A 57-year-old man with leukocytosis and sphenoid sinus disease
Digital Journal of Ophthalmology 2020
Volume 26, Number 2
April 24, 2020
DOI: 10.5693/djo.03.2019.09.003
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Ansuya P. Deosaran, MD | Department of Ophthalmology, Louisiana State University, New Orleans, Louisiana
Ahmaida Zeglam, MD | Department of Ophthalmology, University of Florida, Gainesville, Florida
Mary K. Wilson, BS | College of Medicine, University of Florida, Gainesville, Florida
Andres Gonzalez, MD | Department of Ophthalmology, University of Florida, Gainesville, Florida
Matthew J. Gray, MD | Department of Ophthalmology, University of Florida, Gainesville, Florida

A 57-year-old man with a past medical history of coronary artery disease, chronic sinusitis, allergic rhinitis, and history of sinus surgery on intranasal steroids presented to an outside emergency room with worsening sinusitis symptoms of 4-5 days’ duration. On arrival, labs revealed a leukocytosis, and computed tomography (CT) of the maxillofacial region revealed significant sphenoid sinus disease, with mild mucosal thickening in the right ethmoid and frontal sinuses. He was admitted for treatment with antibiotics. The following day, the patient felt his swelling and pain had improved but noted acutely decreased vision in his right eye. CT angiography of the head on this day revealed right periorbital edema and cellulitis, with occlusion versus thrombus of the right superior ophthalmic vein and engorgement of the medial and inferior rectus muscles. There was also opacification of the right sphenoid and maxillary sinus (Figure 1). He was started on heparin by Neurology. Two days after admission, he experienced increasing right periorbital swelling, redness, and ptosis. He was transferred to University of Florida, Gainesville, for ophthalmological examination.

Figure 1
Thin slice, contrast-enhanced computed tomography (CT) in an axial plane at two levels show opacification of the right sphenoid and maxillary sinuses, indicated with arrows. Figure 1A demonstrates significant proptosis of the right eye, with early postseptal infiltration in the form of inflammatory stranding of the retro-orbital fatty tissue with reactive osteitis. Figure 1B, a lower axial cut, better demonstrates the opacification of the right maxillary sinus.

On examination at our institution, visual acuity was no light perception in the right eye and 20/30 in the left eye. Intraocular pressure (IOP) was 25 mm Hg in the right eye and 15 mm Hg in the left eye. The right pupil was 5 mm and nonreactive, with a relative afferent pupillary defect by reverse testing due to lack of light perception in that eye. Extraocular motility in the right eye was nonexistent. Anterior segment examination of the right eye revealed proptosis, complete ptosis, and chemosis. Dilated fundus examination of the right eye revealed disc pallor, with blurred disc margins, macular cherry red spot, attenuated vasculature, and a pale, ischemic retina. Findings suggested a possible cavernous sinus thrombosis from infection. Examination of the left eye was unremarkable.

Three days after his initial admission, the proptosis worsened, and the IOP increased to 45 mm Hg in the right eye. The following day, the left eye had new proptosis, decreased visual acuity (20/60), and an increase in IOP to 22 mm Hg. Extraocular motility of the left eye appeared restricted in all gazes. Anterior examination revealed proptosis, ptosis, and chemosis. Dilated fundus examination remained normal.

Five days after admission, visual acuity in the left eye also progressed to no light perception. His pupil was fixed at 5 mm and nonreactive. Extraocular motility was nonexistent. He developed neck stiffness, left lower extremity and forehead numbness, and intermittent confusion.

Ancillary Testing
Magnetic resonance imaging was deferred because of his implanted defibrillator. Five days after admission, CT showed multiple subacute infarcts in the frontoparietal region and right anterior frontal, temporal, and occipital lobes. There was also early postseptal infiltration and reactive osteitis (Figure 2). CT was repeated that day because of his declining clinical status and revealed progression, with ring-enhancing lesions throughout the maxillofacial region, suggesting abscess formation in the infratemporal and middle cranial fossae.

Initial bacterial blood cultures grew Enterobacter cloacae; fungal blood cultures had no growth. Four days after admission, lumbar puncture revealed leukocytosis, with increased polymorphonucleocytes and monocytes despite negative viral, bacterial, fungal, and amoeba cultures of the cerebral spinal fluid.

Six days after admission, and 5 days after an urgent sinus sphenoidotomy, surgical pathology revealed nonseptate hyphae consistent with zygomycetes of the Mucor family. Repeat endoscopic sinus debridement noted no focal necrotic tissue.

Figure 2
Contrast-enhanced CT imaging in an axial plane demonstrating postseptal infiltration (asterisk) and reactive osteitis (arrow).

The patient was initially admitted for intravenous ampicillin/sulbactam, intranasal steroids, and one dose of intravenous dexamethasone.

His IOP spikes on day 2 in the right eye and day 3 in the left eye were treated with brimonidine 0.2%, dorzolamide 2%, and timolol 0.5% each twice daily in the right eye.

Three days after admission, an urgent sinus sphenoidotomy showed no necrotic tissue, purulence, or fungal debris. He was transitioned to vancomycin, cefepime, metronidazole, and amphotericin. On post-admission day 11, he became diaphoretic, obtunded, and hypotensive, with no response to resuscitation. He was transitioned to comfort care and died that day.

Differential Diagnosis
The differential diagnosis for invasive fungal sinusitis includes an infection with Aspergillus, Rhizopus, Mucorales, Fusarium, and dematiaceous fungi.(1,2). These fungi cause tissue necrosis, vascular thrombosis, and infarction (2). Among these, the most likely fungi are Aspergillus and Rhizopus species.(2) Identification of the organism is made with culture, immunohistochemistry, and in situ hybridization.(2,3)

Diagnosis and Discussion
Mucormycosis is the third most common invasive fungal infection, following Aspergillosis and Candidiasis, and has high morbidity and mortality.(4) Rhino-cerebral-orbito mucormycosis (RCOM) is associated with diabetes mellitus, hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplant.(5) High-dose glucocorticoids, chronic antibiotics, long-term neutropenia, deroxamine, chronic renal failure, major burns, severe trauma, and acquired immune deficiency syndrome predispose to RCOM.(6,7)

Although rare, RCOM in immunocompetent individuals has been reported. An analysis of the literature of mucormycosis in immunocompetent, otherwise healthy individuals found 81 of 212 patients (38.2%) presenting with RCOM.(7) The present report reveals the need to have a high index of suspicion for RCOM in immunocompetent patients, especially if they are clinically deteriorating despite appropriate antibiotics.

Early diagnosis, removal or reversal of risk factors, prompt antifungals, and surgical debridement of devitalized tissue optimize RCOM outcomes.(8) Additionally, early evaluation and diagnosis of sinus mucormycosis helps prevent orbital invasion. Recognizing early findings such as fever, facial pain with swelling, nasal mucosal ulceration/necrosis, sinusitis, decreased visual acuity, and headache assists in timely diagnosis.(6,9) Amphotericin B is associated with increased response rates and survival.(8) Prompt amphotericin B initiation is recommended because a delay of >6 days is associated with increased mortality.(10) Early surgical debridement of necrotic tissue is fundamental. Necrotic tissue can decrease antifungal penetration, decreasing drug effectiveness.(11)

Tissue cultures are not necessarily reliable, because samples often fail to grow Mucor. Debridement biopsies help identify Mucor on tissue preparations using direct microscopy. Improved outcomes are associated with therapeutic decisions made based on frozen tissue sections.(12) Furthermore, Mucor tissue infections may manifest without a black necrotic eschar, as in our case. Mucormycosis must be considered irrespective of tissue presentation.

Mortality rates of RCOM range from 30% to 69%.(4) Despite following standard practice guidelines, our patient’s prognosis was poor. We hypothesize that intranasal steroids may have predisposed our immunocompetent patient. Local steroids likely suppressed immune responses, rendering the nasal mucosa susceptible to fungal colonization. An intensive literature search found no other reports of local steroid therapy with RCOM.

Rapidly deteriorating RCOM may occur in both immunocompromised and immunocompetent individuals. A high index of suspicion must be held in patients with signs and symptoms suspicious for mucormycosis sinusitis, especially if an immunocompetent individual is on intranasal steroids. Prompt administration of antifungal medications and debridement of necrotic tissues are recommended in all patients with RCOM.

Literature Search
PubMed was searched on July 21, 2016, without date restriction, for English-language results, using the following terms: rhino-orbital-cerebral mucormycosis, mucor, and immunocompetent.

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