressive glomerulonephritis (RPGN) and lung haemorrhage.
• Pathology: Diffuse proliferative GN with crescent formation, leading to rapid renal damage.
• Inflammatory injury damages type IV collagen in kidneys + lungs.

Epidemiology

• Incidence: 0.5-1 per million per year.
• There is a slight male preponderance.

Classification 🧩

• Goodpasture’s Syndrome: Kidneys + Lungs both affected.
• Anti-GBM Disease: Limited to kidneys or lungs.

Aetiology 🔬

• Autoantibodies against the noncollagenous (NC-1) domain of the alpha3 chain of type IV collagen.
• Targets: Glomerular basement membrane (GBM) + Alveolar basement membrane.

Clinical Features 🚨

• 🫁 Pulmonary: Haemoptysis, dyspnoea, diffuse alveolar haemorrhage on CXR.
• 🩸 Renal: Haematuria, proteinuria, rapidly progressive AKI.
• 🧠 Nephritic syndrome / RPGN: Oedema, hypertension, oliguria.
• ⚠️ Progresses over days to weeks → untreated = ESRF + death.

Investigations 🔍

• Bloods: FBC (anaemia from bleeding), ↑ESR/CRP, U&Es (AKI).
• Urine: Haematuria, proteinuria, red cell casts.
• CXR: Patchy alveolar infiltrates = pulmonary haemorrhage.
• CT chest: Patchy alveolar infiltrates = pulmonary haemorrhage.
• Bronchoalveolar lavage if suspected alveolar hemorrhage without hemoptysis. Lavage fluid that becomes increasingly hemorrhagic after sequential sampling, and the presence of hemosiderin-laden macrophages is a hallmark cytologic feature of blood in the alveolar space.
• Serology: Anti-GBM antibodies (+/- ANCA if overlap with vasculitis).
• Renal Biopsy: Linear IgG staining along GBM (classical!) + crescentic GN.

Pulmonary Haemorrhage

Differential Diagnosis ⚖️

• Granulomatosis with Polyangiitis (GPA, Wegener’s): ANCA positive, granulomatous inflammation, NOT linear IgG staining.
• Systemic lupus erythematosus: Antibodies to double-stranded DNA and reduced serum complement levels
• Microscopic polyangiitis: ANCA to myeloperoxidase (MPO-ANCA, or perinuclear ANCA [p-ANCA])

Management 🛠️ (Renal Emergency!)

• 💊 Immunosuppression: High-dose steroids (Prednisolone 1 mg/kg or Methylprednisolone) + later cyclophosphamide or Rituximab.
• 🧪 Plasma Exchange: Rapidly clears circulating Anti-GBM antibodies. Initiate ASAP.
• 🫁 Supportive: Manage AKI, oxygen for pulmonary haemorrhage.
• 🩺 Renal Transplant: Consider if ESRF, but only after antibody titres are negative (otherwise recurrence risk).
• Relapse is rare and is more commonly associated with patients who are also positive for ANCA

Exam Clinical Pearl ✨

👉 Think Goodpasture’s in a patient with haematuria + haemoptysis. 🔑 Biopsy clue = linear IgG deposition (vs granular in post-strep GN, lupus).

Cases - Goodpasture’s Syndrome (Anti-GBM disease)

• Case 1 - Pulmonary–renal syndrome 🫁🩸: A 26-year-old man presents with haemoptysis, breathlessness, and dark urine. Exam: pulmonary crackles, hypertension. Bloods: creatinine 290 µmol/L, Hb 8 g/dL. Urine: red cell casts. CXR: diffuse alveolar infiltrates. Anti-GBM antibodies positive. Diagnosis: Goodpasture’s syndrome with pulmonary haemorrhage and rapidly progressive GN. Managed with high-dose steroids, plasma exchange, and cyclophosphamide.
• Case 2 - Renal-limited disease 🧪: A 41-year-old woman presents with fatigue, oedema, and worsening renal function. No respiratory symptoms. Urine: proteinuria, haematuria. Biopsy: crescentic GN with linear IgG staining on immunofluorescence. Diagnosis: renal-limited anti-GBM disease. Managed with plasma exchange and immunosuppression; prognosis poor if advanced renal failure at presentation.
• Case 3 - Environmental trigger 🚬: A 33-year-old man, a heavy smoker, presents with acute haemoptysis after a recent influenza-like illness. Exam: tachypnoea, hypoxia. Labs: anti-GBM antibody strongly positive, CXR shows bilateral alveolar shadows. He develops oliguria with rising creatinine over days. Diagnosis: Goodpasture’s syndrome precipitated by smoking and viral infection. Managed with ICU support, plasma exchange, and immunosuppressive therapy.

Teaching Point 🩺: Goodpasture’s (anti-GBM) disease is a rare autoimmune disorder causing pulmonary haemorrhage and rapidly progressive GN. Classic features = haemoptysis + haematuria. Triggers include smoking and viral infections. Urgent treatment with plasma exchange, corticosteroids, and cyclophosphamide can be life-saving.