Granulomatosis with Polyangiitis (Wegener Granulomatosis)
The correct diagnosis is (b) granulomatosis with polyangiitis (Wegener granulomatosis), based on the classic triad of upper respiratory tract disease (persistent sinusitis with epistaxis), lower respiratory tract involvement (productive cough with brown sputum suggesting pulmonary hemorrhage), and glomerulonephritis (proteinuria, hematuria, and RBC casts), combined with positive ANCA serology. 1
Diagnostic Reasoning
Key Clinical Features Supporting GPA
Upper respiratory tract involvement occurs in >90% of GPA patients, and this patient's 2-month history of persistent sinus pain, congestion, and epistaxis is a hallmark presentation 1
Lower respiratory tract disease is evident from the productive cough with brown sputum (suggesting alveolar hemorrhage), which occurs in >95% of patients with pulmonary GPA 1
Renal involvement manifests as pauci-immune necrotizing crescentic glomerulonephritis, demonstrated here by proteinuria, hematuria, and RBC casts—a pathognomonic finding for GPA 1, 2
Systemic manifestations including the purpuric rash on lower legs, constitutional symptoms (20-lb weight loss, fevers, myalgias, arthralgias) are common in GPA and reflect active systemic vasculitis 1
Laboratory Confirmation
Positive ANCA is present in 80-90% of GPA cases and is highly specific for this diagnosis, with PR3-ANCA (c-ANCA) being the predominant pattern 1, 2
Elevated ESR of 60 mm/hr reflects the active systemic inflammation characteristic of GPA 1
Negative ANA effectively excludes systemic lupus erythematosus 2
Excluding Alternative Diagnoses
Why Not Eosinophilic Granulomatosis with Polyangiitis (EGPA)?
EGPA requires blood eosinophilia >10% and elevated IgE, which are absent in this case 1
Only 35-40% of EGPA patients are ANCA-positive, and when present it is usually p-ANCA/MPO rather than c-ANCA 1
EGPA more frequently involves cardiac disease and gastrointestinal symptoms, which are not described here 1
Why Not Polyarteritis Nodosa?
PAN is an ANCA-negative medium-vessel vasculitis, making it incompatible with the positive ANCA in this patient 1
PAN does not typically cause glomerulonephritis or upper respiratory tract involvement 1
Why Not Rheumatoid Arthritis?
While positive rheumatoid factor can occur in approximately 5% of GPA patients, RA does not cause necrotizing glomerulonephritis, severe sinusitis with epistaxis, or pulmonary hemorrhage 1
The renal findings (RBC casts, glomerulonephritis) are not features of RA 2
Why Not Systemic Lupus Erythematosus?
The negative ANA makes SLE highly unlikely 2
While ANCA can rarely be positive in SLE (typically p-ANCA/MPO in 20% of cases), the negative ANA combined with the classic GPA triad makes this diagnosis untenable 3
Clinical Pitfalls to Avoid
Do not dismiss the diagnosis based on atypical ANCA patterns—while PR3-ANCA (c-ANCA) is most common in GPA, p-ANCA/MPO positivity can occur in severe cases 4
Positive rheumatoid factor should not mislead you toward RA—RF positivity can occur as a non-specific finding in GPA patients with atypical ANCA 1
The brown sputum is critical—this suggests pulmonary hemorrhage from alveolar capillaritis, a life-threatening manifestation requiring urgent immunosuppression 1
Immediate Next Steps
Obtain tissue confirmation through biopsy of an affected organ (kidney, lung, or nasal mucosa) to demonstrate necrotizing vasculitis and granulomatous inflammation 2
Initiate urgent treatment with high-dose glucocorticoids combined with either rituximab or cyclophosphamide, as untreated GPA has a mean survival of only 5 months 2
Consider plasma exchange if there is evidence of severe pulmonary hemorrhage or rapidly progressive renal failure 1