Granulomatosis with Polyangiitis (GPA, Wegener's Granulomatosis)
The most likely diagnosis is granulomatosis with polyangiitis (GPA), a systemic necrotizing vasculitis that characteristically presents with pulmonary cavitary lesions and glomerulonephritis causing hematuria with red blood cell casts.
Clinical Reasoning
This patient's constellation of findings creates a highly specific diagnostic pattern:
Pulmonary-renal syndrome: The combination of large cavitary nodules with diffuse alveolar opacities on chest X-ray alongside hematuria with red blood cell casts indicates simultaneous lung and kidney involvement, which is the hallmark of GPA 1
Systemic inflammatory features: The one-month history of constitutional symptoms (fatigue, weight loss, fever) with failure to respond to antibiotics suggests a non-infectious inflammatory process rather than typical bacterial pneumonia 1
Renal manifestations: Red blood cell casts specifically indicate glomerulonephritis, not simple urinary tract infection. This finding, combined with pulmonary cavitation, is pathognomonic for pulmonary-renal syndromes, with GPA being the most common cause 1
Key Differential Considerations
While the presentation could theoretically suggest several diagnoses, the specific combination of findings makes GPA most likely:
Why Not Tuberculosis?
- TB would be considered given the chronic cough, weight loss, fever, and cavitary lesions 1
- However, TB does not explain the glomerulonephritis with red blood cell casts. TB can cause sterile pyuria and hematuria from genitourinary TB, but red blood cell casts indicate glomerular disease, not TB 2, 3
- TB should still be ruled out with sputum acid-fast bacilli smears and cultures, especially given the chronic infection history and failure to improve with antibiotics 1
Why Not Chronic Pulmonary Aspergillosis?
- Fungal infection could cause cavitary lesions and chronic symptoms in someone with underlying lung disease 4, 5
- However, fungal infections do not cause glomerulonephritis with red blood cell casts 6
- The renal findings are the key differentiator that points away from purely infectious etiologies 1
Why Not Bacterial Pneumonia?
- The one-month duration and failure to respond to antibiotics argues strongly against typical bacterial pneumonia 1
- Bacterial pneumonia does not cause red blood cell casts or glomerulonephritis 1
Diagnostic Approach
Immediate testing should include:
- c-ANCA (anti-PR3 antibodies): Positive in 90% of generalized GPA cases with renal involvement 1
- Urinalysis with microscopy: Already shows hematuria and RBC casts, confirming glomerulonephritis 1
- Serum creatinine and renal function: To assess degree of kidney involvement 1
- Sputum AFB smears and cultures: To definitively exclude TB given the cavitary lesions 1, 7
- Chest CT scan: To better characterize the cavitary lesions and assess for other findings suggestive of vasculitis 8
Tissue diagnosis may be needed:
- Bronchoscopy with biopsy or transbronchial biopsy can show necrotizing granulomatous inflammation 8
- Renal biopsy shows necrotizing crescentic glomerulonephritis and is often diagnostic 1
Critical Management Considerations
Do not delay treatment if GPA is strongly suspected based on clinical presentation and positive c-ANCA, as untreated GPA has high mortality from rapidly progressive glomerulonephritis and pulmonary hemorrhage 1
Empiric TB treatment may be warranted while awaiting cultures if TB prevalence is high in your region, as the cavitary lesions and chronic symptoms are consistent with TB 1
Monitor for pulmonary hemorrhage, which can occur with GPA and presents as worsening dyspnea, hemoptysis, and dropping hemoglobin with increasing alveolar infiltrates 1
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