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EN4.34 | Granulomatous Diseases of Nose — SDL Guide (Part 2)

Diagnosis and Differential Diagnosis

Arriving at the specific diagnosis within the granulomatous nasal disease group requires combining the clinical profile — demographic factors, endemic area, associated systemic features, and the morphology of nasal lesions — with the histopathological findings. No single investigation replaces the biopsy, but the pre-biopsy clinical analysis determines which stains and cultures are requested on the specimen, which systemic investigations accompany it, and how urgently the result must be acted upon. The distinction between infective granulomatous disease (which requires specific antimicrobial treatment) and autoimmune/inflammatory granulomatous disease (which requires immunosuppression) is the most consequential diagnostic decision in this group — administering immunosuppression to an undiagnosed patient with nasal TB, for instance, could cause rapid dissemination of the infection with potentially fatal consequences. Conversely, withholding immunosuppression from a patient with GPA risks progressive renal failure and pulmonary haemorrhage. This therapeutic risk asymmetry reinforces why tissue diagnosis is non-negotiable before any treatment is started, and why the diagnostic framework must explicitly address both infective and autoimmune causes simultaneously rather than assuming one and excluding the other.

A practical diagnostic framework for the unknown nasal granuloma:

When a patient presents with chronic nasal crusting, septal perforation, or a granulomatous nasal mass unresponsive to standard antibiotic treatment, the approach is:

1. History — duration, geographic origin, occupation (wood/agricultural/construction work), travel, HIV/immunocompromise status, TB contacts, history of STIs, systemic symptoms (haemoptysis, haematuria, skin lesions, joint pain).
2. Anterior rhinoscopy and endoscopy — morphology of lesions; strawberry surface = rhinosporidiosis; indurated stenosis = rhinoscleroma; bleeding crusting + saddle nose = GPA or TB.
3. Systemic examination — chest auscultation, lymph nodes, skin (lupus pernio = sarcoidosis; hypopigmented anaesthetic patches = leprosy; erythema nodosum = sarcoidosis/TB).
4. Targeted investigations — biopsy (always), plus ANCA/renal screen (if GPA suspected), ACE/CXR (sarcoidosis), TB workup (Mantoux/CBNAAT), syphilis serology.

Distinguishing septal perforation causes:

A septal perforation in the cartilaginous septum is the key physical sign that triggers investigation for granulomatous disease. The differential for septal perforation includes:
- Granulomatous disease (GPA, TB, leprosy, syphilis, rhinoscleroma) — the conditions covered in this SDL;
- Trauma (septal surgery, nose-picking, cocaine inhalation — cocaine causes vasconstriction of septal vessels leading to ischaemic perforation);
- Industrial exposure (chromate fumes — chrome-plating workers, tannery workers);
- Idiopathic (a significant proportion of septal perforations remain unexplained even after thorough investigation).

Key diagnostic distinguishing features:

Disease	Key Diagnostic Clue
TB nose	Caseating granuloma; AFB/CBNAAT positive; systemic TB features
Rhinoscleroma	Mikulicz cells + Russell bodies on histology; Klebsiella on culture
Rhinosporidiosis	Strawberry polyp; sporangia on histology; endemic India/Sri Lanka
GPA	c-ANCA positive; necrotising vasculitis on biopsy; renal involvement
Sarcoidosis	Non-caseating granuloma; BHL on CXR; elevated ACE; lupus pernio
Leprosy	Anterior nasal destruction; skin + nerve involvement; slit-skin smear
Syphilis	Saddle nose (tertiary/congenital); gumma; VDRL/TPHA positive

Principles of Management

Management of granulomatous nasal diseases is entirely condition-specific — the correct identification of the underlying aetiology is essential because the treatments are fundamentally different (and applying the wrong treatment can cause harm: immunosuppression in active infection, or antitubercular therapy in GPA, are both inappropriate and potentially dangerous).

Tuberculosis of the nose:
Standard six-month antitubercular therapy: 2 months of HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) followed by 4 months of HR (isoniazid, rifampicin) — the 2HRZE/4HR DOTS regimen. Notification and contact tracing as required. Surgical intervention (debridement of necrotic tissue, reconstruction of saddle-nose deformity) is deferred until disease is bacteriologically controlled.

Rhinoscleroma:
Prolonged antibiotic therapy — ciprofloxacin or tetracyclines (doxycycline) for months to years; the bacterium is sensitive to these agents and treatment must continue until the lesion is clinically and histologically resolved. Surgical debridement removes obstructive granulation tissue; nasal or laryngeal stenosis may require serial dilatation. Rhinoscleroma is a notoriously chronic disease and requires long-term follow-up.

Rhinosporidiosis:
Complete surgical excision with a wide margin is the treatment — simple polypectomy with snare or forceps causes haemorrhage and near-certain recurrence because the tumour-like mass must be removed with its entire base and pedicle. Electrocautery of the base after excision reduces recurrence. No antifungal drug has proven efficacy against Rhinosporidium seeberi; dapsone is sometimes used empirically as an adjunct. Recurrence is the major problem, particularly in patients who continue to bathe in contaminated water sources.

Granulomatosis with Polyangiitis (GPA):
GPA is an immunological disease requiring immunosuppressive induction therapy:
- Induction: Cyclophosphamide (oral or IV pulse) plus high-dose oral prednisolone — OR — rituximab (anti-CD20 monoclonal antibody) + prednisolone; the RAVE trial established rituximab as non-inferior to cyclophosphamide for induction, with potentially fewer adverse effects in some patient groups.
- Maintenance: Once remission is achieved (typically 3–6 months), switch to azathioprine or methotrexate + low-dose prednisolone to maintain remission; rituximab is also used for maintenance.
- Co-trimoxazole (trimethoprim-sulfamethoxazole) at prophylactic doses is added to reduce Pneumocystis jirovecii pneumonia risk from immunosuppression, and it has some evidence of reducing GPA relapse in limited (localised) disease.
- ENT surgical input: endoscopic debridement of necrotic nasal tissue; management of subglottic stenosis (a complication of tracheal GPA involvement).

Sarcoidosis of the nose:
Systemic corticosteroids (oral prednisolone) for symptomatic nasal sarcoidosis — typically 20–40 mg/day with gradual tapering. Intranasal topical corticosteroids and saline douching for localised nasal symptoms. Hydroxychloroquine and methotrexate are steroid-sparing agents for chronic disease.

Leprosy:
Multidrug therapy (MDT) as per WHO protocol: paucibacillary leprosy = rifampicin + dapsone × 6 months; multibacillary leprosy = rifampicin + dapsone + clofazimine × 12 months. Nasal cartilage destruction is irreversible — ENT surgery for reconstruction (saddle nose) is cosmetic and functional after the disease is controlled.

Syphilis:
Primary and secondary syphilis: benzathine penicillin G IM single dose (2.4 million units). Tertiary/neurosyphilis: IV penicillin G for 10–14 days. Saddle-nose and gumma manifestations of tertiary syphilis are treated primarily with penicillin; surgical reconstruction of nasal deformity may be considered after disease control.

Self-Assessment: Granulomatous Diseases of the Nose

Test your clinical reasoning on granulomatous nasal disease identification and management with these structured scenarios.

Scenario 1: A 50-year-old retired fisherman from coastal Tamil Nadu presents with bilateral nasal obstruction and a smooth, lobulated, reddish mass in the right nasal cavity. The surface shows multiple white dots scattered across it. He says he bathed in a village pond daily as a child and young adult. Histopathology of the excised mass shows large sporangia at various stages of maturation within a thickened mucosa. What is the diagnosis, treatment, and the most important post-treatment instruction?

Expected answer: Rhinosporidiosis, caused by Rhinosporidium seeberi. Treatment: complete surgical excision with adequate margins and cauterisation of the base — NOT simple polypectomy. Post-treatment instruction: avoid bathing in stagnant ponds or rivers, as re-exposure leads to recurrence. The white dots on the surface are mature sporangia visible to the naked eye — a clinically pathognomonic feature.

Scenario 2: In your ophthalmology clinic rotation, you see a 35-year-old female with bilateral violaceous, indurated skin plaques over her nose and cheeks. She also reports chronic nasal stuffiness and a dry cough for 8 months. Her chest X-ray shows bilateral hilar lymphadenopathy. What is the unifying diagnosis, and which investigation helps confirm it?

Expected answer: Sarcoidosis. The skin lesion is lupus pernio (violaceous indurated plaque over nose/cheeks — characteristic of cutaneous sarcoidosis). Bilateral hilar lymphadenopathy is the classic CXR finding. Serum ACE (elevated in ~60% of active sarcoidosis), nasal or skin biopsy showing non-caseating granulomas (no central necrosis, epithelioid macrophages with giant cells but intact granuloma centre), and CT chest confirm the diagnosis. Treatment: systemic corticosteroids.

Scenario 3: How do you distinguish septal perforation due to GPA from septal perforation due to cocaine inhalation or industrial chromate exposure?

Expected answer: History: cocaine inhalation (drug history) or occupational chromate exposure (chrome plating, tannery work) versus systemic features of GPA (epistaxis, haemoptysis, haematuria). Serology: c-ANCA (anti-PR3) is strongly positive in GPA, negative in cocaine/chromate perforation. Histopathology: GPA shows necrotising granulomatous vasculitis with fibrinoid necrosis of vessel walls; cocaine/chromate shows ischaemic necrosis without granulomas. Other systemic findings: GPA has renal and pulmonary involvement; cocaine/chromate do not. The distinction matters because GPA requires immunosuppression, while cocaine/chromate perforation requires cessation of exposure.