Rhinocerebral mucormycosis
Authors: Adegbola Samuel OA , Banerjee Ashis , Mulcahy Michael P 
Published: May 2014

A 77-year-old woman presented to the emergency department with worsening unsteadiness on her feet over the preceding 2 months. She had sustained a mechanical fall leading to head injury 3 weeks before presentation, followed by increasing confusion (as reported by her husband). She also gave a 2-day history of numbness overlying the left cheek bone. Her past medical history included type 2 diabetes mellitus (for which she was on metformin), hypothyroidism (for which she was on thyroxine replacement), and hypercholesterolaemia. Two months before presentation, she had been diagnosed with idiopathic thrombocytopaenic purpura, for which she was on high-dose prednisolone. The remainder of the history and review of systems were non-contributory.

At the time of admission, she was alert and oriented. She was pyrexial (temperature 37.7°C), other vital signs being within normal limits. On physical examination, she had a Glasgow Coma Score of 15/15 and mini-mental state exam of 7/10. There was mild sensory loss in the left maxillary area to light touch, with preserved sensation in the other divisions of the trigeminal nerve. Otherwise cranial and peripheral nervous system exam was unremarkable. No abnormalities were detected on intra-oral or on systemic examination.

Initial investigations demonstrated poor glycaemic control with a haemoglobin A1c concentration of 12.8%. She also had a neutrophilic leukocytosis and elevated acute phase reactants. She underwent a computed tomography (CT) scan of her head (in view of the history of mechanical fall, confusion and unsteadiness on her feet), which was normal. Initial management involved intravenous rehydration, commencement of an insulin sliding scale and antibiotics for urinary tract sepsis. She was weaned off steroid therapy and her diabetes control subsequently improved. During the first week in hospital, she developed progressive numbness and swelling of the left side of her face. Examination showed erythema around the left cheek, soft tissue proliferation on the left nasolabial fold with some serous discharge from the left nostril, and a pigmented necrotic area on the hard palate with clearly defined margins (Figure 1). There was surrounding whitish exudate associated with the palatal lesion. CT scan of the paranasal sinuses indicated radio-opacity in the left maxillary sinus compatible with unilateral sinusitis, with intact palatal and antral walls. Initial biopsy of the palatal lesion demonstrated severe necrotizing active inflammation with microabscess formation, fat necrosis and vasculitis. Stains for fungi were negative and no viral inclusions were seen.

A rheumatology opinion was sought to consider a possible diagnosis of Wegener's granulomatosis. This was deemed unlikely, as she had no underlying rheumatological disease, and despite a vasculitis screen revealing a positive peri-nuclear anti-neutrophil cytoplasmic antibody, her anti-proteinase3 and antimyeloperoxidase antibodies were within normal limits.

The palatal necrosis continued to progress despite intravenous antibiotics, so she underwent surgical debridement of the necrotic palatal mucosa. She continued to deteriorate, with left facial palsy and left sensori-neural deafness. Further CT imaging of her temporal bones showed a ‘moth-eaten’ appearance with lytic bony changes of her petrous temporal bones (Figure 2). Histological examination of specimens from the palatal debridement demonstrated ulceration, necrotizing sialometaplasia, extensive necrosis, and numerous large non-septate hyphae and spores.

The radiological and histological features thus confirmed rhinocerebral mucormycosis with skull base osteomyelitis. She underwent further urgent debridement involving the palatine bone, lateral nasal wall and all visible necrotic tissue. Eight weeks after admission, at the time of definitive diagnosis, intravenous AmBisome (liposomal amphotericin) was commenced at 1 mg/kg/day, increasing at a dose of 1 mg/kg over 5 days to 5 mg/kg/day. She failed to respond significantly to this treatment, and posoconazole was subsequently added on microbiological advice. She continued to deteriorate, becoming increasingly breathless and hypoxic. A chest X-ray demonstrated a granular appearance of both lungs fields, thought to be in keeping with a pulmonary invasion of the infection. A few days later, she went into respiratory arrest from which she could not be resuscitated.