Invasive fatal rhino-orbito-cerebral mucormycosis in diabetic ketoacidosis

A 52-year-old Indian woman presented to hospital with a one-week history of right-sided retroorbital pain and facial swelling. She had no other significant past medical history. On examination, she was found to be apyrexial with a pulse rate of 100 min and confused. She also had evidence of right-sided periorbital cellulitis. Cranial nerve examination confirmed decreased visual acuity in the right eye (6/9) but with a full range of extraocular muscle movements. She was also noted to have an ipsilateral mild facial nerve weakness (House-Brackmann classification grade II). Blood tests revealed a neutrophilic leukocytosis (31.6 x 10/L) with a C-reactive protein of 456 mg/ L and random blood glucose of 56.1 mmol/L. Urine dipstick analysis identified the presence of ketones and blood gas analysis confirmed a metabolic acidosis. A clinical diagnosis of diabetic ketoacidosis was made and the patient was treated aggressively with intravenous fluid replacement, intravenous antibiotics (co-amoxiclav and metronidazole) and commenced on an insulin sliding scale. An extended CT of the head including both orbits confirmed right periorbital cellulitis, with a degree of stranding of the extraconal adipose tissue consistent with Chandler classification grade II (Figure 1). There was no evidence of any intra-orbital collection or intracranial extension. However, imaging of the paranasal sinuses confirmed complete opacification of the right nasal cavity, maxillary and frontal sinuses, which were, therefore, presumed the source of sepsis. The patient underwent an urgent endoscopic exploration under general anaesthesia. This revealed a large necrotic mass in the right nasal cavity which was excised and biopsies sent for histopathology, microscopy and sensitivity. Histopathological assessment revealed fungal invasion. The fungal hyphae were seen to be broad and distorted, branching at right angles and surrounded by extensive necrotic debris. No septae were present. The right nasal cavity and the involved paranasal sinuses were exenterated and irrigated. In view of the intraoperative findings and the histopathology report, parenteral amphotericin B was also added to the treatment regime. Despite an initial transient improvement in terms of her temperature and conscious level, the cranial neuropathies persisted and she subsequently deteriorated becoming more confused and losing vision completely from the right eye. An MRI scan of the head revealed evidence of predominantly right frontal cerebritis with early abscess formation (Figure 2). This was arising through direct extension from the nasal cavity into the frontal lobes, through the cribiform plate. Re-accumulation of fluid and thickening of the mucosa in the paranasal sinuses was evident radiologically but now with disease also affecting the sphenoid and ethmoid sinuses. Further surgery including a right maxillectomy was performed, via a lateral rhinotomy approach. An orbital exenteration was also done as the right eyewas found to be necrotic. The frontal sinus was opened and the mass seen to be extending into the dura. The dura was, therefore, also opened and DECLARATIONS