Differential Diagnosis and Treatment for Unilateral Non-Healing Septal Ulceration with Crusting in ANA-Positive Patient
Primary Differential Diagnosis
Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) is the most likely diagnosis in this patient with unilateral septal ulceration, crusting, positive ANA, and negative multiplex screen, particularly given the absence of drug use history. 1
Key Differential Considerations:
Primary Diagnosis:
- Granulomatosis with polyangiitis (GPA) - Most common cause of persistent nasal crusting, bleeding, and septal perforation in this clinical context 1
Other Important Considerations:
- NK/T cell lymphoma - Can mimic GPA with progressive midline destruction 1
- Sarcoidosis - Presents with crusting and granulomatous inflammation 1
- Systemic lupus erythematosus (SLE) - Given positive ANA, though nasal septal perforation is uncommon 1
- Tuberculosis or fungal infection (rhinosporidiosis) - Must be excluded 1
- Cocaine-induced midline destructive disease - Already excluded by history 1
Essential Diagnostic Workup
Immediate Laboratory Testing:
Serologic Testing:
- c-ANCA with PR3-ELISA - First-line test with 99% specificity and 73% sensitivity for systemic GPA, but drops to 50% in limited disease 1
- p-ANCA with MPO-ELISA - To evaluate for EGPA or atypical GPA 1
- ESR and CRP - Typically elevated in active vasculitis 1
- Complete blood count with differential - To assess for eosinophilia (EGPA) or cytopenias 1
- Comprehensive metabolic panel - To evaluate renal function (proteinuria, microscopic hematuria, red cell casts suggest systemic involvement) 1
- Urinalysis - Essential to detect early renal involvement 1
Additional Autoantibody Testing (given positive ANA):
- Anti-dsDNA antibodies - To evaluate for SLE 1, 2
- Anti-ENA panel (anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La) - To characterize ANA specificity 2, 3
- Complement levels (C3, C4) - Low levels suggest active SLE 1, 3
Imaging Studies:
CT Scan of Sinuses:
- Look for combination of bone destruction (60-75%), septal loss (59%), and new bone formation (50-78%) highly suspicious for GPA 1
- Early disease may show only non-specific mucosal thickening (87%) 1
Chest CT:
- Essential to identify pulmonary involvement: diffuse infiltration, multiple pulmonary nodules (2-4cm), or large necrotic cavitating masses 1
MRI of Sinuses (if available):
- "Tramlines" sign - fat signal from sclerotic sinus wall with high-signal on T1-weighted sequences suggests GPA 1
Tissue Diagnosis:
Nasal/Sinus Biopsy:
- Endoscopically-directed biopsy after cleaning and decongesting provides better yield than random mucosal biopsy 1
- Look for three key findings: granulomatous inflammation, necrosis, and vasculitis affecting small-to-medium vessels 1
- Nasal biopsy has 47% sensitivity but 96% specificity and 78% positive predictive value in c-ANCA negative, localized GPA 1
- Send tissue in both saline (for culture) and formalin (for histology) 1
- Culture for tuberculosis, fungi, and bacteria 1
Treatment Algorithm
If GPA is Confirmed or Highly Suspected:
Immediate Management:
For Limited Sinonasal Disease (no systemic involvement):
- High-dose systemic corticosteroids (prednisone 1mg/kg/day) for remission induction 1
- Methotrexate can be used for non-organ threatening disease as alternative to cyclophosphamide 1
- Rituximab (anti-CD20 monoclonal antibody) - Now widely used and equivalent to cyclophosphamide for remission induction, superior in relapsing disease 1
- RAVE study demonstrated rituximab's efficacy in 197 patients 1
For Generalized/Severe Disease:
- High-dose systemic steroids PLUS pulsed cyclophosphamide for rapid remission induction to limit organ damage 1
- Rituximab as alternative or in relapsing disease 1
Maintenance Therapy:
- Low-dose prednisolone 1
- Azathioprine or mycophenolate mofetil as steroid-sparing agents 1
- Rituximab for maintenance 1
Local Nasal Care (Essential for All Patients):
- Saline or alkaline nasal irrigations 1
- Topical corticosteroid sprays or drops 1
- Nasal lubricants (25% glucose and glycerine drops, honey ointment, or aqueous gel) 1
- Regular debridement of crusts 1
If SLE is Suspected (based on ANA pattern and additional testing):
For Mucosal Involvement:
- Hydroxychloroquine for constitutional symptoms and mucosal lesions 4
- Short-term oral glucocorticoids for acute inflammatory manifestations 4
- Topical corticosteroids for local lesions 5
If Diagnosis Remains Uncertain:
Empiric Treatment While Awaiting Results:
- Avoid empiric immunosuppression until tissue diagnosis or strong serologic confirmation 1
- Continue local nasal care (saline irrigation, lubricants) 1
- Consider empiric anti-tuberculosis therapy if high clinical suspicion and endemic area 1
Critical Prognostic Information
Without Treatment:
- Mean survival of systemic GPA is only 5 months 1
With Modern Treatment:
- Mean survival improved to 21.7 years from diagnosis 1
- ~10% never achieve remission 1
- Relapses occur in up to 50% of individuals 1
- Mortality rates of 5% or higher still reported 1
Better Prognosis Indicators:
- ENT-limited presentation has 98% 5-year survival vs 78% for systemic presentation 1
- ENT involvement is independent predictor of better outcome (OR 0.37) 1
Common Pitfalls to Avoid
Do not rule out GPA based on negative c-ANCA alone - sensitivity drops to 50% in limited sinonasal disease 1
Do not dismiss positive ANA as excluding GPA - approximately 5% of GPA patients have positive p-ANCA/MPO, and ANA can be positive 1
Do not rely solely on nasal mucosal biopsy - often reported as "consistent with" rather than definitively diagnostic; sinus tissue provides better yield 1
Do not forget to image lungs and check renal function - systemic involvement dramatically changes prognosis and treatment intensity 1
Do not perform nasal septal surgery if disease is active - high risk of perforation 1
Do not use ANA titer alone for diagnosis - requires clinical correlation and specific antibody testing 1, 2