Cox’s Conference: Mucormycosis

In this week’s Ambulatory Cox’s Conference, Dr. Jasmine Sukumar presented a case of a 50 year old man with history of alcohol cirrhosis, uncontrolled diabetes, and rectal cancer on chemotherapy who presented with right sided vision loss for 1 day. Our expert discussant, Dr. Pearlie Chong guided us through infectious complications to consider in an immunocompromised host.

The differential diagnosis for our patient with acute persistent vision loss included diabetic retinopathy with vitreous hemorrhage, retinal detachment, glaucoma, retinal artery or vein occlusion, optic neuritis, and giant cell arteritis. On exam the patient was found to have swelling and redness of the right eye with associated cranial nerve deficits. Based on the exam and the patient’s past medical history, we had to consider potentially less common etiologies of vision loss including intracranial malignancy (or metastasis), CMV retinitis, or invasive fungal infection. Imaging of the head and sinuses revealed thickening of the right ethmoid and maxillary sinus as well as a large soft-tissue mass in the retroorbital area. Surgical biopsies were performed that showed broad, irregularly branched hyphae with rare septations consistent with Rhizopus oryzae.

Mucormycosis Pearls:

·     Mucormycosis is a life-threatening fungal infection that typically affects immunocompromised patients as well as those with diabetes mellitus.

·     Infections in humans are most commonly caused by Rhizopus, Mucor, and Rhizomucor. These organisms are ubiquitous in nature and commonly found in soil and decaying vegetation.

·     In addition to immunocompromised patients, those with hemochromatosis (particularly those receiving deferoxamine therapy) and burn/trauma patients are also at risk of mucormysosis.

Clinical Presentation:

·     Most common clinical presentation in rhino-orbital-cerebral infection caused by inhalation of spores into the paranasal sinuses.

o     Common presenting complaints are fever, headache, nasal congestion, purulent nasal discharge, and sinus pain.

o     If the infection spreads beyond the sinuses, nearby structures can be involved resulting in perinasal swelling, palate eschars, and erythema or necrosis of the skin overlying the sinuses or orbit.

o     Signs of orbital involvement include periorbital edema, proptosis, and blindness as in our patient. Spread to the nearby cavernous sinus can result in cranial nerve palsies.1

·     Mucormycosis can also present with pulmonary, gastrointestinal, cutaneous, renal, or isolated CNS involvement. Disseminated disease occurs in severely immunocompromised patients.

·     Interestingly, many diabetic patients had ketoacidosis at the time of presentation.2

Diagnosis:

·     As Mucormycosis is a rapidly progressive, fatal disease, prompt diagnosis and empiric treatment is crucial.

·     Diagnosis relies on identification of the organism in tissue by histopathology, which requires a tissue biopsy. Cultures often yield no growth.

·     The 1,3-beta-D-glucan assay and the Aspergillus galactomannan assay will be negative in these patients.

Treatment:

·     Treatment requires both surgical deridement of involved tissues as well as antifungal therapy.

·     It is also important to eliminate any potential predisposing factors for this infection including hyperglycemia, deferoxamine administration, immunosuppressive medications, and neutropenia.

·     First line therapy is intravenous amphotericin B at 5-10mg/kg daily. After a patient has shown clinical improvement, the patient can be transitioned to posaconazole.3

·     Some data suggests improved patient outcomes with addition of caspofungin to amphotericin B compared to amphotericin B monotherapy. However larger studies are needed to establish whether combination therapy is truly beneficial.4

·     Despite appropriate antifungal therapy, aggressive surgical debridement is required for adequate disease control.

References:

1.     Yohai RA, Bullock JD, Aziz AA, Markert RJ. Survival factors in rhino-orbital-cerebral mucormycosis. Surv Ophthalmol 1994; 39:3.

2.     McNulty JS. Rhinocerebral mucormycosis: predisposing factors. Laryngoscope 1982; 92:1140.

3.     McCarthy M, Rosengart A, Schuetz AN, et al. Mold infections of the central nervous system. N Engl J Med 2014; 371:150.

4.     Reed C, Bryant R, Ibrahim AS, et al. Combination polyene-caspofungin treatment of rhino-orbital-cerebral mucormycosis. Clin Infect Dis 2008; 47:364.