Fatal Consequences Of An Ear Infection

Case Report

Fatal consequences of an ear infection Xenia L Stalpers, Mijke Smink-Bol, Paul E Verweij, Pieter Wesseling, Gert W van Dijk Lancet 2009; 373: 1658 Canisius-Wilhelmina Hospital, Department of Neurology (X L Stalpers MD, G W van Dijk MD), Department of Pathology (Prof P Wesseling MD), Nijmegen, Netherlands; Radboud University Nijmegen Medical Center, Department of Pathology (M Smink-Bol MD, Prof P Wesseling MD), Department of Medical Microbiology (Prof P E Verweij MD), Nijmegen, Netherlands Correspondence to: Xenia L Stalpers, Canisius-Wilhelmina Hospital, Department of Neurology, Weg door Jonkerbos 100, 6532 SZ, Nijmegen, Netherlands [email protected]

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In August, 2006, a 75-year-old non-diabetic, non-alcoholic man with hypertension and atrial fibrillation was admitted to the Internal Medicine department with low grade fever, increasing otalgia, otorrhoea, dysphagia, and hoarseness. He had suffered from bilateral tympanic membrane perforation, intermittent otalgia, and otorrhoea for 12 years. In May, 2006, his otolaryngologist had prescribed ofloxacin ear drops and oral ciprofloxacin for otalgia and otorrhoea. In June, 2006, he was admitted to the Ear, Nose and Throat department with a 3-week history of left peripheral facial nerve palsy, left trigeminal sensory loss, and general discomfort. He was afebrile, with a serum C-reactive protein concentration of 72 mg/L; other laboratory tests were normal. CT and MRI of the head showed clouding of the left mastoid without intracranial pathology or meningeal enhancement (figure A); chest radiography was normal. A diagnosis of mastoiditis was made, and ceftazidime and flucloxacillin were started. Surgical exploration of the left mastoid showed granulation tissue in the external auditory canal and around the ossicles. Microscopically this tissue showed chronic-active necrotising inflammation; cultures (including those for fungi) were negative. After 2 weeks, the patient was discharged in fair condition. In the current admission, besides earlier described cranial nerve dysfunction, a partial left glossopharyngeal and vagal nerve palsy were diagnosed by the consulting otolaryngologist. C-reactive protein was 57 mg/L with normal white cells. Culture of discharge from the ear grew Pseudomonas aeruginosa, and amoxicillin (empirically started on admission) was replaced by meropenem. B

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2 weeks later, still in hospital and being treated with meropenem, he developed headache, neck pain, and a left abducens nerve palsy. Repeated chest radiography and MRI of the brain were normal. Cerebrospinal fluid (CSF) analysis showed only a mild pleocytosis (leucocytes 17×10⁶ per L). The clinical picture suggested a chronic (basal) meningitis, but blood and CSF cultures remained negative. The patient refused meningeal biopsy and further treatment, had progressive difficulty in swallowing, and died 3 weeks later in hospital from pneumonia. Autopsy showed a focal purulent prepontine leptomeningeal exudate (figure B). Microscopically, multiple septated and branched hyphae were detected in this exudate and in the left middle and internal ear (figure C), combined with chronic-active necrotising inflammation. The inflammation extended into the skull base and cranial nerves. A mould cultured from the exudate was characterised as Pseudallescheria boydii by sequence-analysis of parts of the β-tubulin gene. P boydii can cause a wide variety of clinical diseases and is commonly found in soil, polluted water, and manure. P boydii infections of the central nervous system (CNS), meninges, and mastoid are very rare and generally occur in immunocompromised, near drowning, and trauma patients, but have also been reported in patients without one of these risk factors.1–3 There was no suspicion of immunocompromise in our patient, and postmortem HIV PCR analysis from lymph node and heart tissues were negative. Diagnosis of CNS involvement by P boydii is often delayed because of non-specific clinical presentation, difficulty in obtaining and culturing appropriate specimens, and because of histological similarity of P boydii to other fungi, such as aspergillus. In our patient the fungus most likely gained access to the ear and CNS through tympanic membrane perforation. In patients with P boydii mastoiditis, surgical intervention, adequate anti-fungal therapy, and identification and control of underlying immunological conditions are essential. Voriconazole is suggested as the treatment of choice.3 Awareness of P boydii as a cause of chronic mastoiditis and meningitis may allow early diagnosis and treatment, thereby increasing the chance of resolution. Contributors All authors contributed to writing and revising this report, XS as main author and GWvD as senior author. XS had no role in management of the patient. MSB and PW participated in the autopsy and histopathological investigations. PV contributed to microbiological investigations. GWvD contributed to the patient’s management.

Figure: MRI, macroscopy, and microscopy (A) Axial T1-weighted magnetic resonance image with intravenous gadolinium showing high signal intensity of the left mastoid (arrow), without intracranial pathology. (B) Macroscopic view of the anterior side of the brainstem with a focal purulent exudate (arrow). (C) Extensive active and necrotising inflammation in the left os petrosum with dispersed septated and branched hyphae (PAS staining, original magnification ×400).

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References 1 Benham RW, Georg LK. Allescheria boydii, causative agent in a case of meningitis. J Invest Dermatol 1948; 10: 99–110. 2 Kershaw P, Freeman R, Templeton D, et al. Pseudallescheria boydii infection of the central nervous system. Arch Neurol 1990; 47: 468–72. 3 Cortez KJ, Roilides E, Quiroz-Telles F, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev 2008; 21: 157–97.

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