Allergic Fungal Sinusitis

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).

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
• 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
• Proptosis
• Ptosis
• Extraocular motility limitation
• Orbital apex syndrome
• Tearing
• Cavernous sinus syndrome

Testing

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

• Imaging Features
  • MRI demonstrates isointense or hypointense inflammatory tissue on T1, hypointense and flow void on T2 because allergic mucin is thick and dry
  • With orbital involvement, CT scan demonstrates inflammatory mass eroding into the orbit and thick allergic mucin in sinuses
  • Inflammatory mass may extend into orbit and intracranially
• Histology
  • Examination of tissue and mucus is required to make the diagnosis
  • Histopathologic evidence of non-angioinvasive 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)
• Serology
  • 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)

• Younger patients, second and third decades
• No gender predilection
• 90% have history of allergic rhinitis
• Hot, humid climate
• Atopy might be a predisposing factor.
• Cluster of cases has been observed post-hurricane season (J Neuro-ophthalmol 2012; 32:197).

• Bent and Kuhn criteria:
  1. type 1 hypersensitivity to fungi
  2. nasal polyposis
  3. characteristic radiographic finding of serpiginous areas of high attenuation
  4. eosinophilic mucin
  5. positive fungal stain

• 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.
• 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

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.