Makindo Medical Notes

Related Subjects: Granulomatosis with Polyangiitis (GPA, formerly Wegener's) | Goodpasture's Syndrome (Anti-GBM Disease) | Respiratory Failure | Acute Kidney Injury

Early diagnosis and immunosuppression are key to reducing damage. If suspicious, get an urgent cANCA (proteinase 3). Without intervention, GPA can destroy kidneys within weeks.

About

• Described by Dr. Friedrich Wegener, a German pathologist, in 1936.
• Wegener was a member of the Nazi party during WWII.
• Now called Granulomatosis with Polyangiitis (GPA).

Aetiology

• Systemic vasculitis affecting the upper respiratory tract, lungs, and kidneys.
• Early diagnosis is crucial for preventing irreversible organ damage.

Epidemiology

• Affects 3 in 100,000 people in the USA.
• Mean age of onset is 50, with males and females equally affected.
• 90% of cases are observed in Caucasians.

Granuloma Formation

Aetiology

• A medium-sized vasculitis, possibly a hypersensitivity reaction to an external antigen.
• Eradicating Staphylococcus aureus carriage reduces the risk of recurrence.
• Renal disease is present in 40% of patients at presentation, eventually affecting up to 90%.

Clinical Presentation

• Fever, night sweats, lethargy, and malaise.
• Ear, Nose, and Throat: Rhinorrhoea, epistaxis, sinusitis, otitis media, nasal perforation, and saddle nose.
• Lungs: Cough, haemoptysis, pulmonary haemorrhage (causing a falsely high transfer factor or Kco), alveolar shadowing, and cavitary lesions.
• Kidneys: Hypertension, haematuria, focal necrotizing glomerulonephritis (characteristic renal lesion), pauci-immune necrotizing glomerulonephritis.
• Others: Uveitis, vasculitis causing red-eye, proptosis (eye bulging).

Investigations

• FBC: Anaemia, elevated WCC.
• Renal Function: Elevated urea and creatinine.
• Inflammatory Markers: Raised CRP and ESR.
• Complement Levels: Low.
• CXR: Nodular masses, infiltrates, cavitation, or pulmonary haemorrhage.
• Urinalysis: Proteinuria or haematuria. A renal biopsy may be needed if abnormalities are found. Significant dysmorphic RBCs or RBC casts indicate glomerular disease.
• HRCT Chest: Diffuse alveolar haemorrhage, cavitary nodules, consolidations, airspace opacities, and airway stenosis.
• cANCA: Antiproteinase-3 (PR3) antibodies, positive in 80-90% of cases. There is a close correlation between ANCA titers and disease activity.
• pANCA: Anti-myeloperoxidase (MPO) antibodies, positive in 10-20% of cases.
• Biopsy: Nasal biopsy can show granulomata. Tissue biopsy from affected organs (ENT, lung) is also helpful.
• DLCO: High with alveolar haemorrhage due to Hb binding to CO.
• Bronchoalveolar Lavage (BAL): Used for suspected pulmonary disease.
• Associated necrotizing glomerulonephritis requires monitoring U&E, CRP, and urinalysis.

CT Scan

CT scan of GPA shows multiple cavitary (arrows) and non-cavitary (arrowheads) pulmonary nodules.

Management

• GPA is associated with significant morbidity and mortality from irreversible organ damage or immunosuppressive therapy. Without treatment, 90% of patients die within two years of diagnosis.
• High-dose Prednisone: 1 mg/kg/day or methylprednisolone 1g for 3 doses.
• Azathioprine and methotrexate are typically used for maintenance therapy.
• Methotrexate (MTX) or Rituximab (RTX): For non-severe disease.
• Cyclophosphamide (CYC) or Rituximab: For severe disease.
• Rituximab Maintenance: Prolong infusions for up to 42 months for high-risk relapse patients (e.g., those with PR3 ANCAs).
• Long-term use of Mupirocin cream may help prevent Staphylococcus aureus nasal carriage, reducing relapse risk.
• Co-trimoxazole should be given as prophylaxis against Pneumocystis jirovecii and staphylococcal colonization.
• PLEX (Plasma Exchange): patients with severe renal disease (creatinine >500 umol/L).

References

• Common and Uncommon Manifestations of GPA at Chest CT: Radiologic-Pathologic Correlation