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Acute Invasive Fungal Sinusitis (IFS)

Overview
While fortunately still a relatively rare disease, the increasing incidence, fulminant course, and need for emergent management of acute invasive fungal sinusitis (IFS) make this a diagnosis that cannot be missed. Seen almost exclusively in immunocompromised patients (most commonly due to hematologic malignancy, transplant patients, or poorly controlled diabetes), consults to rule out IFS can be relatively common in tertiary care centers. Fever of unknown origin, sinusitis symptoms, or incidentally discovered abnormality on sinus imaging may trigger this consult. It is important to maintain a high index of suspicion in order to identify cases as early as possible. The diagnosis of IFS is based primarily on history and physical exam findings with histopathological confirmation. While diagnosis is clinical, imaging can be helpful in determining extent of disease. CT of the sinuses may show non-specific unilateral mucosal thickening, but bony destruction may be evident in more advanced disease. An MRI of the face with gadolinium is preferred to evaluate the extent of soft tissue involvement, intracranial extension, and potential loss of nasal mucosal enhancement due to angioinvasion.

Presenting signs and symptoms are variable, ranging from asymptomatic or mild sinus mucosal involvement to vision changes and cranial nerve deficits. In cases of delayed treatment, patients may experience nasal or palatal anesthesia, restricted extraocular movements, diplopia, proptosis or even mental status changes. Physical examination most commonly reveals necrosis or insensate pale mucosa of the head of the middle turbinate; however, less commonly the inferior turbinate, septum, or nasal floor may be involved. The most common fungal pathogens are species of Aspergillus among patients with poorly controlled diabetes and Mucormycosis in patients with hematologic malignancy. When suspected, biopsy should be taken at the border of the abnormal tissue (including both normal and abnormal tissue) and sent to the laboratory for immediate frozen section and fungal staining. If suspected, emergent treatment includes intravenous antifungals, wide surgical resection, and, if possible, treatment of underlying immunosuppressive disease process is necessary to reduce morbidity and mortality for this once universally fatal condition. Even in cases of early diagnosis and treatment, IFS has a high mortality rate, especially in patients with a non-reversible underlying disease process.

Key Supplies for IFS Consultation

  • Appropriate PPE including mask, eye protection, gloves, and gown

  • Headlight

  • Nasal Speculum

  • Rigid endoscope (with monitor & tower)

  • Antifog solution (Fred)

  • Frazier tip suction (Size 9 or 10)

  • Bayonet, alligator, or other grasping instruments

  • Cup forceps

  • Specimen cup, sterile saline

  • Oxymetazoline for hemostasis after biopsy

  • Pledgets for hemostasis after biopsy

  • Absorbable and nonabsorbable packing in case persistent bleeding ensues after biopsy

Management

  • See patient emergently and obtain history with attention to symptom progression, presence of fever, sinusitis symptoms (facial pressure, nasal congestion, rhinorrhea, hyposmia etc.), vision changes, and potential causes of immunosuppression

  • Physical exam should include a detailed cranial nerve nasal and sinus exam with endoscopy. Importantly, if a patient has significant crusting, this should be debrided to allow for examination of the mucosa. Mucosal sensation of the middle turbinate, palate, or any suspicious areas should be assessed

  • Basic labs should include CBC, CMP, and blood cultures

  • A sinus CT without contrast is usually obtained prior to consultation but should be ordered emergently in all suspected cases. This may also be useful for stereotactic navigation in the operating room, if needed

    • If obvious disease is present and obtaining imaging studies would delay emergent intervention, it may be delayed to allow for timely operative debridement

  • If abnormal tissue is identified, a sizable biopsy should be taken of the border of the abnormal tissue with cup forceps and placed in saline and sent (or personally delivered) for immediate frozen section and fungal staining; a second biopsy for cultures should be considered

    • Negative biopsy result

      • If suspicion for IFS is very high, consider taking a second biopsy, following with frequent, serial endoscopic examinations, or proceed to the operating room for thorough examination, biopsy, and resection if indicated

    • Positive biopsy result

      • A positive biopsy with fungal invasion requires surgical resection of all involved tissues with cleared margins intraoperatively. Imaging should be reviewed to determine resectability in the case of intracranial or major vessel involvement. In cases of advanced disease requiring large soft-tissue resections, goals of care should be discussed with the patient and family prior to proceeding

  • Consider involvement of Ophthalmology or Neurosurgery depending on extent of disease

  • Initiation of systemic antifungals with involvement of Infectious Disease specialists

    • Liposomal amphotericin B at 5mg/kg daily is an option though the toxicity of this drug requires close monitoring

    • Early fungal identification may allow treatment with less toxic and/or more efficacious antifungals such as posaconazole or voriconazole (if susceptible Aspergillus species are identified)

  • Reversal of immunosuppression when feasible

  • Typically requires a multidisciplinary input and care 

    • Patients in diabetic ketoacidosis require aggressive parenteral hydration and correction of acidosis with close electrolyte monitoring (generally managed by Medicine or ICU teams)

    • Neutropenic patients may require white blood cell transfusions and granulocyte colony stimulating factors such as filgrastim (generally managed by Hematology). Despite treatments, reversal in these patients may not be adequate

  • Consider topical sinus rinse with amphotericin B

    • Although there is not strong evidence for the efficacy of topical antifungal medications, it may be considered in this disease

  • Patient should be admitted to the ICU with serial endoscopic examinations, and potentially serial surgical resections in the case of disease progression. Close monitoring continues until disease is controlled and patient’s underlying disease is addressed, if possible

Example Procedure Note 

  • Procedure: Nasal biopsy
    After obtaining written and verbal consent from the patient, topical anesthetic was applied (Afrin and 2% lidocaine in 1:1 mixture). The rigid zero-degree endoscope was used to examine the bilateral nasal passages. The nasal mucosa appeared ___. An area that was concerning for invasive fungal sinusitis, located at the ___, was biopsied using a cup forceps. The biopsy was sent for frozen section pathology and fungal staining. Bleeding from the biopsy site was managed with ___. The patient tolerated the procedure well.

References

  1. Adelson, R.T., et al. (2013). Fungal Rhinosinusitis. In J.J. Johnson, C.A. Rosen. (Eds.), Bailey’s Head and Neck Surgery-Otolaryngology 5e (pp. 557-572). Baltimore, MD: Lippincott Williams & Wilkins. 

  2. Benninger, M.S., et al (2020). Acute Rhinosinusitis: Pathogenesis, Treatment, and Complications. In P.W. Flint, et al (Eds.), Cummings Otolaryngology Head and Neck Surgery 7e (pp. 643-648). Philadelphia, PA: Elsevier.

  3. Ergun O, Tahir E, Kuscu O, Ozgen B, Yilmaz T. Acute Invasive Fungal Rhinosinusitis: Presentation of 19 Cases, Review of the Literature, and a New Classification System. J Oral Maxillofac Surg. 2017;75(4):767.e1-767.e9. doi:10.1016/j.joms.2016.11.004