Chronic Invasive Fungal Rhinosinusitis

Chronic invasive fungal rhinosinusitis is slowly progressive infection of the sinuses and adjacent tissues by fungi, lasting over 12 weeks, with tissue invasion. It includes chronic invasive and granulomatous forms, and may extend to the orbit and skull base.

Aspergillus flavus is the commonest cause in many tropical regions (Sudan, India, Pakistan, Saudi Arabia), including in immunocompetent patients, while Aspergillus fumigatus, Mucorales and others occur in immunocompromised and diabetic patients. Mortality is 50% to 80% in untreated or immunosuppressed disease. The granulomatous form is mostly seen in young adults in endemic areas.

Pathophysiology.

Fungal hyphae invade the mucosa, bone and vessels slowly. The chronic invasive form has a dense fibrous reaction and the granulomatous form has non-caseating granulomas with giant cells.

Unilateral nasal blockage, facial or retro orbital pain, headache, proptosis, visual loss, ophthalmoplegia, cheek swelling and, in advanced disease, cranial nerve palsies. Fever is uncommon.

Red flags.

• Visual loss or ophthalmoplegia.
• Black eschar or necrotic tissue (consider mucormycosis).
• Cavernous sinus or intracranial extension.
• Diabetic ketoacidosis or neutropenia.

Nasal endoscopy shows mucosal thickening, crusting or necrotic tissue. CT shows soft tissue opacification with bone destruction, and a hyperdense area; magnetic resonance imaging shows extension into the orbit, skull base and cavernous sinus. Biopsy with histology (Grocott methenamine silver stain showing hyphae in tissue), culture and PCR confirms the diagnosis. Serum galactomannan and beta-D-glucan help. Check glucose, HbA1c, blood counts and HIV status.

Differential diagnosis.

• Acute invasive fungal rhinosinusitis.
• Fungal ball.
• Allergic fungal rhinosinusitis.
• Sinonasal malignancy.
• Granulomatosis with polyangiitis.
• Tuberculosis and other granulomatous disease.

Combine surgical debridement of infected and necrotic tissue (endoscopic or open) with prolonged systemic antifungal treatment, and correct the underlying cause (glucose control, reducing immunosuppression).

• Voriconazole: 6 mg/kg IV every 12 hours for 2 doses, then 4 mg/kg IV every 12 hours or 200 mg orally twice daily (300 mg twice daily if weight is over 40 kg and the response is poor) for at least 6 to 12 weeks and often months; maximum 600 mg daily orally; monitor trough levels (target 1 to 5.5 micrograms/mL), liver tests, visual symptoms and skin; reduce the maintenance dose by half in mild to moderate cirrhosis, and use oral rather than IV when creatinine clearance is under 50 mL/min.
• Liposomal amphotericin B (mucormycosis or voriconazole failure): 5 mg/kg IV once daily for at least 2 to 4 weeks until improvement; maximum 10 mg/kg daily; monitor creatinine, potassium, magnesium and infusion reactions; extend the interval in renal impairment.
• Itraconazole (granulomatous form, or step down): 200 mg orally twice daily for 3 to 6 months or more; maximum 400 mg daily; monitor serum levels (target over 1 microgram/mL), liver tests and heart failure; avoid in heart failure and with interacting drugs; reduce in hepatic impairment.

Exenteration is considered for orbital involvement with extensive disease.

Monitoring. Endoscopy and imaging every 4 to 6 weeks at first; drug levels, liver tests and glucose each month.

Referral and escalation. ENT, skull base surgery, infectious disease and ophthalmology urgently.

Special groups. Diabetes needs insulin control, and transplant recipients need immunosuppression review.