What is the differential diagnosis and plan of care for a 53-year-old non-smoker presenting with unilateral septal non-healing ulceration, nasal congestion, crusting, pain, chronic cough with increased productivity, and weight loss?

Differential Diagnosis and Plan of Care

Immediate Priority: Rule Out Life-Threatening and Destructive Conditions

This patient requires urgent evaluation for granulomatosis with polyangiitis (GPA/Wegener's), invasive fungal sinusitis, malignancy, and tuberculosis given the constellation of unilateral nasal ulceration, constitutional symptoms (weight loss), and chronic productive cough. 1

Critical Red Flags Present:

• Unilateral nasal septal ulceration (non-healing >4 weeks) suggests destructive process, not simple rhinosinusitis 1
• Weight loss indicates systemic disease requiring immediate workup 1
• Chronic productive cough may represent pulmonary involvement of systemic disease 1
• Non-smoker status makes simple chronic bronchitis less likely 1

Differential Diagnosis (Prioritized by Mortality Risk)

High-Risk Diagnoses Requiring Immediate Evaluation:

1. Granulomatosis with Polyangiitis (GPA/Wegener's Granulomatosis)

• Presents with nasal septal ulceration, crusting, and systemic symptoms 1
• Can cause nasal septal perforation if untreated 1
• Pulmonary involvement explains productive cough and weight loss 1

2. Invasive Fungal Sinusitis (Mucormycosis)

• Presents with nasal ulcers, epistaxis, and systemic symptoms 1
• Critical pitfall: While classically seen in immunocompromised patients, must be excluded in any patient with non-healing nasal ulceration 1
• Requires aggressive debridement and systemic antifungal therapy 1

3. Malignancy (Squamous Cell Carcinoma, Lymphoma, or Sinonasal Tumor)

• Unilateral obstruction with pain and non-healing ulceration is malignancy until proven otherwise 1
• Weight loss supports neoplastic process 1
• Hyposmia/anosmia may be present 1

4. Tuberculosis or Atypical Mycobacterial Infection

• Chronic productive cough with weight loss is classic presentation 1
• Can cause nasal septal ulceration and perforation 1

Moderate-Risk Diagnoses:

5. Cocaine-Induced Nasal Septal Perforation/Ulceration

• Causes non-healing septal ulceration and perforation 1
• Presents with crusting and nasal congestion 1
• Must obtain confidential substance use history 1

6. Chronic Bacterial Rhinosinusitis with Complications

• Less likely given unilateral presentation and constitutional symptoms 1
• Would not typically cause weight loss 1

7. Rhinitis Medicamentosa

• Can cause nasal septal perforation with prolonged topical decongestant use 1
• Does not explain weight loss or productive cough 1

8. Atrophic Rhinitis

• Causes nasal crusting and dryness but typically bilateral 1
• Does not explain weight loss 1

Diagnostic Workup Algorithm

Immediate (Within 24-48 Hours):

Step 1: Obtain Urgent Laboratory Studies

• Complete blood count with differential (eosinophilia suggests GPA or allergic fungal disease) 1
• Erythrocyte sedimentation rate and C-reactive protein (elevated in GPA, malignancy, TB) 1
• c-ANCA/PR3 and p-ANCA/MPO antibodies (positive in 90% of active GPA) 1
• Chest radiograph (evaluate for pulmonary infiltrates, masses, or cavitary lesions) 1

Step 2: Obtain Sinus CT Scan

• CT is gold standard for evaluating sinonasal disease and bony destruction 1
• Look for: bone erosion (malignancy, invasive fungal disease), septal perforation, ostiomeatal complex obstruction 1
• Do not delay CT imaging when destructive process is suspected 1

Step 3: Direct Visualization and Biopsy

• Rhinolaryngoscopy with biopsy of ulcerated tissue is mandatory 1
• Send tissue for: histopathology, fungal culture, mycobacterial culture, and bacterial culture 1
• Look for granulomatous inflammation (GPA, TB), fungal hyphae, or malignant cells 1

Within 1 Week:

Step 4: Pulmonary Evaluation

• Chest CT if chest radiograph abnormal or high suspicion for systemic disease 1
• Sputum culture for acid-fast bacilli (three samples) and routine bacteria 1
• Consider pulmonology referral for bronchoscopy if pulmonary infiltrates present 1

Step 5: Additional Serologic Testing (If Initial Workup Negative)

• Antinuclear antibody, rheumatoid factor (other vasculitides) 1
• HIV testing (immunocompromised state predisposes to opportunistic infections) 1
• Serum immunoglobulins (immunodeficiency evaluation) 1

Management Plan

Immediate Management (Before Diagnosis Confirmed):

Do NOT initiate empiric antibiotic therapy for presumed bacterial sinusitis in this patient 1

• The presentation does not meet criteria for acute bacterial rhinosinusitis 1
• Antibiotics will not treat the likely underlying conditions and may delay diagnosis 1

Symptomatic Relief Only:

• Nasal saline irrigation for crusting 1
• Avoid topical decongestants (risk of rhinitis medicamentosa) 1
• Pain control with acetaminophen or NSAIDs 1

Urgent Referrals:

1. Otolaryngology (ENT) - Within 24-48 Hours

• For rhinolaryngoscopy and tissue biopsy 1
• Surgical debridement if invasive fungal disease confirmed 1

2. Rheumatology - If c-ANCA Positive or High Suspicion for GPA

• Initiation of immunosuppressive therapy (cyclophosphamide or rituximab plus corticosteroids) 1
• Early treatment critical to prevent organ damage and mortality 1

3. Infectious Disease - If Fungal or Mycobacterial Disease Suspected

• Antifungal therapy selection and monitoring 1
• Anti-tuberculous therapy if TB confirmed 1

4. Oncology - If Malignancy Confirmed

• Staging and treatment planning 1

Common Pitfalls to Avoid

1. Do not diagnose "chronic sinusitis" and prescribe antibiotics without imaging and biopsy 1

• Unilateral presentation with constitutional symptoms demands tissue diagnosis 1

2. Do not attribute symptoms to upper airway cough syndrome (UACS) without excluding destructive processes 1

• While chronic cough can be from UACS, weight loss and non-healing ulceration indicate systemic disease 1

3. Do not delay biopsy waiting for imaging results 1

• Tissue diagnosis is essential and should proceed urgently 1

4. Do not assume immunocompetence excludes invasive fungal disease 1

• While more common in immunocompromised patients, invasive fungal sinusitis can occur in immunocompetent hosts 1

5. Do not forget to obtain confidential substance use history 1

• Cocaine use is a common cause of nasal septal perforation and ulceration 1

If Initial Workup Negative for High-Risk Diagnoses

Only after excluding GPA, malignancy, invasive fungal disease, and TB, consider:

• Chronic bacterial rhinosinusitis: Treat with antibiotics effective against H. influenzae, S. pneumoniae, and anaerobes for minimum 3 weeks 2
• Upper airway cough syndrome: First-generation antihistamine/decongestant (brompheniramine plus pseudoephedrine) 1
• Asthma evaluation: Spirometry and methacholine challenge if UACS treatment fails 2
• GERD evaluation: Empiric proton pump inhibitor trial if cough persists after treating UACS and asthma 2

However, given this patient's presentation, benign causes are unlikely and aggressive workup for life-threatening conditions must proceed immediately.