Etiology

• Immunoglobulin E (Ig-E) mediated, eosinophil predominant hypersensitivity reaction to fungi in paranasal sinuses
• Mycotoxins from dying fungus can stimulate release of proinflammatory cytokines (Eur Arch Oto-Rhino-Laryngol 2012; 269:1155).
• Aspergillus species the most common pathogen
• • Aspergillus fumigatis and flavis
• Other reported fungal pathogens include trichosporon species, and from the demitaceous (dark-pigmented) family including Curvularia, Bipolaris (Am J Ophthalmol 1988; 105:366), Alternaria (Am J Ophthalmol 1999; 127:189).

Epidemiology

• Younger patients, second and third decades
• No gender predilection
• 90% have history of allergic rhinitis

History

• Chronic sinus pressure
• Chronic nasal discharge with thick mucus
• History of nasal polyposis
• Allergy
• Asthma
• Diplopia with orbital and/or intracranial extension
• Visual loss (Br J Ophthalmol 1988; 72:127)
• Tearing
• Periorbital erythema and edema
• Pertinent negatives: There should be no history of immunosuppression.

Clinical features

• Large quantities of allergic mucin in the paranasal sinuses
• thick mucus
• necrotic eosinophils
• Charcot-Leyden crystals
• sparse fungal mycelial elements
• Nasal polyposis
• Inflammatory mass extends into orbit and intracranially
• Proptosis
• Ptosis
• Extraocular motility limitation
• Orbital apex syndrome
• Cavernous sinus thrombosis
• Visual loss from suprasellar compression by inflammatory mass (J Neuro-ophthalmol 2012; 32:197)
• Surgical decompression of optic nerve might be indicated (J Otolaryngol Otol 2011; 125:381).
• Nasolacrimal duct obstruction (OPRS 2011; 27:e98)
• Chronic dilation of the lacrimal sac (Orbit 2013; 32:143)
• Allergic mucin with eosinophilia fills the dilated lacrimal sac and adjoining sinuses.
• Sixth nerve palsy — potentially reversible (Am J Rhinol Allerg 2013; 27:432)
• The abducens nerve is most medial in the cavernous sinus, making it highly susceptible to sphenoid sinus disease.

Testing

(Curr Opin Allerg Clin Immunol 2012; 12:629)

• Examination of tissue and mucus is required to make the diagnosis
• With orbital involvement, CT scan demonstrates inflammatory mass eroding into the orbit and thick allergic mucin in sinuses
• MRI demonstrates isointense or hypointense inflammatory tissue on T1, hypointense and flow void on T2 because allergic mucin is thick and dry
• Histopathologic evidence of non-invasive fungal sinusitis
• Histopathology of allergic mucin
• Absence of granulomas (differentiates from granulomatous sinusitis)
• Absence of necrosis or giant cell reaction (differentiates from invasive fungal sinusitis)
• Peripheral eosinophilia
• High total serum Ig-E
• Ig-E specific for particular fungi
• Fungus in allergic mucin is dying and fragmented, not vital, therefore difficult to culture (Curr Opin Allerg Clin Immunol 2012; 12:629)

• Hot, humid climate
• Atopy might be a predisposing factor.
• Cluster of cases has been observed post-hurricane season (J Neuro-ophthalmol 2012; 32:197).

• Chronic rhinosinusitis can also be caused by (Laryngoscope 2013; 123:S15-27)
• Aspirin exacerbated respiratory disease
• Triad of aspirin sensitivity, asthma, and nasal polyps
• Asthmatic sinusitis with or without allergy
• Reactive airway disease with or without positive allergy test
• Nonasthmatic sinusitis with or without allergy
• No reactive airway disease with or without positive allergy test
• Cystic fibrosis — positive sweat test or genetic evaluation
• Other fungal sinus diseases and bacterial sinus

Natural history

• Patients with long standing allergic fungal sinusitis can develop invasive fungal sinusitis including invasive intracranial aspergillosis (Med Mycol 2012; 50:179).
• Both orbits can be affected by very large inflammatory mass (Arch Ophthalmol 1996; 114:767).
• Some are mixed cases of invasive and allergic fungal sinusitis.

Medical therapy

• Oral steroids are recommended (Int Forum Allerg Rhinol 2013; 3:104).
• Typically requires 3–4 weeks of treatment
• Intranasal corticosteroids as adjunctive therapy
• Oral antifungal medication might be needed despite absence of invasive infection.
• Most cases reported in the ophthalmic literature have not been treated with oral antifungal medication (OPRS 2000; 16:72).
• Utility and safety of oral antifungal treatment for allergic fungal sinusitis has been questioned (Am J Rhinol Allerg 2012; 26:141).
• Based on meta-analysis of 6 double-blind randomized trials
• Ophthalmic morbidity might warrant use
• Topical antifungal agents can reduce chronic presence on mucosa.
• Utility and safety of topical antifungal treatment has also been questioned (Cochrane Database Syst Dis 2011; 8:CD008263).
• Based on 5 studies
• Leukotriene receptor antagonists to reduce allergic reaction
• Montelukast (Singulair)
• Oral antihistamine might potentiate the effect.

Surgery

• Endoscopic removal of polyps and inflammatory material (Curr Opin Allerg Clin Immunol 2012; 12:629)
• Establish aeration and drainage of involved sinuses.
• Valuable first step in treatment
• Remove allergic mucin.
• Functional endoscopic sinus surgery
• Anterior and posterior ethmoidectomy
• Sphenoidotomy
• Frontal sinus trephination

Other management considerations

• Saline nasal lavage to reduce fungal load
• Allergic immunotherapy can reduce hypersensitivity (Curr Opin Allerg Clin Immunol 2012; 12:629).

Common treatment responses, follow-up strategies

• Improvement takes several days to a week or more.
• In 6 cases of orbital involvement with proptosis, there was no recurrence after treatment with mean follow-up of 34 months (range 8–48 months) (Am J Ophthalmol 1999; 127:189).
• One patient had severe, but reversible, visual loss.
• Two patients had limited extraocular motility, one with diplopia; all was reversible.
• Another 3 cases of orbital involvement remained disease free during follow-up ranging 12–36 months (OPRS 2000; 16:72).
• Can be chronic disease, with periods of exacerbation

• Morbidity of antifungal medications
• Morbidity of steroid medications

Invasive inflammatory mass can produce permanent deficits if not treated.

Katzenstein proposed an allergic form of chronic fungal sinusitis in 1983 (J Allergy Clin Immunol 1983;72:8).

1. Klapper SR, Lee AG, Patrinely JR, Stewart M, Alford EL: Orbital involvement in allergic fungal sinusitis. Ophthalmology. 1997; 104:2094.
2. Han JK: Subclassification of chronic rhinosinusitis. Laryngoscope. 2013; 123:S15-27.
3. Katzenstein AL, Sale SR, Greenberger PA. Allergic Aspergillus sinusitis: a newly recognized form of sinusitis. J Allergy Clin Immunol. 1983; 72:89-93.
4. Sridhar J, Lam BL, Sternau L: Neuro-ophthalmic manifestations of fungal disease associated with posthurricane environment. J Neuro-ophthalmol 2012; 32:197.
5. Carter KD, Graham SM, Carpenter KM: Ophthalmic manifestations of allergic fungal sinusitis. Am J Ophthalmol. 1999; 127:189.
6. Chang WJ, Tse DT, Bressler KL, Casiano RR, Rosa RH, Johnson TE: Diagnosis and management of allergic fungal sinusitis with orbital involvement. Ophthal Plast Reconstr Surg. 2000; 16:72.