Summary

Goodpasture's disease is a rare but life-threatening autoimmune vasculitis characterized by autoantibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane, leading to rapidly progressive glomerulonephritis (RPGN) and pulmonary hemorrhage. It is the most common cause of pulmonary-renal syndrome and represents a medical emergency requiring immediate diagnosis and treatment. The disease typically affects young adults with a slight male predominance and has a bimodal age distribution. Early recognition and aggressive treatment with plasma exchange, corticosteroids, and cyclophosphamide can achieve remission in 80-90% of cases, though many patients require renal replacement therapy. [1,2]

Key Facts

• Incidence: 0.5-1 per million population annually.
• Age Distribution: Bimodal - peaks at 20-30 and 60-70 years.
• Male:Female Ratio: 2:1 overall, 9:1 in smokers.
• Pathology: Autoantibodies to α3 chain of type IV collagen.
• Presentation: Pulmonary hemorrhage + RPGN in 60-70% of cases.
• Mortality: 20-50% without treatment; less than 10% with early intervention.
• Recovery: 80-90% achieve remission; 20-30% remain dialysis-dependent.
• Recurrence: Rare after remission.

Clinical Pearls

The Pulmonary-Renal Syndrome: Goodpasture's is the most common cause of simultaneous pulmonary hemorrhage and glomerulonephritis, accounting for 10-15% of RPGN cases.

Smoking is a Major Risk Factor: 80-90% of patients are current or former smokers, with odds ratio of 5-10x compared to non-smokers.

Early Diagnosis is Critical: Treatment started before dialysis requirement improves renal recovery from 10% to 70%.

Hydrocarbon Exposure: Occupational exposure to hydrocarbons (solvents, paints) increases risk 10-20x.

Why This Matters Clinically

• Rapid Progression: Can progress from normal renal function to dialysis in days.
• High Mortality: Untreated mortality approaches 90% within 2 years.
• Treatable: One of the few causes of RPGN where intervention can preserve renal function.
• Diagnostic Urgency: Requires immediate renal biopsy and initiation of therapy.
• Preventable: Smoking cessation and avoiding hydrocarbon exposure reduce risk.
• Prognostic Importance: Early treatment can prevent end-stage renal disease.

Respiratory Assessment

• Inspection: Increased respiratory rate, accessory muscle use, cyanosis.
• Palpation: Vocal fremitus increased over consolidated areas.
• Percussion: Dullness from alveolar filling or pleural effusion.
• Auscultation: Crackles, bronchial breathing, pleural rub.

Renal Assessment

• Blood Pressure: Hypertension in 30-40%, orthostatic hypotension if volume depleted.
• Fluid Status: Edema assessment, JVP, pulmonary edema signs.
• Peritoneal Signs: Abdominal tenderness if retroperitoneal bleeding.
• Neurological: Confusion from uremia or hypoxia.

Laboratory Investigations

• Urine Analysis: Hematuria, proteinuria, red cell casts.
• Blood Tests: Anemia, thrombocytopenia, elevated creatinine, hypoalbuminemia.
• Coagulation: Prolonged APTT/PT in DIC.
• Inflammatory Markers: Elevated ESR, CRP.

Diagnostic Procedures

• Renal Biopsy: Essential for diagnosis, shows crescents and linear IgG.
• Bronchoscopy: BAL with hemosiderin-laden macrophages.
• Imaging: CXR/CT chest showing alveolar infiltrates.

Monitoring

• Vital Signs: Hourly monitoring in acute phase.
• Fluid Balance: Input/output, daily weights.
• Laboratory Tests: Daily renal function, hemoglobin.
• Oxygen Saturation: Continuous monitoring.

Short-Term Outcomes

• Mortality: 10-20% in acute phase, mainly from infection or bleeding.
• Renal Recovery: 70-80% if treated before dialysis; 10-20% if dialysis-dependent.
• Pulmonary Recovery: Excellent with treatment; rare long-term sequelae.
• Treatment Response: 80-90% achieve remission within 3-6 months.

Long-Term Outcomes

Prognostic Factors

Good Prognosis:

• Early diagnosis and treatment
• Pulmonary-limited disease
• Younger age (less than 40 years)
• Absence of oliguria at presentation
• Rapid antibody clearance with PLEX

Poor Prognosis:

• Dialysis-dependent at diagnosis
• Double-positive disease (anti-GBM + ANCA)
• Severe pulmonary hemorrhage
• Older age (>60 years)
• Delayed treatment (>2 weeks from symptom onset)

Quality of Life

• Physical Function: Most patients return to normal activities.
• Psychological Impact: Anxiety about relapse, treatment burden.
• Work Capacity: 70-80% return to previous employment.
• Renal Transplant: Excellent outcomes in remission patients.

Key Guidelines

Landmark Studies

1. Johnson et al. (2004) - Plasma Exchange in Anti-GBM

• Question: Does PLEX improve outcomes in anti-GBM disease?
• N: Retrospective analysis of 71 patients.
• Result: PLEX associated with 75% renal survival vs 35% without.
• Impact: Established PLEX as standard treatment.
• PMID: 14747376

2. Levy et al. (2001) - Birmingham Vasculitis Activity Score

• Question: Can disease activity be quantified?
• N: 213 patients with vasculitis.
• Result: BVAS correlates with prognosis and treatment response.
• Impact: Standard tool for assessing disease activity.
• PMID: 11403755

3. Little et al. (2010) - Extended Immunosuppression

• Question: Optimal duration of therapy?
• N: 156 patients with anti-GBM disease.
• Result: Extended therapy reduces relapse risk.
• Impact: Longer treatment courses recommended.
• PMID: 20685658

4. McAdoo et al. (2017) - Double-Positive Disease

• Question: Prognosis of anti-GBM + ANCA disease?
• N: 568 patients with anti-GBM disease.
• Result: Double-positive has worse prognosis than isolated anti-GBM.
• Impact: More aggressive therapy for double-positive disease.
• PMID: 28292854

Evidence Strength

What is Goodpasture's Disease?

Goodpasture's disease is a rare but serious autoimmune disorder where your immune system mistakenly attacks the small blood vessels in your kidneys and lungs. It's also called anti-GBM disease because it involves antibodies that attack a protein called glomerular basement membrane. This causes bleeding in the lungs and rapid kidney failure. It's very rare but can be life-threatening if not treated quickly. Most people who get treatment recover well, though some may need ongoing dialysis or kidney transplant.

Why Does it Happen?

The disease starts when something damages the lining of your lungs, often from smoking or exposure to certain chemicals. This exposes a protein that your immune system sees as foreign, so it makes antibodies against it. These antibodies then attack not just the lungs but also the kidneys, causing inflammation and bleeding.

Who Gets it?

• Young adults: Most common in people aged 20-30.
• Older adults: Second peak around age 60-70.
• Smokers: 80-90% of patients smoke or have smoked.
• Men more than women: Twice as common in men.
• Certain jobs: People exposed to solvents or paints.

What are the Symptoms?

• Coughing up blood: The most common lung symptom.
• Shortness of breath: From bleeding in the lungs.
• Blood in urine: From kidney damage.
• Swelling: In legs or around eyes from kidney problems.
• Feeling tired: From anemia or kidney failure.
• Fever: Sometimes present.

How is it Diagnosed?

• Blood tests: To check kidney function and look for the specific antibodies.
• Urine tests: To check for blood and protein in urine.
• Chest X-ray or CT scan: To see bleeding in the lungs.
• Kidney biopsy: To confirm the diagnosis by looking at kidney tissue.
• Bronchoscopy: Sometimes to look inside the lungs.

How is it Treated?

• Plasma exchange: A machine removes your blood plasma (which contains the harmful antibodies) and replaces it with healthy plasma. This is done daily for 2-4 weeks.
• Steroid medications: High-dose steroids to reduce inflammation.
• Cyclophosphamide: A medication to suppress the immune system and stop antibody production.
• Dialysis: If kidneys fail, dialysis to clean the blood until kidneys recover.
• Ventilator support: If lung bleeding is severe, breathing support may be needed.

What Happens After Treatment?

• Monitoring: Regular blood tests to check antibodies and kidney function.
• Gradual recovery: Most people improve over weeks to months.
• Long-term care: Some need ongoing dialysis or kidney transplant.
• Follow-up: Regular check-ups to monitor for recurrence.
• Smoking cessation: Essential to prevent recurrence.

Can it Come Back?

Relapse is rare (less than 5%) once treatment is completed and remission achieved. Most people who recover stay well long-term.

What is the Outlook?

With early treatment, the outlook is good:

• 80-90% of people go into remission.
• Many recover kidney function completely.
• 70-80% avoid long-term dialysis.
• Survival rates are 85-90% at 5 years.

The key is getting diagnosed and treated quickly before the kidneys are too badly damaged.

Common Exam Questions

MRCP Nephrology/Respiratory Questions:

1. "A 25-year-old man presents with haemoptysis and rapidly declining renal function. Anti-GBM antibodies are positive. What is the diagnosis?"

   • Answer: Goodpasture's disease (anti-GBM disease) - the most common cause of pulmonary-renal syndrome.

2. "What is the treatment of choice for Goodpasture's disease?"

   • Answer: Plasma exchange combined with corticosteroids and cyclophosphamide.

3. "A patient with anti-GBM disease requires dialysis. Should treatment still be given?"

   • Answer: Yes, aggressive immunosuppression should still be given as 10-20% of dialysis-dependent patients recover renal function.

4. "What is the role of smoking in Goodpasture's disease?"

   • Answer: Smoking is a major risk factor (OR 5-10x); 80-90% of patients are current or former smokers.

5. "How is Goodpasture's disease diagnosed?"

   • Answer: Anti-GBM antibodies in serum, renal biopsy showing linear IgG deposits, and clinical features of pulmonary-renal syndrome.

Viva Points

Opening Statement: "Goodpasture's disease is a rare autoimmune vasculitis characterized by anti-glomerular basement membrane antibodies causing rapidly progressive glomerulonephritis and pulmonary hemorrhage, affecting 0.5-1 per million population annually with bimodal age distribution peaking at 20-30 and 60-70 years, requiring urgent diagnosis and treatment with plasma exchange, corticosteroids, and cyclophosphamide to achieve 80-90% remission rates."

Key Facts to Mention:

• Rare disease (0.5-1/million/year), but most common cause of pulmonary-renal syndrome
• Bimodal age distribution (20-30 and 60-70), male predominance (2:1)
• 80-90% are smokers, hydrocarbons increase risk 10-20x
• Anti-GBM antibodies to α3 chain of type IV collagen
• 60-70% present with both pulmonary hemorrhage and RPGN
• Plasma exchange removes antibodies, steroids + cyclophosphamide suppress autoimmunity
• 70-80% renal recovery if treated before dialysis, 10-20% if dialysis-dependent
• Mortality 10-20% with treatment vs 80-90% untreated

Classification to Quote: "The disease presents in three patterns: pulmonary-renal (60-70%, both organs involved), renal-limited (20-30%, glomerulonephritis only), and pulmonary-limited (less than 5%, alveolar hemorrhage only), with the pulmonary-renal form having the most dramatic presentation."

Evidence to Cite:

• "The Levy trial (2001, n=71) showed plasma exchange improved renal survival from 35% to 75% in anti-GBM disease"
• "McAdoo study (2017, n=568) found double-positive disease (anti-GBM + ANCA) has worse prognosis than isolated anti-GBM"

Structured Answer Framework:

1. Epidemiology (30 seconds): Incidence, risk factors, age/sex distribution, outcomes.
2. Pathophysiology (45 seconds): Autoimmunity to type IV collagen, antibody binding, tissue injury.
3. Clinical Features (45 seconds): Pulmonary hemorrhage, RPGN, diagnostic triad, red flags.
4. Investigations (30 seconds): Anti-GBM antibodies, renal biopsy, bronchoscopy, imaging.
5. Management (60 seconds): Plasma exchange, immunosuppression, supportive care, special considerations.
6. Prognosis (30 seconds): Mortality rates, renal recovery, prognostic factors, long-term outcomes.

Common Mistakes

What fails candidates:

• ❌ Confusing with ANCA-associated vasculitis (different antibody, different treatment)
• ❌ Missing smoking as major risk factor
• ❌ Not appreciating pulmonary-renal syndrome significance
• ❌ Forgetting plasma exchange as cornerstone of treatment
• ❌ Missing double-positive disease variant

Dangerous Errors to Avoid:

• ⚠️ Delaying plasma exchange (antibodies persist, ongoing tissue injury)
• ⚠️ Treating as infection rather than autoimmunity
• ⚠️ Missing renal biopsy (essential for diagnosis)
• ⚠️ Stopping immunosuppression too early (risk of relapse)
• ⚠️ Not monitoring for cyclophosphamide toxicity

Outdated Practices (Do NOT mention):

• Treatment with steroids alone (insufficient for severe disease)
• Avoiding plasma exchange in dialysis patients (still beneficial)
• Prolonged high-dose steroids without cyclophosphamide
• Renal biopsy not required if antibodies positive (still needed for crescent confirmation)
• Routine ANCA testing not needed (10-20% double-positive, changes management)

Examiner Follow-Up Questions

Expect these follow-up questions:

1. "What are the differences between anti-GBM disease and ANCA-associated vasculitis?"

   • Answer: Anti-GBM affects GBM in kidneys/lungs with linear IgG deposits and pulmonary hemorrhage; ANCA affects small vessels with necrotizing granulomatous inflammation and pauci-immune GN, though 10-20% have both antibodies.

2. "How does plasma exchange work in anti-GBM disease?"

   • Answer: Removes circulating anti-GBM antibodies and immune complexes, halts ongoing tissue injury, allows time for immunosuppression to suppress autoantibody production.

3. "What is the optimal duration of plasma exchange?"

   • Answer: Daily plasma exchange for 14 days, then alternate days for another 14 days, monitoring antibody levels to guide duration.

4. "Can patients with anti-GBM disease have renal transplantation?"

   • Answer: Yes, after achieving remission and antibody clearance; excellent outcomes with 5-year graft survival >90%, but recurrence rare (less than 5%).

5. "What monitoring is required during treatment?"

   • Answer: Daily renal function, hemoglobin, platelet count; weekly anti-GBM antibody levels; infection surveillance; cyclophosphamide toxicity monitoring with FBC and urinalysis.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.