What is the possible diagnosis for a patient presenting with syncope, neutrophil-predominant leukocytosis, proteinuria, heavy right renal atrophy, and ground glass opacities on thoracic computed tomography (CT) scan?

Granulomatosis with Polyangiitis (GPA/Wegener's Granulomatosis)

The constellation of neutrophilic leukocytosis, proteinuria, renal atrophy, and ground glass opacities on thoracic CT in a patient presenting with syncope strongly suggests granulomatosis with polyangiitis (GPA), particularly given the pulmonary-renal syndrome pattern.

Clinical Reasoning

This patient presents with a classic pulmonary-renal syndrome requiring urgent evaluation:

• Neutrophil-predominant leukocytosis (30,000) with negative CRP is unusual for typical infection but characteristic of systemic vasculitis, where neutrophil activation occurs without proportionate acute phase reactant elevation 1

• Proteinuria (2+) with normal kidney function suggests active glomerular disease, though the heavy right renal atrophy indicates chronic damage from prior disease activity 2, 3

• Ground glass opacities at lower basal surfaces on thoracic CT represent alveolar hemorrhage or capillaritis, a hallmark of pulmonary vasculitis 4

• Syncope in this context likely results from either pulmonary hemorrhage causing hypoxemia, cardiac involvement from vasculitis, or systemic inflammatory effects 4

Differential Diagnosis Considerations

Primary Consideration: ANCA-Associated Vasculitis (GPA)

• The pulmonary-renal syndrome pattern with neutrophilic leukocytosis is pathognomonic for ANCA-associated vasculitis 1
• Ground glass opacities in the lower lung fields suggest diffuse alveolar hemorrhage, which occurs in 10-30% of GPA cases 4
• Unilateral renal atrophy suggests prior focal vasculitic involvement with chronic ischemic damage 3

Alternative Diagnoses to Exclude

Goodpasture syndrome (anti-GBM disease):

• Also presents with pulmonary-renal syndrome but typically shows more symmetric bilateral ground glass opacities 1
• Less likely to cause marked neutrophilic leukocytosis
• Requires anti-GBM antibody testing for differentiation

Systemic lupus erythematosus with lupus nephritis:

• Can cause proteinuria and pulmonary involvement 4, 1
• However, neutrophilic leukocytosis of 30,000 would be atypical; lupus more commonly causes leukopenia
• Ground glass opacities in lupus pneumonitis have different distribution patterns 4

Microscopic polyangiitis:

• Another ANCA-associated vasculitis that presents similarly 1
• Clinical distinction from GPA requires tissue biopsy showing granulomatous inflammation in GPA

Urgent Diagnostic Workup Required

Immediate Laboratory Testing

• ANCA serologies (c-ANCA/PR3 and p-ANCA/MPO) are essential, as 90% of GPA cases are c-ANCA/PR3 positive 1
• Anti-GBM antibodies to exclude Goodpasture syndrome 1
• Complement levels (C3, C4) to evaluate for immune complex disease 1
• Urinalysis with microscopy to assess for dysmorphic red blood cells and red cell casts indicating glomerulonephritis 3, 1
• Quantitative proteinuria (protein:creatinine ratio) to establish baseline severity 2

Imaging Considerations

• The thoracic CT findings of ground glass opacities require urgent evaluation, as they may represent life-threatening alveolar hemorrhage 4
• High-resolution CT (HRCT) with thin sections (1-2mm) can better characterize the ground glass pattern and identify centrilobular nodules or cavitary lesions suggestive of GPA 4
• Cardiac imaging is not routinely indicated for syncope evaluation unless cardiac etiology is suspected on initial assessment 4

Tissue Diagnosis

• Kidney biopsy is the gold standard for diagnosing glomerulonephritis and should be performed urgently given proteinuria and concern for rapidly progressive disease 4, 3, 1
• Expected findings in GPA include pauci-immune necrotizing crescentic glomerulonephritis 1
• Bronchoscopy with bronchoalveolar lavage should be considered if alveolar hemorrhage is suspected, showing progressively bloodier aliquots and hemosiderin-laden macrophages 5

Critical Management Considerations

Immediate Stabilization

• Assess respiratory status urgently, as ground glass opacities may represent active alveolar hemorrhage requiring ICU-level care 4, 5
• Monitor hemoglobin closely for evidence of ongoing pulmonary hemorrhage 4

Treatment Initiation

• If ANCA-associated vasculitis is confirmed, immediate immunosuppression with high-dose corticosteroids (methylprednisolone 500-1000mg IV daily for 3 days) combined with cyclophosphamide or rituximab is life-saving 4, 1
• Do not delay treatment pending biopsy results if clinical suspicion is high and patient is deteriorating 1

Common Pitfalls to Avoid

• Do not attribute syncope solely to vasovagal causes without excluding life-threatening pulmonary or cardiac involvement 4
• Do not dismiss normal kidney function tests as excluding significant renal disease; proteinuria with unilateral atrophy suggests chronic damage with compensatory function from the contralateral kidney 2, 3
• Do not delay bronchoscopy beyond 6-8 weeks if ground glass opacities persist, as this may represent organizing pneumonia, infection, or progressive vasculitis requiring different management 5
• Routine comprehensive laboratory testing has limited utility in syncope evaluation per ACC/AHA guidelines, but targeted testing for systemic disease is essential when clinical features suggest vasculitis 4