What are the differential diagnoses and management plan for a patient presenting with a unilateral intranasal septal ulcer that has not responded to conservative measures, with no history of smoking or drug use?

Unilateral Intranasal Septal Ulcer: Differential Diagnosis and Management Plan

For a unilateral nasal septal ulcer unresponsive to conservative treatment in a non-smoker without drug use history, you must pursue tissue biopsy with ANCA and ACE testing to exclude Wegener's granulomatosis, sarcoidosis, and malignancy before considering the diagnosis idiopathic. 1, 2

Differential Diagnoses (Prioritized by Clinical Significance)

Granulomatous/Autoimmune Disease (Most Critical to Exclude)

• Wegener's granulomatosis (Granulomatosis with polyangiitis): Unilateral presentation is common, and patients often present with nasal obstruction rather than epistaxis 2
• Sarcoidosis: Can present with nasal septal ulceration and granulomatous inflammation 1, 2
• Midline granuloma: Associated with destructive nasal lesions 1

Infectious Etiologies

• Leishmaniasis: Anterior nasal septum is the most commonly involved area in New World mucosal leishmaniasis; perforation may be palpated and visualized 1
• Tuberculosis: Presents with stellate ulcers with undermined edges 1
• Invasive fungal infection: Consider in immunocompromised patients; lesions may appear brick red or black necrotic areas 1

Neoplastic Disease

• Nasal malignancies: Present with unilateral nasal obstruction (66.7%) and epistaxis (55%); may not be visible on anterior rhinoscopy alone 1
• Inverted papilloma: Characterized by polypoid appearance and unilateral location 1

Other Causes

• Trigeminal trophic syndrome: Characterized by trigeminal anesthesia, nasal alar ulceration, and facial paresthesia; appearance after trigeminal ablation is diagnostic 3
• Factitious disorder: Self-induced lesions with normal trigeminal function and patient denial of manipulation 3
• Idiopathic: Diagnosis of exclusion (47% of cases in one series) 2

Diagnostic Work-Up Algorithm

Step 1: Pre-Biopsy Blood Work (Mandatory)

Before proceeding with biopsy, obtain the following to exclude contraindications and provide diagnostic clues 1:

• Complete blood count: Rule out anemia, leukemia, or other hematologic disorders 1
• Coagulation studies: Exclude bleeding diathesis before biopsy 1
• Fasting blood glucose: Hyperglycemia predisposes to invasive fungal infection 1
• HIV antibody and syphilis serology: Rule out infectious causes 1
• ANCA (anti-neutrophil cytoplasmic antibody): Successfully identifies Wegener's granulomatosis 2
• ACE (angiotensin converting enzyme): Supports diagnosis of sarcoidosis 2
• ESR and CRP: Limited diagnostic value but may support inflammatory conditions 2

Step 2: Nasal Endoscopy (Essential for Unilateral Disease)

Perform nasal endoscopy to examine the entire nasal cavity and nasopharynx, as unilateral lesions may harbor malignancy not visible on anterior rhinoscopy. 1

• Nasal endoscopy is specifically recommended for recurrent unilateral nasal bleeding or when concern exists for unrecognized pathology 1
• Examine for posterior nasal cavity and nasopharyngeal masses that may present with epistaxis 1
• Look for brick red or black necrotic areas suggestive of invasive fungal disease 1

Step 3: Tissue Biopsy (Indicated for Ulcers >2 Weeks or Treatment-Refractory)

Biopsy should be performed for oral/nasal ulceration persisting over 2 weeks or not responding to 1-2 weeks of treatment. 1

Critical caveat: In a retrospective study of 74 patients with septal perforation/ulcer, biopsy showed non-specific findings in 55% of cases and only contributed to diagnosis when ANCA/ACE were abnormal or malignancy was suspected 2

• Biopsy technique: Obtain adequate tissue from ulcer edge and base 1
• Send specimens for:
  • Histopathology (H&E staining) 1
  • Fungal staining and culture (if invasive fungal disease suspected) 1
  • Mycobacterial culture (if tuberculosis suspected) 1
  • Leishmania PCR and culture (if endemic area or travel history) 1
  • Immunohistochemistry (if neoplasm suspected) 1

Step 4: Imaging (Selective Use)

• CT scan: Not routine but indicated for severe disease, immunocompromised state, suspected complications, or before surgery 1
• MRI: May help differentiate neoplastic from inflammatory disease 1

Management Plan Based on Diagnosis

If ANCA Positive (Wegener's Granulomatosis)

• Refer to rheumatology immediately for immunosuppressive therapy 2
• Biopsy confirms diagnosis but treatment should not be delayed if clinical suspicion is high 1

If ACE Elevated (Sarcoidosis)

• Biopsy showing non-caseating granulomas supports diagnosis 2
• Refer to pulmonology for systemic evaluation and treatment 1

If Leishmaniasis Confirmed

• Tissue specimens from nasal septum should be collected by otolaryngologist 1
• Microscopy, culture, and PCR from tissue specimens 1
• Refer to infectious disease for systemic antileishmanial therapy 1

If Malignancy Identified

• Urgent referral to otolaryngology-head and neck surgery 1
• Staging and multidisciplinary tumor board discussion 1

If Invasive Fungal Disease

• Immediate biopsy with fungal staining and culture 1
• Aggressive surgical debridement plus systemic antifungal therapy 1
• Early diagnosis is critical for prognosis 1

If Idiopathic (Diagnosis of Exclusion)

After excluding all above etiologies with negative ANCA, ACE, biopsy, and cultures 2:

Conservative management:

• Nasal saline irrigation 2-3 times daily: First-line treatment for moisturization and crust removal 4, 5
• Avoid topical decongestants: Will further dry nasal mucosa 5
• Intranasal corticosteroids with caution: May worsen dryness; use lowest effective dose and direct spray away from septum 5
• Monitor nasal septum periodically: Check for mucosal erosions that may precede perforation 1

Surgical options if conservative measures fail:

• Extracellular matrix scaffold (MatriStem®): Novel approach showing complete symptom relief in small case series 6
• Unilateral inferior meatal mucosal flap: Simple technique with good outcomes for perforations up to 26mm 7
• Septal dermoplasty or flap reconstruction: Traditional approaches but no therapy has demonstrated consistent improvement 6

Common Pitfalls to Avoid

• Do not assume idiopathic diagnosis without ANCA and ACE testing: These tests successfully identified Wegener's and sarcoidosis when biopsy was non-diagnostic 2
• Do not rely on biopsy alone: 55% of biopsies show non-specific findings 2
• Do not miss malignancy: Unilateral lesions require nasal endoscopy as tumors may not be visible on anterior rhinoscopy 1
• Do not delay biopsy in suspected invasive fungal disease: Early diagnosis is critical for patient prognosis 1
• Do not prescribe oral antihistamines: Anticholinergic effects worsen nasal dryness 5
• Avoid surgical reconstruction in factitious disorder: High recurrence rate; psychiatric referral is primary treatment 3